Chemistry of Magnesium and Zinc Complexes Supported by Bulky Ancillary Ligands and their Applications in the Ring-Opening Polymerization Studies of Cyclic Esters
DISSERTATION
Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University
By
Pasco M. Wambua, B.Sc., M.Sc.
Graduate Program in Chemistry
The Ohio State University
2014
Dissertation Committee:
Professor Malcolm H. Chisholm, Advisor
Professor James A. Cowan
Professor T.V. RajanBabu
Professor Yann Guezennec
Copyright by
PASCO WAMBUA
2014
Abstract
A series of magnesium and zinc complexes supported by bulky ancillary ligands of the form (TMP)MgnBu(L), (BDI*)MgnBu(L) and (TMP)Zn(X) were synthesized where TMP = 1,5,9-trimesityldipyrromethene, BDI* = (3-[2,6-diisopropylphenyl)amino]-
5-[(2.6-diisopropylphenyl)imino]-2,2,6,6-tetramethyl-hept-3-ene), L = THF, 2-MeTHF,
i pyridine and DMAP, X = N(SiMe3)2, OPr and OCMe2CO(O)Et. These were all characterized and applied in the study of ring-opening polymerization (ROP) of cyclic esters. All complexes ring-open and sustain the polymerization of lactide (LA) and ε- caprolactone (ε-CL) in solution. The magnesium catalyst series was shown to initiate
ROP via a β-H atom transfer generating an alkoxide and sequential elimination of 1- butene. The TMP supported catalyst systems show a good stereoselectivity in the ring- opening polymerization of rac-Lactide (rac-LA) with Pr values ranging between 0.80 -
0.96 with higher values observed in THF solvent. Copolymerization of rac-LA with ε-
CL, when both monomers are present at the same time in a reaction mixture, only led to the ROP of rac-LA. Initial ROP of ε-CL with subsequent addition of the rac-LA resulted in stereoblock PLA-b-PCL but the vice-versa could not be attained. This was shown to be as a result of chelation of the ketonic group to the metal center that upon ROP of LA inhibits the enchainment of ε-CL. This was further proved by the synthesis of the model compound (TMP)Zn(OCMe2COOEt) where its carbonyl group, in solution and solid state, was shown to be chelated.
ii
Role of solvent was investigated and we indeed observed that THF accelerated the
ROP of ε-CL while suppressing that of LA. A detailed explanation of this phenomenon is given in chapter 4.
iii
Dedication
This document is dedicated to my entire family and in particular my parents, Joseph and
Beata Wambua.
iv
Acknowledgments
I wish to convey my deepest gratitude to my mentor and advisor, Professor
Malcolm. H. Chisholm. His timely guidance, continuous and persistent mentoring to bring out the best in me, his patience and understanding are priceless and I cannot thank him enough. I would also like to express my gratitude to my committee members
Professor T.V. RajanBabu and Professor James A. Cowan for their contributions towards my graduate school growth and success.
I wish to also acknowledge Dr. Judith Gallucci and Christopher Durr for their contributions to my dissertation in solving the crystal structures, Dr. Tanya Young for all the cumulative hours she spend assisting me in the NMR spectroscopy facility and
Professor Sherwin Singer for his words of encouragement over the years. I wish to sincerely thank Chisholm group members for their support, past and present, in particular
Dr. Kittisak Choojun, Dr. Ruaraidh McIntosh, Dr. Chandrani Chatterjee, Dr. Vesal
Naseri, Dr. Alexandre Bernard and Vagulejan Balasanthiran. I want to also express my gratitude to the Department of Chemistry and Biochemistry, The Ohio State University for granting me the opportunity to pursue my graduate studies.
Lastly, I wish to thank my family members who have stood by me through my ups and downs during my graduate school journey. My Parents Joseph and Beata
Wambua, my siblings John, Martin, Thomas and Paul Wambua, my Aunty Victoria
v
Ndonye, my cousin Celina Ndonye and her family Dr. Patrick Wachira, Foe and Naike. I wish to thank my wife Jane Mburu and sons Brown and Sonic Muindi.
vi
Vita
December 2005 ...... B.S. Chemistry, Moi University, Kenya
2006 – 2008...... Senior Chemist, ARM Cement Ltd,
Mombasa, Kenya
August 2011 ...... M.Sc. Chemistry, The Ohio State University
January 2009 to present ...... Graduate Research Associate and Graduate
Teaching Assistant, Department of
Chemistry and Biochemistry, The Ohio
State University
Publication
1. Chisholm, M.H.; Choojun, K.; Gallucci, J. C.; Wambua, P.M. Chem. Sci. 2012, 3,
3445-3457
Fields of Study
Major Field: Chemistry
vii
Table of Contents
Abstract ...... ii
Dedication ...... iv
Acknowledgments...... v
Vita ...... vii
Table of Contents ...... viii
List of Tables ...... xiii
List of Figures ...... xv
CHAPTER 1: INTRODUCTION ...... 1
1.1 Review on Grignard reagents ...... 1
1.1.1 Preparation and solvent effects of Grignard reagents ...... 1
1.1.2 Coordination of Grignard reagents in solution and solid state ...... 4
1.1.3 Reaction mechanism for Grignard reagents ...... 5
1.1.4 Highly reactive functionalized Grignard reagents ...... 8
1.2 Chemistry of organozinc reagents ...... 12
1.2.1 History of organozinc chemistry ...... 12
1.2.2 Transmetallation reactions of organozinc reagents...... 15 viii
1.2.3 Nature and structure of organozinc reagents ...... 17
1.3 Green biodegradable polymers...... 18
1.3.1 Mechanism for ring-opening polymerization of lactide ...... 20
1.3.2 Lactide stereocontrol ...... 23
1.3.3 Complexes for lactide ring-opening polymerization (ROP) ...... 25
1.4 Summary ...... 29
CHAPTER 2: METHODS FOR EXPERIMENTS AND GENERAL
CONSIDERATIONS ...... 31
2.1 General considerations ...... 31
2.2 Physical measurements ...... 32
2.3 General procedure for lactide ring opening polymerization ...... 32
2.4 General procedure for studying the kinetics of rac-lactide polymerization...... 33
2.5 General procedure for studying the kinetics of ε-caprolactone polymerization. 33
13 2.6 CO2 insertion experiments ...... 34
2.7 General reactions with alcohols, secondary amines, and ketones ...... 34
2.8 Crystallographic studies ...... 34
CHAPTER 3: CONCERNING THE CHEMISTRY OF MAGNESIUM
COMPLEXES SUPPORTED BY TMPH = 1,5,9-TRIMESITYLDIPYRROMETHENE
AND BDI*H = (3-[(2,6 DIISOPROPYLPHENYL) AMINO]-5-[(2,6-
DIISOPROPYLPHENYL) IMINO]-2,2,6,6-TETRAMETHYL-HEPT-3-ENE)...... 36 ix
3.1 Introduction ...... 36
3.2 Chemistry of (TMP)MgnBuTHF)...... 38
3.2.1 Synthesis of (TMP)MgnBu(THF) ...... 38
3.2.2 Solution NMR studies of (TMP)MgnBu(THF) ...... 38
3.2.3 Reaction of (TMP)MgnBu(THF) with benzophenone and diphenyl
methanol ...... 41
3.2.4 Reactions of (TMP)MgnBu(THF) with lactide ...... 44
3.2.5 Reactions of (TMP)MgnBu(THF) with carbon dioxide ...... 45
3.3 Single X-ray crystallographic studies ...... 47
3.3.1 (TMP)MgnBu(THF) ...... 47
3.3.2 (TMP)MgOtBu(THF) ...... 51
3.4 Ring-opening polymerization studies of lactide...... 55
3.5 Kinetics studies of lactide and ε-caprolactone using (TMP)MgnBu(L) and
(BDI*)MgnBu(L) where L = THF, 2-MeTHF, Py, DMAP ...... 62
3.6 Synthesis and characterization ...... 66
CHAPTER 4: COMPARATIVE STUDY PERTAINING TO THE REMARKABLE
ROLE OF SOLVENT, THF VERSUS DICHLOROMETHANE, IN THE RING-
OPENING POLYMERIZATION OF LACTIDE AND ε-CAPROLACTONE BY
MAGNESIUM AND ZINC CATALYSTS ...... 73
4.1 Introduction ...... 73 x
4.2 Results and discussion ...... 74
4.3 Crystal structure studies ...... 96
i 4.3.1 [(TMP)ZnOPr ]2 ...... 96
4.3.2 (TMP)ZnN(SiMe3)2 ...... 99
4.3.3 (TMP)Zn(OCMe2COOCH2CH3) ...... 102
4.4 Synthesis...... 104
CHAPTER 5: THE HOMO- AND CO-POLYMERIATION STUDIES OF LACTIDE
AND ε-CAPROLACTONE USING MAGNESIUM AND ZINC INITIATORS
SUPPORTED BY 1,5,9-TRIMESITYLDIPYRROMETHENE ...... 107
5.1 Introduction ...... 107
5.2 Results and discussion ...... 107
5.2.1 Solution and melt homopolymerization of ε-caprolactone using
i [(TMP)ZnO Pr]2 ...... 107
5.2.2 Copolymerization studies of rac-LA and ε-CL using Mg and Zn catalysts
110
5.3 Synthesis...... 115
CHAPTER 6: VARIABLE TEMPERATURE NMR SPECTROSCOPIC SOLUTION
STUDIES ON THE DYNAMIC EXCHANGE OF MAGNESIUM AND ZINC
COMPLEXES SUPPORTED BY 1,5,9 - TRIMESITYLDIPYRROMETHENE LIGAND
(TMP) 117
xi
6.1 Introduction ...... 117
6.2 Results and discussions ...... 117
REFERENCES ...... 133
xii
List of Tables
Table 1.1: Effect of the addition of lithium salts on the formation of 4- methoxyphenylmagnesium chloride at 25oC 21 ...... 10
Table 3.1: Selected bond distances (Å) and Angles (o) for (TMP)MgnBu(THF) ...... 49
Table 3.2: Data collection parameters for (TMP)MgnBu(THF) ...... 50
Table 3.3: Selected Bond distances (Å) and Angles (o) for (TMP)MgOBut(THF) ...... 53
Table 3.4: Data collection parameters for (TMP)MgOtBu(THF) ...... 54
Table 3.5: rac-LA polymerization by (TMP)MgnBu(L) ([Cat.] = 3.47mM, [LA]o/[Cat.] =
100, at 25 oC) ...... 57
Table 3.6: rac-LA polymerization by (BDI*)MgnBu(L) ([Cat.] = 3.47mM, [LA]o/[Cat.] =
100, at 25 oC) ...... 58
Table 3.7: rac-LA polymerization by (TMP)MgnBu(THF) ([Cat.] = 3.47mM,
[LA]o/[Cat.] = 100, at 25 oC) ...... 59
Table 3.8: Selected normal and homonuclear decoupled 1H NMR spectra of poly-rac- lactide ...... 61
n Table 3.9: Summary of kapp for the ROP of rac-LA in DCM. (TMP)Mg Bu(L) = 2.33mM, rac-LA = 0.14M ...... 64
Table 3.10: Summary of kapp for the ROP of ɛ-Caprolactone in DCM using
(TMP)MgnBu(L) ...... 65
Table 4.1: Rates of ROP of rac-Lactide and ε-Caprolactone using magnesium initiators 77 xiii
Table 4.2: Rates of ROP of rac-Lactide and ε-Caprolactone using zinc initiators ...... 77
i Table 4.3: Crystallographic data collection parameters for [(TMP)ZnOPr ]2 ...... 98
Table 4.4: Crystallographic data collection parameters for (TMP)ZnN(SiMe3)2 ...... 101
Table 4.5: Crystallographic data collection parameters for (TMP)Zn(OCMe2COOEt) . 103
xiv
List of Figures
Figure 1.1: Solvent effect on the synthesis of tetraorganylborate complexes ...... 2
Figure 1.2: Synthesis of halide-free R2Mg compounds in 1,4-dioxane ...... 3
Figure 1.3: Solvent effect on diastereoselectivity ...... 3
Figure 1.4: Schlenk equilibrium ...... 4
Figure 1.5: Various magnesium coordinations in solid state ...... 5
Figure 1.6: Grignard reagent formation via radical intermediates pathway 17 ...... 6
Figure 1.7: Proposed Grignard reagent formation mechanism 16,17 ...... 6
Figure 1.8: One-step concerted mechanism for Grignard reagent with alkyl transfer and
β-hydrogen transfer respectively 19 ...... 7
Figure 1.9: Preparation of highly functionalized arymagnesium halides via iodine- magnesium exchange ...... 8
- + Figure 1.10: The formation of the reactive species iPrMgCl2 Li ...... 10
Figure 1.11: Preparation of mixed Mg/Li amides 28 ...... 11
Figure 1.12: Reformatsky reaction 34 ...... 13
Figure 1.13: Hunsdiecker reaction ...... 13
Figure 1.14: Simmons-Smith reaction 36 ...... 13
Figure 1.15: Palladium catalyzed cross-coupling reaction with zinc homoenolates 37,38,40
...... 14
Figure 1.16: Synthesis of organozinc reagents using Rieke zinc 41 ...... 15 xv
Figure 1.17: 1,1-bimetallic reagent 40 ...... 15
Figure 1.18: Polyfunctional ketone and SN2 substitution product obtained from zinc cuprates reactions 40 ...... 16
40 Figure 1.19: Cyclization reaction catalyzed by palladium in presence of Et2Zn ...... 17
Figure 1.20: Possible structures of organozinc reagents 40 ...... 18
Figure 1.21: Lactide life cycle 69...... 19
Figure 1.22: Catalytic conversion of 5-hydroxymethylfurfural (HMF) to caprolactone 77
...... 20
Figure 1.23: Coordination– insertion mechanism; M metal, OR alkoxide group, Ln ligand(s) 68 ...... 21
Figure 1.24: Inter-chain transesterification ...... 22
Figure 1.25: Intra-chain transesterification ...... 22
Figure 1.26: Chain transfer mechanism 68,69 ...... 22
Figure 1.27: Stereoisomers of Lactide 87 ...... 23
Figure 1.28: Lactide tacticities resulting from ring opening polymerization69 ...... 24
Figure 1.29: Enantiomeric site control 68 ...... 25
Figure 1.30: Example of amine bis(phenolate) ligand yttrium complex 99...... 26
Figure 1.31: Bulky trispyrazolylborate calcium alkoxide ...... 27
i Figure 1.32: Coates et al. [(BDI)Zn(OPr )]2 complex ...... 28
Figure 1.33: (BDI)MgOtBu(THF) monomeric structure ...... 29
Figure 3.1: (A) (TMPH) ligand (B) Resonance structure of β-diiminato ligand ...... 37
xvi
Figure 3.2: Expanded α – proton region of the magnesium and zinc alkyl complexes shoeing a AA’XX’ pattern...... 39
Figure 3.3: Homonuclear decoupled 1H NMR spectra of (TMP)MgnBu(THF) showing the
α-protons region...... 40
Figure 3.4: Simulation of (TMP)MgBun(THF) α-protons using the topspin ...... 41
Figure 3.5: 1H NMR showing products of the reaction between (TMP)MgnBu(THF) and benzophenone...... 42
Figure 3.6: Six-membered ring transition state for β–hydrogen transfer ...... 42
Figure 3.7: 1H NMR showing products of the reaction between (TMP)MgnBu(THF) and diphenyl methanol...... 43
Figure 3.8: Possible routes for the ring-opening polymerization of lactide ...... 44
Figure 3.9: 1H NMR evidence for the lactide ROP mechanism via β-hydrogen transfer using (TMP)MgnBu(THF). 1-Butene is generated upon the ring-opening polymerization of lactide...... 45
n 13 Figure 3.10: (TMP)Mg Bu(THF) reaction with CO2 ...... 46
Figure 3.11: 1H NMR for (TMP)MgnBu(THF) showing the butyl region before and after
13 13 CO2 insertion. Notice the α - proton signal after CO2 insertion attains a normal triplet.
...... 46
Figure 3.12: ORTEP drawing of (TMP)MgnBu(THF) with thermal ellipsoids drawn at the
50% probability level. The structure shows a distorted tetrahedral geometry about the Mg metal centre. All hydrogen atoms are omitted for clarity ...... 48
xvii
Figure 3.13: ORTEP drawing of (TMP)MgOBut(THF) with thermal ellipsoids drawn at the 50% probability level. All hydrogen atoms are omitted for clarity...... 52
Figure 3.14: Best superposition of the molecular structures of (BDI*)MgBun(THF) in green and (TMP)MgBun(THF) in red showing the relative disposition of the aryl ligands and the greater steric pressure of mesityl groups in the pyrromethene ligand, TMP, on the pocket of the n-butyl group ...... 60
Figure 3.15: Kinetics expression...... 62
Figure 3.16: Semilogarithmic plots of rac-Lactide conversion with time in CH Cl at 25 2 2 o n C with (TMP)Mg Bu(L) ...... 63
Figure 3.17: Semilogarithmic plots of ɛ-caprolactone conversion with time in CH Cl at 2 2
o n 25 C with (TMP)Mg Bu(L) ...... 64
Figure 3.18: Semilogarithmic plots of rac-Lactide conversion with time in CH Cl at 25 2 2 o n C with (BDI*)Mg Bu(L) ...... 65
Figure 3.19: Semilogarithmic plots of ɛ-Caprolactone conversion with time in CH Cl at 2 2
o n 25 C with (BDI*)Mg Bu(L) ...... 66
Figure 4.1: TMP, BDI* and BDI Mg and Zn initiators for ROP of lactide and ε- caprolactone ...... 76
° n Figure 4.2: Polymerization of rac-LA in CH2Cl2 at 25 C using (TMP)MgBu (THF) as an
-1 2 initiator ([rac-LA]o= 0.139 M;( ) [rac-LA]o/[cat.] = 98, kapp = 0.256 min (linear fit, R
-1 2 = 0.95); ( )[rac-LA]o/[cat.] = 84, kapp = 0.304 min (linear fit, R = 0.95); ( ) [rac-
xviii
-1 2 LA]o/[cat.] = 66, kapp = 0.378 min (linear fit, R = 0.96); ( )[rac-LA]o/[cat.] = 59, kapp
= 0.477 min-1 (linear fit, R2 = 0.98)) ...... 80
n Figure 4.3: Plot of ln kapp vs ln[(TMP)MgBu (THF)] of rac-LA polymerization using
n (TMP)MgBu (THF) as an initiator ( in CH2Cl2, 25°C, [rac-LA]o = 0.139 M); ( )y =
1.077x + 5.725 (linear fit, R² = 0.97) ...... 80
Figure 4.4: Polymerization of rac-LA in THF at 25°C using (TMP)MgBun(THF) as an
-1 2 initiator ([rac-LA]o= 0.208 M;( ) [rac-LA]o/[cat.] = 98, kapp = 0.0951 min (linear fit, R
-1 2 = 0.99); ( )[rac-LA]o/[cat.] = 79, kapp = 0.120 min (linear fit, R = 0.99); ( ) [rac-
-1 2 LA]o/[cat.] = 59, kapp = 0.158 min (linear fit, R = 0.99)) ...... 81
n Figure 4.5: Plot of ln kapp vs ln[(TMP)MgBu (THF)] of rac-LA polymerization using
n (TMP)MgBu (THF) as an initiator ( in THF, 25°C, [rac-LA]o = 0.208 M); ( )y = 1.000x
+ 3.81 (linear fit, R² = 0.99) ...... 81
° n Figure 4.6: Polymerization of ε-CL in CH2Cl2 at 25 C using (TMP)MgBu (THF) as an
-1 2 initiator ([ε-CL]o= 0.263M;( ) [ε-CL]o/[cat.] = 334, kapp = 0.688 min (linear fit, R =
-1 2 0.99); ( )[ε-CL]o/[cat.] = 243, kapp = 1.26 min (linear fit, R = 0.99); ( ) [ε-CL]o/[cat.]
-1 2 = 137, kapp = 1.89 min (linear fit, R = 0.99)) ...... 82
n Figure 4.7: Plot of ln kapp vs ln[(TMP)MgBu (THF)] of ε-CL polymerization using
n (TMP)MgBu (THF) as an initiator (in CH2Cl2, 25°C, [ε-CL]o = 0.263 M); ( )y = 1.083x
+ 7.469 (linear fit, R² = 0.93) ...... 82
° Figure 4.8: Polymerization of ε-CL in 25% V THF in CH2Cl2 at 25 C using
n (TMP)MgBu (THF) as an initiator ([ε-CL]o= 0.250M;( ) [ε-CL]o/[cat.] = 248, kapp = 3.01
-1 2 -1 2 min (linear fit, R = 0.99); ( )[ε-CL]o/[cat.] = 213, kapp = 3.98 min (linear fit, R =
xix
-1 2 0.99); ( ) [ε-CL]o/[cat.] = 186, kapp = 4.29 min (linear fit, R = 0.99); ( ) [ε-CL]o/[cat.]
