University of Windsor Scholarship at UWindsor Electronic Theses and Dissertations Theses, Dissertations, and Major Papers 9-13-2019 Metal-Mediated Vinylogous Nazarov Cyclization Reaction Somaiah Khalid Almubayedh University of Windsor Follow this and additional works at: https://scholar.uwindsor.ca/etd Recommended Citation Almubayedh, Somaiah Khalid, "Metal-Mediated Vinylogous Nazarov Cyclization Reaction" (2019). Electronic Theses and Dissertations. 7798. https://scholar.uwindsor.ca/etd/7798 This online database contains the full-text of PhD dissertations and Masters’ theses of University of Windsor students from 1954 forward. These documents are made available for personal study and research purposes only, in accordance with the Canadian Copyright Act and the Creative Commons license—CC BY-NC-ND (Attribution, Non-Commercial, No Derivative Works). Under this license, works must always be attributed to the copyright holder (original author), cannot be used for any commercial purposes, and may not be altered. Any other use would require the permission of the copyright holder. Students may inquire about withdrawing their dissertation and/or thesis from this database. For additional inquiries, please contact the repository administrator via email ([email protected]) or by telephone at 519-253-3000ext. 3208. METAL-MEDIATED VINYLOGOUS NAZAROV CYCLIZATION REACTION By Somaiah Khalid Almubayedh A Dissertation Submitted to the Faculty of Graduate Studies through the Department of Chemistry and Biochemistry in Partial Fulfillment of the Requirements for the Degree of Doctor of Philosophy at the University of Windsor Windsor, Ontario, Canada © 2019 Somaiah K. Almubayedh Metal-Mediated Vinylogous Nazarov Cyclization Reaction by Somaiah Khalid Almubayedh APPROVED BY: _____________________________ R. Dembinski, External Examiner Oakland University _____________________________ I. Al-Aasm School of the Environment _____________________________ J. Rawson Department of Chemistry and Biochemistry _____________________________ S. Johnson Department of Chemistry and Biochemistry _____________________________ J. Green, Advisor Department of Chemistry and Biochemistry September 13, 2019 DECLARATION OF ORIGINALITY I hereby certify that I am the sole author of this thesis and that no part of this dissertation has been published or submitted for publication. I declare that, to the best of my knowledge, my dissertation does not infringe upon anyone’s copyright nor violate any proprietary rights and that any ideas, procedures, or any other material from the work other people included in my dissertation, published or otherwise, are fully acknowledged in accordance with the standard referencing practices. Furthermore, to the extent that I have included copyright material that surpasses the bounds of fair dealing within the meaning of the Canada Copyright Act, I certify that I have obtained written permission from the copyright owner(s) to include such material(s) in my dissertation. I declare that this is a true copy of my dissertation, including any final revisions, as approved by my dissertation committee and the Graduate Studies office, and that this dissertation has not been submitted for a higher degree to any other University or Institution. iii ABSTRACT The Nazarov cyclization reaction has been used as an effective method to synthesize cyclopentanones. While 6-membered ring systems can be available by way of the homo Nazarov variant, 7-membered ring formation involving a Nazarov-type reaction is very rare, and completely unknown thermally. Using the established concept of the ability of the alkyne-Co2(CO)6 moiety to enable the formation of g-carbonyl cations and the good stability of this generated cation, 7-membered ring formation via the vinylogous Nazarov reaction with electron deficient enones has been investigated. The desired aryl substituted enyone-Co2(CO)6 complex precursors for the cyclization reaction have been prepared from commercially available starting materials, using a series of reactions that include Sonogashira cross-coupling, desilylation, organolithium reactions with aldehydes, oxidation and complexation reactions. The treatment of the respective complex precursors, using SnCl4 as a suitable Lewis acid, successfully generated cycloheptynone-Co2(CO)6 complexes. The substitution effects have been examined, showing that introducing a bulky group at the a-position to the carbonyl enhances the cyclization efficiency by enabling the desired s-trans/s-trans conformation. On the other hand, b-substituting with an R group other than H atom reduces the reaction rate and allows formation of the desired 7-membered ring only in very low yield. Preparation of appropriate dienynone-Co2(CO)6 complex substrates allowed expansion of the reaction scope to