TMAF-Catalyzed Conjugate Addition of Oxazolidinone and Thiols

Abstract

TMAF (Me 4 NF) is a useful catalyst for the conjugate addition of oxazolidinone and thiols to a range of Michael acceptors including esters, ketones, nitroolefins and cinnamaldehyde.In 1947, Knunyants and coworkers reported the first examples of organic reactions promoted by a fluoride ion. 1 This initial report has since been followed by many others, installing the fluoride-mediated generation of anions (either via fluorodesilylation of organosilicon substrates or through fluorodeprotonation) for selective bond-forming reactions to an important place in modern organic synthesis. 2 While metal fluorides (e.g. KF and CsF) were used extensively in former times, 2a,b reports concerning with the use of tetraalkylammonium fluorides (R 4 NF) are increasingly widespread and are testament to the increasing value of these reagents in organic synthesis. 3 Applications have culminated in the development of chiral non-racemic ammonium fluoride ions and their use in some impressive catalytic asymmetric C-C bond forming processes. 4Otherwise, the conjugate addition of carbamates to unsaturated carboxylic acid derivatives provides the most direct access to the synthetically useful b-amino acid core. The weakly nucleophilic properties of carbamates have precluded the development of such methodologies which, in turn, have only been recently the subject of investigations. 5 In this context, the 1,4-alkylation of oxazolidinone is an interesting process in its own right, regarding the occurrence of pharmaceuticals incorporating an oxazolidinone moiety, 6 and in conjunction with the fact that oxazolidinone constitutes a 'naked' ethanolamine fragment. Within a general program aimed at developing new applications in aza Michael reactions, 7,8 we have been interested in evaluating the potential of ammonium fluorides keeping in mind that this approach could further readily open to an enantioselective variant. 4 The popularity of ammonium fluorides as catalysts for the Michael addition of nitroalkanes and active methylene pronucleophiles to a variety of acceptors has long been recognized. 2b Recently, TMAF has been demonstrated as an efficient catalyst for the conjugate addition of simple enolates derived from a-trialkylsilyl esters. 9 The conjugate addition of thiols under guidance of TBAF has also been established, but the study remained limited to a restricted range of activated olefins. 10 We communicate herein an extension of the useful potential of ammonium fluorides in organic synthesis, by demonstrating their effectiveness as catalysts for the quite rare 5 conjugate addition of oxazolidinone to various electrophilic olefins. We also present some results that broaden the scope of the usable thiol/acceptor combinations. In the first part of this work, we evaluated the conjugate addition of oxazolidinone 1a to various enoates (Table 1). We initially chose TMAF as a source of anhydrous catalyst. A first series of experiments using methyl crotonate 2b as a model substrate allowed us to select acetonitrile as the more convenient solve...