Lehigh Preserve Institutional Repository Mechanistic Studies on the Effect of Additives in SmI2-Mediated Reactions Choquette, Kimberly Ann 2013 Find more at https://preserve.lib.lehigh.edu/ This document is brought to you for free and open access by Lehigh Preserve. It has been accepted for inclusion by an authorized administrator of Lehigh Preserve. For more information, please contact [email protected]. Mechanistic Studies on the Effect of Additives in SmI2-Mediated Reactions by Kimberly A. Choquette Presented to the Graduate and Research Committee of Lehigh University in Candidacy for the Degree of Doctor of Philosophy In Department of Chemistry Lehigh University May 20, 2013 2013 Copyright Kimberly A. Choquette ii Approved and recommended for acceptance as a dissertation in partial fulfillment of the requirements for the degree of Doctor of Philosophy Kimberly A. Choquette Mechanistic Studies on the Effect of Additives in SmI2-Mediated Reactions April 3, 2013 ____________________________________ Defense Date ___________________________________________ Dr. Robert A. Flowers, II, Chair Dissertation Director ____________________________________ Approved Date Committee Members: ___________________________________________ Dr. Ned Heindel, Member ___________________________________________ Dr. Natalie Foster, Member ___________________________________________ Dr. Patrick Wernett, Outside Member iii Acknowledgements I would like to give a very sincere thank you to my advisor, Dr. Flowers. I will always appreciate the support you gave me, even at times when I was struggling in classes or in the lab. The confidence you had in me helped me build that confidence in myself, and grow into a research chemist. I could never thank you enough for that. I also have to thank Sada, who trained me and mentored me in my first years in the Flowers group. Thank you for your patience and kindness toward me, I am certain I would not have gotten through my first years at Lehigh without you helping me through the millions of questions I had. The camaraderie and sense of community in the Flowers’ group is incredible, and I learned so much from all of the grad students I have had the opportunity to work in lab with: Brian, Jim, Sherri, Todd, Niki, Gaby, Esther, Rajni, Godfred and Teshia. I am very grateful to have had my graduate career in a lab where all of the students were genuinely interested in each other’s work, and instead of competition, we all helped each other rise up to greater standards. Also, thanks for making life at Lehigh fun and not just a job. I don’t know how I could have shown up every day if I didn’t know that if I needed to take a break from the lab that someone would be happy to escape and walk to the bookstore with me. Thank you to Brian Casey, for helping me so much, keeping me sane in lab, and being a great friend. Thank you very much to my husband, Matthew. You have always showed unwavering support for all my decisions, in and before grad school, and I could not be more grateful for how much you are always there for me. For my Dad and Mom, who raised two strong-willed women, I don’t think I would have gotten through any of my schooling without the work ethic you instilled in me. Dad, I will never forget your advice iv to “reach higher than you might think you can, what’s the worst that can happen?” Your guidance is what led me believe I could give grad school a shot, and you were right! To my Choquette family: thank you for always being so patient and understanding with my schedule all of these years. You are all always so supportive, I couldn’t ask for a more loving family. To my very best friend, Kim Bucha, thank for always being there for me and being an ear to listen to my problems. Kim and Katie Young, thank you for forcing me to go on weekend adventures with you and giving me time to laugh and relax. Chrissy, thank you for being a great friend and sister, calming me down when I’m stressed out and helping me get by all of these years. You always make me know how proud you are of me, and that is an amazing feeling that I will never take for granted. And really, I think this is all due to Mrs. Graeca, who made PJAS and science seem so cool to a 7th grader. Thanks, Coach. v Table of Contents Acknowledgements……………………………………………………………………….iv Table of Contents……………………………………………...………………………….vi List of Figures………...……………………………………………………………...…..xii List of Tables…………………………………………...………………………………..xv List of Schemes…………………………………………………………………………xvii Solvent Abbreviations………………………………………………………………….xxii Abstract……………………………………………………………………………………1 Chapters 1. Introduction to SmI2 as a single electron reductant 1.1 Samarium Diiodide……………………………..……………………………..3 1.2 Role of Additives…………………………….