University of Alberta Cobalt(III)-Mediated Cycloalkenyl-Alkyne Cycloaddition and Cycloexpansion Reactions by Bryan Chi Kit Chan A thesis submitted to the Faculty of Graduate Studies and Research in partial fulfillment of the requirements for the degree of Doctor of Philosophy Chemistry ©Bryan Chi Kit Chan Spring 2010 Edmonton, Alberta Permission is hereby granted to the University of Alberta Libraries to reproduce single copies of this thesis and to lend or sell such copies for private, scholarly or scientific research purposes only. Where the thesis is converted to, or otherwise made available in digital form, the University of Alberta will advise potential users of the thesis of these terms. The author reserves all other publication and other rights in association with the copyright in the thesis and, except as herein before provided, neither the thesis nor any substantial portion thereof may be printed or otherwise reproduced in any material form whatsoever without the author's prior written permission. Examining Committee Jeffrey M. Stryker, Chemistry, University of Alberta Martin Cowie, Chemistry, University of Alberta Jillian M. Buriak, Chemistry, University of Alberta Frederick G. West, Chemistry, University of Alberta William C. McCaffrey, Chemical Engineering, University of Alberta Lisa Rosenberg, Chemistry, University of Victoria Abstract A comprehensive investigation of cycloalkenyl-alkyne coupling reactions mediated by cobalt(III) templates is presented. The in situ derived cationic η3- cyclohexenyl complexes of cobalt(III) react with some terminal alkynes to afford either η1,η4-bicyclo[4.3.1]decadienyl or η2,η3-vinylcyclohexenyl products, depending on the type and concentration of the alkyne. The mechanism for this cyclohexenyl-alkyne cycloaddition reaction is consistent with the previously reported cobalt-mediated [3 + 2 + 2] allyl-alkyne coupling reaction. The carbon-carbon bond activation/cyclopentenyl-alkyne ring expansion process was also studied using the 1,3-di-tert-butylcyclopentadienyl cobalt system. A modified synthetic strategy to the requisite half-sandwich cobalt(I) cyclopentadiene precursor was developed using cobalt(II) acetoacetonate, avoiding the use of simple cobalt(II) halides which are prone to ligand disproportionation. Furthermore, the preparation of the cobalt(III) 4 cyclopentenyl precursor, (t-Bu2C5H3)Co(η -C5H6), was accomplished via hydride addition to the easily prepared cobalticenium complex [(t-Bu2C5H3)Co(C5H5)]BF4 and avoids the use of the thermally sensitive (t-Bu2C5H3)Co(ethylene)2. Disubstituted alkynes such as 2-butyne or diphenylacetylene undergo cyclopentenyl coupling to afford the corresponding η5-cycloheptadienyl products, albeit in lower yields compared to the pentamethylcyclopentadienyl cobalt system. The 1,3-di-tert-butylcyclopentadienyl ancillary ligand shows unique and unusual reactivity, coupling with tert-butylacetylene to afford a novel spiro[4.5]decatrienyl complex. Ultimately, the poor isolated yields of seven- membered products demonstrate that the disubstituted cyclopentadienyl ligand system is a poor candidate for future studies in this area. A mechanistic investigation of the cobalt-mediated carbon-carbon bond activation process was performed. Cationic cobalt η2-vinyl complexes were proposed as viable intermediates in the activation process and synthetic routes to these compounds were examined. However, the resulting vinyl complexes were unstable and could not be directly isolated and characterized. Preparation of cobalt vinyl complexes in the presence of cycloalkadienes did not furnish the expected cycloexpanded products, suggesting alternative routes to the cobalt vinyl intermediates are necessary. During the course of the mechanistic 4 investigation, a high-yielding alternative synthetic procedure for (C5Me5)Co(η - butadiene) from the easily prepared precursor, [(C5Me5)CoI2]n, was found, circumventing the use of the thermally sensitive (C5Me5)Co(ethylene)2. Acknowledgements First and foremost, I would like to express my gratitude to my research advisor, Professor Jeffrey Stryker, for providing a creative and encouraging atmosphere during my time here. I also wish to acknowledge and thank former and current members of the Stryker Group that have provided me with motivation, thoughtful discussions and research insights. In no particular order, they are: Dr. Ross Witherell, Dr. David Norman, Dr. Rick Bauer, Dr. Owen Lightbody, Paul Fancy, Dr. Takahiro Saito, Kai Ylijoki, Andrew Kirk, Jeremy Gauthier, and Dr. Robin Hamilton. In particular, I would like to thank Dr. Masaki Morita for being a repository of chemical knowledge. The staff of analytical and spectral services is also thanked for their assistance in characterizing compounds, especially Drs. Bob McDonald and Michael Ferguson for the numerous X-ray structure determinations. Lastly, I would like to thank my friends and family for their support, encouragement and understanding. Table of Contents Page Chapter 1. Introduction and Background .................................................... 