Computational Mechanistic Studies of Decamethyldizincocene Formation and the Enantioselective Reactive Nature of a Chiral Neutral Zirconium Amidate Complex by Steven Scott Hepperle B.Sc. Honours, University of Regina, Canada, 2004 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY in The Faculty of Graduate Studies (Chemistry) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) August 2011 c Steven Scott Hepperle 2011 Abstract Computational methods were employed to study the surprising 2004 synthesis of de- 5 camethyldizincocene, Zn2(η −C5Me5)2, which was the first molecule to have a di- rect, unbridged bond between two first-row transition metals. The computational re- 5 1 sults show that the methyl groups of decamethylzincocene, Zn(η −C5Me5)(η −C5Me5), affect the transition-state stability of its reaction with ZnEt2 (or ZnPh2) through steric hindrance, and this allows a counter-reaction, the homolytic dissociation of 5 1 5 1 Zn(η −C5Me5)(η −C5Me5) into Zn(η −C5Me5)• and (η −C5Me5)• radicals to occur, 5 1 and since no such steric hindrance exists when zincocene, Zn(η −C5H5)(η −C5H5), is used as a reactant, its dissociation never occurs. Experimentally, it was found that forming decamethyldizincocene is more efficient when using a reducing agent (e.g., KH) and ZnCl2 as opposed to a ZnR2 reagent. The computational results show that the methyl groups of decamethylzincocene have a similar indirect effect on the reaction. When zincocene is used, the reaction with + 1 − KH favours the route that results in the formation of the zincate, K [Zn(η −C5H5)3] . + 1 − However, the path of formation for the zincate K [Zn(η −C5Me5)3] is simply not favourable kinetically or thermodynamically, so the formation of decamethyldizincocene 5 1 is the only option when Zn(η −C5Me5)(η −C5Me5) is used. Finally, it had been found that a particular chiral neutral zirconium amidate com- plex makes an effective catalyst for cyclizing primary aminoalkenes in a highly enan- tioselective fashion. The computational analysis indicates that the reason why one enantiomer is favoured is because of steric interference with the catalytic backbone that is non-existent with the other enantiomer, and this affects the major transition states throughout the cycle. This finding agrees with the experimental hypothesis. ii Preface An early version of Chapter 2 (the reactions of zincocene and decamethylzincocene with ZnEt2) was published in the Journal of Physical Chemistry (2008) with my research supervisor (Y.A. Wang) as the principal investigator (Hepperle, S.S.; Wang, Y.A. J. Phys. Chem. A 2008, 112, 9619-9622).1 The remainder of Chapter 2 as well as Chapter 3 is currently unpublished pending final data. Again, Dr. Wang is the principal investigator on this work. The research in Chapter 4 was performed in collaboration with a Ph. D. student, Yue Chen, at Beijing Normal University in China. Yue Chen performed all calcula- tions on the σ−bond insertion mechanism while I worked on the [2+2] cycloaddition mechanism. Before the collaboration began, Chen performed many calculations on the [2+2] mechanism as well which served as a check against my data. Due to time constraints, Chen provided me with the sterically correct starting geometries for the final transition state (zregeneration) for both the R and S conformers. Otherwise, the [2+2] data presented in this thesis (and the upcoming publication) were compiled by me. Yue Chen will be the primary author of this work while I will be the secondary author. Principal Investigators in this work include Guofu Zi and Weihei Fang (Beijing Normal University) with Laurel L. Schafer and Yan Alexander Wang (University of British Columbia). iii Table of Contents Abstract ....................................... ii Preface ....................................... iii Table of Contents ................................. iv List of Tables ................................... vii List of Figures ................................... x List of Abbreviations . xiii Acknowledgements ................................ xiv Dedication ..................................... xvi 1 Introduction .................................. 1 1.1 Discussion of Computational Chemistry . 1 1.1.1 Simplifying an Impossibly-Sized System . 1 1.1.2 Introducing the Electronic Wave Function . 2 1.1.3 The Born-Oppenheimer Approximation . 3 1.1.4 The Orbital . 4 1.1.5 Building the Electronic Wave Function . 7 1.1.6 Hartree-Fock Self-Consistent Field Method . 9 iv Table of Contents 1.1.7 Geometry Optimizations . 13 1.1.8 Density Functional Theory . 13 1.1.9 Configuration Interaction . 16 1.1.10 Møller-Plesset Second-order Perturbation Theory . 17 1.1.11 Solvent Effects . 18 1.1.12 Vibrational Frequencies of Molecules . 19 1.1.13 Equilibrium Statistical Mechanics . 21 1.2 Metallocene Chemistry and Decamethyldizincocene . 24 1.3 Enantioselective Catalysis with Primary Aminoalkenes . 27 2 Formation of Decamethyldizincocene via Decamethylzincocene and ZnR2 ...................... 