Alkene Metathesis: Applications in the Synthesis of Novel Organometallic Complexes, and Mechanistic Investigations

Alkene metathesis: applications in the synthesis of novel organometallic complexes, and mechanistic investigations

Den Naturwissenschaftlichen Fakultäten der Friedrich-Alexander-Universität Erlangen-Nürnberg zur Erlangung des Doktorgrades

vorgelegt von Giovanni Pietro Rachiero aus Toronto (Kanada)

Als Dissertation genehmigt von den Naturwissenschaftlichen Fakultäten der Universität Erlangen-Nürnberg

Tag der mündlichen Prüfung: 02 Oktober 2008 Vorsitzender der Promotionskommission: Prof. Dr. E. Bänsch Erstberichterstatter: Prof. Dr. J. A. Gladysz Zweitberichterstatter: Prof. Dr. H. Gröger

A mia madre Telma e mio padre Giovanni Con infinito affetto e gratitudine

Ogni Sapienza viene dal Signore ed è sempre con Lui. Siracide 1,1

Die vorliegende Arbeit wurde am Institut für Organische Chemie der Friedrich-Alexander- Universität Erlangen-Nürnberg unter Anleitung von Prof. Dr. John A. Gladysz angefertigt.

Acknowledgements

First of all I would like to express my sincere gratitude to my supervisor Prof. Dr. John A. Gladysz for giving me the opportunity to carry out research in the field of Alkene Metathesis, and for his constant scientific support. Many thanks to all my past and present colleagues for their help and entertainment. I am grateful to the administrative and technical staff of the Institute of Organic Chemistry of the Friedrich-Alexander University of Erlangen-Nürnberg. A particular thank is for Pamela Engerer and Dr. Frank Hampel. I will be always in debt to my friend Prof. Christine Hahn for her help during my first period in Erlangen and for her suggestions during the writing of this thesis. Thanks to Dr. Deprapasad Mandal and Tobias Fiedler for reading this thesis. A special place is for Katrin. Grazie, tesoro mio. Thanks to my sister Teresa, her husband Agostino, their children Manuela e Giuseppe for their support. I dedicate this thesis to my parents. I thank my Mum Telma and Dad Giovanni for their wonderful love and precious encouragement. Thanks for everything you taught me. vi

Table of Contents

Zusammenfassung x Abstract xiii List of Figures xvi List of Schemes xxi List of Tables xxiv

1. General Introduction 1 1.1. General concepts 1

1.2. Applications of alkene metathesis 3 1.2.1. Cross metathesis (CM). 3 1.2.2. Ring opening metathesis polymerization (ROMP) . 5 1.2.3. Ring closing metathesis (RCM). 6 1.2.4. Future perspectives of alkene metathesis. 8 1.3. Aims of this work 8 1.4. References and notes 10

2. Mechanistic study on the activity of a Hoveyda-type catalyst 13 2.1. Introduction 13 2.1.1. Chauvin and Hérisson alkene metathesis mechanism. 13 2.1.2. Background of ruthenium technology. 14 2.1.3. Grubbs-type catalysts. 16 2.1.4. Hoveyda-type catalysts. 17 2.2. Project design 19 2.3. Results 20 2.3.1. Syntheses of Hoveyda's second generation catalysts. 20

2.3.2. Mass spectrometry experiments. 24 vii

2.4. Discussion 28 2.4.1. Boomerang mechanism. 28 2.4.2. Mass spectrometry experiments. 30 2.5. Conclusions 37 2.6. Experimental section 38 2.7. References and notes 50

3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine)ligands 54 3.1. Introduction 54 3.1.1. Rope-skipping rotors. 54 3.1.2. Gyroscope-like complexes. 57 3.2. Project design 57 3.3. Results 58 3.3.1. Syntheses of alkene-containing pyridines. 58 3.3.2. Syntheses of alkene-containing bis(pyridine) complexes. 62 3.3.3. Syntheses of gyroscope-like complexes. 70 3.3.4. Substitution reactions. 76 3.3.5. Crystallography. 77 3.4. Discussion 83 3.4.1. Ligands. 83

3.4.2. Complexes. 83 3.4.3. Gyroscope-like complexes. 85 3.4.4. Spectroscopy. 86 3.4.5. Mass spectra and thermal stability. 89 3.4.6. Crystal structures. 89 3.4.7. Future directions. 96 3.5 Conclusions 97 viii

3.6. Experimental section 98 3.7. References and notes 127

4. Novel ruthenium-based carbene complexes 132 4.1. Introduction 132 4.1.1. Developments of ruthenium technology. 132 4.1.2. Carbyne and carbide complexes. 134 4.2. Project design 135 4.3. Results 135 4.3.1. Alkene-containing pyridines. 135 4.3.2. Alkene-containing rhenium complexes. 136 4.3.3. VT NMR experiments with alkene-containing pyridines. 139 4.3.4. VT NMR experiments with alkene-containing rhenium complexes. 153 4.3.5. Preparative reactions. 166 4.4. Discussion 169 4.4.1. Alkene-containing rhenium complexes. 169 4.4.2. Crystal structure. 170 4.4.3. Heterobimetallic ruthenium-rhenium carbyne complexes. 171 4.4.4. Future directions. 172 4.5. Conclusions 173

4.6. Experimental section 174 4.7. References and notes 181

5. Crystallography 185 5.1. Data collection and structure refinement 185 5.2. Data deposition 187 5.3. Crystallographic tables 188 ix

5.4. References and notes 190

Curriculum vitae x

Zusammenfassung

Kapitel 1 liefert einen Überblick über die Alkenmetathese-Reaktion. Kapitel 2 beschreibt die Aktivität des Hoveyda-Metathese-Katalysators der zweiten Generation mit Hilfe von massenspektrometrischen Untersuchungen. Reduktion von

(CD3)2CO mit NaBH4 liefert 2-Propanol-d6 (6-d6, 53%). Reaktion von 6-d6 mit HBr ergibt 2-Brompropan-d6 (3-d6, 63%). Anschließende O-Alkylierung von Salicylaldehyd mit 3-d6 (Base Cs2CO3) führt zu 2-Isopropoxybenzaldehyd-d6 (4-d6, 60%). Wittig- + − Reaktion von 4-d6 (Ph3PCH3 Br , t-BuOK) liefert 2-Isopropoxystyrol-d6 (1-d6, 35%).

Nitrierung von Mesitylen-d12 ergibt 1,3,5-Trimethylnitrobenzol-d11 (12-d11, 74%).

Katalytische Hydrierung von 12-d11 führt zu 2,4,6-Trimethylanilin-d11 (7-d11, 76%).

Kondensation von Glyoxal mit 7-d11 (2 äquiv) liefert das Diimin Glyoxal-bis(2,4,6- trimethylphenylimin)-d22 (9-d22, 90%). Reaktion von 9-d22 mit NaBH4 ergibt das Diamin

N,N'-Bis(2,4,6-trimethylphenyl)ethylendiamin-d22 dihydrochlorid (10-d22, 83%). Reaktion von 10-d22 mit HC(OEt)3 führt zu 1,3-Bis(2,4,6-trimethylphenyl)imidazolinium-d22 chlorid (2-d22, 84%). Reaktion von Ru(=CHPh)(PCy3)2(Cl)2 (13) mit 2-d22 (Hexan, t-

BuOK) ergibt Ru(=CHPh)(H2IMes-d22)(PCy3)(Cl)2 (14-d22, 57%). Behandlung von 14- d22 mit 1-d6 in Gegenwart von CuCl liefert (H2IMes-d22)(Cl2)Ru=CH-o-OC6H4(i-Pr-d6)

(15-d28, 85%). Gemische von 15-d28 und sein natürliches Analogon 15-d0 werden in "Crossover-Experimenten" eingesetzt; abhängig von den Reaktionsbedingungen kann der

Katalysator rein oder als Mischung 15-d0/15-d6/15-d22/15-d28 zurückgewonnen werden. Letzteres steht mit einem Bumerang-Mechanismus im Einklang. Kapitel 3 beschreibt die Synthese und Charakterisierung von gyroskopähnlichen Molekülen mit zweifach trans-ständigen Bispyridin-Liganden. Reaktionen von 2,6-

NC5H3(CH2Br)2 mit CH2=CHCH2MgBr (1.0 M in Diethylether), und HO(CH2)nCH=CH2 + − (n = a, 1; b, 2; c, 3; d, 4) in Gegenwart von C6H5CH2N(CH3)3 Cl liefern die alkenhaltigen Pyridine 2,6-NC5H3(CH2CH2CH=CH2)2 (21, 60%), bzw. 2,6-

NC5H3(CH2O(CH2)nCH=CH2)2 (22a-d, 45-55%). Reaktionen von 3,5-NC5H3(COCl)2 mit HO(CH2)nCH=CH2 (n = a, 1; b, 2; c, 3; d, 4; e, 5; f, 6; g, 8) ergeben 3,5-

NC5H3(COO(CH2)nCH=CH2)2 (29a-g, 41-90%). Williamson Ether Synthesen von 2,6-

NC5H3Br2 und HO(CH2)nCH=CH2 (n = a, 1; b, 2) ergeben 2,6-

NC5H3(O(CH2)nCH=CH2)2 (45-55%). Quadratisch-planare Komplexe von einigen der beschriebenen substituierten Pyridine werden synthetisiert.

Reaktion von [RhCl(coe)2]2 (coe = Cycloocten) mit 22a ergibt trans-

Rh(Cl)(CO)[2,6-NC5H3(CH2OCH2CH=CH2)2]2 (26%). PtCl2 wird mit 22a,b und 29a,c-g versetzt und führt zu trans-PtCl2[2,6-NC5H3(CH2O(CH2)nCH=CH2)2]2 (trans-31a, 88%; trans-31b, 26%), bzw. trans-PtCl2[3,5-NC5H3(COO(CH2)nCH=CH2)2]2 (trans-32a,c-g,

63-94%). Rektionen von trans-(PhCN)2PdCl2 mit 29e und 21 ergeben trans-PdCl2[3,5-

NC5H3(COO(CH2)5CH=CH2)2]2 (94%) bzw. trans-PdCl2[2,6-

NC5H3(CH2CH2CH=CH2)2]2 (trans-34, 15%). Behandlung von trans-31a,b und trans- 32d-g mit 13 und anschließende Hydrierung (Katalysator Pd/C) ergibt die gyroskopähnlichen Komplexe trans-PtCl2[2,6,2',6'-

(NC5H3(CH2O(CH2)2n+2OCH2)2H3C5N)] (trans-35a,b, 10-22%), bzw. trans-

PtCl2[3,5,3',5'-(NC5H3(COO(CH2)2n+2COO)2H3C5N)] (trans-36d-g, 14-45%). Die Reaktion von trans-34 mit 13 liefert nach säulenchromatographischer

Reinigung trans-PdCl2[2,6,2',6'-(NC5H3((CH2)2CH=CH(CH2)2)2H3C5N)] (trans-37, 55-

58%). Anschließende Hydrierung (Katalysator PtO2) ergibt trans-PdCl2[2,6,2',6'-

(NC5H3((CH2)6)2H3C5N)] (trans-38, 58-62%). Die Reaktion von trans-32c mit PhC≡CH, in Gegenwart von CuI, liefert trans-Pt(Cl)(C≡CPh)[3,5-NC5H3(COO(CH2)3CH=CH2)2]2 (trans-39c, 18%). Die Kristallstrukturen von trans-31a, trans-35a, trans-35b, trans-36e, und trans-38 wurden bestimmt und analysiert. Kapitel 4 beschreibt die Reaktivität der Grubbs-Metathese-Katalysatoren der ersten und zweiten Generation mit alkenhaltigen Pyridinen und Rhenium-Komplexen mit Hilfe 5 von NMR Studien. Behandlung von (R)-(η -C5H5)Re(NO)(PPh3)(CH3) ((R)-40) mit

xii

+ – Ph3C PF6 und CH2=CHCH2MgBr (1.0 M in Diethylether) liefert nach Umkristallisation 5 den Butenyl-Rheniumkomplex (R)-(η -C5H5)Re(NO)(PPh3)(CH2CH2CH=CH2) ((R)-45, + – 50%). Analoge Behandlung von (R)-40 mit Ph3C PF6 und CH2=CHCH2CH2MgBr (0.5 M in THF) ergibt nach säulenchromatographischer Reinigung den Pentenyl- 5 Rheniumkomplex (R)-(η -C5H5)Re(NO)(PPh3)(CH2CH2CH2CH=CH2) ((R)-46, 45%). Äquimolare Mengen der alkenhaltigen Rhenium-Komplexe (R)-43, (R)-45, und (R)-46, und alkenhaltige Pyridine 22a, 25b, und 29g werden mit 13 oder

Ru(=CHPh)(H2IMes)(PCy3)(Cl)2 versetzt. Die Reaktionen werden mit Hilfe von Tieftemperatur-NMR-Messungen verfolgt. Die Reaktion von (R)-45 (2 äquiv) mit 13 5 liefert (η -C5H5)Re(NO)(PPh3)(CH2)2(CH=)Ru(PCy3)2(Cl)2 (49%) in ≥ 90% Reinheit, bestimmt durch 31P{1H}-NMR-Spektroskopie. Die Kristallstruktur von (R)-46 wurde bestimmt und analysiert.

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Abstract

Chapter 1 provides an overview on alkene metathesis reaction. Chapter 2 describes a mass spectrometric investigation of the activity of Hoveyda's second generation metathesis catalyst. Reduction of (CD3)2CO with NaBH4 affords 2- propanol-d6 (6-d6, 53%). Treatment of 6-d6 with HBr gives 2-bromopropane-d6 (3-d6,

63%). Subsequent O-alkylation of salicylaldehyde with 3-d6 (Cs2CO3 base) yields 2- + − isopropoxybenzaldehyde-d6 (4-d6, 60%). Wittig olefination of 4-d6 (Ph3PCH3 Br , t-

BuOK) affords 2-isopropoxystyrene-d6 (1-d6, 35%). Nitration of mesitylene-d12 gives

1,3,5-trimethylnitrobenzene-d11 (12-d11, 74%). Catalytic hydrogenation of 12-d11 yields

2,4,6-trimethylaniline-d11 (7-d11, 76%). Condensation of glyoxal with 7-d11 (2 equiv) affords the diimine glyoxal-bis(2,4,6-trimethylphenylimine)-d22 (9-d22, 90%). Treatment of 9-d22 with NaBH4 gives the diamine N,N'-bis(2,4,6-trimethylphenyl)ethylenediamine- d22 dihydrochloride (10-d22, 83%). Reaction of 10-d22 with HC(OEt)3 leads to 1,3- bis(2,4,6-trimethylphenyl)imidazolinium-d22 chloride (2-d22, 84%). Reaction of

Ru(=CHPh)(PCy3)2(Cl)2 (13) with 2-d22 (hexanes, t-BuOK) gives Ru(=CHPh)(H2IMes- d22)(PCy3)(Cl)2 (14-d22, 57%). Treatment of 14-d22 with 1-d6 in the presence of CuCl yields (H2IMes-d22)(Cl2)Ru=CH-o-OC6H4(i-Pr-d6) (15-d28, 85%). Mixtures of 15-d28 and its natural abundance analog 15-d0 are utilized in crossover experiments; depending upon conditions, the recovered catalyst can be either unscrambled or a 15-d0/15-d6/15-d22/15- d28 mixture. The latter is consistent with a boomerang mechanism. Chapter 3 describes the synthesis and characterization of gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands. Reactions of 2,6-NC5H3(CH2Br)2 with

CH2=CHCH2MgBr (1.0 M in diethyl ether), and HO(CH2)nCH=CH2 (n = a, 1; b, 2; c, 3; + − d, 4) in the presence of C6H5CH2N(CH3)3 Cl afford alkene containing pyridines 2,6-

NC5H3(CH2CH2CH=CH2)2 (21, 60%), and 2,6-NC5H3(CH2O(CH2)nCH=CH2)2 (22a-d,

45-55%), respectively. Reactions of 3,5-NC5H3(COCl)2 with HO(CH2)nCH=CH2 (n = a,

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1; b, 2; c, 3; d, 4; e, 5; f, 6; g, 8) give 3,5-NC5H3(COO(CH2)nCH=CH2)2 (29a-g, 41-90%).

Williamson ether syntheses involving 2,6-NC5H3Br2 and HO(CH2)nCH=CH2 (n = a, 1; b,

2) yield 2,6-NC5H3(O(CH2)nCH=CH2)2 (45-55%). Square planar complexes of most of the preceding substituted pyridines are synthesized.

Reaction of [RhCl(coe)2]2 (coe = cyclooctene) with 22a gives trans-

Rh(Cl)(CO)[2,6-NC5H3(CH2OCH2CH=CH2)2]2 (26%). PtCl2 is treated with 22a,b and

29a,c-g to give trans-PtCl2[2,6-NC5H3(CH2O(CH2)nCH=CH2)2]2 (trans-31a, 88%; trans-

31b, 26%) and trans-PtCl2[3,5-NC5H3(COO(CH2)nCH=CH2)2]2 (trans-32a,c-g, 63-94%), respectively. Reactions of trans-(PhCN)2PdCl2 with 29e and 21 afford trans-PdCl2[3,5-

NC5H3(COO(CH2)5CH=CH2)2]2 (94%) and trans-PdCl2[2,6-

NC5H3(CH2CH2CH=CH2)2]2 (trans-34, 15%), respectively. Treatment of trans-31a,b and trans-32d-g with 13 and subsequent hydrogenation (Pd/C catalyst) gives the gyroscope- like complexes trans-PtCl2[2,6,2',6'-(NC5H3(CH2O(CH2)2n+2OCH2)2H3C5N)] (trans-

35a,b, 10-22%) and trans-PtCl2[3,5,3',5'-(NC5H3(COO(CH2)2n+2COO)2H3C5N)] (trans- 36d-g, 14-45%), respectively. The reaction of trans-34 with 13 affords trans-PdCl2[2,6,2',6'-(NC5H3((CH2)2CH=CH(CH2)2)2H3C5N)] (trans-37, 55-58%) after column chromatography. Subsequent hydrogenation (PtO2 catalyst) gives trans-PdCl2[2,6,2',6'-(NC5H3((CH2)6)2H3C5N)] (trans-38, 58-62%). The reaction of trans-32c with PhC≡CH, in the presence of CuI, affords trans-Pt(Cl)(C≡CPh)[3,5-

NC5H3(COO(CH2)3CH=CH2)2]2 (trans-39c, 18%). The crystal structures of trans-31a, trans-35a, trans-35b, trans-36e, and trans-38 are determined and analyzed. Chapter 4 describes an NMR study of the reactivity of Grubbs' first and second generation metathesis catalysts with alkene-containing pyridines and rhenium complexes. 5 + – Sequential treatment of (R)-(η -C5H5)Re(NO)(PPh3)(CH3) ((R)-40) with Ph3C PF6 and 5 CH2=CHCH2MgBr (1.0 M in diethyl ether) affords the butenyl complex (R)-(η -

C5H5)Re(NO)(PPh3)(CH2CH2CH=CH2) ((R)-45, 50% after recrystallization). Analogous

+ – treatment of (R)-40 with Ph3C PF6 and CH2=CHCH2CH2MgBr (0.5 M in THF) gives 5 the pentenyl rhenium complex (R)-(η -C5H5)Re(NO)(PPh3)(CH2CH2CH2CH=CH2) ((R)- 46, 45% after column chromatography). Equimolar quantities of the alkene-containing rhenium complexes (R)-43, (R)-45, and (R)-46, and alkene-containing pyridines 22a, 25b, and 29g are combined with 13 or Ru(=CHPh)(H2IMes)(PCy3)(Cl)2. The reactions are monitored by low temperature NMR. The reaction of (R)-45 (2 equiv) with 13 yields (η5-

C5H5)Re(NO)(PPh3)(CH2)2(CH=)Ru(PCy3)2(Cl)2 (49%) in ≥ 90% purity, as assayed by 31P{1H} NMR. The crystal structure of (R)-46 is determined and analyzed.

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LIST OF FIGURES

Figure 1.1. Alkene metathesis catalysts. Figure 1.2. Examples of new generation of alkene metathesis catalysts. Figure 2.1. First examples of alkene metathesis catalysts. Figure 2.2. Grubbs' first generation catalyst. Figure 2.3. Grubbs' second generation catalyst. Figure 2.4. Hoveyda's first generation catalyst. Figure 2.5. Hoveyda's second generation catalyst. Figure 2.6. Variants of Hoveyda's second generation catalyst. Figure 2.7. Ligands in Hoveyda's second generation catalyst. Figure 2.8. FAB-MS (experiment 1). Figure 2.9. FAB-MS (experiment 2a). Figure 2.10. FAB-MS (experiment 3). Figure 2.11. FAB-MS (experiment 4). Figure 2.12. FAB-MS experiment 5a (left) and 5b (right). Figure 2.13. MALDI-MS experiments. Figure 2.14. ESI-MS experiment 1 (left) and experiment 2 (right). Figure 2.15. Supported variants of Hoveyda's second generation catalyst. Figure 2.16. Partial FAB-MS for experiment 1.

Figure 2.17. Deconvolution data for experiment 1. Figure 2.18. Partial FAB-MS for experiment 2a (educt 16). Figure 2.19. Deconvolution data for experiment 2a (educt 16), 2b (educt 17), and 2c (educt 18) (0.1 M, 1.5 mol% catalyst loading, rt). Figure 2.20. Partial FAB-MS for experiment 3. Figure 2.21. Deconvolution data for experiment 3. Figure 2.22. Deconvolution data for experiment 4 (0.1 M, 1.5 mol% catalyst loading, xvii

educt 16, rt). Figure 2.23. Rate profile for the educts 16, 17, and 18 (0.1 M, 1.5 mol% catalyst loading, rt). Figure 2.24. Rate profile for the educt 17 (0.1 M, 1.5 mol% catalyst loading, T = 2 °C). Figure 2.25. Deconvolution data after 10 min in presence (5a) and in absence (5b) of the educt 17 (0.1 M, 1.5 mol% catalyst loading, T = 2 °C). Figure 2.26. Rate profile for the educt 17 (0.01 M, 1.0 mol% catalyst loading, rt).

Figure 2.27. Theoretical (bottom) and experimental (top) isotope envelopes of 15-d0. Figure 3.1. Model of rope-skipping rotor. Figure 3.2. Representative cyclophanes. Figure 3.3. Ginsburg's rope-skipping rotor. Figure 3.4. Helder's rope-skipping rotor. Figure 3.5. Molecular turnstiles. Figure 3.6. Garcia-Garibay's molecular rotors. Figure 3.7. Gladysz-type gyroscope-like complexes. Figure 3.8. Partial 1H NMR spectra of 22a (bottom) and trans-30 (top). Figure 3.9. Selected enantiotopic and diastereotopic groups in trans-30. Figure 3.10. Partial 1H NMR spectra of 22a (bottom) and trans-31a (top). Figure 3.11. Selected enantiotopic and homotopic groups in trans-31a. Figure 3.12. Partial 1H NMR spectra of trans-31b (bottom) trans-31b after RCM

(middle), and trans-35b (top). Figure 3.13. Partial 1H NMR spectra of trans-32e (bottom) trans-32e after RCM (middle), and trans-36e (top). Figure 3.14. Thermal ellipsoid plots (50% probability) of trans-31a; view along Cl1-Pt- Cl2 axis (top); view along N1-Pt-N2 axis (middle); view from above the coordination plane (bottom). Figure 3.15. Thermal ellipsoid plots (50% probability) of trans-35a; view along Cl1-Pt- xviii

Cl2 axis (top); view along N1-Pt-N2 axis (middle); view from above the coordination plane (bottom). Figure 3.16. Thermal ellipsoid plots (50% probability) of trans-35b; view along Cl1-Pt- Cl2 axis (top); view along N1-Pt-N2 axis (middle); view from above the coordination plane (bottom). The three disordered atoms are depicted in their dominant conformation. Figure 3.17. Thermal ellipsoid plots (50% probability) of trans-36e; view along Cl1-Pt- Cl2 axis (top); view along N1-Pt-N2 axis (middle); view from above the coordination plane (bottom). The disordered atoms are depicted in their dominant conformation. Figure 3.18. Thermal ellipsoid plots (50% probability) of trans-38; view along Cl1-Pd- Cl2 axis (top); view along N1-Pd-N2 axis (middle); view from above the coordination plane (bottom). Figure 3.19. Representative space filling model for trans-31a. Figure 3.20. Representative space filling model for trans-35a. Figure 3.21. Representative space filling model for trans-35b. Figure 3.22. Representative space filling model for trans-36e. Figure 3.23. Representative space filling model for trans-38. Figure 3.24. Example of calculation summarized in Table 3.16 using trans-35b; vdW = van der Waals.

Figure 3.25. Packing diagram for trans-31a with (left) and without (right) spokes. Figure 3.26. Packing diagram for trans-35a with (left) and without (right) spokes. Figure 3.27. Packing diagram for trans-35b with (left) and without (right) spokes. Figure 3.28. Packing diagram for trans-36e with (left) and without (right) spokes. Figure 3.29. Packing diagram for trans-38 with (left) and without (right) spokes. Figure 3.30. Scheme of contact-modulated CMR with two conformations. Figure 4.1. Design concepts for thermally switchable metathesis catalyst precursors. xix

Figure 4.2. Representative N-ruthenium chelates following motif II. Figure 4.3. Representative N-ruthenium chelates following motif III. Figure 4.4. Sarkar's heterobimetallic precursors. Figure 4.5. Butenschön's heterobimetallic precursor. Figure 4.6. Examples of carbyne (XV) and carbide complexes (XVI, XVII, XVIII, and XIX). Figure 4.7. Alkene-containing pyridine studied in this chapter. Figure 4.8. Thermal ellipsoid plot (50% probability) of (R)-46. The disordered atom C4 is depicted in the predominant conformation. Figure 4.9. Partial 1H NMR spectra of VT experiment 1. Figure 4.10. Partial 31P{1H} NMR spectra of VT experiment 1. Figure 4.11. Partial 1H NMR spectra of VT experiment 2. Figure 4.12. Partial 31P{1H} NMR spectra of VT experiment 2. Figure 4.13. Partial 1H NMR spectra of VT experiment 3. Figure 4.14. Partial 31P{1H} NMR spectra of VT experiment 3. Figure 4.15. Partial 1H NMR spectra of VT experiment 4. Figure 4.16. Partial 31P{1H} NMR spectra of VT experiment 4. Figure 4.17. Partial 1H NMR spectra of VT experiment 5. Figure 4.18. Partial 31P{1H} NMR spectra of VT experiment 5. Figure 4.19. Partial 1H NMR spectra of VT experiment 6.

Figure 4.20. Partial 31P{1H} NMR spectra of VT experiment 6.

Figure 4.21. Partial 1H NMR spectra of VT experiment 3 (25 °C): styrene signals. Figure 4.22. Partial 1H NMR spectra of VT experiment 7. Figure 4.23. Partial 31P{1H} NMR spectra of VT experiment 7. Figure 4.24. Partial 1H NMR spectra of VT experiment 8. Figure 4.25. Partial 31P{1H} NMR spectra of VT experiment 8. Figure 4.26. Partial 1H NMR spectra of VT experiment 9. xx

Figure 4.27. Partial 31P{1H} NMR spectra of VT experiment 9. Figure 4.28. Partial 1H NMR spectra of VT experiment 10. Figure 4.29. Partial 31P{1H} NMR spectra of VT experiment 10. Figure 4.30. Partial 1H NMR spectra of VT experiment 11. Figure 4.31. Partial 31P{1H} NMR spectra of VT experiment 11. Figure 4.32. Partial 1H NMR spectra of VT experiment 12. Figure 4.33. Partial 31P{1H} NMR spectra of VT experiment 12.

Figure 4.34. Partial 1H NMR spectra of VT experiment 9 (25 °C): styrene signals. Figure 4.35. 1H NMR spectrum of 47 (top), and expanded sections (middle, bottom).

Figure 4.36. Examples of η1-allyl rhenium complexes. Figure 4.37. Types of "staggered" Re-C1 rotamers in allyl or alkyl complexes (η5-

C5H5)Re(NO)(PPh3)(CH2R). Figure 4.38. Possible C1-C2 conformations in η1-allyl rhenium complexes. Figure 4.39. Werner's ruthenium-carbyne complexes.

xxi

LIST OF SCHEMES

Scheme 1.1. Ion metathesis. Scheme 1.2. Alkene metathesis. Scheme 1.3. Types of alkene metathesis reactions. Scheme 1.4. Statistical distribution of CM products. Scheme 1.5. Two-step selective CM with alkene dimers. Scheme 1.6. CM in a metal coordination sphere. Scheme 1.7. CM in a metal coordination sphere. Scheme 1.8. Mechanism of ROMP reaction. Scheme 1.9. ROMP in a metal coordination sphere. Scheme 1.10. ROMP in a metal coordination sphere. Scheme 1.11. ROMP in a metal coordination sphere. Scheme 1.12. Reaction pathway in RCM. Scheme 1.13. RCM within a ligand. Scheme 1.14. Synthesis of platinum and rhodium complexes of singly trans-spanning diphosphines. Scheme 2.1. Chauvin and Hérisson catalytic cycle. Scheme 2.2. Mechanism of metathesis for Grubbs' first generation catalyst. Scheme 2.3. Proposed mechanism of Hoveyda's first generation catalyst.

Scheme 2.4. Operative scheme for the analysis of the boomerang mechanism.

Scheme 2.5. Synthesis of 1-d0.

Scheme 2.6. Synthesis of 1-d6.

Scheme 2.7. Synthesis of 2-d0.

Scheme 2.8. Synthesis of 7-d11. Scheme 2.9. Direct synthesis of 2,4,6-trimethylaniline.

Scheme 2.10. Synthesis of 2-d22. xxii

Scheme 2.11. Synthesis of 14-d0 and 14-d22.

Scheme 2.12. Synthesis of 15-d0 (top) and 15-d28 (bottom). Scheme 2.13. Hoveyda and Kingsbury crossover experiment. Scheme 3.1. Synthesis of Vögtle's rope-skipping rotor. Scheme 3.2. Previous data from Lambert. Scheme 3.3. Synthesis of 21. Scheme 3.4. Synthesis of 22a-d. Scheme 3.5. Synthesis of 25a,b. Scheme 3.6. Synthesis of 29a-g. Scheme 3.7. Synthesis of trans-30. Scheme 3.8. Synthesis of trans-31a,b. Scheme 3.9. Synthesis of trans-32a,c-g. Scheme 3.10. Synthesis of trans-33e. Scheme 3.11. Synthesis of trans-34. Scheme 3.12. Attempted RCM of trans-30. Scheme 3.13. Syntheses of trans-35a,b (top) and trans-36d-g (bottom). Scheme 3.14. Synthesis of trans-38. Scheme 3.15. Attempted substitution reactions with trans-31a. Scheme 3.16. Synthesis of trans-39c. Scheme 3.17. Reactivity of pincer-platinum complexes of 2,6 (bottom) and 3,5 (top)

disubstituted alkene-containing pyridines. Scheme 3.18. Atropisomerism in substituted pyridine complexes. Scheme 4.1. Synthesis of vinyl complex (R)-43. Scheme 4.2. Synthesis of (R)-45. Scheme 4.3. Synthesis of (R)-46. Scheme 4.4. Synthesis of 47 (top) and 48 (bottom). Scheme 4.5. Synthesis of 49 (top) and 50 (bottom). xxiii

Scheme 4.6. Synthesis of η1-allyl rhenium complexes. Scheme 4.7. Direct synthesis of square-planar monochloride ruthenium-carbyne complex. Scheme 4.8. Original objective: synthesis of XXIX. xxiv

LIST OF TABLES

Table 3.1. Selected 1H NMR [δ/ppm] and IR data [cm–1] for the alkene-containing pyridines.

Table 3.2. Selected 13C{1H} NMR data [δ/ppm] for the alkene-containing pyridines. Table 3.3. Alternative procedures for the synthesis of trans-30.

Table 3.4. Selected 1H NMR [δ/ppm] and IR data [cm–1] for the alkene-containing bis(pyridine) complexes.

Table 3.5. Selected 13C{1H} NMR data [δ/ppm] for the alkene-containing bis(pyridine) complexes. Table 3.6. Thermal stability data [ºC].

Table 3.7. Selected 1H NMR data [δ/ppm] for the gyroscope-like complexes. Table 3.8. Selected 13C{1H} NMR data [δ/ppm] for the gyroscope-like complexes. Table 3.9. Thermal stability data [ºC]. Table 3.10. Key bond lenghts [Å] and angles [°].

Table 3.11. 1H NMR coordination shifts [Δδ; δ/ppm] for the alkene-containing

bis(pyridine) complexes (CDCl3). Table 3.12. 1H NMR coordination shifts [Δδ; δ/ppm] for the gyroscope-like complexes

(CDCl3). Table 3.13. 13C{1H} NMR coordination shifts [Δδ; δ/ppm] for the alkene-containing

bis(pyridine) complexes (CDCl3). Table 3.14. 13C{1H} NMR coordination shifts [Δδ; δ/ppm] for the gyroscope-like

complexes (CDCl3). Table 3.15. Pt-Cl and Pt-N bond lengths [Å] in trans-31a and related pyridine complexes.

Table 3.16. Key distances [Å] involving rotator and stator atoms for the gyroscope-like complexes. xxv

Table 3.17. Angles [°] between sets of gyroscope-like complexes with parallel axes in the solid state. Table 4.1. Key bond lengths [Å] and angles [°] for (R)-46.

Table 4.2. Selected 1H NMR data [δ/ppm] at 25 ºC for experiments 1, 3, and 5. Table 4.3. Selected 31P{1H} NMR data [δ/ppm] at 25 ºC for experiments 1, 3, and 5. Table 4.4. Selected 1H NMR data [δ/ppm] at 35 ºC for experiments 2, 4, and 6. Table 4.5. Selected 31P{1H} NMR data [δ/ppm] at 35 ºC for experiments 2, 4, and 6. Table 4.6. Selected 1H NMR data [δ/ppm] at 25 ºC for experiments 9 and 11. Table 4.7. Selected 31P{1H} NMR data [δ/ppm] at 25 ºC for experiments 9 and 11. Table 4.8. Selected 1H NMR data [δ/ppm] at 35 ºC for experiments 10 and 12. Table 4.9. Selected 31P{1H} NMR data [δ/ppm] at 35 ºC for experiments 10 and 12. Table 4.10. Selected 1H NMR data [δ/ppm] for 47, 48, 49, and 50. Table 4.11. Selected 31P{1H} NMR data [δ/ppm] for 47, 48, 49, and 50. Table 5.1. Summary of crystallographic data for trans-31a, trans-35a, trans-35b.

Table 5.2. Summary of crystallographic data for trans-36e·2CHCl3, trans-38, (R)-46.

xxvi

General Introduction

Aim of the chapter

This chapter provides a brief review on the alkene metathesis reaction. A major aim of this compact overview is to exemplify applications of alkene metathesis to transition- metal-containing substrates.

1.1. General concepts

The word metathesis derives from the Greek µεταθεσιζ, µετα (meta = change) and θεσιζ (tithemi = place), and means transposition. A general example of metathesis would be a double decomposition and reorganization of two compounds. For example, ions might exchange in order to produce new and more stable ion pairs (Scheme 1.1).

A+ B + C+ D A+ D + C+ B

Scheme 1.1. Ion metathesis.

The same concept can be applied to alkene metathesis, as shown in Scheme 1.2. The strong bond in the alkene, the C=C double bond, is broken during the reaction and the RCH= fragments are exchanged between the alkenes.

R1 R2 R1 R2 catalyst

+ +

R3 R4 R3 R4

Scheme 1.2. Alkene metathesis.

At the beginning, industrial use of metathesis was confined exclusively to simple alkenes.1 In the last years, with the advent of new catalytic systems, metathesis has become 2 1. General Introduction ______

one of the most powerful chemical carbon-carbon bond construction methods. Its applications cover widespread fields, from organic chemistry to polymer, medicinal, and materials chemistry.2-4 Metathesis can be categorized in three types: cross metathesis in which two different alkenes undergo an intermolecular transformation to produce a new olefinic product (Scheme 1.3 - eqn. 1); ring opening metathesis polymerization, a procedure that involves the opening of cyclic alkenes to give polymeric compounds (Scheme 1.3 - eqn. 2); ring closing metathesis, which enables the formation of cyclic compounds (Scheme 1.3 - eqn. 3).

+ (1) R1 R2

(2)

(3)

Scheme 1.3. Types of alkene metathesis reactions.

Most metathesis reactions require only a catalyst or catalyst system and no other additional reagent. Furthermore, most are energetically neutral and generally reversible. A suitable catalytic system can attain equilibrium rapidly, also with high substrate/catalyst ratios. The development of alkene metathesis is dependent on the discovery of efficient metal-carbene catalysts. Grubbs' catalysts (I and II), Schrock's catalysts (III), and Hoveyda's catalysts (IV and V) are some of the most representative examples (Figure 1.1).2,4

N N N N PCy3 PCy3 N Cl Cl Cl Cl Ru Ru Mo Ph Ru Ru Cl Cl R O Cl Cl O R O O PCy3 PCy3

I II III IV V

Figure 1.1. Alkene metathesis catalysts.

1. General Introduction 3 ______

1.2. Applications of alkene metathesis

1.2.1. Cross metathesis (CM). Cross metathesis has found interesting application in industry such as in the Shell Higher Olefin and Phillips Olefin processes.5,6 In case of terminal alkenes the by-product of CM is the volatile ethylene, which in a non-closed system will shift the equilibrium towards the products. In general, for every CM of terminal alkenes VI and VII, it is possible to get not only the product IX but also the homodimers VIII and X as outlined in Scheme 1.4.

R2 VIII

R2 + R2 R1

R1 IX VI VII

R1 X

Scheme 1.4. Statistical distribution of CM products.

The product selectivity and the efficiency are central issues in CM. The principal objective is to get high yields of the cross product simplifying the total number of species through the minimization of the competitive dimerization. Some strategies have been demonstrated to be effective. One of these is summarized in Scheme 1.5. The terminal alkene XI is first homodimerized in presence of catalyst II. Subsequently, the product XII in excess is treated with a second terminal alkene XIII to give the cross product XIV.

II R1 R2 2 R1 R1 R1

XI XII R2 XIV XIII

Scheme 1.5. Two-step selective CM with alkene dimers.

This strategy ensures high yields and selectivity in presence of various functional 4 1. General Introduction ______

groups.7 It was argued that the excess of homodimer XII could favor the preferential formation of a more stable ruthenium alkylidene rather than a methylidene intermediate. The high reactivity of II and V towards conjugated electron withdrawing alkenes opened interesting new scenarios for CM reactions. Their utilization in metathesis transformations ensures high cross-product/dimer ratios and also an excellent E/Z selectivity.8 Lovely and co-workers synthesized the complexes XVII as summarized in Scheme 1.6.9 This represented one of the first examples of CM in a metal coordination sphere. A complete consumption of the secondary alcohol was accomplished with high catalyst loading (20%). The products were isolated in good yields (with Z = Ph, 56%, E:Z 17:1).

OH OH

+ I Fe Z Fe

XV XVI XVII

Z = Ph, CH2OAc CO2Me, CH2SiMe3

Scheme 1.6. CM in a metal coordination sphere.

As outlined in Scheme 1.7, Kawai and co-workers synthesized the heterodimer XXI in high yield using a Schrock-type catalyst, with very small amounts of the respective homodimers XX and XXII.10 Low temperatures and the utilization of benzene and chloroform as solvents favored the formation of the heterodimer.

Ar XX

Fe Fe + Ar

XXI XVIII XIX

XXII

Scheme 1.7. CM in a metal coordination sphere. 1. General Introduction 5 ______

1.2.2. Ring opening metathesis polymerization (ROMP). Two aspects characterize the mechanism of the ROMP reaction. First, the catalyst and cyclic alkene form a metallabicyclic intermediate XXIII as shown in Scheme 1.8. Subsequent productive cleavage of XXIII generates a "new" acyclic alkene in which the catalyst is a part of the growing polymer chain XXIV.11

R R M M M n R

XXIII XXIV

Scheme 1.8. Mechanism of ROMP reaction.

The relief of ring strain is the second important aspect and represents the driving force. Therefore, the reaction is generally irreversible. In a typical ROMP reaction, polymers with very narrow ranges of molecular weights are produced, unlike standard polymerization methods such as free radical polymerization, and polydispersities are typically in a range of 1.03 to 1.10.12 The utilization of ROMP with alkenes in metal coordination spheres enabled the synthesis of processable organometallic polymers with opto-electrical properties.13 Ferrocene has represented an attractive moiety for incorporation into the backbone of organic polymers. Thus, Tilley and co-workers described the polymerization of the ansa-(vinyl)ferrocene monomer XXV as depicted in Scheme 1.9. The homopolymer XXVI is not soluble in organic solvents such as toluene, 14 CH2Cl2, DMSO, and THF.

III Ph Fe Fe n PhCHO

PhMe2C XXV XXVI

Scheme 1.9. ROMP in a metal coordination sphere.

The constant problem of solubility was solved by Lee and co-workers by introducing a t-butyl group in the [4]ferrocenophane XXVII (Scheme 1.10).15 6 1. General Introduction ______

III Fe Fe

n XXVII XXVIII

Scheme 1.10. ROMP in a metal coordination sphere.

Grubbs, Lewis and co-workers reported further similar examples of polymers derived from ferrocenophanes (XXX and XXXII) as summarized in Scheme 1.11.16

III Fe Fe

n XXIX XXX

OCH OCH3 3

III Fe Fe

n XXXI XXXII

Scheme 1.11. ROMP in a metal coordination sphere.

1.2.3. Ring closing metathesis (RCM). The catalytic cycle in RCM begins with an initiation phase, with generation of the active complex XXXIII shown in Scheme 1.12. This species is equivalent to XXIV in Scheme 1.8.

(Closure)

XXXIV

M R (Oligomerization) + M

XXXIII Metal fragment (Decomposition)

Scheme 1.12. Reaction pathway in RCM.

Productive RCM requires that XXXIII ring close to give a relatively strain-free cyclic alkene (XXXIV) although thermodynamic limitations can be circumvented by removing the ethylene co-product. In any RCM, oligomerization represents a competing 1. General Introduction 7 ______

reaction. Increasing the temperature and decreasing the concentration of the substrate can limit the competitive oligomerization. On the other side, the same conditions favor catalyst decomposition, and thus require the utilization of high catalyst loadings. Over the last decade, RCM has become an important tool for the synthesis of metal complexes with uncoordinated alkenes.17 In the last years, the Gladysz group has systematically studied alkene metatheses of metal-containing substrates. Several types of cyclizations were investigated in the context of coordinatively saturated and unsaturated complexes. The first examples involved RCM of complexes with ligands that contained two terminal vinyl groups.18 One example is shown in Scheme 1.13.

TfO TfO

I Re Re ON PPh 3 ON PPh3 S S

XXXV XXXVI

Scheme 1.13. RCM within a ligand.

Subsequent applications led to more challenging macrocycles with trans-spanning ligands. As shown in Scheme 1.14, singly trans-spanning diphosphine complexes were synthesized by RCM through the catalyst I.18

F 5 F5 F5

H2 (1.0 atm), I 10% Pd/C Ph2P Pt PPh2 Ph2P Pt PPh2 Ph2P Pt PPh2 Cl Cl Cl

XXXVII XXXVIII XXXIX

H2 (4.9 atm), CO CO CO I RhCl(PPh3)3 Ph2P Rh PPh2 Ph2P Rh PPh2 Ph2P Rh PPh2 Cl Cl Cl

XL XLI XLII

Scheme 1.14. Synthesis of platinum and rhodium complexes of singly trans-spanning diphosphines. 8 1. General Introduction ______

Later, Gladysz and co-workers extended Scheme 1.14 to complexes of doubly and triply trans-spanning diphosphines. These results will be described in Chapter 3.

1.2.4. Future perspectives of alkene metathesis. Several facets of alkene metathesis still remain unexplored and unresolved. The synthesis of new and more robust catalysts represents a crucial aspect for future study. In particular, the applicability of the method in industrial processes is strictly correlated with a drastic decreasing of the catalyst loadings. In this direction, the discovery of more active catalysts and the detailed understanding of the decomposition pathways are fundamental.19 As shown in Figure 1.2, new classes of alkene metathesis catalysts are emerging. A notable example is XLVI, which enables catalysis in water.20 Precursors such as XLVII show unique activity for the synthesis of cyclic polymers.21

OPEG-Me

R' N N R' R' N N R' R' N N R' N N R'

Cl Cl Cl Cl Ru Ru Ru Ru Cl Cl Cl Cl O O NO2 O PCy3 Ph

XLIII XLIV XLV XLVI

Figure 1.2. Examples of new generation of alkene metathesis catalysts.

