Florida State University Libraries Electronic Theses, Treatises and Dissertations The Graduate School 2011 Gold (I)-Catalyzed Claisen Rearrangement of Allenyl Vinyl Ethers: A Synthetic and Mechanistic Approach Kassem M. Hallal Follow this and additional works at the FSU Digital Library. For more information, please contact [email protected] THE FLORIDA STATE UNIVERSITY COLLEGE OF ARTS AND SCIENCES GOLD (I)-CATALYZED CLAISEN REARRANGEMENT OF ALLENYL VINYL ETHERS; A SYNTHETIC AND MECHANISTIC APPROACH By KASSEM M. HALLAL A Dissertation submitted to the Department of Chemistry and Biochemistry in partial fulfillment of the requirements for the degree of Doctor of Philosophy Degree Awarded: Spring Semester, 2011 The members of the committee approve the dissertation of Kassem M. Hallal defended on March 18, 2011. _______________________________________ Marie E. Krafft Professor Directing Dissertation _______________________________________ Thomas C. S. Keller III University Representative _______________________________________ Robert A. Holton Committee Member _______________________________________ Gregory B. Dudley Committee Member _______________________________________ William T. Cooper Committee Member Approved: ____________________________________________________________ Joseph B. Schlenoff, Chair, Department of Chemistry and Biochemistry The Graduate School has verified and approved the above-named committee members. ii This work is dedicated To My soul mate, lovely wife zeinab, My baby Mohammad And also to my parents Mohammad & Kamela And to My brothers and lovely sister Youssef, Hamzeh and Fatima & My Great professor Prof. Marie E. Krafft iii ACKNOWLEDGEMENTS Starting my PhD career at Florida State University was one of the most important stages in my life. Throughout the past five years, I learned a lot of things about chemistry and science, however, the most important thing which I learned was the chemistry of life. I would like to express my gratitude to all the people whom I met at Florida State University and to all the lovely and friendly people I met and lived with, in this country. Primarly, I would like to express my sincerest gratitude to my professor Marie E. Krafft, for giving me this opportunity to join her research group, for her guidance, patience and support. For me, Dr. Krafft was more than an advisor, her understanding, kindness and sympathy with me in many of the hard times I had, made me feel that she was the friend and mother whom I was in need in these situations. I am grateful to all my committee members, Professor R. A. Holton, Professor G.B. Dudley, Professor W.T. Cooper, and T. C. S. Keller for all their helpful corrections and notes. I would also like to express my special thanks to Professor Joseph Schlenoff and Prof. Ali Safa for helping me to apply to FSU and to all the professors and staff at the chemistry department for their help and support. I am grateful to Dr. John Cran who taught me all the experimental techniques at the beginning of my Ph.D. career and for all the experience he shared with me during this time. I would also thank all the members in our group Dr. Andrew franklin, Dr. Dinesh Vidani, and Gabe Loyo. I would also like to thank Kyle Manning who helped me at the end of my project. I would also like to thank all my friends, Imad, Sami, Abdulkader, and Ali, for their friendship and support during this period. Finally, all this work wouldn’t have been completed without the help and support of my almighty God and without the prayers of my parents Mohammad, Kamela, my brothers Youssef and Hamzeh, my lovely little sister Fatima and my lovely wife Zeinab. iv TABLE OF CONTENTS List of Tables……………………………………………………………………………………viii List of Figures………………………………………………………………………………….....ix Standard List of Abbreviations ...……………….……………..………………………………..xiv Abstract……………………………………………………………………………………….…xix I. INTRODUCTION .……………...……...……………...……………………………….………1 A. Homogenous Gold Catalysis …………...………………...……………….………………..1 1. Historical overview………………………………………………………………….. 1 2. Chemical properties of gold ……………………………………………………...…..2 3. Gold-cation -ligand interaction……………………………………………………...3 B. Claisen Rearrangement ……………………………………………………………………13 1. Introduction…………………….……….……………………….…………………..13 2. Reaction mechanism………………………………………………………………...13 3. Factors affecting the reaction rate ……………………………………….………….14 4. Lewis acid catalysis of the Claisen Rearrangement.………………………….……. 19 5. Asymmetric catalysis………………………………………………………………..22 6. Synthesis of Organic Building Blocks via Claisen Rearrangement…………………22 II. GOLD (I)-CATALYZED CLAISEN REARRANGEMENT OF ALLENYL VINYL ETHERS; SYNTHESIS OF 1,3-DIENES…………………...………….....……………………26 1. Introduction…………………………………………………….……………………26 2. Synthesis of dienes via isomerization reactions…………………………..