1 Section 1. General Introduction.......................................................... 1 Section 2. Metal-Mediated Allyl-Alkyne Coupling Reactions .............. 8 A. Introduction .......................................................................... 8 B. Catalytic Allyl-Alkyne Coupling Processes ............................. 10 C. Stoichiometric Allyl-Alkyne Coupling Reactions .................... 22 D. Multiple Allyl-Alkyne Coupling Reactions .............................. 32 E. [3 + 2] Allyl-Alkyne Cycloaddition Reactions .......................... 37 Conclusions ....................................................................................... 41 Chapter 2. [3 + 2 + 2] Allyl-Alkyne Cycloaddition Reactions of Agostic Cobalt Cyclohexenyl Complexes......................................................... 42 Section 1. Introduction ..................................................................... 42 A. [3 + 2 + 2] Allyl-Alkyne Cycloaddition Reactions .................... 43 B. Cobalt-Mediated [5 + 2] Cyclopentenyl-Alkyne Cycloaddition Reactions Involving Carbon-Carbon Bond Activation ............ 54 C. Cobalt-Mediated Cyclopentenyl-Acetylene Cycloaddition Reactions ............................................................................. 60 D. Project Goals ........................................................................ 64 Section 2. Results and Discussion ...................................................... 65 A. Cobalt η3-Cyclohexenyl-Acetylene Cycloaddition Reactions .. 65 3 B. Reactions of (C5Me5)Cobalt η -Cycloheptenyl and η3-Cyclooctenyl Complexes with Alkynes ............................. 88 C. Conclusions .......................................................................... 92 Chapter 3. 1,3-Di-tert-butylcyclopentadienyl Cobalt Complexes ................ 95 Section 1. Introduction ..................................................................... 95 A. Synthetic Routes to Cobaltocene Complexes ....................... 102 B. Project Goals ....................................................................... 104 Section 2. Results and Discussion ..................................................... 106 A. Preparation of 1,3-Di-tert-butylcyclopentadienyl Cobalt Templates ........................................................................... 106 B. Ring-Expansion Reactions of the (1,3-Di-tert- cyclopentadienyl)cobalt(η3-cyclopentenyl Complex With Alkyne ........................................................................ 127 C. Reactions of the (1,3-Di-tert-butylcyclopentadienyl)cobalt η3-Cyclohexenyl, η3-Cycloheptenyl, and η3-Cyclooctenyl Complexes with Alkynes...................................................... 139 D. Synthesis of Acyclic η5-Pentadienyl Complexes of Cobalt ..... 143 E. Conclusions.......................................................................... 153 Chapter 4. Mechanism and Intermediates in the Cyclopentenyl/Alkyne Carbon-Carbon Bond Activation Process ........................................... 155 Section 1. Introduction .................................................................... 155 A. Activation of Carbon-Carbon σ-Bonds in Strained Ring Systems .............................................................................. 157 B. Carbonyl Group Activation of Carbon-Carbon σ-Bonds ........ 159 C. Nitrile Group Activation of Carbon-Carbon σ-Bonds ............ 161 D. Proximity Effects ................................................................. 164 E. β-Carbon Elimination and Aromatization ............................. 168 F. Activation by Electrophilic Cobalt Complexes ....................... 176 G. Activation by Electrophilic Titanium Complexes .................. 177 H. Mechanistic Proposals for the [5 + 2] η3-Cyclopentenyl- Alkyne Cycloaddition/Carbon-Carbon Bond Activation Process ............................................................................... 180 I. General Formation of η2-Vinyl/1-Metalacyclopropene Complexes .......................................................................... 188 Section 2. Results and Discussion ..................................................... 193 A. Vinyl Grignard Addition to Cobalt(III) Precursors ................. 193 B. Vinyl Grignard Addition to Cobalt(II) Precursors .................. 200 C. Strong Acid Addition to Cobalt Mono-Alkyne Complex ........ 210 D. Conclusions and Future Goals.............................................. 213 Chapter 5. Experimental Procedures