non-aromatic starting materials. Successful reductive decomplexation of the cycloheptynone-Co2(CO)6 unit also was demonstrated. iv DEDICATION I dedicate this research to my sweet daughter Ritaj and my son Rakan, my beloved husband Mohammed, and to my parents Sondos and Khalid who gave me all their love and care. No words can express my gratitude for them, for they have always supported and encouraged me. ACKNOWLEDGMENTS First and foremost, I would like to express my sincere gratitude to my advisor Prof. James Green for the continuous support of my Ph.D. study and related research, for this patience, motivation, and immense knowledge. His support and guidance helped me in all the time of research and writing of this thesis. Beside my advisor, I would like to thank the rest of my thesis committee: Prof. Jeremy Rawson and Prof. Sam Johnson, for their insightful comments and encouragement, and for reading my thesis, but also for the hard question which motivated me to widen my research from various perspectives, and Dr. Ihsan Al-Aasm for his willingnes to act as the outside examiner. I would also like to thank past and present members of the Green group: Dr. Mariam Mehdi, Page Penner, Nathan Bazinski, Scott Adams and Brent St Onge and Jeff Battersby for all their advice, assistance, support, and friendship. I would like to extend further thanks to Matt Revington for his assistance with the NMR spectroscopy, to Joe Lichaa for all his technical support, and to Chemistry and Biochemistry department members in the surrounding labs and department for their friendship, interactions, and for sharing their chemicals. The big thanks to the v administrative staff: Marlene Bezaire and Elizabeth Kickham for their assistance during my four years at the University of Windsor; to the CCC previous and current staff: Jerry and Alina. I thank to Audithya Nyayachavadi for his assistance with the UV spectroscopy. I would like to give special thanks for Mohammad Tarawneh of the Chemistry department at the University of Jordan in Amman, who provided me an opportunity to tap his expertise in Chemistry for sharing the knowledge, and for valuable comments during my Ph.D. work. Finally, I must express my very profound gratitude to my parents and to my spouse for providing me with unfailing support and continuous encouragement throughout my years and years of study, and to my siblings. This accomplishment would not have been possible without them. Thank you. vi TABLE OF CONTENTS DECLARATION AND ORIGINALITY .......................................................................... iii ABSTRACT ....................................................................................................................... iv DEDICATION .................................................................................................................... v ACKNOWLEDGMENT ..................................................................................................... v LIST OF FIGURES .......................................................................................................... xii LIST OF SCHEMES ........................................................................................................ xiii LIST OF TABLES ........................................................................................................... xix LIST OF ABBREVIATIONS ........................................................................................... xx CHAPTER 1 INTRODUCTION ...................................................................................... 1 1.1 THE NICHOLAS REACTION .............................................................................. 1 1.1.1 STEREOCHEMISTRY OF THE NICHOLAS REACTION ......................... 7 1.2 NICHOLAS REACTIONS: SCOPE OF NUCLEOPHILES ............................... 12 1.2.1 NICHOLAS REACTION WITH HYDRIDE NUCLEOPHILES ................. 12 1.2.2 NICHOLAS REACTION WITH ARENE AND HETEROARENE NUCLEOPHILES ..................................................................................................... 13 1.2.3 NICHOLAS REACTION WITH ALLYLSILANE AND ALLYLSTANNANE NUCLEOPHILES ................................................................. 16 1.2.4 NICHOLAS REACTION WITH ENOLIC NUCLEOPHILES ................... 18 vii 1.2.5 NICHOLAS REACTION WITH SILYL ENOL ETHER NUCLEOPHILE …………………………………………………………............................19 1.2.6 THE REACTION OF ELECTROPHILES WITH COBALT- COORDINATED ENYNES ..................................................................................... 20 1.3 ANGLE STRAINED CYCLOALKYNES ........................................................... 24 1.3.1 STABILIZATION OF CYCLOALKYNES WITH TRANSITION METALS OTHER THAN COBALT .......................................................................................