Alkene metathesis will continue to be a powerful method for the synthesis of biologically active molecules. The necessity to isolate extremely pure compounds for clinical applications brings the need for the catalyst to be easily recovered and re-used. Catalysts bound on polymeric supports were developed to address these problems. The support can minimize the trace metal impurities and, at the same time, improve catalyst recovery.22

1.3. Aims of this work

1. General Introduction 9 ______

This thesis covers several aspects of alkene metathesis. In Chapter 2, a mass spectrometric investigation of the mechanism of a Hoveyda-type catalyst is outlined. In Chapter 3, metal complexes containing two trans pyridines, each with two terminal alkenes, are synthesized. Subsequent RCM and hydrogenation affords, in appropriate cases, new classes of molecular gyroscopes with doubly trans-spanning bis(pyridine) ligands. Their physical and chemical properties are investigated. In Chapter 4, an NMR study of the reactivity of Grubbs-type catalysts with alkene-containing pyridines and rhenium complexes is described. 10 1. General Introduction ______

1.4. References and notes

(1) Banks, R. L. CHEMTECH 1986, 16, 112. (2) For books: (a) Olefin Metathesis and Metathesis Polymerization, Ivin, R. H. and Mol, J. C. Eds.; Accademic Press, New York, 1997. (b) Alkene Metathesis in Organic Chemistry, Fürstner, A. Ed.; Springer, Berlin, 1998. (c) Handbook of Metathesis, Grubbs, R. H. Ed.; Wiley-VCH, Weinheim, 2003, vols. 1-3: Catalyst Development (vol. 1); Applications in Organic Synthesis (vol. 2); Applications in Polymer Synthesis (vol. 3). (3) For reviews see: (a) Fürstner, A. Angew. Chem., Int. Ed. 2000, 39, 3012. (b) Grubbs, R. H. Tetrahedron 2004, 60, 7117. (c) Trnka, T. T.; Grubbs, R. H. Acc. Chem. Res. 2001, 34, 18. (d) Chang, S.; Grubbs, R. H. Tetrahedron 1998, 54, 4413. (e) Schrock, R. R. Chem. Rev. 2002, 102, 145. (f) Schrock, R. R. in Topics in Organometallic Chemistry. Alkene Metathesis in Organic Synthesis (Ed.: A. Fürstner), Springer, Berlin, 1998, vol. 1, pp 1-36. (g) Connor, S. J.; Blechert, S. Angew. Chem., Int. Ed. 2003, 42, 1900. (h) Schuster, M.; Blechert, S. Angew. Chem., Int. Ed. Engl. 1997, 36, 2036. (i) Buchmeiser, M. R. Chem. Rev. 2000, 100, 1565. (l) Armstrong, S. K. J. Chem. Soc., Perkin Trans. 1 1998, 371. (4) Hoveyda, A. H.; Schrock, R. R. Chem. Eur. J. 2001, 7, 945. (5) (a) Freitas, E. R.; Gum, C. R. Chem. Eng. Prog. 1979, 75, 73. (b) Shell International Chemical Company, SHOP-Linear Alpha Olefins (Company publication),

1982. (6) Phillips Petroleum Company, Hydrocarbon Process. 1967, 46, 232 (7) (a) Blackwell, H. E.; O'Leary, D. J.; Washenfelder, R. A.; Miura, K.; Grubbs, R. H. Tetrahedron Lett. 1999, 40, 1091. (b) Goldberg, S. D.; Grubbs, R. H. Angew. Chem. 2002, 114, 835; Angew. Chem., Int. Ed. 2002, 41, 807. (8) For examples of applications see: (a) Chatterjee, A. K.; Grubbs, R. H. Angew. Chem. 2002, 114, 3304; Angew. Chem., Int. Ed. 2002, 41, 3171. (b) Gessler, S.; Randl, S.; 1. General Introduction 11 ______

Wakamatsu, H.; Blechert, S. Synlett 2001, 430. (c) Cavazzini, M.; Montanari, F.; Pozzi, G.; Quici, S. J. Fluorine Chem. 1999, 94, 183. (9) Seshadri, H.; Lovely, C. J. Org. Lett. 2000, 2, 327. (10) (a) Yasuda, T.; Abe, J.; Iyoda, T.; Kawai, T. Chem. Lett. 2001, 812. (b) Yasuda, T.; Abe, J.; Iyoda, T.; Kawai, T. Adv. Synth. Catal. 2002, 344, 705. (11) Tumas, W.; Grubbs, R. H. Science 1989, 243, 907. (12) (a) Gilliom, L. R.; Grubbs, R. H. J. Am. Chem. Soc. 1986, 108, 733. (b) Wallace, K. C.; Schrock, R. R. Macromolecules 1987, 20, 448. (c) Wallace, K. C.; Schrock, R. R.; Feldman, J.; Cannizzo, L. F.; Grubbs, R. H. Macromolecules 1987, 20, 1169. (13) Marks, T. J. Science 1985, 227, 881. (14) Buretea, M. A.; Tilley, T. D. Organometallics 1997, 16, 1507. (15) Heo, R. W.; Somoza, F. B.; Lee, T. R. J. Am. Chem. Soc. 1998, 120, 1621. (16) Stanton, C. E.; Lee, T. R.; Pudelski, J. K.; Callstrom, M. R.; Erickson, M. S.; McLaughlin, M. L.; Lewis, N. S.; Grubbs, R. H. Macromolecules 1989, 22, 3205. (17) For examples of applications see: (a) Paley, R. S.; Estroff, L. A.; Gauget, J.- M.; Hunt, D. K.; Newlin, R. C. Org. Lett. 1999, 18, 955. (b) Sültemeyer, J.; Dötz, K. H.; Hupfer, H.; Nieger, M. J. Organomet. Chem. 2000, 606, 26. (c) Licandro, E.; Maiorana, S.; Vandoni, B.; Perdicchia, D.; Paravidino, P.; Baldoli, C. Synlett 2001, 757. (d) Green, J. R. Synlett 2001, 353. (e) Burlison, J. A.; Gray, J. M.; Young, D. G. J. Tetrahedron Lett. 2001,

42, 5363. (f) Young, D. G. J.; Burlison, J. A.; Peters, U. J. Org. Chem. 2003, 68, 3494. (g) Maity, B. C.; Swamy, V. M.; Sarkar, A. Tetrahedron Lett. 2001, 42, 4373. (h) Ng, P. L.; Lambert, J. N. Synlett 1999, 1749. (18) (a) Martín-Alvarez, J. M.; Hampel, F.; Arif, A. M.; Gladysz, J. A. Organometallics 1999, 18, 955. (b) Bauer, E. B.; Ruwwe, J.; Martín-Alvarez, J. M.; Peters, T. B.; Bohling, J. C.; Hampel, F.; Szafert, S.; Lis, T.; Gladysz, J. A. Chem. Commun. 2000, 2261. (c) Ruwwe, J.; Martín-Alvarez, J. M.; Horn, C. R.; Bauer, E. B.; Szafert, S.; Lis, T.; 12 1. General Introduction ______

Hampel, F.; Cagle, P. C.; Gladysz, J. A. Chem. Eur. J. 2001, 7, 2261. (19) Hong, S. H.; Wenzel, A. G.; Salguero, T. T.; Day, M. W.; Grubbs, R. H. J. Am. Chem. Soc. 2007, 127, 7961. (20) Hong, S. H.; Grubbs, R. H. J. Am. Chem. Soc. 2006, 128, 3508. (21) Bielawski, C. W.; Benitez, D.; Grubbs, R. H. Science 2006, 297, 2041. (22) Chiral Catalyst Immobilization and Recycling, De Vos, D. E.; Vankelecom, I. F. J.; Jacobs, P. A. Eds.; VCH-Wiley, Weinheim, 2000. 2

Mechanistic study on the activity of a Hoveyda-type catalyst

Aim of the chapter

The first part of the chapter gives an overview about alkene metathesis catalysts. The possibility of a boomerang mechanism involving the 2-isopropoxystyrene ligand in Hoveyda's second generation catalyst for a typical RCM reaction was probed by labeling studies and mass spectrometry.

2.1. Introduction

2.1.1. Chauvin and Hérisson alkene metathesis mechanism. Ziegler-type systems MoO3/Al2O3/LiAlH4 and MoO3/Al2O3/Et3Al can be considered the first examples of catalysts effective in alkene metathesis processes.1 Calderon and co-workers 2 provided a similar recipe consisting of a mixture of WCl4/EtOH/EtAlCl2 in 1:4:1 ratio. The utilization of multicomponent systems involving early transition metal precursors reflected a pure trial and error approach, and was not based upon any mechanistic insight or evidence regarding the active species. Chauvin and Hérisson were the first to advance the theory of the involvement of metal alkylidenes, publishing a mechanistic proposition in 1971.3 Studies on the alkylidene species migration in metathesis reactions,4 and the discovery of catalysts with metal double bonds including under appropriate conditions Fisher carbenes such as 5 W[=C(OMe)Me](CO)5, supported their model. 14 2. Mechanistic study on the activity of a Hoveyda-type catalyst ______

Chauvin and Hérisson proposed that alkene metathesis involves the interconversion of an alkene and a metal alkylidene. The process occurs via a metallacyclobutane through [2+2] cycloadditions and cycloreversions as described in Scheme 2.1. The metal carbene species I reacts with the alkene, forming a metallocyclobutane intermediate II. This intermediate then cleaves, yielding ethylene and a new metal alkylidene III. The ethylene formed contains one methylene from the catalyst and one from the alkene. The metal alkylidene III reacts with another molecule of alkene to yield another metallocyclobutane intermediate IV. Finally, on decomposition in the forward direction, this intermediate yields the alkene S and the metal carbene species I that is ready to enter another catalytic cycle.

R1 M R1 I R1 S M M

R1 R1 R1 IV II

R1 M

R1 III

Scheme 2.1. Chauvin and Hérisson catalytic cycle.

The discovery of Schrock carbenes,6 and the fundamental contributions of Casey,7 Katz,8 Grubbs9 and co-workers can be counted as support of the reliability of the Chauvin and Hérisson model.

2.1.2. Background of ruthenium technology. The studies of Chauvin and Hérisson influenced the catalyst development in terms of design rationale and understanding of the activity. New homogeneous early transition metal precursors were synthesized. Osborn (V),10 Basset (VI),11 and Schrock-type catalysts (VII-a, VII-b, and VIII)12 were among the most interesting examples (Figure 2.1).

2. Mechanistic study on the activity of a Hoveyda-type catalyst 15 ______

Br O O ArO Cl N W W W O O M Ph O Br O O OEt2 O F3C F3C CF3 CF3

V VI VII-a (M = Mo) VIII VII-b (M = W)

Figure 2.1. First examples of alkene metathesis catalysts.

Schrock-type catalysts stand prominent in this class of complexes. They exhibit high activity, leading to effectiveness in different types of alkene metathesis reactions.13 On the other side, the most relevant drawback is the oxophilicity of the metal center, which translates into an extremely high sensitivity to oxygen and moisture. Therefore, their utilization is limited by the need for an inert atmosphere and absolutely purified, dried, and degassed solvents and reagents. Ruthenium allowed the limits of the early transition metal precursors to be overcome. Such systems react preferentially with carbon-carbon double bonds rather than other functional groups as alcohols, aldehydes and other polar or protic groups, permitting the utilization of the catalyst in less exacting conditions. The complex IX represented the first example of an active ruthenium alkylidene precursor.14

PPh3 Cl Ru Ph Cl

PPh3 Ph IX

The results achieved with IX were very stimulating in terms of initiation behavior and functional group tolerance. However, the utilization remained limited to the ROMP of highly strained monomers. A systematic investigation on the ligand properties extended the applicability of ruthenium catalysts. In particular, the benzylidene precursor X reported in Figure 2.2, in which the easily initiated benzylidene moiety combined with the presence of bulky and electron donating PCy3 ligand, served as starting point for the development of all ruthenium 16 2. Mechanistic study on the activity of a Hoveyda-type catalyst ______

technology.15

PCy3 Cl Ru Cl

PCy3

Figure 2.2. Grubbs' first generation catalyst.

2.1.3. Grubbs-type catalysts. The commercial availability of X facilitated its utilization in a wide variety of fields, from the synthesis of pharmaceutical intermediates to the production of polymers.16 The understanding of the reaction pathway again became fundamental for further developments.17 As outlined in Scheme 2.2, two possible pathways were proposed: a dissociative and an associative one; experimental evidences favored the former.

- PCy3

PCy3 PCy3 PCy3 PCy3 + RCH=CH2 Ph Cl Cl Cl Ph Cl Ru Ru Ru Ru X-c Cl Ph Cl Ph Cl Cl PCy3 + PCy3 R R - RCH=CH R 2 RCH=CH2 X X-a X-b

RCH=CH2 CH2=CH2 Ph PCy3 PCy3 Cl Cl Ru Ru Cl Cl R R R X-g X-d

PCy3 PCy3 Cl Cl Ru Ru Cl Cl

R R R RCH=CH2 R X-f X-e R S

Scheme 2.2. Mechanism of metathesis for Grubbs' first generation catalyst.

Catalyst X enters the cycle upon loss of one of the phosphine ligands. The π-acidic alkene coordinates to the vacant site of the 14-electron species forming species X-a, which undergoes a [2+2] cycloaddition to produce metallocyclobutane X-b. A productive step 2. Mechanistic study on the activity of a Hoveyda-type catalyst 17 ______

gives the species X-c, which is followed by the expulsion of styrene and coordination of a second alkene to give the species X-d. This transforms to the metallocyclobutane X-e when the alkene is coordinated with a proper geometry. Cycloreversion and decoordination give the cross metathesis product S from X-e. The carbene species X-f with the coordinated alkene follows a similar way to generate via X-g the second metathesis product – ethylene. With the removal of ethylene, the reaction becomes irreversible and shifts towards the propagating species X-d; the catalytic cycle is completed and can start again. The benzylidene precursor XI represented a decisive breakthrough in the research of more active catalysts.18

N N

Cl Ru Cl

PCy3

N-heterocyclic carbene ligands, introduced by Hermann and co-workers, are stronger σ donors and less labile in comparison with phosphines.19 These ligands could enable the dissociation of the phosphine and stabilize the electron-deficient intermediates as result of its steric and electron-donating properties. In particular the catalyst XII, in which the N-heterocyclic carbene is characterized by a saturated backbone, has activity comparable with the early transition metal precursors (Figure 2.3).20

N N

Cl Ru Cl

PCy3

XII

Figure 2.3. Grubbs' second generation catalyst.

2.1.4. Hoveyda-type catalysts. The discovery of XIII in Figure 2.4 is a serendipitous result of Hoveyda and co-workers in the course of studies of molybdenum- 18 2. Mechanistic study on the activity of a Hoveyda-type catalyst ______

and ruthenium-catalyzed conversions of cycloalkenyl ethers to 2-substituted chromene.21 Catalyst XIII proved to have a unique stability, as it can be recovered after the reaction through simple column chromatography and reused in many catalytic cycles without apparent loss of activity.21

PCy3 Cl Ru Cl O

XIII

Figure 2.4. Hoveyda's first generation catalyst.

However, its application was limited to educts containing terminal alkenes. In analogy with the development of Grubbs-type catalysts, the introduction of the N- heterocyclic carbene ligand shown in XIV improved the reactivity without affecting the recoverability of the catalyst (Figure 2.5).22

N N

Cl Ru Cl O

XIV

Figure 2.5. Hoveyda's second generation catalyst.

As outlined in Figure 2.6, a large family of derivatives of XIV was developed by Blechert (supported variant XV), Grela (XVI), Curran (fluorous variant XVII) and others.23

N N N N N N

Cl Cl Cl Ru Ru Ru Cl Cl Cl

O O NO2 O (CH2)2C8F17

XV XVI XVII

Figure 2.6. Variants of Hoveyda's second generation catalyst.

2. Mechanistic study on the activity of a Hoveyda-type catalyst 19 ______

Hoveyda proposed a mechanistic scenario in which the initiation step that gives XIII-a results in the release of styrene XVIII (Scheme 2.3). The conversion of XIII-a to the product S, through the metallocyclobutane intermediate XIII-b, releases the Ru- methylene species XIII-c. In presence of an excess of alkene, the species XIII-c enters the propagation cycle to give the product S and, at the same time, release of ethylene. Importantly, the styrene XVIII can encounter XIII-c, when all of the educt has been consumed, leading to XIII again. The last step would explain the recovery of the catalyst, and is commonly termed a boomerang step.21

A. Initiation

R PCy PCy3 PCy3 3 Cl Cl Cl Ru Ru O Ru Cl Cl Cl R O R S R

O XIII XIII-a XIII-b XVIII XIII-c PCy3 Cl Ru Cl C. Termination

R R

PCy3 Cl Ru Cl B. Propagation R

Scheme 2.3. Proposed mechanism of Hoveyda's first generation catalyst.

2.2. Project design

The project is designed with the aim to investigate the mechanism of Hoveyda's second generation catalyst with a classical double-labeling crossover experiment as outlined in Scheme 2.4. First, the natural abundance and labeled catalysts XIV-d0 and

XIV-d28 were synthesized. On the basis of the proposed mechanism, the first question to address becomes whether the XIV-d6 and XIV-d22 crossover products are detected during or after the reaction. Naturally, it is necessary to establish the absence of an independent reaction, as well as other controls. In one limit, the absence of XIV-d6 and XIV-d22 20 2. Mechanistic study on the activity of a Hoveyda-type catalyst ______

crossover products indicates there is no crossover, which eliminates a boomerang mechanism. In another limit, there is a statistical amount of crossover, which when combined with control experiments can provide strong evidence for a boomerang mechanism. Finally, there are also intermediate scenarios, where the amount of crossover varies during the reaction.

D CD3 D3C D N N D3C N N CD3

Cl D CD3 D3C D Ru Cl Ru Cl Cl O O R R R R XIV-d0 XIV-d22

boomerang mechanism?

Educt Product

D CD3 D3C D N N D3C N N CD3 Cl D CD3 D3C D Ru Cl Ru Cl Cl O O D3C D3C CD3 CD3

XIV-d28 XIV-d6

Scheme 2.4. Operative scheme for the analysis of the boomerang mechanism.

2.3. Results

2.3.1. Syntheses of Hoveyda's second generation catalysts. The synthesis of natural abundance Hoveyda's second generation catalyst was accomplished from ligands 1- d0 and 2-d0 (Figure 2.7).

N N O H

1-d0 2-d0

Figure 2.7. Ligands in Hoveyda's second generation catalyst.

As outlined in Scheme 2.5, the 2-isoproxystyrene 1-d0 was obtained through O- alkylation of salicylaldehyde starting from 2-bromopropane 3-d0. Cs2CO3 was used as a 2. Mechanistic study on the activity of a Hoveyda-type catalyst 21 ______

base. The reaction was carried out under mild conditions and was completed in a short time

(5 h). The aldehyde 4-d0 was isolated by column chromatography in good yield (70%).

Subsequently, the Wittig olefination of 4-d0 was conducted in THF using t-BuOK to deprotonate the phosphonium salt.

Br O t-BuOK O O + Cs2CO3 Ph3PCH3 Br O

3-d0 4-d0 1-d0, overall yield: 35%

Scheme 2.5. Synthesis of 1-d0.

As shown in Scheme 2.6, the synthesis of the corresponding labeled 2- isopropoxystyrene 1-d6 was carried out starting from commercial (CD3)2CO (5-d6).

Reduction of 5-d6 was effected with NaBH4. The alcohol 6-d6 was isolated by distillation

(53%). Subsequent treatment with HBr and distillation gave the 2-bromopropane 3-d6 in good yield (63%). From 3-d6, the procedure was identical to that for 1-d0.

O OH Br

D3C CD3 D3C CD3 D3C CD3 NaBH4 HBr

5-d6 6-d6 3-d6

Cs2CO3 HO

CD3 + CD3 Ph3PCH3 Br O CD O CD 3 t-BuOK 3 O

4-d6 1-d6, overall yield: 7%

Scheme 2.6. Synthesis of 1-d6.

The preparation of the N-heterocyclic carbene 2-d0 was carried out starting from 24a 2,4,6-trimethylaniline 7-d0 and glyoxal 8-d0 as outlined in Scheme 2.7. The diimine 9- d0 was obtained as yellow solid from the condensation of 8-d0 with two equivalents of 7- d0. The subsequent treatment of 9-d0 with NaBH4 in THF represents a convenient method to access diamines with sterically demanding nitrogen substituents. The addition of HCl to 22 2. Mechanistic study on the activity of a Hoveyda-type catalyst ______

the reaction mixture led to the precipitation of the diamine dihydrochloride 10-d0 in good yield (> 70%). The final reaction with HC(OEt)3 effects cyclization with formation of the imidazolinium salt 2-d0 as a colorless solid.

NH2 . O n-Propanol NaBH4 NH HCl 2 + N N O HCl NH.HCl

7-d0 8-d0 9-d0

10-d0

HC(OEt)3

N N

H 2-d0, overall yield: 15%

Scheme 2.7. Synthesis of 2-d0.

The starting material for the synthesis of the labeled N-heterocyclic carbene was 7- d11 (Scheme 2.8). The synthesis involved nitration of commercially available 11-d12 to give 12-d11, followed by catalytic hydrogenation. The labeled trimethylaniline was isolated in good yield (76%).

D acetic NO2 NH2 D3C CD3 anhydride D3C CD3 Pd/C 10% D3C CD3

D D HNO3 D D H2, 1.0 atm D D

CD3 CD3 CD3

11-d12 12-d11 7-d11, overall yield: 76%

Scheme 2.8. Synthesis of 7-d11.

An alternative route would involve the direct amination of mesitylene in the presence of (CH3)3SiN3 and CF3SO3H. The reaction was tested with unlabeled substrate with good results according to a procedure reported by Olah (Scheme 2.9).25

NH2 (CH)3SiN3

CF3SO3H

11-d0 7-d0, 62%

Scheme 2.9. Direct synthesis of 2,4,6-trimethylaniline. 2. Mechanistic study on the activity of a Hoveyda-type catalyst 23 ______

As outlined in Scheme 2.10, 7-d11 was utilized as starting material in the 24b preparation of 2-d22. In this last case, the results were improved from those in Scheme 2.7 in terms of overall yield (63%). Furthermore, reactions could be easily scaled up.

CD3 D D

NH2 D CD D C D 3 3 D3C CD3 D3C CD3 2-propanol NaBH O 4 NH.HCl 2 + D3C N N CD3 D D O H2O HCl . D CD D C D NH HCl CD3 3 3 D3C CD3

7-d11 8-d0 9-d22 D D CD3

10-d22

HCO2H HC(OEt)3

Cl D CD3 D3C D

D3C N N CD3

D CD3 H D3C D

2-d22, overall yield: 63%

Scheme 2.10. Synthesis of 2-d22.

24b The syntheses of 14-d0 and 14-d22 were carried out as reported in the literature as a modification of a one-pot synthesis described by Nolan.26 Grubbs' first generation catalyst 13, 2-d0 or 2-d22, and t-BuOK were refluxed in hexanes for one day under an inert atmosphere (Scheme 2.11).

D CD3 D3C D

D3C N N CD3 N N PCy 2-d 3 2-d D CD3 D3C D 22 Cl 0 Cl Ru Ru Cl Ru Cl Cl Cl PCy3 PCy3 PCy3

14-d , 57% 13 22 14-d0, 60%

Scheme 2.11. Synthesis of 14-d0 and 14-d22.

The method enabled the avoidance of salt contamination and hydride formation.

After conversion of 13 to 14-d0 or 14-d22, the addition of 2-propanol/water (1:1 v/v) to the reaction mixture permits the extraction of unreacted salts and phosphine oxide. Finally, catalysts were isolated by simple filtration in good yields. As outlined in Scheme 2.12, 24 2. Mechanistic study on the activity of a Hoveyda-type catalyst ______

Grubbs' second generation catalysts 14-d0 and 14-d22 were treated, respectively, with 1-d0 and 1-d6 in presence of the phosphine scavenger CuCl to encourage the PCy3 dissociation and induce the chelation of 2-isopropoxystyrene to the ruthenium center.22a

N N N N CuCl Cl Cl Ru Ru Cl Cl 1-d0 O PCy3

14-d0 15-d0, 81%

D CD3 D3C D D CD3 D3C D

D3C N N CD3 D3C N N CD3 CuCl D CD3 D3C D D CD3 D3C D Cl Ru Cl Ru Cl Cl 1-d6 O PCy3 D3C CD3 14-d22 15-d28, 85%

Scheme 2.12. Synthesis of 15-d0 (top) and 15-d28 (bottom).

Hoveyda's second generation catalysts 15-d0 and 15-d28 were isolated in high yields (> 80%) as bright green solids after column chromatography. Both catalysts were stable in air. The labeled products were characterized by NMR and IR spectroscopy, and mass spectrometry as summarized in the experimental section.

2.3.2. Mass spectrometry experiments. Mass spectroscopic investigations were conducted using three techniques: FAB-MS, MALDI-MS and ESI-MS. 4,4- Dicarboethoxy-1,6-heptadiene (16), N,N-diallyl-4-methylbenzenesulfonamide (17), and 4,4-dicarboethoxy-2-methyl-1,6-heptadiene (18) were utilized as educts.

CH3

CO2Et CO2Et

CO2Et CO2Et O S O

16 17 18

FAB-MS was the first ionization technique to be used. As depicted in Figure 2.8, the influence of the ionization technique was evaluated in experiment 1. The catalytic 2. Mechanistic study on the activity of a Hoveyda-type catalyst 25 ______

mixture was composed of 15-d0 and 15-d28 in an arbitrary molar ratio. The solid blend was dissolved in pentane/CH2Cl2 (1:1 v/v) and the solution stirred for 5 min at room temperature. The solvent was removed and a fraction analyzed. No crossover was observed.

D CD3 D3C D

D3C N N CD3 N N

D CD3 D3C D Cl Ru Cl Ru Cl Cl O O

D3C CD3

15-d28 15-d0 No educt

Catalyst FAB-MS

Figure 2.8. FAB-MS (experiment 1).

The isotope distribution of catalysts in the presence of the educts 16, 17, and 18 was defined, respectively, in experiments 2a, 2b, and 2c. The experiment 2a is outlined in Figure 2.9. The concentration of the educt and the catalyst loading were, respectively,

0.100 M in CH2Cl2 and 1.5 mol%. The experiments were conducted at room temperature. The catalyst was partially retrieved as a green solid by column chromatography. The amount of crossover varied with the educt.

D CD3 D3C D

D3C N N CD3 N N

D CD3 D3C D Cl Cl Ru Ru Cl Cl O O

D3C CD3

15-d28 15-d0 Educt 16

After column EtO2C CO2Et chromatography Product

16-a Catalyst FAB-MS

Figure 2.9. FAB-MS (experiment 2a).

Operative conditions (volume of solvent, catalyst loading, and temperature) 26 2. Mechanistic study on the activity of a Hoveyda-type catalyst ______

identical to experiments 2a-c were employed in experiment 3 in a control analysis (Figure 2.10). The reaction was carried out in absence of educt. The catalyst was recovered with the same procedure. No crossover was observed within detection limits.

D CD3 D3C D

D3C N N CD3 N N

D CD3 D3C D Cl Cl Ru Ru Cl Cl O O

D3C CD3

15-d28 15-d0 No educt

After column chromatography

Catalyst FAB-MS

Figure 2.10. FAB-MS (experiment 3).

In experiment 4, educt 16 was utilized in a time-monitored analysis (Figure 2.11). The concentration of the educt, the catalyst loading, and the temperature were identical to those in experiment 2a. Aliquots of the solution (1.0 mL) were withdrawn and immediately analyzed. The magnitude of crossover was lower with respect to that in experiment 2a.

D CD3 D3C D

D3C N N CD3 N N

D CD3 D3C D Cl Cl Ru Ru Cl Cl O O

D3C CD3

15-d28 15-d0

Educt 16

Catalyst + FAB-MS Product

Figure 2.11. FAB-MS (experiment 4).

As shown in Figure 2.12, the isotope distribution of catalysts in the presence and in absence of educt 17 was defined in experiments 5a and 5b, respectively. The concentration of the educt and the catalyst loading were 0.100 M in CH2Cl2 and 1.5 mol%. The reaction 2. Mechanistic study on the activity of a Hoveyda-type catalyst 27 ______

was conducted at 2 °C (ice-water bath). An aliquot (1.0 mL) of the solution was withdrawn after 10 min and immediately analyzed. Identical operative conditions were utilized in the control experiment 5b.

D CD3 D3C D D CD3 D3C D

D3C N N CD3 N N D3C N N CD3 N N D CD D C D D CD D C D 3 3 Cl 3 3 Cl Ru Ru Cl Ru Cl Ru Cl Cl Cl Cl O O O O

D3C D3C CD3 CD3

15-d28 15-d0 15-d28 15-d0

Educt 17 No educt

Catalyst + FAB-MS Catalyst FAB-MS Product

Figure 2.12. FAB-MS experiment 5a (left) and 5b (right).

MALDI-MS was the second ionization technique. The general procedure is schematized in Figure 2.13. A background was defined for every experiment. An initial aliquot of solution (0.001 mL) was analyzed immediately after addition of the catalyst. The remaining measurements were registered at regular intervals for 2 h.

D CD3 D3C D

D3C N N CD3 N N

D CD D C D 3 3 Cl Cl Ru Ru Cl Cl O O

D3C CD3

15-d28 15-d0

Educt

The reaction was monitored by GC Catalyst + MALDI-MS Product

Figure 2.13. MALDI-MS experiments.

At the same time, the progress of the reaction was monitored by GC. The catalytic mixture was composed of 15-d0 and 15-d28 in an arbitrary molar ratio. The first and second experiments were accomplished at room temperature in the presence of educts 16 and 17. The concentration of educt and the catalyst loading were, respectively, 0.100 M in 28 2. Mechanistic study on the activity of a Hoveyda-type catalyst ______

CH2Cl2 and 1.5 mol%. In a third experiment, a lower concentration of 16 was used

(0.0100 M in CH2Cl2, 1.0 mol% catalyst loading, and room temperature). This ensured a slower conversion of the educt. Finally, crossover was monitored by ESI-MS (Figure 2.14). Two analyses were accomplished with diene 17 at room temperature. The catalytic mixture was again composed of 15-d0 and 15-d28 in an arbitrary molar ratio. In experiment 1, the concentration of 17 and the catalyst loading were, respectively, 0.0100 M in CH2Cl2 and 1.0 mol%. Aliquots of the solution (1.0 mL) were withdrawn every 20 min for two hours, diluted with dry CH2Cl2 (1.0 mL), and immediately analyzed. In experiment 2, the concentration of 17 was increased to 0.100 M in CH2Cl2. The reaction was carried out utilizing a higher catalyst loading (1.5 mol%). Aliquots of the solution were withdrawn, diluted in 2.0 mL of CH3CN, and immediately analyzed.

D CD3 D3C D D CD3 D3C D D C N N CD 3 3 N N D3C N N CD3 N N

D CD3 D3C D D CD D C D Cl 3 3 Cl Ru Ru Cl Ru Cl Ru Cl Cl Cl Cl O O O O D3C D3C CD3 CD3

15-d28 15-d0 15-d28 15-d0

Educt 17 Educt 17

Catalyst + Product Catalyst + Product ESI-MS ESI-MS (dilution in CH2Cl2) (dilution in CH3CN)

Figure 2.14. ESI-MS experiment 1 (left) and experiment 2 (right).

2.4. Discussion

2.4.1. Boomerang mechanism. The reliability of the model proposed for the activity of Hoveyda-type catalysts remains an unclear point. Hoveyda and Kingsbury have recently demonstrated that the boomerang mechanism is, at least, partially operative.27

Their experiment was carried out by three supported variants of Hoveyda's second generation catalyst XIX-d8, XX, and XXI (Figure 2.15). 2. Mechanistic study on the activity of a Hoveyda-type catalyst 29 ______

D D D D N N N N

Cl Cl Ru O Ru Cl O Cl O O O O O O O Cl Cl O Ru O O Ru Cl Cl

N N N N D D D D

XIX-d8 XX

N N

Cl Ru Cl O O O

XXI

Figure 2.15. Supported variants of Hoveyda's second generation catalyst.

As outlined in Scheme 2.13, two pellets with XIX-d8, one with XX, and one with XXI (10 mol% overall catalyst loading) were prepared and utilized in five consecutive RCM experiments in the presence of the substrate XXII. The conversion in each case is

> 99% in 2 h. The reactions were conducted in CH2Cl2 (0.2 M, 22 °C). The RCM product XXIII was isolated in each case as an off white solid in 99% yield. After each experiment, the pellets were rinsed with CH2Cl2 (2 × 2.0 mL, 15 min) to ensure complete removal of unbound catalysts. After 5 RCM experiments, the pellets containing XIX-d8 were separated and collected in a vial. The vial was charged with 0.5 mL of a solution of XVIII in CH2Cl2 (0.1 M), capped, and heated at 40 °C. The colorless solution became progressively green (2 h). The solvent was removed and the procedure was repeated until when variation of color was no longer observed (5 times). The solutions were combined, and dried. The resulting oily green residue was chromatographed on silica gel (rinsed with 1 CH2Cl2). The solvent was removed and the resulting solid was analyzed by H NMR.

Hoveyda-type catalysts XXIV, XXV, and XIV-d0 were detected in a 98:1:1 ratio. The last data confirmed that a measurable (2% total) amount of crossover occurred. A control was carried out by the same procedure but in absence of the substrate. Analysis of the resulting samples after column chromatography did not reveal any signs of pellet-to-pellet crossover.

30 2. Mechanistic study on the activity of a Hoveyda-type catalyst ______

N O S O O CH2Cl2, 2 h, 22 °C O N S 2 pellets of XIX-d8 1 pellet of XX O 1 pellet of XXI XXII XXIII

5 RCM experiments

2 pellets of XIX-d8 are isolated

D D D D N N N N N N

CH Cl 2 h, 40 °C Cl Cl Cl 2 2, Ru + Ru + Ru 2 pellets of XIX-d8 + O Cl Cl Cl O O O

XVIII XXIV XXV XIV-d0

98 : 1 : 1 (by 1H NMR)

Scheme 2.13. Hoveyda and Kingsbury crossover experiment.

The boomerang mechanism is suggested also in other examples with analogous catalytic systems.28 Nevertheless, it is well known that certain catalyst precursors can act more via a "soup bone" mechanism.29 In this last case, a small amount of catalyst is irreversibly transformed to an active species. This small amount is responsible for all turnovers. At the end of the reaction, it is the untransformed catalyst that has never entered the catalytic cycle that is recovered. Thus, just like a soup bone that is fished out to make a second stew, a portion of activity is lost in each cycle, such that the effectiveness gradually diminishes. Immobilization becomes much less relevant, since no active catalyst is actually recovered.

2.4.2. Mass spectrometry experiments. Isotope labeling represents one of the most useful means to investigate reaction mechanisms.30 The method involves the substitution of atoms with the same chemical properties but with different atomic masses and, in this context, mass spectrometry represents a powerful analytical tool.31 FAB-MS was utilized in a first phase of the investigation. This is a relatively soft ionization technique that provides molecular ions and normally only limited fragmentation, and hence spectra that are easier to interpret.32 2. Mechanistic study on the activity of a Hoveyda-type catalyst 31 ______

In the first experiment the influence of the technique on the catalyst was investigated. The results are shown in Figure 2.16 for experiment 1.

Figure 2.16. Partial FAB-MS for experiment 1.

Basically, for deconvolution calculations, the isotope envelopes of 15-d0, 15-d6, + 15-d22, and 15-d28 species were considered as reference. Then, respectively, M (m/z = + + + 626) and M + 6 (m/z = 632) ion ratios for 15-d0 and 15-d6, and M (m/z = 654) and M –

6 (m/z = 648) ion ratios for 15-d28 and 15-d22 were determined. These correspond to the most intense peaks in both the experimentally observed and theoretically calculated isotope envelopes. The linear combination that best reproduces the experimental data was evaluated,33 as further detailed in the experimental section. The absence of crossover within the detection limits confirmed that the technique does not effect any exchange of styrene ligands (Figure 2.17).

Figure 2.17. Deconvolution data for experiment 1.

32 2. Mechanistic study on the activity of a Hoveyda-type catalyst ______

In the second series of experiments, the exchange of styrene ligands between 15-d0 and 15-d28 was evaluated in the presence of the educt. The results for educt 16 are shown in Figure 2.18.

Figure 2.18. Partial FAB-MS for experiment 2a (educt 16).

As noted above, 16 was exposed to a 1.5 mol% catalyst loading. The results were compared with those of the other two educts, 17 and 18. In particular, 18 is interesting owing to the electronic and steric properties associated with the additional methyl group.

CH2Cl2 was chosen as optimal solvent in terms of conversion of educts as preliminary tests confirmed. The products were isolated in high yields after column chromatography (> 80%), demonstrating the effectiveness of the method. As shown in Figure 2.19, crossover was observed for all educts highlighting a relation between the presence of the alkene and crossover. The magnitude varies somewhat with the educt.

Figure 2.19. Deconvolution data for experiment 2a (educt 16), 2b (educt 17), and 2c (educt 18) (0.1 M, 1.5 mol% catalyst loading, rt).

2. Mechanistic study on the activity of a Hoveyda-type catalyst 33 ______

As a control, the third experiment was carried out in absence of educt. The operative conditions (temperature, reaction time, volume of solvent, and catalyst loading) were identical to the previous one in order to provide a baseline for comparison. The catalyst was recovered through an identical workup, and the exchange of styrene ligands between 15-d0 and 15-d28 was evaluated. The results are shown in Figure 2.20.

Figure 2.20. Partial FAB-MS for experiment 3.

As summarized in Figure 2.21, the absence of crossover confirmed that silica gel, as stationary phase, does not play any role in the ligand exchange.

Figure 2.21. Deconvolution data for experiment 3.

Furthermore, the results indicated clearly that the alkene influences the ligand exchange within the detection limits. The data for experiment 4 in the presence of the educt 16 could be considered as support for this last observation (Figure 2.22). The presence of crossover is confirmed even though, interestingly, the magnitude is lower in comparison with experiment 2a. 34 2. Mechanistic study on the activity of a Hoveyda-type catalyst ______

Figure 2.22. Deconvolution data for experiment 4 (0.1 M, 1.5 mol% catalyst loading, educt 16, rt).

In general, our operative conditions allowed a rapid conversion to the product, irrespective of the educt. The rate profiles in Figure 2.23 confirmed this behavior. Therefore, it was difficult to verify whether a release-return mechanism was present already at the beginning of the reaction or whether this process occurred only in a second phase when the concentration of the educt was depleted.

100

60 educt 16 educt 17 educt 18 40 Conversion (%)

0 0 10 20 30 40 50 60 t (min)

Figure 2.23. Rate profile for the educts 16, 17, and 18 (0.1 M, 1.5 mol% catalyst loading, rt).

In experiment 5a, the educt 17 was employed at low temperature (2 °C, ice-water bath), in an attempt to get this information. Ring closing metathesis of 17 was monitored by GC in the presence of an internal standard and the conversion was determined as a function of time (Figure 2.24). 2. Mechanistic study on the activity of a Hoveyda-type catalyst 35 ______

100

40 Conversion (%) 20

0 0 1 2 3 4 5 6 t (h)

Figure 2.24. Rate profile for the educt 17 (0.1 M, 1.5 mol% catalyst loading, T = 2 °C).

The rate profile showed a slower conversion of the educt 17 in comparison with the reaction carried out at room temperature under the same operative conditions. As outlined in Figure 2.25, the magnitude of crossover was small (≤ 11%). However, the control experiment 5b again confirmed clearly that the alkene influences the ligand exchange. Thus can be assumed as a further evidence of the validity of Hoveyda's model.

Figure 2.25. Deconvolution data after 10 min in presence (5a) and in absence (5b) of the educt 17 (0.1 M, 1.5 mol% catalyst loading, T = 2 °C).

In order to check the FAB-MS results, MALDI-MS was chosen for a second analysis. MALDI-MS works in soft ionization conditions and produces primarily singly charged ions, so even complex mixtures can be analyzed. On the other side, the utilization of a matrix and the concomitant matrix-sample co-crystallization can result in a low shot- 36 2. Mechanistic study on the activity of a Hoveyda-type catalyst ______

to-shot reproducibility.34 The aim of a first series of experiments was to verify the results achieved by FAB- MS. Subsequently, 16 was investigated under slower catalytic conditions (0.0100 M, 1.0 mol% catalyst loading). In general, the results obtained by MALDI-MS were not satisfying in terms of both reproducibility of the method and data interpretation. On the basis of these outcomes, a different technique was considered. In the recent years, ESI-MS found increasing use as a mass spectrometric method.35 One of the reasons is the powerful ability to investigate species in solution even in vanishingly low concentrations and in complex mixtures. The educt 17 was utilized at room temperature in two experiments. In the first, the concentration of the educt and the catalyst loading were, respectively, 0.0100 M and 1.0 mol%. These conditions ensure a slower conversion of the educt (Figure 2.26). No external agents assisted the ionization processes to avoid any possible contaminant. The resulting overall picture was quite different in comparison with FAB-MS since only 15-d0 and 15- d28 envelopes were observed within detection limits in the area of interest (m/z = 626-654).

100

40 Conversion (%)

0 0 1 2 3 4 5 6 t (h)

Figure 2.26. Rate profile for the educt 17 (0.01 M, 1.0 mol% catalyst loading, rt).

Then, experiment 2b was reproduced using ESI-MS. CH3CN was utilized as dilution solvent and reaction quencher. Furthermore, it assisted the ionization processes. In both cases, crossover was not detected within detection limits in the region of interest. In 2. Mechanistic study on the activity of a Hoveyda-type catalyst 37 ______

particular, no overlapping isotope envelopes were observed within detection limits in the area of the most intense peaks at m/z = 639 and m/z = 667 corresponding to 19-d0 and 19- d28.

D CD D C D 2+ 3 3 2+

N N D3C N N CD3

D CD3 D3C D Ru + 2 CH3CN Ru + 2 CH3CN O O

D3C CD3 19-d 0 19-d28

2.5. Conclusions

In the course of this study, an isotopically labeled Hoveyda-type catalyst (15-d28) was prepared together with the corresponding natural abundance version (15-d0). The catalytic mixture (15-d28/15-d0) was utilized to conduct RCM reactions. Mass spectrometric analyses of the recovered catalyst were conducted using various ionization techniques. Some suggested that a boomerang mechanism could be considered realistic. In these cases, crossover or isotope scrambling between the ruthenium moiety and dissociable alkylidene ligand occurred. On the other side, other data did not support a unique, predominant boomerang mechanism. The magnitude of crossover was sometime small (≤ 11%), depending upon slight changes in conditions, workup, procedures, the ionization technique, and educt for reactions in which the analysis was carried out directly from the solution without isolating the catalyst by column chromatography. On the other side, crossover increased markedly when the catalyst was recovered by column chromatography. These findings pose interesting scenarios for the mechanism of activity of these important classes of catalysts, the further investigation of which will demand distinct advances in analytical methodologies and instrumentation. 38 2. Mechanistic study on the activity of a Hoveyda-type catalyst ______

2.6. Experimental section

General data. Reactions were carried out under dry nitrogen atmospheres using conventional Schlenk techniques unless noted. Workups were carried out in air. Chemicals were treated as follows: hexanes, distilled from sodium for reactions or simple distillation for chromatography; CH2Cl2, distilled from CaH2 for reactions or simple distillation for chromatography; toluene and THF, distilled from Na/benzophenone; ethanol, distilled from magnesium turnings; CH3CN (Roth, 98%) distilled from CaH2 and stored in glove box for ESI-MS experiment 2 or simple distillation; salicylaldehyde (Aldrich, 97%), acetic anhydride (Grüssig, 97%), 2-propanol, acetone, diethyl ether, pentane, and ethyl acetate, simple distillation; CD2Cl2 and CDCl3 (Deutero GmbH), stored over molecular sieves;

DMSO-d6 (Aldrich), mesitylene-d12 (11-d12, Aldrich or Acros), (CD3)2CO (5-d6, + − Aldrich), Ph3PCH3 Br (Lancaster, 98+%), Cs2CO3 (Lancaster, 99+%), CuCl (Aldrich,

99.99%), t-BuOK (Fluka or Acros, 98+%), glyoxal (8-d0, Lancaster, 40% w/w aqueous solution), NaBH4 (Acros), HNO3 (Merck, 100%), Pd/C (Acros, 10%), HCl (Staub, 37% aqueous solution), HBr (Fluka, 48% aqueous solution), MgSO4 (Riedel-de Haën), NaOH

(Grüssig, 99%), CaO (Riedel-de Haën), HC(OEt)3 (Acros, 99+%), HCO2H (Grüssig, 100%), celite (Macherey-Nagel), silica gel (Macherey-Nagel, 60 M),

Ru(=CHPh)(PCy3)2(Cl)2 (13, Aldrich), and 4,4-dicarboethoxy-1,6-heptadiene (16, Acros, 98%) used as received. N,N-Diallyl-4-methylbenzenesulfonamide (17),36 4,4- 37 dicarboethoxy-2-methyl-1,6-heptadiene (18), and (H2IMes)(Cl2)Ru=CH-o-OC6H4(i-Pr) 22a (15-d0) were synthesized by literature procedures. NMR spectra were recorded at ambient probe temperature on Jeol 400 MHz and Bruker 300-400 MHz FT spectrometers. IR spectra were recorded on an ASI React IR®- 1000 instrument. Mass spectra were recorded on Micromass Zabspec, MALDI 3 Telsa FT ICR, and Thermo Finnigan TS Quantum instruments for the FAB, MALDI, and ESI-MS experiments, respectively. 2. Mechanistic study on the activity of a Hoveyda-type catalyst 39 ______

38 2-Bromopropane-d6 (3-d6). A two-necked round bottom flask was charged with

NaBH4 (3.42 g, 90.4 mmol) and H2O (30 mL) and fitted with a condenser. A solution of 5- d6, (10.004 g, 156.00 mmol) in H2O (15 mL) was added dropwise over 30 min with stirring. The solution was refluxed (3 h). The 2-propanol-d6 (6-d6) was distilled and then refluxed over CaO (1 h). A second distillation gave 6-d6 as clear liquid (5.423 g, 81.99 mmol, 53%).

A round bottom flask was charged under air with 6-d6 (2.903 g, 43.89 mmol). Aqueous 48% HBr (21.0 mL) was added dropwise over 20 min with stirring. The sample was slowly distilled between 58 °C and 125 °C, until the volume was reduced by one half.

The aqueous layer of the distillate was separated. The organic layer was dried (MgSO4) to give 3-d6 (4.02 g, 31.1 mmol, 63%).

1 NMR (δ, CDCl3): H 4.26 (br s, 1H, CH(CD3)2).

39 2-Isopropoxybenzaldehyde-d6 (4-d6). A round bottom flask was charged with

3-d6 (1.054 g, 8.171 mmol), salicylaldehyde (0.333 g, 2.727 mol), Cs2CO3 (1.604 g, 4.923 mmol), and CH3CN (35 mL) with stirring, and fitted with a condenser. The mixture was refluxed (5 h). The solvent was removed by rotary evaporation. The yellow residue was dissolved in diethyl ether (45 mL), which was washed with water (4 × 15 mL) and aqueous

NaOH (2.0 M, 70 mL), and dried (MgSO4). The solvent was removed by rotary evaporation. The residue was chromatographed on silica gel (15 × 1 cm column, 5:1 v/v hexanes/diethyl ether). The solvents were removed from the product-containing fractions by rotary evaporation and oil pump vacuum to give 4-d6 as a yellow oil (0.274 g, 1.61 mmol, 60%).