-1 2 = 149, kapp = 5.17 min (linear fit, R = 0.99)) ...... 83
n Figure 4.9: Plot of ln kapp vs ln[(TMP)MgBu (THF)] of ε-CL polymerization using
n (TMP)MgBu (THF) as an initiator (25% V THF in CH2Cl2, 25°C, [ε-CL]o = 0.250 M);
( )y = 1.02x + 8.171 (linear fit, R² = 0.96) ...... 83
° n Figure 4.10: Polymerization of rac-LA in CH2Cl2 at 25 C using BDI*MgBu (THF) as an
-1 2 initiator ([rac-LA]o= 0.174 M;( ) [rac-LA]o/[cat.] = 261, kapp = 0.132 min (linear fit, R
-1 2 = 0.99); ( )[rac-LA]o/[cat.] = 171, kapp = 0.176 min (linear fit, R = 0.99); ( ) ([rac-
-1 2 LA]o/[cat.] = 116, kapp = 0.3293 min (linear fit, R = 0.99); ( )[rac-LA]o/[cat.] = 99,
-1 2 kapp = 0.351 min (linear fit, R = 0.97)) ...... 84
n Figure 4.11: Plot of ln kapp vs ln [BDI*Mg Bu(THF)] of rac-LA polymerization using
n BDI*Mg Bu(THF) as an initiator in CH2Cl2, 25°C, [rac-LA]o = 0.174 M); ( )y = 1.09x +
5.906 (linear fit, R² = 0.96) ...... 84
Figure 4.12: Polymerization of rac-LA in THF at 25°C using (BDI*)MgBun(THF) as an
-2 -1 initiator ([rac-LA]o= 0.347 M;( ) [rac-LA]o/[cat.] = 227, kapp = 2.00*10 min (linear
2 -2 -1 2 fit, R = 0.99); ( )[rac-LA]o/[cat.] = 177, kapp = 2.86 *10 min (linear fit, R = 0.99);
-2 -1 2 ( )[rac-LA]o/[cat.] = 113, kapp = 4.09 *10 min (linear fit, R = 0.99)) ...... 85
n Figure 4.13: Plot of ln kapp vs ln [(BDI*)Mg Bu(THF)] of rac-LA polymerization using
n BDI*Mg Bu(THF) as an initiator in THF, 25°C, [rac-LA]o = 0.347 M); ( )y = 1.00x +
2.64 (linear fit, R² = 0.97) ...... 85
° n Figure 4.14: Polymerization of ε-CL in CH2Cl2 at 25 C using (BDI*)MgBu (THF) as an
-1 2 initiator ([ε-CL]o= 0.270M;( ) [ε-CL]o/[cat.] = 167, kapp = 0.33 min (linear fit, R =
xx
-1 2 0.96); ( )[ε-CL]o/[cat.] = 222, kapp = 0.202 min (linear fit, R = 0.99); ( ) [ε-CL]o/[cat.]
-1 2 = 290, kapp = 0.189 min (linear fit, R = 0.99); ( ) [ε-CL]o/[cat.] = 377, kapp = 0.130 min-1 (linear fit, R2 = 0.99)) ...... 86
n Figure 4.15: Plot of ln kapp vs ln [(BDI*)Mg Bu(THF)] of ε-CL polymerization using
n (BDI*)Mg Bu(THF) as an initiator in CH2Cl2, 25°C, [ε-CL]o = 0.270 M); ( )y = 1.08x +
5.801 (linear fit, R² = 0.93) ...... 86
° Figure 4.16: Polymerization of ε-CL in 10% V THF in CH2Cl2 at 25 C using
n (BDI*)MgBu (THF) as an initiator ([ε-CL]o= 0.270M;( ) [ε-CL]o/[cat.] = 181, kapp =
-3 -1 2 -3 -1 6.90*10 s (linear fit, R = 0.99); ( ) [ε-CL]o/[cat.] = 237, kapp = 5.30*10 s (linear
2 -3 -1 2 fit, R = 0.99); ( ) [ε-CL]o/[cat.] = 308, kapp = 4.00*10 s (linear fit, R = 0.99)) ...... 87
n Figure 4.17: Plot of ln kapp vs ln[(BDI*)MgBu (THF)] of ε-CL polymerization using
n (BDI*)MgBu (THF) as an initiator (10% THF in CH2Cl2, 25°C, [ε-CL]o = 0.250 M);
( )y = 1.02x + 2.425 (linear fit, R² = 0.99) ...... 87
° i Figure 4.18: Polymerization of ε-CL at 25 C using [(TMP)ZnOPr ]2 as an initiator ([ε-
i -1 CL]o= 0.298 M, [(TMP)ZnOPr ]2] = 6.02 mM;( ) CH2Cl2, kapp = 0.0434 min (linear fit,
2 -1 2 R = 0.99); ( ) THF, kapp = 0.710 min (linear fit, R = 0.99) ...... 88
° Figure 4.19: Polymerization of ε-CL at 25 C using (TMP)ZnN(SiMe3)2 as an initiator ([ε-
-1 CL]o= 0.298 M, [(TMP)ZnN(SiMe3)2] = 6.02 mM;( ) CH2Cl2, kapp = 0.0034 min
2 -1 2 (linear fit, R = 0.99); ( ) THF, kapp = 0.131 min (linear fit, R = 0.99) ...... 88
° Figure 4.20: Polymerization of rac-LA at 25 C using (BDI)ZnN(SiMe3)2 as an initiator
-1 ([rac-LA]o= 0.298 M, [(BDI)ZnN(SiMe3)2] = 6.02 mM;( ) CH2Cl2, kapp = 0.0358 min
2 -1 2 (linear fit, R = 0.99); ( ) THF, kapp = 0.0138 min (linear fit, R = 0.99) ...... 89
xxi
° Figure 4.21: Polymerization of ε-CL at 25 C using (BDI)ZnN(SiMe3)2 as an initiator ([ε-
-1 CL]o= 0.298 M, [(BDI)ZnN(SiMe3)2] = 6.02 mM;( ) CH2Cl2, kapp = 0.238 min (linear
2 -1 2 fit, R = 0.99); ( ) THF, kapp = 1.11 min (linear fit, R = 0.99) ...... 89
Figure 4.22: Representations of the structures of (BDI)M(OCMe2COOEt) ...... 90
Figure 4.23: Representation of the structure of (TMP)Zn(OCMe2COOEt) ...... 90
Figure 4.24: FTIR spectra for (TMP)Zn(OCMe2COOEt) in DCM ...... 91
Figure 4.25: FTIR spectra for (TMP)Zn(OCMe2COOEt) in THF ...... 91
Figure 4.26: Dynamic (variable temperature) NMR studies showing stacked 1H NMR spectra of (TMP)Zn(OCMe2COOEt) (0.035M) compound in toluene-d8 ...... 92
Figure 4.27: Expanded aromatic region of dynamic (variable temperature) NMR studies
1 showing stacked H NMR spectra of (TMP)Zn(OCMe2COOEt) (0.035M) compound in
o toluene-d8. The coalescence temperature (Tc) is approximately 15 C ...... 93
Figure 4.28: Dynamic (variable temperature) NMR studies showing stacked 1H NMR spectra of (TMP)Zn(OCMe2COOEt) (0.035M) compound in THF-d8 ...... 94
Figure 4.29: Expanded aromatic region of dynamic (variable temperature) NMR studies
1 showing stacked H NMR spectra of (TMP)Zn(OCMe2COOEt) (0.035M) compound in
o THF-d8. The coalescence temperature (Tc) is approximately -85 C ...... 95
i Figure 4.30: ORTEP representations of [(TMP)ZnOPr ]2 with thermal ellipsoids drawn at
50% probability level: (a) Full representation with only hydrogens removed for clarity,
(b) View of dimer core with hydrogens and mesityls removed for clarity...... 97
Figure 4.31: ORTEP representations of (TMP)ZnN(SiMe3)2 with thermal ellipsoids drawn at 50% probability level: (a) Full representation with only hydrogens removed for
xxii clarity, (b) Side view of (TMP)ZnN(SiMe3)2 core with hydrogens and mesityls removed for clarity...... 100
Figure 4.32: ORTEP representations of (TMP)Zn(OCMe2COOEt) with thermal ellipsoids drawn at 50% with hydrogens removed for clarity...... 102
i Figure 5.1: Plot of % conversion vs time of ε-caprolactone in THF using [(TMP)ZnO Pr]2 at 0 oC. [ε-CL] = 0.287 M, [Cat] = 3.78 mM...... 108
Figure 5.2: Plot of molecular weight (Mn) and polydispersity Index (PDI) vs %
i o conversion of ε-Caprolactone in THF using [(TMP)ZnO Pr]2 at 0 C. [ε-CL] = 0.287 M,
[Cat] = 3.78 mM. Plot shows a well-controlled living polymerization ...... 109
Figure 5.3: Plot of Mn and PDI vs M/I of ε-Cl in melt polymerization using
i o [(TMP)ZnO Pr]2 at 110 C...... 109
Figure 5.4: Copolymerization of rac-LA with ε-CL using both the Mg and Zn catalyst precursors only gives PRLA in Solution. Resting state of catalyst in polymerization of
LA quenches enchainment of ε-CL monomer...... 111
Figure 5.5: Illustration of coordination insertion mechanism for the ROP of LA and ε-CL.
Indicates ketonic carbonyl for ring-opened LA monomer is favored to chelate to the metal unlike the one for ε-CL...... 112
Figure 5.6: Homo- and co-polymerization of rac-LA with ε-CL using
(TMP)MgnBu(THF) in DCM...... 112
Figure 5.7: Homo- and co-polymerization of rac-LA with ε-CL using (TMP)MgnBu(2-
MeTHF) in DCM ...... 113
xxiii
Figure 5.8: Homo- and co-polymerization of rac-LA with ε-CL using
(TMP)MgnBu(THF) in DCM ...... 113
Figure 5.9: Homo- and co-polymerization of rac-LA with ε-CL using (TMP)MgnBu(Py) in DCM ...... 114
Figure 5.10: Homo- and co-polymerization of rac-LA with ε-CL using
(TMP)ZnN(SiMe3)2 in C6D6 ...... 114
Figure 5.11: Model compound (TMP)Zn(OCOMe2COOEt) shows no activity for ROP of
ε-CL during homo- or copolymerization of ε-CL with LA...... 115
Figure 6.1: Representation of the trigonal planar complex of the TMP ligand ...... 118
1 Figure 6.2: Variable temperature H 500 MHz NMR of 0.035mM (TMP)ZnN(SiMe3)2 in
Toluene-d8. (* = Toluene-d8 protio impurities)...... 123
Figure 6.3: Expanded mesityl aromatic region variable temperature 1H 500 NMR MHz of
n 0.035mM (TMP)Mg Bu(DMAP) in Toluene-d8. (* = Toluene-d8 protio impurities). ... 124
Figure 6.4: Variable temperature 1H 500 NMR MHz of 0.035mM (TMP)MgnBu(Py) in
THF-d8. (* = THF-d8 protio impurities)...... 125
Figure 6.5: Expanded aromatic region variable temperature 1H 500 NMR MHz of
n 0.035mM (TMP)Mg Bu(Py) in Toluene-d8. (* = Toluene-d8 protio impurities)...... 126
Figure 6.6: Expanded mesityl methyl region variable temperature 1H 500 NMR MHz of
n 0.035mM (TMP)Mg Bu(Py) in Toluene-d8. (* = Toluene-d8 protio impurities)...... 127
Figure 6.7: Variable temperature 1H 500 MHz NMR of 0.035mM
(TMP)Zn(OCMe2COOEt) in Toluene-d8 showing the expanded mesityl aromatic region.
(* = Toluene-d8 protio impurities) ...... 128
xxiv
Figure 6.8: Variable temperature 1H 500 MHz NMR of 0.035mM
(TMP)Zn(OCMe2COOEt) in THF-d8 showing the expanded mesityl aromatic region. (* =
THF-d8 protio impurities)...... 129
1 i Figure 6.9: Variable temperature H 500 MHz NMR of 0.035mM [(TMP)Zn(O Pr)]2 in
THF-d8. (* = THF-d8 protio impurities)...... 130
Figure 6.10: Expanded methyl region variable temperature 1H 500 MHz NMR of
i 0.035mM [(TMP)ZnO Pr]2 in Toluene-d8...... 131
Figure 6.11: Expanded aromatic-mesityl region variable temperature 1H 500 MHz NMR
i of 0.035mM [(TMP)ZnO Pr]2 in Toluene-d8. (* = Toluene-d8 protio impurities) ...... 132
xxv
CHAPTER 1: INTRODUCTION
1.1 Review on Grignard reagents
Grignard reagents, formulated as “RMgX”, are arguably the most used organometallic reagents in synthetic chemistry as well as in the industrial production of building blocks for applications in the pharmaceutical and food industry. Victor
Grignard, then a graduate student under the advisory of Professor P. Barbier in France, discovered the highly reactive Grignard reagents in 1900. 1 This development ushered in a new era in organometallic chemistry thus replacing the slow reacting organozinc reagents. 2 Grignard was consequently awarded in 1912 the Nobel Prize in chemistry for his work.
1.1.1 Preparation and solvent effects of Grignard reagents
The common preparative route of Grignard reagents involves refluxing of magnesium metal with an alkyl or aryl halide (RX) in an ethereal solvent. Manipulations of the reactants and solvents is carried out under standard Schlenk or glovebox technique in order to keep oxygen and water from interfering with the reaction. Initial addition of alkyl or aryl halide (10 to 20%) into magnesium turnings leads to an exothermic reaction
1 resulting into the corresponding ‘RMgX’ Grignard reagent hence necessary safety precaution should be taken. 3,4
The choice of solvent in Grignard reactions is crucial and mostly dictated by the desired chemistry, cost, safety and reactivity. Brown and Racherla 5 illustrated the effect of diethyl ether versus THF in their synthesis of tetraorganylborate complexes and observed that the yield was significantly affected depending on the solvent used.
Reaction of ethylmagnesium bromide and triethylboron in ethyl ether (EE) shows little or no reaction but the same reaction proceeds to completion in THF to give tetraethyl boron
5 magnesium bromide, Et4BMgBr (Figure 1).
Figure 1.1: Solvent effect on the synthesis of tetraorganylborate complexes
Magnesium dihalides have poor solubility in hydrocarbon solvents and this has been exploited to provide a cost effective method for the synthesis of diorganomagnesium derivatives. 6–8 For instance, use of 1,4-dioxane in some Grignard reagents precipitates out the magnesium dihalide (MgX2) and this has been explored in
9–11 the synthesis of halide free diorganomagnesium reagents R2Mg (Figure 2).
2
Figure 1.2: Synthesis of halide-free R2Mg compounds in 1,4-dioxane
Diastereoselectivity, while using Grignard reagents, can also be influenced by solvent choice as was demonstrated by Nagano et al. (Figure 1.3). 12
Figure 1.3: Solvent effect on diastereoselectivity
In summary, chemistry of Grignard reagents is usually influenced by the choice of solvent. Ethereal solvents have traditionally been the preferred choice in synthesis of
Grignard reagents due to their high solubility. 13 However they possess very low flash
o o points (e.g. Et2O, -45 C) in comparison to THF (-15 C), which is a safety hazard. They are also relatively expensive compared to THF and hydrocarbon solvents. 4,13,14
3
1.1.2 Coordination of Grignard reagents in solution and solid state
Initial proposal on the existence of equilibrium for Grignard reagents in ether solvent was suggested by Abegg 15 and later extensive studies by Schlenk and Schlenk 9 resulted in what is now commonly referred to as the Schlenk equilibrium (Figure 4) where the R and X represent alkyl and halide respectively. Overall Grignard reagents are monomeric in solution.
Figure 1.4: Schlenk equilibrium
In solid state, Grignard reagents can exist as four to six coordinate 4,16,17 (Figure
1.5). However, most of them crystalize with a distorted tetrahedral structure. In cases where the ligands can fit around the magnesium center the coordination can be expanded to five or six resulting in a trigonal bipyramidal or octahedral structure. 17 The coordinating solvents contribute to the stabilization of the magnesium reagents besides serving as an indicator for the Schlenk equilibrium position.
4
Figure 1.5: Various magnesium coordinations in solid state
1.1.3 Reaction mechanism for Grignard reagents
To this date the mechanism by which organomagnesium reagents takes place is still inconclusive and continues to draw a lot of debate. However, experimental evidence exists in favor of a radical pathway 4,16 as well as a one-step concerted mechanism. 16
Kharasch and Reinmuth 18 first suggested that formation of Grignard reagents proceed via radical reactions involving the adherence of radicals to the metal surface. This proposal was further supported by Hamdouchi and Walborsky (HW) 4 together with Garst and
Ungváry (GU) 16 although they remarkably differ in the details. However, they both agree that, during Grignard reactions where a Grignard reagent (RMgX) is formed by reacting magnesium metal (Mg), organic halide (RX) and the appropriate solvent (SH), Grignard radicals (R•) exist as intermediates along a pathway R (Figure 6). By products of RR,
17 RH, R(-H), and MgX2 may also be present. Along the pathway R, these intermediate radicals may undergo reduction (r), coupling /disproportionation (c), solvent abstraction
(s) as well as a first-order or pseudo-first-order reaction (q). 17
5
Figure 1.6: Grignard reagent formation via radical intermediates pathway 17
HW argue that almost all of the alkyl intermediate radicals (R•) remain adsorbed on the magnesium surface 4 but GU is for the idea that this radical intermediates diffuse in solution. 16 This is further illustrated by the three mechanisms proposed below (Figure 7) in which case HW supports the AAD and ADD mechanism route while GU exclusively argues for the DDD mechanism where “A” and “D” implies R• adsorbed on the magnesium surface or diffused in solution respectively. The above mechanism is discussed in depth by GU (page 185-275). 16
Figure 1.7: Proposed Grignard reagent formation mechanism 16,17
6
In a one-step concerted mechanism, the Grignard reagent usually reacts via an alkyl transfer or through β-hydrogen elimination process. The latter case is only viable if a β-hydrogen exist on the alkyl group of the Grignard reagent RMgX. 16,19,20 In the event that a substrate is orientated coplanar to the Grignard reagent and ends up forming a six- membered ring transition state then the β-hydrogen transfer product is dominant (Figure
8). 19,20
Figure 1.8: One-step concerted mechanism for Grignard reagent with alkyl transfer and β-hydrogen transfer respectively 19
In the last four decades or so tremendous progress has been made in understanding the reaction mechanisms of Grignard reagents with ketones as the main substrates. To date there is an overwhelming consensus across the scientific world that these reactions take place via a single electron transfer (radical) or by polar/concerted mechanism. The reaction mechanism pathway seems to be dictated by both substrate reduction potential and organomagnesium species oxidation potentials. 4
7
1.1.4 Highly reactive functionalized Grignard reagents
A century after the discovery of Grignard reagents, a new generation of very reactive polyfunctinalized organomagnesium reagents have paved a new phase in organomagnesium chemistry. These were debuted by the novel pioneer work of Knochel
21 et. al. They take the general form of “RMgX.LiCl” or “R2NMgX.LiCl” and are commonly referred to as “turbo Grignard reagents”. 21 Their advantages over the traditional Grignard reagents is that they show enhanced kinetic basicity, superb regioselectivity and have a broad functional group tolerance that include aromatic and heteroaromatic substrates. 21,22 Usually polyfunctionalized organometallic compounds are synthesized through metal-halogen exchange. 23,24,25 Knochel et al. synthesized various highly functionalized arymagnesium halides through the iodine–magnesium exchange reaction (Figure 9). 25 This reactions were carried out at relatively mild conditions that allowed for tolerance of sensitive carbonyl group derivatives, e.g. nitriles, esters, amides and resulted in high yields. 25,26
Figure 1.9: Preparation of highly functionalized arymagnesium halides via iodine- magnesium exchange
8
The Br/Li exchange is generally faster and proceeds in relatively mild conditions.
However the Br/Mg exchange is very slow requiring harsh conditions and results in low yields hence limiting its synthetic applications. 21,27 Knochel et.al., while investigating on the Br/Mg exchange using various lithium salts (Table 1), discovered that addition of 1 equivalent of LiCl led to a significant increased yield in the formation of 4- methoxyphenylmagnesium chloride (Table 1, entry 6). 21 A much better yield was achieved in the case where a concentrated solution of iPrMgCl.LiCl was applied (Table
1, entry 11) and this was the first “turbo Grignard reagent” reported by the Knochel group. 21 This was an illustration of the LiCl promoter effect in the Br/Mg exchange reaction.
9
Table 1.1: Effect of the addition of lithium salts on the formation of 4- methoxyphenylmagnesium chloride at 25oC 21
They postulated that the high reactivity of this complex (iPrMgCl.LiCl) resulted from the breakdown of the polymeric aggregates due to the addition of the LiCl hence leading to
- + the reactive species, iPrMgCl2 Li (Figure 11).
- + Figure 1.10: The formation of the reactive species iPrMgCl2 Li
The discovery of this turbo Grignard reagents was very significant since a wide range of functionalized aryl- and heteroarylmagnesium reagents could now be cheaply prepared in high yields under mild temperature conditions using iPrMgCl.LiCl. Other analogues of
10 the form “R2NMgCl.LiCl” that demonstrated higher activities, solubility and regioselectivity were later reported by this group (Figure 12). 28
Figure 1.11: Preparation of mixed Mg/Li amides 28
11
1.2 Chemistry of organozinc reagents
1.2.1 History of organozinc chemistry
Zinc metal is generally found in nature as the 24th most abundant element. Its ease of extraction makes it easily available and cheap despite its low occurrence in the earth’s crust. It’s essential to human growth and its deficiency in the human body has been accredited to various health issues 29 especially in children where it causes retarded growth, susceptible immunity to diseases and even delayed sexual maturation. 30 Zinc ion is usually closely associated with magnesium ion due to their semblance of ionic radii size and oxidation charge of +2. However, magnesium is generally more reactive.
The advent of organozinc chemistry can be traced back to 1849 when Edward
Frankland, a chemist at the University of Marburg Germany, discovered diethylzinc by heating ethyl iodide in the presence of zinc powder under hydrogen gas atmosphere. 2,31
These were the first organometallic reagents to be reported. The diethylzinc was highly pyrophoric. Application of these organozinc reagents towards organic electrophiles was disappointing due to their low reactivity leading to their replacement with the highly reactive organomagnesium reagents in late 1800’s. 4 For most part of early to mid-1900’s organozinc reagents were rarely applied in synthesis other than in the Reformatsky reaction 32–34 (Figure 12) involving zinc enolates. This reaction was discovered by Sergey
Nikolaevich Reformatsky, a Russian chemist, in 1887 33 by condensing ketones with organozinc derivatives of α-halo esters to realize β-hydroxy acids. Synthesis of these β- hydroxy acids was popular by this reaction since use of the more reactive organomagnesium reagents led to the production of other products. 12
Figure 1.12: Reformatsky reaction 34
However, progress towards the synthesis of functionalized organozinc reagents was realized by Hunsdiecker in 1942 where he prepared various functionalized organozinc reagents (Figure 13). 35
Figure 1.13: Hunsdiecker reaction
In 1958, use of zinc-copper coupling proved to be successful in the cyclopropanation reactions known as the Simmons-Smith reaction. 36 In this reaction H.