32 2.1 Strategy and Methods . 32 2.2 Results and Discussion . 34 2.2.1 Neutral-Charge Electrostatic Dizincocene Formation via ZnEt2 5 1 and Zn(η −C5H5)(η −C5H5) ................... 35 2.2.2 Neutral-Charge Electrostatic Decamethyldizincocene Formation 5 1 via ZnEt2 and Zn(η −C5Me5)(η −C5Me5) . 35 2.2.3 Radical Dissociation of Parent Zincocenes . 38 2.2.4 Reaction of Parent Zincocenes with Other ZnR2 Reagents . 38 2.3 Summary and Further Work . 42 3 Formation of Decamethyldizincocene via KH and ZnCl2 ................................. 43 3.1 Strategy and Methods . 43 3.2 Results and Discussion . 47 3.2.1 Reaction of 1 and 5 with KH . 47 3.2.2 Reaction of 1 and 5 with KH and ZnCl2 . 50 v Table of Contents 3.3 Summary and Future Work . 58 4 Enantioselective Catalysis of Primary Aminoalkenes via a Chiral Neu- tral Zirconium Amidate Complex ..................... 59 4.1 Strategy and Methods . 59 4.2 Results and Discussion . 60 4.3 Summary and Future Work . 67 5 Conclusion ................................... 68 Bibliography .................................... 71 Appendices Appendix A - Calculated Energies for Chapter 2 . 77 Appendix B - Calculated Energies for Chapter 3 . 83 Appendix C - Calculated Energies for Chapter 4 . 88 vi List of Tables 2.1 Energy compilation of zsymmetric and the energy difference (in kcal/mol) between the symmetric process and radical dissociation of the parent zin- cocene. 41 3.1 Reaction energies (in kcal/mol) of 1 and 5 reacting with KH (from Fig- ures 3.2 and 3.3, respectively). Energies are relative to separated reactants. 50 3.2 Reaction energies (in kcal/mol) of 1 and 5 reacting with KH and ZnCl2 (from Figures 3.11 and 3.12, respectively). Energies are relative to sep- arated reactants. 57 A.1 Reaction energies (in hartrees) of 5 reacting with ZnEt2. B3LYP thermal corrections were at 263 K and MP2 single point energies used IEF-PCM for diethyl ether.) . 77 A.2 Reaction energies (in hartrees) of 1 reacting with ZnEt2. B3LYP thermal corrections were at 263 K and MP2 single point energies used IEF-PCM for diethyl ether.) . 78 A.3 Reaction energies (in hartrees) of 5 reacting with ZnMe2. B3LYP ther- mal corrections were at 263 K and MP2 single point energies used IEF- PCM for diethyl ether.) . 78 A.4 Reaction energies (in hartrees) of 1 reacting with ZnMe2. B3LYP ther- mal corrections were at 263 K and MP2 single point energies used IEF- PCM for diethyl ether.) . 79 A.5 Reaction energies (in hartrees) of 5 reacting with ZniPr2. B3LYP ther- mal corrections were at 263 K and MP2 single point energies used IEF- PCM for diethyl ether.) . 79 vii List of Tables A.6 Reaction energies (in hartrees) of 1 reacting with ZniPr2. B3LYP ther- mal corrections were at 263 K and MP2 single point energies used IEF- PCM for diethyl ether.) . 80 A.7 Reaction energies (in hartrees) of 5 reacting with ZnPh2. B3LYP thermal corrections were at 263 K and MP2 single point energies used IEF-PCM for diethyl ether.) . 80 A.8 Reaction energies (in hartrees) of 1 reacting with ZnPh2. B3LYP thermal corrections were at 263 K and MP2 single point energies used IEF-PCM for diethyl ether.) . 81 A.9 Homolytic dissociation energy components for (in hartrees) for 5, 6, 1, and 3. Raw ROB3LYP complex energies include counterpoise correc- tions. B3LYP Thermal corrections were at 263 K and MP2 single point energies used IEF-PCM for diethyl ether. ROMP2 SP Counterpoise corrections computed separately using counterpoise optimized B3LYP geometries. zc = CpZnCp, dz = CpZnZnCp, dmz = Me5CpZnCpMe5, dmdz = Me5CpZnZnCpMe5......................... 82 B.1 Homolytic dissociation energy components for (in hartrees) for 3 and 6 (Step 3a), and CpZnK and Me5CpZnK (Step 2a). Raw ROB3LYP complex energies include counterpoise corrections. B3LYP Thermal cor- rections were at 263 K and MP2 single point energies used IEF-PCM for Tetrahydrofuran. ROMP2 SP Counterpoise corrections computed sepa- rately using counterpoise optimized B3LYP geometries. dz = CpZnZnCp, dmdz = Me5CpZnZnCpMe5......................... 83 B.2 Reaction energies (in hartrees) of 5 reacting with KH. B3LYP thermal corrections were at 293 K and MP2 single point energies used IEF-PCM for tetrahydrofuran. 84 B.3 Additional reaction energies (in hartrees) of 5 reacting with KH as well as ZnCl2. B3LYP thermal corrections were at 293 K and MP2 single point energies used IEF-PCM for tetrahydrofuran. 85 B.4 Reaction energies (in hartrees) of 1 reacting with KH. B3LYP thermal corrections were at 293 K and MP2 single point energies used IEF-PCM for tetrahydrofuran. 86 viii List of Tables B.5 Additional reaction energies (in hartrees) of 1 reacting with KH as well as ZnCl2. B3LYP thermal corrections were at 293 K and MP2 single point energies used IEF-PCM for tetrahydrofuran. 87 C.1 Reaction energies (in hartrees) for the catalytic cycle for the S product. B3LYP thermal corrections were at 383 K and MP2 single point energies used IEF-PCM for toluene. 88 C.2 Reaction energies (in hartrees) for the catalytic cycle for the R product.