1 4 3 NMR (δ, CDCl3): H 10.49 (s, 1H, CHO), 7.81 (dd, 1H, JHH = 1.9 Hz, JHH = 8.0

Hz, Haryl), 7.53-7.48 (m, 1H, Haryl), 6.99-6.96 (m, 2H, Haryl), 4.65 (s, 1H, CH(CD3)2); 40 2. Mechanistic study on the activity of a Hoveyda-type catalyst ______

13 1 C{ H} 190.1 (s, C=O), 160.6 (s, Caryl), 135.7 (s, Caryl), 128.2 (s, Caryl), 125.7 (s, Caryl), 1 120.3 (s, Caryl), 113.4 (s, Caryl), 70.5 (s, CH(CD3)2), 21.0 (sept, JCD = 19.3 Hz, CD3). 43 + MS: 171 ([4-d6 + H] , 100%). IR (cm−1, liquid film): 3083 (w), 3030 (w), 2917 (w), 2815 (m), 2723 (m), 1692 (s), 1620 (m), 1590 (m), 1478 (s), 1450 (s), 1390 (m), 760 (s), 696 (s).

40 + 2-Isopropoxystyrene-d6 (1-d6). A Schlenk flask was charged with Ph3PCH3 Br− (0.508 g, 1.42 mmol), t-BuOK (0.399 g, 3.56 mol), and THF (3 mL). The mixture was cooled to 0 °C with stirring. After 30 min, a solution of 4-d6 (0.242 g, 1.42 mmol) in THF (2.5 mL) was added. The cooling bath was removed. After 12 h, water was added (15 mL).

The organic layer was separated. The aqueous layer was extracted with diethyl ether (5 × 10 mL). The organic layer and extracts were combined, washed with brine (70 mL), and dried (MgSO4). The solvent was removed by rotary evaporation. The residue was chromatographed on silica gel (20 × 1 cm column, 98:2 v/v pentane/ethyl acetate). The solvents were removed from the product-containing fractions by rotary evaporation and oil pump vacuum to give 1-d6 as a light yellow oil (0.0845 g, 5.02 mmol, 35%).

1 4 3 NMR (δ, CDCl3): H 7.40 (dd, 1H, JHH = 1.7 Hz, JHH = 7.6 Hz, Haryl), 7.14- 3 3 7.08 (m, 1H, Haryl), 6.98 (dd, 1H, JHH = 17.8 Hz, JHH = 11.2 Hz, CH=), 6.84-6.78 (m, 3 2 3 2H, Haryl), 5.63 (dd, 1H, JHH = 17.8 Hz, JHH = 1.6 Hz, =CHEHZ), 5.15 (dd, 1H, JHH = 2 13 1 11.2 Hz, JHH = 1.6 Hz, =CHEHZ), 4.43 (s, 1H, CH(CD3)2); C{ H} 155.2 (s, Caryl),

132.0 (s, CH=), 128.7 (s, Caryl), 127.9 (s, Caryl), 126.5 (s, Caryl), 120.8 (s, Caryl), 114.2 (s, 1 Caryl), 113.9 (s, =CH2), 70.5 (s, CH(CD3)2), 21.4 (sept, JCD = 19.3 Hz, CD3). 43 + MS: 169 ([1-d6 + H] , 100%). IR (cm−1, liquid film): 3085 (w), 3033 (w), 2923 (w), 2231 (m), 1625 (m), 1596 (m), 1482 (s), 1453 (s), 1291 (m), 1239 (s), 1108 (s), 1030 (s), 998 (s), 905 (s), 883 (s), 747 (s). 2. Mechanistic study on the activity of a Hoveyda-type catalyst 41 ______

41 1,3,5-Trimethylnitrobenzene-d11 (12-d11). A round bottom flask was charged under air with 100% HNO3 (0.34 mL, g, 8.2 mmol) and acetic anhydride (3.3 mL). The solution was cooled to 0 °C with stirring. A solution of 11-d12 (0.945 g, 7.14 mmol) in acetic anhydride (1.7 mL) was added dropwise over 5 min. The cooling bath was removed. The mixture was stirred for 1 h, and poured onto crushed ice. The pale yellow precipitate was isolated by filtration, washed with cold water, and dried by oil pump vacuum. _ Recrystallization from hexanes at 20 °C gave 12-d11 as light yellow blocks (0.934 g, 5.30 mmol, 74%).

13 1 NMR (δ, CDCl3): C{ H} 149.8 (s, Caryl, i-NO2), 140.0 (s, Caryl, p-NO2), 129.4 1 1 (s, Caryl, o-NO2), 129.1 (t, JCD = 24.4 Hz, Caryl, m-NO2), 20.2 (sept, JCD = 19.3 Hz, 1 CD3, p-NO2), 16.9 (sept, JCD = 19.3 Hz, CD3, o-NO2). 43 + MS: 177 ([12-d11 + H] , 100%). IR (cm−1, powder film): 2867 (w), 2236 (w), 2113 (w), 2070 (w), 1590 (m), 1576

(m), 1509 (s, ν(NO2)), 1360 (s, ν(NO2)), 1046 (s), 878 (s), 826 (s), 785 (s), 690 (m), 664 (m).

42 2,4,6-Trimethylaniline-d11 (7-d11). A Schlenk flask was charged with 12-d11, (0.800 g, 4.54 mmol), 10% Pd/C (0.483 g, 0.454 mmol Pd), toluene (22 mL), and ethanol

(22 mL), flushed with H2, and fitted with a balloon of H2 (1.0 atm). The mixture was stirred (3 d) and passed through a celite plug (5 × 1.5 cm), which was repeatedly washed with hot ethanol (5 × 10 mL). The solvents were removed from the filtrate by rotary evaporation. The residue was dissolved in hexanes and passed through a plug of silica gel

(4 cm) in a Pasteur pipette. The solvent was removed by oil pump vacuum to give 7-d11 as an amber oil (0.503 g, 3.44 mmol, 76%).

1 13 1 NMR (δ, CDCl3): H 3.45 (br s, 2H, NH2); C{ H} 140.5 (s, Caryl, i-NH2), 128.8 42 2. Mechanistic study on the activity of a Hoveyda-type catalyst ______

1 (t, JCD = 23.6 Hz, Caryl, m-NH2), 127.2 (s, Caryl, p-NH2), 121.9 (s, Caryl, o-NH2), 19.7 1 1 (sept, JCD = 19.3 Hz, CD3, p-NH2), 17.0 (sept, JCD = 19.3 Hz, CD3, o-NH2). 43 + MS: 147 ([7-d11 + H] , 100%). IR (cm−1, liquid film): 3346 (w), 3381 (w), 2227 (w), 2189 (w), 2111 (w), 2065 (w), 1617 (s), 1440 (s), 1301 (w), 1216 (w), 1046 (m), 672 (m).

24b Glyoxal-bis(2,4,6-trimethylphenylimine)-d22 (9-d22). A round bottom flask was charged with 8-d0 (40% w/w aqueous solution; 0.216 g, 0.0864 g of glyoxal, 1.49 mmol), 2-propanol (3 mL), and H2O (4.5 mL). The solution was cooled to 0 °C with stirring. Then 7-d11 (0.435 g, 2.97 mmol) was added. A yellow solid immediately precipitated, and the cooling bath was removed. After 24 h, the yellow precipitate was isolated by filtration and washed with water (3 × 10 mL). Acetone (15 mL) was added to the wet solid. The resulting suspension was concentrated by rotary evaporation. The sample was dried by oil pump vacuum to give 9-d22 as a yellow solid (0.420 g, 1.34 mmol, 90%).

1 13 1 NMR (δ, CDCl3): H 8.16 (s, 2H, 2N=CH); C{ H} 163.4 (s, N=CH), 147.5 (s, 1 Caryl, i-N), 134.0 (s, Caryl, p-N), 128.6 (t, JCD = 24.4 Hz, Caryl, m-N), 126.4 (s, Caryl, o- 1 1 N), 19.8 (sept, JCD = 19.3 Hz, CD3, p-N), 17.3 (sept, JCD = 19.3 Hz, CD3, o-N). 43 + + MS: 315 ([9-d22 + H] , 100%), 296 ([9-d22 − CD3] , 60%). IR (cm−1, solid film): 2961 (w), 2930 (w), 2860 (w), 2250 (w), 2227 (w), 2162 (w), 2108 (w), 2065 (w), 1729 (m), 1610 (s), 1413 (s), 1274 (s), 1158 (m), 1108 (m), 1042 (m), 687 (m), 664 (m).

N,N'-Bis(2,4,6-trimethylphenyl)ethylenediamine-d22 dihydrochloride (10- 24b d22). A Schlenk flask was charged with 9-d22 (0.410 g, 1.30 mmol) and THF (6 mL).

The solution was cooled to 0 °C with stirring. Then NaBH4 (0.163 g, 4.31 mmol) was 2. Mechanistic study on the activity of a Hoveyda-type catalyst 43 ______

added in one portion. Next, aqueous 37% HCl (0.211 g, 2.11 mmol) was added dropwise over 10 min. After 20 min, HCl (3.0 M, 10 mL) was added dropwise. The cooling bath was removed. After 1 h, the white precipitate was isolated by filtration, washed with water (3 × 10 mL) and acetone/diethyl ether (5:95 w/w, 2 × 10 mL), and dried by oil pump vacuum to give 10-d22 as a white powder (0.422 g, 1.08 mmol, 83%).

1 13 1 NMR (δ, DMSO-d6): H 3.51 (br s, 2H, 2NH), 3.38 (s, 4H, 2NCH2); C{ H} 1 136.0 (s, Caryl, p-N), 134.3 (s, Caryl, o-N), 131.0 (s, Caryl, i-N), 129.9 (t, JCD = 24.4 Hz, 1 1 Caryl, m-N), 46.6 (s, NCH2), 19.0 (sept, JCD = 19.3 Hz, CD3, p-N), 17.1 (sept, JCD =

19.3 Hz, CD3, o-N). 43 + + MS: 390 (10-d22 , 34%), 319 ([10-d22 − 2HCl] , 100%). IR (cm−1, powder film): 3354 (w), 3258 (w), 2633 (w), 2254 (w), 2111 (w), 2069 (w), 1629 (s), 1559 (s), 1471 (s), 1424 (s), 1189 (m), 1146 (m), 1108 (m), 1046 (s), 980 (s), 803 (w), 726 (w), 691 (m).

1,3-Bis(2,4,6-trimethylphenyl)imidazolinium-d22 chloride (H2IMes-d22) (2- 24b d22). A Schlenk flask was charged with 10-d22 (0.405 g, 1.03 mmol) and HC(OEt)3 (3.5 mL). Three drops of 100% HCO2H were added with stirring. The mixture was heated at 120 °C (5 h), and cooled to room temperature. Hexanes (5 mL) was added, and the mixture was stirred for 1 h. The precipitate was isolated by filtration, washed with hexanes (4 × 5 mL), and dried by oil pump vacuum to give 2-d22 as a white powder (0.316 g, 0.866 mmol, 84%).

1 13 1 NMR (δ, DMSO-d6): H 9.08 (s, 1H, im-H), 4.54 (s, 4H, 2NCH2); C{ H} 160.2 1 (s, NCN), 139.3 (s, Caryl, p-N), 135.1 (s, Caryl, o-N), 131.0 (s, Caryl, i-N), 129.1 (t, JCD = 1 24.4 Hz, Caryl, m-N), 50.9 (s, NCH2), 20.5 (sept, JCD = 19.3 Hz, CD3, p-N), 17.3 (sept, 1 JCD = 19.3 Hz, CD3, o-N). 44 2. Mechanistic study on the activity of a Hoveyda-type catalyst ______

43 + MS: 330 ([2-d22 − Cl] , 100%). IR (cm−1, powder film): 3246 (m), 2968 (m), 2864 (m), 2633 (w), 2239 (w), 1752 (s), 1621 (s), 1424 (s), 1351, 1266 (s), 1181 (s), 1046 (s), 884 (s), 764 (m), 687 (w), 664 (w).

24b Ru(=CHPh)(H2IMes-d22)(PCy3)(Cl)2 (14-d22). A Schlenk flask was charged, under an argon flow, with 2-d22 (0.180 g, 0.493 mmol), 13 (0.253 g, 0.308 mol), t-BuOK (0.0719 g, 0.641 mol), and freshly distilled hexanes (8 mL), and attached to a vacuum line. The purple suspension was degassed for 2 min by oil pump vacuum without cooling and stirred at 60 °C (24 h). The resulting brown suspension was cooled to room temperature and stirred in air for 3 min after addition of 2-propanol/water (1:1 v/v, 5 mL). The precipitate was isolated by filtration, washed with 2-propanol/water (1:1 v/v, 2 × 3 mL) and hexanes (2 × 3 mL), and dried overnight by oil pump vacuum to give 14-d22 as a brownish-pink solid (0.153 g, 0.176 mmol, 57%). Alternatively, the precipitate was chromatographed on silica gel with gradient elution (15 × 1 cm column, 7:1 v/v hexanes/diethyl ether to 100% diethyl ether).

1 NMR (δ, CD2Cl2): H 19.02 (s, 1H, Ru=CH), 7.40-7.33, 7.14-6.88 (2 m, 5H, 31 1 Haryl), 3.96 (s, 4H, 2CH2N), 2.28-2.17, 1.46-1.22, 1.09-0.86 (3 m, 33H, 3PCy3); P{ H} 30.6 (s). 43 + + MS: 870 (14-d22 , 20%), 835 ([14-d22 − Cl] , 10%), 370 (unknown, 100%), 330 + ([2-d22 + H] , 50%). IR (cm−1, powder film): 3061 (w), 2930 (m), 2849 (m), 2351 (s), 1664 (w), 1586 (w), 1588 (w), 1475 (m), 1440 (s), 1258 (s), 1117 (m), 1092 (s), 896 (m), 845 (m), 741 (m), 687 (w).

22a (H2IMes-d22)(Cl2)Ru=CH-o-OC6H4(i-Pr-d6) (15-d28). A Schlenk flask was 2. Mechanistic study on the activity of a Hoveyda-type catalyst 45 ______

charged with CuCl (0.0184 g, 0.186 mmol), 14-d22 (0.135 g, 0.155 mmol), and CH2Cl2 (5 mL) under an argon flow, and fitted with a condenser. A solution of 1-d6 (0.0365 g, 0.217 mol) in CH2Cl2 (3 mL) was added, under argon, dropwise over 5 min with stirring. The slurry was refluxed (1 h), cooled, and concentrated by oil pump vacuum. The slurry was passed through a Pasteur pipette containing a plug of cotton (2 cm).44 The filtrate was chromatographed on silica gel with gradient elution (8 × 1 cm column, 1:1 to 3:7 v/v pentane/CH2Cl2). A green band was collected. The solvents were removed by oil pump vacuum to give 15-d28 as a bright green solid (0.086 g, 0.132 mmol, 85%).

1 NMR (δ, CDCl3): H 16.56 (s, 1H, Ru=CH), 7.50-7.46 (m, 1H, Haryl), 6.93 (dd, 4 3 3 1H, JHH = 1.5 Hz, JHH = 7.4 Hz, Haryl), 6.89-6.85 (m, 1H, Haryl), 6.80 (d, 1H, JHH = 13 1 8.3 Hz, Haryl), 4.83 (br s, 1H, w1/2 = 5.2 Hz, CH(CD3)2, 4.18 (s, 4H, 2NCH2); C{ H} 1 296.5 (apparent q, JCN = 60.4 Hz, NCN), 211.9 (s, Ru=CH), 152.8 (s, Caryl), 145.9 (s, 1 Caryl), 145.8 (s, Caryl), 139.0 (s, Caryl), 130.0 (s, Caryl), 129.7 (t, JCD = 24.4 Hz, Caryl),

129.3 (s, Caryl), 123.2 (s, Caryl), 122.7 (s, Caryl), 113.3 (s, Caryl), 75.1 (s, CH(CD3)2), 51.9 1 1 (s, NCH2), 21.2 (sept, JCD = 19.3 Hz, CD3), 20.4 (sept, JCD = 19.3 Hz, CD3), 17.2 (sept, 1 JCD = 19.3 Hz, CD3). 43 + + MS: 654 (15-d28 , 40%), 619 ([15-d28 − Cl] , 20%), 424 (unknown, 100%). IR (cm−1, powder film): 2962 (m), 2925 (m), 2848 (m), 2248 (w), 2124 (w), 2067 (w), 1588 (w), 1476 (m), 1453 (m), 1258 (s), 1092 (s), 1013 (s), 797 (s), 749 (m), 687 (w).

FAB-MS (experiment 1). A Schlenk flask was charged with 15-d0 (0.0305 g,

0.0487 mmol) and 15-d28 (0.0246 g, 0.0376 mmol). Then pentane/CH2Cl2 were added (4 mL, 1:1 v/v). The solution was stirred for 5 min. The solvents were removed by oil pump vacuum to give the blend 15-d0/15-d28 as a green solid, which was analyzed by FAB-MS.

FAB-MS (experiment 2a). A round bottom flask was charged with 16 (0.140, 46 2. Mechanistic study on the activity of a Hoveyda-type catalyst ______

0.583 mmol) and CH2Cl2 (3.8 mL) with stirring. A solution of 15-d0/15-d28 (experiment 1;

0.0056 g, 0.0088 mmol, 1.5 mol%) in CH2Cl2 (2.0 mL) was added dropwise over 1 min (the resulting solution is 0.100 M in 16). After 2 h, the solvent was removed by rotary evaporation. The residue was chromatographed on silica gel (10 × 2 cm column, 3:1 hexanes/CH2Cl2). The solvents were removed from the RCM product-containing fractions by rotary evaporation and oil pump vacuum to give 16-a as a light yellow oil (0.108 g,

0.509 mmol, 87%). The column was flushed with CH2Cl2. A green band was collected.

The solvent was removed by rotary evaporation and oil pump vacuum to give 15-d0/15-d28 as a green solid (0.0049 g, 0.0077 mmol, 87%), which was analyzed by FAB-MS.

FAB-MS (experiment 3). A round bottom flask was charged with 15-d0/15-d28

(experiment 1; 0.0056 g, 0.0088 mmol) and CH2Cl2 (5.8 mL) with stirring. After 2 h, the solvent was removed by rotary evaporation. The residue was chromatographed on silica gel (10 × 2 cm column, 3:1 hexanes/CH2Cl2). The column was flushed with CH2Cl2. A green band was collected. The solvent was removed by rotary evaporation and oil pump vacuum to give 15-d0/15-d28 as a green solid (0.0054 g, 0.0085 mmol, 98%), which was analyzed by FAB-MS.

FAB-MS (experiment 4). A round bottom flask was charged with 16 (0.246 g,

1.024 mmol) and CH2Cl2 (6.0 mL) with stirring. A solution of 15-d0/15-d28 (experiment 1;

0.0098 g, 0.0153 mmol, 1.5 mol%) in CH2Cl2 (4.2 mL) was added (the resulting solution is 0.100 M in 16). Aliquots of the solution (1.0 mL) were withdrawn after 6, 12, and 24 min, portions (0.004-0.006 mL) of which were immediately analyzed by FAB-MS.

FAB-MS (experiment 5a). A round bottom flask was charged with 17 (0.130 g,

0.517 mmol) and CH2Cl2 (3.2 mL) with stirring. The solution was cooled to 2 °C (ice- water bath). A solution of 15-d0/15-d28 (experiment 1; 0.0050 g, 0.078 mmol, 1.5 mol%) 2. Mechanistic study on the activity of a Hoveyda-type catalyst 47 ______

in CH2Cl2 (2.0 mL) was added (the resulting solution is 0.100 M in 17). After 10 min, an aliquot of the solution (1.0 mL) was withdrawn, a portion (0.004 mL) of which was immediately analyzed by FAB-MS.

FAB-MS (experiment 5b). A round bottom flask was charged with 15-d0/15-d28

(experiment 1; 0.0050 g, 0.078 mmol, 1.5 mol%) and CH2Cl2 (5.2 mL) with stirring. The solution was cooled to 2 °C (ice-water bath). After 10 min, an aliquot (1.0 mL) was withdrawn, a portion (0.004 mL) of which was immediately analyzed by FAB-MS.

MALDI-MS experiments (typical procedure). A vial was charged with 15- d0/15-d28 (experiment 1; 0.0055 g, 0.0086 mmol, 1.5 mol%) and CH2Cl2 (2.0 mL) with stirring. After 1 min, an aliquot (0.001 mL) was withdrawn and analyzed by MALDI-MS.

A round bottom flask was charged with 16 (0.138 g, 0.574 mmol) and CH2Cl2 (3.7 mL) with stirring. The solution of 15-d0/15-d28 was added (the resulting solution is 0.100 M in 16). A first aliquot (0.001 mL) was immediately withdrawn and analyzed by MALDI-MS. After 10 min, a second aliquot (1.0 mL) was withdrawn, portions (0.001 mL) of which were analyzed by GC and MALDI-MS every 10 min for 2 h.

ESI-MS (experiment 1). In a glove box, a round bottom flask was charged with 17 (0.0250, 0.0995 mmol) and CH2Cl2 (7.0 mL) with stirring. A solution of 15-d0/15- d28 (experiment 1; 0.00064 g, 0.000995 mmol (Mettler Toledo AB135-S/Fact microbalance), 1.0 mol%) in CH2Cl2 (3.0 mL) was added (the resulting solution is 0.0100 M in 17). Aliquots (1.0 mL) were withdrawn every 20 min for 2 h and diluted with 1.0 mL of CH2Cl2. A portion (0.500 mL) of each aliquot was withdrawn and immediately analyzed by ESI-MS.

ESI-MS (experiment 2). In a glove box, a round bottom flask was charged 48 2. Mechanistic study on the activity of a Hoveyda-type catalyst ______

with 17 (0.126, 0.501 mmol) and CH2Cl2 (3.0 mL) with stirring. A solution of 15-d0/15- d28 (experiment 1; 0.0048 g, 0.075 mmol, 1.5 mol%) in CH2Cl2 (2.0 mL) was added (the resulting solution is 0.100 M in 17). Aliquots (0.006 mL) were withdrawn after 2, 5, 8, 11,

14, and 24 min and diluted with 2.0 mL of CH3CN. A portion (0.500 mL) of each aliquot was withdrawn and immediately analyzed by ESI-MS.

Method for calculation of isotope scrambling in FAB-MS experiments.45 In Figure 2.27, the experimental observed and theoretically calculated46 isotope envelopes for natural abundance 15 (15-d0) are depicted.

Figure 2.27. Theoretical (bottom) and experimental (top) isotope envelopes of 15-d0.

Both were assumed to be transferrable to 15-d6, 15-d22, and 15-d28. Software that would fit an experimental spectrum to a linear combination of isotopomers could not be found. Thus, as a rough measure of the 15-d0/15-d6/15-d22/15-d28 ratios, the intensities of the m/z = 626/632/648/654 ions (the most intense of each isotopomer envelope) were compared. 2. Mechanistic study on the activity of a Hoveyda-type catalyst 49 ______

The experimentally observed peak intensities for each recovered catalyst (m/z = 626/632/648/654) were fit to two linear equations. Matrix diagonalization by the Gauss- 47 Jordan method provided the relative contributions for 15-d0, 15-d6, and 15-d22, 15-d28. Essentially identical results were obtained when the calculations were based upon the second most intense ions of the isotope envelopes (m/z = 628/634/650/656). It also made no difference whether the calculations were based upon the experimentally observed or theoretically calculated relative ion intensities within the envelope (Figure 2.27). 50 2. Mechanistic study on the activity of a Hoveyda-type catalyst ______

2.7. References and notes

(1) (a) H. S. Eleuterio, US 3074918 and DE 1072811, filed 1957. (b) E. F. Peters; B. L. Evering, US 2963447, filed 1957. (2) (a) Calderon, N. Acc. Chem. Res. 1972, 5, 127. (b) Chen, H. Y.; Scott, K. W.; Calderon, N. Tetrahedron Lett. 1967, 8, 3327. (c) Ofstead, E. A.; Ward, J. P.; Judy, K. W.; Scott, J.; Calderon, N. J. Am. Chem. Soc. 1968, 90, 4133. (3) Hérisson, J.-L.; Chauvin, Y. Makromol. Chem. 1971, 141, 161. (4) (a) Moulijn, J. A.; Boelhouwer, J.; Mol, J. C. J. Chem. Soc., Chem. Commun. 1968, 633. (b) Visser, F. R.; Boelhouwer, J.; Mol, J. C. J. Catal. 1970, 17, 114. (c) Motroni, G.; Motta, L.; Dall'Asta, G. J. Polym. Sci., Part A: Polym. Chem. 1972, 10, 1601. (5) Maasböl, A.; Fischer, E. O. Angew. Chem., Int. Ed. Engl. 1964, 3, 580. (6) For reviews see: (a) Schrock, R. R. Acc. Chem. Res. 1979, 12, 98. (b) Schrock, R. R. Chem. Rev. 2002, 102, 145. (7) (a) Casey, C. P.; Burkhardt, T. J. J. Am. Chem. Soc. 1973, 95, 5833. (b) Casey, C. P.; Burkhardt, T. J. J. Am. Chem. Soc. 1974, 96, 7808. (8) (a) McGinnis, J.; Katz, T. J. J. Am. Chem. Soc. 1975, 97, 1592. (b) McGinnis, J.; Hurwitz, S.; Katz, T. J. J. Am. Chem. Soc. 1976, 98, 605. (c) McGinnis, J.; Altus, S.; Katz, T. J. J. Am. Chem. Soc. 1976, 98, 606. (d) McGinnis, J.; Lee, S. J.; Katz, T. J. J. Am. Chem. Soc. 1976, 98, 7818.

(9) (a) Burk, P. L.; Carr, D. D.; Grubbs, R. H. J. Am. Chem. Soc. 1975, 97, 3265. (b) Burk, P. L.; Carr, D. D.; Hoppin, C.; Grubbs, R. H. J. Am. Chem. Soc. 1976, 98, 7818. (10) Kress, J.; Osborn, J. A. J. Am. Chem. Soc. 1983, 105, 6346. (11) Coutier, J. L.; Paillet, M.; Leconte, M.; Weiss, K.; Basset, J.-M. O. Angew. Chem., Int. Ed. Engl. 1992, 31, 628. (12) (a) Bazan, G. C.; Khosravi, E.; Feast, W. J.; Gibson, V. C.; O'Reagan, M. B.; Thomas, J. K.; Davis, W. M.; Schrock, R. R. J. Am. Chem. Soc. 1990, 112, 8378. (b) 2. Mechanistic study on the activity of a Hoveyda-type catalyst 51 ______

Bazan, G. C.; Oskam, J. H.; Cho, H.-N.; Park, L. Y.; Schrock, R. R. J. Am. Chem. Soc. 1991, 113, 6899. (c) Feldmann, J.; Canizzo, L. F.; Grubbs, R. H.; Schrock, R. R. Macromolecules 1987, 20, 1169. (13) For reviews see: Schrock, R. R. Tetrahedron 1999, 55, 8141. (14) Nguyen, S. T.; Johnson, L. K.; Ziller, J. W.; Grubbs, R. H. J. Am. Chem. Soc. 1992, 114, 3974. (15) Nguyen, S. T. Doctoral Dissertation, California Institute of Technology, 1995. (16) Handbook of Metathesis, Grubbs, R. H. Ed.; Wiley/VCH, New York, 2003. (17) (a) Dias, E. L.; Nguyen, S. T.; Grubbs, R. H. J. Am. Chem. Soc. 1997, 119, 3887. (b) Sanford, M. S.; Ulman, M.; Grubbs, R. H. J. Am. Chem. Soc. 2001, 123, 6543. (c) Sanford, M. S.; Love, J. A.; Day, M. W.; Grubbs, R. H. J. Am. Chem. Soc. 2003, 125, 10103. (d) Adlhart, C.; Chen, P. Helv. Chim. Acta 2000, 83, 2192. (e) Adlhart, C.; Hinderling, C.; Baumann, P.; Chen, P. J. Am. Chem. Soc. 2000, 122, 8204. (f) Hansen, S. M.; Rominger, F.; Metz, M.; Hofmann, P. Chem. Eur. J. 1999, 5, 557. (g) Meier, R. J.; Aagaard, O. M.; Buda, F. J. Mol. Catal. A: Chem. 2000, 160, 189. (h) Cavallo, L. J. Am. Chem. Soc. 2002, 124, 8965. (i) Costabile, C.; Cavallo, L. J. Am. Chem. Soc. 2004, 126, 9592. (l) Bernardi, F.; Bottoni, A.; Miscione, G. P. Organometallics 2003, 22, 93. (18) Scholl, M.; Trnka, T. M.; Morgan, J. P.; Grubbs, R. R. Tetrahedron Lett. 1999, 40, 2247. (19) Weskamp, T.; Schattenmann, W. C.; Spiegler, M.; Hermann, W. A. Angew.

Chem., Int. Ed. 1998, 37, 2490. (20) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999, 1, 953. (21) Kingsbury, J. S.; Harrity, J. P. A.; Bonitatebus Jr., P. J.; Hoveyda, A. H. J. Am. Chem. Soc. 1999, 121, 791. (22) (a) Garber, S. B.; Kingsbury, J. S.; Gray, B. L.; Hoveyda, A. H. J. Am. Chem. Soc. 2000, 122, 8168. (b) Van Veldhuizen, J. J.; Gillingham, D. G.; Garber, S. B.; Kataoka, O.; Hoveyda, A. H. J. Am. Chem. Soc. 2003, 125, 12502. 52 2. Mechanistic study on the activity of a Hoveyda-type catalyst ______

(23) (a) Gessler, S.; Randl, S.; Blechert, S. Tetrahedron Lett. 2000, 41, 9973. (b) Dunne, A. M.; Mix, S.; Blechert, S. Tetrahedron Lett. 2003, 44, 2733. (c) Zaja, M.; Connon, S. J.; Dunne, A. M.; Rivard, M.; Buschmann, N.; Jiricek, J.; Blechert, S. Tetrahedron 2003, 59, 6545. (d) Krause, J. O.; Nuyken, O.; Wurst, K.; Buchmeiser, M. R. Chem. Eur. J. 2004, 10, 777. (e) Yao, Q.; Zhang, Y. J. Am. Chem. Soc. 2004, 126, 74. (f) Michrowska, A.; Bujok, R.; Harutyunyan, S.; Sashuk, V.; Dolgonos, G.; Grela, K. J. Am. Chem. Soc. 2004, 126, 9318, and references therein. (g) Courchay, F. C.; Sworen, J. C.; Wagener, K. B. Macromolecules 2003, 36, 8231. (h) Matsugi, M.; Curran, D. P. J. Org. Chem. 2005, 70, 1636. (24) (a) Schmutzler, R.; Krafczyk, R.; Craig, H. A.; Goerlich, J. R.; Marshall, W. J.; Unverzagt, M.; Arduengo III, A. J. Tetrahedron 1999, 55, 14523. (b) Trnka, T. M.; Morgan, J. P.; Sanford, M. S.; Wihelm, T. E.; Scholl, M.; Choi, T.-L.; Ding, S.; Day, M. W.; Grubbs, R. H. J. Am. Chem. Soc. 2003, 125, 2546. (25) Ernst, T. D.; Olah, G. A. J. Org. Chem. 1989, 54, 1203. (26) Jafarpour, L.; Hillier, A. C.; Nolan, S. P. Organometallics 2002, 21, 442. (27) Kingsbury, J. S.; Hoveyda, A. H. J. Am. Chem. Soc. 2005, 127, 4510. (28) (a) Ahmed, M.; Barrett, A. G. M.; Braddock, D. C.; Cramp, S. M.; Procopiu, P. A. Tetrahedron Lett. 1999, 40, 8657. (b) Ahmed, M.; Arnauld, T.; Barrett, A. G. M.; Braddock, D. C.; Procopiu, P. A. Synlett 2000, 1007. (29) Rocaboy, C.; Gladysz, J. A. New J. Chem. 2003, 27, 39.

(30) Isotopic Studies of Heterogeneous Catalysis, Ozaki, A. Ed.; Kondasha/Academic Press, New York, 1977. (31) Heumann, K. G. Int. J. Mass Spectrom. 1982, 45, 87. (32) Kane-Maguire L. A. P.; Kanitz, R.; Sheil, M. M. J. Organomet. Chem. 1995, 486, 243. (33) For an application of this method see: Crocco, G. L.; Gladysz, J. A. J. Am. Chem. Soc. 1988, 110, 6110. 2. Mechanistic study on the activity of a Hoveyda-type catalyst 53 ______

(34) Mass spectrometry of Inorganic and Organometallic Compounds, Henderson, W.; McIndoe, J. S. Eds.; John Wiley and Sons Ltd, Chichester, 2005. (35) For reviews see: (a) Colton, R.; D' Agostino, A.; Traeger, J. C. Mass Spectrom. Rev. 1995, 14, 79. (a) Shepherd, R. E. Coord. Chem. Rev. 2003, 247, 147. (36) Varray, S.; Lazaro, R.; Lamaty, F. Organometallics 2003, 22, 2426. (37) Kirkland, T. A.; Grubbs, R. H. J. Org. Chem. 1997, 63, 7310. (38) (a) McNally, J. P.; Cooper, J. N. Organometallics 1988, 7, 1704. (b) Duar, Y.; Bravermann, S. J. Am. Chem. Soc. 1990, 112, 5830. (39) Lee, J. C.; Yuk, J. Y.; Cho, S. H. Synth. Commun. 1995, 25, 1367. (40) Smith, M. B.; Kwon, T. W. Synth. Commun. 1992, 22, 2865. (41) (a) Masnovi, J. M.; Sankararaman, S.; Kochi, J. K. J. Am. Chem. Soc. 1989, 111, 2263. (42) Ruwwe, J.; Martí-Alvarez, J. M.; Horn, C. R.; Bauer, E. B.; Szafer, S.; Lis, T.; Hampel, F.; Cagle, P. C., Gladysz, J. A. Chem. Eur. J. 2001, 7, 3931. (43) FAB, 3-NBA, m/z (%); the peaks correspond to the most intense signal of the isotope envelope. (44) The passage of the slurry through a cotton plug enables the removal of copper- phosphine precipitates that can complicate the chromatography. (45) The method was applied to interpret the FAB-MS spectra. Representative examples are illustrated in Figures 2.16, 2.18, and 2.20.

(46) For an example of isotope envelope calculator see on the web: http://winter.group.shef.ac.uk/chemputer/isotopes.html. (47) For another recent application of this method in a mass spectrometric crossover experiment, see: Venkatraman, S.; Denmark, S. E. J. Org. Chem. 2006, 71, 1668. 3

Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands

Aim of the chapter

The first part of the chapter gives a short overview about molecular rope-skipping rotors and gyroscopes. The aim of the chapter is to present the results of a study concerning the synthesis and the characterization of new classes of doubly trans-spanning bis(pyridine) complexes.

3.1. Introduction

3.1.1. Rope-skipping rotors. The term "molecular rotor" indicates a molecule that consists of two parts that can easily rotate relative to each other. Two components characterize a molecular rotor: the part with a larger moment of inertia, known as the stator, and the part with a smaller moment of inertia, known as the rotator. Although motion is always a function of the frame of the observer, the former is commonly viewed as "stationary". Rope-skipping rotors represent a class of molecular rotors of particular interest.1 The rope-skipping rotor I consists of a cyclic core to whose opposite extremities are attached the two ends of a chain that can swing around the core (Figure 3.1).

Figure 3.1. Model of rope-skipping rotor.

Cyclophanes can be considered the prototype of molecular rope-skipping rotors. 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands 55 ______

Examples of cyclophanes are illustrated in Figure 3.2.2

II III

Figure 3.2. Representative cyclophanes.

Ginsburg and co-workers were the first to synthesize molecular paddlanes in 1973. In an attempt to isolate the singly linked rope-skipping rotor IV, they obtained only the dimeric structure V (Figure 3.3).1

O O O O O O (CH2)n

(CH2)n

(CH2)n O O O O O O

IV V

Figure 3.3. Ginsburg's rope-skipping rotor.

Helder and Wynberg performed variable temperature NMR on the rope-skipping rotor VI (Figure 3.4). They established a strict dependence between the rotation processes and the temperature.3

NC H

(CH2)n

NC H

Figure 3.4. Helder's rope-skipping rotor.

As shown in Scheme 3.1, Vögtle and Mew reported analogous complexes in which the central unit is a triptycene.4 Compound VIII was synthesized by pyrolysis of the disulfone VII. Their NMR analysis showed that the triptycene could not rotate inside the cavity of the chain for any of the lengths assayed. Models indicated that the chain was wedged between two phenyl groups of the triptycene, which is borne out in the 56 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands ______diastereotopicity of the phenyl protons. In particular, the NMR analysis highlighted that two phenyl groups are equivalent and the third is magnetically different.

O S O Δ

O (CH2)n S (CH2)n+2 O

VII VIII

Scheme 3.1. Synthesis of Vögtle's rope-skipping rotor.

Bedard and Moore provided further interesting examples (Figure 3.5).5 They attached a substituted p-diethynylbenzene group to the interior of a phenylethynyl macrocyclic framework. The rotation of the internal phenylene group, as a function of its substituents, was analyzed by NMR.

R = a, H b, CH2OCH3 c, CH2O(3,5-C6H3(t-Bu)2) IX

Figure 3.5. Molecular turnstiles.

Recently, Garcia-Garibay and co-workers have reported designed crystals in which phenylene groups could rotate in the cavity created by the substituents on the phenylene rotator. Examples are shown in Figure 3.6.6

X XI

Figure 3.6. Garcia-Garibay's molecular rotors. 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands 57 ______

3.1.2. Gyroscope-like complexes. The term "gyroscope-like molecule" refers to a particular subset of rope-skipping rotors in which a central core is surrounded with more than one chain. As outlined in Figure 3.7, Gladysz and co-workers have systematically studied gyroscope-like complexes with doubly (XII) and triply (XIII, XIV, and XV) trans-spanning diphosphines.7 The desymmetrization of the rotor, as in XIV, opened possibilities for driven motion in a rotating electric field.

Ph P P P P OC X X X' Pt X Fe CO X' M X Re ( ) = (CH2)n OC X' X P P P P Ph XII XIII XIV XV n = 10, 12, 14, 18 n = 10, 12, 14 n = 14 n = 14 M = Pt, Pd, Rh X = Cl, X' = C6F5 X = CO, X' = Cl, Br X = Cl, X' = Cl, CO

Figure 3.7. Gladysz-type gyroscope-like complexes.

In this type of molecular device, the cage insulates the rotator from external mechanical interferences and provides a potential support to anchor the molecule.

3.2. Project design

In 1999, Lambert and Ng reported the gyroscope-like complex XVII, which represents the first doubly trans-spanning bis(pyridine) gyroscope-like species.8

N Grubbs' first N gen. cat. Cl Pd Cl Cl Pd Cl CH2Cl2, 30 h N N

XVI XVII, 80%

Scheme 3.2. Previous data from Lambert.

They synthesized the palladium complex XVI by reaction of the alkene containing pyridine 2,6-NC5H3(CH2CH2CH=CH2)2 with trans-(PhCN)2PdCl2. No yield was reported for this reaction. The crystal structure of XVI showed an orthogonal orientation of the 58 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands ______pyridines respect to the palladium square plane and a coplanar arrangement of the pyridine with respect to the first three carbon atoms of the alkene chain. However, the data for this structure have never been deposited in the Cambridge Crystallographic Data Centre. The complex XVI (0.033 M) was treated with Grubbs' first generation catalyst (3 charges, 5 mol% each) in ring closing metathesis (RCM). After workup, the gyroscope-like complex XVII was isolated in 80% yield by column chromatography. The structure of XVII was supported by NMR and mass spectrometry. The =CH 1H NMR signal was reported as a multiplet. A crystal structure showed two Z CH=CH linkages. However, the data for this structure have never been deposited in the Cambridge Crystallographic Data Centre. Control experiments were conducted with the free ligand 2,6-

NC5H3(CH2CH2CH=CH2)2 and its acetate salt. No simple metathesis products were detected. Shortly after this publication appeared, Lambert left chemistry for another career. In my investigation, similar alkene-containing pyridines are designed as potential ligands. Modifications are introduced, respectively, in the structure and position of the alkene chains in order to analyze their influence on the reactivity when ligated to metallic centers. This approach enables the synthesis of complexes analogous to the Lambert substrate XVI. It is necessary to monitor the behavior of the complexes in the presence of Grubbs-type catalysts in RCM to define optimal conditions for the synthesis of gyroscope- like complexes. Subsequent catalytic hydrogenation is necessary to simplify the geometric motifs. Finally, in appropriate cases, it is crucial to analyze the desymmetrization of the rotor in model complexes.

3.3. Results

3.3.1. Syntheses of alkene-containing pyridines. As shown in Scheme 3.3, reaction of 2,6-C5H3N(CH2Br)2 (20) with an excess of CH2=CH2CHMgBr (1.0 M in 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands 59 ______diethyl ether, 2.5 equiv) in THF provided the known alkene-containing pyridine 2,6- 9 NC5H3(CH2CH2CH=CH2)2 (21). The product was isolated by column chromatography on silica gel as a yellow oil in good yield (60%).

BrMg Br Br N THF N 20 21, 60%

Scheme 3.3. Synthesis of 21.

As outlined in Scheme 3.4, the one-pot reactions of 20 with the alcohols

HO(CH2)nCH=CH2 (n = a, 1; b, 2; c, 3; d, 4), in presence of the quaternary ammonium + − salt C6H5CH2N(CH3)3 Cl (20 mol%), gave the diethers 2,6-

NC5H3(CH2O(CH2)nCH=CH2)2 (22a-d). The diethers 22a and 22d had been reported previously.10,11

Ph Cl N

Br Br O O + Br O N N N n n HO n n

20 n = 1, 22a, 55% 23a-d 2, 22b, 55%

3, 22c, 45% 4, 22d, 47%

Scheme 3.4. Synthesis of 22a-d.

This protocol, which has been previously applied to benzyl halides,12 enables an efficient conversion of 20 under mild conditions in the presence of an excess of alcohol (4-

6 equiv). Column chromatography on silica gel provided 22a-d in good yields (45-55%). A

+ − lower yield (30%) of 22a was obtained when C6H5CH2N(CH2CH3)3 Cl was utilized. Formation of the monosubstituted products 23a-d (Scheme 3.4) could also be observed. 1H NMR data for 23a are summarized in experimental section. The synthesis of 22a was also attempted with microwave heating (10 min, and 700 W). In this case, the dibromopyridine 20 was recovered as unreacted.

As illustrated in Scheme 3.5, the preparations of 2,6-NC5H3(O(CH2)nCH=CH2)2 60 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands ______

(25a,b) were conducted from 2,6-NC5H3Br2 (24) and HO(CH2)nCH=CH2 (n = a, 1; b, 2) by classical Williamson ether syntheses. The sodium alkoxides were first generated in situ from reaction of sodium with an excess of alcohol. Column chromatography afforded 25a,b as light yellow oils in moderate yields (35%). Formation of the monosubstituted products 26a,b was also observed. 1H NMR data for 26b are summarized in the experimental section.

Na + Br N n n n Br HO O N O Br N O n 24 n = 1, 25a, 35% 26a,b 2, 25b, 35%

Scheme 3.5. Synthesis of 25a,b.

The syntheses of diesters 3,5-NC5H3(COO(CH2)nCH=CH2)2 (29a-g) (n = a-d; e, 5; f, 6; g, 8) were accomplished in two steps as outlined in Scheme 3.6. The pyridine dicarboxylic acid 3,5-NC5H3(COOH)2 (27) was first reacted with SOCl2. This known 13 reaction is catalyzed by DMF and gave 3,5-NC5H3(COCl)2 (28) in quantitative yields.

The pyridine 28 was combined with a slight excess (2.2-3.0 equiv) of HO(CH2)nCH=CH2 11 (n = a, 1; b, 2; c, 3; d, 4; e, 5; f, 6; g, 8) in dry CH2Cl2. After basic workup, 29a-g were isolated in good yields (41-90%) as yellow viscous oils. The diesters 29d and 29g have been reported previously.11,14

O O O O O O SOCl HO HO OH 2 Cl Cl n n O O n

N DMF N N

27 28, 99% n = 1, 29a, 59%

2, 29b, 89%

3, 29c, 84%

4, 29d, 90%

5, 29e, 70%

6, 29f, 41% 8, 29g, 67%

Scheme 3.6. Synthesis of 29a-g.

The alkene-containing pyridines were characterized by NMR (1H and 13C{1H}), 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands 61 ______

IR, and mass spectrometry. Selected spectroscopic data are summarized in Tables 3.1 and 3.2.

Table 3.1. Selected 1H NMR [δ/ppm][a] and IR data [cm–1] for the alkene-containing pyridines.

Alkene- NMR IR containing pyridine o-H m-H p-H CH O OCH pyr pyr pyr 2 2 (liquid film) 6.96 7.50 3076 (s) - - - 21 [7.7][b] [7.7][c] 749 (m) 7.33 7.68 4.12 3084 (w), - 4.64[d] 22a [7.7][b] [7.7][c] [1.4, 5.6][e] 787 (m) 7.36 7.73 3.63 3080 (w), - 4.64[d] 22b [7.7][b] [7.7][c] [6.7][c] 787 (s) 7.35 7.71 3.57 3076 (w), - 4.60[d] 22c [7.7][b] [7.7][c] [6.5][c] 787 (s) 7.32 7.68 3.54 3078 (w), - 4.59[d] 22d [7.7][b] [7.7][c] [6.5][c] 785 (s) 6.33 7.49 4.32 3080 (w), - - 25a [7.9][b] [7.9][c] [1.4, 5.6][e] 787 (m) 6.28 7.47 4.32 3080 (w), - - 25b [7.9][b] [7.9][c] [6.9][c] 787 (m) 9.35 8.85 4.85 3080 (w), - - 29a [2.1][f] [2.1][g] [1.3, 5.8][e] 747 (s) 9.33 8.82 4.42 3082 (w), - - 29b [2.1][f] [2.1][g] [6.7][c] 746 (s) 9.33 8.81 4.41 3076 (w), - - 29c [2.1][f] [2.1][g] [6.7][c] 749 (s) 9.37 8.85 4.41 3078 (w), - - 29d [2.1][f] [2.1][g] [6.7][c] 745 (s) 9.36 8.85 4.39 3076 (w), - - 29e [2.1][f] [2.1][g] [6.7][c] 745 (s) 9.36 8.85 4.39 3076 (w), - - 29f [2.1][f] [2.1][g] [6.7][c] 745 (s) 9.36 8.86 4.39 3076 (w), - - 29g [2.1][f] [2.1][g] [6.7][c] 745 (s) [a] spectra recorded at room temperature in CDCl3. The o/m/p designations are in reference to the nitrogen atom. [b] 3 doublet [ JHH, Hz]. [c] 3 triplet [ JHH, Hz]. [d] singlet. [e] 4 3 double of triplets [ JHH, JHH, Hz]. [f] 4 doublet [ JHH, Hz]. [g] 4 triplet [ JHH, Hz]. 62 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands ______

Table 3.2. Selected 13C{1H} NMR data [δ/ppm] for the alkene-containing pyridines.[a],[b] Alkene- containing o-C [c] m-C [c] p-C [c] CH O[c] OCH [c] CO[c] pyridine pyr pyr pyr 2 2

21 160.9 120.0 136.4 - - -

22a 157.9 119.8 137.2 72.9 71.8 -

22b 158.0 119.7 137.2 73.7 70.3 -

22c 158.2 119.7 138.2 73.7 70.6 -

22d 157.8 120.8 138.5 74.5 70.2 -

25a 162.1 101.6 141.0 - 66.5 -

25b 162.6 101.3 140.6 - 65.0 -

29a 154.1 125.9 137.9 - 66.2 163.9

29b 153.2 126.0 138.0 - 64.3 165.2

29c 154.4 126.6 138.0 - 65.5 164.8

29d 154.1 126.3 138.7 - 65.7 164.6

29e 154.1 126.2 138.5 - 65.8 164.5

29f 154.1 126.2 138.8 - 65.9 164.5

29g 154.1 126.2 139.1 - 65.9 164.5 [a] spectra recorded at room temperature in CDCl3. The o/m/p designations are in reference to the nitrogen atom. [b] for the 13C assignments see reference 42. [c] singlet.