E. Simmons and R. D. Smith refluxed unsubstituted alkenes with methylene iodide in the presence of a zinc-copper couple to obtain cyclopropanes (Figure 14).
Figure 1.14: Simmons-Smith reaction 36
13
Key progress in organochemistry was also achieved by Nakamura and Kuwajima et al.37 in their pioneering work with zinc homoenolates (Figure 15). They found conditions for reacting various electrophiles with the zinc homoenolates to form carbon- carbon bond. 37 This work was further advanced by the palladium catalyzed cross- coupling reactions (Figure 15) of organic halides with organozinc reagents developed by
Negishi 38–40, who in 2010 was awarded a Nobel prize in chemistry for his work on palladium-catalyzed cross-coupling reactions in organic synthesis.
Figure 1.15: Palladium catalyzed cross-coupling reaction with zinc homoenolates 37,38,40
The work of Rieke et al 41 is worthy of mention. The synthesis of highly reactive zinc (Rieke Zinc) from zinc halide reduction using lithium naphthalenide led to the production of alkyl/aryl /vinyl halides. The Rieke zinc undergoes oxidative addition to the halides realizing the respective organozinc reagents (Figure 16). This was a significant progress in the organozinc chemistry since any application in this field was more or less limited to reagents that could only be synthesized through the insertion of zinc powder into the respective alkyl iodide. 42
14
Figure 1.16: Synthesis of organozinc reagents using Rieke zinc 41
The successful synthesis of allylic zinc reagents by Gaudemar 43,44 provided a nucleophilic allylic anion source which was further explored by Knochel et al. 42,45 to prepare novel bimetallic reagents containing both zinc and magnesium that can be reacted sequentially with electrophiles to obtain products of type A (Figure 17). This
Figure 1.17: 1,1-bimetallic reagent 40
1.2.2 Transmetallation reactions of organozinc reagents
In general, organozinc reagents have low reactivity. This can be significantly boosted via transmetallation to give highly reactive transition metal organometallics that show an enhanced reactivity towards a wide variety of carbon electrophiles that otherwise are only moderately reactive in the presence of organozinc reagents. 40,46 The zinc center has empty p-orbitals that enable transmetallation reactions to take place as well as its low lying d-orbitals that enable the coordination and activation of these organic electrophiles.
46 Some of the common metals that have been applied in organozinc transmetallation include copper, cobalt, palladium, nickel and manganese. Zinc cuprates, generally 15 depicted as RCu(CN)ZnX, 47,48 where X is a bromide or iodide have been reacted with acid chlorides under mild conditions to generate polyfunctional ketones (Figure 18).
Allylation reactions, in the presence of these zinc-cuprates, proceed under very mild
o 40 conditions (0-25 C, 0.5-1h) to give highly regioselective SN2 substitution products
(Figure 18). 37,49–51
Figure 1.18: Polyfunctional ketone and SN2 substitution product obtained from zinc cuprates reactions 40
Cross-coupling reactions between palladium (0) and organozinc reagents (Figure 19), pioneered by Negishi, 39,52 have found a wide array of applications. 52–55
16
40 Figure 1.19: Cyclization reaction catalyzed by palladium in presence of Et2Zn
1.2.3 Nature and structure of organozinc reagents
In general organozinc reagents exist in three main classes: i) Organozinc halides, generally represented as RZnX, are easily prepared by the direct insertion of zinc into
42 organic halides; ii) Diorganozincs (R2Zn) that are popularly prepared by iodine/boron-
40,47 zinc exchange method; and iii) Lithium and magnesium zincates (Li/MgXR3Zn), that are more reactive than the organozinc halides or diorganozincs, are easily synthesized by transmetallation reactions. 56–59
Several structures have been observed with organozinc reagents. The diorganozincates (R2Zn) are usually monomeric while their counterpart’s, organozinc halides (RZnX), exist as dimers or higher aggregates through bridging halides (Figure
20). 60 Other higher complex structures have also been reported 61 as shown in the near cubic structure of the organozinc alcoholate shown below (Figure 20).
17
Figure 1.20: Possible structures of organozinc reagents 40
1.3 Green biodegradable polymers
Synthetic polymers are ubiquitous in our daily lives and have found applications in packaging, building materials, agricultural industry, food sector, aerospace, auto industry etc. However, their inability to degrade is a major environmental challenge since they are sourced from fossil fuel, a non-renewable resource, and eventually end up in landfills. In the last two decades or so there has been a steady concerted effort towards seeking an alternative feedstock for polymer synthesis other than from petroleum. This emanates from various factors ranging from the need to curb global warming, reduce environmental pollution as a result of the non-degradable petroleum based plastics and the sustainability of future energy supply. This is also compounded by the uncertainty debate surrounding the petroleum reserves which are predicted to dry out by the end of this century. 62,63 Currently, polymer production is estimated to be in the excess of 230 million tonnes per year 64,65 while the alternative biodegradable polymer production is estimated to be at a 30% annual growth.66 One promising alternative is the use of polyhydroxyl alkanoates 67 that can be derived from bio-renewable resources either through the condensation process or the ring-opening polymerization of cyclic esters.68
Lactide, a monomer derived from corn fermentation (Figure 21), 69 is one promising 18 candidate for substituting the petroleum based polymers. It’s been widely applied in the medical field for bone fixation, 70 a drug delivery agent, 71–73 and tissue engineering scaffold. 74–76 Polylactide has also found use in the cosmetic industry where it has been utilized to encapsulate anti-wrinkle agent retinyl retinoate leading to a faster wrinkle improvement. Other applications include the agricultural and packaging industries.
Figure 1.21: Lactide life cycle 69
Caprolactone is also another promising candidate that can be derived from renewable resources such as biomass (Figure 22). 77 The catalytic conversion of the 5- hydroxymethylfurfural (HMF), that is obtained from biomass, leads to the production of caprolactone as shown in figure 22 below. The homo- and copolymers of caprolactone with lactide have also found a broad application in the medical and pharmaceutical field.
78,79
19
Figure 1.22: Catalytic conversion of 5-hydroxymethylfurfural (HMF) to caprolactone 77
1.3.1 Mechanism for ring-opening polymerization of lactide
The ring-opening polymerization of cyclic esters can take place using organic catalysts, 80,81 enzymes 82,83 or by coordination catalysis 68,69,84,85. The coordination- insertion mechanism for the ring-opening polymerization of lactide is shown in figure 23 below in which case the carbonyl ketonic oxygen of the lactide monomer coordinates onto the metal of the initiator complex. This activates a nucleophilic attack on the ketonic carbon by the metal alkoxide bond which leads to the ring opened monomer insertion into the metal alkoxide bond. 68 A new metal alkoxide bond is generated by the acyl bond cleavage and this serves to propagate the polymerization of incoming new monomers as shown in figure 23.
20
Figure 1.23: Coordination– insertion mechanism; M metal, OR alkoxide group, Ln ligand(s) 68
It is worth mentioning that other competing side reactions namely transesterification, chain transfer and epimerization take place during chain propagation.
Inter-chain transesterification (Figure 1.24) is usually less pronounced during the initial monomer enchainment but as the lactide concentration decreases it becomes more noticeable and likely leads to a broad polymer molecular weight distribution (greater than
1). 69,68 On the other hand, intra-chain transesterification results in the formation of cyclic oligomers that results in the reduction of the overall polymer molecular weight (Figure
1.25). This also leads to a loss of stereoselectivity in cases where meso- or rac-lactide are polymerized resulting from scrambling of the stereocenters along the growing polymer chain.
21
Figure 1.24: Inter-chain transesterification
Figure 1.25: Intra-chain transesterification
There are two ways through which chain transfer takes place; (1) Two metal centers bridged with alkoxides ligands can undergo a bimolecular reaction leading to chain transfer (Figure 1.26 A) (2) addition of an alcohol into an active growing polymer chain attached to a metal center, LnMOP, where OP represents the growing chain, M is metal and L represents the organic ligand (Figure 1.26 B). 69
Figure 1.26: Chain transfer mechanism 68,69
22
Overall a well-controlled polymerization requires that the initiation rate to be greater than the propagation rate. In addition the propagation rate has also to be faster than the chain transfer or termination.68,69
1.3.2 Lactide stereocontrol
Lactide has three stereoisomers, meso-[R,S(D,L)], RR(D)- and SS(L)-lactide, as shown in Figure 1.27 below due to the presence of two stereocenters.86 The rac-lactide is a 50:50 mixture between SS and RR enantiomers.
Figure 1.27: Stereoisomers of Lactide 87
Stereocontrol of lactide, during its polymerization, is important since this will influence the polymers’ mechanical and physical properties, degree of crystallinity, rate of chemical and biological degradation. 88,89 Polymerization of meso-lactide can result in a syndiotactic polymer in which case you have sequential stereocenters of opposite relative configuration (RS)n or an heterotactic polymer in which case you have an (RRSS)n sequence. The heterotactic polymer, amorphous in nature, can also be obtained by the 23 ring-opening polymerization of rac-lactide. On the other hand, syndiotactic polymer is crystalline with a melting point of 170–180oC. 89 A better melting point is observed with the stereocomplex polymer (220–230oC) which is usually obtained from a 1:1 mixture of poly-(L)-LA and poly-(D)-LA. Isotactic polymer is realized from the polymerization of a
D- or L-Lactide while the stereoblock polylactide results from the polymerization of rac- lactide using an initiator with a pre-marked preference for polymerizing the L- or D-
Lactide.90 The various lactide tacticities are shown in Figure 1.28below.
Figure 1.28: Lactide tacticities resulting from ring-opening polymerization69
Two mechanisms exist for lactide stereocontrol; (i) Chain end control - in which case the incoming monomer stereoselectivity is governed by the last enchained monomer.
These systems also tend to incooperate bulky ligands around the active metal center. (ii)
Enantiomeric site control – happens with the use of a chiral initiator (Figure 1.29)
24 whereby the stereochemistry of the incoming lactide is controlled by the chirality of the ancillary ligand.
Figure 1.29: Enantiomeric site control 68
1.3.3 Complexes for lactide ring-opening polymerization (ROP)
The ability to control stereoselectivity of the lactide polymer plays an important role in the design and development of new catalysts. Application of the resulting polylactide will influence choice of the initiator depending on the preferred polymer
91 tacticity. Tin octanoate (Sn(oct)2), a water and moisture stable commercially used catalyst precursor, is a popular choice for the melt ring-opening polymerization of lactide and gives high molecular weight polymer with relatively good molecular weight distribution (PDI). What makes it also attractive is the fact that it does not suffer from ligand scrambling as is the case with many single-site metal-alkoxides. It however lacks the ability for sterecontrol.
Homoleptic and heteroleptic group 3 complexes have also been applied in the
ROP of lactide especially yttrium due to their high polymerization rates. 92 Clusters of the
93 form Ln5( -O)(OR)13 were the first ones to be reported. Yttrium, scandium and lutetium complexes supported with 1,ω-dithiaalkanediyl-bridged bisphenolato (OSSO) 25 ligands were reported by Okuda et. al. which exhibited high heteroselectivity ranging
94,95 from Ps 0.88 to 0.94. Carpentier et. al. reported the first series of group 3 complexes
(Figure 1.30) supported by the amine bis(phenolate) ligand system that has now been widely studied.96–99 This (ONO(O))-type ligand systems (Figure 1.30) have exhibited greater heterotactic selectivity with a Pi of 0.95.
Figure 1.30: Example of amine bis(phenolate) ligand yttrium complex 99
Aluminium complexes have been the most studied among group 13 complexes for the lactide ring opening polymerization. Their high iso-selectivity has contributed to their popularity in these studies although their draw back lies in their slow activity. 100 Various ligand systems have been employed ranging from porphyrin,101 salen 98,102,103 and salan.
104
Divalent homogeneous single-site magnesium, calcium and zinc complexes have also been synthesized and applied in the ROP studies. The polarity of the metal – alkoxide bond is one factor, besides sterics, that influence the reactivity of the complexes.
Single-site metal alkoxide complexes of the form LnMOR are more reactive towards the ring opening polymerization of lactides compared to their dimeric analogues owing to the fact that bridged alkoxides are less nucleophilic. 69 The group 2 complexes (magnesium
26 and calcium) show high activity towards the ROP of lactide but they are not usually kinetically persistent since they are prone to ligand scrambling and catalyst death. 105,106
The adoption of bulky ancillary ligand systems into these complexes can mitigate the ligand scrambling and their deactivation of the active catalyst during polymerization.
This will also limit the complexes, especially for magnesium, from undergoing the
Schlenk equilibrium. The first well defined calcium tris-pyrazolyl borate complexes
(Figure 1.31) 107 were reported by Chisholm et. al. and showed high reactivity and stereoselectivity towards lactide polymerization.106
Figure 1.31: Bulky trispyrazolylborate calcium alkoxide
The pioneering work by Coates et al. employing the anionic bulky ligand 2-[(2,6- diisopropylphenyl)amino]-4-[(2,6-diisopropylphenyl)imino]pent-2-ene (BDIH) to
i develop the zinc alkoxide complex, [(BDI)Zn(OPr )]2, showed in Figure 1.32 below awoke more interest by many other researchers in the lactide polymerization field. 108
This alkoxide showed good activity at room temperature, high stereoselectivity and a narrow molecular weight distribution (PDI = 1.10) towards rac- and meso-lactide.
27
i Figure 1.32: Coates et al. [(BDI)Zn(OPr )]2 complex
The Coates group also synthesized a dimeric β-diiminate magnesium alkoxide
i ([BDIMgO Pr]2) analogue to their zinc alkoxide dimer mentioned above. This exhibited more activity towards the ROP of rac-lactide with 97% conversion in 2 minutes ( [Mg] =
2mM, [LA]/[Mg] = 200) although giving atactic polymer and broad molecular weight distribution (PDI = 1.59).108 At the same time Chisholm et al. reported the monomeric analogue of the magnesium β-diiminate [(BDI)MgOtBu(THF)] 105 showed in Figure 1.33 below which also exhibited good activity with polymerization of 100 equivalence of rac- lactide in 2 minutes. Solvent dependency was also noted in the ROP of rac-lactide whereby atactic polymer was realized in dichloromethane (DCM) as compared to the
90% heterotactic polymer in tetrahydrofuran (THF). Modification of the BDI ligand system with ether appendages on the ortho position of the phenyl group was also carried out by Gibson et al. 109 and Chisholm et al. 110 with activity improvement only noticeable for zinc complexes as compared to earlier reported β-diiminate zinc analogues. Chivers et al. 111,112 also carried out backbone modification on the BDI ligand but the corresponding magnesium complexes showed poor activity, stereocontrol and low molecular weights compared to those earlier reported by Coates 108 and Chisholm 105 groups. 28
Figure 1.33: (BDI)MgOtBu(THF) monomeric structure
1.4 Summary
Substantial progress has been made in the past decade or so towards developing single–site homogeneous catalysts for ring-opening polymerization of cyclic esters.
Polylactide, a popular polymer that is currently widely applied in the medical and pharmaceutical field, has emerged as a good candidate in the search for a sustainable replacement of synthetic polymers derived from petroleum feedstocks. Since polyesters are popularly used as specialty polymers there is a need to develop catalysts that can be industrially viable as far as production cost and polymer properties are concerned. This initiators need to exhibit good stereoselectivity, controlled polymerization with high molecular weight as well as high activity and low toxicity. Group 2 and 12 magnesium and zinc metals respectively have shown good promise as far as activity and controlled lactide polymerization is concerned. These metals are also biocompatible which makes their use attractive towards polymerization of lactides that are applied in the medical and pharmaceutical field unlike the toxic, highly active industrially used catalyst, Sn(Oct)2.
29
We have developed various magnesium and zinc complexes using bulky ancillary ligands and carried out various studies including; (i) Ring-opening polymerization studies of cyclic esters, such as lactide and ε-caprolactone. (ii) Solvent studies using coordinating and non-coordinating solvents. (iii) Dynamic solvent exchange at variant temperatures with the aim of understanding the mechanism of the active species during polymerization process. The magnesium complexes have exhibited much higher activity rates than their zinc counterparts although the latter show better stereocontrol in the ROP of rac-lactide.
These details will be discussed in the coming chapters.
30
CHAPTER 2: METHODS FOR EXPERIMENTS AND GENERAL CONSIDERATIONS
2.1 General considerations
Reactions involving the synthesis of magnesium and zinc complexes as well as their application in the ring opening polymerization of cyclic esters were carried out in a drybox or under standard Schlenk line techniques. All glassware was dried overnight in the oven at 150o C before use in the glovebox. Hexane, tetrahydrofuran, toluene and benzene were distilled under dry nitrogen atmosphere from potassium metal, sodium/benzophenone, sodium metal and calcium hydride respectively. The solvents were stored over 4 Å molecular sieves that were previously dried at 150o C in the oven under vacuum for a minimum of 8 hours. L- and rac-Lactide were purchased from Sigma
Aldrich, sublimed three times, crystalized one time from dry toluene in the freezer and dried overnight at 40o C under vacuum before use. ε-Caprolactone was stirred for several hours over calcium hydride before distilling under vacuum. 1,5,9- trimesityldipyrromethene ligand (TMPH),113 (TMP)Li.THF,113 (TMP)ZnCl,113 β- diiminato ligand (3-[(2,6-diisopropylphenyl)amino]-5-[(2,6-diisopropylphenyl) imino]-
2,2,6,6-tetramethyl-hept-3-ene)(BDI*H),114 BDI*MgBun(THF)114 were synthesized
n according to literature procedures. Di-n-butyl magnesium {( Bu)2Mg, 1 M in heptane}, anhydrous zinc dichloride, 2.5 M nButyl lithium in hexane, tert-butanol, 1.0 M
31 phenethylmagnesium chloride in THF, 1.0 M of diethyl zinc in hexane and diisopropylamide were bought from Sigma Aldrich and used as received. Carbon dioxide was purchased from The BOC Group, Inc and used as received. Benzene-d6, dichloromethane-d2, tetrahydrofuran-d8, and toluene-d8 were purchased from Cambridge
Isotopes and were distilled over calcium hydride under a nitrogen atmosphere and stored over 4 Å molecular sieves prior to use.
2.2 Physical measurements
1 13 H and C NMR spectra were acquired in CD2Cl2, CDCl3, C6D6, toluene-d8 and
THF-d8 on Bruker DPX-400 and 500 MHz NMR spectrometers. These were referenced to the residual protic impurity peaks; (CD2Cl2, δ 5.32; CDCl3, δ 7.26, C6D6, δ 7.16,
1 toluene-d8, δ 2.09 and THF-d8, δ 3.58 for H NMR; and C6D6, δ 128.39; CD2Cl2, δ 53.8,
13 toluene-d8, δ 127.96 and THF-d8, δ 67.21 for C NMR). Gel permeation chromatography
(GPC) analyses were performed using THF as the eluent solvent at 40o C while maintaining a 1mL/min flow rate on a Waters 1525 binary HPLC pump and Waters 2414 refractive index detector equipped with styragel HR 2 and 4 columns (7.8 x 300 mm).
Calibration on the GPC molecular weights was performed using polystyrene standard.
Matrix assisted laser desorption/ionization time-of-flight mass spectroscopy spectra
(MALDI-TOF MS) were recorded using a Bruker Microflex mass spectrometer at 28 kV.
2.3 General procedure for lactide ring-opening polymerization
In the glovebox a Schlenk flask with a magnetic stirrer was charged with lactide
(0.50g, 3.47 mmol) and dissolved with 7.00 mL selected solvents. A second Schlenk
32 flask was charged with the magnesium complexes (0.347 mmol) and dissolved in 3.00 mL toluene. Both flasks were removed from the glovebox and attached to a Schlenk line.
To the lactide solution, at room temperature, was added the magnesium complex solution. Aliquots were taken out of the stirred solution at 1.5 min and 3.0 min and immediately quenched with 1 drop of 0.5 M HCl. The aliquots were then dried under a dynamic vacuum and analyzed by 1H NMR spectroscopy and GPC.
2.4 General procedure for studying the kinetics of rac-lactide polymerization
A Schlenk flask was charged with 0.50 grams rac-lactide in methylene dichloride.
To this solution was added methylene chloride to make the total volume of the reaction equal to 15.00 mL. ([rac-LA]o = 0.23 M) The solution was stirred at room temperature under a nitrogen atmosphere. Then, the equivalence amounts of 0.0350M catalyst initiator in toluene (0.60 – 1.00 mL) was introduced. At appropriate time intervals, 0.5-
1.0 mL aliquots were taken out of the stirred solution and immediately quenched with 1 drop of 0.5 M HCl. The aliquots were then dried under a dynamic vacuum and analyzed by 1H NMR spectroscopy.
2.5 General procedure for studying the kinetics of ε-caprolactone polymerization
A Schlenk flask was charged with 0.60 mL of ε-caprolactone and the calculated amount of methylene dichloride was added to make the final volume of the solution
20.00 mL. ([CL]o = 0.27 M) The solution was stirred at room temperature under nitrogen gas. Then, the equivalence amounts of 0.0350M catalyst initiator in toluene (0.60 – 1.00 mL) was introduced. At the desired time intervals, 0.5-1.0 mL aliquots were removed and
33 quenched with 1 drop of 0.5 M HCl. Solvents were then removed under a dynamic vacuum and analyzed by 1H NMR spectroscopy.
13 2.6 CO2 insertion experiments
The high-pressure NMR tube was charged with a solution of (BDI)MgBun(THF) in toluene-d8 and then was frozen in liq. N2. The frozen tube was evacuated and then
13 dried CO2 was introduced. After carefully warming to room temperature, the NMR spectra were recorded.
