University of Tennessee, Knoxville TRACE: Tennessee Research and Creative Exchange Doctoral Dissertations Graduate School 12-2012 Boron and Metal Catalyzed C-C and C-H Bond Formation Adam Barret Pippin [email protected] Follow this and additional works at: https://trace.tennessee.edu/utk_graddiss Part of the Organic Chemistry Commons Recommended Citation Pippin, Adam Barret, "Boron and Metal Catalyzed C-C and C-H Bond Formation. " PhD diss., University of Tennessee, 2012. https://trace.tennessee.edu/utk_graddiss/1553 This Dissertation is brought to you for free and open access by the Graduate School at TRACE: Tennessee Research and Creative Exchange. It has been accepted for inclusion in Doctoral Dissertations by an authorized administrator of TRACE: Tennessee Research and Creative Exchange. For more information, please contact [email protected]. To the Graduate Council: I am submitting herewith a dissertation written by Adam Barret Pippin entitled "Boron and Metal Catalyzed C-C and C-H Bond Formation." I have examined the final electronic copy of this dissertation for form and content and recommend that it be accepted in partial fulfillment of the requirements for the degree of Doctor of Philosophy, with a major in Chemistry. George W. Kabalka, Major Professor We have read this dissertation and recommend its acceptance: John E. Bartmess, David M. Jenkins, Kimberly D. Gwinn Accepted for the Council: Carolyn R. Hodges Vice Provost and Dean of the Graduate School (Original signatures are on file with official studentecor r ds.) Boron and Metal Catalyzed C-C and C-H Bond Formation A Dissertation Presented for the The Doctor of Philosophy Degree The University of Tennessee, Knoxville Adam Barret Pippin December 2012 DEDICATION To my wife, Stacey, You have been my support through the good and bad. Thank you for your unconditional love. I will always be your “chem-god.” To my parents, Without your love, support, and encouragement, I might not have made it through graduate school. Thank you for always being there for me. ii ACKNOWLEDGEMENTS There are many people who deserve to be acknowledged for their effort, support and influence in helping me to pursue a Ph.D. in chemistry. First, I would like to express my sincerest appreciation to my advisor Dr. George Kabalka, for his guidance, patience, and financial support throughout my graduate school experience. He provided an ideal, stress-free environment to learn and practice chemistry. In addition, he taught me the finer parts of teaching others, and helped me pursue a future career during a difficult economy. There are not enough words to express my gratitude and appreciation for the opportunities I have received while working with Dr. Kabalka. I would also like to acknowledge Dr. Min-Liang Yao. His insight and advice greatly helped me learn organic chemistry, on paper and in practice. I would also like to thank my committee members and instructors: Dr. John Bartmess, Dr. David Jenkins, and Dr. Kim Gwinn. In particular, special thanks to: Dr. John Bartmess, for his willingness to answer impromptu questions about chemistry, safety, and teaching; Dr. Shawn Campagna, for sharing his knowledge, and help running the organic tutorial center; Dr. Shane Foister, for a unique class experience and his style of teaching organic reaction mechanisms; Dr. David Baker, for his discussions regarding chemical synthesis. The faculty of the department of chemistry unselfishly offered their expertise, experience, help through my graduate career. Special thanks to Pam Roach for help with everything related to the Kabalka Group and the copy machine; Bill Gurley for his help iii on computer related issues; Carlos Steren for help with the NMR spectrometer when it was not functioning properly. I would like to express my sincerest thanks to the members of the Kabalka group for their friendship, generosity, and for providing a pleasant working experience in the laboratory. Special thanks to: Mike Quinn for his advice on chemistry and life in general; Kelly Hall for her friendship and her help in difficult situations; and the rest of the past and present boron group members: David Blevins, Vitali Coltruclu, Thomas Moore, Travis Quick, Aarif Shaikh, and Li Yong. I would also like to thank the undergrads that served under me, for their help with cleaning glassware and other tedious tasks. Finally, I am deeply grateful to my wife and my family. They have provided essential encouragement and guidance through the good times, and bad. To all my friends who made graduate school a great experience, thank you for your loyalty, trust, and acceptance. Without the support of those close to me, I would have never made it this far. iv ABSTRACT Research efforts focused on the use of boron and metals to form new carbon- carbon and carbon-hydrogen bonds are summarized in this dissertation. Several novel reactions have been developed. These include: the deoxygenation of benzylic alcohols using chloroboranes, alkenylation of benzylic alcohols using boron trichloride, and dialkynylation of aryl aldehydes using dialkynylboron chloride. Numerous applications of these novel reactions have been developed. These include alternate routes to diphenylmethanes and 1,4-diynes from easily prepared dialkynylboron chlorides. In addition, E and Z alkenyl halides can now be prepared using boron trichloride without the use of butyllithium. The stereochemistry of the alkenyl halide can be altered using various reaction conditions. This type of methodology and previously reported indium allylation chemistry was applied to the synthesis of naturally occurring lactones. v TABLE OF CONTENTS Chapter 1 - Introduction .................................................................................................. 1 1.1 Scope of this Dissertation ......................................................................................... 1 1.1.1 Historical aspects of C-C and C-H bond formation ........................................... 1 1.1.2 Historical Aspects of Boron and Metals in Organic Synthesis .......................... 2 1.1.3 Reactions of Boron Trihalides in Organic Chemistry ........................................ 3 1.1.3 Reactions of Indium in Organic Chemistry ....................................................... 6 1.2 Alcohol Functional Group Conversion ..................................................................... 8 1.3 Reductions in Organic Chemistry ............................................................................. 9 1.4 Alkenylation, Alkynylation, and Allylation of Carbonyl Groups ........................... 10 1.4.1 Carbonyl Chemistry ......................................................................................... 10 1.4.2 Alkenylation ..................................................................................................... 11 1.4.3 Alkynylation .................................................................................................... 13 1.4.4 Allylation ......................................................................................................... 13 1.5 Haloboration of Alkynes ......................................................................................... 14 1.6 Statement of Problem .............................................................................................. 16 Chapter 2 – Deoxygenation of Benzylic Alcohols using Boron Dihalides .................. 17 2.1 Introduction ............................................................................................................. 17 2.2 Results and Discussion ........................................................................................... 18 2.3 Conclusion .............................................................................................................. 21 2.4 Experimental ........................................................................................................... 22 2.4.1 General Methods .............................................................................................. 22 2.4.2 Typical Reaction Procedure ............................................................................. 22 2.4.3 Characterization of Compounds 201-212 ........................................................ 23 Chapter 3 – Alkenylation of Benzylic Alcohols with Boron Trihalides ..................... 25 3.1 Introduction ............................................................................................................. 25 3.2 Results and Discussion ........................................................................................... 27 3.3 Mechanistic Study ................................................................................................... 31 vi 3.4 Conclusion .............................................................................................................. 34 3.5 Experimental Details ............................................................................................... 35 3.5.1 General Methods .............................................................................................. 35 3.5.2 Typical Reaction Procedure ............................................................................. 35 3.5.3 Characterization of Compounds 301-308 ........................................................ 36 Chapter 4 – Dialkynynlation of Aryl Aldehydes Using Dialkynylboron Chloride ... 39 4.1 Introduction ............................................................................................................. 39 4.2 Results