3.3.2. Syntheses of alkene-containing bis(pyridine) complexes. The above alkene-containing pyridines were utilized for syntheses of trans rhodium, platinum, and palladium-based complexes. As shown in Scheme 3.7, the rhodium complex [RhCl(coe)2]2 (coe = cyclooctene) was reacted with a slight excess of 22a (2.2 equiv) in refluxing 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands 63 ______methanol/toluene. A stream of CO was bubbled through the mixture. Column chromatography and recrystallization afforded trans-Rh(Cl)(CO)[2,6-

NC5H3(CH2OCH2CH=CH2)2]2 (trans-30) as a yellow solid in moderate yield (26%). The complex was stable in air on time scale of months.

1. methanol/toluene O O (reflux) N Cl Rh CO [RhCl(coe)2]2 + O O N 2. CO N O O

22a trans-30, 26%

Scheme 3.7. Synthesis of trans-30.

The rhodium complex trans-30 was characterized by NMR (1H and 13C{1H}) and IR spectroscopy, mass spectrometry, DSC, and thermogravimetric and microanalyses, as summarized in the experimental section. Only a single set of pyridine ligand NMR 1 resonances was observed, indicative of a trans geometry. The CH2OCH2CH= H NMR signals of 22a and trans-30 were particularly diagnostic. As shown in Figure 3.8, the singlet of 22a at 4.64 ppm (bottom) was split in two doublets at lower field at 5.76 ppm and 5.64 ppm (top) in trans-30.

5.76 ppm 5.64 ppm

4.64 ppm

Figure 3.8. Partial 1H NMR spectra of 22a (bottom) and trans-30 (top).

As illustrated in Figure 3.9, the presence of two doublets for trans-30 can be easily rationalized. The protons Ha and Hb are diastereotopic, as their interconversion is not 64 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands ______

possible by any symmetry operation. In contrast, Ha and Hc are enantiotopic; they can be interconverted by a mirror symmetry plane situated perpendicular to the N-Rh-N plane, containing the Cl-Rh-CO vector. When rotation around the rhodium-nitrogen bond occurs,

Ha exchanges with Hb', which is in turn enantiotopic to Hb. When this is rapid on the NMR scale, only a single signal would be expected. Hence, rotation of the pyridine ligand or the Cl-Rh-CO rotator must have a significant barrier even in these non-gyroscope-like complexes.

R R Ha Hc

Hb COHd N Rh N

Ha' Cl Hc' R Hb' Hd' R

Figure 3.9. Selected enantiotopic and diastereotopic groups in trans-30.

Alternative synthetic pathways were investigated in order to improve the yield of trans-30. The results are summarized in Table 3.3.15 Further attempts to extend the synthesis to the ligands 22b-d were not successful.

Table 3.3. Alternative procedures for the synthesis of trans-30.

equiv t t Synthesis Complex Solvent refluxing bubbling CO Yield 22a (h) (h)

1 [RhCl(cod)]2 benzene 4.2 0.5 0.5 8%

2 [RhCl(cod)]2 hexanes/CH2Cl2 4 1 1 10%

3 [RhCl(cod)]2 benzene 6 3 1 14%

4 [RhCl(coe)2]2 benzene 4.2 0.5 0.5 7%

5 [RhCl(coe)2]2 MeOH/toluene 6 1 1 17%

6 [RhCl(coe)2]2 MeOH/toluene 6 2 1 22%

Two different series of trans platinum-based complexes were synthesized. In the first PtCl2 was combined with the ligands 22a-d as outlined in Scheme 3.8.

3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands 65 ______

O O benzene n N n PtCl Cl Pt Cl 2 + O O 80 °C n N n N n O O n

n = 1, 22a trans-31a, 88%

2, 22b trans-31b, 26%

3, 22c trans-31c, not formed

4, 22d trans-31d, not formed

Scheme 3.8. Synthesis of trans-31a,b.

In the first experiment, PtCl2 was reacted with a slight excess of 22a (2.2 equiv) in benzene at 80 °C for 5 d. Column chromatography gave trans-PtCl2[2,6-

NC5H3(CH2OCH2CH=CH2)2]2 (trans-31a) in 88% yield as a pale yellow solid. An analogous reaction and workup with 22b afforded trans-PtCl2[2,6-

NC5H3(CH2O(CH2)2CH=CH2)2]2 (trans-31b) in moderate yield (26%). However, analogous procedures with 22c,d did not afford the target molecules trans-31c,d. Complexes trans-31a,b were stable in air for prolonged periods. As described below, a crystal structure of trans-31a established a trans geometry. The complexes were characterized by IR and NMR (1H and 13C{1H}) spectroscopy, mass spectrometry, DSC, and thermogravimetric and microanalyses. As shown in Figure 3.10, the CH2OCH2CH= 1H NMR signal was shifted from 4.64 ppm in 22a (bottom) to 5.82 ppm in trans-31a (top).

5.82 ppm

4.64 ppm

Figure 3.10. Partial 1H NMR spectra of 22a (bottom) and trans-31a (top).

As sketched in Figure 3.11, the CH2OCH2CH= protons are either homotopic (Ha, 66 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands ______

1 Hd and Hb, Hc) or enantiotopic (Ha, Hc and Hb, Hd). Hence, a single H NMR resonance is expected, in accord with Figure 3.10.

R H R a Hc

Hb Cl Hd N Pt N

Ha' Cl Hc' R Hb' Hd' R

Figure 3.11. Selected enantiotopic and homotopic groups in trans-31a.

In a second series of experiments, PtCl2 was reacted similarly with 29a,c-g to give trans-PtCl2[3,5-NC5H3(COO(CH2)nCH=CH2)2]2 (trans-32a,c-g). The results are summarized in Scheme 3.9.

O O

n O O n O O benzene N n O O n PtCl2 + Cl Pt Cl N 80 °C N O O n n O O

n = 1, 29a trans-32a, 87%

3, 29c trans-32c, 84% (56%, synthesis with trans-(PhCN)2PtCl2)

4, 29d trans-32d, 92%

5, 29e trans-32e, 94%

6, 29f trans-32f, 63% 8, 29g trans-32g, 78%

Scheme 3.9. Synthesis of trans-32a,c-g.

In this series of complexes, the trans coordination could not be verified by crystallography as several attempts to obtain suitable crystals failed. However, the crystal structure of a gyroscope-like complex derived from trans-32e is described below. For comparative purposes, the synthesis of trans-32c was also carried out using trans-(PhCN)2PtCl2 as the starting material. The one-pot procedure with PtCl2 is more efficient and convenient, as the synthesis of trans-(PhCN)2PtCN2 is not necessary. All products were obtained in good yields (63-92%) as air stable yellow or pale yellow solids.

As summarized in Scheme 3.10, the palladium complex trans-(PhCN)2PdCl2 was 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands 67 ______combined with 29e as well. An analogous procedure and workup afforded trans-

PdCl2[3,5-NC5H3(COO(CH2)5CH=CH2)2]2 (trans-33e) in almost quantitative yields (94%).

O O

5 O O 5

O O N benzene trans-(PhCN)2PdCl2 + 5 O O 5 Cl Pd Cl 80 °C N N

O O 5 5 O O 29e trans-33e, 94%

Scheme 3.10. Synthesis of trans-33e.

As summarized in Scheme 3.11, trans-(PhCN)2PdCl2 was also combined with the ligand 21 using a slight modification of the Lambert procedure described in section 3.2.8,16

Column chromatography on silica gel gave trans-PdCl2[2,6-NC5H3(CH2CH2CH=CH2)2]2 (trans-34) in low yields (15%) as a pale yellow solid. Importantly, a black precipitate formed during the reaction.

N benzene trans-(PhCN)2PdCl2 + Cl Pd Cl N 80 °C N

21 trans-34, 15%

Scheme 3.11. Synthesis of trans-34.

Both complexes trans-33e and trans-34 were stable in air for prolonged periods. They were characterized analogously to the other new complexes above. Selected spectroscopic (1H NMR, IR, and 13C{1H} NMR) and thermal data for all the preceding complexes are summarized in Tables 3.4-3.6.

68 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands ______

Table 3.4. Selected 1H NMR [δ/ppm][a] and IR data [cm–1] for the alkene-containing bis(pyridine) complexes.

NMR IR Complex (powder

o-Hpyr, m-Hpyr p-Hpyr CH2O OCH2 film) 7.59 7.81 5.76 [15.0][d], 4.29 3088 (w), - trans-30 [7.8][b] [7.8][c] 5.64 [15.0][d] [1.4, 5.5][e] 787 (s) 7.58 7.78 4.27 3092 (w), - 5.82[f] trans-31a [7.9][b] [7.9][c] [1.5, 5.5][e] 787 (s) 7.58 7.78 3.84 3074 (w), - 5.81[f] trans-31b [7.9][b] [7.9][c] [6.6][c] 796 (s) 9.68 9.02 4.92 3082 (w), - - trans-32a [1.8][g] [1.8][h] [1.2, 5.9][e] 745 (s) 9.68 8.99 4.46 3082 (w), - - trans-32c [1.8][g] [1.8][h] [6.7][c] 742 (s) 9.67 8.99 4.44 3075 (w), - - trans-32d [1.8][g] [1.8][h] [6.7][c] 742 (s) 9.67 8.98 4.43 3080 (w), - - trans-32e [1.8][g] [1.8][h] [6.7][c] 741 (s) 9.66 8.98 4.43 3080 (w), - - trans-32f [1.8][g] [1.8][h] [6.7][c] 741 (s) 9.66 8.98 4.42 3080 (w), - - trans-32g [1.8][g] [1.8][h] [6.7][c] 741 (s) 9.59 8.97 4.43 3082 (w), - - trans-33e [1.8][g] [1.8][h] [6.8][c] 742 (s) 7.12 7.61 3080 (w), - - - trans-34 [7.7][b] [7.7][c] 807 (s) 9.96 9.01 4.43 3076 (w), - - trans-39c [1.9][g] [1.9][h] [6.6][c] 741 (s) [a] spectra recorded at room temperature in CDCl3. The o/m/p designations are in reference to the nitrogen atom. [b] 3 doublet [ JHH, Hz]. [c] 3 triplet [ JHH, Hz]. [d] 4 doublet [ JRhH, Hz]. [e] 4 3 double of triplets [ JHH, JHH, Hz]. [f] singlet. [g] 4 doublet [ JHH, Hz]. [h] 4 triplet [ JHH, Hz]. 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands 69 ______

Table 3.5. Selected 13C{1H} NMR data [δ/ppm] for the alkene-containing bis(pyridine) complexes.[a],[b]

[c] [c] [c] [c] [c] [c] Complex o-Cpyr m-Cpyr p-Cpyr CH2O OCH2 CO

trans-30 162.2 121.5 138.0 73.4 72.1 -

trans-31a 161.5 121.5 139.0 72.2 71.3 -

trans-31b 161.3 121.5 138.9 71.9 70.9 -

trans-32a 157.6 128.4 140.1 - 67.1 162.1

trans-32c 157.6 128.5 140.1 - 66.1 162.0

trans-32d 157.5 128.5 140.0 - 66.6 162.1

trans-32e 157.5 128.6 140.0 - 66.8 162.1

trans-32f 157.5 128.6 140.0 - 66.8 162.1

trans-32g 157.4 128.6 140.1 - 67.3 162.1

trans-33e 157.1 128.2 140.4 - 66.8 162.2

trans-34 163.3 122.2 138.2 - - -

trans-39c 158.6 128.9 140.1 - 66.4 162.7 [a] spectra recorded at room temperature in CDCl3. The o/m/p designations are in reference to the nitrogen atom. [b] for the 13C assignments see reference 43. [c] singlet.

70 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands ______

Table 3.6. Thermal stability data [°C].

TGA DSC mp °C[b] Complex [a] mass loss (onset) Ti/Te/Tp/Tc/Tf capillary

trans-30 114.7 79.2/102.6/106.5/109.1/114.8[c] 106-108

trans-31a 163.1 107.5/152.0/154.9/156.5/168.3[c] 148-150

trans-31b 167.9 90.7/109.9/110.8/112.1/135.3[c] 106-108

trans-32a 145.3 [d] 178-180

trans-32c 176.3 72.5/95.5/97.6/99.9/133.3[c] 92-94

49.4/56.6/58.6/61.8/62.6[c] trans-32d 165.3 63.0/65.7/67.3/68.5/68.5[c] 74-76 75.5/76.7/79.3/80.8/83.2[c]

48.5/52.1/53.6/55.6/57.3[c] trans-32e 165.7 74-76 70.4/79.3/81.1/82.9/99.8[c]

trans-32f 171.8 60.8/68.5/70.7/72.3/82.7[c] 66-68

34.5/39.5/41.6/43.6/47.0[c] trans-32g 177.5 68-70 50.6/68.3/70.3/72.1/87.2[c]

28.9/29.4/31.5/33.9/36.7[c] trans-33e 160.0 55-57 41.8/57.8/61.0/63.9/71.2[c]

[a] for Ti/Te/Tp/Tc/Tf abbreviations consult reference 38. [b] conventional melting point apparatus. [c] endotherm. [d] no change in heat capacity was registered in the temperature range 25-160 ºC.

3.3.3. Syntheses of gyroscope-like complexes. The preceding rhodium, platinum and palladium complexes were exposed to Grubbs' first and second generation catalysts in

RCM reactions under slightly different operative conditions (concentration of educt and 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands 71 ______mode of addition of the catalyst) in order to define effective procedures for the synthesis of monomeric gyroscope-like complexes. In appropriate cases, RCM was followed by catalytic hydrogenation. The first RCM attempts were performed with rhodium-based complex trans-30 (Scheme 3.12). The complex was treated with Grubbs' first generation catalyst (10-15 mol%) both at high concentration (0.017 M) and low concentration (0.00201 M). Upon workup, there was not evidence for any gyroscope-like complex, or the starting material.

O O O O Grubbs' first N N gen. cat. Cl Rh CO Cl Rh CO N O O N O O

trans-30

Scheme 3.12. Attempted RCM of trans-30.

In the second series of experiments, platinum-based complexes were investigated as outlined in Scheme 3.13.

O O 1. Grubbs' first O O n N n N gen. cat. Cl Pt Cl 2n-1 Cl Pt Cl 2n-1 N 2. Pd/C, H2 n O O n N O O

trans-31a,b n = 1, trans-35a, 10% (8%, Grubbs' second gen. cat.)

2, trans-35b, 22%

O O O O O O n O O n 1. Grubbs' first N N gen. cat. 2n-1 2n-1 Cl Pt Cl Cl Pt Cl 2. Pd/C, H2 N N O O O O n n O O O O

trans-32d-g n = 4, trans-36d, 20% (12%, Grubbs' second gen. cat.)

5, trans-36e, 45%

6, trans-36f, 18% 8, trans-36g, 14%

Scheme 3.13. Syntheses of trans-35a,b (top) and trans-36d-g (bottom).

72 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands ______

Ring closing metathesis of trans-31a,b and trans-32d-g were carried out in dilute

CH2Cl2 solutions (0.00199-0.00202 M). Grubbs' first generation catalyst (10 mol%) was added at room temperature as a CH2Cl2 solution in one portion. With the synthesis involving trans-31a, a white precipitate was generated few minutes after the addition of the catalyst. The reactions were monitored by 1H NMR. Complete cyclization was achieved after 24 h. The mixtures were chromatographed on a short column of alumina. Thus ensures the removal of the metathesis catalyst and permits a first separation of oligomeric/polymeric species.

Hydrogenations were performed with Pd/C in ethanol/toluene (1.0 atm of H2, 3 d, room temperature).17 The reaction mixtures were passed through a short column of celite.

The gyroscope-like complexes trans-PtCl2[2,6,2',6'-

(NC5H3(CH2O(CH2)2n+2OCH2)2H3C5N)] (trans-35a,b) and trans-PtCl2[3,5,3',5'-

(NC5H3(COO(CH2)2n+2COO)2H3C5N)] (trans-36d-g) were isolated as air stable yellow or white solids after precipitation. With trans-35a and trans-36d, Grubbs' second generation catalyst was also investigated (10 mol%). The results were similar to those with Grubbs' first generation catalyst. Partial 1H NMR spectra for the starting material, intermediate, and product from two representative sequences are provided in Figure 3.12 and 3.13.

CH2Cl2

Figure 3.12. Partial 1H NMR spectra of trans-31b (bottom), trans-31b after RCM (middle), and trans-35b (top). 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands 73 ______

Figure 3.13. Partial 1H NMR spectra of trans-32e (bottom), trans-32e after RCM (middle), and trans-36e (top).

Subsequently, the palladium complexes trans-33e (Scheme 3.10) and trans-34 were similarly investigated. Good results were achieved with trans-34, as summarized in Scheme 3.14. As noted in Scheme 3.2, the first step in this sequence has been studied by Lambert.8

N Grubbs' first N N gen. cat. PtO2 Cl Pd Cl Cl Pd Cl Cl Pd Cl H2 N N N

trans-34, 15% trans-37, 55-58% trans-38, 58-62%

Scheme 3.14. Synthesis of trans-38.

A white precipitate was generated after addition of the first aliquot of Grubbs' first generation catalyst. The reaction was monitored by 1H NMR. Complete cyclization was achieved after 24 h. The yields of trans-37 (55-58%) were lower than Lambert's (80%). 1 The =CH H NMR signal was a multiplet (δ 6.05-5.97, CDCl3), suggesting a mixture of

Z/E C=C isomers. The subsequent hydrogenation was carried out under 1.0 atm of H2 for 3 d at room temperature in CH2Cl2 with PtO2 as catalyst. The gyroscope-like complex trans-PdCl2[2,6,2',6'-(NC5H3((CH2)6)2H3C5N)] (trans-38) was isolated in good yields (58-62%) by column chromatography. All of the preceding gyroscope-like complexes were characterized by NMR (1H and 13C{1H}) and IR spectroscopy, mass spectrometry, DSC, and thermogravimetric and microanalyses. Selected data are summarized in Tables 3.7-3.9. 74 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands ______

Table 3.7. Selected 1H NMR data [δ/ppm] for the gyroscope-like complexes.[a]

Complex o-Hpyr m-Hpyr p-Hpyr CH2O OCH2

7.53 7.80 - 5.95[d] 3.97-3.94[e] trans-35a [7.7][b] [7.7][c] 7.56 7.79 3.89 - 5.90[d] trans-35b [7.8][b] [7.8][c] [6.5][c] 9.68 9.12 4.44 - - trans-36d [1.8][f] [1.8][g] [5.8][c] 9.66 9.12 4.45 - - trans-36e [1.8][f] [1.8][g] [5.9][c] 9.65 9.10 4.46 - - trans-36f [1.8][f] [1.8][g] [5.9][c] 9.65 9.10 4.45 - - trans-36g [1.8][f] [1.8][g] [5.9][c] 7.11 7.54 - - - trans-38 [7.7][b] [7.7][c] [a] spectra recorded at room temperature in CDCl3. The o/m/p designations are in reference to the nitrogen atom. [b] 3 doublet [ JHH, Hz]. [c] 3 triplet [ JHH, Hz]. [d] singlet. [e] multiplet. [f] 4 doublet [ JHH, Hz]. [g] 4 triplet [ JHH, Hz].

Table 3.8. Selected 13C{1H} NMR data [δ/ppm] for the gyroscope-like complexes.[a],[b]

[c] [c] [c] [c] [c] [c] Complex o-Cpyr m-Cpyr p-Cpyr CH2O OCH2 CO

trans-35a 161.0 125.6 139.5 72.5 69.9 -

trans-35b 161.5 121.5 138.9 70.7 69.6 -

trans-36d 157.1 128.6 141.0 - 67.2 162.1

trans-36e 157.0 128.9 141.2 - 67.1 162.1

trans-36f 157.2 128.9 141.0 - 66.9 162.1

trans-36g 157.1 128.8 141.6 - 66.9 162.2

trans-38 165.1 123.8 139.0 - - - [a] spectra recorded at room temperature in CDCl3. The o/m/p designations are in reference to the nitrogen atom. [b] for the 13C assignments see reference 43. [c] singlet. 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands 75 ______

Table 3.9. Thermal stability data [°C].

TGA DSC mp °C[b] Complex [a] Mass loss (onset) Ti/Te/Tp/Tc/Tf capillary

trans-35a 160.0 [c] [d]

trans-35b 231.6 126.7/166.3/170.1/174.7/182.0[e] [f]

trans-36d 253.2 159.5/167.8/194.6/201.7/209.4[e] [g]

trans-36e 63.5/63.5/69.8/74.0/74.0[e] 220.3 75.0/80.4/86.8/91.8/101.0[e] 214-216 208.8/213.9/223.9/229.5/229.5[e]

trans-36f 217.6 137.1/146.0/152.4/154.3/154.3[e] 150-152

trans-36g 165.3 143.5/178.9/187.0/190.3/192.2[e] 182-184

trans-38 159.6 [c] [h]

[a] for Ti/Te/Tp/Tc/Tf abbreviations consult reference 38. [b] conventional melting point apparatus. [c] no change in heat capacity was registered in the temperature range [25-160 ºC]. [d] the sample slightly darkened at 150 °C. It turned black with heating without liquefying (230 °C). [e] endotherm. [f] the sample slightly darkened at 200 °C. It turned black with heating without liquefying (280 °C). [g] the sample slightly darkened at 190 °C. It turned black with heating without liquefying (260 °C). [h] the sample slightly darkened at 150 °C. It turned black with heating without liquefying (240 °C).

76 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands ______

3.3.4. Substitution reactions. As outlined in the sections 3.3.2 and 3.3.3, different types of complexes were isolated and characterized. All complexes, with the exception of trans-30, featured a symmetrical rotor. Attempts to introduce a modification of the rotor and, in appropriate cases, desymmetrization were first pursued utilizing trans-31a (Scheme 3.15).18 In all cases, the complex trans-31a was recovered unreacted (≥ 80%).

O O N NC Pt Cl N O O

O O N 1.3 equiv CH2Cl2, + - Et4N CN reflux, 3d 4 KCN NC Pt CN

N O O O O O O N PhC CH N MeOH/CH2Cl2 Cl Pt C C Ph Cl Pt Cl

N CH Cl /i-Pr NH N O O 2 2 2 O O CuI

trans-31a AgNO3/KCN O O N CH3MgBr NC Pt CN

N O O O O N

H3C Pt CH3 N O O

Scheme 3.15. Attempted substitution reactions with trans-31a.

As shown in Scheme 3.16, a successful result was achieved when trans-32c was treated with PhC≡CH (1.4 equiv) in the presence of CuI. The reaction was conducted in 19 CH2Cl2/i-PrNH2 (10:1 v/v). The complex trans-Pt(Cl)(C≡CPh)[3,5-

NC5H3(COO(CH2)3CH=CH2)2]2 (trans-39c) was isolated in low yields (18%) and characterized by NMR (1H and 13C{1H}) and IR spectroscopy, and mass spectrometry.

O O O O

N PhC CH N Cl Pt Cl Cl Pt C C Ph

N CH2Cl2/i-Pr2NH N CuI O O O O

O O O O trans-32c trans-39c, 18%

Scheme 3.16. Synthesis of trans-39c. 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands 77 ______

3.3.5. Crystallography. X-ray quality crystals were obtained for trans-31a, trans- 35a, trans-35b, trans-36e, and trans-38. The complex trans-31a exhibited a two fold symmetry axis containing the N-Pt-N vector and an orthogonal mirror plane containing the Cl-Pt-Cl vector. The complexes trans-35a and trans-38 showed an inversion center at platinum and palladium, respectively. The structures were solved as described in Chapter 5. Key bond lengths [Å] and angles [°] are listed in Table 3.10. In the structure of trans-31a, one methylene group was disordered, but this could not be resolved. In trans-35b, three methylene groups were disordered and were refined to a 81:19 occupancy ratio. In trans-36e, several sets of methylene groups were disordered, which were refined to 66:34, 65:35, and 73:27 occupancy ratios. Views of the molecular structures are shown in Figures 3.14-3.18.

Table 3.10. Key bond lengths [Å] and angles [º].

trans-31a[a] trans-35a[a] trans-35b[a] trans-36e[a] trans-38[b]

bond lengths

M-Cl1 2.2926(14) 2.3048(8) 2.3060(7) 2.2824(17) 2.3126(4)

M-Cl2 2.2926(14) 2.3048(8) 2.3060(7) 2.2919(16) 2.3126(4)

M-N1 2.033(5) 2.050(3) 2.048(2) 2.004(4) 2.0637(12)

M-N2 2.033(5) 2.050(3) 2.048(2) 2.011(4) 2.0637(12)

bond angles

N1-M-N2 180.0 180.0 180.000(1) 179.20(16) 180.0

C11-M-Cl2 180.0 180.00(3) 180.00(2) 178.71(6) 180.000(3)

C11-M-N1 90.0 90.66(8) 90.64(7) 90.00(3) 90.84(3)

Cl2-M-N2 90.0 90.66(8) 90.64(7) 90.78(12) 90.84(3)

C11-M-N2 90.000(1) 89.34(8) 89.36(7) 89.35(13) 89.16(3)

Cl2-M-N1 90.000(1) 89.34(8) 89.36(7) 89.85(13) 89.16(3) [a] M = Pt. [b] M = Pd.

78 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands ______

Figure 3.14. Thermal ellipsoid plots (50% probability) of trans-31a; view along Cl1-Pt-Cl2 axis (top); view along N1-Pt-N2 axis (middle); view from above the coordination plane (bottom).

3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands 79 ______

Figure 3.15. Thermal ellipsoid plots (50% probability) of trans-35a; view along Cl1-Pt-Cl2 axis (top); view along N1-Pt-N2 axis (middle); view from above the coordination plane (bottom).

80 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands ______

Figure 3.16. Thermal ellipsoid plots (50% probability) of trans-35b; view along Cl1-Pt-Cl2 axis (top); view along N1-Pt-N2 axis (middle); view from above the coordination plane (bottom). The three disordered atoms are depicted in their dominant conformation. 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands 81 ______

Figure 3.17. Thermal ellipsoid plots (50% probability) of trans-36e; view along Cl1-Pt-Cl2 axis (top); view along N1-Pt-N2 axis (middle); view from above the coordination plane (bottom). The disordered atoms are depicted in their dominant conformation. 82 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands ______

Figure 3.18. Thermal ellipsoid plots (50% probability) of trans-38; view along Cl1-Pd-Cl2 axis (top); view along N1-Pd-N2 axis (middle); view from above the coordination plane (bottom). 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands 83 ______

3.4. Discussion

3.4.1. Ligands. As shown in Schemes 3.3-3.6, several types of alkene-containing pyridines are easily prepared. Pyridine 21 was synthesized by coupling of a Grignard reagent to the dibromolutidine 20, while 22a-d and 25a,b were prepared by Williamson ether syntheses, which represents the best method for the synthesis of symmetrical and unsymmetrical ethers. The syntheses of 22a-d were accomplished under mild conditions in a one-pot reaction in the presence of the alcohol, a quaternary ammonium salt, and 20. Quaternary ammonium salts are known as phase-transfer catalyst (PTC) in the Williamson synthesis.20 They can increase the solubility of alkoxides by offering a more lipophilic counter-ion. Examples of their utilization as PTC were reported with various alcohols, benzyl halides, and sodium hydroxide.21 However, they are not stable in alkaline solution at high temperature.22 The reaction was carried out in absence of a base. The method was effective independent of the length of alkene chain. The synthesis of 25a-b involved the treatment of the dibromopyridene 24 with an alkoxide previously generated in situ (Scheme 3.5). The products were isolated always in moderate yields. The monosubstituted pyridines 25a-b were the main products under the conditions employed. However, I did not attempt to optimize this reaction, which presumably could have been taken to higher conversion. Finally, the syntheses of 29a-g could be accomplished from the bis(acyl chloride) 28, which has been previously used as a precursors to diesters.11

3.4.2. Complexes. Transition metal complexes of pyridines are of great interest due to their properties and applications, e. g. in electron and energy transfer processes, as antitumor agents, and components for molecular devices.23 The ability of pyridine and similar nitrogen heterocycles to bind palladium,24 platinum,25 and rhodium26 has been widely described. To the best of my knowledge, the first and only prior example of a 84 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands ______gyroscope-like complex with doubly trans-spanning bis(pyridine) ligands was reported by Lambert and Ng.8 In my work, modified versions of the Lambert complex were sought. The rhodium complex trans-30, shown in Scheme 3.7, exhibited an unsymmetrical central unit. The CO ligand enables the introduction of a dipole moment. In the synthesis of trans-30, the complexes [RhCl(cod)]2 or [RhCl(coe)2]2 were combined with the alkene-containing pyridine 22a. Several protocols were followed in order to optimize the yields. In the first series, the reaction was carried out with very poor results in hexanes/CH2Cl2 or benzene.

In another series, [RhCl(coe)2]2 was used as starting material in methanol/toluene. The yields were improved although they continued to be modest (≤ 26%). On the basis of these results, different approaches were investigated. There is an 27 extensive literature involving simple adducts of pyridine and PtX2 fragments. Therefore, the alkene-containing pyridines 22a-d and 29a,c-g were treated with various platinum precursors. In the first case, the platinum complex trans-31a was isolated in high yields (88%). Surprisingly, lower yields were achieved with trans-31b (26%). Finally, the product was not formed in presence of 22c and 22d. Perhaps the pendant double bonds afford chelated byproducts as the methylene chain is lengthened. As outlined in Scheme 3.9, the subsequent utilization of the 3,5-disubstituted pyridines 29a,c-g afforded the desired complexes trans-32a,c-d in good yields independently from the length of the methylene chain. The same methodology was applied to the synthesis of palladium-based complex trans-33e. The results were in line with those of trans-32e. As outlined in Scheme 3.11, Lambert's complex trans-34 was prepared in the last series of experiments. The complex was isolated in low yields; this may be connected with the formation of a black gummy precipitate, presumably containing palladium (0). Finally, attempts to modify the rotor were carried out utilizing first trans-31a as model complex. As outlined in Scheme 3.15, all efforts were unsuccessful. Substitution of one ligand in the rotor was successful in the case of a 3,5-disubstituted pyridine complex, 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands 85 ______trans-32c. This suggests that 2,6-disubstituted pyridine ligands sterically hinder substitution reactions.

3.4.3. Gyroscope-like complexes. Ring closing metatheses were attempted with all complexes described in section 3.3.2. The first successful results were achieved with the platinum complexes (Scheme 3.13). The reactions were carried out in high dilution to minimize the formation of polymers and oligomers. General and facile methodologies were developed for trans-35a,b and trans-36d-g, independently from the structure of the complex. Subsequently, the palladium complex trans-34 was utilized in RCM, and the essential details of Lambert's earlier report were confirmed. The white precipitate formed shortly after catalyst addition presumably represents oligomeric and/or polymeric species. The hydrogenation of trans-37 provided the new gyroscope-like complex trans-38 in good yields (Scheme 3.14). Van Koten and co-workers reported ring closing metatheses of alkene containing pyridines in metal pincer complexes.28 Although these have not been applied to gyroscope-like molecules, he has used them as springboards to a variety of other novel organometallic and metal-free complexes. Some representative transformations are shown in Scheme 3.17.

O O O NH O 1. Grubbs' first O O gen. cat. Pt N N + N 2. NaCl O O - NH O BF4 O t = 2 h O O

100% 0%

O O O NH 1. Grubbs' first gen. cat. Pt N N + N 2. NaCl NH BF - 4 t = 48 h O O O 50% 50%

Scheme 3.17. Reactivity of pincer-platinum complexes of 2,6 (bottom) and 3,5 (top) disubstituted alkene-containing pyridines. 86 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands ______

The first reaction suggests that trans-32d-g might afford byproducts of the type XVIII in Scheme 3.13. However, none were detected.

2n-1 O O

O O

N Cl Pt Cl N

O O

2n-1

XVIII

3.4.4. Spectroscopy. Since all NMR spectra were recorded in CDCl3, it was a simple matter to calculate the coordination chemical shifts of the pyridine ligands Δδ = 1 δcomplex − δfree ligand. As summarized in Tables 3.11 and 3.12, the H NMR data give positive Δδ values, indicating downfield shifts upon coordination. As summarized in Tables 3.13 and 3.14, the 13C NMR signals also exhibit downfield shifts. The Δδ values are greater for the substituted carbon atoms. The generally uniform trends provide additional support for analogous coordination geometries (trans).

3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands 87 ______

Table 3.11. 1H NMR coordination shifts [Δδ; δ/ppm] for the alkene-containing bis(pyridine) complexes (CDCl3). Alkene- containing Complex o-Hpyr m-Hpyr p-Hpyr Σ(Δδ) pyridine 21 trans-34 - 0.16 0.11 0.43

22a trans-30 - 0.26 0.13 0.65

22a trans-31a 0.25 0.10 0.60

22b trans-31b - 0.22 0.05 0.49

29a trans-32a 0.33 - 0.17 0.83

29c trans-32c 0.35 - 0.18 0.88

29c trans-39c 0.63 - 0.20 1.46

29d trans-32d 0.30 - 0.14 0.74

29e trans-32e 0.31 - 0.13 0.75

29e trans-33e 0.23 - 0.12 0.58

29f trans-32f 0.30 - 0.13 0.73

29g trans-32g 0.30 - 0.12 0.72

1 Table 3.12. H NMR coordination shifts [Δδ; δ/ppm] for the gyroscope-like complexes (CDCl3). Alkene- containing Complex o-Hpyr m-Hpyr p-Hpyr Σ(Δδ) pyridine[a] 21 trans-38 - 0.15 0.04 0.34

22a trans-35a - 0.20 0.12 0.52

22b trans-35b - 0.20 0.06 0.46

29d trans-36d 0.31 - 0.27 0.89

29e trans-36e 0.30 - 0.27 0.87

29f trans-36f 0.29 - 0.25 0.83

29g trans-36g 0.29 - 0.24 0.82

[a] for the precursor complex. 88 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands ______

Table 3.13. 13C{1H} NMR coordination shifts [Δδ; δ/ppm] for the alkene-containing bis(pyridine) complexes (CDCl3). Alkene- containing Complex o-Cpyr m-Cpyr p-Cpyr Σ(Δδ) pyridine 21 trans-34 2.4 2.2 1.8 11.0

22a trans-30 4.3 1.7 0.8 12.8

22a trans-31a 3.6 1.7 1.8 12.4

22b trans-31b 3.3 1.8 1.7 11.9

29a trans-32a 3.5 2.5 2.2 14.2

29c trans-32c 3.2 1.9 2.1 12.3

29c trans-39c 4.2 2.3 2.1 15.1

29d trans-32d 3.4 2.2 1.3 12.5

29e trans-32e 3.4 2.4 1.5 13.1

29e trans-33e 3.0 2.0 1.9 11.9

29f trans-32f 3.4 2.4 1.2 12.8

29g trans-32g 3.3 2.4 1.0 12.4

13 1 Table 3.14. C{ H} NMR coordination shifts [Δδ; δ/ppm] for the gyroscope-like complexes (CDCl3). Alkene- containing Complex o-Cpyr m-Cpyr p-Cpyr Σ(Δδ) pyridine[a] 21 trans-38 4.2 3.8 2.6 18.6

22a trans-35a 3.1 5.8 2.3 20.1

22b trans-35b 3.5 1.8 1.7 12.3

29d trans-36d 3.0 2.3 2.3 12.9

29e trans-36e 2.9 2.7 2.7 13.9

29f trans-36f 3.1 2.7 2.2 13.8

29g trans-36g 3.0 2.6 2.5 13.7

[a] for the precursor complex. 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands 89 ______

3.4.5. Mass spectra and thermal stability. All ligands showed a strong molecular ion (80-100%). All alkene-containing pyridine complexes gave the ions [M+] and [M – Cl]+. In many cases, the signal of the free ligand was observed (100%). In the case of gyroscope-like complexes, the ions [M+] and [M – Cl]+ were observed. The intensities of the molecular ions ranged between 25% and 100%. Ions derived from a free cyclophane-like bis(pyridine) ligand were not detected. Thermal data are summarized in Tables 3.6 and 3.9. All alkene-containing pyridine complexes, with only the exception of trans-32a, and the gyroscope-like complexes trans- 36e-g, exhibited an endotherm in the range where the melting point is visually registered. For the gyroscope-like complexes trans-35a, trans-35b, trans-36d, and trans-38, a melting point was not observed. The samples turned black with heating, without liquefying.

3.4.6. Crystal structures. The crystal structures of trans-31a, trans-35a, trans- 35b, trans-36e, and trans-38 exhibit a variety of interesting features. In Figures 3.19-3.23, space filling models that exclude hydrogens atoms are depicted. Consider the non-gyroscope like complex trans-31a first. The Pt-Cl and Pt-N bond lengths (2.2926(14) Å; 2.033(5) Å) are similar to those of other platinum-based pyridine complexes, as summarized in Table 3.15.29-31

Table 3.15. Pt-Cl and Pt-N bond lengths [Å] in trans-31a and related pyridine complexes.

R R N HO OH Cl Pt Cl N N N N Complex N Cl Pt Cl Cl Pt Cl Cl Pt Cl Cl Pt Cl R R N N N N HO OH

trans-31a 2.299(3) Pt-Cl bond (Å) 2.2926(14) 2.306(2) 2.304(2) 2.308(5) 2.297(3)

2.003(8) Pt-N bond (Å) 2.033(5) 2.041(6) 2.024(5) 1.98(1) 2.031(11)

Also, the N-o-Cpyr-C1-O1 segment exhibits an anti conformation with a torsion angle of ±172.45°. Although the Pt-Cl and Pt-N bond lengths do not vary significantly in 90 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands ______

the crystallographically characterized gyroscope-like complexes, the N-o-Cpyr-C1-X conformations do (vide supra). Importantly, the crystal structure of trans-31a shows that the terminal vinyl groups are pre-organized – one from each trans pyridine above and below the platinum coordination plane – for intramolecular ring closing metathesis. Thus, the moderate yield observed for many metathesis/hydrogenation sequences is somewhat surprising.

Figure 3.19. Representative space filling model for trans-31a.

The space filling model for the gyroscope-like complex trans-35a exhibits a very small void space (Figure 3.20), consequences of which are examined below. Also two N-o-

Cpyr-C-O segments were now gauche, and the other two anti (torsion angles ±91.45° and ±148.66°). These relationships are more evident in Figure 3.15 above. Gauche segments direct the "spokes" connecting the pyridine ligands out of the metal coordination plane.

Figure 3.20. Representative space filling model for trans-35a.

The spokes connecting the pyridine ligands in trans-35b contain ten sp3 hybridized 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands 91 ______atoms, as opposed to only eight for trans-35a. Accordingly, somewhat more void space is evident in the space filling model (Figure 3.21). The four N-o-Cpyr-C-O segments exhibit anti conformations (torsion angles –174.01°, 174.01°, 155.23°, and 178.76°).

Figure 3.21. Representative space filling model for trans-35b.

When the spokes bridge the 3 and 5 positions of the respective pyridine ligands, as in trans-36e, a much greater amount of void space is evident, as depicted in Figure 3.22.

The p-Cpyr-m-Cpyr-C1-O1 and p-Cpyr-m-Cpyr-C32-O32 segments exhibit syn conformations with torsion angles of –8.25° and 4.58°. This renders the oxygen atoms accessible to surfaces or other binding sites.

Figure 3.22. Representative space filling model for trans-36e.

The spokes connecting the pyridine ligands in the palladium complex trans-38 contain only six sp3 hybridized atoms. Accordingly, little or no void space is evident in 92 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands ______

Figure 3.23. The N-o-Cpyr-C1-C2 and N-o-Cpyr-C6-C5 segments exhibit gauche conformations (torsion angles ±78.13° and ±85.06°).

Figure 3.23. Representative space filling model for trans-38.

As summarized in Table 3.16, the interior space of the gyroscope-like complexes can be quantified. The radius of the rotator is approximated by summing the M-Cl bond length and the van der Waals radius of chlorine. The distances between the metal and the remote carbon atoms of each spoke of the gyroscope-like complex are calculated utilizing the two carbon atoms closest to the plane of the MCl2 rotator. The van der Waals radius of an sp3 carbon atom (1.70 Å)32 is subtracted from the shortest distance. The resulting values can be viewed as a "horizontal clearance" or "bridge height". A representative example is sketched in Figure 3.24.

Figure 3.24. Example of calculation summarized in Table 3.16 using trans-35b; vdW = van der Waals. 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands 93 ______

Table 3.16. Key distances [Å] involving rotator and stator atoms for the gyroscope-like complexes.

trans-35a[a] trans-35b[a] trans-36e[a] trans-38[b]

2.282 M-Cl 2.305 2.306 2.292 2.313 M-Cl plus vdW 4.032 4.055 4.056 4.063 radius of Cl 4.042 [c] M to Ca 4.187 6.075 9.357 4.282 [c] M to Cb 4.667 6.499 9.478 4.565 [d] M-Cdistal 2.487 4.375 7.657 2.582 M-C[e] 2.967 4.799 7.778 2.865 [a] M = Pt. [b] M = Pd. [c] distances (non-bonded) from platinum and palladium to the remote carbon atoms of the macrocycle that are closest to the plane of the rotator (Ca, Cb). [d] the shortest of the previous two distances, minus van der Waals of carbon (1.70 Å). [e] the longest of the previous two distances, minus van der Waals of carbon (1.70 Å).

The data in Table 3.16 clearly indicate that there is insufficient clearance for the

MCl2 rotators in trans-35a and trans-38 to rotate. As noted above, these have the lowest "void space". The radii of the rotators (4.055-4.063 Å) are much greater than the clearance offered by the spokes (2.487-2.582 Å). However, the longer spokes in trans-35b (ten sp3 hybridized atoms) increase the distance to the distal carbon (4.375 Å) such that PtCl2 rotation could occur without carbon/chlorine van der Waals contact. Nonetheless, note that the anti N-o-Cpyr-C-O segments in Figure 3.21 will also severely restrict PtCl2 rotation. Importantly, trans-36e, in which the spokes bridge the three and five pyridine positions, features a much longer distance to the distal carbon (7.657 Å). Furthermore, there are no constraining ortho substituents. Hence, this complex is likely a functional rotor. However, the symmetry is too high for this to be probed by conventional solution phase NMR techniques. With respect to the steric barriers associated with ortho substituents, some non- crystallographic data merit emphasis. A number of complexes of the formula 29,31 trans-PtCl2(2-NC5H4X)2 have been characterized, where X is an ortho substituent. These have been observed to exist as two isomers in solution, derived from restricted 94 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands ______rotation about the platinum-nitrogen bond. As depicted in Scheme 3.16, they are analogous to classical organic atropisomers. To the best of my knowledge, no activation barriers are yet available. However in the case of the 2-picoline adduct, a lower limit of 17.0 kcal/mol could be set.29

X X X Cl Cl N Pt N N Pt N Cl Cl X

Scheme 3.18. Atropisomerism in substituted pyridine complexes.

Lattice packing is also of interest. The platinum complex trans-31a crystallizes in the Cmca space group, with Z = 4 and V = 2759.69(9) Å3. It has two sets of molecules with parallel Cl-Pt-Cl axes as illustrated in Figure 3.25. Within one set, the Pt···Pt distance is 8.889 Å.

Figure 3.25. Packing diagram of trans-31a with (left) and without (right) spokes.

The gyroscope-like complex trans-35a crystallizes in a P21/c space group, with Z = 2 and V = 1148.16(7) Å3. Similarly to trans-31a, trans-35a has two sets of molecules with parallel Cl-Pt-Cl axes as illustrated in Figure 3.26. Within one set, the Pt···Pt distance is 7.911 Å.

Figure 3.26. Packing diagram of trans-35a with (left) and without (right) spokes. 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands 95 ______

The gyroscope-like complex trans-35b crystallizes in a P-1 space group, with Z = 1 and V = 651.84(2) Å3. As illustrated in Figure 3.27, all complexes have parallel Cl-Pt-Cl axes.

Figure 3.27. Packing diagram of trans-35b with (left) and without (right) spokes.

The gyroscope-like complex trans-36e crystallizes in a P-1 space group, with Z = 2 and V = 2409(8) Å3. As with the previous structure, all complexes have parallel Cl-Pt-Cl axes (Figure 3.28).

Figure 3.28. Packing diagram of trans-36e with (left) and without (right) spokes.

Finally, the gyroscope-like complex trans-38 crystallizes in a P21/c space group, with Z = 2 and V = 1017.13(4) Å3. As illustrated in Figure 3.29, trans-38 has two sets of molecules with parallel axes. Within one set, the distance Pd···Pd distance is 11.163 Å.

Figure 3.29. Packing diagram of trans-38 with (left) and without (right) spokes. 96 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands ______

In the case of trans-31a, trans-35a, and trans-38, the relationship between the two sets of molecules with non-parallel axes can be quantified in several ways. One approach is to define one least squares plane consisting of the six atoms of two parallel Cl-Pt-Cl axes of one set, and the analogous plane of the other set. Alternatively, the angles between the planes defined by the Cl-Pt-Cl axis and a pyridine ligand nitrogen atom can be taken (Table 3.17).