2.7 General reactions with alcohols, secondary amines, and ketones
In a Schlenk flask or J-young NMR tube was charged with a solution of the n- butyl magnesium complexes in benzene-d6 or toluene and to these the appropriate amount of alcohol, secondary amine, or ketone was added. The formation of the compound (TMP)Mg(OCHPh2)(THF) was the product in reactions involving either the addition of Ph2C=O or Ph2CHOH. In the case of zinc amide, addition of the alcohols gave the corresponding alkoxides.
2.8 Crystallographic studies
Single crystal X-ray diffraction data were collected on a Nonius KappaCCD diffractometer at low temperature using an Oxford Cryosystems Cryostream Cooler. The crystals were coated with a Fomblin oil due to their air-sensitive nature. A combination of phi and omega scans with a frame width of 1° was used for the data collections. Data
34 integration was done with Denzo,115 and scaling and merging of the data was done with
Scalepack.115 The structures were solved by direct methods in SHELXS-97.116 Full- matrix least-squares refinements based on F2 were performed in SHELXL-97,116 as incorporated in the WinGX package.117 Neutral atom scattering factors were used and include terms for anomalous dispersion.118
35
CHAPTER 3: CONCERNING THE CHEMISTRY OF MAGNESIUM COMPLEXES SUPPORTED BY TMPH = 1,5,9- TRIMESITYLDIPYRROMETHENE AND BDI*H = (3-[(2,6 DIISOPROPYLPHENYL) AMINO]-5-[(2,6-DIISOPROPYLPHENYL) IMINO]-2,2,6,6-TETRAMETHYL-HEPT-3-ENE).
3.1 Introduction
The chemistry of Grignard reagents has become synonymous with organic synthesis for over a century because of the ease with which these reagents can be applied in many synthetic processes. Their broad functional group tolerance, that includes aromatic and heteroaromatic substrates, especially the turbo Grignard reagents have made them very attractive in both the academic and industrial research field.
Our research group is interested in the chemistry of s-block metal complexes of the form LM-OR(solvent), where M = Mg or Ca, as well as well-defined complexes for single-site ring opening polymerization of cyclic esters such as lactide and ε- caprolactone. We have also carried out some reactivity studies with zinc complexes due to the fact that it’s radii is quiet similar to that of Mg2+ (~ 0.80 Å) and so we reasoned that their chemistry should be somewhat similar. Some outstanding work has already been reported for C-H activation of the otherwise relatively inert bonds from the Mulvey and
Strathclyde school of s-block chemistry.119,120 We set out to synthesize, characterize and carry out reactivity studies of single site magnesium complexes supported by bulky bidentate ancilliary ligands. This would render the reagents less susceptible to the 36
Schlenk equilibrium as is the case with Grignard reagents, hence enabling long storage of these compounds in an inert atmosphere or solvent. We reasoned that the use of the ligand, 1,5,9-trimesityldipyrromethene (TMPH)113 and 3-[(2,6-diisopropylphenyl)amino]-
5-[(2,6-diisopropylphenyl)imino]-2,2,6,6-tetramethyl-hept-3-ene(BDI*H)114 would induce stereocontrol in the ring opening polymerization reactions of biodegradable cyclic esters and preferably some stereoselectivity in the ring-opening polymerization of rac- lactide. Preference for the TMPH ligand (Figure 3.1) was driven by the fact that its negative charge is evenly delocalized over its aromatic framework, hence effectively subjecting it to just being a spectator ligand. In comparison, β-diiminato ligand has some resemblance to TMPH ligand framework. However, its negative charge can be localized over one nitrogen or the unprotected β-CH (Figure 3.1) accounting for its known participation in certain reactions.121
Figure 3.1: (A) (TMPH) ligand (B) Resonance structure of β-diiminato ligand
37
3.2 Chemistry of (TMP)MgnBuTHF)
3.2.1 Synthesis of (TMP)MgnBu(THF)
The title compound was prepared at room temperature with the reaction of TMPH
n and approximately 1.20 equivalence of ( Bu)2Mg in THF. An orange powder was realized after removing all the volatiles under dynamic vacuum. Single x-ray crystals were grown overnight from a concentrated hexane solution in the freezer.
3.2.2 Solution NMR studies of (TMP)MgnBu(THF)
The (TMP)MgnBu(THF) showed an unexpected α – proton pattern that deviated from the anticipated usual triplet. This prompted us to investigate other magnesium and zinc alkyl compounds as well containing MgCH2CH2R protons namely
n (TMP)MgCH2CH2Ph(THF) and (TMP)Zn Bu (Figure 3.2). Homonuclear proton decoupling of the butyl group indicated that there is a small long range coupling between the α and γ protons which we anticipated has something to do with the unexpected pattern
1 (Figure 3.3). We initially thought that the complex nature of the Mg-CH2CH2- H signals was due to an effective lack of a mirror plane in the molecule containing the MgC(O) plane and that the spectra arose from an ABXY spin system. Upon simulation, using the topspin program, we soon realized that the best fit occurred as the chemical shifts from A
→ B and X →Y (Figure 3.4). We were confidently able to conclude that the spectrum was a true representation of an AA’XX’ spectrum and only arises when there is a significant thermodynamic preference along the chain for the anti-Mg-CH2CH2-R
38 configuration. This phenomena is not observed in the case where the R = H and hence the
α-CH2 protons assume a simple quartet.
Whitesides et. al122 first observed the AA’XX’ pattern in 3,3–dimethylbutyl chloride and bis (3,3–dimethyl butyl) magnesium. In the former, steric hindrance orients
t the butyl group anti to the chloride atom, hence the –CH2Cl protons become chemically equivalent but magnetically unequivalent. This makes them couple differently to the –
CH2C(CH3)3 protons hence accounting for the AA’XX’ pattern.
Figure 3.2: Expanded α – proton region of the magnesium and zinc alkyl complexes shoeing a AA’XX’ pattern.
39
Figure 3.3: Homonuclear decoupled 1H NMR spectra of (TMP)MgnBu(THF) showing the α-protons region.
40
Figure 3.4: Simulation of (TMP)MgBun(THF) α-protons using the topspin program. Long range coupling of the α to γ protons was evident although with a small J-coupling (L = TMP ligand)
3.2.3 Reaction of (TMP)MgnBu(THF) with benzophenone and diphenyl methanol
(TMP)MgnBu(THF) was reacted with benzophenone and diphenyl methanol with the aim of probing its reactivity. Both reactions were carried out in a J-young tube. The reaction with benzophenone proceeds with the β – hydrogen transfer resulting in the formation of an alkene (1- butene) (Figure 3.5). This can be viewed as going through a six-membered ring transition state (Figure 3.6). On the other hand, reaction of
(TMP)MgnBu(THF) with diphenyl methanol initiates with the C-Mg bond attacking the hydroxyl group of the alcohol. The hydrogen abstraction leads to the formation of butane and an alkoxide (Figure 3.7).
41
Figure 3.5: 1H NMR showing products of the reaction between (TMP)MgnBu(THF) and benzophenone.
Figure 3.6: Six-membered ring transition state for β–hydrogen transfer
42
Figure 3.7: 1H NMR showing products of the reaction between (TMP)MgnBu(THF) and diphenyl methanol.
43
3.2.4 Reactions of (TMP)MgnBu(THF) with lactide
The ring opening polymerization of rac-lactide can initiate via the magnesium- carbon bond of the butyl group attack to the carbonyl carbon of the lactide (route 1 in
Figure 3.8) giving an nBu end group or through a β-hydrogen atom transfer (route 2 in
Figure 3.8) that leads to a hydrogen end group on the polymer chain (Figure 3.8). In the case of (TMP)MgnBu(THF), NMR evidence clearly supported the ring opening polymerization of lactide proceeding via β-hydrogen atom transfer to give poly-L-lactide and generation of 1-butene (Figure 3.9). These results are reminiscent of the ketone
(benzophenone) reactions discussed in the previous section where 1-butene is generated along with (TMP)Mg(OCHPh2)THF. Reactions of n-butyl Grignard reagents with ketones,
especially of the kind Ph2CO, are well known to proceed via β-hydrogen atom transfer to the ketonic carbon and not by C-C bond formation. However, these reactivities with lactides have not been widely published.
Figure 3.8: Possible routes for the ring-opening polymerization of lactide
44
Figure 3.9: 1H NMR evidence for the lactide ROP mechanism via β-hydrogen transfer using (TMP)MgnBu(THF). 1-Butene is generated upon the ring-opening polymerization of lactide.
3.2.5 Reactions of (TMP)MgnBu(THF) with carbon dioxide
The reactions of (TMP)MgnBu(THF) with carbon dioxide was studied only in
13 high-pressure NMR tubes where CO2 was introduced to an initially frozen solution of the n-butylmagnesium complex in toluene-d8. These reactions proceeded very rapidly and
1H NMR spectroscopy (Figure 3.10 and Figure 3.11) revealed the disappearance of the α-
13 CH2 proton resonances of the n-butyl ligand together with the appearance of a C signal in the 13C{1H} NMR spectrum at δ ~ 180 ppm typical of a carboxylate C-13 resonance
13 and supportive of the formation of the pentanoate ligand O2 CCH2CH2CH2CH3. We
n were not able to isolate any compound of the formula (TMP)MgO2CBu (THF).
45
n 13 Figure 3.10: (TMP)Mg Bu(THF) reaction with CO2
THF THF α 13 β & γ After CO2 Insertion δ
δ
THF THF
γ Before 13CO Insertion 2 α β
3.5 3.0 2.5 2.0 1.5 1.0 0.5 0.0 -0.5 -1.0 ppm
Figure 3.11: 1H NMR for (TMP)MgnBu(THF) showing the butyl region before and after 13 13 CO2 insertion. Notice the α - proton signal after CO2 insertion attains a normal triplet.
46
3.3 Single X-ray crystallographic studies
3.3.1 (TMP)MgnBu(THF)
An ORTEP drawing showing the molecular structure of compound 1 is given in
Figure 3.12. Selected bond distances and angles are given in Table 3.1. The structure has a distorted tetrahedral geometry about the magnesium centre. The ligand’s
N(1)MgN(2)C(6)C(5)C(4) plane is perpendicular to the Mg-OTHF axis. The mesityl groups on C1 and C9 appear to be perpendicular to the N(1)MgN(2)C(6)C(5)C(4) plane forming a tight pocket around the magnesium centre. Part of the THF ligand is disordered along C(41), C(42) and C(15) with angles C(41)-C(42a)-C(43a) and C(44a)-C(43a)-
C(42a) at 100.7(7)o and 101.9(7)o respectively. The bond distances of Mg-N(1), Mg-
N(2), Mg-OTHF and Mg-C(37) are comparable from 2.0557(15)Å to 2.122(2)Å. The N(1)-
Mg-N(2) angle associated with the ligand is 89.97(6)o, while angles of N(1)-Mg-C(37) and N(2)-Mg-C(37) are 130.49(8)o and 130.87(8)o respectively. Summation of the three angles gives a total of 351o indicating a significant distortion from the tetrahedral geometry of 328.5o.
47
Figure 3.12: ORTEP drawing of (TMP)MgnBu(THF) with thermal ellipsoids drawn at the 50% probability level. The structure shows a distorted tetrahedral geometry about the Mg metal centre. All hydrogen atoms are omitted for clarity
48
Table 3.1: Selected bond distances (Å) and Angles (o) for (TMP)MgnBu(THF)
A B Distance (Å) A B C Angle (º)
Mg N1 2.0841(16) N1 Mg N2 89.97(6)
Mg N2 2.0808(16) N1 Mg C37 130.49(8)
Mg C37 2.122(2) N1 Mg O 96.13(6)
Mg O 2.0557(15) N1 C1 C10 118.86(16)
C41 O 1.450(2) N1 C4 C5 125.07(16)
C44a O 1.424(19) N2 Mg C37 130.87(8)
C43a C44a 1.505(8) O Mg N2 97.70(6)
C41 C42a 1.505(6) N2 C9 C28 119.82(17)
C42a C43a 1.515(9) N2 C6 C5 124.93(17)
C4 N1 1.395(2) C38 C37 Mg 124.56(17)
C6 N2 1.401(2) C44a O Mg 124.6(5)
C4 C5 1.402(3) C41 O Mg 125.49(12)
C5 C6 1.401(2) O Mg C37 103.04(8)
C37 C38 1.502(3) C37 C38 C39 115.6(2)
C38 C39 1.566(3) C40 C39 C38 112.8(2)
C39 C40 1.480(4) Mg N1 C1 125.85(13)
Mg N2 C9 127.49(13)
C6 C5 C4 127.60(17)
C41 C42a C43a 100.7(7)
C42a C43a C44a 101.9(7)
49
Table 3.2: Data collection parameters for (TMP)MgnBu(THF)
Formula C44 H54 Mg N2 O Formula weight 651.20 Temperature 180(2) K Wavelength 0.71073 Å Crystal system triclinic Space group P1 Unit cell dimensions a = 9.3070(1) Å = 87.957(1)° b = 11.3957(1) Å = 81.710(1)° c = 19.4004(2) Å = 71.960(1)° Volume 1935.92(3) Å3 Z 2 Density (calculated) 1.117 Mg/m3 Absorption coefficient 0.080 mm-1 F(000) 704 Crystal size 0.15 x 0.19 x 0.31 mm3 Theta range for data collection 2.12 to 25.04° Index ranges -11<=h<=11, -13<=k<=13, -23<=l<=23 Reflections collected 50524 Independent reflections 6839 [R(int) = 0.046] Completeness to theta = 25.04° 99.9 % Refinement method Full-matrix least-squares on F2 Data / restraints / parameters 6839 / 27 / 462 Goodness-of-fit on F2 1.038 Final R indices [I>2sigma(I)] R1 = 0.0491, wR2 = 0.1284 R indices (all data) R1 = 0.0846, wR2 = 0.1470 Largest diff. peak and hole 0.339 and -0.214 e/Å3
50
3.3.2 (TMP)MgOtBu(THF)
An ORTEP drawing showing the molecular structure of
(TMP)MgOtBu(THF) is given in Figure 3.14. Selected bond distances and angles are given in Table 3.3. It’s interesting to note that besides the main magnesium complex, two solvent molecules of THF were crystalized in the asymmetric unit. Several similarities and slight differences can be compared with the (TMP)MgnBu(THF) structure. The Mg-
OTHF bond distance is 2.044(17)Å which is slightly shorter to that of Mg-C in
(TMP)MgnBu(THF). The (TMP)MgOtBu(THF) N(1) – Mg and N(2) – Mg bond distances are 2.067(18)Å and 2.066(18) respectively, which again is slightly shorter to the corresponding (TMP)MgnBu(THF) bond distances. The structure adopts a distorted tetrahedral geometry about the magnesium centre. The C(1)N(1)C(4)C(5)C(6)N(2)C(9) plane appears to be planar while the mesityl groups on C(1), C(5) and C(9) are perpendicular to the N(1)-Mg-N(2)-C(6)-C(5)-C(4) plane. The arrangement of the aryl ligands crowd the THF and OBut ligands which most likely is responsible for the much larger Mg-O(1)-C(37) angle of 164o and a smaller N(2)-Mg-O(2) angle of 97.78o. Angles associated with N(1)-Mg-N(2), N(1)-Mg-O(1) and N(2)-Mg-O(1) are 92.41(7)o,
124.03(8)o and 124.36(8)o, respectively. The summation of this three angles is 340o indicating somewhat a significant distortion from the normal tetrahedral geometry.
A close resemblance exist between (TMP)MgOtBu(THF) and
(BDI)MgOtBu(THF)105 synthesized by our group. The two compounds bond distances of
Mg – N, Mg – OTHF and Mg – OtBu are almost perfectly equal. The N – Mg – N angles of
(TMP)MgOtBu(THF) and (BDI)MgOtBu(THF) are 92.41(7)o and 92.20(9)o respectively.
51
Figure 3.13: ORTEP drawing of (TMP)MgOBut(THF) with thermal ellipsoids drawn at the 50% probability level. All hydrogen atoms are omitted for clarity.
52
Table 3.3: Selected Bond distances (Å) and Angles (o) for (TMP)MgOBut(THF)
A B Distance (Å) A B C Angle (º)
N1 Mg 2.067(18) N2 Mg N1 92.41(7)
N2 Mg 2.066(18) O1 Mg N1 124.03(8)
Mg O1 1.804(18) O2 Mg N1 98.80(7)
Mg O2 2.044(17) N2 Mg O1 124.36(8)
C6 N2 1.402(3) N2 Mg O2 97.78(7)
C4 N1 1.400(3) O1 Mg O2 113.67(9)
C4 C5 1.404(3) Mg O2 C44 128.33(16)
C5 C6 1.401(3) C41 O2 Mg 123.27(14)
C9 N2 1.342(3) C37 O1 Mg 163.66
C9 C28 1.487(3) C43 C44 O2 107.6(3)
C1 N1 1.343(3) O2 C41 C42 105.6(2)
C1 C10 1.490(3)
C41 O2 1.456(3)
C44 O2 1.434(3)
C41 C42 1.498(4)
C42 C43 1.455(5)
C43 C44 1.425(4)
53
Table 3.4: Data collection parameters for (TMP)MgOtBu(THF)
Formula C44 H54 Mg N2 O2 · 2(C4 H8 O) Formula weight 811.41 Temperature 180(2) K Wavelength 0.71073 Å Crystal system monoclinic
Space group P21/c Unit cell dimensions a = 18.1220(2) Å b = 14.9771(2) Å c = 18.2681(2) Å = 103.969(1)° Volume 4811.60(10) Å3 Z 4 Density (calculated) 1.120 Mg/m3 Absorption coefficient 0.081 mm-1 F(000) 1760 Crystal size 0.15 x 0.35 x 0.38 mm3 Theta range for data collection 2.27 to 25.05° Index ranges -21<=h<=21, -17<=k<=17, -21<=l<=21 Reflections collected 77883 Independent reflections 8489 [R(int) = 0.055] Completeness to theta = 25.05° 99.5 % Refinement method Full-matrix least-squares on F2 Data / restraints / parameters 8489 / 31 / 563 Goodness-of-fit on F2 1.028 Final R indices [I>2sigma(I)] R1 = 0.0602, wR2 = 0.1608 R indices (all data) R1 = 0.1069, wR2 = 0.1876 Largest diff. peak and hole 0.508 and -0.244 e/Å3
54
3.4 Ring-opening polymerization studies of lactide
Our study of the ring-opening polymerization (ROP) of lactide showed that all the
(TMP)MgnBu(L) and (BDI*)MgnBu(L) series, where L = THF, 2-MeTHF, pyridine and
4-dimethylaminopyridine (DMAP), are effective initiators for lactide polymerization
(Table 3.5 and Table 3.6). The (TMP)MgnBu(L) series exhibited preference for forming heterotactic polylactide in the ring-opening polymerization of rac-lactide with Pr (defined as the percentage fractional probability of forming the heterotactic tetrads isi/sis) values ranging from 96% – 98% in THF and 72% – 80% in DCM solvent. However, the
(BDI*)MgnBu(L) series complexes exhibited no stereoselectivity towards rac-Lactide in
DCM giving only atactic poly-l-lactide. A slight improvement was only noticeable for
BDI*MgnBu(THF) when 100 and 1000 equivalence of THF was added in which case the
Pr improved from 50% to 59% and 65% respectively (Table 3.6). These observations for
(BDI*)MgnBu(THF) are different from those that we earlier observed in our research group when using (BDI)MgnBu(THF) as an initiator for the ring-opening polymerization of rac-lactide in which case the addition of 50 to 1000 equivalence of THF led to a big
20 jump in stereoselectivity with Pr values of 68% to 95% respectively. Addition of 100 to
1000 equivalence of THF into the polymerization reaction of rac-lactide using
n (TMP)Mg Bu(THF) as an initiator also led to a slight improvement in the Pr values from
80% to 86% and 89% respectively.20 The BDI* supported catalysts systems are also roughly 1.5 times as fast as the TMP supported catalyst systems.
The above observations can be explained in part due to the fact that the TMP ligand bite angle about the metal center is statistically smaller than that of BDI* or BDI
55 ligand. The arrangement of the aryl groups of these ligands is different too with the TMP mesityl groups asserting more steric influence as compared to the 2,6-diisopropylphenyl groups in BDI or BDI*. This can be seen in the more constrained Mg-CH2CH2CH2CH3 structure of (TMP)MgnBu(THF) (see Figure 3.1). Regarding the
(BDI)/(BDI*)MgnBu(THF) and (TMP)MgnBu(THF), a closer approach for looking into the different steric influence of the two ligands on the “pocket’ in which the nBu and THF ligands lie is by superposition of the two molecules (see Figure 3.14). From the superposition, we can assert that the steric influence of the TMP supported catalyst system has a lot to do with the stereoselectivity of rac-lactide. The contrary is also true as far as the rate of ring-opening polymerization is concerned in which case the BDI supported catalyst systems show a faster rate due to the fact that the incoming monomer substrate can easily access the metal active site as compared to the constrained pocket of the TMP supported catalyst system. In general, the ROP of lactide was relatively slower in neat THF as compared to DCM. This is due to the fact that THF, a coordinating solvent, competes with the lactide monomer in coordinating to the active metal centre hence resulting in the slow polymerization process.
The polymer molecular weights were also determined by gel permeation chromatography (gpc). The Mn values, even when corrected by the factor of 0.58, were still higher than those calculated based on % monomer consumption. This we believe emanates from the decomposition of the reactive n-butylmagnesium complexes (see
Table 3.5). Homonuclear decoupled 1H NMR spectra are shown in Table 3.8.