…………26 3. Results and discussion………………………………………………...…………….28 4. Generality of the procedure…………………………………...…………………….34 5. Effect of the electronic nature of the C-4 substituent on the reaction rate……….…39 v 6. Conclusion………………………………………..………………………………...45 III. MECHANISTIC STUDY OF THE GOLD (I)-CATALYZED CLAISEN REARRANGE- MENT OF ALLENYL VINYL ETHERS………..……………………………….…………….46 A. Ligand Effects……………………………………………………………………………..46 1. Introduction………………………………………………………………………….46 2. N-heterocyclic carbene (NHC) ligands……………………………………………...47 3. NHC ligands in gold catalysis……………………………………………………….50 4. NHC ligands versus phosphine ligands……………………………………………..52 5. Results and discussion………………………………………………………………53 B. Mechanism of the gold-catalyzed Claisen rearrangement of allenyl vinyl ethers………....60 1. First proposed mechanism “coordination of gold to the allene” ……………………60 2. Second proposed mechanism “coordination of gold to the vinyl ether”…............…62 3. Third proposed mechanism “coordination of gold to the vinyl ether and allene”... ..65 4. Substituent effects “Cation- interaction” ...………………………………………..66 C. Kinetic study……………………….………………………………………………………67 1. Order in vinyl ether………………………………………………………………….67 2. Order in gold………………………………………………………………………...69 3. Interpretation of results…………………………………………………..………….72 D. Conclusion…………….. …………………………………..……………………………...75 IV. EXPERIMENTAL SECTION………………………………………………………………76 A. General information…………………………………………………………………..……76 B. Synthesis of substrates……………………………………………………………………..77 1. General procedure for synthesis of propargylic alcohols …………………………..77 2. General procedure for synthesis of allenols…………………………………………78 3. General procedure for synthesis of allenyl vinyl ethers……………………………..80 C. General procedure for the gold (I)-catalyzed Claisen rearrangement of allenyl vinyl ether……………………………...………………………………………………………..…..88 D. Ligand effects on the gold (I)-catalyzed Claisen rearrangement of allenyl vinyl ethers..…98 vi E. Kinetic analysis of the gold (I)-catalyzed Claisen rearrangement………...……………….99 1. General procedure for kinetic experiments………………………………………….99 2. Order in vinyl ether……………………………………………………...…………..99 3. Order in gold………………………….…………………………….……………...100 APPENDIX……………………………………………………………………………………..101 NMR SPECTRA………………………………………………………………………………..101 REFERNCES…………………………………………………………………………………...178 BIOGRAPHICAL SKETCH…………………………………………………………………..188 vii LIST OF TABLES Table 1. Substituents' effect on the rate of the Claisen rearrangement ................................... 16 Table 2. Catalyst screening. .................................................................................................. 30 Table 3. Optimization of reaction conditions using AuClPPh3/AgSbF6. ................................ 32 Table 4. Optimization of reaction conditions ........................................................................ 33 Table 5. Scope of the reaction. .............................................................................................. 36 Table 6. Rearrangement of subtrates with aromatic substitution at C-4. ................................ 40 Table 7. Effect of additives on the rate of rearrangement of 32c. ........................................... 44 Table 8. co stretching frequencies in LNi(CO)3 complexes. .................................................. 55 Table 9. Ligand effects on reaction rate. ............................................................................... 56 Table 10. %Vbur for ligands in LAuCl complexes. ................................................................ 59 Table 11. Rearrangement of allenyl vinyl ethers under thermal and catalytic conditions. ...... 61 Table 12. Change of [VE] & [P] with time. ........................................................................... 67 Table 13. kobs (R0) at different catalyst concentrations. ......................................................... 71 viii LIST OF FIGURES Figure 1. Gold catalysts with different ligands. ..................................................................... 31 Figure 2. Proposed transition state of the gold(I)-catalyzed Claisen rearrangement of allenyl vinyl ethers analogous to the propargyl Claisen rearrangement ............................................. 42 Figure 3. Common structure of NHC's (A), Singlet electronic configuration of NHC's (B). .. 47 Figure 4. Molecular orbitals of NHC's. ................................................................................. 48 Figure 5. Gold ligands .......................................................................................................... 54 Figure 6. Plot of [VE], [P] and ([VE] + [P]) vs. time. ...........................................................