………………………………..4 1.2.1 Coordinating Additives……………………………………………...4 1.2.1.1 Hexamethylphosphoramide……………………………….6 1.2.1.2 DMPU and TMU………………………………………….9 1.2.1.3 Glycols and Ethers……………………………………….12 1.2.2 Proton Sources……………………………………………………..15 1.2.2.1 Alcohols………………………………………………….16 1.2.2.2 SmI2 and Water………………………………………..…23 1.2.3 Transition Metal Salts……………………………………………...31 1.3 SmI2 in Organic Synthesis……………………………………………………35 1.3.1 Organosamarium Intermediates……………………………………35 1.3.2 Grignard and Barbier Reaction…………………………………….38 vi 1.3.3 Reformatsky-Type Reactions………………………………………42 1.3.4 Ketyl-Olefin Coupling……………………………………………..48 1.3.5 Halide-Olefin Coupling……………………………………………52 1.3.6 Pinacol Coupling…………………………………………………...53 1.4 Project Goals…………………………………………………………………59 2. SmI2 Reduction of an Aldehyde vs. α,β–Unsaturated Ester 2.1 Background and Significance………………………………………………..60 2.1.1 SmI2 Reduction of Various Functional Groups……………………60 2.1.2 SmI2 in Cascade Syntheses………………………………………...65 2.1.3 Selective Cyclization of Functionalized Dialdehyde Compounds…69 2.2 Experimental…………………………………………………………………72 2.2.1 Materials…………………………………………………………...72 2.2.2 Instrumentation…………………………………………………….72 2.2.3 Methods…………………………………………………………….73 2.2.3.1 Synthesis of 3-butyl-3,6,6-trimethylcyclohex-1-ene methylcarboxylate………………..………………………………73 2.2.3.2 General Procedure for SmI2 Reduction…………………75 2.2.3.3 General Procedure for Stopped-Flow Studies……………75 2.3 Results………………………………………………………………………..76 2.3.1 Kinetic Data………………………………………………………..76 2.3.1.1 Pseudo-First Order Rates………………………………...77 2.3.1.2 Radical Traps…………………………………………….79 2.3.1.3 Initial Rates………………………………………………82 vii 2.3.2 Computational Data………………………………………………..84 2.4 Conclusions…………………………………………………………………..86 3. Impact of HMPA on the Samarium Barbier Reaction 3.1 Background and Significance………………………………………………..89 3.1.1 SmI2 and HMPA in Organic Reactions……………………………89 3.1.2 Samarium-Barbier Reaction………………………………………..93 3.2 Experimental…………………………………………………………………99 3.2.1 Materials…………………………………………………………...99 3.2.2 Instrumentation…………………………………………………...100 3.2.3 Methods…………………………………………………………...100 3.2.3.1 General Procedure for the Samarium Barbier Reaction..100 3.2.3.2 General Procedure for Stopped-Flow Studies…………..101 3.2.3.3 General Procedure for NMR Experiments……………...102 3.3 Results………………………………………………………………………102 3.3.1 Kinetic Analysis of Samarium Barbier Reagents………………...102 3.3.2 DFT Calculations…………………………………………………106 3.3.3 NMR Titration Experiments……………………………………...107 3.3.4 Proposed Mechanism of the Samarium Barbier Reaction with HMPA…………………………………………………………………..110 3.3.4.1 Derivation of Rate Equation……………………………110 3.3.4.2 Derived Equation Fit to Saturation Plots……………….112 3.3.4.3 Proposed Mechanism…………………………………...115 viii 3.3.5 Samarium Barbier Reaction with Secondary and Tertiary Alkyl Halides.…………………………………………………………………116 3.3.5.1 Kinetic Analysis of Samarium Barbier Reagents………117 3.3.5.2 NMR Titration Experiments……………………………120 3.4 Conclusions…………………………………………………………………121 4. Catalytic Ni(II) in SmI2 Reactions: Sm(II) or Ni(0) Chemistry? 4.1 Background and Significance………………………………………………122 4.1.1 Transition metal salts in SmI2 reactions……………………..……122 4.2 Experimental………………………………………………………………..126 4.2.1 Materials………………………………………………………….126 4.2.2 Instrumentation………………………………………………...…127 4.2.3 Methods…………………………………………………………...128 4.2.3.1 General Procedure for the Samarium Barbier Reaction with Ni(II)………………………….………………………………...128 4.2.3.2 General Procedure for Stopped-Flow Studies…………..128 4.2.3.3 Procedure for the Preparation of TEM Samples………..129 4.3 Results………………………………………………………………………129 4.3.1 UV-Vis Identification of Ni(0)…………………………………...129 4.3.2 TEM Images of Ni Nanoparticles………………………………...131 4.3.3 Kinetic Data: Reaction Progress Kinetic Analysis……………….131 4.3.4 Proposed Mechanism……………………………………………..143 4.4 Conclusions…………………………………………………………………144 5. Sm-H2O—Reduction of Lactones ix 5.1 Background and Significance………………………………………………145 5.1.1 SmI2-H2O Reduction Systems……………………………………146 5.1.2 SmI2-H2O Reduction of Lactones………………………………...148 5.2 Experimental………………………………………………………………..157 5.2.1 Materials………………………………………………………….157 5.2.2 Instrumentation…………………………………………………...157 5.2.3 Methods…………………………………………………………...158 5.2.3.1 General Procedure for Lactone Reduction with SmI2- H2O……………………………………………………………………..158 5.2.3.2 General Procedure for Stopped-Flow Studies…………158 5.3 Results…………………………………………………………......………..159 5.3.1 Lactone Reductions……………………………………………….159 5.3.2 Kinetic Analysis of SmI2-H2O Reduction of Lactones…………...161 5.4 Conclusions…………………………………………………………………166 6. Sm-H2O-Amine Reduction System 6.1 Background and Significance………………………………………………168 6.1.1 SmI2-H2O and SmI2-Amine Additive Systems…………………...168 6.1.2 SmI2-H2O-Amine