56
Table 3.5: rac-LA polymerization by (TMP)MgnBu(L) ([Cat.] = 3.47mM, [LA]o/[Cat.] = 100, at 25 oC)
57
Table 3.6: rac-LA polymerization by (BDI*)MgnBu(L) ([Cat.] = 3.47mM, [LA]o/[Cat.] = 100, at 25 oC)
58
Table 3.7: rac-LA polymerization by (TMP)MgnBu(THF) ([Cat.] = 3.47mM, [LA]o/[Cat.] = 100, at 25 oC)
59
Figure 3.14: Best superposition of the molecular structures of (BDI*)MgBun(THF) in green and (TMP)MgBun(THF) in red showing the relative disposition of the aryl ligands and the greater steric pressure of mesityl groups in the pyrromethene ligand, TMP, on the pocket of the n-butyl group
60
Table 3.8: Selected normal and homonuclear decoupled 1H NMR spectra of poly-rac- lactide
A. A. Normal 1H NMR for poly-rac-lactide obtained from ROP of rac-LA in neat THF using initiator (TMP)MgnBu(THF)
B. Homonuclear decoupled B 1H NMR spectra for poly-rac-lactide (A above) obtained from ROP of rac-LA in neat THF using initiator (TMP)MgnBu(THF) with a Pr of 0.96
C C. Homonuclear decoupled 1H NMR spectra for poly-rac-lactide obtained from ROP of rac-LA in neat DCM using initiator (BDI*)MgnBu(THF) with Pr of 0.50
D D. Homonuclear decoupled 1H NMR spectra for poly-rac-lactide obtained from ROP of rac-LA in 100 equivalence THF in DCM using initiator (BDI*)MgnBu(THF) with Pr of 0.65
61
3.5 Kinetics studies of lactide and ε-caprolactone using (TMP)MgnBu(L) and
(BDI*)MgnBu(L) where L = THF, 2-MeTHF, Py, DMAP
The kinetics study usually sheds light into the rates of various catalytic initiators and may give us insight into the design and development of more active catalysts. This also does assist in determining the order of the initiators and substrates involved in a reaction as illustrated in Figure 3.15 below where one can either determine the rate of the catalyst by either monitoring the kapp or kp = propagation rate as well as x = order of the reaction.
Figure 3.15: Kinetics expression
We monitored the rate of ring-opening polymerization of rac-lactide and ε- caprolactone using (TMP)MgnBu(L) and (BDI*)MgnBu(L) where L = THF, 2-MeTHF, pyridine and 4-dimethylaminopyridine (DMAP). The effect of changing the ligand L was noticeable in the difference of the kapp values as shown in Figure 3.16, Figure 3.17, Figure
3.18 and Figure 3.19 and summarized in Table 3.9 and Table 3.10. The polymerization rates followed the trend in the order of (TMP)MgnBu(2-MeTHF) > (TMP)MgnBu(THF)
62
> (TMP)MgnBu(Py) > (TMP)MgnBu(DMAP). This order was also observed in the case of BDI19 and BDI* (Figure 3.18 and Figure 3.19) supported catalyst systems although the rates of polymerization for (BDI*)MgnBu(2-MeTHF) and (BDI*)MgnBu(THF) was almost the same with very small deviation. The rate of polymerization for ε-caprolactone was also faster compared to that of lactide in the BDI/BDI* and TMP supported catalyst systems.
Figure 3.16: Semilogarithmic plots of rac-Lactide conversion with time in CH Cl at 25 2 2 o n C with (TMP)Mg Bu(L)
63
n Table 3.9: Summary of kapp for the ROP of rac-LA in DCM. (TMP)Mg Bu(L) = 2.33mM, rac-LA = 0.14M
Figure 3.17: Semilogarithmic plots of ɛ-caprolactone conversion with time in CH Cl at 2 2 o n 25 C with (TMP)Mg Bu(L)
64
Table 3.10: Summary of kapp for the ROP of ɛ-Caprolactone in DCM using (TMP)MgnBu(L)
Figure 3.18: Semilogarithmic plots of rac-Lactide conversion with time in CH Cl at 25 2 2 o n C with (BDI*)Mg Bu(L)
65
Figure 3.19: Semilogarithmic plots of ɛ-Caprolactone conversion with time in CH Cl at 2 2 o n 25 C with (BDI*)Mg Bu(L)
3.6 Synthesis and characterization
(TMP)MgnBu(THF): In a 25ml Schlenk flask TMPH (0.93 g, 1.87 mmol) was dissolved with THF (15 mL). From another Schlenk flask di-n-butylmagnesium (2.25 ml,
2.15 mmol) was added dropwise via cannula immediately changing reaction color from light to dark orange. The reaction was stirred for 5 h at room temperature then THF was removed under dynamic vacuum to give an orange solid. Washing with hexane precipitated out the product as an orange powder. Cannula filtration and drying under vacuum afforded the product in quantitative yield. Fine crystals were obtained from a
1 concentrated hexane solution left overnight in the freezer. H NMR (400 MHz, C6D6):
6.88 (s, 6H, meta-C6H2(CH3)2), 6.78 (d, JHH = 4 Hz, 2H, pyrrole C-H), 6.21 (d,
66
JHH = 4 Hz, 2H, pyrrole C-H), 3.38 (m, 4H, THF), 2.30 (s, 6H, para-C6H2(CH3)3), 2.27
(s, 3H, para-C6H2(CH3)3), 2.24 (s, 12H, ortho-C6H2(CH3)3), 2.20 (s, 6H, ortho-
n C6H2(CH3)3), 1.36 (m, 2H, γ-CH), 1.17 (m, 4H, THF), 1.36 (m, 2H, γ-Bu ), 1.07 (t, 3H, δ-
n n n 13 Bu ), 1.02 (m, 2H, β-Bu ), -0.51 (AA’XX’Y, 2H, α-Bu ). C NMR (400 MHz, C6D6):
162.25, 146.86, 141.35, 137.87, 137.37, 137.20, 134.52, 132.47, 119.48, 69.16, 33.17,
32.79, 25.71, 21.78, 21.07, 20.49, 14.77, 7.33.
(TMP)Mg(CH2CH2Ph)THF, 2: (TMP)Li.THF (0.220 g, 0.384 mmol) was dissolved with 10 ml toluene in a 25 ml Schlenk flask. In another flask
(PhCH2CH2)MgCl (0.46 ml, 0.461 mmol) was mixed with toluene (10 ml). Both flasks were partially frozen in liquid nitrogen. (PhCH2CH2)MgCl thawing solution was dropwise added to the thawing solution of (TMP)Li.THF. Mixture was stirred for 4 h at room temperature. The solvent was removed in vacuo to give a deep orange solid.
Washing with benzene extracts the product and precipitates out LiCl. Solvent was removed in vacuo to give a bright orange solid (0.231g, 86.5%). X-ray single crystals were grown by placing a concentrated toluene solution in a freezer. 1H NMR (400 MHz,
C6D6): 7.26-7.28 (m, 2H, ortho-ArH), 7.32-7.35 (m, 3H, meta and para- ArH), 6.89 (s,
6H, meta-C6H2(CH3)2), 6.78 (d, JHH = 4 Hz, 2H, pyrrole C-H), 6.22(d, JHH = 4 Hz, 2H, pyrrole C-H), 3.30 (m, 4H, THF), 2.33-2.38 (m, 2H, β-CH), 2.29 (s, 6H, para-C6H2(CH3)3), 2.28 (s, 3H, para-C6H2(CH3)3), 2.24 (s, 6H, ortho-C6H2(CH3)3), 2.22
(s, 12H, ortho-C6H2(CH3)3), 1.16 (m, 4H, THF), -0.636 to -0.592 (m, 2H, α-CH).
67
(TMP)MgOBut(THF): (TMP)MgnBu(THF) (0.30 g, 0.461 mmol) was dissolved in 10 ml THF. tBuOH (44 µl, 0.461 mmol) was mixed with THF (5 ml) in a separate flask before adding it dropwise into the solution of compound 1. The overall mixture was stirred for 1 h at room temperature. Solvent removal under dynamic vacuum pump affords an orange solid in quantitative yield. X-ray-suitable single crystals were grown from a concentrated solution of THF placed in the freezer overnight. 1H NMR (400 MHz,
C6D6): 6.88 (s, 6H, meta-C6H2(CH3)2), 6.76 (d, JHH = 4 Hz, 2H, pyrrole C-H), 6.18 (d,
JHH = 4 Hz, 2H, pyrrole C-H), 3.46 (m, 4H, THF), 2.29 (s, 18H, ortho-C6H2(CH3)3), 2.27
(s, 3H, para-C6H2(CH3)3), 2.23 (s, 6H, para-C6H2(CH3)3), 1.18 (m, 4H, THF), 0.99 (s,
t 13 9H, OBu ). C NMR (400 MHz, C6D6): 162.47, 146.75, 141.67, 137.98, 137.81, 137.54,
137.37, 137.22, 134.68, 132.80, 119.89, 69.41, 35.51, 25.60, 21.54, 21.28, 20.49, 1.75
(TMP)MgnBu(Py): A 50ml Schlenk flask with a stir bar was charged with
TMPH (0.60 g, 1.20 mmol) along with 20ml toluene inside the glovebox. In another 25ml
Schlenk flask di-n-butylmagnesium (1.32 ml, 1.10 equivalence) was added. Both flasks were connected to the Schlenk line and the di-n-butylmagnesium was added dropwise via cannula to the TMPH solution and let to stir for 15 minutes. Pyridine (97 µl, 1.20 mmol) was then added to the reaction mixture using a micro syringe. The reaction was let to stir for another hour before removing all the volatiles under dynamic vacuum to give a bright orange powder in quantitative yield. This was washed one time with 5 ml hexane. Single x-ray crystals were obtained overnight from a concentrated toluene solution in the
1 freezer. H NMR (400 MHz, toluene d8): 8.12 (m, 2H, py), 6.91 (m, 2H, meta-
68
C6H2(CH3)2), 6.84 (d, 2H, pyrrole C-H), 6.77 ( m, 1H, py), 6.78 (s, 4H, meta-
C6H2(CH3)2), 6.44 (m, 2H, py), 6.20 (d, 2H, pyrrole C-H), 2.37 (s, 6H, ortho-
C6H2(CH3)3), 2.28 (s, 3H, para-C6H2(CH3)3), 2.16 (s, 6H, para-C6H2(CH3)3), 1.98 (m,
n n n 12H, ortho-C6H2(CH3)3), 1.46 (m, 2H, γ-Bu ), 1.22 (m, 2H, β-Bu ), 1.11 (t, 3H, δ-Bu ), -
0.51 (2H, α-Bun).
(TMP)MgnBu(DMAP): In the glovebox, a 50ml Schlenk flask with a stir bar was charged with TMPH (1.02 g, 2.05 mmol) along with 20 ml toluene. In another 25ml
Schlenk flask di-n-butylmagnesium (2.05 ml, 1.00 equivalence) was added. Both flasks were connected to the Schlenk line and the di-n-butylmagnesium was was added dropwise via cannula to the TMPH solution and let to stir for 30 minutes. DMAP (0.25 g,
2.05 mmol) previously dissolved in a 5 ml toluene was then transferred via cannula to the
n (TMPMg Bu)2 solution. The reaction was let to stir for another hour before removing all the volatiles under dynamic vacuum to give a light orange powder in quantitative yield.
This was washed one time with 5 ml hexane. Single x-ray crystals were obtained overnight from a concentrated toluene solution in the freezer. 1H NMR (400 MHz, toluene d8): 7.81 (m, 2H, DMAP), 6.89 (m, 2H, meta-C6H2(CH3)2), 6.79 (s, 4H, meta-
C6H2(CH3)2), 6.77 (d, 2H, pyrrole C-H), 6.20 (d, 2H, pyrrole C-H), 5.85 (m, 2H, DMAP),
2.42 (s, 6H, ortho-C6H2(CH3)3), 2.29 (s, 3H, para-C6H2(CH3)3), 2.21 (s, 6H, DMAP),
n 2.15 (m, 6H, para-C6H2(CH3)3), 2.05 (s, 12H, ortho-C6H2(CH3)3), 1.35 (m, 2H, γ-Bu ),
1.13 (m, 2H, β-Bun), 1.06 (t, 3H, δ-Bun), -0.6340 (2H, α-Bun).
69
(TMP)MgnBu(Py): A 50ml Schlenk flask with a stir bar was charged with
TMPH (0.60 g, 1.20 mmol) along with 20ml toluene inside the glovebox. In another 25ml
Schlenk flask di-n-butylmagnesium (1.32 ml, 1.10 equivalence) was added. Both flasks were connected to the Schlenk line and the di-n-butylmagnesium was was added dropwise via cannula to the TMPH solution and let to stir for 15 minutes. Pyridine ( 97
µl, 1.20 mmol) was then added to the reaction mixture using a micro syringe. The reaction was let to stir for another hour before removing all the volatiles under dynamic vacuum to give a bright orange powder in quantitative yield. This was washed one time with 5 ml hexane. Single x-ray crystals were obtained overnight from a concentrated
1 toluene solution in the freezer. H NMR (500 MHz, THF-d8): 8.50 (2H, o-H Pyridine),
7.65 (p, 1H, Py), 7.24 (m, 2H, m-H Pyridine), 6.96 (m, 2H, meta-C6H2(CH3)2), 6.82 (m,
4H, meta-C6H2(CH3)2), 6.48 (d, 2H, pyrrole C-H), 6.11 (d, 2H, pyrrole C-H), 2.36 (s, 3H, para-C6H2(CH3)3), 2.23 (s, 6H, ortho-C6H2(CH3)3), 2.17 (s, 6H, para-C6H2(CH3)3), 2.06
n n (m, 12H, ortho-C6H2(CH3)3), 0.77 (m, 2H, γ-Bu ), 0.58 (t, 3H, δ-Bu ), 0.57 (m, 2H, β-
Bun), -1.33 (2H, α-Bun).
* n * n (BDI )Mg Bu(2-MeTHF): A mixture of BDI H (1 g, 1.99 mmol) and ( Bu)2Mg
(2.60 ml, 1.30 equivalence) in pentane was refluxed for 6 hours and let to cool down for atleast 1 hour. Approximately 10 equivalence of 2-MeTHF was added via a syringe at room temperature and the reaction mixture was allowed to stir for another 1 hour before removing all the solvent under vacuum affording the title compound as a yellow solid in quantitative yield. Single x-ray crystals were grown from a concentrated pentane solution
70
o 1 at -23 C. H NMR (400 MHz, toluene-d8, 27°C): 6.97 (m, 6H, ArH), 5.35 (s, 1H, β-CH),
3.80 (m, 1H, 2-MeTHF), 3.73 (m, 1H, 2-MeTHF), 3.53 (m, 1H, 2-MeTHF), 3.27 (m, 4H,
n CHMeMe`), 1.61 (m, 4H, 2-MeTHF), 1.50 (m, 2H, β-Bu ), 1.29 (d, 12H, CHMe2), 1.26
(d, 12H, CHMe2`),1.17 (s, 18H, (α-CMe3)2), 1.13 (d, 3H, 2-MeTHF), 1.11 (m, 2H, γ-
Bun), 0.79 (t, 3H, δ-Bun), -0.67 (2H, α-Bun)
* n * n (BDI )Mg Bu(DMAP): A mixture of BDI H (1 g, 1.99 mmol) and ( Bu)2Mg
(2.60 ml, 1.30 equivalence) in pentane was refluxed for 6 hours and let to cool down for atleast 1 hour. DMAP (0.31 g, 2.59 mmol) previously dissolved in pentane in another schlenk flask was transferred via cannula at room temperature to the main reaction mixture flask and allowed to stir for another 1 hour before removing all the solvent under vacuum affording the title compound as a bright orange solid in quantitative yield. Single x-ray crystals were grown from a concentrated pentane solution at -23o C. 1H NMR (500
MHz, toluene-d8, rt.): 8.48 (br, 2H, o-H DMAP), 7.04 (m, 6H, ArH), 5.95 (d, 2H, m-H
DMAP), 5.48 (s, 1H, β-CH), 3.57 (br, 2H, CHMeMeʹ), 3.14 (br, 2H, CHMeMeʹ), 2.06 (s,
6H, CH3 DMAP), 1.55 (d, 12H, CHMe2), 1.52 (d, 12H, CHMe2), 1.33 ( br singlet, 18H,
n n n (α-CMe3)2), 1.22 (m, 2H, β-Bu ), 1.21 (m, 2H, γ-Bu ), 0.931 (t, 3H, δ-Bu ), -0.378
(AAʹXXʹY, 2H, α-Bun).
* n * n (BDI )Mg Bu(Py): A mixture of BDI H (1 g, 1.99 mmol) and ( Bu)2Mg (2.60 ml, 1.30 equivalence) in pentane was refluxed for 6 hours and let to cool down for at least
1 hour. Approximately 3 equivalence of pyridine was added via a microsyringe at room
71 temperature and the reaction mixture was allowed to stir for another 1 hour before removing all the solvent under dynamic vacuum affording the title compound as a orange solid in quantitative yield. Single x-ray crystals were grown from a concentrated pentane solution at -23o C. 1H NMR (500 MHz, toluene-d8, rt.): 8.78 (br, 2H, o-H Pyridine), 7.09
(br, 1H, p-H Pyridine), 6.99 (m, 6H, ArH), 6.61 (m, 2H, m-H Pyridine), 5.45 (s, 1H, β-
CH), 3.16 (br, 4H, CHMeMeʹ), 1.23 (d, 12H, CHMe2), 1.21 (d, 12H, CHMe2), 1.20 ( br
n n n singlet, 18H, (α-CMe3)2), 1.08 (m, 2H, β-Bu ), 1.07 (m, 2H, γ-Bu ), 0.882 (t, 3H, δ-Bu ),
-0.421 (AAʹXXʹY, 2H, α-Bun).
(BDI*)MgOtBu(THF): A 50ml Schlenk flask with a stir bar was charged with
(BDI*)MgnBu(THF) (1.00 g, 1.53 mmol) along with 25 ml THF inside the glovebox. This flask was attached to the Schlenk line and tBuOH (0.18 ml, 1.84 mmol) was added dropwise using a 1 ml syringe. The reaction was allowed to stir for two hours before removing all the volatiles under dynamic vacuum affording the title compound as an off-
1 white solid in quantitative yield. H NMR (400 MHz, toluene-d8, 27°C): 7.04 (m, 6H,
ArH), 5.28 (s, 1H, β-CH), 3.93. (m, 4H, O(CH2CH2)2), 3.29 (sept, 4H, CHMeMe`), 1.45
(m, 4H, O(CH2CH2)2), 1.42 (d, 12H, CHMe2), 1.36 (d, 12H, CHMe2`), 1.14 ( br singlet,
18H, (α-CMe3)2), 0.86 (s, 9H, O(CMe3)).
72
CHAPTER 4: COMPARATIVE STUDY PERTAINING TO THE REMARKABLE ROLE OF SOLVENT, THF VERSUS DICHLOROMETHANE, IN THE RING-OPENING POLYMERIZATION OF LACTIDE AND ε- CAPROLACTONE BY MAGNESIUM AND ZINC CATALYSTS
4.1 Introduction
In this study of the ring-opening polymerization of cyclic esters, we employed the use of the s-block elements, such as magnesium, which are notably kinetically labile in solution hence posing a challenge in regards to their synthesis and application of single- site metal promoted catalysts. The metal ligand interactions are essentially electrostatic and directional covalent bonds, as in transition metal chemistry, are not formed. The geometry as well as coordination number are largely determined by steric factors associated with ligands encapsulating the M2+ ion. On the contrary, Zn2+ ions are softer and show significantly more covalent character though they are still kinetically labile.
Since Mg2+ and Zn2+ are of almost identical size with ionic radii of ~0.8 Ǻ, we envisioned that a comparison of their relative coordination properties and reactivity can be useful in the determination of reaction pathways.123 On the other hand, the role of solvent certainly influences the chemical reactions of these metal ions since they are carried out in a solvent media. Weakly coordinating solvents such as alkane and aromatic solvents can act as weakly coordinating ligands while oxygen donors, such as ethers, can coordinate relatively tenaciously and can be considered as spectator ligands.
73
We did note significant solvent effects in the ring-opening polymerization of lactide, LA, and ε- caprolactone, CL, to form polylactide, PLA and polycaprolactone,
PCL by these magnesium and zinc catalyst initiators of the form LMR(L´), where L = 3-
[(2,6-diisopropylphenyl)amino]-5-[(2,6- diisopropylphenyl)imino]2,2,6,6,-tetramethyl- hept-3-ene) BDI*, or 1,5,9- trimesityldipyrromethene, TMP, M = Mg or Zn, R = Bun,
i N(SiMe3)2, or OPr , L´ = THF. The rate of formation of PCL is greatly increased in THF relative to benzene or methylene chloride whereas THF was shown to suppress the rate of the formation of PLA in otherwise identical reaction conditions. We do offer a plausible explanation proposal based on the solvent interaction with the resting state of the metal ions during the catalytic reaction.
4.2 Results and discussion
In this study, we employed the use of magnesium and zinc initiators shown in
n 20 i Figure 4.1. The (TMP)Mg Bu(THF) , (TMP)ZnN(SiMe3)2, [(TMP)ZnO Pr]2 and
(BDI*)MgnBu(THF)114 were synthesized in our research group while the
108 (BDI)ZnN(SiMe3)2 synthesis was previously reported by Coates group. These initiators were shown to be active in the ring-opening polymerization of lactide and ε-caprolactone.
Concerning the zinc initiators, we were able to continuously monitor some of the reactions in benzene (C6D6) using the NMR spectroscopy due to the fact that they were sufficiently slow. However, this was not possible for the magnesium initiators since they are too fast to be monitored on the NMR time scale. The ROP rates of LA and ε-CL are summarized in Table 4.1 and Table 4.2. No error bars are given in either Table 4.1 or
o Table 4.2 for the kp values quoted because the temperature 25±1 C was not controlled 74 rigorously and with extremely reactive initiators, such as magnesium alkyls, some trace decomposition is possible. However, with that stated we have confidence that the quoted values are good to ± 10% since the experiments were conducted several times. In addition, we have extensive experience in handling air sensitive materials. We were therefore able to draw the following conclusions based on the observed general trends without any doubt 1) The β-diketiminate complexes are notably more reactive than the dipyrrole (TMP) supported complexes. This we attribute to a combination of steric factors, which crowd the pocket of reactivity and greater ligand charge stabilization due to the lower π* orbitals of pyrrole groups. 2) The magnesium complexes are 2 to 3 orders of magnitude more active relative to their zinc analogs. This is understandable as the
Mg2+ ion is more electrophilic and the polarity of the M-OR bond is greater for Mg relative to the more covalent Zn2+ ion. 3) Simply indisputable is the fact that THF accelerates the ROP of ε-CL relative to DCM and benzene (benzene data are not given but where determined were within the experimental error comparable to those in DCM).