Table 3.17. Angles [°] between sets of gyroscope-like complexes with parallel axes in the solid state.[a]

Plane used trans-31a trans-35a trans-35b trans-36e trans-38

Cl1-M-Cl2 + Cl1-M-Cl2 57.92 82.46 - - 44.15

C11-M-Cl2 + N[b] 57.92 75.62 - - 66.42 [a] the values indicate the angles between the planes defined by the indicated atoms. [b] a pyridine ligand nitrogen atom that is bound to M.

3.4.7. Future directions. There is an intense and extensive interest in molecular rotors as gyroscope-like molecules.33 In this class of nano-devices, the rotators can feature a dipole moment that enables their alignment to an external electric field as in compasses, or forces unidirectional rotation in a rotating electric field as in gyroscopes.33 All my complexes exhibited a symmetrical rotator. In contrast to the results achieved with triply trans-spanning diphosphine complexes, there has been only very limited success concerning the modification of the rotator. Hence, an extensive and systematic study is needed to define effective substitution processes. The desymmetrization of the rotator will enable classical NMR analysis of the rotation rate in solution. The second challenge will consist of the modification of the molecular architecture of the stator that enables an "anchorage" to a suitable surface. Surface-mounted molecular rotors show a great and unexplored potential.34 The modification of the cage to provide a chemical "platform" to the physical, and in particular, chemical absorption on a surface opens interesting perspectives for the control of the motions in molecular electronics. In 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands 97 ______this context, one important method is the attachment of conducting molecules to a gold surface.35 In appropriate cases, molecular rotors could act as conformational molecular rectifiers (CMR) if the conductivities depend on the angle of rotation either through changes in the electronic structure or through a communication I/O type (connection or separation) of two conducting elements of the molecule. An example, reported by Troisi and Ratner, is sketched in Figure 3.30.36

------

S S + + + + + + + +

Figure 3.30. Scheme of contact-modulated CMR with two conformations.

3.5. Conclusions

In summary, reactions of alkene-containing pyridines 2,6-

NC5H3(CH2CH2CH=CH2)2, 2,6-NC5H3(CH2O(CH2)nCH=CH2)2 (n = a, 1; b, 2; c, 3; d,

4), 2,6-NC5H3(O(CH2)nCH=CH2)2 (n = a, 1; b, 2), and 3,5-

NC5H3(COO(CH2)nCH=CH2)2 (n = a, 1; b, 2; c, 3; d, 4; e, 5; f, 6; g, 8) with

[RhCl(coe)2]2 (methanol/toluene solvent), trans-(PhCN)2PtCl2 (benzene solvent), PtCl2

(benzene solvent), and trans-(PhCN)2PdCl2 (benzene solvent) afforded, in appropriate cases, the corresponding rhodium, platinum and palladium complexes. These were subjected, using Grubbs-type catalysts, to RCM/hydrogenation sequences reactions. Successful results were achieved only with platinum and palladium complexes. New classes of doubly trans-spanning bis(pyridine) gyroscope-like complexes could be isolated in low to moderate yields. This study was supported by crystallographic data, the analysis of which offered additional insights into the rotor function. 98 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands ______

3.6. Experimental section

General data. Reactions were carried out under dry nitrogen atmospheres using conventional Schlenk techniques. Workups were carried out in air. Chemicals were treated as follows: CH2Cl2, distilled from CaH2 or simple distillation (for workups); benzene, toluene, and THF, distilled from Na/benzophenone; methanol and ethanol, distilled from magnesium turnings; diethyl ether, ethyl acetate, pentane, hexanes, and HOCH2CH=CH2

(98%, Fluka), simple distillation; CDCl3 (Deutero GmbH), stored over molecular sieves;

2,6-NC5H3(CH2Br)2 (20, Aldrich, 98%), 2,6-NC5H3Br2 (24, Aldrich, 98%), + − C6H5CH2N(CH3)3 Cl (Aldrich, 97%), HO(CH2)2CH=CH2 (Acros Organics, 96%),

HO(CH2)3CH=CH2 (Acros Organics, 97%), HO(CH2)4CH=CH2 (Acros Organics, 99%),

HO(CH2)5CH=CH2 (TCI, > 96%), HO(CH2)6CH=CH2 (TCI, > 96%),

HO(CH2)8CH=CH2 (Aldrich, 97%), DMF (Acros, 99+%), 3,5-NC5H3(COOH)2 (27,

Aldrich), NaHCO3 (Grüssig), NH4Cl (Grüssig), NaOH (Grüssig), CH2=CH2CHMgBr (1.0

M in diethyl ether, Fluka), SOCl2 (Acros, 99.7%), trans-(PhCN)2PtCl2 (Alfa Aesar, 98%), trans-(PhCN)2PdCl2 (Acros, 99%), [RhCl(coe)2]2 (Acros, 97%), PtCl2 (ABCR, 99.9%),

Ru(=CHPh)(PCy3)2(Cl)2 (Aldrich), silica gel (60 M, Macherey-Nagel), alumina (neutral,

Macherey-Nagel), MgSO4 (Riedel-de Haën), celite (Macherey-Nagel), CuI (Acros,

99.9%), i-Pr2NH (Fluka 99%), PhC≡CH (Acros, 98%), PtO2 (Aldrich), and Pd/C

(Lancaster or Acros, 10%) were used as purchased. Ru(=CHPh)(H2IMes)(PCy3)(Cl)2 was synthesized by standard literature procedures.37 NMR spectra were recorded at ambient probe temperature on standard 300 or 400 MHz FT spectrometers. IR spectra were recorded on an ASI React IR®-1000 instrument. Differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) data were recorded with a Mettler-Toledo DSC821 instrument and treated by standard methods.38 Mass spectra were obtained using a Micromass Zabspec instrument (FAB),39 or a

Shimadzu Biotech Axima Confidence instrument (MALDI).40 Microanalyses were 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands 99 ______conducted on a Carlo Erba EA1110 CHN instrument. Thin-layer chromatography (TLC) ® was carried out on ALUGRAM SIL G/UV254 (Macherey-Nagel) and visualized by UV.

9 2,6-NC5H3(CH2CH2CH=CH2)2 (21). A round bottom flask was charged with 20 (2.000 g, 7.549 mmol), and THF (76 mL). The solution was cooled to 0 °C with stirring.

After 15 min, CH2=CHCH2MgBr (19 mL, 1.0 M in diethyl ether, 19.0 mmol) was added dropwise over 20 min. The cooling bath was removed. After 18 h, cold saturated aqueous

NH4Cl (20 mL) was added dropwise over 20 min. The organic layer was collected, washed with water (3 × 20 mL), and dried (MgSO4). The solvent was removed by rotary evaporation. The orange residue was chromatographed on silica gel (40 × 3 cm column, 5:1 v/v hexanes/ethyl acetate). The solvents were removed by rotary evaporation and oil pump vacuum from the product-containing fractions to give 21 as a yellow oil (0.847 g,

4.52 mmol, 60%; Rf (TLC) = 0.90).

41 1 3 3 NMR (δ, CDCl3): H 7.50 (t, 1H, JHH = 7.7 Hz, p-Hpyr), 6.96 (d, 2H, JHH = 3 3 3 7.7 Hz, m-Hpyr), 5.88 (ddt, 2H, JHHtrans = 17.0 Hz, JHHcis = 10.3 Hz, JHH = 6.6 Hz, 3 2 2CH=), 5.05 (dd, 2H, JHHtrans = 17.1 Hz, JHH = 1.9 Hz, 2 =CHEHZ), 4.97 (dd, 2H, 3 2 3 JHHcis = 10.2 Hz, JHH = 1.3 Hz, 2 =CHEHZ), 2.87 (t, 4H, JHH = 7.8 Hz, 2CH2), 2.49 3 13 1 42 (q, 4H, JHH = 7.4 Hz, 2CH2); C{ H} 160.9 (s, o-Cpyr), 137.9 (s, CH=), 136.4 (s, p-

Cpyr), 120.0 (s, m-Cpyr), 114.9 (s, =CH2), 37.8 and 34.0 (2 s, 2CH2). 39a + + MS: 188 ([21 + H] , 80%), 133 ([21 − CH2CH2CH=CH2] , 100%). IR (cm−1, oil film): 3076 (w), 2922 (m), 2853 (w), 1640 (m), 1579 (s), 1455 (s), 996 (s), 911 (s), 804 (m), 749 (m).

12 2,6-NC5H3(CH2OCH2CH=CH2)2 (22a). A Schlenk flask was charged with 20 + (3.300 g, 12.45 mmol), HOCH2CH=CH2 (3.620 g, 62.32 mmol), and C6H5CH2N(CH3)3 Cl− (0.464 g, 2.50 mmol, 20 mol%), and fitted with a condenser. The solution was refluxed 100 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands ______with stirring (24 h), cooled to room temperature, and poured into 20 mL of water. The organic layer was separated. The aqueous layer was extracted with CH2Cl2 (4 × 10 mL). The organic layer and the extracts were combined, washed with water (3 × 20 mL) and saturated aqueous NaHCO3 (4 × 20 mL), and dried (MgSO4). The solvent was removed by rotary evaporation. The yellow residue was chromatographed on silica gel (40 × 3 cm column, 4:1 v/v hexanes/ethyl acetate). The solvents were removed from the product- containing fractions by rotary evaporation and oil pump vacuum to give 22a as a light 1 13 1 yellow oil (1.503 g, 6.86 mmol, 55%; Rf (TLC) = 0.46). The H and C{ H} NMR data agreed well with those previously reported.10

41 1 3 3 NMR (δ, CDCl3): H 7.68 (t, 1H, JHH = 7.7 Hz, p-Hpyr), 7.33 (d, 2H, JHH = 3 3 3 7.7 Hz, m-Hpyr), 5.98 (ddt, 2H, JHHtrans = 17.2 Hz, JHHcis = 10.4 Hz, JHH = 5.6 Hz, 3 2 2CH=), 5.34 (dd, 2H, JHHtrans = 17.2 Hz, JHH = 1.6 Hz, 2 =CHEHZ), 5.23 (dd, 2H, 3 2 4 JHHcis = 10.4 Hz, JHH = 1.5 Hz, 2 =CHEHZ), 4.64 (s, 4H, 2CH2O), 4.12 (dt, 4H, JHH = 3 13 1 42 1.4 Hz, JHH = 5.6 Hz, 2OCH2CH=); C{ H} 157.9 (s, o-Cpyr), 137.2 (s, p-Cpyr), 134.4

(s, CH=), 119.8 (s, m-Cpyr), 117.3 (s, =CH2), 72.9 and 71.8 (2 s, CH2OCH2). MS:39a 220 ([22a + H]+, 100%). IR (cm−1, oil film): 3084 (w), 2918 (s), 2853 (m), 1648 (w), 1594 (m), 1459 (m), 1347 (m), 1100 (s), 992 (s), 922 (s), 787 (m).

Data for 2,6-NC5H3(CH2Br)(CH2OCH2CH=CH2) (23a). This byproduct was isolated from the preceding reaction by continued elution of the column with hexanes/ethyl acetate (4:1 v/v; Rf (TLC) = 0.55).

1 41 3 3 H NMR (δ, CDCl3): 7.70 (t, 1H, JHH = 7.8 Hz, p-Hpyr), 7.39 (d, 1H, JHH = 3 3 7.7 Hz, m-Hpyr), 7.34 (d, 1H, JHH = 7.7 Hz, m-Hpyr), 5.98 (ddt, 1H, JHHtrans = 17.2 Hz, 3 3 3 2 JHHcis = 10.4 Hz, JHH = 5.6 Hz, CH=), 5.34 (dd, 1H, JHHtrans = 17.2 Hz, JHH = 1.6 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands 101 ______

3 2 Hz, =CHEHZ), 5.23 (dd, 1H, JHHcis = 10.4 Hz, JHH = 1.5 Hz, =CHEHZ), 4.64 (s, 2H, 4 3 CH2O), 4.53 (s, 2H, CH2Br), 4.12 (dt, 2H, JHH = 1.4 Hz, JHH = 5.6 Hz, OCH2CH=).

2,6-NC5H3(CH2O(CH2)2CH=CH2)2 (22b). Pyridine 20 (2.000 g, 7.548 mmol), + − HO(CH2)2CH=CH2 (2.721 g, 37.74 mmol), and C6H5CH2N(CH3)3 Cl (0.280 g, 1.51 mmol, 20 mol%) were combined in a procedure analogous to that for 22a. An identical workup gave 22b as a light yellow oil (1.020 g, 4.326 mmol, 55%; Rf (TLC) = 0.42).

41 1 3 3 NMR (δ, CDCl3): H 7.73 (t, 1H, JHH = 7.7 Hz, p-Hpyr), 7.36 (d, 2H, JHH = 3 3 3 7.7 Hz, m-Hpyr), 5.87 (ddt, 2H, JHHtrans = 17.1 Hz, JHHcis = 10.3 Hz, JHH = 6.8 Hz, 3 2 2CH=), 5.09 (dd, 2H, JHHtrans = 17.2 Hz, JHH = 1.6 Hz, 2 =CHEHZ), 4.99 (dd, 2H, 3 2 3 JHHcis = 10.2 Hz, JHH = 1.3 Hz, 2 =CHEHZ), 4.64 (s, 4H, 2CH2O), 3.63 (t, 4H, JHH = 3 13 1 42 6.7 Hz, 2OCH2CH2), 2.44 (q, 4H, JHH = 6.7 Hz, 2CH2); C{ H} 158.0 (s, o-Cpyr),

137.2 (s, p-Cpyr), 135.1 (s, CH=), 119.7 (s, m-Cpyr), 116.5 (s, =CH2), 73.7 (s, CH2O), 70.3

(s, OCH2CH2), 34.2 (s, CH2). MS:39a 248 ([22b + H]+, 100%). IR (cm−1, oil film): 3080 (w), 2910 (s), 2860 (m), 1640 (w), 1455 (m), 1351 (m), 1112 (s), 992 (s), 915 (s), 787 (s).

2,6-NC5H3(CH2O(CH2)3CH=CH2)2 (22c). Pyridine 20 (3.000 g, 11.32 mmol), + − HO(CH2)3CH=CH2 (5.860 g, 68.03 mmol), and C6H5CH2N(CH3)3 Cl (0.420 g, 2.26 mmol) were combined in a procedure analogous to that for 22a. An identical workup gave

22c as a colorless oil (1.412 g, 5.127 mmol, 45%; Rf (TLC) = 0.43).

41 1 3 3 NMR (δ, CDCl3): H 7.71 (t, 1H, JHH = 7.7 Hz, p-Hpyr), 7.35 (d, 2H, JHH = 3 3 3 7.7 Hz, m-Hpyr), 5.83 (ddt, 2H, JHHtrans = 17.0 Hz, JHHcis = 10.3 Hz, JHH = 6.7 Hz, 3 2 2CH=), 5.03 (dd, 2H, JHHtrans = 17.2 Hz, JHH = 2.0 Hz, 2 =CHEHZ), 4.99 (dd, 2H, 102 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands ______

3 2 3 JHHcis = 10.2 Hz, JHH = 2.0 Hz, 2 =CHEHZ), 4.60 (s, 4H, 2CH2O), 3.57 (t, 4H, JHH = 13 1 6.5 Hz, 2OCH2CH2), 2.20-2.14 (m, 4H, 2CH2), 1.79-1.72 (m, 4H, 2CH2); C{ H} 158.2 42 (s, o-Cpyr), 138.2 (s, p-Cpyr), 137.2 (s, CH=), 119.7 (s, m-Cpyr), 114.8 (s, =CH2), 73.7 (s,

CH2O), 70.6 (s, OCH2CH2), 30.3 and 28.9 (2 s, 2CH2). MS:39a 276 ([22c + H]+, 100%). IR (cm−1, oil film): 3076 (w), 2937 (m), 2864 (m), 1640 (s), 1594 (s), 1445 (s), 1347 (s), 1116 (s), 992 (s), 911 (s), 787 (s).

2,6-NC5H3(CH2O(CH2)4CH=CH2)2 (22d). Pyridine 20 (1.000 g, 3.774 mmol), + − HO(CH2)4CH=CH2 (1.512 g, 15.10 mmol), and C6H5CH2N(CH3)3 Cl (0.140 g, 0.754 mmol) were combined in a procedure analogous to that for 22a. An identical workup gave

22d as light yellow oil (0.542 g, 1.79 mmol, 47%; Rf (TLC) = 0.46).

41 1 3 3 NMR (δ, CDCl3): H 7.68 (t, 1H, JHH = 7.7 Hz, p-Hpyr), 7.32 (d, 2H, JHH = 3 3 3 7.7 Hz, m-Hpyr), 5.79 (ddt, 2H, JHHtrans = 17.0 Hz, JHHcis = 10.3 Hz, JHH = 6.7 Hz, 3 2 2CH=), 4.98 (dd, 2H, JHHtrans = 17.1 Hz, JHH = 1.8 Hz, 2 =CHEHZ), 4.93 (dd, 2H, 3 2 3 JHHcis = 10.2 Hz, JHH = 1.6 Hz, 2 =CHEHZ), 4.59 (s, 4H, 2CH2O), 3.54 (t, 4H, JHH =

6.5 Hz, 2OCH2CH2), 2.09-2.01 (m, 4H, 2CH2), 1.68-1.62 (m, 4H, 2CH2), 1.51-1.45 (m, 13 1 42 4H, 2CH2); C{ H} 157.8 (s, o-Cpyr), 138.5 (s, p-Cpyr), 136.8 (s, CH=), 120.8 (s, m-

Cpyr), 115.1 (s, =CH2), 74.5 (s, CH2O), 70.2 (s, OCH2CH2), 33.8, 30.3, and 28.7 (3 s,

3CH2). MS:39a 304 ([22d + H]+, 100%). IR (cm−1, oil film): 3078 (w), 2941 (m), 2870 (m), 1645 (s), 1600 (s), 1448 (s), 1350 (s), 1120 (s), 994 (s), 915 (s), 785 (s).

2,6-NC5H3(OCH2CH=CH2)2 (25a). A round bottom flask was charged with sodium (0.582 g, 25.32 mmol), and HOCH2CH=CH2 (4.407 g, 75.98 mmol) was added 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands 103 ______over 5 min with stirring. The flask was fitted with a condenser. The mixture was refluxed until the sodium dissolved (2 h). Pyridine 24 (1.000 g, 4.221 mmol) was added, and the mixture was refluxed (3 h). After 1 h, a yellow solution had formed, which was cooled to room temperature and poured into water (20 mL). The organic layer was separated. The aqueous layer was extracted with diethyl ether (3 × 15 mL). The organic layer and the extracts were combined and dried (MgSO4). The solvent was removed by rotary evaporation. The residue was chromatographed on silica gel (40 × 3 cm column, 4:1 v/v hexanes/CH2Cl2). The solvents were removed from the product-containing fractions by rotary evaporation and oil pump vacuum to give 25a as a light yellow oil (0.2825 g, 1.477 mmol, 35%; Rf (TLC) = 0.34).

41 1 3 3 NMR (δ, CDCl3): H 7.49 (t, 1H, JHH = 7.9 Hz, p-Hpyr), 6.33 (d, 2H, JHH = 3 3 3 7.9 Hz, m-Hpyr), 6.09 (ddt, 2H, JHHtrans = 16.9 Hz, JHHcis = 10.9 Hz, JHH = 5.7 Hz, 3 2 2CH=), 5.39 (dd, 2H, JHHtrans = 17.2 Hz, JHH = 1.5 Hz, 2 =CHEHZ), 5.26 (dd, 2H, 3 2 4 3 JHHcis = 10.4 Hz, JHH = 1.2 Hz, 2 =CHEHZ), 4.32 (dt, 4H, JHH = 1.4 Hz, JHH = 5.6 13 1 42 Hz, 2OCH2); C{ H} 162.1 (s, o-Cpyr), 141.0 (s, p-Cpyr), 133.7 (s, CH=), 117.4 (s,

=CH2), 101.6 (s, m-Cpyr), 66.5 (s, OCH2). MS:40 192 ([25a + H]+, 100%). IR (cm−1, oil film): 3080 (w), 2953 (m), 2856 (m), 1602 (s), 1579 (s), 1440 (s), 1309 (s), 1231 (s), 1143 (m), 1042 (s), 992 (s), 922 (s), 787 (m), 729 (s).

2,6-NC5H3(O(CH2)2CH=CH2)2 (25b). Pyridine 24 (1.000 g, 4.221 mmol), sodium (0.582 g, 25.32 mmol), and HO(CH2)2CH=CH2 (5.477 g, 75.96 mmol) were combined in a procedure analogous to that for 25a. An identical workup gave 25b as a light yellow oil (0.3238 g, 1.477 mmol, 35%; Rf (TLC) = 0.34).

41 1 3 3 NMR (δ, CDCl3): H 7.47 (t, 1H, JHH = 7.9 Hz, p-Hpyr), 6.28 (d, 2H, JHH = 104 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands ______

3 3 3 7.9 Hz, m-Hpyr), 5.91 (ddt, 2H, JHHtrans = 17.1 Hz, JHHcis = 10.3 Hz, JHH = 6.8 Hz, 3 2 2CH=), 5.16 (dd, 2H, JHHtrans = 17.2 Hz, JHH = 1.7 Hz, 2 =CHEHZ), 5.10 (dd, 2H, 3 2 3 JHHcis = 10.2 Hz, JHH = 1.6 Hz, 2 =CHEHZ), 4.32 (t, 4H, JHH = 6.9 Hz, 2OCH2), 2.58- 13 1 42 2.50 (m, 4H, 2CH2); C{ H} 162.6 (s, o-Cpyr), 140.6 (s, p-Cpyr), 134.4 (s, CH=), 116.8

(s, =CH2), 101.3 (s, m-Cpyr), 65.0 (s, OCH2), 33.3 (s, CH2CH=). MS:39a 220 ([25b + H]+, 100%). IR (cm−1, oil film): 3080 (w), 2953 (m), 2853 (m), 1606 (s), 1579 (s), 1444 (s), 1316 (s), 1235 (s), 1143 (m), 1027 (s), 988 (s), 915 (s), 787 (m), 729 (s).

Data for 2,6-NC5H3(CH2Br)(O(CH2)2CH=CH2)2 (26b) This byproduct was isolated from the preceding reaction by continued elution of the column with hexanes/CH2Cl2 (4:1 v/v; Rf (TLC) = 0.43).

1 41 3 3 H NMR (δ, CDCl3): 7.42 (dd, 1H, JHH = 8.2 Hz, JHH = 7.5 Hz, p-Hpyr), 7.06 4 3 4 3 (dd, 1H, JHH = 0.7 Hz, JHH = 7.5 Hz, m-Hpyr), 6.99 (dd, 1H, JHH = 0.7 Hz, JHH = 8.2 3 3 3 Hz, m-Hpyr), 5.90 (ddt, 1H, JHHtrans = 17.1 Hz, JHHcis = 10.3 Hz, JHH = 6.8 Hz, CH=), 3 2 3 5.17 (dd, 1H, JHHtrans = 17.2 Hz, JHH = 1.7 Hz, =CHEHZ), 5.10 (dd, 1H, JHHcis = 10.2 2 3 Hz, JHH = 1.2 Hz, =CHEHZ), 4.37 (t, 2H, JHH = 6.7 Hz, OCH2), 2.58-2.50 (m, 2H,

CH2).

13 3,5-NC5H3(COCl)2 (28). A round bottom flask was charged with 27 (2.000 g,

11.97 mmol) and freshly distilled toluene (21 mL). Then SOCl2 (60 mL) was added over 10 min with stirring, followed by eight drops of DMF. The flask was fitted with a condenser. The mixture was refluxed until a yellow solution formed (2 h), and was then cooled to room temperature. The toluene and excess SOCl2 were removed by rotary evaporation. The oily residue was dried under oil pump vacuum to give 28 as a light yellow solid (2.425 g, 11.88 mmol, 99%). 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands 105 ______

1 41 4 4 H NMR (δ, CDCl3): 9.51 (d, 2H, JHH = 2.3 Hz, o-Hpyr), 8.99 (t, 1H, JHH =

2.3 Hz, p-Hpyr).

11 3,5-NC5H3(COOCH2CH=CH2)2 (29a). A round bottom flask was charged with

28 (1.224 g, 6.002 mmol) and CH2Cl2 (20 mL). The solution was cooled to 0 °C with stirring. Then HOCH2CH=CH2 (0.7442 g, 13.16 mmol) was added dropwise over 20 min. The cooling bath was removed. After 1 h, the flask was fitted with a condenser. The solution was refluxed (5 h) and cooled to room temperature. The solvent was removed by rotary evaporation. Hexanes was added (10 mL). The off-white residue was collected by filtration and washed with hexanes until a white solid was obtained (8 × 5 mL). The solid was dissolved in CH2Cl2 (20 mL), washed with aqueous NaOH (1.0 M, 4 × 5 mL), and dried (MgSO4). The solvent was removed by rotary evaporation and oil pump vacuum to give 29a as a light yellow oil (0.8732 g, 3.535 mmol, 59%). The 1H and 13C{1H} NMR data agreed well with those previously reported.11

41 1 4 4 NMR (δ, CDCl3): H 9.35 (d, 2H, JHH = 2.1 Hz, o-Hpyr), 8.85 (t, 1H, JHH = 3 3 3 2.1 Hz, p-Hpyr), 6.02 (ddt, 2H, JHHtrans = 17.2 Hz, JHHcis = 10.4 Hz, JHH = 5.8 Hz, 3 2 2CH=), 5.40 (dd, 2H, JHHtrans = 17.2 Hz, JHH = 1.4 Hz, 2 =CHEHZ), 5.30 (dd, 2H, 3 2 4 3 JHHcis = 10.4 Hz, JHH = 1.2 Hz, 2 =CHEHZ), 4.85 (dt, 4H, JHH = 1.3 Hz, JHH = 5.8 13 1 42 Hz, 2OCH2); C{ H} 163.9 (s, CO), 154.1 (s, o-Cpyr), 137.9 (s, p-Cpyr), 131.4 (s,

CH=), 125.9 (s, m-Cpyr), 119.0 (s, =CH2), 66.2 (s, OCH2). MS:39a 248 ([29a + H]+, 100%). IR (cm−1, oil film): 3080 (w), 2931 (m), 2863 (w), 1727 (s), 1312 (m), 1240 (s), 1112 (m), 912 (m), 747 (s).

3,5-NC5H3(COO(CH2)2CH=CH2)2 (29b). Pyridine 28 (0.400 g, 1.96 mmol),

CH2Cl2 (6.5 mL), and HO(CH2)2CH=CH2 (0.423 g, 5.88 mmol) were combined in a 106 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands ______procedure analogous to that for 29a. An identical workup gave 29b as a light yellow oil (0.482 g, 1.75 mmol, 89%).

41 1 4 4 NMR (δ, CDCl3): H 9.33 (d, 2H, JHH = 2.1 Hz, o-Hpyr), 8.82 (t, 1H, JHH = 3 3 3 2.1 Hz, p-Hpyr), 5.84 (ddt, 2H, JHHtrans = 17.1 Hz, JHHcis = 10.3 Hz, JHH = 6.8 Hz, 3 2 2CH=), 5.22 (dd, 2H, JHHtrans = 17.1 Hz, JHH = 1.3 Hz, 2 =CHEHZ), 5.11 (dd, 2H, 3 2 3 JHHcis = 10.2 Hz, JHH = 1.1 Hz, 2 =CHEHZ), 4.42 (t, 4H, JHH = 6.7 Hz, 2OCH2), 2.53 3 13 1 42 (q, 4H, JHH = 6.7 Hz, 2CH2CH=); C{ H} 165.2 (s, CO), 153.2 (s, o-Cpyr), 138.0 (s, p-Cpyr), 135.7 (s, CH=), 126.0 (s, m-Cpyr), 115.4 (s, =CH2), 64.3 (s, OCH2), 33.5 (s,

CH2CH=). MS:39a 276 ([29b + H]+, 100%). IR (cm−1, oil film): 3082 (w), 2940 (m), 2865 (w), 1730 (s), 1312 (m), 1242 (s), 1112 (m), 913 (m), 746 (s).

3,5-NC5H3(COO(CH2)3CH=CH2)2 (29c). Pyridine 28 (1.500 g, 7.349 mmol),

CH2Cl2 (24 mL), and HO(CH2)3CH=CH2 (1.392 g, 16.16 mmol) were combined in a procedure analogous to that for 29a. An identical workup gave 29c as a light yellow oil (1.865 g, 6.148 mmol, 84%).

41 1 4 4 NMR (δ, CDCl3): H 9.33 (d, 2H, JHH = 2.1 Hz, o-Hpyr), 8.81 (t, 1H, JHH = 3 3 3 2.1 Hz, p-Hpyr), 5.87 (ddt, 2H, JHHtrans = 17.2 Hz, JHHcis = 11.0 Hz, JHH = 5.9 Hz, 3 2 2CH=), 5.03 (dd, 2H, JHHtrans = 17.1 Hz, JHH = 1.7 Hz, 2 =CHEHZ), 4.98 (dd, 2H, 3 2 3 JHHcis = 10.2 Hz, JHH = 1.2 Hz, 2 =CHEHZ), 4.41 (t, 4H, JHH = 6.7 Hz, 2OCH2), 2.25- 13 1 42 2.20 (m, 4H, 2CH2), 1.93-1.86 (m, 4H, 2CH2); C{ H} 164.8 (s, CO), 154.4 (s, o-Cpyr),

138.0 (s, p-Cpyr), 137.9 (s, CH=), 126.6 (s, m-Cpyr), 115.4 (s, =CH2), 65.5 (s, OCH2), 30.4 and 28.1 (2 s, 2CH2). MS:39a 304 ([29c + H]+, 100%). 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands 107 ______

IR (cm−1, oil film): 3076 (w), 2932 (m), 2858 (w), 1720 (s), 1312 (m), 1231 (s), 1103 (m), 913 (m), 749 (s).

3,5-NC5H3(COO(CH2)4CH=CH2)2 (29d). Pyridine 28 (2.000 g, 9.799 mmol),

CH2Cl2 (32 mL), and HO(CH2)4CH=CH2 (2.160 g, 21.57 mmol) were combined in a procedure analogous to that for 29a. An identical workup gave 29d as a light yellow oil (2.917 g, 8.802 mmol, 90%).

41 1 4 4 NMR (δ, CDCl3): H 9.37 (d, 2H, JHH = 2.1 Hz, o-Hpyr), 8.85 (t, 1H, JHH = 3 3 3 2.1 Hz, p-Hpyr), 5.80 (ddt, 2H, JHHtrans = 17.0 Hz, JHHcis = 10.3 Hz, JHH = 6.7 Hz, 3 2 2CH=), 5.02 (dd, 2H, JHHtrans = 17.1 Hz, JHH = 1.5 Hz, 2 =CHEHZ), 4.97 (dd, 2H, 3 2 3 JHHcis = 10.2 Hz, JHH = 1.1 Hz, 2 =CHEHZ), 4.41 (t, 4H, JHH = 6.7 Hz, 2OCH2), 2.18- 13 1 2.13 (m, 4H, 2CH2), 1.87-1.80 (m, 4H, 2CH2), 1.61-1.54 (m, 4H, 2CH2); C{ H} 164.6 42 (s, CO), 154.1 (s, o-Cpyr), 138.7 (s, p-Cpyr), 137.6 (s, CH=), 126.3 (s, m-Cpyr), 114.7 (s,

=CH2), 65.7 (s, OCH2), 33.6, 25.8, and 25.3 (3 s, 3CH2). MS:39a 332 ([29d + H]+, 100%). IR (cm−1, oil film): 3078 (w), 2937 (m), 2860 (w), 1724 (s), 1309 (m), 1235 (s), 1107 (m), 909 (m), 745 (s).

3,5-NC5H3(COO(CH2)5CH=CH2)2 (29e). Pyridine 28 (1.500 g, 7.349 mmol),

CH2Cl2 (24 mL), and HO(CH2)5CH=CH2 (1.850 g, 16.20 mmol) were combined in a procedure analogous to that for 29a. An identical workup gave 29e as a light yellow oil (1.838 g, 5.113 mmol, 70%).

41 1 4 4 NMR (δ, CDCl3): H 9.36 (d, 2H, JHH = 2.1 Hz, o-Hpyr), 8.85 (t, 1H, JHH = 3 3 3 2.1 Hz, p-Hpyr), 5.80 (ddt, 2H, JHHtrans = 17.0 Hz, JHHcis = 10.3 Hz, JHH = 6.7 Hz, 3 2 2CH=), 5.01 (dd, 2H, JHHtrans = 17.1 Hz, JHH = 1.7 Hz, 2 =CHEHZ), 4.96 (dd, 2H, 108 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands ______

3 2 3 JHHcis = 10.2 Hz, JHH = 1.0 Hz, 2 =CHEHZ), 4.39 (t, 4H, JHH = 6.7 Hz, 2OCH2), 2.10- 13 1 2.08 (m, 4H, 2CH2), 1.84-1.77 (m, 4H, 2CH2), 1.50-1.45 (m, 8H, 4CH2); C{ H} 164.5 42 (s, CO), 154.1 (s, Cpyr, o-N), 138.5 (s, p-Cpyr), 137.9 (s, CH=), 126.2 (s, m-Cpyr), 114.6

(s, =CH2), 65.8 (s, OCH2), 33.5, 28.5, 28.3, and 25.3 (4 s, 4CH2). MS:39a 360 ([29e + H]+, 100%). IR (cm−1, oil film): 3076 (w), 2934 (m), 2860 (w), 1725 (s), 1309 (m), 1235 (s), 1104 (m), 911 (m), 745 (s).

3,5-NC5H3(COO(CH2)6CH=CH2)2 (29f). Pyridine 28 (1.800 g, 8.819 mmol),

CH2Cl2 (29 mL), and HO(CH2)6CH=CH2 (2.488 g, 19.42 mmol) were combined in a procedure analogous to that for 29a. After workup, the yellow residue was chromatographed on silica gel (45 × 3 cm column, 4:1 v/v hexanes/ethyl acetate). The solvent was removed by rotary evaporation from the product-containing fractions to give

29f as a light yellow oil (1.408 g, 3.633 mmol, 41%; Rf (TLC) = 0.80).

41 1 4 4 NMR (δ, CDCl3): H 9.36 (d, 2H, JHH = 2.1 Hz, o-Hpyr), 8.85 (t, 1H, JHH = 3 3 3 2.1 Hz, p-Hpyr), 5.81 (ddt, 2H, JHHtrans = 17.0 Hz, JHHcis = 10.2 Hz, JHH = 6.7 Hz, 3 2 2CH=), 5.00 (dd, 2H, JHHtrans = 17.2 Hz, JHH = 2.1 Hz, 2 =CHEHZ), 4.94 (dd, 2H, 3 2 3 JHHcis = 10.2 Hz, JHH = 2.1 Hz, 2 =CHEHZ), 4.39 (t, 4H, JHH = 6.7 Hz, 2OCH2), 2.07- 13 1 2.03 (m, 4H, 2CH2), 1.85-1.76 (m, 4H, 2CH2), 1.45-1.51 (m, 12H, 6CH2); C{ H} 164.5 42 (s, CO), 154.1 (s, o-Cpyr), 138.8 (s, p-Cpyr), 137.9 (s, CH=), 126.2 (s, m-Cpyr), 114.4 (s,

=CH2), 65.9 (s, OCH2), 33.6, 28.7, 28.6, 28.5, and 25.8 (5 s, 5CH2). MS:39a 388 ([29f + H]+, 100%). IR (cm−1, oil film): 3076 (w), 2930 (s), 2856 (m), 1725 (s), 1309 (s), 1235 (s), 1104 (s), 911 (s), 745 (s).

3,5-NC5H3(COO(CH2)8CH=CH2)2 (29g). Pyridine 28 (1.480 g, 7.251 mmol), 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands 109 ______

CH2Cl2 (24 mL), and HO(CH2)8CH=CH2 (2.503 g, 16.02 mmol) were combined in a procedure analogous to that for 29a. An identical workup gave 29g as a light yellow oil

(2.152 g, 4.858 mmol, 67%; Rf (TLC) = 0.85).

41 1 4 4 NMR (δ, CDCl3): H 9.36 (d, 2H, JHH = 2.1 Hz, o-Hpyr), 8.86 (t, 1H, JHH = 3 3 3 2.1 Hz, p-Hpyr), 5.81 (ddt, 2H, JHHtrans = 17.0 Hz, JHHcis = 10.3 Hz, JHH = 6.7 Hz, 3 2 2CH=), 5.23 (dd, 2H, JHHtrans = 17.1 Hz, JHH = 1.8 Hz, 2 =CHEHZ), 4.99 (dd, 2H, 3 2 3 JHHcis = 10.2 Hz, JHH = 1.2 Hz, 2 =CHEHZ), 4.39 (t, 4H, JHH = 6.7 Hz, 2OCH2), 2.06- 13 1 2.02 (m, 4H, 2CH2), 1.81-1.76 (m, 4H, 2CH2), 1.46-1.33 (m, 20H, 10CH2); C{ H} 42 164.5 (s, CO), 154.1 (s, o-Cpyr), 139.1 (s, p-Cpyr), 137.9 (s, CH=), 126.2 (s, m-Cpyr),

114.2 (=CH2), 65.9 (s, OCH2), 33.7, 29.3, 29.1, 29.0, 28.8, 28.6, 25.9 (7 s, 7CH2). MS:39a 444 ([29g + H]+, 100%). IR (cm−1, oil film): 3076 (w), 2926 (s), 2856 (m), 1729 (s), 1309 (s), 1235 (s), 1100 (s), 907 (s), 745 (s).

trans-Rh(Cl)(CO)[2,6-NC5H3(CH2OCH2CH=CH2)2]2 (trans-30). A Schlenk flask was charged with [RhCl(coe)2]2 (0.430 g, 0.599 mmol) and methanol/toluene (1:1 v/v, 22 mL) with stirring. A solution of 22a (0.564 g, 2.58 mmol) in methanol/toluene (1:1 v/v, 4 mL) was added dropwise over 10 min. The flask was fitted with a condenser. The mixture was refluxed (2 h), cooled to room temperature, and filtered under nitrogen. The orange solution was aspirated with CO (1 h). The solvents were removed by oil pump vacuum and the residue was chromatographed on silica gel (10 × 2 cm column, 4:1 v/v hexanes/ethyl acetate). An orange band was collected. The solvents were removed by rotary evaporation and oil pump vacuum. The residue was dissolved in CH2Cl2 (ca. 1 mL). The solution was layered with pentane (20 mL). After 24 h at −4 °C, the supernatant was carefully decanted from the precipitate, which was dried by oil pump vacuum to give trans-30 as light orange solid (0.090 g, 0.149 mmol, 26%), mp (capillary) 106-108 °C. 110 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands ______

DSC (Ti/Te/Tp/Tc/Tf): 79.2/102.6/106.5/109.1/114.8 °C (endotherm). TGA: onset of mass loss, 114.7 °C. Anal. Calcd. for C27H34ClN2O5Rh: C: 53.61, H: 5.67, N: 4.63. Found: C: 52.57, H: 6.83, N: 4.09.

41 1 3 3 NMR (δ, CDCl3): H 7.81 (t, 2H, JHH = 7.8 Hz, p-Hpyr), 7.59 (d, 4H, JHH = 3 3 3 7.8 Hz, o-Hpyr), 6.08 (ddt, 4H, JHHtrans = 17.2 Hz, JHHcis = 10.6 Hz, JHH = 5.4 Hz, 4 4 4CH=), 5.76 (d, 4H, JRhH = 15.0 Hz, 2CH2O), 5.64 (d, 4H, JRhH = 15.0 Hz, 2CH2O), 3 2 3 5.46 (dd, 4H, JHHtrans = 17.2 Hz, JHH = 1.6 Hz, 4 =CHEHZ), 5.33 (dd, 4H, JHHcis = 2 4 3 10.4 Hz, JHH = 1.5 Hz, 4 =CHEHZ), 4.29 (dt, 8H, JHH = 1.4 Hz, JHH = 5.5 Hz, 13 1 1 43 4OCH2); C{ H} 183.6 (d, JRhC = 70.3 Hz, CO), 162.2 (s, o-Cpyr), 138.0 (s, p-Cpyr),

134.1 (s, CH=), 121.5 (s, m-Cpyr), 117.7 (s, =CH2), 73.4 and 72.1 (2s, CH2OCH2). MS:39a 576 ([30 − CO]+, 40%), 569 ([30 − Cl]+, 20%), 321 ([30 − 22a − 2Cl]+, 100%), 220 ([22a + H]+, 30%).

−1 IR (cm , powder film): 3088 (w), 3015 (w), 2860 (m), 2837 (w), 1945 (s, νCO), 1610 (m), 1583 (w), 1471 (m), 1332 (m), 1239 (w), 1116 (s), 1007 (s), 988 (m), 787 (s).

trans-PtCl2[2,6-NC5H3(CH2OCH2CH=CH2)2]2 (trans-31a). A Schlenk flask was charged with PtCl2 (0.513 g, 1.93 mmol), benzene (19 mL), and 22a (0.930 g, 4.24 mmol), and fitted with a condenser. The mixture was refluxed with stirring (5 d), and cooled to room temperature. After 2 d, a yellow solution had formed. The solvent was removed by rotary evaporation and the yellow residue was chromatographed on silica gel

(10 × 2 cm column, CH2Cl2). A single yellow band was collected. The solvent was removed by rotary evaporation, Hexanes was added (10 mL). The residue was collected by filtration, washed with hexanes (10 × 3 mL), and dried overnight by oil pump vacuum to give trans-31a as a yellow solid (1.196 g, 1.698 mmol, 88%), mp 148-150 °C. DSC

(Ti/Te/Tp/Tc/Tf): 107.5/152.0/154.9/156.5/168.3 °C (endotherm). TGA: onset of mass loss,

163.1 °C. Anal. Calcd. for C26H34Cl2N2O4Pt: C, 44.32; H, 4.86; N, 3.98. Found: C, 43.39; 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands 111 ______

H, 4.86; N, 3.79.

41 1 3 3 NMR (δ, CDCl3): H 7.78 (t, 2H, JHH = 7.9 Hz, p-Hpyr), 7.58 (d, 4H, JHH = 3 3 3 7.9 Hz, m-Hpyr), 6.04 (ddt, 2H, JHHtrans = 17.2 Hz, JHHcis = 10.6 Hz, JHH = 5.4 Hz, 3 2 4CH=), 5.82 (s, 8H, 4CH2O), 5.44 (dd, 4H, JHHtrans = 17.2 Hz, JHH = 1.6 Hz, 4 3 2 =CHEHZ), 5.30 (dd, 4H, JHHcis = 10.4 Hz, JHH = 1.5 Hz, 4 =CHEHZ), 4.27 (dt, 8H, 4 3 13 1 43 JHH = 1.5 Hz, JHH = 5.5 Hz, 4OCH2); C{ H} 161.5 (s, o-Cpyr), 139.0 (s, p-Cpyr),

134.0 (s, CH=), 121.5 (s, m-Cpyr), 117.9 (s, =CH2), 72.2 and 71.3 (2s, CH2OCH2). MS:39a 705 (31a+, 10%), 669 ([31a − Cl]+, 40%), 220 ([22a + H]+, 100%). IR (cm−1, powder film): 3092 (w), 3015 (w), 2868 (m), 2837 (m), 1613 (m), 1471 (m), 1332 (m), 1239 (w), 1123 (s), 1107 (s), 911 (s), 787 (s).

trans-PtCl2[2,6-NC5H3(CH2O(CH2)2CH=CH2)2]2 (trans-31b). A Schlenk flask was charged with PtCl2 (0.477 g, 1.79 mmol), benzene (15 mL), and 22b (0.914 g, 3.70 mmol), and fitted with a condenser. The mixture was refluxed with stirring (7 d), and cooled to room temperature. After 4 d, a yellow solution had formed. The solvent was removed by rotary evaporation and the residue was chromatographed on silica gel (20 × 2 cm column, 4:1 v/v hexanes/ethyl acetate). The solvents were removed by rotary evaporation from the product-containing fractions. Hexanes was added (15 mL). The residue was collected by filtration, washed with hexanes (10 × 3 mL), and dried overnight by oil pump vacuum to give trans-31b as a yellow solid (0.354 g, 0.465 mmol, 26%; Rf

(TLC) = 0.59), mp (capillary) 106-108 °C. DSC (Ti/Te/Tp/Tc/Tf): 90.7/109.9/110.8/112.1/135.3 °C (endotherm). TGA: onset of mass loss, 167.9 °C. Anal.

Calcd. for C30H42Cl2N2O4Pt: C, 47.37; H, 5.57; N, 3.68. Found: C, 47.25; H, 5.55; N, 3.62.

41 1 3 3 NMR (δ, CDCl3): H 7.78 (t, 2H, JHH = 7.9 Hz, p-Hpyr), 7.58 (d, 4H, JHH = 112 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands ______

3 3 3 7.9 Hz, m-Hpyr), 5.94 (ddt, 4H, JHHtrans = 17.1 Hz, JHHcis = 10.3 Hz, JHH = 6.8 Hz, 3 2 4CH=), 5.81 (s, 8H, 4CH2O), 5.19 (dd, 4H, JHHtrans = 17.2 Hz, JHH = 1.8 Hz, 4 3 2 3 =CHEHZ), 5.12 (dd, 4H, JHHcis = 10.2 Hz, JHH = 1.8 Hz, 4 =CHEHZ), 3.84 (t, 8H, JHH 13 1 43 = 6.6 Hz, 4OCH2), 2.55-2.50 (m, 8H, 4CH2); C{ H} 161.3 (s, o-Cpyr), 138.9 (s, p-

Cpyr), 134.8 (s, CH=), 121.5 (s, m-Cpyr), 116.9 (s, =CH2), 71.9 (s, CH2O), 70.9 (s,

OCH2CH2), 34.2 (s, CH2). MS:39a 760 (31b+, 5%), 725 ([31b − Cl]+, 30%), 248 ([22b + H]+, 100%). IR (cm−1, powder film): 3074 (w), 2981 (w), 2866 (m), 1613 (m), 1475 (m), 1352 (m), 1120 (s), 1027 (m), 911 (s), 796 (s).

trans-PtCl2[3,5-NC5H3(COOCH2CH=CH2)2]2 (trans-32a). A Schlenk flask was charged with 29a (0.790 g, 3.198 mmol), PtCl2 (0.4051 g, 1.523 mmol), and benzene (15 mL), and fitted with a condenser. The mixture was refluxed with stirring (12 h), and cooled to room temperature. After 1 h, a yellow solution had formed. The solvent was removed by rotary evaporation. The yellow residue was chromatographed on silica gel (20 × 2 cm column, 4:1 v/v hexanes/ethyl acetate). A single yellow band was collected. The solvent was removed by rotary evaporation. Hexanes was added (15 mL). The residue was collected by filtration, washed with hexanes (7 × 2 mL), and dried by oil pump vacuum to give trans-32a as a yellow solid. (1.004 g, 1.321 mmol, 87%), mp (capillary) 178-180 °C.

