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Ml 48106 18 BEDFORD ROW. LONDON WC1R 4EJ, ENGLAND 8100236 R o y , G l e n n M ic h a e l * * NEW LITHIO CARBANIONS AND THEIR REACTIONS WITH CARBONYL COMPOUNDS The Ohio Slate University PH.D. 1980 University Microfilms International 300 N. Zeeb Road, Ann Arbor, MI 48106 NEW LITHIO CARBANIONS AND THEIR REACTIONS WITH CARBONYL COMPOUNDS DISSERTATION Presented in Partial Fulfillment of the Requirements for the Degree Doctor of Philosophy in the Graduate School of The Ohio State University By Glenn M. Roy, B.A., M.S. * * # # # The Ohio State University 1980 Reading Committee: Approved By Dr. Jack Hine Dr. Matthew Platz Philip dL MagnusU Dr. Larry Robertson Department of Chemistry To LeAnn and Brooks Michael ACKNOWLEDGEMENTS I would like to thank the NIH and NSP for financial' support of my research program. Mr. Dick Weisenberger is thanked for mass spectral support and Dr. Charles Cottrell for his NMR work. The members of the P. D. Magnus research group, 1975-1980, are thanked for their close association and camaraderie. Professor P. D. Magnus is kindly thanked for his constant patience, support and guidance during my degree program. I personally give thanks to my wife, Lee Ann, for typing the rough details of this manuscript and then giving birth to our son, Brooks. iii VITA December 5, 1953.........Born, East Paterson, New Jersey 1975..................... B.A., St. Michael's College, Winooski, Vermont 1975-1977................ Teaching Assistant, Chemistry Department, The Ohio State University, Columbus, Ohio 1977......................M.S., The Ohio State University Columbus, Ohio 1977-1980................ Research Associate, Chemistry Department, The Ohio State University, Columbus, Ohio PUBLICATIONS Selected Cleavage of 1,4-Cieole, G.L. Grady and G. Roy, Cosmetics and Perfumery, Vol. 90, 1975, p. ^9. A Short Synthesis of Prontalin and Latia Luciferin, P.D. Magnus and G. Roy, J. Chem. Soc. Chem. Comm., 1978, 297. Methoxymethyltrimethylsilane, A New Reagent for Reductive Nucleophilic Acylation, P.D. Magnus and G. Roy, J. Chem. Soc. Chem. Comm., 1979, 822. a-Lithiohexamethylphosphoramide-Formation and Reaction with Carbonyl Compounds, P.D. Magnus and G. Roy, Synthesis, 1980, 575. FIELDS OF STUDY Organic Chemistry. Professor P.D. Magnus Chemistry. Professor G.L. Grady iv TABLE OP CONTENTS Page DEDICATION............................................ ii ACKNOWLEDGEMENTS............. ill VITA................................... iv ABBREVIATIONS........................................ vi PART I * INTRODUCTION............................... 1 RESULTS.................................... 6 EXPERIMENTAL............................... 70 PART II INTRODUCTION............................... 143 RESULTS.................................... 152 EXPERIMENTAL............................... l8l PART III INTRODUCTION............................... 228 RESULTS.................................... 232 EXPERIMENTAL............................... 237 REFERENCES TO PART 1 ................................. 245 REFERENCES TO PART II................................ 251 REFERENCES TO PART III............................... 255 v ABBREVIATIONS n-BuLi n-butyllithium s-BuLi s-butyllithium t-BuLi t-butyllithium THE tetrahydrofuran MgSOi* magnesium sulfate Na2S0i» sodium sulfate BP3Et20 boron trifluoride etherate complex EtOAc ethyl acetate Et20 diethyl ether DMSO dimethyl sulfoxide TMEDA N,N,N’,N'-tetramethylethylenediamine LDA lithium diisopropylamide TLC, PLC thin layer chromatography, preparative layer chromatography mm millimeters of mercury mmol millimole (s) br.s, t, t, m broad singlet, doublet, triplet, multiplet (NMR) br. s, m, w broad strong, moderate, weak (IR) -TMS trimethylsilyl group -OMe, OAc, Ac methoxyl group, acetoxy group, acyl group Me, Et methyl group, ethyl group vi R.T. room temperature PCC pyridinium chlorochromate LAH lithium aluminum hydride min minutes h hour petrol high boiling petroleum ether (60°-90°C) CF3CO2H trifluroacetic acid MeOH methanol CaH2 calcium hydride NHi»Cl ammonium chloride NaHC03 sodium bicarbonate vii GENERAL INTRODUCTION OF EACH PART PART I The first part of this dissertation deals with homologation of aldehydes and ketones to their respective aldehydes or ketones. This trans­ formation is carried out using a method that was developed in our laboratory. It was our intention to explore the scope and limitations of the reagents, chloromethyltrimethylsilane and a-chloroethyltrimethylsilane as they are used to prepare new epoxysilane intermediates of important synthetic potential. PART II The second part describes the preparation of a new reagent, methoxymethyltrimethylsilane. The lithiation of this silane had been attempted in other laboratories without success. We were successful in adding this lithiated species to several carbonyl compounds thus illustrating the use of a new homologation reagent. PART III The third part merely describes an unprecedented observation that a common solvent, HMPA, can be lithiated and added to carbonyl compounds. This observation now serves as a caution to those synthetic chemists who use this solvent in alkyl lithium media since it not only acts as a solvent but also as a reagent that can prepare new intermediates never before studied. viii PART PART I INTRODUCTION The recent surge in the development of organo- silicon chemistry into the more general areas of organic synthesis has produced many interesting reactions that demonstrate the synthetically useful properties of silicon.1 Apart from the Peterson reaction2 and associated procedures3 little synthetic use is made of organosilicon chemistry since silicon reagents to a large extent are comparatively inaccessible to the non-specialist. The use of silicon reagents in modifying the reactivity of an organic substrate has presented excellent potential for development. Silicon functionalized epoxides have been shown to be useful in the formation of ketones,11 >5 olefinsf’7 vinyl ethers and halogen compounds.8 The studies of a, 3-epoxysilanes by Hudrlik0 illustrate reactions with nucleophiles under acidic conditions giving vinyl bromides, enolacetates, enolethers and enamides. The preparation of the substrate silane epoxide was usually accomplished by epoxidation of vinyl silanes9 which them­ selves are not readily procurred, or by hydrosilylation with MeCl2SiH catalyzed by chloroplatinic acid, reaction 1 with MeMgX and epoxidation.10 A new method for generation of a,3-epoxysilanes was recently developed1* that circum­ vented the laborious procedures known. Many adducts have been prepared and a few limitations on the preparation of a,3-epoxysilanes by this methods have been described.12 The first major synthetic use of a-silyl carbanions was described by Peterson.2>13 Deprotonation of readily available a-chloromethyl- trimethylsilane or a-chloroethyltrimethylsilane1 *»15 with sec-butyllithium in THF at -78°C with TMEDA gave lithio reagents 1 (CTC) and 2 (MCTC) that add cleanly •V *v to carbonyl compounds to give a,3-epoxysilanes. Several new, unreported adducts and their pertinent use in synthesis are to be described here. The reagents illustrate the process of reductive nucleophilic acylation.16 While colleagues have prepared other adducts as well, to the present time no incorpora­ tion of the method has appeared in any natural product synthetic strategy by other authors. However, we reported that Prontalin 3 an aggregation pheromone, and Latia Luciferin 4 a bioluminescent substrate can be prepared17 using this organosilicon chemistry. In the last few years there has been a prolific number of publications describing the use of