Indeed, the magnesium reactions in neat THF are so fast that reliable kp values were not obtainable by the methods employed but the reactions carried out in DCM with a 10%
(Table 4.1, entry 8) to 25% (Table 4.1, entry 4 and 12) by volume of THF reveal the pronounced acceleration that THF induces. The converse is true for the role of THF in the
ROP of rac-LA: relative to DCM, THF suppresses the rate. Table 4.2 data for the zinc complexes supports the above role of the ancillary ligands and the role of THF solvent as promoting ROP of ε-CL and suppressing that of ROP of LA.
75
TMPMgnBu(THF) BDI*MgnBu(THF)
TMPZnN(SiMe3)2 BDIZnN(SiMe3)2
i [TMPZnO Pr]2
Figure 4.1: TMP, BDI* and BDI Mg and Zn initiators for ROP of lactide and ε- caprolactone
76
Table 4.1: Rates of ROP of rac-Lactide and ε-Caprolactone using magnesium initiators
-1 -1 Entry Initiator Monomer Solvent kp (M s ) 1 TMPMgnBu(THF) rac-LA DCM 5.11 2 TMPMgnBu(THF) rac-LA THF 0.71 3 TMPMgnBu(THF) ε-Cl DCM 29 4** TMPMgnBu(THF) ε-Cl THF 59 5 BDI*MgnBu(THF) rac-LA DCM 6.12 6 BDI*MgnBu(THF) rac-LA THF 0.24 7 BDI*MgnBu(THF) ε-Cl DCM 5.51 8*** BDI*MgnBu(THF) ε-Cl THF 11.3 9 BDIMgBun(THF)19 rac-LA DCM 10.7 10 BDIMgBun(THF)19 rac-LA THF 3.0 11 BDIMgBun(THF)19 ε-Cl DCM 110 12** BDIMgBun(THF)19 ε-Cl THF 482 ** = 25% THF, *** = 10% THF
Table 4.2: Rates of ROP of rac-Lactide and ε-Caprolactone using zinc initiators
-1 -1 Entry Initiator Monomer Solvent kapp (M s ) i -4 1 [(TMP)ZnO Pr]2 ε-Cl DCM 7.23 * 10 i -2 2 [(TMP)ZnO Pr]2 ε-Cl THF 1.18 * 10 -5 3 (TMP)ZnN(SiMe3)2 ε-Cl DCM 5.67 * 10 -3 4 (TMP)ZnN(SiMe3)2 ε-Cl THF 2.19 * 10 -4 5 (BDI)ZnN(SiMe3)2 rac-LA DCM 5.92*10 -4 6 (BDI)ZnN(SiMe3)2 rac-LA THF 2.30*10 -3 7 (BDI)ZnN(SiMe3)2 ε-Cl DCM 3.96*10 -1 8 (BDI)ZnN(SiMe3)2 ε-Cl THF 1.80*10
While the molecular structures of the magnesium n-butyl complexes are shown to have THF coordinated 20,114 the related alkyl zinc complexes are almost undoubtedly three-coordinate as has been shown by Parkin.124 It is however important to note that once the alkyl complexes initiate the ROP, the living catalytically active species have M-
OR, metal-alkoxide bonds. The replacement of the metal-alkyl bond by the metal- alkoxide, a more electronegative group, promotes coordination and in the solid-state
i i dimeric alkoxides are seen as in the structures of [(BDI)MgOPr ]2 and [(BDI)ZnOPr ]2 77
108 i reported by Coates and in [(TMP)ZnOPr ]2 reported here (Figure 4.30). In general, the zinc complexes tend to be monomeric in solution while the magnesium alkoxides have been shown to coordinate THF both in the solid-state and in solution for which dynamic exchange, with added THF, has been reported recently by our research group to proceed by both interchange dissociative and associative processes.125,126 More evidence indicating only the mononuclear metal species are actively involved in the ROP process comes from the kinetics studies that reveal the ROP of LA and ε-CL is 1st order in metal complex (See Figures 4.3 to 4.17). The resting state of zinc promoted polymerization of lactide was originally suggested by Coates to involve a chelation of the growing polymer
108 127 chain. Our group recently reported the complexes (BDI)M(OCMe2COOEt) which indeed contain the chelating ligand (Figure 4.22) as well as (TMP)Zn(OCMe2COOEt) reported here (Figure 4.23 and Figure 4.32). IR studies revealed that these 4-coordinate structures are maintained in solution (Figure 4.24 and Figure 4.25) and dynamic (variable temperature) NMR studies provided strong evidence of reversible chelation for M = Zn
(Figure 4.26 to 4.29) while for both metals evidence was found for reversible coordination of THF.125,126 In the case of ROP of the ε-CL no evidence was found by IR of related chelation of the ketonic oxygen. This would not be expected to be as likely as it would require the formation of a 9-membered ring in contrast to the five-membered ring as shown in (Figure 4.22 and Figure 4.23).
Considering the above discussion, it is possible to speculate on the role of the solvent and propose the following. In the ROP of LA, the resting state of the catalyst is the four-coordinate M2+ ion. This is subject to reversible associative reactions with either
78
THF or LA and the competitive nature of THF binding suppresses the uptake and ring- opening of LA. Benzene and DCM are weaker ligating solvents and the rate of LA ROP is faster in these solvents. In the case of the ROP of ɛ-CL the resting state of the catalyst is the solvated LM(OR), an otherwise formally 3-coordinate metal complex. Here THF is a much better ligand as seen in related structurally characterized THF ligated alkoxides:
LM(OBut)(THF).20,114 THF will increase the polarity of the M-OR bond and enhance the ring-opening event via a five-coordinate metal center. If this speculation and hypothesis is correct then both ring-opening of LA and ɛ-CL proceed via 5-coordinate metal centers.
In the case of LA the presence of THF competes with the coordination of substrate whereas in the ROP of ɛ-CL the THF activates the M-OR bond. THF and other donating ligands such as DME and TMEDA are well known to activate the s-block metal-alkyl bonds by favoring solvated metal centers and a similar effect is proposed here for the metal-alkoxide bond.
79
° n Figure 4.2: Polymerization of rac-LA in CH2Cl2 at 25 C using (TMP)MgBu (THF) as an -1 2 initiator ([rac-LA]o= 0.139 M;( ) [rac-LA]o/[cat.] = 98, kapp = 0.256 min (linear fit, R -1 2 = 0.95); ( )[rac-LA]o/[cat.] = 84, kapp = 0.304 min (linear fit, R = 0.95); ( ) [rac- -1 2 LA]o/[cat.] = 66, kapp = 0.378 min (linear fit, R = 0.96); ( )[rac-LA]o/[cat.] = 59, kapp = 0.477 min-1 (linear fit, R2 = 0.98))
n Figure 4.3: Plot of ln kapp vs ln[(TMP)MgBu (THF)] of rac-LA polymerization using n (TMP)MgBu (THF) as an initiator ( in CH2Cl2, 25°C, [rac-LA]o = 0.139 M); ( )y = 1.077x + 5.725 (linear fit, R² = 0.97)
80
Figure 4.4: Polymerization of rac-LA in THF at 25°C using (TMP)MgBun(THF) as an -1 2 initiator ([rac-LA]o= 0.208 M;( ) [rac-LA]o/[cat.] = 98, kapp = 0.0951 min (linear fit, R -1 2 = 0.99); ( )[rac-LA]o/[cat.] = 79, kapp = 0.120 min (linear fit, R = 0.99); ( ) [rac- -1 2 LA]o/[cat.] = 59, kapp = 0.158 min (linear fit, R = 0.99))
n Figure 4.5: Plot of ln kapp vs ln[(TMP)MgBu (THF)] of rac-LA polymerization using n (TMP)MgBu (THF) as an initiator ( in THF, 25°C, [rac-LA]o = 0.208 M); ( )y = 1.000x + 3.81 (linear fit, R² = 0.99)
81
° n Figure 4.6: Polymerization of ε-CL in CH2Cl2 at 25 C using (TMP)MgBu (THF) as an -1 2 initiator ([ε-CL]o= 0.263M;( ) [ε-CL]o/[cat.] = 334, kapp = 0.688 min (linear fit, R = -1 2 0.99); ( )[ε-CL]o/[cat.] = 243, kapp = 1.26 min (linear fit, R = 0.99); ( ) [ε-CL]o/[cat.] -1 2 = 137, kapp = 1.89 min (linear fit, R = 0.99))
n Figure 4.7: Plot of ln kapp vs ln[(TMP)MgBu (THF)] of ε-CL polymerization using n (TMP)MgBu (THF) as an initiator (in CH2Cl2, 25°C, [ε-CL]o = 0.263 M); ( )y = 1.083x + 7.469 (linear fit, R² = 0.93)
82
° Figure 4.8: Polymerization of ε-CL in 25% V THF in CH2Cl2 at 25 C using n (TMP)MgBu (THF) as an initiator ([ε-CL]o= 0.250M;( ) [ε-CL]o/[cat.] = 248, kapp = 3.01 -1 2 -1 2 min (linear fit, R = 0.99); ( )[ε-CL]o/[cat.] = 213, kapp = 3.98 min (linear fit, R = -1 2 0.99); ( ) [ε-CL]o/[cat.] = 186, kapp = 4.29 min (linear fit, R = 0.99); ( ) [ε-CL]o/[cat.] -1 2 = 149, kapp = 5.17 min (linear fit, R = 0.99))
n Figure 4.9: Plot of ln kapp vs ln[(TMP)MgBu (THF)] of ε-CL polymerization using n (TMP)MgBu (THF) as an initiator (25% V THF in CH2Cl2, 25°C, [ε-CL]o = 0.250 M); ( )y = 1.02x + 8.171 (linear fit, R² = 0.96)
83
° n Figure 4.10: Polymerization of rac-LA in CH2Cl2 at 25 C using BDI*MgBu (THF) as an -1 2 initiator ([rac-LA]o= 0.174 M;( ) [rac-LA]o/[cat.] = 261, kapp = 0.132 min (linear fit, R -1 2 = 0.99); ( )[rac-LA]o/[cat.] = 171, kapp = 0.176 min (linear fit, R = 0.99); ( ) ([rac- -1 2 LA]o/[cat.] = 116, kapp = 0.3293 min (linear fit, R = 0.99); ( )[rac-LA]o/[cat.] = 99, -1 2 kapp = 0.351 min (linear fit, R = 0.97))
n Figure 4.11: Plot of ln kapp vs ln [BDI*Mg Bu(THF)] of rac-LA polymerization using n BDI*Mg Bu(THF) as an initiator in CH2Cl2, 25°C, [rac-LA]o = 0.174 M); ( )y = 1.09x + 5.906 (linear fit, R² = 0.96)
84
Figure 4.12: Polymerization of rac-LA in THF at 25°C using (BDI*)MgBun(THF) as an -2 -1 initiator ([rac-LA]o= 0.347 M;( ) [rac-LA]o/[cat.] = 227, kapp = 2.00*10 min (linear 2 -2 -1 2 fit, R = 0.99); ( )[rac-LA]o/[cat.] = 177, kapp = 2.86 *10 min (linear fit, R = 0.99); -2 -1 2 ( )[rac-LA]o/[cat.] = 113, kapp = 4.09 *10 min (linear fit, R = 0.99))
n Figure 4.13: Plot of ln kapp vs ln [(BDI*)Mg Bu(THF)] of rac-LA polymerization using n BDI*Mg Bu(THF) as an initiator in THF, 25°C, [rac-LA]o = 0.347 M); ( )y = 1.00x + 2.64 (linear fit, R² = 0.97)
85
° n Figure 4.14: Polymerization of ε-CL in CH2Cl2 at 25 C using (BDI*)MgBu (THF) as an -1 2 initiator ([ε-CL]o= 0.270M;( ) [ε-CL]o/[cat.] = 167, kapp = 0.33 min (linear fit, R = -1 2 0.96); ( )[ε-CL]o/[cat.] = 222, kapp = 0.202 min (linear fit, R = 0.99); ( ) [ε-CL]o/[cat.] -1 2 = 290, kapp = 0.189 min (linear fit, R = 0.99); ( ) [ε-CL]o/[cat.] = 377, kapp = 0.130 min-1 (linear fit, R2 = 0.99))
n Figure 4.15: Plot of ln kapp vs ln [(BDI*)Mg Bu(THF)] of ε-CL polymerization using n (BDI*)Mg Bu(THF) as an initiator in CH2Cl2, 25°C, [ε-CL]o = 0.270 M); ( )y = 1.08x + 5.801 (linear fit, R² = 0.93)
86
° Figure 4.16: Polymerization of ε-CL in 10% V THF in CH2Cl2 at 25 C using n (BDI*)MgBu (THF) as an initiator ([ε-CL]o= 0.270M;( ) [ε-CL]o/[cat.] = 181, kapp = -3 -1 2 -3 -1 6.90*10 s (linear fit, R = 0.99); ( ) [ε-CL]o/[cat.] = 237, kapp = 5.30*10 s (linear 2 -3 -1 2 fit, R = 0.99); ( ) [ε-CL]o/[cat.] = 308, kapp = 4.00*10 s (linear fit, R = 0.99))
n Figure 4.17: Plot of ln kapp vs ln[(BDI*)MgBu (THF)] of ε-CL polymerization using n (BDI*)MgBu (THF) as an initiator (10% THF in CH2Cl2, 25°C, [ε-CL]o = 0.250 M); ( )y = 1.02x + 2.425 (linear fit, R² = 0.99)
87
° i Figure 4.18: Polymerization of ε-CL at 25 C using [(TMP)ZnOPr ]2 as an initiator ([ε- i -1 CL]o= 0.298 M, [(TMP)ZnOPr ]2] = 6.02 mM;( ) CH2Cl2, kapp = 0.0434 min (linear fit, 2 -1 2 R = 0.99); ( ) THF, kapp = 0.710 min (linear fit, R = 0.99)
° Figure 4.19: Polymerization of ε-CL at 25 C using (TMP)ZnN(SiMe3)2 as an initiator ([ε- -1 CL]o= 0.298 M, [(TMP)ZnN(SiMe3)2] = 6.02 mM;( ) CH2Cl2, kapp = 0.0034 min 2 -1 2 (linear fit, R = 0.99); ( ) THF, kapp = 0.131 min (linear fit, R = 0.99)
88
° Figure 4.20: Polymerization of rac-LA at 25 C using (BDI)ZnN(SiMe3)2 as an initiator -1 ([rac-LA]o= 0.298 M, [(BDI)ZnN(SiMe3)2] = 6.02 mM;( ) CH2Cl2, kapp = 0.0358 min 2 -1 2 (linear fit, R = 0.99); ( ) THF, kapp = 0.0138 min (linear fit, R = 0.99)
° Figure 4.21: Polymerization of ε-CL at 25 C using (BDI)ZnN(SiMe3)2 as an initiator ([ε- -1 CL]o= 0.298 M, [(BDI)ZnN(SiMe3)2] = 6.02 mM;( ) CH2Cl2, kapp = 0.238 min (linear 2 -1 2 fit, R = 0.99); ( ) THF, kapp = 1.11 min (linear fit, R = 0.99)
89
Figure 4.22: Representations of the structures of (BDI)M(OCMe2COOEt)
Figure 4.23: Representation of the structure of (TMP)Zn(OCMe2COOEt)
90
Figure 4.24: FTIR spectra for (TMP)Zn(OCMe2COOEt) in DCM
Figure 4.25: FTIR spectra for (TMP)Zn(OCMe2COOEt) in THF
91
Figure 4.26: Dynamic (variable temperature) NMR studies showing stacked 1H NMR spectra of (TMP)Zn(OCMe2COOEt) (0.035M) compound in toluene-d8
92
Figure 4.27: Expanded aromatic region of dynamic (variable temperature) NMR studies 1 showing stacked H NMR spectra of (TMP)Zn(OCMe2COOEt) (0.035M) compound in o toluene-d8. The coalescence temperature (Tc) is approximately 15 C
93
Figure 4.28: Dynamic (variable temperature) NMR studies showing stacked 1H NMR spectra of (TMP)Zn(OCMe2COOEt) (0.035M) compound in THF-d8
94
Figure 4.29: Expanded aromatic region of dynamic (variable temperature) NMR studies 1 showing stacked H NMR spectra of (TMP)Zn(OCMe2COOEt) (0.035M) compound in o THF-d8. The coalescence temperature (Tc) is approximately -85 C
95
4.3 Crystal structure studies
i 4.3.1 [(TMP)ZnOPr ]2
i An ORTEP single X-ray structure of [(TMP)ZnO Pr]2 is shown in Figure 4.30 and the crystallographic data collection parameters are provided on Table 4.3. The dimeric structure is found in the monoclinic space group. A crystallographically imposed C2 axis contains the bridging oxygen atoms. The structure has a distorted tetrahedral geometry about the zinc centre.
a)
96
b)
i Figure 4.30: ORTEP representations of [(TMP)ZnOPr ]2 with thermal ellipsoids drawn at 50% probability level: (a) Full representation with only hydrogens removed for clarity, (b) View of dimer core with hydrogens and mesityls removed for clarity.
97
i Table 4.3: Crystallographic data collection parameters for [(TMP)ZnOPr ]2
Chemical Formula C78H88N4O2Zn2 Formula Weight 1244.26 Temperature (K) 150(2) Space Group Monoclinic, C2/c a (Å) 28.6695(8) b (Å) 12.2437(3) c (Å) 25.3442(6) (o) β (o) 122.0030(10) (o)
V (Å3) 7544.3(3) Z 4
Dcalcd (Mg/m3) 1.095 Crystal Size (mm) 0.31 X 0.31 X 0.15 Theta range for data collection 1.68 to 25.02o ,(Mo, K) (mm-1) 0.679 F(000) 2640 Reflections collected 51292 Unique reflections 6674 [R(int)= 0.040] Completeness to theta max 100.0% Data/restraints/parameters 6674 / 0 / 399
R1a (%) (all data) 3.39 (4.92) wR2b(%)(all data) 8.73 (9.21) Goodness-of-fit on F2 1.058 Largest diff. peak and hole (e Å-3) 0.465 and -0.244
98
4.3.2 (TMP)ZnN(SiMe3)2
An ORTEP drawing showing the molecular structure of (TMP)ZnN(SiMe3)2 is given in Figure 4.31 and the crystallographic data collection parameters are given in
Table 4.4. The structure has a distorted trigonal planar geometry about the zinc centre.
The bonds of N-Zn-N’, N-Zn-N” and N’-Zn-N” are 94.47o, 133.20o and 129.32o respectively giving a summation of 356.99o. An interesting observation is the anagostic
128 interaction between the hydrogens on the carbon labelled C and the Zn metal (Figure
4.31). These anagostic interactions bond distance ranges between 2.3 – 2.9 Å unlike the agostic interactions whose bond distance between the metal and hydrogen range from 1.8
– 2.3 Å. 128,129 The shortest distance of hydrogen to zinc on this carbon is 2.79 Å which is noticeably shorter compared to the shortest hydrogen-zinc distance of 3.03 Å on the carbon labelled C’. The –ZnN(SiMe3)2 group is clearly bent out of plane defined by
ZnNN’ (see Figure 4.31 b).
99
a)
b)
Figure 4.31: ORTEP representations of (TMP)ZnN(SiMe3)2 with thermal ellipsoids drawn at 50% probability level: (a) Full representation with only hydrogens removed for clarity, (b) Side view of (TMP)ZnN(SiMe3)2 core with hydrogens and mesityls removed for clarity.
100
Table 4.4: Crystallographic data collection parameters for (TMP)ZnN(SiMe3)2
Formula C42H55N3Si2Zn Formula weight 723.44 Temperature 150(2) K Wavelength 0.71073 A Crystal system Monoclinic, Space group P 21/c Unit cell dimensions a = 12.8501(2) A alpha = 90 deg. b = 16.1086(3) A beta = 96.5350(10) deg. ° c = 19.8251(3) A gamma = 90 deg. ° Volume 4077.07(12) Å3 Z 4 Density (calculated) 1.179 Mg/m3 Absorption coefficient 0.692 mm-1 F(000) 1544 Crystal size 0.350 x 0.350 x 0.190 mm3 Theta range for data collection 1.595 to 27.479 deg ° Index ranges -16<=h<=16, -20<=k<=20, - 25<=l<=25 Reflections collected 70290* / Independent reflections 9328 [R(int) = 0.058* Completeness to theta = 25.04° 100 % Refinement method Full-matrix least-squares on F2 Data / restraints / parameters 9328 / 0 / 448 Goodness-of-fit on F2 1.045 Final R indices [I>2sigma(I)] R1 = 0.0436, wR2 = 0.1060 R indices (all data) R1 = 0.0759, wR2 = 0.1193 Largest diff. peak and hole 0.477 and -0.409 e/Å3
101
4.3.3 (TMP)Zn(OCMe2COOCH2CH3)
An ORTEP single X-ray structure of (TMP)Zn(OCMe2COOEt) is shown in
Figure 4.32 below and the crystallographic data collection parameters are provided on
Table 4.5. The structure shows a five membered ring with oxygen (O”) of the carbonyl group chelated to the zinc metal.
Figure 4.32: ORTEP representations of (TMP)Zn(OCMe2COOEt) with thermal ellipsoids drawn at 50% with hydrogens removed for clarity.