TGA: onset mass loss, 145.3 °C. Anal. Calcd. for C26H26Cl2N2O8Pt: C, 41.06; H, 3.45; N, 3.68. Found: C, 40.65; H, 3.18; N, 3.53.

41 1 4 4 NMR (δ, CDCl3): H 9.68 (d, 4H, JHH = 1.8 Hz, o-Hpyr), 9.02 (t, 2H, JHH = 3 3 3 1.8 Hz, p-Hpyr), 6.05 (ddt, 4H, JHHtrans = 16.9 Hz, JHHcis = 10.6 Hz, JHH = 6.2 Hz, 3 2 4CH=), 5.47 (dd, 4H, JHHtrans = 17.2 Hz, JHH = 1.3 Hz, 4 =CHEHZ), 5.39 (dd, 4H, 3 2 4 3 JHHcis = 10.3 Hz, JHH = 1.1 Hz, 4 =CHEHZ), 4.92 (dt, 8H, JHH = 1.2 Hz, JHH = 5.9 13 1 43 Hz, 4OCH2); C{ H} 162.1 (s, CO), 157.6 (s, o-Cpyr), 140.1 (s, p-Cpyr), 130.8 (s, 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands 113 ______

CH=), 128.4 (s, m-Cpyr), 120.0 (s, =CH2), 67.1 (s, OCH2). MS:39a 760 (32a+, 20%), 725 ([32a − Cl]+, 18%). IR (cm−1, powder film): 3082 (w), 2968 (m), 2895 (m), 1733 (s), 1652 (m), 1598 (m), 1447 (m), 1301 (s), 1251 (s), 1135 (s), 1112 (s), 980 (s), 911 (s), 745 (s).

trans-PtCl2[3,5-NC5H3(COO(CH2)3CH=CH2)2]2 (trans-32c). A. A Schlenk flask was charged with 29c (0.847 g, 2.80 mmol), trans-(PhCN)2PtCl2 (0.600 g, 1.27 mmol), and benzene (28 mL), and fitted with a condenser. The solution was refluxed with stirring (3 h) and cooled to room temperature. The solvent was removed by rotary evaporation. The residue was chromatographed on silica gel (20 × 2 cm column, 4:1 v/v hexanes/ethyl acetate). A single yellow band was collected. The solvent was removed by rotary evaporation. Hexanes was added (15 mL). The residue was collected by filtration, washed with hexanes (10 × 2 mL), and dried by oil pump vacuum to give trans-32c as a yellow solid (0.620 g, 0.710 mmol, 56%).

B. Pyridine 29c (1.000 g, 3.297 mmol), PtCl2 (0.400 g, 1.50 mmol), and benzene (33 mL) were combined in a procedure analogous to that for trans-32c. An identical workup gave trans-32c as a yellow solid (1.098 g, 1.258 mmol, 84%), mp (capillary) 92-94

°C. DSC (Ti/Te/Tp/Tc/Tf): 72.5/95.5/97.6/99.9/133.3 °C (endotherm). TGA: onset of mass loss, 176.3 °C. Anal. Calcd. for C34H42Cl2N2O8Pt: C, 46.79; H, 4.85; N, 3.21. Found: C, 46.23; H, 4.56; N, 3.04.

41 1 4 4 NMR (δ, CDCl3): H 9.68 (d, 4H, JHH = 1.8 Hz, o-Hpyr), 8.99 (t, 2H, JHH = 3 3 3 1.8 Hz, p-Hpyr), 5.86 (ddt, 4H, JHHtrans = 17.0 Hz, JHHcis = 10.3 Hz, JHH = 6.7 Hz, 3 2 4CH=), 5.12 (dd, 4H, JHHtrans = 17.2 Hz, JHH = 1.3 Hz, 4 =CHEHZ), 5.06 (dd, 4H, 3 2 3 JHHcis = 10.3 Hz, JHH = 1.1 Hz, 4 =CHEHZ), 4.46 (t, 8H, JHH = 6.7 Hz, 4OCH2), 2.28- 13 1 2.23 (m, 8H, 4CH2), 1.98-1.91 (m, 8H, 4CH2); C{ H} 162.0 (s, CO), 157.6 (s, o- 42 Cpyr), 140.1 (s, p-Cpyr), 137.0 (s, CH=), 128.5 (s, m-Cpyr), 115.8 (s, =CH2), 66.1 (s, 114 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands ______

OCH2), 30.0 and 27.6 (2 s, 2CH2). MS:39a 872 (32c+, 30%), 836 ([32c − Cl]+, 10%), 304 (29c+, 100%). IR (cm−1, powder film): 3128 (w), 3082 (w), 2958 (m), 2926 (m), 1722 (s), 1645 (m), 1607 (m), 1447 (s), 1305 (s), 1251 (s), 1112 (s), 981 (s), 911 (s), 742 (s).

trans-PtCl2[3,5-NC5H3(COO(CH2)4CH=CH2)2]2 (trans-32d). Pyridine 29d

(1.002 g, 3.018 mmol), PtCl2 (0.382 g, 1.437 mmol), and benzene (14 mL) were combined in a procedure analogous to that for trans-32a. An identical workup gave trans-32d as a yellow solid (1.234 g, 1.329 mmol, 92%), mp (capillary) 74-76 °C. DSC (Ti/Te/Tp/Tc/Tf):

49.4/56.6/58.6/61.8/62.6 °C (endotherm); (Ti/Te/Tp/Tc/Tf): 63.0/65.7/67.3/68.5/68.5 °C

(endotherm); (Ti/Te/Tp/Tc/Tf): 75.5/76.7/79.3/80.8/83.2 °C (endotherm). TGA: onset mass loss, 165.3 °C. Anal. Calcd. for C38H50Cl2N2O8Pt: C, 49.14; H, 5.43; N, 3.02. Found: C, 48.69; H, 5.42; N, 2.73.

41 1 4 4 NMR (δ, CDCl3): H 9.67 (d, 4H, JHH = 1.8 Hz, o-Hpyr), 8.99 (t, 2H, JHH = 3 3 3 1.8 Hz, p-Hpyr), 5.83 (ddt, 4H, JHHtrans = 17.0 Hz, JHHcis = 10.3 Hz, JHH = 6.7 Hz, 3 2 4CH=), 5.07 (dd, 4H, JHHtrans = 17.1 Hz, JHH = 1.9 Hz, 4 =CHEHZ), 5.01 (dd, 4H, 3 2 3 JHHcis = 10.2 Hz, JHH = 1.9 Hz, 4 =CHEHZ), 4.44 (t, 8H, JHH = 6.7 Hz, 4OCH2), 2.19- 13 1 2.13 (m, 8H, 4CH2), 1.89-1.81 (m, 8H, 4CH2), 1.61-1.53 (m, 8H, 4CH2); C{ H} 162.1 43 (s, CO), 157.5 (s, o-Cpyr), 140.0 (s, p-Cpyr), 138.0 (s, CH=), 128.5 (s, m-Cpyr), 115.2 (s,

=CH2), 66.6 (s, OCH2), 33.2, 27.9, and 25.1 (3 s, 3CH2). MS:39a 928 (32d +, 30%), 893 ([32d − Cl]+, 30%), 332 ([29d + H]+, 100%). IR (cm−1, powder film): 3113 (w), 3075 (w), 2950 (m), 2920 (m), 1730 (s), 1645 (m), 1607 (m), 1452 (s), 1267 (s), 1112 (s), 966 (s), 911 (s), 742 (s).

trans-PtCl2[3,5-NC5H3(COO(CH2)5CH=CH2)2]2 (trans-32e). Pyridine 29e

(0.853 g, 2.373 mmol), PtCl2 (0.300 g, 1.128 mmol), and benzene (11 mL) were combined 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands 115 ______in a procedure analogous to that for trans-32a. An identical workup gave trans-32e as a yellow solid (1.042 g, 1.058 mmol, 94%), mp (capillary) 74-76 °C. DSC (Ti/Te/Tp/Tc/Tf): 48.5/52.1/53.6/55.6/57.3 °C (endotherm); 70.4/79.3/81.1/82.9/99.8 °C (endotherm); TGA: onset mass loss, 165.7 °C. Anal. Calcd. for C42H58Cl2N2O8Pt: C, 51.22; H, 5.94; N, 2.84. Found: C, 51.71; H, 6.19; N, 2.93.

41 1 4 4 NMR (δ, CDCl3): H 9.67 (d, 4H, JHH = 1.8 Hz, o-Hpyr), 8.98 (t, 2H, JHH = 3 3 3 1.8 Hz, p-Hpyr), 5.83 (ddt, 4H, JHHtrans = 17.1 Hz, JHHcis = 10.3 Hz, JHH = 6.7 Hz, 3 2 4CH=), 5.04 (dd, 4H, JHHtrans = 18.1 Hz, JHH = 2.5 Hz, 4 =CHEHZ), 4.99 (dd, 4H, 3 2 3 JHHcis = 10.2 Hz, JHH = 1.2 Hz, 4 =CHEHZ), 4.43 (t, 8H, JHH = 6.7 Hz, 4OCH2), 2.13- 13 1 2.09 (m, 8H, 4CH2), 1.88-1.81 (m, 8H, 4CH2), 1.47-1.50 (m, 16H, 8CH2); C{ H} 162.1 43 (s, CO), 157.5 (s, o-Cpyr), 140.0 (s, p-Cpyr), 138.5 (s, CH=), 128.6 (s, m-Cpyr), 114.7 (s,

=CH2), 66.8 (s, OCH2), 33.5, 28.4, 28.3, and 25.3 (4 s, 4CH2). MS:39a 984 (32e+, 4%), 949 ([32e − Cl]+, 14%), 360 (29e+, 100%). IR (cm−1, powder film): 3130 (w), 3080 (w), 2926 (m), 2856 (m), 1722 (s), 1447 (m), 1305 (s), 1247 (s), 1127 (s), 984 (s), 907 (s), 741 (s).

trans-PtCl2[3,5-NC5H3(COO(CH2)6CH=CH2)2]2 (trans-32f). Pyridine 29f

(1.410 g, 3.641 mmol), PtCl2 (0.440 g, 1.66 mmol) and benzene (15 mL) were combined in a procedure analogous to that for trans-32a. An identical workup gave trans-32f as a yellow solid (0.906 g, 0.870 mmol, 63%), mp (capillary) 66-68 °C. DSC (Ti/Te/Tp/Tc/Tf): 60.8/68.5/70.7/72.3/82.7 °C (endotherm). TGA: onset mass loss, 171.8 °C. Anal. Calcd. for C46H66Cl2N2O8Pt: C, 53.07; H, 6.39; N, 2.69. Found: C, 52.62; H, 6.44; N, 2.63.

41 1 4 4 NMR (δ, CDCl3): H 9.66 (d, 4H, JHH = 1.8 Hz, o-Hpyr), 8.98 (t, 2H, JHH = 3 3 3 1.8 Hz, p-Hpyr), 5.82 (ddt, 4H, JHHtrans = 17.1 Hz, JHHcis = 10.2 Hz, JHH = 6.8 Hz, 3 2 4CH=), 5.01 (dd, 4H, JHHtrans = 17.0 Hz, JHH = 2.3 Hz, 4 =CHEHZ), 4.95 (dd, 4H, 116 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands ______

3 2 3 JHHcis = 10.1 Hz, JHH = 1.1 Hz, 4 =CHEHZ), 4.43 (t, 8H, JHH = 6.7 Hz, 4OCH2), 2.09- 13 1 2.03 (m, 8H, 4CH2), 1.83-1.81 (m, 8H, 4CH2), 1.45-1.42 (m, 24H, 12CH2); C{ H} 43 162.1 (s, CO), 157.5 (s, o-Cpyr), 140.0 (s, p-Cpyr), 138.8 (s, CH=), 128.6 (s, m-Cpyr),

114.4 (s, =CH2), 66.8 (s, OCH2), 33.6, 28.7, 28.6, 28.5, and 25.7 (5 s, 5CH2). MS:39a 1040 (32f+, 2%), 1005 ([32f − Cl]+, 20%), 388 ([29f + H]+, 100%). IR (cm−1, powder film): 3127 (w), 3080 (w), 2926 (s), 2856 (m), 1718 (s), 1606 (m), 1447 (s), 1305 (s), 1225 (s), 1127 (s), 968 (s), 911 (s), 741 (s).

trans-PtCl2[3,5-NC5H3(COO(CH2)8CH=CH2)2]2 (trans-32g). Pyridine 29g

(0.652 g, 1.47 mmol), PtCl2 (0.178 g, 0.668 mmol), and benzene (7 mL) were combined in a procedure analogous to that for trans-32a. An identical workup gave trans-32g as a yellow solid (0.600 g, 0.520 mmol, 78%), mp (capillary) 68-70 °C. DSC (Ti/Te/Tp/Tc/Tf): 34.5/39.5/41.6/43.6/47.0 °C (endotherm); 50.6/68.3/70.3/72.1/87.2 °C (endotherm). TGA: onset mass loss, 177.5 °C. Anal. Calcd. for C54H82Cl2N2O8Pt: C, 56.24; H, 7.17; N, 2.43. Found: C, 55.93; H, 7.12; N, 2.38.

41 1 4 4 NMR (δ, CDCl3): H 9.66 (d, 4H, JHH = 1.8 Hz, o-Hpyr), 8.98 (t, 2H, JHH = 3 3 3 1.8 Hz, p-Hpyr), 5.82 (ddt, 4H, JHHtrans = 17.0 Hz, JHHcis = 10.3 Hz, JHH = 6.7 Hz, 3 2 4CH=), 5.00 (dd, 4H, JHHtrans = 17.1 Hz, JHH = 2.1 Hz, 4 =CHEHZ), 4.95 (dd, 4H, 3 2 3 JHHcis = 10.2 Hz, JHH = 2.1 Hz, 4 =CHEHZ), 4.42 (t, 8H, JHH = 6.7 Hz, 4OCH2), 2.08- 13 1 2.04 (m, 8H, 4CH2), 1.86-1.79 (m, 8H, 4CH2), 1.45-1.34 (m, 40H, 20CH2); C{ H} 43 162.1 (s, CO), 157.4 (s, o-Cpyr), 140.1 (s, p-Cpyr), 139.6 (s, CH=), 128.6 (s, m-Cpyr),

114.6 (s, =CH2), 67.3 (s, OCH2), 34.2, 29.9, 29.7, 29.6, 29.4, 28.9, 26.2 (7 s, 7CH2). MS:39a 1152 (32g+, 5%), 1117 ([32g − Cl]+, 50%), 444 ([29g + H]+, 100%). IR (cm−1, powder film): 3127 (w), 3080 (w), 2922 (s), 2853 (m), 1733 (s), 1718 (s), 1606 (m), 1447 (m), 1305 (s), 1262 (s), 1127 (s), 1108 (s), 992 (s), 911 (s), 741 (s).

3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands 117 ______

trans-PdCl2[3,5-NC5H3(COO(CH2)5CH=CH2)2]2 (trans-33e). A round bottom flask was charged with trans-(PhCN)2PdCl2 (0.350 g, 0.912 mmol), benzene (10 mL), and 29e (0.719 g, 2.00 mmol), and fitted with a condenser. The solution was refluxed with stirring (2 h) and cooled to room temperature. The solvent was removed by rotary evaporation. The residue was chromatographed on silica gel (20 × 2 cm column, 4:1 v/v hexanes/ethyl acetate). A single yellow band was collected. The solvents were removed by rotary evaporation. Hexanes was added (15 mL). The light orange residue was collected by filtration, washed with hexanes (10 × 2 mL) and dried by oil pump vacuum to give trans- 33e as a yellow solid (0.770 g, 0.859 mmol, 94%), mp (capillary) 55-57 °C.

(Ti/Te/Tp/Tc/Tf): 28.9/29.4/31.5/33.9/36.7 °C (endotherm); 41.8/57.8/61.0/63.9/71.2 °C

(endotherm). TGA: onset of mass loss, 160 °C. Anal. Calcd. for C42H58Cl2N2O8Pd: C, 56.28; H, 6.52; N, 3.13. Found: C, 56.29; H, 6.62; N, 3.19.

41 1 4 4 NMR (δ, CDCl3): H 9.59 (d, 4H, JHH = 1.8 Hz, o-Hpyr), 8.97 (t, 2H, JHH = 3 3 3 1.8 Hz, p-Hpyr), 5.83 (ddt, 4H, JHHtrans = 17.0 Hz, JHHcis = 10.3 Hz, JHH = 6.7 Hz, 3 2 4CH=), 5.04 (dd, 4H, JHHtrans = 17.1 Hz, JHH = 1.9 Hz, 4 =CHEHZ), 4.98 (dd, 4H, 3 2 3 JHHcis = 10.2 Hz, JHH = 2.0 Hz, 4 =CHEHZ), 4.43 (t, 8H, JHH = 6.8 Hz, 4OCH2), 2.12- 13 1 2.09 (m, 8H, 4CH2), 1.88-1.82 (m, 8H, 4CH2), 1.53-1.47 (m, 16H, 8CH2); C{ H} 162.2 43 (s, CO), 157.1 (s, o-Cpyr), 140.4 (s, p-Cpyr), 138.6 (s, CH=), 128.2 (s, m-Cpyr), 114.7 (s,

=CH2), 66.8 (s, OCH2), 33.5, 28.4, 28.3, and 25.3 (4 s, 4CH2). MS:39a 859 ([33e − Cl]+, 5%), 606 (unknown, 10%), 464 ([33e − 29e − 2Cl]+, 60%), 360 ([29e + H]+, 100%). IR (cm−1, powder film): 3082 (w), 2927 (s), 2858 (m), 1730 (s), 1607 (w), 1444 (m), 1313 (s), 1251 (s), 1128 (s), 981 (s), 911 (s), 742 (s).

8 trans-PdCl2[2,6-NC5H3(CH2CH2CH=CH2)2]2 (trans-34). A Schlenk flask was charged with trans-(PhCN)2PdCl2 (0.527 g, 1.37 mmol), benzene (15 mL), and 21 (0.565 118 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands ______g, 3.02 mmol), and fitted with a condenser. The solution was refluxed (40 min). A black precipitate formed after 5 min. The mixture was cooled to room temperature and filtered. The solvent was removed by rotary evaporation. The residue was chromatographed on silica gel (30 × 1 cm column, 3:1 v/v hexanes/CH2Cl2). The solvents were removed from the product-containing fractions by rotary evaporation and oil pump vacuum to give trans-

34 as a yellow solid. (0.112 g, 0.203 mmol, 15%; Rf (TLC) = 0.31).

41 1 3 3 NMR (δ, CDCl3): H 7.61 (t, 2H, JHH = 7.7 Hz, p-Hpyr), 7.12 (d, 4H, JHH = 3 3 3 7.7 Hz, m-Hpyr), 6.05 (ddt, 4H, JHHtrans = 17.0 Hz, JHHcis = 10.4 Hz, JHH = 6.5 Hz, 3 2 4CH=), 5.23 (dd, 4H, JHHtrans = 17.1 Hz, JHH = 1.6 Hz, 4 =CHEHZ), 5.14 (dd, 4H, 3 2 3 JHHcis = 10.2 Hz, JHH = 1.1 Hz, 4 =CHEHZ), 4.42 (t, 8H, JHH = 7.5 Hz, 4CH2), 2.85 3 13 1 43 (q, 8H, JHH = 7.2 Hz, 4CH2); C{ H} 163.3 (s, o-Cpyr), 138.2 (s, p-Cpyr), 136.8 (s,

CH=), 122.2 (s, m-Cpyr), 116.4 (s, =CH2), 38.7 and 32.1 (2 s, 2CH2). MS:39a 517 ([34 − Cl]+, 30%), 292 (unknown, 100%), 188 ([21 + H]+, 80%). IR (cm−1, powder film): 3080 (m), 2964 (m), 2868 (m), 2934 (m), 2856 (m), 1644 (m), 1606 (m), 1575 (m), 1471 (s), 1262 (s), 1096 (s), 915 (s), 807 (s).

trans-PtCl2[2,6,2',6'-(NC5H3(CH2O(CH2)4OCH2)2H3C5N)] (trans-35a). A. A two-necked round bottom flask was charged with trans-31a (0.250 g, 0.355 mmol),

CH2Cl2 (173 mL), fitted with a condenser, and flushed with N2 (5 min). A solution of

Ru(=CHPh)(PCy3)2(Cl)2 (0.0292 g, 0.0355 mmol, 10 mol%) in CH2Cl2 (5 mL) was added dropwise over 30 min with stirring (the resulting solution is 0.00199 M in trans-31a). The mixture was refluxed (24 h). A precipitate formed after 30 min. The mixture was cooled to room temperature and the solvent was removed by rotary evaporation. The residue was chromatographed on alumina (15 × 2 cm column, CH2Cl2). A single light yellow band was collected. The solvent was removed by rotary evaporation and oil pump vacuum. A round bottom flask was charged with the residue (metathesis product), 10% Pd/C (0.0263 g, 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands 119 ______

0.0246 mmol of Pd), toluene (10 mL), and ethanol (10 mL), flushed with H2, and fitted with a balloon of H2 (1.0 atm). The mixture was stirred (3 d) and passed through a pad of celite (7 × 2 cm, rinsed with CH2Cl2). The filtrate was concentrated by oil pump vacuum (to ca. 1 mL), and layered carefully with hexanes (20 mL). After 24 h at −4 °C, the supernatant was carefully decanted from the precipitate, which was dried by oil pump vacuum to give trans-35a as an off white solid. (0.0221 g, 0. 0338 mmol, 10%).

B. Solutions of trans-31a (0.250 g, 0.355 mmol) in CH2Cl2 (173 mL), and

Ru(=CHPh)(H2IMes)(PCy3)(Cl)2 (0.0292 g, 0.0355 mmol, 10 mol%) in CH2Cl2 (5 mL), were combined in a procedure analogous to A (the resulting solution is 0.00199 M in trans-31a). After hydrogenation, an analogous workup gave trans-35a as an off white solid (0.0182 g, 0. 0279 mmol, 8%). The sample slightly darkened at 150 °C. It turned black with further heating without liquefying (230 °C). TGA: onset of mass loss, 160.0 °C. Anal.

Calcd. for C22H30Cl2N2O4Pt: C, 40.50; H, 4.63; N, 4.29. Found: C, 41.08; H, 4.95; N, 4.04.

41 1 3 3 NMR (δ, CDCl3): H 7.80 (t, 2H, JHH = 7.7 Hz, p-Hpyr), 7.53 (d, 4H, JHH =

7.7 Hz, m-Hpyr), 5.95 (s, 8H, 4CH2O), 3.97-3.94 (m, 8H, 4OCH2CH2), 2.08-2.13 (m, 8H, 13 1 43 4CH2); C{ H} 161.0 (s, o-Cpyr), 139.5 (s, p-Cpyr), 125.6 (s, m-Cpyr), 72.5 and 69.9 (2 s, CH2OCH2), 24.5 (s, CH2). MS:39a 617 ([35a − Cl]+, 30%), 580 (unknown, 100%). IR (cm−1, powder film): 2941 (w), 2914 (w), 2856 (m), 1610 (m), 1471 (m), 1370 (m), 1212 (m), 1123 (s), 1108 (s), 984 (s), 803 (s).

trans-PtCl2[2,6,2',6'-(NC5H3(CH2O(CH2)6OCH2)2H3C5N)] (trans-35b).

Solutions of trans-31b (0.250 g, 0.328 mmol) in CH2Cl2 (160 mL), and

Ru(=CHPh)(PCy3)2(Cl)2 (0.027 g, 0.0328 mmol, 10 mol%) in CH2Cl2 (4 mL), were combined in a procedure analogous to that for trans-35a (the resulting solution is 0.00201 120 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands ______

M in trans-31b). After hydrogenation, an analogous workup gave trans-35b as a white solid (0.0501 g, 0.0706 mmol, overall yield: 22%). The sample slightly darkened at 200 °C. It turned black with further heating without liquefying (280 °C). DSC (Ti/Te/Tp/Tc/Tf): 126.7/166.3/170.1/174.7/182.0 °C

(endotherm). TGA: onset of mass loss, 231.6 °C. Anal. Calcd. for C26H38Cl2N2O4Pt: C, 44.07%, 5.41%, N 3.95%. Found: C 43.51%, H 5.31%, N 3.66%.

41 1 3 3 NMR (δ, CDCl3): H 7.79 (t, 2H, JHH = 7.8 Hz, p-Hpyr), 7.56 (d, 4H, JHH = 3 7.8 Hz, m-Hpyr), 5.90 (s, 8H, 4CH2O), 3.89 (t, 8H, JHH = 6.5 Hz, 4OCH2), 1.92-1.89 (m, 13 1 43 8H, 4CH2), 1.70-1.68 (m, 8H, 4CH2); C{ H} 161.5 (s, o-Cpyr), 138.9 (s, p-Cpyr),

121.5 (s, m-Cpyr), 70.7 (s, CH2O), 69.6 (s, OCH2), 26.1 and 23.0 (2 s, 2CH2). MS:39a 709 (38b+, 60%), 673 ([38b − Cl]+, 50%), 636 (unknown, 100%). IR (cm−1, powder film): 2943 (w), 2866 (w), 1614 (m), 1468 (m), 1367 (m), 1213 (w), 1112 (s), 1012 (m), 965 (m), 811 (s).

trans-PtCl2[3,5,3',5'-(NC5H3(COO(CH2)10COO)2H3C5N)] (trans-36d). A. A round bottom flask was charged with trans-32d (0.250 g, 0.269 mmol) and CH2Cl2 (130 mL), fitted with a condenser, and flushed with N2 (5 min). A solution of

Ru(=CHPh)(PCy3)2(Cl)2 (0.0220 g, 0.0269 mmol, 10 mol%) in CH2Cl2 (4 mL) was added dropwise over 30 min with stirring (the resulting solution is 0.00201 M in trans-32d). The mixture was refluxed (24 h) and cooled to room temperature. The solvent was removed by rotary evaporation. The residue was chromatographed on alumina (20 × 2 cm column,

CH2Cl2). A single yellow band was collected. The solvent was removed by rotary evaporation and oil pump vacuum. A round bottom flask was charged with the residue (metathesis product), 10% Pd/C (0.0343 g, 0.0322 mmol of Pd), toluene (10 mL), and ethanol (10 mL), flushed with H2, and fitted with a balloon of H2 (1.0 atm). The mixture was stirred (3 d), and passed through a pad of celite (7 × 2 cm, CH2Cl2). The filtrate was 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands 121 ______concentrated by oil pump vacuum (to ca. 1 mL) and layered carefully with hexanes (20 mL). After 24 h at −4 °C, the supernatant was carefully decanted from the precipitate, which was dried by oil pump vacuum to give trans-36d as a pale yellow solid (0.0469 g, 0.0535 mmol, 20%).

B. Solutions of trans-32d (0.218 g, 0.235 mmol) in CH2Cl2 (110 mL), and

Ru(=CHPh)(H2IMes)(PCy3)(Cl)2 (0.0200 g, 0.0235 mmol, 10 mol%) in CH2Cl2 (7 mL), were combined in a procedure analogous to A (the resulting solution is 0.00201 M in trans-32d). After hydrogenation, an analogous workup gave trans-36d as a pale yellow solid (0.0250 g, 0.0285 mmol, 12%). The sample slightly darkened at 190 °C. With further heating, it slowly turned black without liquefying (260 °C). DSC (Ti/Te/Tp/Tc/Tf): 159.5/167.8/194.6/201.7/209.4 °C (endotherm). TGA: onset of mass loss, 253.2 °C. Anal.

Calcd. for C34H46Cl2N2O8Pt: C 46.58%, H 5.29%, N 3.20%. Found: C 45.75%, H 5.41%, N 3.09%.

41 1 4 4 NMR (δ, CDCl3): H 9.68 (d, 4H, JHH = 1.8 Hz, o-Hpyr), 9.12 (t, 2H, JHH = 3 1.8 Hz, p-Hpyr), 4.44 (t, 8H, JHH = 5.8 Hz, 4OCH2), 1.87-1.81 (m, 8H, 4CH2), 1.71-1.63 13 1 43 (m, 8H, 4CH2), 1.54-1.47 (m, 16H, 8CH2); C{ H} 162.1 (s, CO), 157.1 (s, o-Cpyr),

141.0 (s, p-Cpyr), 128.6 (s, m-Cpyr), 67.2 (s, OCH2), 29.3, 28.6, 28.5, and 26.5 (4s, 4 CH2). MS:39a 876 (36d+, 30%), 840 ([36d − Cl]+, 60%), 817 (unknown, 100%). IR (cm−1, powder film): 3074 (w), 2935 (m), 2850 (m), 1738 (s), 1599 (w), 1460 (w), 1390 (w), 1267 (s), 1104 (m), 1004 (m), 958 (s), 749 (s).

trans-PtCl2[3,5,3',5'-(NC5H3(COO(CH2)12COO)2H3C5N)] (trans-36e).

Solutions of trans-32e (0.250 g, 0.253 mmol) in CH2Cl2 (120 mL), and

Ru(=CHPh)(PCy3)2(Cl)2 (0.021 g, 0.0253 mmol, 10 mol%) in CH2Cl2 (5 mL) were combined in a procedure analogous to that for trans-36d (the resulting solution is 0.00202

M in trans-32e). After hydrogenation, an analogous workup gave trans-36e as a light 122 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands ______yellow solid (0.105 g, 0.113 mmol, 45%), mp (capillary) 214-216 °C. DSC

(Ti/Te/Tp/Tc/Tf): 63.5/63.5/69.8/74.0/74.0 °C (endotherm), 75.0/80.4/86.8/91.8/101.0 °C (endotherm), 208.8/213.9/223.9/229.5/229.5 °C (endotherm). TGA: onset of mass loss,

220.3 °C. Anal. Calcd. for C38H54Cl2N2O8Pt: C, 48.92; H, 5.84; N, 3.00. Found: C, 48.52; H, 5.83; N, 3.00.

41 1 4 4 NMR (δ, CDCl3): H 9.66 (d, 4H, JHH = 1.8 Hz, o-Hpyr), 9.12 (t, 2H, JHH = 3 1.8 Hz, p-Hpyr), 4.45 (t, 8H, JHH = 5.9 Hz, 4OCH2), 1.82-1.89 (m, 8H, 4CH2), 1.60-1.53 13 1 43 (m, 8H, 4CH2), 1.48-1.40 (m, 24H, 12CH2); C{ H} 162.1 (s, CO), 157.0 (s, o-Cpyr),

141.2 (s, p-Cpyr), 128.9 (s, m-Cpyr), 67.1 (s, OCH2), 29.0, 28.6, 28.4, 28.3, and 26.3 (5 s,

5CH2). MS:39a 932 (36e+, 100%), 897 ([36e − Cl]+, 80%), 859 (unknown, 70%), IR (cm−1, powder film): 3084 (w), 3061(w), 2926 (m), 2853 (m), 1737 (s), 1463 (w), 1444 (w), 1266 (s), 1243 (s), 1112 (m), 1046 (m), 965 (m), 748 (s), 687 (m).

trans-PtCl2[3,5,3',5'-(NC5H3(COO(CH2)14COO)2H3C5N)] (trans-36f).

Solutions of trans-36f (0.250 g, 0.240 mmol) in CH2Cl2 (115 mL), and

Ru(=CHPh)(PCy3)2(Cl)2 (0.0197 g, 0.024 mmol, 10 mol%) in CH2Cl2 (5 mL), were combined in a procedure analogous to that for trans-36d (the resulting solution is 0.00200 M in trans-32f). After hydrogenation, an analogous workup gave trans-36f as a light yellow solid (0.0420 g, 0.0425 mmol, overall yield: 18%), mp (capillary) 150-152 °C.

DSC (Ti/Te/Tp/Tc/Tf): 137.1/146.0/152.4/154.3/154.3 °C (endotherm). TGA: onset of mass loss, 217.6 °C. Anal. Calcd. for C42H62Cl2N2O8Pt: C, 51.01; H, 6.32; N, 2.83. Found: C, 49.52, H, 5.78; N, 2.74.

41 1 4 4 NMR (δ, CDCl3): H 9.65 (d, 4H, JHH = 1.8 Hz, o-Hpyr), 9.10 (t, 2H, JHH = 3 1.8 Hz, p-Hpyr), 4.46 (t, 8H, JHH = 5.9 Hz, 4OCH2), 1.83-1.81 (m, 8H, 4CH2), 1.45-1.40 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands 123 ______

13 1 43 (m, 40H, 20CH2); C{ H} 162.1 (s, CO), 157.2 (s, o-Cpyr), 141.0 (s, p-Cpyr), 128.9 (s, m-Cpyr), 66.9 (s, OCH2), 28.9, 28.8, 28.7, 28.6, 28.4, 25.8 (6 s, 6CH2), MS:39a 988 (36f+, 50%), 953 ([36f − Cl]+, 30%), 915 (unknown, 100%). IR (cm−1, powder film): 3127 (w), 3107 (w), 2922 (s), 2853 (m), 1718 (s), 1606 (m), 1447 (m), 1305 (s), 1258 (s), 1108 (s), 799 (s), 741 (s), 683 (s).

trans-PtCl2[3,5,3',5'-(NC5H3(COO(CH2)18COO)2H3C5N)] (trans-36g).

Solutions of trans-32g (0.230 g, 0.20 mmol) in CH2Cl2 (95 mL), and

Ru(=CHPh)(PCy3)2(Cl)2 (0.0248 g, 0.0301 mmol, 15 mol%) in CH2Cl2 (5 mL), were combined in a procedure analogous to that for trans-32d (the resulting solution is 0.00200 M in trans-32g). After hydrogenation, an analogous workup gave trans-36g as a light yellow solid. (0.0301 g, 0.0272 mmol, overall yield: 14%), mp (capillary) 182-184 °C.

DSC (Ti/Te/Tp/Tc/Tf): 143.5/178.9/187.0/190.3/192.2 °C (endotherm). TGA: onset of mass loss, 202 °C. Anal. Calcd. for C50H78Cl2N2O8Pt: C, 54.54; H, 7.14; N, 2.54. Found: C, 54.13; H, 7.08; N, 2.33.

41 1 4 4 NMR (δ, CDCl3): H 9.65 (d, 4H, JHH = 1.8 Hz, o-Hpyr), 9.10 (t, 2H, JHH = 3 1.8 Hz, p-Hpyr), 4.45 (t, 8H, JHH = 5.9 Hz, 4OCH2), 1.85-1.82 (m, 8H, 4CH2), 1.45-1.29 13 1 43 (m, 56H, 28CH2); C{ H} 162.2 (s, CO), 157.1 (s, o-Cpyr), 141.6 (s, p-Cpyr), 128.8 (s, m-Cpyr), 66.9 (s, OCH2), 29.2, 29.0, 28.9, 28.7, 28.5, 27.8, 26.8, 25.6 (8 s, 8CH2). MS:39a 1101 (36g+, 25%), 1066 [36g − Cl]+, 35%), 1027 (unknown, 10%). IR (cm−1, powder film): 3080 (w), 2926 (s), 2853 (m), 1737 (s), 1598 (m), 1459 (m), 1266 (s), 1243 (s), 1162 (s), 1112 (s), 973 (s), 930 (s), 749 (s), 683 (s).

8 trans-PdCl2[2,6,2',6'-(NC5H3((CH2)2CH=CH(CH2)2)2H3C5N)] (trans-37). A two-necked round bottom flask was charged with trans-34 (0.108 g, 0.196 mmol) and

CH2Cl2 (5 mL). A solution of Ru(=CHPh)(PCy3)2(Cl)2 (0.0081 g, 0.098 mmol, 5 mol%) 124 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands ______

in CH2Cl2 (1.5 mL) was added dropwise over 10 min with stirring (the resulting solution is 0.0301 M in trans-34). A precipitate formed after 20 min. After 6 h, a second charge of

Ru(=CHPh)(PCy3)2(Cl)2 (0.0081 g, 5 mol%) was added as a solid. After 18 h, a final charge of Ru(=CHPh)(PCy3)2(Cl)2 (0.0081 g, 5 mol%) was added. The mixture was stirred for additional 6 h. Water (15 mL) and CH2Cl2 (15 mL) were added. After 30 min, the organic layer was separated. The aqueous layer was extracted with CH2Cl2 (3 × 15 mL). The organic layer and the extracts were combined, dried (MgSO4), and concentrated by rotary evaporation. The residue was chromatographed on silica gel (25 × 1 cm column, 7:3 v/v hexanes/ethyl acetate). The solvents were removed from the product-containing fractions by rotary evaporation and oil pump vacuum to give trans-37 as a light yellow solid (0.0563 g, 0.114 mmol, 58%; Rf (TLC) = 0.30).

1 41 3 3 H NMR (δ, CDCl3): 7.62 (t, 2H, JHH = 7.7 Hz, p-Hpyr), 7.12 (d, 4H, JHH = 3 7.7 Hz, m-Hpyr), 6.05-5.97 (m, 4H, 4CH=), 4.00 (t, 8H, JHH = 7.5 Hz, 4CH2), 3.28-3.18

(m, 8H, 4CH2).

trans-PdCl2[2,6,2',6'-(NC5H3((CH2)6)2H3C5N)] (trans-38). A round bottom flask was charged with trans-37 (0.0702 g, 0.142 mmol), PtO2 (0.0048 g, 0.021 mmol, 15 mol%), CH2Cl2 (14 mL), flushed with H2, and fitted with a balloon of H2 (1.0 atm). The mixture was stirred (3 d). The solvent was removed by rotary evaporation. The residue was chromatographed on alumina (10 × 2 cm column, CH2Cl2). The solvent was removed from the product-containing fractions by rotary evaporation and oil pump vacuum to give trans-

38 as a light yellow solid (0.044 g, 0.088 mmol, 62%, Rf (TLC) = 0.46). The sample slightly darkened at 150 °C. It turned black with further heating without liquefying (240

°C). TGA: onset of mass loss, 159.6 °C. Anal. Calcd. for C22H30Cl2N2Pd: C, 52.87%, H 6.05%, N 5.60%. Found: C 52.42%, H 6.60%, N 4.88%.

3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands 125 ______

41 1 3 3 NMR (δ, CDCl3): H 7.54 (t, 2H, JHH = 7.7 Hz, p-Hpyr), 7.11 (d, 4H, JHH =

7.7 Hz, m-Hpyr), 3.94-3.89 (m, 8H, 4CH2), 2.72-2.55 (m, 8H, 4CH2), 2.02-1.85 (m, 8H, 13 1 43 4CH2); C{ H} 165.1 (s, o-Cpyr), 139.0 (s, p-Cpyr), 123.8 (s, m-Cpyr), 40.6, 26.3 and

25.2 (3 s, 3CH2). MS:39b 501 (38+, 60%), 486 (unknown, 100%), 428 ([39 − 2Cl]+, 20%). IR (cm−1, powder film): 3069 (w), 2961 (m), 2926 (m), 2868 (m), 1644 (m), 1606 (m), 1575 (m), 1463 (s), 1262 (m), 1092 (s), 1019 (s), 915 (s), 791 (s), 757 (s).

19 trans-Pt(Cl)(C≡CPh)[3,5-NC5H3(COO(CH2)3CH=CH2)2]2 (trans-39c). A round bottom flask was charged with trans-32c (0.124 g, 0.142 mmol), CuI (0.0027 g,

0.014 mmol) and CH2Cl2/i-Pr2NH (10:1 v/v, 12 mL) with stirring. Then PhC≡CH (0.0207 g, 0.199 mmol) in CH2Cl2/i-Pr2NH (2 mL) was added dropwise over 5 min. The flask was fitted with a condenser. The solution was refluxed (3 d) and cooled to room temperature. The solvents were removed by rotary evaporation and oil pump vacuum. The residue was chromatographed on silica gel with gradient elution (25 × 2 cm column, 4:1 v/v hexanes/ethyl acetate to 100% ethyl acetate). The solvents were removed from the product- containing fractions by rotary evaporation and oil pump vacuum. The residue was dissolved in CH2Cl2 (ca. 1 mL) and layered carefully with hexanes (20 mL). After 24 h at −4 °C, the supernatant was decanted from the precipitate, which was dried by oil pump vacuum to give trans-39c as a pale yellow solid (0.0245 g, 0.0261 mmol, 18%; Rf (TLC) = 0.12 in 4:1 v/v hexanes/ethyl acetate).

41 1 4 4 NMR (δ, CDCl3): H 9.96 (d, 4H, JHH = 1.9 Hz, o-Hpyr), 9.01 (t, 2H, JHH = 3 3 1.9 Hz, p-Hpyr), 7.24-7.13 (m, 5H, Ph), 5.85 (ddt, 4H, JHHtrans = 17.1 Hz, JHHcis = 10.3 3 3 2 Hz, JHH = 6.7 Hz, 4CH=), 5.08 (dd, 4H, JHHtrans = 17.1 Hz, JHH = 1.9 Hz, 4 =CHEHZ), 3 2 3 5.02 (dd, 4H, JHHcis = 10.3 Hz, JHH = 1.9 Hz, 4 =CHEHZ), 4.43 (t, 8H, JHH = 6.6 Hz, 13 1 4OCH2), 2.25-2.20 (m, 8H, 4CH2), 1.94-1.87 (m, 8H, 4CH2); C{ H} 162.7 (s, CO), 126 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands ______

43 158.6 (s, o-Cpyr), 140.1 (s, p-Cpyr), 137.7 (s, CH=), 132.1 (s, o-Ph), 128.9 (s, m-Cpyr),

128.3 (s, p-Ph), 127.2 (s, m-Ph), 126.5 (s, i-Ph), 115.7 (s, =CH2), 94.0 and 85.0 (2 s, C≡C),

66.4 (s, OCH2), 30.4 and 28.1 (2 s, 2CH2). MS:39a 938 (39c+, 100%)

−1 IR (cm , powder film): 3076 (w), 2961 (w), 2907 (w), 2351 (m), 2131 (m, νC≡C), 1725 (s), 1640 (m), 1598 (m), 1444 (m), 1305 (s), 1262 (s), 1239 (s), 1112 (s), 984 (s), 911 (s), 741 (s). 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands 127 ______

3.7. References and notes

(1) Hahn, E. H.; Bohm, H.; Ginsburg, D. Tetrahedron Lett. 1973, 14, 507. (2) Cyclophanes, Keehn, P. M.; Rosenfeld, S. M. Eds.; Academic Press, New York, 1983. (3) Helder R.; Wynberg H. Tetrahedron Lett. 1973, 14, 4321. (4) Vögtle, F.; Mew, P. K. T. Angew. Chem., Int. Ed. Engl. 1978, 17, 60. (5) Bedard, T. C.; Moore, J. S. J. Am. Chem. Soc. 1995, 117, 10662. (6) (a) Dominguez, Z.; Strouse, H.; Garcia-Garibay, M. A. J. Am. Chem. Soc. 2002, 124, 2398. (b) Dominguez, Z.; Khuong, T.-A.; Dang, H.; Sanrame, C. N.; Nuñez, J. E.; Garcia-Garibay, M. A. J. Am. Chem. Soc. 2003, 125, 8827. (c) Khuong, T.-A.; Zepeda, G.; Ruiz, R.; Khan, S. I.; Garcia-Garibay, M. A. Cryst. Growth Des. 2004, 4, 15. (d) Godinez, C. E.; Zepeda, G.; Mortko, C. J.; Dang, H.; Garcia-Garibay, M. A. J. Org. Chem. 2004, 69, 1652. (e) Karlen, S. D.; Garcia-Garibay, M. A. Chem. Commun. 2005, 189. (f) Cizmecyian, D.; Yonutas, H.; Karlen, S. D.; Garcia-Garibay, M. A. Solid State Mag. Res., 2005, 28, 1. (g) Khuong, T.-A.; Nuñez, J. E.; Godinez, C. E.; Garcia-Garibay, M. A. Acc. Chem. Res. 2006, 39, 413. (h) Karlen, S. D.; Jarowski, P. D.; Santillan, R.; Horansky, R. D.; Winston, E. B.; Price, J. C.; Clarke, L. I.; Garcia-Garibay, M. A. Phys. Rev. B 2006, 74, 54036. (i) Nuñez, J. E.; Natarajan, A.; Khan, S. I.; Garcia-Garibay, M. A. Org. Lett. 2007, 9, 3559. (l) Garcia-Garibay, M. A. Angew. Chem., Int. Ed. 2007, 46, 8945. (m) Garcia-Garibay, M. A. Nature 2008, 7, 431. (7) (a) Bauer, E. B.; Ruwwe, J.; Martín-Alvarez, J. M.; Peters, T. B.; Bohling, J. C.; Hampel, F.; Szafert, S.; Lis, T.; Gladysz, J. A. Chem. Commun. 2000, 2261. (b) Ruwwe, J.; Martín-Alvarez, J. M.; Horn, C. R.; Bauer, E. B.; Szafert, S.; Lis, T.; Hampel, F.; Cagle, P. C.; Gladysz, J. A. Chem. Eur. J. 2001, 7, 3931. (c) Shima, T.; Bauer, E. B.; Hampel, F.; Gladysz, J. A. Dalton Trans. 2004, 1012. (d) Shima, T.; Hampel, F.; Gladysz, J. A. Angew.

