Louisiana State University LSU Digital Commons LSU Doctoral Dissertations Graduate School 2007 Synthesis and functionalizations of tetrapyrrole derivatives Lijuan Jiao Louisiana State University and Agricultural and Mechanical College, [email protected] Follow this and additional works at: https://digitalcommons.lsu.edu/gradschool_dissertations Part of the Chemistry Commons Recommended Citation Jiao, Lijuan, "Synthesis and functionalizations of tetrapyrrole derivatives" (2007). LSU Doctoral Dissertations. 1309. https://digitalcommons.lsu.edu/gradschool_dissertations/1309 This Dissertation is brought to you for free and open access by the Graduate School at LSU Digital Commons. It has been accepted for inclusion in LSU Doctoral Dissertations by an authorized graduate school editor of LSU Digital Commons. For more information, please [email protected]. SYNTHESIS AND FUNCTIONALIZATIONS OF TETRAPYRROLE DERIVATIVES A Dissertation Submitted to the Graduate Faculty of the Louisiana State University and Agricultural and Mechanical College in partial fulfillment of the requirements for the degree of Doctor of Philosophy In The Department of Chemistry by Lijuan Jiao B.S., Shandong University, China 2000 M. S., University of Science and Technology of China, 2003 December, 2007 DEDICATION This Dissertation is dedicated to my parents in China for their unconditional love, their continuous support, and their understanding of every decision that I made throughout of my life. 谨以此文献给我远在中国的亲爱的父母，感谢他们这麽多年以来所给予我的无微不 至的关爱,默默无闻的支持与理解。 ii ACKNOWLEDGEMENTS First of all, I would like to give my sincere thanks to my advisor - Professor Kevin M. Smith. He is a great advisor that every student would ask for. He also has great personality. He is kind, generous, optimistic and knowledgeable. He provided me abundant guidance, freedom and support, and continuous encouragement throughout my Ph.D. studies. He led me into porphyrin chemistry and provided me with invaluable opportunities to know porphyrins and to enjoy porphyrin research. He has always been there for me when I need suggestions and help with my research, and also to help with my career plan and job interviews. Without his unconditional support, my Ph.D. studies would have been more lengthy. I will always be proud of once being his student and having worked under his guidance. My special thanks go to Professor Graça Vicente. She is a wonderful woman, independent, brilliant, but also kind and always willing to provide help to all of her students. She helped me with everything ever since I first met with her at LSU. She gave me suggestions in my studies, research, job interview and even my everyday life. It is hard to study in a science major, especially for a woman. Some time, I felt so frustrated that I even thought about quitting. But she was there, set a role model for me, and let me regain confidence to continue my studies and my research. She let me know how to balance career and everyday life. My special thanks also go to Professor William Crowe, Professor Brian Hales and Professor Henry James. Professor William Crowe is a great teacher, and he is also a kind, generous and knowledgeable person. I really enjoy his great lectures in the Organic Chemistry class. He cared about his students and tries his best to help us to learn essential organic chemistry. I also enjoyed my research discussions with him, which were very helpful for smoothing my research process. Professor Brian Hales gave me great lectures in the ―Bioinorganic Chemistry‖ iii classes, which helped me to learn interesting things outside of organic chemistry. I thank Professor Henry James for being on my committee. My special thanks also go to Ms. Sherry Wilkes. She has provided her generous help to us ever since my husband and I first arrived at LSU. Her generous support continued throughout our doctoral studies. My thanks also go to my colleges: Dr. Frank Fronczek in the LSU X-ray facility for those beautiful X-rays of my crystals; Dr. Tracy McCarley in the LSU-MS facility for teaching me how to operate the MALDI-MS; Mr. Guangyu Li and Dr. Dale Treleaven for training me to do NMR; Dr. Thomas Weldeghiorghis for the 2D-NMRs in the chlorin-e6 project; Mr. Tim Jensen for helping me to learn cell-culture techniques and fluorescence microscopy; Dr. Irena Nesterova from Dr. Soper’s research group for teaching me how to do fluoroesence quantum yield experiments and her helpful chemistry discussions. My thanks also go to everyone from both the Smith and Vicente research groups, especially Wei Liu, Celinah Mwakwari, Jianming Lu, Brahma Ghosh and Michael Easson for once being my lab mates and making working in the lab comfortable. My thanks also go to the other group members: Owendi Ongayi, Vijay Gottumukula, Jodie Hargus, Ravi