102
Table 4.5: Crystallographic data collection parameters for (TMP)Zn(OCMe2COOEt)
Chemical Formula C42H48N2O3Zn Formula Weight 694.19 Temperature (K) 150(2) Space Group Monoclinic, C2/c a (Å) 13.1220(5) b (Å) 21.1057(6) c (Å) 13.3316(6) (o) β (o) 94.504(2) (o)
V (Å3) 3680.8(2) Z 4
Dcalcd (Mg/m3) 1.253 Crystal Size (mm) 0.270 x 0.230 x 0.150 mm Theta range for data collection 1.557 to 25.048 deg.o ,(Mo, K) (mm-1) 0.679 F(000) 2640 Reflections collected 43322* Unique reflections 6503 [R(int) = 0.048*] Completeness to theta max 99.9 % Data/restraints/parameters 6503 / 70 / 474
R1a (%) (all data) 3.89 (9.83) wR2b(%)(all data) 5.87 (11.21) Goodness-of-fit on F2 1.058 Largest diff. peak and hole (e Å-3) 0.458 and -0.427
103
4.4 Synthesis
130 Zn[N(SiMe3)2]2: In a glovebox anhydrous zinc chloride (4.80 g, 35.2 mmol) and approximately two equivalents of lithium bis(trimethylsilyl)amide (12.0 g, 71.7 mmol) were charged into two separate 250ml Schlenk flasks. These were then connected to a Schlenk line and placed under nitrogen. THF (75 ml) was introduced into the flasks and then partially frozen in liquid nitrogen. The thawing solution of lithium bis(trimethylsilly)amide was added dropwise into the thawing solution of zinc chloride.
The reaction was allowed to stir for six hours at room temperature before removing the
THF under vacuum. Toluene (50 ml) was added to extract the title compound and precipitate out lithium chloride. The toluene solution was filtered through a medium porosity frit with Celite. The solution was concentrated in vacuum to afford colorless oil
(10.0 g, 73.5 % yield). 1H NMR (400 MHz, C6D6): singlet at 0.21 ppm.
(TMP)ZnN(SiMe3)2: A 50ml Schlenk flask was charged with TMPH (1.23 g,
2.47 mmol) and Zn(N(SiMe3)2)2 (1.00 ml , 2.47 mmol) in toluene (35 ml) inside the glovebox. This was refluxed for 15 h. The solution was cooled to room temperature before all volatiles were removed under dynamic vacuum to give the title compound as a brick red solid in quantitative yield (1.76 g, 98% yield). Crystals were grown overnight in
o 1 a concentrated toluene solution at -25 C. H NMR (400 MHz, C6D6): 6.84 (s, 4H, m-
C6H2(CH3)3), 6.82 (s, 2H, m-C6H2(CH3)3), 6.71 (d, JHH = 4Hz, 2H, pyrrole C–H), 6.13 (d,
JHH = 4Hz, 2H, pyrrole C–H), 2.27 (s, 12H, o- C6H2(CH3)3), 2.24 (s, 6H, p-C6H2(CH3)3),
2.23 (s, 3H, p-C6H2(CH3)3), 2.18 (s, 6H, o-C6H2(CH3)3), -0.036 (s, 18H, CH3) ppm. 13C
104
{1H} NMR (500 MHz, C6D6): δ/ppm 162.6, 145.9, 140.7, 138.6, 136.9, 135.8, 133.2,
132.9, 129.1, 120.1, 21.3, 21.2, 19.9, 4.98.
i [(TMP)ZnOPr ]2: To a solution of (TMP)ZnN(SiMe3)2 (0.62 g, 0.86 mmol) in toluene (10 ml) at 0 oC was added 2-propanol (66 μL, 0.86 mmol). The solution was stirred for 30 minutes before the solvent was removed under dynamic vacuum to give a bright orange solid. This was washed one time with 5 ml dry benzene to remove trace impurities (0.40 g, 75% yield). Crystals were grown from a concentrated toluene solution
o 1 overnight at -25 C. H NMR (400 MHz, Toluene-d8): 7.02 (s, 1H, m-C6H2(CH3)3), 6.94
(s, 2H, m-C6H2(CH3)3), 6.81 (s, 1H, m-C6H2(CH3)3), 6.73 (s, 2H, m-C6H2(CH3)3), 6.66 (d,
JHH = 4Hz, 2H, pyrrole C–H), 6.09 (d, JHH = 4Hz, 2H, pyrrole C–H), 2.99 (m, 1H,
OCH(CH3)2), 2.63 (s, 3H, p- C6H2(CH3)3), 2.31 (s, 3H, p- C6H2(CH3)3), 2.24 (s, 6H, o-
C6H2(CH3)3),2.14 (s, 6H, o- C6H2(CH3)3), 2.12 (s, 6H, o- C6H2(CH3)3), 2.04 (s, 3H, p-
13 C6H2(CH3)3), 0.32 (d, 6H, JHH = 5.9Hz, OCH(CH3)2) ppm. C {1H} NMR (500 MHz,
Toluene-d8): δ/ppm 145.4, 142.9, 138.7, 138.5, 137.6, 137.5, 137.0, 136.6, 134.8, 133.5,
120.2, 65.7, 28.6, 21.9, 21.9, 21.6, 21.5, 19.9.
(TMP)Zn(OCMe2COOEt): A 50ml Schlenk flask was charged with
TMPZnN(SiMe3)2 (0.70 g, 0.97 mmol) in toluene (15 ml) and placed in an icebath. Ethyl
2-hydroxy -2-methyl propanoate (HOCMe2COOCH2CH3) was added using a 1 ml syringe (0.13 ml, 0.97 mmol). The solution was stirred for 30 minutes before removing all volatiles under dynamic vacuum to give the title compound as a bright orange solid
(0.62g, 0.93 mmol, 92.5 %). Single X-ray crystals were grown from a concentrated solution of dichloromethane in a freezer (-23 oC) overnight. 1H NMR (400 MHz, THF-
105 d8): 6.97 (s, 2H, m-C6H2(CH3)3), 6.75 (s, 4H, m-C6H2(CH3)3), 6.54 (d, JHH = 4Hz, 2H, pyrrole C–H), 6.13 (d, JHH = 4Hz, 2H, pyrrole C–H), 4.06 (q, 2H, -OCH2CH3), 2.36 (s,
3H, p-C6H2(CH3)3), 2.20 (s, 6H, o- C6H2(CH3)3), 2.18 (s, 6H, p-C6H2(CH3)3), 2.08 (s,
13 12H, o-C6H2(CH3)3), 1.18 (t, 3H, -OCH2CH3), 0.362 (s, 6H, -C(CH3)2) ppm. C {1H}
NMR (500 MHz, Toluene-d8): δ/ppm 161.9, 146.0, 140.7, 133.8, 132.4, 119.1, 74.18,
62.8, 29.5, 13.9, 1.36.
106
CHAPTER 5: THE HOMO- AND CO-POLYMERIATION STUDIES OF LACTIDE AND ε-CAPROLACTONE USING MAGNESIUM AND ZINC INITIATORS SUPPORTED BY 1,5,9-TRIMESITYLDIPYRROMETHENE
5.1 Introduction
The polymers of polylactide, polycaprolactone and their copolymers are amongst the most widely applied in the medical and pharmaceutical field due to their biocompatibility and biodegradability properties. 78,131 Their physical properties can be tuned to allow for the achievement of desirable properties. For instance, polycaprolactone semi-crystalline nature allows it to be more permeable to drugs unlike the amorphous polylactide that is hardly permeable to many drugs.131 In addition, the half-life of polylactide is about a few weeks in-vivo compared to one year for polycaprolactone. 131
Adjusting of these copolymers compositions allows for the fine tuning of their permeability and degradability properties. A lot of research in this area has produced either random132,133 or block 134–136 copolymers of lactide and ε-caprolactone.
5.2 Results and discussion
5.2.1 Solution and melt homopolymerization of ε-caprolactone using
i [(TMP)ZnO Pr]2
i The [(TMP)ZnO Pr]2 was applied in the homopolymerization study of ε- caprolactone (ε-Cl) in THF as shown in Figure 5.1 below. This was carried out at 0 oC in order to slow down the reaction rate since this proceeds extremely fast in THF as
107
i discussed in chapter 4. [(TMP)ZnO Pr]2 ring opens and sustains the polymerization of ε-
Cl with 80 % conversion in about 7 minutes. This shows a well-controlled and living polymerization as the theoretical (calculated Mn) and experimental (GPC Mn) molecular weights agree closely and the the polydispersity index (PDI) was between 1.02 and 1.03 implying negligible to no transesterification (Figure 5.2). However, in melt polymerization at 110 oC a broad PDI of 1.94 to 2.03 was observed indicating some transesterifiaction (Figure 5.3).
i Figure 5.1: Plot of % conversion vs time of ε-caprolactone in THF using [(TMP)ZnO Pr]2 at 0 oC. [ε-CL] = 0.287 M, [Cat] = 3.78 mM.
108
Figure 5.2: Plot of molecular weight (Mn) and polydispersity Index (PDI) vs % i o conversion of ε-Caprolactone in THF using [(TMP)ZnO Pr]2 at 0 C. [ε-CL] = 0.287 M, [Cat] = 3.78 mM. Plot shows a well-controlled living polymerization
Figure 5.3: Plot of Mn and PDI vs M/I of ε-Cl in melt polymerization using i o [(TMP)ZnO Pr]2 at 110 C.
109
5.2.2 Copolymerization studies of rac-LA and ε-CL using Mg and Zn catalysts
In our study of copolymerization of rac-LA and ε-CL, we observed that the Mg and Zn initiators ring-open and sustain the polymerization of rac-LA in solution but the presence of LA completely suppresses the ROP of ε-CL as illustrated in Figures 5.4, 5.6 -
5.11. However, we did observe that initial ring-opening of ε-CL could be sequentially followed by the ROP of LA giving stereoblock PLA-b-PCL but the vice versa could not be attained (Figure 5.6). This phenomenon was initially observed by Jerome’s group137,138 and later by Duda’s group139 but no explanation was given as to what is actually happening on the molecular level. We reasoned that this must have something to do with the resting state of the catalyst precursor upon the ring-opening polymerization of LA that definitely quenches the in-cooperation of the ε-CL monomer. We set out to understand the mechanism behind this phenomenon. We reasoned that upon the ROP of
LA, the ketonic carbonyl group is more favorable to chelate back onto the metal center forming a 5-membered chelated ring unlike in the case of ε-CL where the ring-opened monomer has a 5-carbon chain that would otherwise form a 9-membered ring chelation if the ketonic carbonyl does indeed chelate, a situation that is most likely unfavorable
(Figure 5.5). Our group did recently report on the synthesis of model compounds of the
127 form (BDI)M(OCMe2COOEt) (Figure 4.22) that have a 5-membered ring chelation and clearly show little or no activity towards the ROP of ε-CL. We are also reporting in this work the synthesis of the analog digem compounds of the form
(TMP)Zn(OCMe2COOEt) and (TMP)Zn(OCHMeCOOEt) which show no activity towards ROP of ε-CL during its copolymerization with LA but are active towards ROP of
110
LA (see Figure 4.32 and Figure 5.11). This indeed provides prove that the chelation of the ketonic group, upon ROP of LA, does indeed prevent the enchainment of ε-CL. In addition, preference for the ROP of LA over ε-CL during their copolymerization is more so driven by the high degree ring strain of LA.
It is worth noting that, in the case of (TMP)MgnBu(L) where L = 2-MeTHF, THF and pyridine, a significant acceleration of the ROP of LA was observed during the copolymerization of LA with ε-Cl as compared to the homo-polymerization of LA although no activity towards ROP of ε-Cl was observed (Figure 5.7 – 5.9). A plausible explanation could be attributed to ε-Cl forcing the chelation formed from the ring- opening of LA to break hence facilitating faster in-cooperation and initiation of the incoming LA monomer. Further investigation on this phenomenon is ongoing.
Figure 5.4: Copolymerization of rac-LA with ε-CL using both the Mg and Zn catalyst precursors only gives PRLA in Solution. Resting state of catalyst in polymerization of LA quenches enchainment of ε-CL monomer.
111
Figure 5.5: Illustration of coordination insertion mechanism for the ROP of LA and ε-CL. Indicates ketonic carbonyl for ring-opened LA monomer is favored to chelate to the metal unlike the one for ε-CL.
Figure 5.6: Homo- and co-polymerization of rac-LA with ε-CL using (TMP)MgnBu(THF) in DCM.
112
Figure 5.7: Homo- and co-polymerization of rac-LA with ε-CL using (TMP)MgnBu(2- MeTHF) in DCM
Figure 5.8: Homo- and co-polymerization of rac-LA with ε-CL using (TMP)MgnBu(THF) in DCM
113
Figure 5.9: Homo- and co-polymerization of rac-LA with ε-CL using (TMP)MgnBu(Py) in DCM
Figure 5.10: Homo- and co-polymerization of rac-LA with ε-CL using (TMP)ZnN(SiMe3)2 in C6D6
114
Figure 5.11: Model compound (TMP)Zn(OCOMe2COOEt) shows no activity for ROP of ε-CL during homo- or copolymerization of ε-CL with LA.
5.3 Synthesis
(TMP)Zn(OCHMeCOOMe): A 50ml Schlenk flask was charged with
(TMP)ZnN(SiMe3)2 (0.70 g, 0.97 mmol) in toluene (15 ml) and placed in an icebath. L- methyl lactate (HOCHMeCOOMe) was added using a 1 ml syringe (0.13 ml, 0.97 mmol). The title product formed almost immediately crushing out of solution as a brown solid in quantitative yield. This was then let to settle at the bottom of the flask before removing all solvent by cannula filtration. Product was dried by dynamic vacuum.
Product was also very insoluble in many common solvents and proper NMR was
1 acquired in Cd2Cl2. H NMR (400 MHz, CD2Cl2): 6.97 (s, 2H, m-C6H2(CH3)3), 6.76 (s,
4H, m-C6H2(CH3)3), 6.54 (d, JHH = 4Hz, 2H, pyrrole C–H), 6.20 (d, JHH = 4Hz, 2H, pyrrole C–H), 3.69 (s, 3H, -OCH3), 3.30 (q, 1H, -OCHMe), 2.38 (s, 3H, p-C6H2(CH3)3),
115
2.20 (s, 6H, o- C6H2(CH3)3), 2.19 (s, 6H, p-C6H2(CH3)3), 2.06 (s, 6H, o-C6H2(CH3)3),
2.04 (s, 6H, o-C6H2(CH3)3), 0.45 (d, 3H, -OCHMe)
116
CHAPTER 6: VARIABLE TEMPERATURE NMR SPECTROSCOPIC SOLUTION STUDIES ON THE DYNAMIC EXCHANGE OF MAGNESIUM AND ZINC COMPLEXES SUPPORTED BY 1,5,9 - TRIMESITYLDIPYRROMETHENE LIGAND (TMP)
6.1 Introduction
The continued research on Grignard reagents attests to its central significance in organometallic chemistry and has led to more exciting developments such as the turbo-
Grignard reagents 21,28 and the C-H bond activation by employing of alkali-metals.119,120
Organozinc reagents 40,42 and magnesium alkyl groups reactivity are indeed solvent dependent, which can be attributed in part to these ions being kinetically labile as well as being in Schlenk equilibria 9 particularly in polar solvents such as THF. Our use of bulky chelating anionic ligands, such as the TMP and BDI*, was mainly in part to be able to tame and suppress the Schlenk equilibrium of the kinetically labile Mg- and Zn-alkyls.
Since solvation affects the reactivity of these reagents, it is in our interest to investigate the mechanism by which our magnesium and zinc complexes react in solution. This will complement what we already know from the X-ray determined solid-state structures.
6.2 Results and discussions
In this study, a series of Mg and Zn complexes of the form (TMP)MgnBu(L)
i where L = THF, Py and DMAP and (TMP)Zn(X) where X = N(SiMe3)2, O Pr and
OCMe2COOEt were investigated in toluene-d8 and THF-d8 between the temperatures of
117
183 to 353 K. Chemical shift assignments for the various compounds at room temperature are listed in the experimental section of chapters 3 and 4.
Figure 6.1: Representation of the trigonal planar complex of the TMP ligand
From the drawing of the TMP ligand in a trigonal planar complex (Figure 6.1) we can see that we may anticipate four mesityl signals in the ratio 4:2:2:1 corresponding to b:a:c:d. In the aromatic region of the spectrum we can find 4:2 protons for the mesityl groups (z and w as shown) and 2:2 for the pyrrole protons x and y. In a tetrahedral structure (TMP)MX(L) steric crowding may induce restricted rotation about the pyrrole- mesityl C-C bond. This could lead to a 2:2:2:2:1 pattern for the methyl signals. If the tetrahedral ground state structure is present in solution but undergoing a rapid exchange of the coordinated ligand L by either a dissociative or associative process we may anticipate that the spectrum would appear as that for the three coordinate molecule. If the
i structure were dimeric as in [(TMP)ZnO Pr]2 with a lower symmetry then the spectrum could be more complex as we shall describe.
118
1 The H NMR spectra for (TMP)ZnN(SiMe3)2 in toluene-d8 are temperature independent as shown in Figure 6.2. Specifically we observed the appearance of the mesityl methyl groups in the ratio 4:2:2:1 in the region 2.0 - 2.5 ppm and the singlet due to the SiMe3, protons close to 0.0 ppm. The addition of DMAP does not change the spectrum and even in neat THF-d8 the spectra remain the same. Thus even if coordination to the three coordinate complex can occur it does so reversibly and rapidly on the NMR timescale.
The magnesium complexes (TMP)MgnBu(L) where L=THF, Py or DMAP all show similar spectra at room temperature in toluene-d8, namely the appearance of an apparently trigonal planar compound with the additional signals due to L (see Figure 6.3).
The spectra of the complex where L = py in neat THF are also temperature independent but the signals of the py ligand are now present in the chemical shift position of free py
(see Figure 6.4). The variable temperature spectra of the complex where L = py with one equivalent of added py are similarly temperature independent and the proton resonances due to the py are the average of the free and coordinated. From this we can conclude that the py ligand is labile to facile exchange on the NMR time scale.
The variable temperature spectra of the complex where L = py in toluene-d8 are shown in Figure 6.5 and Figure 6.6. With a lowering of the temperature we observed in the aromatic region significant chemical shift of the py protons (2H) from 6.5 to 6.2 and a similar shift (1H) from 6.9 to 6.5 ppm (see Figure 6.5). In the methyl region we see that the signal due to the 4 methyl groups of the pyrrole bound mesityl labelled b in figure 6.1 are broad at room temperature and upon cooling broaden further until they apparently
119 disappear into the baseline at -800C (see Figure 6.6). We attribute the combined 1H NMR observations to reversible py dissociation and that at low temperatures the bound py ligand causes restricted rotation about the pyrrole –mesityl carbon-carbon bond. The up field shift of the py protons can be explained by the py protons of the bound ligand being in the magnetically shielded pocket of the mesityl groups.
In contrast the variable temperature spectra of the complex where L = DMAP in toluene –d8 show little if any temperature dependence for the DMAP protons which leads us to suggest that the stronger donor ligand DMAP is coordinated on the NMR time scale in the temperature region shown. However, upon lowering the temperature the methyl proton signals become more complex but are not fully resolved even at low temperature.
Again this may be due to restricted rotations involving the aryl groups.
As shown in chapter 4 the zinc complex (TMP)Zn(OCMe2COOEt) is four coordinate in the solid-state due to the chelation of the ketonic ester carbonyl oxygen (see
Figure 4.32). Furthermore from IR spectroscopy in DCM and THF (see Figure 4.24 and
Figure 4.25 respectively) this structure is maintained in solution. The 1H NMR spectrum of the complex in toluene-d8 is shown in Figure 6.7 in the aromatic region. The pyrrole proton signals do not show any significant temperature dependence; nor does the meta
CH proton of the carbon-bound mesityl. However, the meta CH signals of the pyrrole bound mesityl broaden upon lowering the temperature and at 0oC are clearly resolved
o into two signals. We can estimate TC ~ 15 C. This is again clear evidence of restricted rotation about the pyrrole –mesityl carbon-carbon bond within the four coordinated Zinc complex.
120
1 We also obtained the variable temperature H NMR spectra in neat THF-d8 and these are shown in Figure 6.8. We now see that the rotation about the pyrrole –mesityl carbon-carbon bond is again frozen out but this time at a notably lower temperature. We
o o can estimate TC ~ -85 C. Even at -95 C there is evidence of dynamic exchange. We attribute the difference in this dynamic behavior to the ability of THF to reversibly coordinate to the Zn (2+) center.
The variable temperature spectra of (TMP)Zn(OCMe2COOEt) in toluene-d8 were also examined in the presence of one equivalent of added py and DMAP. Again with lowering the temperature the signals of the added ligand (Py or DMAP) showed some significant chemical shift dependence as did the signals associated with the chelating
OCMe2COOEt. Again we take this as evidence for the equilibrium between the four and five coordinated Zn2+ ion and note that for the related Mg2+ ion the five coordinated species represents the thermodynamic product at room temperature.
i The variable temperature spectra for the complex [(TMP)ZnOPr ]2 recorded in
THF and toluene-d8 are remarkably different. The spectra in THF are temperature independent and are relatively simple being consistent with an apparent three coordinate zinc complex of the form (TMP)ZnOPri. (See Figure 6.9)
In toluene-d8 the room temperature spectrum in the mesityl methyl region appears as (from downfield to up field, 2.7 to 2.0 ppm) 3H:3H:6H:6H:6H:3H. While an unambiguous assignment of these methyl group is not possible it is clear that there must be a further inequivalence of the mesityl methyls. For a simple four coordinated Zn(2+) center having a mirror plane of symmetry but restricted rotation about the pyrrole –
121 mesityl carbon - carbon bond we would get the former pattern of methyl groups namely
1:2:2:2:2 but here we see 1:1:2:2:2:1. Furthermore, on lowering the temperature, the methyl region shows further removal of degeneracy. In addition the isopropyl methyl signals at δ ~ 0.4 ppm show a clear splitting into two 1:1 signals indicating that they are diastereotopic. (see Figure 6.10)
The aromatic region also shows interesting temperature dependence. Upon lowering the temperature the two pyrrole proton signals, Hx and Hy each split into two
’ signals of equal intensity (Hx, Hx’) and (Hy, Hy ) (see Figure 6.11). There are also changes in the mesityl meta CH signals but these are less clearly resolved. An
i examination of the solid-state molecular structure of the dimer [(TMP)ZnO Pr]2 does indeed indicate this lowering of symmetry even to the point that the isopropyl methyl groups are inequivalent. We must conclude that in toluene-d8 the dimeric structure is
1 maintained even at room temperature. In contrast in THF-d8 the H spectra are consistent with a solvated monomeric species (TMP)ZnOPri(THF) which undergoes rapid exchange of its solvated ligand.