Chem. 2004, 116, 5653; Angew. Chem., Int. Ed. 2004, 43, 5537. (e) Nawara, A. J.; Shima, 128 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands ______

T.; Hampel, F.; Gladysz, J. A. J. Am. Chem. Soc. 2006, 128, 4962. (f) Wang, L.; Shima, T.; Gladysz, J. A. Chem. Commun. 2006, 4075. (g) Wang, L.; Hampel, F.; Gladysz, J. A. Angew. Chem. 2006, 118, 4479; Angew. Chem., Int. Ed. 2006, 45, 4372. (h) Heß, G. D.; Hampel, F.; Gladysz, J. A. Organometallics 2007, 26, 5129. (i) Skopek, K.; Gladysz, J. A. J. Organomet. Chem. 2008, 693, 857. (8) Ng, P. L.; Lambert, J. N. Synlett 1999, 1749. (9) Wibaut, J. P.; Bloemendal, H. Recl. Trav. Chim. Pays-Bas 1958, 77, 123. (10) Lockemeyer, J. R.; Rheingold, A. L.; Bulkowski, J. E. Organometallics 1993, 12, 256. (11) Dijkstra H. P.; Chuchuryukin, A. V.; Sujkerbuijk, B. M. J. M.; van Klink, G. P. M.; Mills, A. M.; Spek, A. L.; van Koten, G. Adv. Synth. Catal. 2002, 344, 771. (12) Yuncheng, Y.; Yulin, J.; Jun, P.; Xiaohui, Z.; Conggui Y. Gazz. Chim. Ital. 1993, 123, 519. (13) Costanzo, S.; Decréau, R. A.; Collman J. P. Org. Lett. 2004, 6, 1033. (14) Chuchuryukin, A. V.; Chase, P. A.; Dijkstra H. P.; Sujkerbuijk, B. M. J. M.; Mills, A. M.; Spek, A. L.; van Klink, G. P. M.; van Koten, G. Adv. Synth. Catal. 2005, 347, 447. (15) (a) Lanfranchi M.; Nobile, C. F.; Pellinghelli, M. A.; Vasapollo, G.; Sacco, A. J. Organomet. Chem. 1986, 312, 249. (b) Guillevic, M.-A.; Rocaboy, C.; Arif., A. M.; Horváth, I. T.; Gladysz, J. A. Organometallics 1998, 17, 707. (16) Lanfranchi M.; Latronico, M.; Nobile, C. F.; Pellinghelli, M. A.; Vasapollo, G. J. Organomet. Chem. 1987, 336, 429. (17) For all complexes, the 1H NMR spectra of an aliquot showed that complete conversion was achieved after 3 d. (18) (a) Cattalini, L.; Guidi, F.; Tobe, M. J. Chem. Soc., Dalton Trans. 1993, 233. (b) Chatt, J.; Shaw, B. L. J. Chem. Soc. 1959, 705.

(19) (a) Adams, C. J.; James, S. L.; Raithby, P. R. Chem. Commun. 1997, 2155. (b) 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands 129 ______

Mongin, C.; Donnio, B.; Bruce, D. W. J. Am. Chem. Soc. 2001, 123, 8426. (20) Freedman, H. H.; Dubois, R. A. Tetrahedron Lett. 1975, 16, 3251. (21) Jiguo, L.; Shuguang, S.; Zhang, Z. Huaxue Shiji 1986, 8, 370. (22) (a) Dou, H. J. M.; Gallo, R.; Hassanaly, P.; Metzger, J. J. Org. Chem. 1977, 42, 4275. (b) Dou, H. J. M.; Komoili-Zadeh, H.; Metzger, J. J. Org. Chem. 1978, 43, 156. (23) (a) Olmsted III, J.; Meyer, T. J. J. Phys. Chem. 1987, 91, 1649. (b) Mandler, D.; Willner, I. J. Phys. Chem. 1987, 91, 3600. (c) Hass, O.; Sandmeyer, B. J. Phys. Chem. 1987, 91, 5072. (d) Li, Z.; Mallouk, T. E. J. Phys. Chem. 1987, 91, 643. (24) For some examples see: (a) Ganis, P.; Saporito, A.; Vitagliano, A.; Valle, G. Inorg. Chim. Acta 1988, 142, 75. (b) Edwards, D. A.; Larter, S. J. Polyhedron 1986, 5, 1213. (c) Maeda, S.; Nishida, Y.; Okawa, H.; Kida, S. Bull. Chem. Soc. Jpn. 1986, 59, 2013. (25) For some examples see: (a) De Felice, V.; Giovannitti, B.; Panunzi, A.; Ruffo, F.; Tesauro, D. Gazz. Chim. Ital. 1993, 123, 65. (b) Goldsworthy, D. H.; Kite, K. J. Organomet. Chem. 1987, 319, 257. (c) Appleton, T. G.; Hall, J. R.; Mathieson, M. T.; Neale, D. W. J. Organomet. Chem. 1993, 453, 307. (26) For some examples see: (a) Suggs, J. W.; Hun, C. H. J. Am. Chem. Soc. 1986, 168, 4679. (b) Zuber, M. Transition Met. Chem. 1986, 11, 5. (c) Cotton, F. A.; Matusz, M. Inorg. Chim. Acta 1988, 143, 45. (27) (a) Kong, P. C.; Rochon, F. D. Can. J. Chem. 1978, 56, 441. (b) Rochon, F. D.; Kong, P. C.; Melanson, R. Can. J. Chem. 1980, 58, 97. (c) Tessier, C.; Rochon, F. D. Inorg. Chim. Acta 2001, 322, 37. (28) Chase P. A.; Lutz, M.; Spek, A. L.; van Klink, G. P. M.; van Koten, G. J. Mol. Catal. A: Chem. 2006, 344, 771. (29) Bensimon, C.; Beauchamp, A. L.; Rochon, F. D. Can. J. Chem. 1996, 74, 2121.

(30) Colamarino, P.; Orioli, P. L. J. Chem. Soc., Dalton Trans. 1975, 1656. 130 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands ______

(31) Tessier, C.; Rochon, F. D. Inorg. Chim. Acta 1999, 295, 25. (32) Bondi, A. J. Phys. Chem. 1964, 68, 441. (33) Kottas, G. S.; Clarke, L. I.; Horinek, D.; Michl, J. Chem. Rev. 2005, 105, 1281. (34) Clarke, L. I.; Horinek, D.; Kottas, G. S.; Varaska, N.; Magnera, T. F.; Hinderer, T. P.; Horansky, R. D.; Michl, J.; Price, J. C. Nanotechnology 2003, 13, 533. (35) (a) Reed, M. A.; Zhou, C.; Mullen, C. J.; Burgin, T. P., Tour, J. M. Science 1997, 278, 252. (b) Kegueris, C.; Bourgoin, J.-P.; Palacin, S.; Esteve, D.; Urbina, C.; Magoga, M.; Joachim, C. Phys. Rev. B 1999, 59, 12505. (c) Reichert, J.; Ochs, R.; Beckmann, D.; Weber, H. B.; Mayor, M.; von Löhneysen, H. Phys. Rev. Lett. 2002, 88, 176804. (d) Reichert, J.; Ochs, R.; Ahlrichs, H.; Beckmann, D.; Weber, H. B.; Mayor, M.; von Löhneysen, H. Chem. Phys. 2002, 281, 113. (e) Mayor, M.; von Hanisch, C.; Weber, H.; Reichert, J.; Beckmann, D. Angew. Chem., Int. Ed. 2002, 41, 1183. (36) Troisi, A.; Ratner, M. A. Nano Lett. 1999, 1, 953. (37) (a) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999, 1, 953. (b) Trnka, T. M.; Morgan, J. P.; Sanford, M. S.; Wilhelm, W. E.; Scholl, M.; Choi, T.; Ding, S.; Day, M.W.; Grubbs, R. H. J. Am. Chem. Soc. 2003, 125, 2546. (38) Cammenga, H. K.; Epple, M. Angew. Chem. 1995, 107, 1284; Angew. Chem., Int. Ed. Engl. 1995, 34, 1171. (39) (a) FAB, 3-NBA, m/z (relative intensity, %); the peaks correspond to the most intense peak of the isotope envelope. (b) FAB, 2-NPOE, m/z (relative intensity, %); the peaks correspond to the most intense peak of the isotope envelope. (40) MALDI, 2,5-DHB, m/z (relative intensity, %); the peaks correspond to the most intense peak of the isotope envelope.

(41) The designations p-Hpyr, m-Hpyr, o-Hpyr, p-Cpyr, m-Cpyr, and o-Cpyr indicate protons and carbon atoms that occupy the 4, 3/5, and 2/6 positions with respect to the pyridine nitrogen atom. 3. Gyroscope-like complexes with doubly trans-spanning bis(pyridine) ligands 131 ______

(42) The pyridine 13C{1H} signals were assigned according to generalizations provided in (a) Spectrometric Identification of Organic Compounds, Silverstein, R. M.; Bassler, G. C.; Morrill, T. Eds.; John Wiley and Sons, New York, 1991, pp. 239-241; (b) and Basic One- and Two- Dimensional NMR Spectroscopy, Friebolin, H. Ed.; Wiley-VCH, Weinheim, 1998, pp. 64-65. (43) Reference 31 establishes that the 13C{1H} NMR signals of a variety of substituted pyridine ligands are shifted only a few ppm upon coordination to square planar platinum (see Table 6 in ref. 31). Hence, analogous assignments have been made for the new rhodium, platinum, and palladium complexes.

Novel ruthenium-based carbene complexes

Aim of the chapter

The first part of this chapter gives a brief overview about recent promising developments in ruthenium-based metathesis technology. In the principal thrust, the results of an NMR study on the reactivity of Grubbs-type catalysts with alkene-containing pyridines and rhenium complexes are described.

4.1 Introduction

4.1.1. Developments of ruthenium technology. In the last years, the discovery of new efficient catalysts has enabled a widespread utilization of alkene metathesis in numerous fields of chemical synthesis. In particular, several ruthenium-based complexes were developed in order to achieve high activities and a spectrum of selectivities.1-3 In particular, three fields gave relevant results. The first one involved applications in polymer science.4 In general, a catalyst for polymer technology has to exhibit a slower initiation step, which enables longer handling of the monomer/catalyst before the beginning of the polymerization.5 On this point, different strategies were considered, as outlined in Figure 4.1.

L1 L1 L1 L1 Cl Cl Cl Cl Ru Ru Ru Ru Cl Cl X Cl R X R L2 L2 L2 L2

I II III IV

L1 : PCy3, H2IMes

Figure 4.1. Design concepts for thermally switchable metathesis catalyst precursors.

One limit would involve an inert ligand L2 in a position trans to L1 (motif I). 4. Novel ruthenium-based carbene complexes 133 ______

Successful examples were not realized up to now because it seems that even ligands that are known to form strong bonds to the ruthenium center are labile in this environment. The chelate effect has been utilized as sketched in motifs II and III. The ligand L2 is either attached to the carbene (motif II) or via X to the ruthenium center (motif III, where X is oxygen, for example). Hoveyda-type catalysts represent the prototype of the motif II.6 Other examples with a chelation of oxygen donor ligands have been described in literature.7 As shown in Figure 4.2, in a second group of complexes, the chelation was via nitrogen donor atoms. Van der Schaaf and co-workers realized the first example (V).8 More recently Grubbs5a (VI), Grela9 (VII), and Slugovc5b (VIII) and co-workers isolated related catalysts.

N N N N N N i-Pr3P

Cl Ru Cl Ru Cl Ru Cl Ru Cl Cl Cl Cl N N N N

N V VI VII VIII

Figure 4.2. Representative N-ruthenium chelates following motif II.

Examples of catalysts based on the motif III were also developed. Grubbs10 (IX) and Verpoort11 (X) and co-workers reported studies in which bidentate Schiff base ligands were utilized, while Herrmann and co-workers tested a N-heterocyclic carbene ligand in combination with chelating pyridinyl-alkoxide ligands (XI) (Figure 4.3).12

N N N R2 N R2 Cl O Ru R1 O Ru Ru Ph O Cl Ph Cl Ph PCy3 N R R2 1 N N R1

IX X XI

Figure 4.3. Representative N-ruthenium chelates following motif III.

Finally, the approach sketched in motif IV, in which X is O or S, involves the use of Fisher carbenes instead of Schrock carbenes.13 A second field of research involved the preparation of analogs of Grubbs-type 134 4. Novel ruthenium-based carbene complexes ______catalysts containing a second metallic center. Examples of application of heterobimetallic compounds can be found in the context of superconducting or semiconducting materials, electrocatalysis and non-linear optics.14 Sarkar and co-workers reported the metathesis of Grubbs' catalyst with vinyl ferrocene and 1-ferrocenyl butadiene.15 The ruthenium/iron complexes in Figure 4.4 could be isolated in high yields.

PCy3 PCy3 Cl Cl Ru Ru Cl Cl PCy3 PCy3 Fe Fe

XII XIII

Figure 4.4. Sarkar's heterobimetallic precursors.

Both complexes were tested in alkene metathesis reactions. In particular, ROMP of norbornene furnished a low polydispersity value (PDI = 1.7). As shown in Figure 4.5, Butenschön and co-workers provided a modified version of Hoveyda's second generation catalyst in which the benzylidene ligand is π-coordinated to the electron-withdrawing 16 CrCO3.

N N

Cl Ru Cl O

CrCO3 XIV

Figure 4.5. Butenschön's heterobimetallic precursor.

4.1.2. Carbyne and carbide complexes. A third field of research involves the isolation of carbyne and carbide complexes directly from the well-known carbene complexes developed for alkene metathesis.17 In heterogeneous catalysis, surface carbides serves as intermediates for the formation of hydrocarbons from synthesis gas, as in the Fischer-Tropsch process.18,19 In homogeneous catalysis, carbyne complexes are known as precursors to active alkyne metathesis catalysts.20 The conversion of carbene into carbyne ligands at ruthenium was accomplished by bulky germanium complexes as 4. Novel ruthenium-based carbene complexes 135 ______

17a Ge[CH(Si(CH3)3)2]2. Examples are shown in Figure 4.6.

PCy N N PCy3 3 PCy3 PCy3 Cl Cl Cl Cl I Ru Ru C Ru C Os C Os C Cl Cl Cl Cl I PCy3 PCy3 PCy3 PCy3 PCy3

XV XVI XVII XVIII XIX

Figure 4.6. Examples of carbyne (XV) and carbide complexes (XVI, XVII, XVIII, and XIX).

The complex XVIII, in particular, represented the first example of carbide complex of any metal other than molybdenum, tungsten, and ruthenium.21

4.2. Project design

The aim of this study is to probe the possibility to isolating new classes of ruthenium-based complexes. The project is designed with three complementary phases. In the first one, alkene-containing pyridines and rhenium complexes were designed. The position, the structure, and the length of alkene chains are modified for the first group of compounds, whereas only the length is modulated for the second. Subsequently, their reactions with the most common metathesis catalysts

Ru(=CHPh)(PCy3)2(Cl)2 (13) and Ru(=CHPh)(H2IMes)(PCy3)(Cl)2 (14) are monitored by low temperature NMR spectroscopy. In the last phase, the information acquired in the spectroscopic analysis is transferred to preparative scale reactions.

4.3. Results

4.3.1. Alkene-containing pyridines. The alkene-containing pyridines 22a, 25b, and 29g were selected for initial experiments (Figure 4.7). The synthesis and the characterization data were reported in Chapter 3.

136 4. Novel ruthenium-based carbene complexes ______

O O

nO O n O O N n O N O n N n n n = 1, 22a n = 2, 25b n = 8, 29g

Figure 4.7. Alkene-containing pyridine studied in this chapter.

4.3.2. Alkene-containing rhenium complexes. A series of chiral rhenium complexes with ligands of the formula (CH2)nCH=CH2 were sought. First, the vinyl rhenium complex (R)-43 (n = 0) was prepared by the route previously reported for the racemate (Scheme 4.1).22 Retention of configuration was presumed in accord with 23 + – abundant precedent. The optical rotation and purities of (R)-41, (R)-42 PF6 , and (R)-43 were not determined.

PF6

1. Ph C+ PF + 3 6 Ph3C PF6 DBU Re Re Re Re Ph3P NO Ph3P NO Ph P Ph3P NO 2. CH3Li 3 NO CH3 CH2 CH CH H3C H C H3C 2

+ – (R)-40 (R)-41, 72% (R)-42 PF6 , 75% (R)-43, 30%

Scheme 4.1. Synthesis of vinyl complex (R)-43.

As shown in Scheme 4.2, the higher homolog (R)-45 (n = 2) was synthesized starting from the methyl complex (R)-40,24 which was sequentially treated with + – Ph3C PF6 and the Grignard reagent CH2=CHCH2MgBr (–78 °C, then room temperature). Recrystallization from CH2Cl2 layered with hexanes gave (R)-45 as small orange square blocks in good yields (50%). Alternatively, (R)-45 could be purified by silica gel column chromatography.

PF6

+ Ph3C PF6 MgBr Re Re Re Ph3P NO Ph3P NO Ph3P NO CH3 CH2 CH2 H2C CH H2C (R)-40 (R)-44 (R)-45, 50%

Scheme 4.2. Synthesis of (R)-45.

4. Novel ruthenium-based carbene complexes 137 ______

As shown in Scheme 4.3, the synthesis of (R)-46 (n = 3) was accomplished from + – (R)-40, which was sequentially treated with Ph3C PF6 and the Grignard reagent

CH2=CHCH2CH2MgBr (–78 °C, then room temperature). Attempts to isolate (R)-46 by crystallization as for (R)-45 were not effective. Purification by silica gel column chromatography afforded (R)-46 in good yields (45%).

PF6 + Ph3C PF6 MgBr Re Re Re Ph3P NO Ph3P NO Ph3P NO CH3 CH2 CH2 H2C

CH2 HC

CH2

(R)-40 (R)-44 (R)-46, 45%

Scheme 4.3. Synthesis of (R)-46.

Alkene-containing rhenium complexes (R)-45 and (R)-46 were characterized by NMR (1H, 13C{1H}, and 31P{1H}) and IR spectroscopy, mass spectrometry, DSC, and thermogravimetric and microanalyses, as summarized in the experimental section. Both complexes could be stored in air for extended periods, and were stable in solution: 1 31 1 variations in H and P{ H} NMR spectra in CD2Cl2 were not visible after one week. 5 25 The allyl complex (η -C5H5)Re(NO)(PPh3)(CH2CH=CH2) has also been reported, 13 1 completing a homologous series spanning 43 to (R)-46. The ReCH2 C{ H} NMR chemical shifts exhibit a monotonic downfield shift. Mass spectroscopic data showed analogous patterns for (R)-45 and (R)-46. Suitable crystals for X-ray analysis were obtained only for (R)-46. X-ray data were collected and refined as described in Chapter 5. The molecular structure of (R)-46 is shown in Figure 4.8. The complex crystallizes in a P212121 space group, with Z = 4 and V = 2491.52(4) Å3. The Re-C1 and Re-C5 distances were, respectively, 2.194(4) Å and 6.600 Å. The P-Re-C1-C2 torsion angle (147.6(4)°) was comparable with that in one 5 26 conformation of the cinnamyl complex (η -C5H5)Re(NO)(PPh3)(CH2CH=CHC6H5). Selected bond lengths and bond angles for (R)-46 are given in Tables 4.1. The 138 4. Novel ruthenium-based carbene complexes ______absolute at rhenium configuration was confirmed by absolute structure Flack's parameter (0.009(8)).27 This established overall retention of configuration from (R)-40. The CH= carbon atom exhibited disorder. It refined to a 57:43 occupancy ratio (C4/C4').

Figure 4.8. Thermal ellipsoid plot (50% probability) of (R)-46. The disordered atom C4 is depicted in the predominant conformation.

Table 4.1. Key bond lengths (Å) and angles [°] for (R)-46.

bond lengths

Re-C1 2.194(4) Re-N 1.748(4) Re-C1 2.3357(10) N-O 1.222(5) Re-C4 5.593 Re-C5 6.600 C1-C2 1.500(6) C2-C3 1.536(7) C3-C4 1.524(9)[a] C4-C5 1.168(10)[a]

bond angles

N-Re-C1 93.67(19) N-Re-P 93.19(12) C1-Re-P 89.87(11) Re-N-O 178.4(4) Re-C1-C2 113.7(3) C1-C2-C3 114.6(4) C2-C3-C4 110.4(5)[a] C3-C4-C5 131.5(9)[a] [a] The value given corresponds to the dominant conformation of the disordered atom C4. 4. Novel ruthenium-based carbene complexes 139 ______

4.3.3. VT NMR experiments with alkene-containing pyridines.

VT NMR experiment 1. The reaction of 22a with 13 in CD2Cl2 was monitored by 1H and 31P{1H} NMR. The sample was warmed from −75 °C to 25 °C, then kept at room temperature and analyzed after 12 h. Selected spectra are given in Figures 4.9 and 4.10. The former shows the region for the Ru=CH signals. The structural assignment methylidene complex 13-a was based upon 1H and 31P{1H} NMR chemical shift data 28 reported in the literature (18.94 and 43.7 ppm, CD2Cl2, room temperature).

PCy3 PCy3 18.94 ppm Cl Cl Ru Ru CH Cl Cl 2 PCy3 PCy3

13 13-a rt (after 12 h)

PCy3 Cl Ru Cl 19.32 ppm CH2R PCy3 25 °C 13-b

19.68 ppm

–75 °C

1 Figure 4.9. Partial H NMR spectra of VT experiment 1. PCy PCy3 3 Cl Cl Ru CH Ru Cl 2 Cl PCy PCy3 3 rt (after 12 h) 13-a 13 36.9 ppm 25 °C

37.2 ppm 5 °C

–75 °C

31 1 Figure 4.10. Partial P{ H} NMR spectra of VT experiment 1. 140 4. Novel ruthenium-based carbene complexes ______

When the sample was warmed from −75 °C to 25 °C, the Ru=CH 1H NMR singlet of 13 shifted from 19.68 ppm to 20.02 ppm (see Figure 4.9). A triplet compatible with an alkylidene species [Ru]=CHCH2R (13-b) was present at 15 °C (19.28 ppm). This slightly shifted at 25 °C (19.32 ppm; see Figure 4.9). The singlet of the methylidene complex

[Ru]=CH2 (13-a, 18.94 ppm; see Figure 4.9) was predominant after 12 h. The 31P{1H} NMR spectra showed a new singlet (37.2 ppm; see Figure 4.10) starting at 5 °C. At 25 °C, the singlet is slightly shifted (36.9 ppm; see Figure 4.10), and other new peaks also began to appear. After 12 h at room temperature, three major signals were present (44.6, 37.4, and 37.0 ppm; see Figure 4.10). The first two could be assigned to 13-a and the starting catalyst 13 (see Figure 4.10).

4. Novel ruthenium-based carbene complexes 141 ______

VT NMR Experiment 2. The reaction of 22a with 14 in CD2Cl2 was monitored by 1H and 31P{1H} NMR. The sample was warmed from −75 °C to 35 °C, then cooled to room temperature and analyzed after 12 h. Selected spectra are given in Figures 4.11 and 4.12. The former shows the region for the Ru=CH signals. The structural assignment methylidene complex 14-a was based upon 1H and 31P{1H} NMR chemical shift data 29 reported in the literature (18.41 and 38.6 ppm, benzene-d6, room temperature).

N N Cl Ru Cl

PCy3 rt (after 12 h) 14

N N N N

Cl 18.64 ppm Cl 17.74 ppm Ru Ru Cl Cl CH2 CH2R PCy3 PCy3 35 °C 14-b 14-a

18.68 ppm –75 °C

Figure 4.11. Partial 1H NMR spectra of VT experiment 2.

N N N N

Cl Cl Ru Ru Cl CH2 Cl PCy3 PCy3 rt (after 12 h) 14-a 14

35 °C

30.1 ppm 25 °C

–75 °C

Figure 4.12. Partial 31P{1H} NMR spectra of VT experiment 2.

142 4. Novel ruthenium-based carbene complexes ______

When the sample was warmed from −75 °C to 35°C, the Ru=CH 1H NMR singlet of 14 shifted from 18.68 ppm to 19.15 ppm (see Figure 4.11). An apparent triplet compatible with an alkylidene species [Ru]=CHCH2R (14-b, 18.64 ppm; see Figure 4.11) and the singlet of the methylidene complex [Ru]=CH2 (14-a, 17.74 ppm; see Figure 4.11) were present at 25 °C and persisted at 35 °C. The 31P{1H} NMR spectra showed a new singlet (30.1 ppm; see Figure 4.12) starting at 25 °C. This persisted at 35 °C. At 35 °C, other new peaks also began to appear. After 12 h at room temperature, the signals present at 37.7 and 30.6 ppm could be assigned to 14-a and the starting catalyst 14 (see Figure 4.12).

4. Novel ruthenium-based carbene complexes 143 ______

VT NMR Experiment 3. The reaction of 25b with 13 in CD2Cl2 was monitored by 1H and 31P{1H} NMR. The sample was warmed from −75 °C to 25 °C, then kept at room temperature and analyzed after 12 h. Selected spectra are given in Figures 4.13 and 4.14. The former shows the region for the Ru=CH signals.

PCy3 Cl Ru Cl PCy3 PCy Cl 3 Ru CH 18.96 ppm Cl 2 PCy 13 3 13-a rt (after 12 h)

PCy3 Cl Ru Cl 19.43 ppm CH R PCy 2 3 25 °C 13-b

19.68 ppm –75 °C

1 Figure 4.13. Partial H NMR spectra of VT experiment 3. PCy3 PCy3 Cl Cl Ru CH Ru Cl 2 Cl PCy3 PCy3

13-a 13

rt (after 12 h)

25 °C

36.8 ppm 5 °C

–75 °C

Figure 4.14. Partial 31P{1H} NMR spectra of VT experiment 3.

144 4. Novel ruthenium-based carbene complexes ______

When the sample was warmed from −75 °C to 25 °C, the Ru=CH 1H NMR singlet of 13 shifted from 19.68 ppm to 20.03 ppm. A triplet compatible with an alkylidene species [Ru]=CHCH2R (13-b) was present at 5 °C (19.39 ppm). This slightly shifted at 25

°C (19.43 ppm; see Figure 4.13). The singlet of the methylidene complex [Ru]=CH2 (13-a, 18.96 ppm; see Figure 4.13) was predominant after 12 h. The 31P{1H} NMR spectra showed a new singlet (36.8 ppm; see Figure 4.14) starting at 5 °C. This persisted at 25 °C. At 25 °C, other new peaks also began to appear. After 12 h at room temperature, three major signals were present (44.5, 37.4, and 36.6 ppm). The first two could be assigned to 13-a and the starting catalyst 13 (see Figure 4.14).

4. Novel ruthenium-based carbene complexes 145 ______

VT NMR Experiment 4. The reaction of 25b with 14 in CD2Cl2 was monitored by 1H and 31P{1H} NMR. The sample was warmed from −75 °C to 35 °C, then cooled to room temperature and analyzed after 12 h. Selected spectra are given in Figures 4.15 and 4.16. The former shows the region for the Ru=CH signals.

N N

Cl Ru Cl

PCy3 14 rt (after 12 h)

N N N N Cl Ru Cl Cl Ru CH CH2R Cl 2 PCy3 18.77 ppm 17.80 ppm PCy3 35 °C 14-b 14-a

18.64 ppm –75 °C

Figure 4.15. Partial 1H NMR spectra of VT experiment 4.

N N

Cl Ru N N Cl PCy3 Cl Ru Cl CH2 14 PCy3 rt (after 12 h) 14-a

31.0 ppm 35 °C

–75 °C

Figure 4.16. Partial 31P{1H} NMR spectra of VT experiment 4.

146 4. Novel ruthenium-based carbene complexes ______

When the sample was warmed from −75 °C to 35 °C, the Ru=CH 1H NMR singlet of 14 shifted from 18.64 ppm to 19.15 ppm. A triplet compatible with an alkylidene species [Ru]=CHCH2R (14-b, 18.77 ppm; see Figure 4.15) and the singlet of the methylidene complex [Ru]=CH2 (14-a, 17.80 ppm; see Figure 4.15) were present at 25 °C and persisted at 35 °C. The 31P{1H} NMR spectra showed a new singlet (31.0 ppm) starting at 35 °C. At 35 °C, other new peaks also began to appear. After 12 h at room temperature, the signals at 37.7 and 30.6 ppm could be assigned to 14-a and the starting catalyst 14 (see Figure 4.16).

4. Novel ruthenium-based carbene complexes 147 ______

VT NMR Experiment 5. The reaction of 29g with 13 in CD2Cl2 was monitored by 1H and 31P{1H} NMR. The sample was warmed from −75 °C to 25 °C, then kept at room temperature and analyzed after 12 h. Selected spectra are given in Figures 4.17 and 4.18. The former shows the region for the Ru=CH signals.

PCy3 PCy3 Cl Cl Ru Ru CH Cl Cl 2 18.98 ppm PCy3 PCy3

13 13-a rt (after 12 h)

PCy3 Cl Ru Cl 19.25 ppm CH R PCy 2 3 25 °C 13-b

19.68 ppm –75 °C

Figure 4.17. Partial 1H NMR spectra of VT experiment 5.

PCy3 PCy3 Cl Cl Ru CH Ru Cl 2 Cl PCy3 PCy3

13-a 13 rt (after 12 h)

36.6 ppm 25 °C

37.0 ppm 5 °C

–75 °C

Figure 4.18. Partial 31P{1H} NMR spectra of VT experiment 5.

148 4. Novel ruthenium-based carbene complexes ______

When the sample was warmed from −75 °C to 25 °C, the Ru=CH 1H NMR singlet of 13 shifted from 19.68 ppm to 20.02 ppm (see Figure 4.17). A triplet compatible with an alkylidene species [Ru]=CHCH2R (13-b, 19.21 ppm) was present at 15 °C. This is slightly shifted at 25 °C (19.25 ppm; see Figure 4.17). The singlet of the methylidene complex

[Ru]=CH2 (13-a, 18.98 ppm; see Figure 4.17) was predominant after 12 h. The 31P{1H} NMR spectra showed a new singlet (37.0 ppm; see Figure 4.18) starting at 5 °C. At 25 °C, the singlet was slightly shifted (36.6 ppm; see Figure 4.18). At 25 °C other new peaks also began to appear. After 12 h at room temperature, the signals present at 44.5 and 37.4 ppm could be assigned to 13-a and the starting catalyst 13 (see Figure 4.18).

4. Novel ruthenium-based carbene complexes 149 ______

VT NMR Experiment 6. The reaction of 29g with 14 in CD2Cl2 was monitored by 1H and 31P{1H} NMR. The sample was warmed from −75 °C to 35 °C, then cooled to room temperature and analyzed after 12 h. Selected spectra are given in Figure 4.19 and 4.20. The former shows the region for the Ru=CH signals.

N N N N

Cl Cl Ru Ru CH Cl Cl 2 PCy PCy3 17.73 ppm 3 14-a rt (after 12 h) 14

N N

Cl Ru Cl CH2R 18.56 ppm PCy3 35 °C 14-b

18.65 ppm –75 °C

Figure 4.19. Partial 1H NMR spectra of VT experiment 6.

N N N N Cl Cl Ru CH Ru Cl 2 Cl PCy 3 PCy3 14-a 14 rt (after 12 h)

35 °C

31.3 ppm 25 °C

–75 °C

31 1 Figure 4.20. Partial P { H} NMR spectra of VT experiment 6.

150 4. Novel ruthenium-based carbene complexes ______

When the sample was warmed from −75 °C to 35 °C, the Ru=CH 1H NMR singlet of 14 shifted from 18.65 ppm to 19.11 ppm (see Figure 4.19). A triplet compatible with an alkylidene species [Ru]=CHCH2R was present at 25 °C (14-b, 18.56 ppm). This persisted at 35 °C (see Figure 4.19). The singlet of the methylidene complex [Ru]=CH2 (14-a, 17.73 ppm; see Figure 4.19) was predominant after 12 h. The 31P{1H} NMR spectra showed a new singlet (31.3 ppm; see Figure 4.20) starting at 25 °C. This persisted at 35 °C. At 35 °C, other new peaks also began to appear. After 12 h at room temperature, the signals present at 37.7 and 30.6 ppm could be assigned to 14-a and the starting catalyst 14 (see Figure 4.20). In all six preceding experiments, the benzylidene ligand of 13 or 14 was partially replaced by an alkylidene derived from the terminal alkene of the pyridine, giving 1 [Ru]=CHCH2R (13-b and 14-b). The H NMR spectra showed a diagnostic triplet in the alkylidene region, due to coupling of the alkylidene proton to the methylene group of the pyridine. In addition, the partial consumption of the benzylidene species [Ru]=CHPh was 1 3 confirmed by the typical CH= H NMR signal of styrene (dd, 6.76 ppm, JHH = 17.7 Hz, 3 JHH = 10.9 Hz; see Figure 4.21).

Figure 4.21. Partial 1H NMR spectrum of VT experiment 3 (25 °C): styrene signals.

31 1 In the P{ H} NMR spectra, a new singlet very close to the PCy3 signals of 13 and 14 was noteworthy. In all experiments, the chemical shift of the methylidene complex 28,29 [Ru]=CH2 (13-a and 14-a) was in agreement with the data reported in literature. Selected 1H and 31P{1H} NMR data are summarized in Tables 4.2-4.5. No significant 4. Novel ruthenium-based carbene complexes 151 ______

resonances due to free PCy3 (11.7 ppm) were observed.

Table 4.2. Selected 1H NMR data [δ/ppm] at 25 °C for experiments 1, 3, and 5.[a] Alkene-containing [Ru]=CHCH R[b] [c] [Ru]=CH [c] pyridine 2 [Ru]=CHPh 2 19.32 22a [4.8] 20.02 18.95 19.43 25b [4.8] 20.03 18.96[d] 19.25 29g [4.9] 20.02 18.98[d] [a] spectra recorded in CD2Cl2. [b] 3 triplet [ JHH, Hz]. [c] singlet. [d] singlet observed after 12 h at room temperature.

Table 4.3. Selected 31P{1H} NMR data [δ/ppm] at 25 °C for experiments 1, 3, and 5.[a]

Alkene-containing PCy3 PCy3 pyridine in 13[b] in 13-b[b]

22a 37.3 36.9

25b 37.3 36.8

29g 37.3 36.6 [a] spectra recorded in CD2Cl2. [b] singlet.

Table 4.4. Selected 1H NMR data [δ/ppm] at 35 °C for experiments 2, 4, and 6.[a] Alkene-containing [Ru]=CHCH R[b] [c] [Ru]=CH [c] pyridine 2 [Ru]=CHPh 2 18.64 22a [3.8] 19.15 17.74 18.77 25b [4.6] 19.15 17.80 18.56 29g [4.7] 19.11 17.73[d] [a] spectra recorded in CD2Cl2. [b] 3 triplet [ JHH, Hz]. [c] singlet. [d] singlet observed after 12 h at room temperature.

152 4. Novel ruthenium-based carbene complexes ______

Table 4.5. Selected 31P{1H} NMR data [δ/ppm] at 35 °C for experiments 2, 4, and 6.[a]

Alkene-containing PCy3 PCy3 pyridine in 14[b] in 14-b[b]

22a 30.4 30.1

25b 30.5 31.0

29g 30.5 31.3 [a] spectra recorded in CD2Cl2. [b] singlet.

Finally, in all six preceding experiments, particularly noteworthy is the much lower reactivity of Grubbs' second generation catalyst with respect to the first generation catalyst. This result is independent of the alkene-containing pyridine.

4. Novel ruthenium-based carbene complexes 153 ______

4.3.4. VT NMR experiments with alkene-containing rhenium complexes.

VT NMR Experiment 7. The reaction of vinyl complex (R)-43 with 13 in CD2Cl2 was monitored by 1H and 31P{1H} NMR. The sample was warmed from −75 °C to 25 °C, then kept at room temperature and analyzed after 12 h at room temperature. Selected spectra are given in Figures 4.22 and 4.23. The former shows the region for the Ru=CH signals.

PCy3 Cl Ru Cl PCy3 rt (after 12 h) 13

25 °C

19.68 ppm –75 °C

Figure 4.22. Partial 1H NMR spectra of VT experiment 7.

rt (after 12 h)

PCy3 Cl Ru Cl 37.4 ppm 25 °C PCy3

13 5 °C

PCy3 Cl Ru Cl Re Ph3P NO –75 °C PCy3 CH H2C 13 (R)-43

Figure 4.23. Partial 31P{1H} NMR spectra of VT experiment 7. 154 4. Novel ruthenium-based carbene complexes ______

When the sample was warmed from −75 °C to 25 °C, the Ru=CH 1H NMR singlet of 13 shifted from 19.68 ppm to 20.02 ppm (see Figure 4.22). No new peaks appeared in the region of the Ru=CH signals. 31 1 The P{ H} NMR spectra showed the gradual disappearance of the PPh3 signal of (R)-43 (22.4 ppm, –75 °C; see Figure 4.23). A new singlet (28.6 ppm) appeared at –75 °C. Between –75 °C and –5 °C, there was little change in the 31P{1H} NMR spectra. At 5 °C, several new peaks also began to appear. The peak at 37.4 ppm could be assigned to the starting catalyst 13 (see Figure 4.23).

4. Novel ruthenium-based carbene complexes 155 ______

VT NMR Experiment 8. The reaction of vinyl complex (R)-43 with 14 in CD2Cl2 was monitored by 1H and 31P{1H} NMR. The sample was warmed from −75 °C to 35 °C, then cooled to room temperature and analyzed after 12 h. Selected spectra are given in Figures 4.24 and 4.25. The former shows the region for the Ru=CH signals.

N N

Cl Ru Cl

PCy3 14 rt (after 12 h)

35 °C

18.68 ppm –75 °C

Figure 4.24. Partial 1H NMR spectra of VT experiment 8.

rt (after 12 h)

30.5 ppm 28.4 ppm 35 °C

N N

Cl Ru Re Cl Ph3P NO CH PCy3 H2C –75 °C 14 (R)-43

Figure 4.25. Partial 31P{1H} NMR spectra of VT experiment 8.

156 4. Novel ruthenium-based carbene complexes ______

When the sample was warmed from −75 °C to 35 °C, the Ru=CH 1H NMR singlet of 14 shifted from 18.68 ppm to 19.10 ppm (see Figure 4.24). No new peaks appeared in the region of the Ru=CH signals. 31 1 The P{ H} NMR spectra showed the gradual disappearance of the PPh3 signal of (R)-43 (22.4 ppm, –75 °C; see Figure 4.25). A new singlet (29.9 ppm) appeared at –75 °C. Between –75 °C and 25 °C, there was little change in the 31P{1H} NMR spectra. At 35 °C only two major peaks were present (30.5 and 28.4 ppm; see Figure 4.25). The first could be assigned to the starting catalyst 14.

4. Novel ruthenium-based carbene complexes 157 ______

VT NMR Experiment 9. The reaction of the Re(CH2)2CH=CH2 complex (R)-45 1 31 1 with 13 in CD2Cl2 was monitored by H and P{ H} NMR. The sample was warmed from −75 °C to 25 °C, then kept at room temperature and analyzed after 12 h. Selected spectra are given in Figures 4.26 and 4.27. The former shows the region for the Ru=CH signals.

PCy3 Cl Ru PCy3 Cl Cl 18.95 ppm PCy Ru CH 3 Cl 2 PCy3 13 13-a rt (after 12 h)

PCy3 Cl Ru Cl 19.03 ppm CH2R PCy3

13-b 25 °C

19.68 ppm –75 °C

Figure 4.26. Partial 1H NMR spectra of VT experiment 9.

PCy3 PCy3 Cl Cl Ru CH Ru Cl 2 Cl PCy3 PCy3

13-a 13 rt (after 12 h)

36.0 ppm 25.4 ppm 25 °C

36.4 ppm 25.1 ppm –15 °C

PCy3 Cl Ru Re Cl Ph3P NO CH PCy3 2 H2C –75 °C 13 CH H2C (R)-45

Figure 4.27. Partial 31P {1H} NMR spectra of VT experiment 9.

158 4. Novel ruthenium-based carbene complexes ______

When the sample was warmed from −75 °C to 25 °C, the Ru=CH 1H NMR singlet of 13 shifted from 19.68 ppm to 20.03 ppm (see Figure 4.26). A triplet compatible with an alkylidene species [Ru]=CHCH2R was present at −5 °C (13-b, 19.00 ppm). This signal slightly shifted at 25 °C. (19.03 ppm; see Figure 4.26) The singlet of the methylidene complex [Ru]=CH2 (13-a, 18.95 ppm; see Figure 4.26) was present after 12 h. The 31P{1H} NMR spectra showed two new singlets (25.1 and 36.4 ppm; see Figure 4.27) starting at –15 °C. At 25 °C, the singlets slightly shifted (25.4 and 36.0 ppm; see Figure 4.27), and other new peaks also began to appear. After 12 h at room temperature, two signals present at 44.5 and 37.4 ppm could be assigned to 13-a and starting catalyst 13.

4. Novel ruthenium-based carbene complexes 159 ______

VT NMR Experiment 10. The reaction of Re(CH2)2CH=CH2 complex (R)-45 1 31 1 with 14 in CD2Cl2 was monitored by H and P{ H} NMR. The sample was warmed from −75 °C to 35 °C, then cooled to room temperature and analyzed after 12 h. Selected spectra are given in Figures 4.28 and 4.29. The former shows the region for the Ru=CH signals.

N N

Cl Ru Cl

PCy3 rt (after 12 h) 14

N N N N

Cl Cl Ru Ru Cl Cl CH2 CH2R 18.40 ppm 17.76 ppm PCy3 PCy3 35 °C 14-b 14-a

18.64 ppm –75 °C

Figure 4.28. Partial 1H NMR spectra of VT experiment 10.

N N

Cl Ru Cl CH2

PCy3 14-a rt (after 12 h)

32.3 ppm 24.3 ppm 35 °C

N N Re Ph3P NO Cl Ru CH2 Cl H2C PCy3 CH –75 °C H2C 14 (R)-45

Figure 4.29. Partial 31P{1H} NMR spectra of VT experiment 10.

160 4. Novel ruthenium-based carbene complexes ______

When the sample was warmed from −75 °C to 35 °C, the Ru=CH 1H NMR singlet of 14 shifted from 18.64 ppm to 19.05 ppm (see Figure 4.28). A triplet compatible with an alkylidene species [Ru]=CHCH2R (14-b, 18.40 ppm; see Figure 4.28) and the singlet of the methylidene complex [Ru]=CH2 (14-a, 17.76 ppm; see Figure 4.28) were present at 35 °C. The 31P{1H} NMR spectra showed two new singlets (32.3 and 24.3 ppm; see Figure 4.29) starting at 35 °C. After 12 h at room temperature, several new signals were present. The signal at 37.7 ppm could be assigned to 14-a.

4. Novel ruthenium-based carbene complexes 161 ______

VT NMR Experiment 11. The reaction of Re(CH2)3CH=CH2 complex (R)-46 in 1 31 1 CD2Cl2 was monitored by H and P{ H} NMR. The sample was warmed from −75 °C to 25 °C, then kept at room temperature and analyzed after 12 h. Selected spectra are given in Figures 4.30 and 4.31. The former shows the region for the Ru=CH signals.

PCy3 PCy3 Cl Cl Ru Ru CH Cl Cl 2 18.97 ppm PCy3 PCy3

13-a rt (after 12 h) 13

PCy3 Cl Ru 19.29 ppm Cl CH2R PCy3 25 °C 13-b

19.68 ppm –75 °C

Figure 4.30. Partial 1H NMR spectra of VT experiment 11.

PCy3 PCy3 Cl Cl Ru CH Ru Cl 2 Cl PCy3 PCy3 13-a 13 rt (after 12 h)

36.0 ppm 26.9 ppm 25 °C 36.8 ppm 26.6 ppm –5 °C

PCy3 Cl Ru Re Cl Ph3P NO CH PCy3 2 H2C –75 °C 13 CH2 HC

CH2 (R)-46

Figure 4.31. Partial 31P{1H} NMR spectra of VT experiment 11.

When the sample was warmed from −75 °C to –15 °C, the Ru=CH 1H NMR singlet 162 4. Novel ruthenium-based carbene complexes ______of 13 shifted from 19.68 ppm to 20.06 ppm (see Figure 4.30). A triplet compatible with an alkylidene species [Ru]=CHCH2R (13-b, 19.37 ppm) and the singlet of the methylidene species [Ru]=CH2 (13-a, 19.16 ppm) were present at –5 °C. These slightly shifted at 25 °C (13-b, 19.29 ppm and 13-a, 18.97 ppm; see Figure 4.30). The 31P{1H} NMR spectra showed two new singlets (36.8 and 26.6 ppm) starting at –5 °C (see Figure 4.31). At 25 °C, the singlets slightly shifted (36.0 and 26.9 ppm; see Figure 4.31), and other new peaks also began to appear. After 12 h at room temperature, several new signals were present. Two signals (44.5 and 37.3 ppm) could be assigned to 13-a and 13 (see Figure 4.31).

4. Novel ruthenium-based carbene complexes 163 ______

VT NMR Experiment 12. The reaction of Re(CH2)3CH=CH2 complex (R)-46 1 31 1 with 14 in CD2Cl2 was monitored by H and P{ H} NMR. The sample was warmed from −75 °C to 35 °C, then cooled to room temperature and analyzed after 12 h. Selected spectra are given in Figures 4.32 and 4.33. The former shows the region for the Ru=CH signals.

N N

Cl N N Ru Cl Cl Ru CH2 PCy3 Cl

PCy3 17.76 ppm rt (after 12 h) 14 14-a

N N

Cl Ru Cl CH2R 18.42 ppm PCy3 35 °C 14-b

18.68 ppm –75 °C

Figure 4.32. Partial 1H NMR spectra of VT experiment 12.

N N N N

Cl Cl Ru Ru CH Cl Cl 2 PCy PCy3 3 14-a 14 rt (after 12 h)

32.2 ppm 26.0 ppm

35 °C

Re N N Ph3P NO CH2 Cl H2C Ru Cl CH2 HC PCy3 –75 °C CH2 14 (R)-46

Figure 4.33. Partial 31P{1H} NMR spectra of VT experiment 12.

164 4. Novel ruthenium-based carbene complexes ______

When the sample was warmed from −75 °C to 35 °C, the Ru=CH 1H NMR singlet of 14 shifted from 18.68 ppm to 19.03 ppm (see Figure 4.32). An apparent triplet compatible with an alkylidene species [Ru]=CHCH2R (14-b, 18.42 ppm; see Figure 4.32) was present at 35 °C. The singlet of the methylidene species [Ru]=CH2 (14-a, 17.76 ppm; see Figure 4.32) was present after 12 h at room temperature. The 31P NMR showed two new singlets (26.0 and 32.2 ppm; see Figure 4.33) starting at 35 °C. After 12 h at room temperature, several new signals were present. Two (37.7 and 30.6 ppm) could be assigned to 14-a and 14 (see Figure 4.33). In the preceding four experiments (9-12), the benzylidene ligand of 13 or 14 was partially replaced by an alkylidene derived from the rhenium complex, giving

[Ru]=CHCH2R (13-b and 14-b). As in the previous experiments with the alkene- 1 containing pyridines, this is indicated by a triplet for the [Ru]=CHCH2R H NMR signal, due to coupling of the alkylidene proton to the methylene group. Furthermore, the 1 3 3 diagnostic CH= H NMR signal of styrene (dd, 6.73 ppm, JHH = 17.7 Hz, JHH = 10.9 Hz) was also observed (see Figure 4.34).