Kumar, Raymond Luguya, Caleb Clark, Boyd Laurent, Hairong Li, Hillary Tanui, Kiran Allam, Giuseppe Pomarico, Anatol Litoshka, Martha Sibrian-Vasquez and Federica Mandoj. My deepest thanks go to my parents, Mr. Congjian Jiao and Ms. Yuying Li. I want to thank them for their love and their continuous support. They provided me with the strength and courage to take opportunities and face challenges throughout my life. I also want to thank my brothers and sisters, Mr. Tao Deng, Mr. Feng Deng, Ms. Mei Deng and Ms. Ping Li. Thanks for all their care, love and interactions in my life. I also want thank all my friends, especially Dr. Fang Chen, for being my best friend and always being there for me. iv My last, but not least, appreciation goes to my loved husband, Mr. Erhong Hao. He always stands next to me and supports me. He provides me with the deepest love, the continuous support and encouragement. He offers me his broad shoulder to let my mind rest when I was exhausted from research. It is him who makes chemistry research romantic and attractive. It is him who always believed in me and kept on pushing me to do my best. It is also him who always reminds me to cherish and follow my dreams, so that I will never lose myself. Without him, I would never be able to finish my doctoral research in such a short period. Also, without him, my life will not be so bright, colorful and lovely. v TABLE OF CONTENTS Dedication…...………………………………………….……………………………..…….…....ii Acknowledgements…..……………………...…………………………………..........................iii Abstract………………..……………………………………………………………..…..….....viii Chapter 1. Introduction……………………………………………………………………...….1 1.1History of Tetrapyrroles……………………………………………………………….…..…...1 1.2Overview of Porphyrins……………………………………….…………………..….….….…5 1.3Benzoporphyrins…………………………….…………………..…………………………....20 1.4Overview of Chlorin-e6 as a PDT Photosensitizer………………………….………...............24 1.5Overview of Porphycenes………….……………………...………………………………….28 1.6References……………………………………...………………………………………..……30 Chapter 2. β, β’-Fused Methylenepropanoporphyrins………………………...……………..37 2.1Introduction…………………………………………………………………………………...37 2.2Results and Discussion………………...……………………………………………………..39 2.3Experiment………………………………………………………………...………………….68 2.4Conclusions and Future Work……………………………………………...……………..….74 2.5References…………………………………………………………………...………………..75 Chapter 3. Benzoporphyrins from the Ring-Closing-Metathesis……….………………...…79 3.1Introduction…………………………………………………………………………………...79 3.2Results and Discussion…………………………………………...…………………………..81 3.3Conclusions……………………………………………………………………...…………....98 3.4Experiment…………………………………………...……………………………………….98 3.5References……………………………………………………………………...…….….…..105 Chapter 4. “Hangman Porphyrin” Analogs………………………………………………....107 4.1Introduction………………………………………………………………………………….107 4.2Results and Discussion………………………………...………………………………...….110 4.3Conclusions…..…………………………...……………………………………………...…121 4.4Experiment…………………………………………………………………………………..121 4.5References…………………………………………………………………………...………130 Chapter 5. Total Synthesis of Porphycenes and Improved Synthesis of 2,2’-Bipyrroles...133 5.1Introduction………………………………………………………………………………….133 5.2Results and Discussion………………………………………………………………...…....138 5.3Conclusions and Future Work…………………………………………..………………......156 5.4Experiment…………………………………………………………………………………..156 5.5References…………………………………………………………………………………...175 Chapter 6. The Unique Regiochemistry of Mono-(L)-aspartylchlorin-e6……………..…..178 6.1Introduction………………………………………………………………………………….178 vi 6.2Results and Discussion………………………………………………………..…………....180 6.3Conclusion……………………………………………………………………………….....192 6.4Experiment………………………………………………………………………………….193 6.5References…………………………………………………………………………………..196 Appendix: Letters of Permission………………...…...………………………………………198 Vita…...…………………………………………………………………………………...……202 vii ABSTRACT Chapter 1 of this Dissertation presents a brief overview of the history of tetrapyrrole derivatives and of their fundamental properties. Overviews of porphyrins, benzoporphyrins, chlorins and porphycenes are presented. Work presented in Chapter 2 through Chapter 4 mainly focuses on the syntheses and functionalization of chromophore-extended porphyrin derivatives. Several new synthetic routes for the syntheses and functionalizations of extended porphyrins either at the β-position or at the meso-position of porphyrin are developed. From these improved synthetic routes, the regio- selective syntheses of porphyrin derivatives are described. Chapter 2 mainly focuses on the syntheses of β,β’-fused methylenepropanoporphyrins and related porphyrin dimers. Chapter 3 mainly describes a new synthetic route for selective synthesis of benzoporphyrin regioisomers and Chapter 4 mainly discusses new work on the