122
1 Figure 6.2: Variable temperature H 500 MHz NMR of 0.035mM (TMP)ZnN(SiMe3)2 in Toluene-d8. (* = Toluene-d8 protio impurities).
123
Figure 6.3: Expanded mesityl aromatic region variable temperature 1H 500 NMR MHz of n 0.035mM (TMP)Mg Bu(DMAP) in Toluene-d8. (* = Toluene-d8 protio impurities).
124
Figure 6.4: Variable temperature 1H 500 NMR MHz of 0.035mM (TMP)MgnBu(Py) in THF-d8. (* = THF-d8 protio impurities).
125
Figure 6.5: Expanded aromatic region variable temperature 1H 500 NMR MHz of n 0.035mM (TMP)Mg Bu(Py) in Toluene-d8. (* = Toluene-d8 protio impurities).
126
Figure 6.6: Expanded mesityl methyl region variable temperature 1H 500 NMR MHz of n 0.035mM (TMP)Mg Bu(Py) in Toluene-d8. (* = Toluene-d8 protio impurities).
127
Figure 6.7: Variable temperature 1H 500 MHz NMR of 0.035mM (TMP)Zn(OCMe2COOEt) in Toluene-d8 showing the expanded mesityl aromatic region. (* = Toluene-d8 protio impurities)
128
Figure 6.8: Variable temperature 1H 500 MHz NMR of 0.035mM (TMP)Zn(OCMe2COOEt) in THF-d8 showing the expanded mesityl aromatic region. (* = THF-d8 protio impurities).
129
1 i Figure 6.9: Variable temperature H 500 MHz NMR of 0.035mM [(TMP)Zn(O Pr)]2 in THF-d8. (* = THF-d8 protio impurities).
130
Figure 6.10: Expanded methyl region variable temperature 1H 500 MHz NMR of i 0.035mM [(TMP)ZnO Pr]2 in Toluene-d8.
131
Figure 6.11: Expanded aromatic-mesityl region variable temperature 1H 500 MHz NMR i of 0.035mM [(TMP)ZnO Pr]2 in Toluene-d8. (* = Toluene-d8 protio impurities)
132
REFERENCES
(1) Grignard, V. Comptes Rendus Hebdomadaires des Seances de l’Academie des Sciences 1900, 130, 1322. (2) Frankland, E. Liebigs Ann. Chem. 1849, 71, 171. (3) Gerritsen, H. G.; Van ’t Land, C. M. Ind. Eng. Chem. Process Des. Dev. 1985, 24, 893. (4) Silverman, G. S.; Rakita, P. E. Handbook of Grignard Reagents; CRC Press, 1996. (5) Brown, H. C.; Racherla, U. S. Organometallics 1986, 5, 391. (6) Smith Jr., W. N. J. Organomet. Chem. 1974, 64, 25. (7) Wakefield, B. J. Organometallic Chemistry Reviews 1966, 1, 131. (8) Glaze, W. H.; Selman, C. M. J. Organomet. Chem. 1966, 5, 477. (9) Schlenk, W.; Schlenk, W. J. Chem. Ber. 1929, 62B, 920. (10) Hartley, E. by: F. R.; Hartley, F. R. The Chemistry of the Metal Carbon Bond, Vol. 4: The Use of Organometallic Compounds in Organic Synthesis; Volume 4 edition.; Wiley: Chichester ; New York, 1987. (11) Andersen, R. A.; Wilkinson, G.; Lappert, M. F.; Pearce, R. In Inorganic Syntheses; Shriver, D. F., Ed.; John Wiley & Sons, Inc., 1979; pp. 262–265. (12) Nagano, H.; Mina, O.; Yoko, M.; kunie, Y. Bull. Chem. Soc. Jpn. 1992, 65, 2814. (13) Kirk-Othmer. Kirk-Othmer Encyclopedia of Chemical Technology, Fuel Resources to Heat Stabilizers; Volume 12 edition.; Wiley-Interscience, 1994. (14) Rakita, P. E.; Aultman, J. F.; Stapleton, L. 1990, 97, 110. (15) Abegg, R. Berichte Dtsch. Chem. Ges. 1905, 38, 4112. (16) Richey, H. G. Grignard Reagents: New Developments; 1 edition.; Wiley, 1999. (17) Garst, J. F.; Soriaga, M. P. Coord. Chem. Rev. 2004, 248, 623. (18) Kharasch, M. S.; Reinmuth, O. Grignard Reactions of Nonmetallic Substances; 1st edition.; Prentice Hall Press. (19) Kittisak, C. CHEMISTRY OF MAGNESIUM ALKYLS COMPLEXES SUPPORTED BY A β–DIIMINATO LIGAND, The Ohio State University: Columbus, Ohio, 2013. (20) Chisholm, M.; Choojun, K.; Gallucci, J.; Wambua, P. Chem. Sci. 2012, 3, 3445. (21) Krasovskiy, A.; Knochel, P. Angew. Chem. Int. Ed. 2004, 43, 3333. (22) Armstrong, D. R.; García-Álvarez, P.; Kennedy, A. R.; Mulvey, R. E.; Parkinson, J. A. Angew. Chem. Int. Ed. 2010, 49, 3185. (23) Hoffmann, R. W.; Hölzer, B.; Knopff, O.; Harms, K. Angew. Chem. Int. Ed. 2000, 39, 3072. (24) Bailey, W. F.; Brubaker, J. D.; Jordan, K. P. J. Organomet. Chem. 2003, 681, 210.
133
(25) Boymond, L.; Rottländer, M.; Cahiez, G.; Knochel, P. Angew. Chem. Int. Ed. 1998, 37, 1701. (26) Jensen, A. E.; Dohle, W.; Sapountzis, I.; Lindsay, D. M.; Vu, V. A.; Knochel, P. Synthesis 2002, 2002, 565. (27) Knochel, P.; Dohle, W.; Gommermann, N.; Kneisel, F. F.; Kopp, F.; Korn, T.; Sapountzis, I.; Vu, V. A. Angew. Chem. Int. Ed. 2003, 42, 4302. (28) Krasovskiy, A.; Krasovskaya, V.; Knochel, P. Angew. Chem. Int. Ed. 2006, 45, 2958. (29) Prasad, A. S. BMJ 2003, 326, 409. (30) Hambidge, K. M.; Krebs, N. F. J. Nutr. 2007, 137, 1101. (31) Elschenbroich, C.; Salzer, A. Organometallics: A Concise Introduction, 2nd Edition; 2nd Edition edition.; John Wiley & Sons Canada, Ltd., 1992. (32) Fürstner, A. Synthesis 1989, 571. (33) Reformatsky, S. J. Russ. Phys. Chem. Soc 1890, 22, 44. (34) Reformatsky, S. N. Ber. Dtsch. Chem. Ges. 1887, 20, 1210. (35) Hunsdiecker, H.; Erlbach, H.; Vogt, E. 722467, 1942. (36) Simmons, H. E.; Smith, R. D. J Am Chem Soc 1958, 80, 5323. (37) Nakamura, E.; Satoshi, A.; Kouichi, S.; Hiroji, O.; Kuwajima, I. J. Am. Chem. Soc. 1987, 109, 8056. (38) Kobayashi, M.; Negishi, E. J. Org. Chem. 1980, 45, 5223. (39) Negishi, E. Acc. Chem. Res. 1982, 15, 340. (40) Knochel, P.; Jones, P. Organozinc Reagents: A Practical Approach; 1 edition.; Oxford University Press, USA, 1999. (41) Lishan, Z.; Wehmeyer, R.; Rieke, R. D. J. Org. Chem. 1991, 56, 1445. (42) Knochel, P.; Singer, R. D. 1993, 93, 2117. (43) Gaudemar, M. Synthesis 1977, 205. (44) Gaudemar, M. Bull. Soc. Chim. Fr. 1962, 974. (45) Knochel, P.; Normant, J. F. Tetrahedron Lett. 1986, 1039. (46) 2013, -April 15. [ ORGANOMETALLICS IN SYNTHESIS, THIRD MANUAL ] By Schlosser, Manfred; John Wiley & Sons, 2013. (47) Knochel, P. Synlett 1995, 393. (48) Knochel, P.; Yeh, M. C. P.; Scott, C.; Talbert, J. J. Org. Chem. 1988, 53, 2390. (49) Knochel, P.; Yeh, M. C. . Tetrahedron Lett. 1988, 29, 2395. (50) Arai, M.; Kawasuji, T.; Nakamura, E. J. Org. Chem. 1993, 58, 5121. (51) Chen, H. G.; Gage, J. L.; Barrett, S. D.; Knochel, P. Tetrahedron Lett. 1990, 31, 1829. (52) Negishi, E.; Bagheri, V.; Chatterjee, S.; Luo, F. T.; Miller, J. A.; Stoll, A. T. Tetrahedron Lett. 1983, 24, 5181. (53) Löffler, A.; Himbert, G. Synthesis 1992, 495. (54) Mignani, G.; Leising, F.; Meyrueix, R.; Samson, H. Tetrahedron Lett. 1990, 31, 4743. (55) Satoshi, H.; Yamashina, N.; Hara, S.; Suzuki, A. Chem. Lett. 1988, 809. (56) Kjonaas, R. A.; Vawter, E. J. J. Org. Chem. 1986, 51, 3993. (57) Kjonaas, R. A.; Hoffer, R. K. J. Org. Chem. 1988, 4133. 134
(58) Kondo, Y.; Takazawa, N.; Yamazaki, C.; Sakamoto, T. J. Org. Chem. 1994, 59, 4717. (59) Uchiyama, M.; Koike, M.; Kameda, M.; Kondo, Y.; Sakamoto, T. J. Am. Chem. Soc 1996, 118, 8733. (60) Knochel, P.; Jones, P. Organozinc Reagents: A Practical Approach; 1 edition.; Oxford University Press, USA, 1999. (61) Coates, G. E.; Ridley, D. J. Chem. Soc. A. 1966, 1064. (62) Miller, R. G.; Sorrell, S. R. Philos. Trans. R. Soc. Math. Phys. Eng. Sci. 2014, 372, 20130179. (63) Gerngross, T. U.; Slater, S. C. Sci. Am. 2000, 283, 36. (64) Chum, P. S.; Swogger, K. W. Prog. Polym. Sci. 2008, 33, 797. (65) Lithner, D.; Larsson, Å.; Dave, G. Sci. Total Environ. 2011, 409, 3309. (66) Leaversuch, R. Plast. Technol. 2002, 48, 66. (67) Doppalapudi, S.; Jain, A.; Khan, W.; Domb, A. J. Polym. Adv. Technol. 2014, 25, 427. (68) Buchard, A.; Bakewell, C. M.; Weiner, J.; Williams, C. K. In Organometallics and Renewables; Meier, M. A. R.; Weckhuysen, B. M.; Bruijnincx, P. C. A., Eds.; Topics in Organometallic Chemistry; Springer Berlin Heidelberg, 2012; pp. 175– 224. (69) Chisholm, M. H. Pure Appl. Chem. 2010, 82, 1647. (70) Ueda, H.; Tabata, Y. Adv. Drug Deliv. Rev. 2003, 55, 501. (71) Tang, L.; Zhao, C.; Xiong, Y.; Wang, A. Int. Orthop. 2010, 34, 755. (72) Blaker, J. J.; Bismarck, A.; Boccaccini, A. R.; Young, A. M.; Nazhat, S. N. Acta Biomater. 2010, 6, 756. (73) Grundmann, S.; van Royen, N.; Pasterkamp, G.; Gonzalez, N.; Tijsma, E. J.; Piek, J. J.; Hoefer, I. E. J. Am. Coll. Cardiol. 2007, 50, 351. (74) Yu, N.; Schindeler, A.; Peacock, L.; Mikulec, K.; Baldock, P.; Ruys, A. J.; Little, D. G. Eur. Cell Mater. 2010, 20, 431. (75) Hasegawa, S.; Neo, M.; Tamura, J.; Fujibayashi, S.; Takemoto, M.; Shikinami, Y.; Okazaki, K.; Nakamura, T. J. Biomed. Mater. Res. A 2007, 81A, 930. (76) Ulery, B. D.; Nair, L. S.; Laurencin, C. T. J. Polym. Sci. Part B Polym. Phys. 2011, 49, 832. (77) Buntara, T.; Noel, S.; Phua, P. H.; Melián-Cabrera, I.; de Vries, J. G.; Heeres, H. J. Angew. Chem. Int. Ed. 2011, 50, 7083. (78) Ghosh, S. J. Chem. Res. 2004, 2004, 241. (79) Domb, A. J.; Kumar, N. Biodegradable Polymers in Clinical Use and Clinical Development; 1 edition.; Wiley: Hoboken, NJ, 2011. (80) Lohmeijer, B. G. G.; Pratt, R. C.; Leibfarth, F.; Logan, J. W.; Long, D.; Dove, A.; Nederberg, F.; Jeongsoo, C.; Wade, C.; Waymouth, R. M.; Hedrick, L. Macromolecules 2006, 39, 8574. (81) Nederberg, F.; Connor, E. F.; Moeller, M.; Glauser, T.; Hedrick, J. L. Angew. Chem. Int. Ed. 2001, 40, 2712. (82) Albertsson, A.-C.; Srivastava, R. K. Adv. Drug Deliv. Rev. 2008, 60, 1077.
135
(83) Numata, keiji; Srivastava, R. K.; Finne-Wistrand, A.; Albertsson, A.-C.; Doi, Y.; Abe, H. Biomacromolecules 2007, 8, 3115. (84) O’Keefe, B. J.; Hillmyer, M. A.; Tolman, W. B. Dalton Trans. 2215. (85) Wheaton, C. A.; Hayes, P. G.; Ireland, B. J. Dalton Trans. 2009, 4832. (86) Kricheldorf, H. R.; Boettcher, C.; Tönnes, K.-U. Polymer 1992, 33, 2817. (87) Chisholm, M. H.; Zhou, Z. In Stereoselective Polymerization with Single-Site Catalysts; CRC Press: Boca Raton, 2007. (88) Chamberlain, B. M.; Cheng, M.; Moore, D. R.; Ovitt, T. M.; Lobkovsky, E. B.; Coates, G. W. J. Am. Chem. Soc. 2001, 123, 3229. (89) Brochu, S.; Prud’homme, R. E.; Barakat, I.; Jerome, R. Macromolecules 1995, 28, 5230. (90) Ovitt, T. M.; Coates, G. W. J. Am. Chem. Soc 2002, 124, 1316. (91) Degée, P.; Dubois, P.; Jérǒme, R.; Jacobsen, S.; Fritz, H.-G. Macromol. Symp. 1999, 144, 289. (92) Platel, R. H.; Hodgson, L. M.; Williams, C. K. Polym. Rev. 2008, 48, 11. (93) Stevels, W. M.; Ankoné, Marc J. K.; Dijkstra, P. J.; Feijen, J. Macromolecules 1996, 29, 6132. (94) Ma, H.; Spaniol, T. P.; Okuda, J. Angew. Chem. Int. Ed. 2006, 45, 7818. (95) Ma, H.; Spaniol, T. P.; Okuda, J. Inorg. Chem. 2008, 47, 3328. (96) Ajellal, N.; Lyubov, D. M.; Sinenkov, M. A.; Fukin, G. K.; Cherkasov, A. V.; Thomas, C. M.; Carpentier, J.-F.; Trifonov, A. A. Chem. – Eur. J. 2008, 14, 5440. (97) Mahrova, T. V.; Fukin, G. K.; Cherkasov, A. V.; Trifonov, A. A.; Ajellal, N.; Carpentier, J.-F. Inorg. Chem. 2009, 48, 4258. (98) Grunova, E.; Kirillov, E.; Evgueni, R.; Carpentier, J.-F. Organometallics 2008, 27, 5691. (99) Bouyahyi, M.; Ajellal, N.; Kirillov, E.; Thomas, C. M.; Carpentier, J.-F. Chem. – Eur. J. 2011, 17, 1872. (100) Kowalski, A.; Duda, A.; Penczek, S. Macromolecules 1998, 31, 2114. (101) Trofimoff, L.; Aida, T.; Inoue, S. Chem. Lett. 1987, 991. (102) Chen, H.-L.; Dutta, S.; Huang, P.-Y.; Lin, C.-C. Organometallics 2012, 31, 2016. (103) Chisholm, M.; Gallucci, J.; Quisenberry, K.; Zhou, Z. Inorg. Chem. 2008, 2613. (104) Du, H.; Velders, A. H.; Dijkstra, P. J.; Sun, J.; Zhong, Z.; Chen, X.; Feijen, J. Chem. – Eur. J. 2009, 15, 9836. (105) Chisholm, M.; Gallucci, J.; Phomphrai, K. Inorg. Chem. 2002, 41, 2785. (106) Chisholm, M.; Gallucci, J.; Phomphrai, K. Inorg. Chem. 2004, 43, 6717. (107) Chisholm, M.; Gallucci, J.; Phomphrai, K. Chem. Commun. 2003, 48. (108) Chamberlain, B. M.; Cheng, M.; Moore, D.; Ovitt, T. M.; Lobkovsky, E. B.; Coates, G. W. J. Am. Chem. Soc 2001, 123, 3229. (109) Dove, A. P.; Gibson, V. C.; Marshall, E. L.; White, A. J. P.; Williams, D. J. Dalton Trans. 2004, 570. (110) Chisholm, M.; Gallucci, J.; Phomphrai, K. Inorg. Chem. 2005, 44, 8004. (111) Chivers, T.; Fedorchuk, C.; Parvez, M. Inorg. Chem. 2004, 43, 2643. (112) Chivers, T.; Fedorchuk, C.; Parvez, M. 2005, 24, 580. (113) King, E. R.; Betley, T. A. Inorg. Chem. 2009, 48. 136
(114) Carla, N. A.; Malcolm, H. C.; Judith, C. G.; Clemens, K. Dalton Trans. 2009, 9237. (115) 1997, -February 26. Methods in Enzymology, Volume 276: Macromolecular Crystallography, Part A; 1 edition.; Academic Press, 1997. (116) sheldrick, G. M. Acta Crystallogr. 2007, 64, 112. (117) Farrugia, L. J. J. Appl. Crystallogr. 1999, 32, 837. (118) Wilson, A. J. C.; Geist, V. Cryst. Res. Technol. 1993, 28, 110. (119) Campbell, R.; Cannon, D.; Garcia-Alvarez, P.; Kennedy, A. R.; Mulvey, R. E.; Robertson, S. D.; Sassmannshausen, J.; Tuttle, T. J. Am. Chem. Soc 2011, 133, 13706. (120) Mulvey, R. E. Acc. Chem. Res. 2009, 42, 743. (121) Moore, D. R.; Cheng, M.; Lobkovsky, E. B.; Coates, G. W. J. Am. Chem. Soc 2003, 125, 11911. (122) Whitesides, G. M.; Witanowski, M.; Roberts, J. D. J. Am. Chem. Soc 1965, 87, 2854. (123) Shannon, R. D. Acta Crystallogr. Sect. A 1976, 32, 751. (124) Pang, K.; Rong, Y.; Parkin, G. Polyhedron 2010, 29, 1881. (125) Chisholm, M. H.; Choojun, K.; Chow, A. S.; Fraenkel, G. Angew. Chem. Int. Ed. 2013, 52, 3264. (126) Chisholm, M. H.; Choojun, K.; Chow, A. S.; Gideon, F.; Gallucci, J. C. Inorg. Chem. 2013, 52, 11302. (127) Balasanthiran, V.; Chisholm, M. H.; Choojun, K.; Durr, C. B. Dalton Trans. 2014, 43, 2781. (128) Brookhart, M.; Green, M. L. H. J. Organomet. Chem. 1983, 250, 395. (129) Brookhart, M.; Green, M. L. H.; Parkin, G. Proc. Natl. Acad. Sci. U. S. A. 2007, 104, 6908. (130) Darensbourg, D. J.; Holtcamp, M.; Struck, G. E.; Zimmer, M. S.; Niezgoda, S. A.; Rainey, P.; Robertson, J. B.; Draper, J. D.; Reibenspies, J. H. J. Am. Chem. Soc 1999, 121, 107. (131) Pearce, E. Contemporary Topics in Polymer Science: Volume 2; Softcover reprint of the original 1st ed. 1977 edition.; Springer, 2012. (132) Darensbourg, D. J.; Karroonnirun, O. Macromolecules 2010, 43, 8880. (133) Shen, Y.; Zhu, K. J.; Shen, Z.; Yao, K.-M. J. Polym. Sci. Part Polym. Chem. 1996, 34, 1799. (134) Song, C. X.; Feng, X. D. Macromolecules 1984, 17, 2764. (135) lahcini, M.; Castro, P. M.; Kalmi, M.; Leskelae, M.; Repo, T. Organometallics 2004, 23, 4547. (136) Wei, Z.; Liu, L.; Yu, F.; Wang, P.; Qu, C.; Qi, M. Polym. Bull. 2008, 61, 407. (137) Vion, J. M.; Jerome, R.; Teyssie, P.; Aubin, M.; Prudhomme, R. E. Macromolecules 1986, 19, 1828. (138) Vanhoorne, P.; Dubois, P.; Jerome, R.; Teyssie, p. Macromolecules 1992, 25, 37. (139) Florczak, M.; Duda, A. Angew. Chem. Int. Ed. 2008, 47, 9088.
137