Figure 4.34. Partial 1H NMR spectrum of VT experiment 9 (25 °C): styrene signals.

31 In the P NMR spectra, the presence of two new singlets close to the PCy3 signal 1 31 1 of 13 and the PPh3 signal of (R)-45 and (R)-46 was noteworthy. Selected H and P{ H} NMR data are summarized in Tables 4.6-4.9.

4. Novel ruthenium-based carbene complexes 165 ______

Table 4.6. Selected 1H NMR data [δ/ppm] at 25 °C for experiments 9 and 11.[a] Alkene-containing [Ru]=CHCH R[b] [c] [Ru]=CH [c] rhenium complex 2 [Ru]=CHPh 2 19.03 (R)-45 [4.6] 20.03 18.95[d] 19.29 (R)-46 [4.7] 20.06 18.97 [a] spectra recorded in CD2Cl2. [b] 3 triplet [ JHH, Hz]. [c] singlet. [d] singlet observed after 12 h at room temperature.

Table 4.7. Selected 31P{1H} NMR data [δ/ppm] at 25 °C for experiments 9 and 11.[a]

Alkene-containing PCy3 PCy3 in PPh3 in rhenium PPh3 in rhenium complex in 13[b] 13-b[b] complex[b] 13-b[b]

(R)-45 37.3 36.0 26.9 25.4

(R)-46 37.6 36.0 27.0 26.9 [a] spectra recorded in CD2Cl2. [b] singlet.

Table 4.8. Selected 1H NMR data [δ/ppm] at 35 °C for experiments 10 and 12.[a] Alkene-containing [Ru]=CHCH R[b] [c] [Ru]=CH [c] rhenium complex 2 [Ru]=CHPh 2 18.40 (R)-45 [4.7] 19.05 17.76 18.42 (R)-46 [4.6] 19.03 17.76[d] [a] spectra recorded in CD2Cl2. [b] 3 triplet [ JHH, Hz]. [c] singlet. [d] singlet observed after 12 h at room temperature.

Table 4.9. Selected 31P{1H} NMR data [δ/ppm] at 35 °C for experiments 10 and 12.[a]

Alkene-containing PCy3 PCy3 in PPh3 in rhenium PPh3 in rhenium complex in 14[b] 14-b[b] complex[b] 14-b[b]

(R)-45 30.5 32.3 26.9 24.3

(R)-46 30.5 32.2 27.0 26.0 [a] spectra recorded in CD2Cl2. [b] singlet. 166 4. Novel ruthenium-based carbene complexes ______

As already pointed out for experiments 1-6, particularly noteworthy is the much lower reactivity of Grubbs' second generation catalyst with respect to the first generation catalyst.

4.3.5. Preparative reactions. The information derived from the preceding NMR experiments was transferred to a preparative scale. Both ruthenium metathesis precursors 13 and 14 were reacted with 22a and 25b following known literature procedures for the synthesis of ruthenium complexes with a chelating nitrogen donor ligand.5,8 Upon workup, there was no evidence of ruthenium-pyridine complexes. A diagnostic 1H NMR Ru=CH triplet (see Tables 4.2 and 4.4), indicative of incorporation of the alkene chain of the pyridine, was never observed in the isolated materials. Preparative experiments with alkene-containing rhenium complexes were conducted with (R)-45 and (R)-46, which unlike (R)-43 showed a clear reactivity towards 13 and 14. However, mass spectrometric analysis carried out on the solution from VT

NMR experiment 7 indicated a peak at m/z = 1008, consistent with the desired cation [(η5- + C5H5)Re(NO)(PPh3)(CH=)Ru(PCy3)(Cl)2] . As outlined in Scheme 4.4, the first series of experiments were carried out with Grubbs' catalyst 13.

PCy PCy3 -78 °C to rt 3 Cl Cl 2 Re + Ru Ru Cl Cl Ph3P NO CH2Cl2 PCy3 Re CH2 PCy3 PPh3 H2C ON CH H2C (R)-45 13 47, 49% (> 90% NMR purity)

PCy PCy3 -78 °C to rt 3 Cl Cl 2 Re + Ru Ru Ph3P NO Cl Cl CH2Cl2 CH2 PCy PCy3 Re 3 PPh3 H2C ON CH2 HC

CH2

(R)-46 13 48, 58% (> 75% NMR purity)

Scheme 4.4. Synthesis of 47 (top) and 48 (bottom). 4. Novel ruthenium-based carbene complexes 167 ______

Complex 13 was treated with 2.0 equiv of (R)-45 in CH2Cl2 at –78 °C, and the mixture was warmed to room temperature. Workup included several washings of the residue with chilled methanol. This methodology enabled the removal mainly of unreacted 13 and provided a product of ≥ 90% purity, as assayed by 31P{1H} NMR. The 1H NMR spectrum showed a triplet for the Ru=CH signal (19.02 ppm) and a singlet for the cyclopentadienyl signal (4.90 ppm) (Figure 4.35).

19.02 ppm

CD2Cl2

4.90 ppm

Figure 4.35. 1H NMR spectrum of 47 (top), and expanded sections (middle, bottom).

Similarly, 13 was combined with 2.0 equiv of (R)-46 in CH2Cl2 at –78 °C. An identical workup proved less effective. The product was isolated in ≥ 75% purity by 31P{1H} NMR. Alternative purifications involving silica gel or neutral alumina column 168 4. Novel ruthenium-based carbene complexes ______chromatography were unsuccessful. Subsequently, as outlined in Scheme 4.5, Grubbs' second generation catalyst 14 was combined with 2.0 equiv of (R)-45 and (R)-46 even though the previous VT NMR experiments indicated a much lower reactivity.

N N N N -78 °C to rt Cl Cl 2 Re + Ru Ru Ph3P NO Cl Cl CH2Cl2 CH2 PCy3 PCy3 Re PPh3 H2C ON CH H2C

(R)-45 14 49

N N N N Cl -78 °C to rt Cl 2 Re + Ru Ru Ph3P NO Cl Cl CH2Cl2 CH2 PCy PCy3 3 Re PPh3 H2C ON CH2 HC

CH2

(R)-46 14 50

Scheme 4.5. Synthesis of 49 (top) and 50 (bottom).

The target complexes 49 and 50 were isolated as crude products after silica gel column chromatography. Characteristic 1H and 31P{1H} NMR signals for 49 and 50 are summarized in Tables 4.10 and 4.11. In both cases, alternative purification methods (washing with chilled methanol and/or recrystallization from benzene layered with hexanes) did not provide better results.

Table 4.10. Selected 1H NMR data [δ/ppm] for 47, 48, 49, and 50.[a] [b] 5 [c] Complex [Ru]=CHCH2R η -C5H5 19.02 4.90 47 [4.6] 19.25 4.92 48 [4.3] 18.41 4.98 49 [4.3] 18.43 4.96 50 [4.7] [a] spectra recorded in CD2Cl2 at room temperature. [b] 3 triplet [ JHH, Hz]. [c] singlet. 4. Novel ruthenium-based carbene complexes 169 ______

Table 4.11. Selected 31P{1H} NMR data [δ/ppm] for 47, 48, 49, and 50.[a] [b] [b] Complex PCy3 PPh3

47 36.0 25.4

48 36.0 26.7

49 32.3 24.3

50 32.2 26.0 [a] spectra recorded in CD2Cl2 at room temperature. [b] singlet.

4.4. Discussion

4.4.1. Alkene-containing rhenium complexes. There are numerous examples of

η1-allyl transition-metal complexes.30 The Gladysz group has reported a family of η1-allyl 5 26 complexes of general formula (η -C5H5)Re(NO)(PPh3)(CH2C(R')=CHR) (Figure 4.36).

Re Re Re ON PPh3 ON PPh3 ON PPh3 CH2 CH2 CH2 H H H3C C C C C C C H H Ph H H H

XX XXI XXII

Figure 4.36. Examples of η1-allyl rhenium complexes.

The allyl complexes were demonstrated to be extremely air sensitive in solution, 5 unlike analogous alkyl complexes analogous such as (R)-(η -C5H5)Re(NO)(PPh3)(CH3). The same behavior was noted for related cyclopentadienyl iron allyl vs. alkyl complexes. In contrast, in solid state, they showed an appreciable stability over several days. As shown in Scheme 4.6, the synthesis of allyl complex XXIII, XXIV, and XXV was accomplished with two alternative routes. In general, the allyl ligand can be introduced either as an allyl ligand (route 1) or as an alkene (route 2). 170 4. Novel ruthenium-based carbene complexes ______

Cl CH R' 2 (1) (2) C Re + Re Re ON PPh3 ON PPh ON C -78 °C to 25 °C 3 t-BuO K PPh3 CH R' Li R H R' 2 C C CH2 H2CR C PF6 R H

XXIII, R = R' = H

XXIV, R = H, R' = CH3 XXV, R = Ph, R' = H

Scheme 4.6. Synthesis of η1-allyl rhenium complexes.

A common and facile operative route was utilized for the syntheses of the homologous butenyl and pentenyl rhenium complexes (R)-45 and (R)-46. The intermediate 5 + – methylidene complex [(η -C5H5)Re(NO)(PPh3)(=CH2)] PF6 (R)-44 was treated with

Grignard reagents CH2=CHCH2MgBr and CH2=CHCH2CH2MgBr to give, respectively, (R)-45 and (R)-46. As reported for the preparation of primary rhenium alkyl complexes 5 30 5 (η -C5H5)Re(NO)(PPh3)(CH2R), a very small amount (< 2%) of (η -

C5H5)Re(NO)(PPh3)(CH3) accompanied the formation of (R)-46. No other alkyl or alkylidene byproducts were found. 5 + – The intermediate methylidene complex [(η -C5H5)Re(NO)(PPh3)(=CH2)] PF6 (R)-44 was reacted with the Grignard reagents for a short time (≤ 30 min). Extension of reaction time, use of a greater excess of Grignard reagent, and lack of reaction quenching drastically reduced yields, sometimes resulting in the bromide complex (η5-

C5H5)Re(NO)(PPh3)(Br) as main product.

4.4.2. Crystal structure. The complex (R)-46 showed P-Re-N, P-Re-C1, and N- Re-C1 bond angles of approximately 90º, as expected for this class of formally octahedral complexes.32 The Re-C1 (2.194(4) Å) bond length was in line with those of cinnamyl 5 26 complex (E)-(η -C5H5)Re(NO)(PPh3)(CH2CH=CHC6H5) (2.192(6) Å), benzyl complex 5 32a 5 (−)-(R)-(η -C5H5)Re(NO)(PPh3)(CH2C6H5) (2.203(8) Å), and (SS,RR)-(η -

C5H5)Re(NO)(PPh3)(CH(CH2C6H5)C6H5) (2.215(4) Å). The C1-C2, C2-C3, and C3-C4 bond lengths can be compared to those found in the cinnamyl complex (1.500(6) vs. 1.486(11) Å; 1.536(7) vs. 1.304(13) Å; 1.524(9) vs. 1.476(13) Å).26 As already described, 4. Novel ruthenium-based carbene complexes 171 ______three different types of "staggered" Re-C1 rotamers are possible in alkyl complexes (η5-

C5H5)Re(NO)(PPh3)(CH2R), as shown in Figure 4.37. From steric considerations, the rotamer A should be the most stable as the C1 substituent residue is between the small nitrosyl and the medium sized cyclopentadienyl ligands. Benzyl complex (R)-(η5- 26 C5H5)Re(NO)(PPh3)(CH2C6H5) adopted a Re-C1 conformation of type A.

R HaS HaR R HaR HaS

ON PPh3 ON PPh3 ON PPh3 HaR HaS R

A B C

Figure 4.37. Types of "staggered" Re-C1 rotamers in allyl 5 or alkyl complexes (η -C5H5)Re(NO)(PPh3)(CH2R).

Interestingly, the P-Re-C1-C2 torsion angle in (R)-46 (147º) is very close to that of the major of the conformations (A') in the cinnamyl complex (143º), and it is comparable with the value of the benzyl complex (157°) (Figure 4.38).

HaS R

ON PPh3 ON PPh3 HaR HaS

A' A"

Figure 4.38. Possible C1-C2 conformations in η1-allyl rhenium complexes.

4.4.3. Heterobimetallic ruthenium-rhenium carbyne complexes. The number of ruthenium-carbyne complexes known in the literature is particularly restricted33 although alkene and alkyne metathesis have a clear mechanistic analogy.34 The ruthenium- carbyne complexes that resemble most closely the Grubbs-type catalysts are shown in Figure 4.39. BAr PCy f Cl 3 Ru CH2R Cl PCy3

R = Ph; XXVI

R = t-Bu; XXVII

Figure 4.39. Werner's ruthenium-carbyne complexes. 172 4. Novel ruthenium-based carbene complexes ______

They were isolated by Werner and co-workers by protonation of the corresponding vinylidene complexes.20e However, Werner-type ruthenium-carbyne complexes did not catalyze alkyne metathesis because they were readily deprotonated to give reactive fourteen valence-electron vinylidene complexes.20e As illustrated in Scheme 4.7, an alternative and effective synthetic route to ruthenium-carbyne complexes was discovered by Johnson and co-workers.17a The method was characterized by direct reaction of Grubbs' first generation catalyst with

Ge[CH(Si(CH3)3)2]2.

GeHClR GeR2 2

PCy3 PCy3 Cl Ru Cl Ru Cl PCy3 PCy3

13 XV

GeR2 : [Ge(CH[SiMe3]2)2]

Scheme 4.7. Direct synthesis of square-planar monochloride ruthenium-carbyne complex.

To the best of my knowledge, examples of heterobimetallic carbyne complexes are not yet reported in literature. My initial efforts were directed at analyzing the reactivity of 13 in the presence of vinyl rhenium complex 43. My principal objective was to isolate the heterobimetallic carbene complex XXIX (Scheme 4.8). It was hoped to subsequently isolate the rhenium-substituted ruthenium carbene complex XXVIII; then the synthesis of the ruthenium-rhenium carbyne XXIX would be attempted by the method of Johnson.

GeR2 GeHClR2

PCy3 PCy 3 PCy Cl CH2Cl2 Cl 3 Re + Ru Ru ON PPh3 Cl Cl Cl Ru Re Re PPh PPh3 CH 3 PCy3 PCy3 PCy3 NO H2C NO

43 13 XXVIII XXIX

GeR2 : [Ge(CH[SiMe3]2)2]

Scheme 4.8. Original objective: synthesis of XXIX.

4.4.4. Future directions. The NMR and the subsequent preparative scale experiments described above have furnished interesting insights about the reactivity of 4. Novel ruthenium-based carbene complexes 173 ______alkene-containing pyridines and rhenium complexes towards Grubbs-type catalysts. The results achieved lay the foundations for further investigations with additional alkenyl complexes for example involving other metals. There are a number of readily available platinum and rhodium systems that could be easily assayed. The resulting

Ru=CHMLn systems might then be elaborated into RuCM "carbide" species.

4.5. Conclusions

This study has used VT NMR to map the reactivity features that control stoichiometric reactions of Grubbs-type catalysts with alkene-containing pyridines and rhenium complexes. As shown by NMR scale investigation, the reactions were more effective in the presence of Grubbs' first generation catalyst. Preparative scale experiments were shown to be feasible in certain cases, but much optimization work remains. 174 4. Novel ruthenium-based carbene complexes ______

4.6. Experimental section

General data. Reactions were carried out under dry nitrogen atmospheres using conventional Schlenk techniques. Workups were carried out in air. Chemicals were treated as follows: CH2Cl2, distilled from CaH2 or simple distillation for chromatography; methanol, distilled from CaH2; hexanes, distilled from sodium or simple distillation for chromatography; benzene, distilled from Na/benzophenone; CD2Cl2 (Deutero GmbH), distilled from CaH2 and stored over molecular sieves; diethyl ether, simple distillation; + – 35 Ph3C PF6 (≥ 95%, Aldrich or Acros) stored under argon at −32 °C;

CH2=CHCH2MgBr (1.0 M in diethyl ether, Fluka), CH2=CHCH2CH2MgBr (0.5 M in THF, Aldrich), alumina (neutral, Macherey-Nagel), silica gel (60 M, Macherey-Nagel),

MgSO4 (Riedel-de Haën), and Ru(=CHPh)(PCy3)2(Cl)2 (13, Aldrich) used as received. 5 24 The complexes (R)-(η -C5H5)Re(NO)(PPh3)(CH3) ((R)-40) and 36 Ru(=CHPh)(H2IMes)(PCy3)(Cl)2 (14) were prepared according to literature procedures. NMR spectra were recorded on standard 300 or 400 MHz FT spectrometers. Variable temperature NMR spectra were recorded on Bruker 400 MHz FT spectrometer. IR spectra and mass spectra were recorded on an ASI React-IR® 1000 and Micromass Zabspec instruments, respectively. Optical rotations were measured as described previously37 using a Perkin Elmer model 341 polarimeter. DSC and TGA data were recorded with a Mettler-Toledo DSC-821 instrument and treated by standard methods.38

Microanalyses were conducted on a Carlo Erba EA1110 CHN instrument.

5 (R)-(η -C5H5)Re(NO)(PPh3)(CH2CH2CH=CH2) ((R)-45). A round bottom flask 24 was charged with (R)-40 (0.200 g, 0.358 mmol) and CH2Cl2 (22 mL). The orange + – solution was cooled to –78 °C with stirring. Then Ph3C PF6 (0.167 g, 0.430 mmol) was added in one portion. After 30 min, CH2=CHCH2MgBr (1.0 M in diethyl ether, 0.43 mL, 0.430 mmol) was added dropwise over 5 min, and the solution was stirred for 30 min. 4. Novel ruthenium-based carbene complexes 175 ______

Degassed water (0.5 mL) was added over 2 min. The cooling bath was removed. The solvent was removed by oil pump vacuum. The residue was extracted with benzene (20 mL). The solution was dried (MgSO4), concentrated by oil pump vacuum (to ca. 5 mL), and filtered through a plug of alumina (4 × 1.5 cm, rinsed with benzene). An orange band was collected. The solvent was removed from the orange band by oil pump vacuum. The sample was taken up in CH2Cl2 (2 mL), layered with hexanes (30 mL), and stored at −20 °C. After 18 h, the small orange square blocks were collected by filtration, washed with hexanes and dried by oil pump vacuum to give (R)-45 (0.107 g, 0.179 mmol, 50%), mp (capillary) 202-204 °C. TGA: onset of mass loss, 188.6 °C. Anal. Calcd. for 589 C27H27NOPRe: C, 54.17; H, 4.55; N, 2.34. Found: C, 54.15; H, 4.47; N, 2.38. [α]22 = –1 −121.4° ± 4° (c = 1.08 mg mL , CH2Cl2). Alternatively, (R)-45 could be purified by column chromatography on silica gel (15

× 1 cm column, 6:4 v/v CH2Cl2/hexanes).

1 3 NMR (δ, CD2Cl2): H 7.44-7.32 (m, 15H, Ph), 5.79 (ddt, 2H, JHHtrans = 17.0 Hz, 3 3 3 JHHcis = 10.1 Hz, JHH = 6.8 Hz, CH=), 4.95 (s, 5H, C5H5), 4.82 (dd, 1H, JHH = 17.1 2 3 2 Hz, JHH = 2.6 Hz, =CHEHZ), 4.72 (dd, 1H, JHH = 10.3 Hz, JHH = 2.4 Hz, =CHEHZ),

2.53-2.28 (m, 2H, CH2CH=CH2), 2.13-1.98 (m, 1H, ReCHH) 1.81-1.66 (m, 1H, ReCHH); 13 1 1 2 C{ H} 145.7 (s, CH=), 136.9 (d, JCP = 51.6 Hz, i-Ph), 134.0 (d, JCP = 10.6 Hz, o-Ph), 3 130.3 (s, p-Ph), 128.6 (d, JCP = 10.6 Hz, m-Ph), 110.8 (s, =CH2), 89.9 (s, C5H5), 46.3 (s, 1 31 1 ReCH2CH2), −10.5 (d, JReC = 5.4 Hz, ReCH2); P{ H} 26.9 (s). 39 + + MS: 599 (45 , 100%), 558 ([45 − CH2CH=CH2] , 40%), 544 ([45 − + CH2CH2CH=CH2] , 50%). –1 IR (cm , powder film): 3057 (w), 2903 (w), 2814 (w), 1610 (s, νNO), 1482 (w), 1436 (w), 1092 (w), 919 (w), 807 (w), 749 (w), 695 (m).

5 (R)-(η -C5H5)Re(NO)(PPh3)(CH2CH2CH2CH=CH2) ((R)-46). A round bottom 176 4. Novel ruthenium-based carbene complexes ______

24 flask was charged with (R)-40 (0.200 g, 0.358 mmol) and CH2Cl2 (22 mL). The orange + – solution was cooled to –78 °C with stirring. Then Ph3C PF6 (0.167 g, 0.430 mmol) was added in one portion. After 30 min, CH2=CHCH2CH2MgBr (0.5 M in THF, 0.860 mL, 0.430 mmol) was added dropwise over 5 min, and the solution was stirred for 30 min. Degassed water (0.5 mL) was added over 2 min. The cooling bath was removed. The solvent was removed by oil pump vacuum and the residue extracted with benzene (20 mL).

The solution was dried (MgSO4), concentrated by oil pump vacuum (to ca. 5 mL) and filtered through a plug of alumina (4 × 1.5 cm, rinsed with benzene). The solvent was removed from the orange band by rotary evaporation. The oily residue was chromatographed on silica gel (15 × 1 cm column, 6:4 v/v CH2Cl2/hexanes). Solvents were removed from the orange band by rotary evaporation and oil pump vacuum. The residue was dissolved in diethyl ether (ca. 3 mL), and hexanes (ca. 10 mL) was added. The solvents were removed by oil pump vacuum to give (R)-46 as an orange solid (0.088 g,

0.143 mmol, 45%), mp (capillary) 140-142 °C. DSC (Ti/Te/Tp/Tc/Tf): 112.1/143.1/147.6/149.6/173.3 °C (endotherm). TGA: onset of mass loss, 188.7 °C. Anal.

Calcd. for C28H29NOPRe: C, 54.89; H, 4.77; N, 2.29. Found: C, 54.98; H, 5.07; N, 2.18. 589 –1 [α]22 = −117.8° ± 3° (c = 1.02 mg mL , CH2Cl2).

1 3 NMR (δ, CD2Cl2): H 7.42-7.34 (m, 15H, Ph), 5.78 (ddt, 1H, JHH = 17.1 Hz, 3 3 3 JHH = 10.3 Hz, JHH = 6.7 Hz, CH=), 4.95 (s, 5H, C5H5), 4.90 (dd, 1H, JHH = 17.0 Hz, 2 3 2 JHH = 2.6 Hz, =CHEHZ), 4.82 (dd, 1H, JHH = 10.2 Hz, JHH = 2.4 Hz, =CHEHZ), 2.06- 13 1 1 1.66 (m, 6H, 3CH2); C{ H} 140.7 (s, CH=), 137.0 (d, JCP = 51.9 Hz, i-Ph), 134.0 (d, 2 3 JCP = 9.8 Hz, o-Ph), 130.3 (s, p-Ph), 128.6 (d, JCP = 9.7 Hz, m-Ph), 113.3 (s, =CH2), 5 1 89.9 (s, η -(C5H5)), 41.6, 40.2 (2 s, ReCH2CH2CH2), −9.5 (d, JReC = 5.3 Hz, ReCH2); 31P{1H} 27.0 (s). 39 + + MS: 613 (46 , 100%), 572 ([46 − CH2CH=CH2] 10%), 544 ([46 − + CH2CH2CH2CH=CH2] , 80%). 4. Novel ruthenium-based carbene complexes 177 ______

–1 IR (cm , powder film): 3057 (w), 2914 (w), 2810 (w), 1617 (s, νNO), 1432 (m), 1089 (m), 996 (m), 899 (m), 811 (m), 745 (s), 699 (s).

VT-NMR Experiment 1. A screw-capped NMR tube was charged with Grubbs- type catalyst 13 (0.0256 g, 0.0311 mmol) and CD2Cl2 (0.2 mL). The tube was cooled to

–78 °C (dry ice-acetone bath). A solution of 22a (0.0068 g, 0.0311 mmol) in CD2Cl2 (0.3 mL) was cooled to –78 °C, and added via syringe. The tube was briefly shaken and transferred to a –75 °C NMR probe. 1H and 31P{1H} NMR spectra were immediately recorded. The reaction was monitored at 10 °C intervals as the probe was warmed from –75 °C to 25 °C. Before data acquisition, the sample was equilibrated for 5 min at each temperature. Subsequently, the sample was removed from the NMR probe, kept at room temperature for 12 h, and final 1H and 31P{1H} NMR analyses were performed.

VT-NMR Experiment 2. Solutions of 14 (0.0251 g, 0.0296 mmol) in CD2Cl2 (0.2 mL), and 22a (0.0065 g, 0.029 mmol) in CD2Cl2 (0.3 mL), were combined in a procedure analogous to that for experiment 1. The reaction was monitored at 10 °C intervals as the probe was warmed from –75 °C to 35 °C.

VT-NMR Experiment 3. Solutions of 13 (0.0246 g, 0.0299 mmol) in CD2Cl2 (0.2 mL), and 25b (0.0066 g, 0.030 mmol) in CD2Cl2 (0.3 mL), were combined in a procedure analogous to that for experiment 1. The reaction was monitored as reported in experiment 1.

VT-NMR Experiment 4. Solutions of 14 (0.0252 g, 0.0297 mmol) in CD2Cl2 (0.2 mL), and 25b (0.0065 g, 0.0297 mmol) in CD2Cl2 (0.3 mL), were combined in a procedure analogous to that for experiment 1. The reaction was monitored as reported in experiment 2. 178 4. Novel ruthenium-based carbene complexes ______

VT-NMR Experiment 5. Solutions of 13 (0.0248 g, 0.0301 mmol) in CD2Cl2 (0.2 mL), and 29g (0.0134 g, 0.0301 mmol) in CD2Cl2 (0.3 mL), were combined in a procedure analogous to that for experiment 1. The reaction was monitored as reported in experiment 1.

VT-NMR Experiment 6. Solutions of 14 (0.0204 g, 0.0240 mmol) in CD2Cl2 (0.2 mL), and 29g (0.0107 g, 0.0240 mmol) in CD2Cl2 (0.3 mL), were combined in a procedure analogous to that for experiment 1. The reaction was monitored as reported in experiment 2.

VT-NMR Experiment 7. Solutions of 13 (0.0179 g, 0.0217 mmol) in CD2Cl2 (0.2 mL), and 43 (0.0124 g, 0.0217 mmol) in CD2Cl2 (0.3 mL), were combined in a procedure analogous to that for experiment 1. The reaction was monitored as reported in experiment 1.

VT-NMR Experiment 8. Solutions of 14 (0.0195 g, 0.0230 mmol) in CD2Cl2 (0.2 mL), and 43 (0.0131 g, 0.0230 mmol) in CD2Cl2 (0.3 mL), were combined in a procedure analogous to that for experiment 1. The reaction was monitored as reported in experiment 2.

VT-NMR Experiment 9. Solutions of 13 (0.019 g, 0.023 mmol) in CD2Cl2 (0.2 mL), and (R)-45 (0.0138 g, 0.0231 mmol) in CD2Cl2 (0.3 mL), were combined in a procedure analogous to that for experiment 1. The reaction was monitored as reported in experiment 1.

VT-NMR Experiment 10. Solutions of 14 (0.0189 g, 0.0222 mmol) in CD2Cl2

(0.2 mL), and (R)-45 (0.0132 g, 0.0222 mmol) in CD2Cl2 (0.3 mL), were combined in a 4. Novel ruthenium-based carbene complexes 179 ______procedure analogous to that for experiment 1. The reaction was monitored as reported in experiment 2.

VT-NMR Experiment 11. Solutions of 13 (0.0180 g, 0.0219 mmol) in CD2Cl2

(0.2 mL), and (R)-46 (0.0134 g, 0.0219 mmol) in CD2Cl2 (0.3 mL), were combined in a procedure analogous to that for experiment 1. The reaction was monitored as reported in experiment 1.

VT-NMR Experiment 12. Solutions of 14 (0.0197 g, 0.0232 mmol) in CD2Cl2

(0.2 mL), and (R)-46 (0.0141 g, 0.0232 mmol) in CD2Cl2 (0.3 mL), were combined in a procedure analogous to that for experiment 1. The reaction was monitored as reported in experiment 2.

5 (η -C5H5)Re(NO)(PPh3)(CH2)2(CH=)Ru(PCy3)2(Cl)2 (47). A Schlenk flask was charged with (R)-45 (0.080 g, 0.136 mmol) and CH2Cl2 (1.7 mL) with stirring. The solution was cooled to −78 °C. Grubbs-type catalyst 13 (0.056 g, 0.068 mmol) in CH2Cl2 (1.7 mL) was added dropwise over 1 min. The cooling bath was removed. After 1 h, the volume of the solvent was reduced under oil pump vacuum (to ca. 1 mL). Chilled methanol was added (5 mL). The resulting precipitate was collected by filtration and washed with several portions of chilled methanol (10 × 2 mL) to give a brownish-pink solid (0.043, 0.033 mmol, 49%).

1 3 NMR (δ, CD2Cl2): H 19.02 (t, 1H, JHH = 4.6 Hz, Ru=CH), 7.52-7.30 (m, 15H,

Haryl), 4.90 (s, 5H, C5H5), 2.56-2.42, 1.92-1.62, 1.58-1.42, 1.32-1.14 (4 m, 70H, 2CH2 and 31 1 2PCy3); P{ H} 50.6 (s, 3%), 37.4 (s, 4%), 36.0 (s, PCy3, 60%), 28.6 (s, 3%), 25.4 (s,

PPh3, 30%). 39 + 5 + MS: 1037 ([47 − PCy3] , 5%), 544 ([(η -C5H5)Re(NO)(PPh3)]) , 40%), 281 180 4. Novel ruthenium-based carbene complexes ______

+ ([PCy3 + H] , 100%). 4. Novel ruthenium-based carbene complexes 181 ______

4.7. References and notes

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5102. (22) Bodner, G. S.; Smith, D. E.; Hatton, W. G.; Heah, P. C.; Georgiou, S.; Rheingold, A. J.; Geib, S. J.; Hutchinson, J. P.; Gladysz, J. A. J. Am. Chem. Soc. 1987, 109, 7688. (23) (a) Kromm, K.; Zwick, B. D.; Meyer, O.; Hampel, F.; Gladysz, J. A. Chem. Eur. J. 2001, 7, 2015. (b) Kromm, K.; Hampel, F.; Gladysz, J. A. Organometallics 2002, 21, 4264. (c) Kromm, K.; Osburn, P. L. ; Gladysz, J. A. Organometallics 2002, 21, 4275. 4. Novel ruthenium-based carbene complexes 183 ______

(d) Kowalczyk, J. J.; Arif, A. M.; Gladysz, J. A. Chem. Ber. 1991, 124, 729. (24) Agbossou, F.; O'Connor, J. E.; Garner, C. M.; Quirós Méndez, N.; Fernandez, J. M.; Patton, A. T.; Ramsden, J. A.; Gladysz, J. A. Inorg. Synth. 1992, 29, 211. (25) Crocco, G. L.; Gladysz, J. A. J. Am. Chem. Soc. 1988, 110, 6110. (26) Bodner, G. S.; Emerson, K.; Larsen, R. D.; Gladysz, J. A. Organometallics 1989, 8, 2399. (27) Flack, H. D. Acta Crystallogr. 1983, A39, 876. (28) Schwab, P.; Ziller, J. W.; Grubbs, R. H. J. Am. Chem. Soc. 1996, 118, 100. (29) Sanford, M. S.; Love, J. A.; Grubbs, R. H. J. Am. Chem. Soc. 2001, 123, 6543. (30) For some examples see: (a) Aris, K. R.; Brown, J. M.; Taylor, K. A. J. Chem. Soc., Dalton Trans. 1974, 2222. (b) Bailey, N. A.; Kita, W. G.; McCleverty, J. A.; Murray, A. J.; Mann, B. E.; Walker, N. W. J. Chem. Soc., Chem. Commun. 1974, 592. (c) Cutler, A.; Ehntholt, D.; Giercing, W. P.; Lennon, P.; Raghu, S.; Rosan, A.; Rosenblum, M.; Tancrede, J.; Wells, D. J. Am. Chem. Soc. 1976, 98, 3495. (d) Lehmkuhl, H.; Bellenbaum, M.; Grundke, J.; Mauermann, H.; Krueger, C. Chem. Ber. 1988, 121, 1719. (31) Kiel, W. A.; Lin G.-Y.; Bodner, G. S.; Gladysz, J. A. J. Am. Chem. Soc. 1983, 105, 4958. (32) (a) Merrifield, J. H.; Strouse, C. E.; Gladysz, J. A. Organometallics 1982, 1, 1204. (b) Kiel, W. A.; Lin, G.-Y.; Constable, A. G.; McCormick, F. B.; Strouse, C. E.; Eisenstein, O.; Gladysz, J. A. J. Am. Chem. Soc. 1982, 104, 4865. (33) Fomine, S.; Vargas, S. M.; Tlenkopatchev, M. A. Organometallics 2003, 22, 93. (34) Coalter, J. N.; Bollinger, J. C.; Eisenstein, O.; Caulton, K. G. New J. Chem. 2000, 24, 925. + – (35) The quality of commercial Ph3C PF6 can vary, and crystallization from

CH2Cl2/benzene or CH2Cl2/hexanes is recommended: Patton, A. T.; Strouse, C. E.; Knobler, C. B.; Gladysz, J. A. J. Am. Chem. Soc. 1983, 105, 5804. (36) (a) Trnka, T. M.; Morgan, J. P.; Sanford, M. S.; Wilhelm, W. E.; Scholl, M.; 184 4. Novel ruthenium-based carbene complexes ______

Choi, T.; Ding, S.; Day, M. W.; Grubbs, R. H. J. Am. Chem. Soc. 2003, 125, 2546. (b) Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999, 1, 953. (37) Dewey, M. A.; Gladysz, J. A. Organometallics 1993, 12, 2390. (38) Cammenga, H. K.; Epple, M. Angew. Chem. 1995, 107, 1284; Angew. Chem., Int. Ed. Engl. 1995, 34, 1171. (39) FAB, 3-NBA, m/z (relative intensity, %); the peaks correspond to the most intense peak of the isotope envelope. 5

Crystallography

5.1. Data collection and structure refinement

A. A concentrated CH2Cl2 solution of trans-31a was layered with hexanes. After 7 d, the yellow blocks were taken directly to a Nonius KappaCCD area detector for data collection as outlined in Table 5.1. Cell parameters were obtained from 10 frames using a 10° scan and refined with 1788 reflections. Lorentz, polarization, and absorption corrections1 were applied. The space group was determined from systematic absences and subsequent least-squares refinement. The structure was solved by direct methods. The parameters were refined with all data by full-matrix-least-squares on F2 using SHELXL- 97.2 Non-hydrogen atoms were refined with anisotropic thermal parameters. The hydrogen atoms were fixed in idealized positions using a riding model. The complex exhibited a two-fold symmetry axis containing the N-Pt-N vector and an orthogonal mirror plane containing the Cl-Pt-Cl vector. The data indicated some disorder at C3, but this could not be resolved. Scattering factors were taken from literature.3

B. A concentrated CHCl3 solution of the trans-35a was layered with hexanes. After 3 d, the pale yellow blocks were analyzed as described with trans-31a (cell parameters were obtained from 10 frames using a 10° scan; refined with 2487 reflections). The structure was solved and refined as with trans-31a and outlined in Table 5.1. The structure exhibited an inversion center at platinum.

C. A concentrated CHCl3 solution of trans-35b was layered with hexanes. The sample was kept at −4 °C. After 3 d, the yellow needles were analyzed as described with 186 5. Crystallography ______trans-31a (cell parameters were obtained from 10 frames using a 10° scan; refined with 2898 reflections). The structure was solved and refined as with trans-31a and outlined in Table 5.1. Three atoms were disordered, which were refined to a 81:19 occupancy ratio (C7/C8/O9 and C7'/C8'/O9').

D. A concentrated CHCl3 solution of trans-36e was layered with hexanes. The sample was kept at −20 °C. After 7 d, the light yellow blocks were analyzed as described with trans-31a (cell parameters were obtained from 10 frames using a 10° scan; refined with 10662 reflections). The structure was solved and refined as with trans-31a and outlined in Table 5.2. Several sets of atoms were disordered, which were refined to 66:34 (C44/C44'), 65:35 (C53/C53'), and 73:27 (C65/C65') occupancy ratios. Large atomic displacement factors for C46-C52 indicated additional disorder, which could not be resolved. The asymmetric unit contained two molecules of CHCl3.

E. A concentrated CHCl3 solution of trans-38 was layered with hexanes. After 7 d, the yellow blocks were analyzed as described with trans-31a (cell parameters were obtained from 10 frames using a 10° scan; refined with 2337 reflections). The structure was solved and refined as with trans-31a and outlined in Table 5.2. The structure exhibited an inversion center at palladium.

F. A concentrated CH2Cl2 solution of (R)-46 was layered with hexanes. After 7 d, the red blocks were analyzed as described with trans-31a (cell parameters were obtained from 10 frames using a 10° scan; refined with 3215 reflections). The structure was solved and refined as with trans-31a and outlined in Table 5.2. One atom was disordered, which was refined to a 57:43 occupancy ratio (C4/C4'). The absolute configuration was confirmed by Flack's parameter (Table 1: theory for correct and inverted structures, 0 and

1).4 5. Crystallography 187 ______

5.2. Data deposition

Crystallographic data for trans-31a, trans-35a, trans-35b, trans-36e⋅2CHCl3, trans-38, and (R)-46 were deposited at the Cambridge Crystallographic Data Centre as supplementary publications. These data can be obtained free of charge via www.ccdc.cam.ac.uk/conts/retrieving/html (or from the Cambridge Crystallographic data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; Fax: (+44) 1223-336-033; or E-mail: [email protected]). 188 5. Crystallography ______

5.3. Crystallographic tables

Table 5.1. Summary of crystallographic data for trans-31a, trans-35a, and trans-35b.[a]

trans-31a. trans-35a. trans-35b.

empirical formula C26H34Cl2N2O4Pt C22H30Cl2N2O4Pt C26H38Cl2N2O4Pt formula weight 704.54 652.47 708.57 crystal system orthorhombic monoclinic triclinic

space group Cmca P21/c P-1 unit cell dimensions: a [Å] 21.4040(3) 7.9107(3) 8.4076(2) b [Å] 8.8892(2) 18.5383(6) 9.4946(2) c [Å] 14.5045(3) 8.6614(3) 9.5479(2) α [°] 90 90 104.722(1) β [°] 90 115.322(2) 98.402(1) γ [°] 90 90 113.070(1) V [Å3] 2759.69(9) 1148.16(7) 651.84(2) Z 4 2 1 ρ calcd [Mgm−3] 1.696 1.887 1.805 µ [mm−1] 5.312 6.375 5.622 F(000) 1392 640 352 crystal size [mm3] 0.30×0.30×0.20 0.10×0.10×0.10 0.25×0.10×0.10 Θ range 2.81 to 27.45 2.82 to 27.49 2.29 to 27.48 index ranges (h,k,l) −27,27; −11,11; −18,18 −10,10; −21,24; −11,11 −10,10; −12,12; −12,12 reflections collected 2994 4714 5680 independent reflections 1619 2638 2293 R(int) 0.0093 0.0217 0.0167 reflections [I>2σ(I)] 1356 1958 2993 completeness to Θ 99.9% (27.5) 99.8% (27.5) 99.9% (27.5) data/restraints/parameters 1619/0/85 2638/0/142 2993/4/170 goodness-of-fit on F2 1.080 1.055 1.048 R indices (final) [I>2σ(I)]

R1 0.0266 0.0226 0.0213

wR2 0.0712 0.0496 0.0539 R indices (all data)

R1 0.0313 0.0375 0.0213

wR2 0.0748 0.0543 0.0539 largest diff. peak/hole [eÅ−3] 1.095/−0.805 1.074/−1.138 0.964/−2.243 [a] data common to all structures: T = 173(2) K; λ = 0.71073 Å.

5. Crystallography 189 ______

[a] Table 5.2. Summary of crystallographic data for trans-36e⋅2CHCl3, trans-38, and (R)-46.

trans-36e·2CHCl3 trans-38. (R)-46.

empirical formula C40H56Cl8N2O8Pt C22H30Cl2N2Pd C28H29NOPRe formula weight 1171.56 499.78 612.69 crystal system triclinic monoclinic orthorhombic

space group P-1 P21/n P212121 unit cell dimensions: a [Å] 13.295(3) 8.3927(2) 8.8385(1) b [Å] 13.880(3) 11.1631(3) 14.0954(1) c [Å] 15.392(3) 10.8626(2) 19.9990(1) α [°] 82.38(3) 90 90 β [°] 67.13(3) 91.922(2) 90 γ [°] 67.03(3) 90 90 V [Å3] 2409.1(8) 1017.13(4) 2491.52(4) Z 2 2 4 ρ calcd [Mgm−3] 1.615 1.632 1.633 µ [mm−1] 3.405 1.185 4.961 F(000) 1176 512 1208 crystal size [mm3] 0.10×0.08×0.05 0.20×0.20×0.15 0.20×0.20×0.15 Θ range 2.12 to 27.53 2.62 to 27.47 2.04 to 27.49 index ranges (h,k,l) −17,17; −18,18; −19,19 −10,10; −14,13; −14,14 −11,11; −18,18; −25,25 reflections collected 20951 4294 5695 independent reflections 11406 2324 5695 R(int) 0.0438 0.0105 0.0000 reflections [I>2σ(I)] 7895 2085 5435 completeness to Θ 99.5% (27.5) 99.8% (27.5) 99.9% (27.5) data / restraints / parameters 11046/33/544 2324/0/124 5695/2/293 goodness-of-fit on F2 0.974 1.070 1.029 R indices (final) [I>2σ(I)]

R1 0.0433 0.0217 0.0248 wR2 0.0939 0.0616 0.0573 R indices (all data)

R1 0.0749 0.0246 0.0272 wR2 0.1048 0.0639 0.0585 absolute structure (Flack) parameter − − 0.009(8) largest diff. peak/hole [eÅ−3] 1.228/−1.009 0.429/−0.849 0.861/−1.319 [a] data common to all structures: T = 173(2) K; λ = 0.71073 Å.

190 5. Crystallography ______

5.4. References and notes

(1) (a) "Collect" data collection software, Nonius B.V., 1998. (b) "Scalepack" data processing software: Otwinowski, Z.; Minor, W. in Methods in Enzymology 1997, 276 (Macromolecular Crystallography, Part A), 307. (2) Sheldrick, G. M.; SHELX-97, Program for refinement of crystal structures, University of Göttingen, 1997. (3) Cromer, D. T.; Waber, J. T. In International Tables for X-ray Crystallography, Ibers, J. A., Hamilton, W. C., Eds.; Kynoch: Birmingham, England, 1974. (4) Flack, H. D. Acta Cryst. 1983, A39, 876. Giovanni Pietro Rachiero Current working address: Henkestrasse, 42 – 91054 Erlangen (Germany) Phone: +49-(0)9131-85-26585 Fax: +49-(0)9131-85-26865 Cell: +49-0160-95331004 [email protected]

Personal data:

Place of birth: Toronto (Canada) Date of birth: 14 May 1969

Education:

FAU Erlangen-Nürnberg, Erlangen (Germany) • Ph.D., Organic Chemistry October 2008 Thesis Title: Alkene metathesis: applications in the synthesis of novel organometallic complexes, and mechanistic investigation. Advisor: Professor John A. Gladysz • Graduate student May 2003 – August 2008

University of Naples-Federico II, Naples (Italy) • Laurea in Industrial Chemistry (Master Degree) July 2002 Thesis Title: Biodegradable polymers for biomedical use containing polyether and polyester sequences. Advisor: Professor Rosario Palumbo • Internship November 2000 – July 2002 • Undergraduate student in Industrial Chemistry October 1994 – July 2002 (Specialization in Research and Development of Products)

Professional Experience:

FAU Erlangen-Nürnberg, Erlangen, (Germany) May 2003 – October 2008 • Teaching Assistant in General Chemistry (Medicine students) • Teaching Assistant in Organic and Organometallic chemistry (Chemistry, and Molecular Science students) • Research Supervision of an Erasmus project February 2008 – July 2008 (collaboration with University of Valencia – Spain) Subject: Alkene metathesis • Research stay in: 1- ETH (Zurich - Switzerland) March 2007 (Prof. P. Chen's group) 2- TAMU -Laboratory of Biological Mass Spectrometry September 2006 (College Station – Texas (USA) (Dr. D. Russell's group) 3- Max Planck Institute für Kohlenforschung (Mülheim an der Ruhr – Germany) August 2005 (Dr. W. Schrader's group)

University of Naples-Federico II, Naples (Italy) October 2002 – April 2003 • Research fellow Research project on the synthesis of polymers for biomedical uses. Advisors: Professors Rosario Palumbo and Giovanni Maglio

Research Skills and Qualifications:

• Bench-top and glove box inert atmosphere techniques. • NMR and IR Spectroscopy, Analytical Chromatography (GC, HPLC, and GPC), Mass Spectrometry (FAB, ESI, and MALDI), Thermal (DSC, TGA, and DMTA) and X-ray analysis. • Languages: Italian, English, and German.

Research Interests: • Organic chemistry, coordination chemistry of transition metals, homogeneous and heterogeneous catalysis, polymer and nanochemistry.

Publications:

• Maglio, G.; Palumbo, R.; Rachiero, G. P.; Vignola, M. C. Macromolecular Bioscience 2002, 2, 293. • Crisci L.; Della Volpe, C.; Maglio, G.; Nese, G.; Palumbo, R.; Rachiero, G. P.; Vignola, M. C. Macromolecular Bioscience 2003, 3, 749.

Presentations:

Poster presentation at the International workshop on Advanced Frontiers in Polymer Science (AFPS 2002), Pisa 12-13 settembre 2002. Poster title: A facile synthetic procedure to prepare hydrophilic PCL-based poly(ether-ester-amide).