Asymmetric Hetero-Michael Additions to α,β-Unsaturated Carboxylic Acids by Multifunctional Boronic Acid Catalysts

Abstract

Several direct asymmetric Michael additions to α,β-unsaturated carboxylic acids with integrated catalysts comprising chiral bifunctional thiourea and arylboronic acid were developed. First, the asymmetric aza-Michael addition of hydroxylamine derivatives efficiently afforded a variety of optically active β-amino acid derivatives. Furthermore, upon detailed investigation of the reaction, tetrahedral borate complexes, comprising two carboxylate molecules, were found to serve as reaction intermediates. Based on this observation, a drastic improvement in product enantioselectivity was achieved upon benzoic acid addition. Second, on merely changing the solvent, the asymmetric thia-Michael addition of arylthiols afforded both enantiomers of the adducts, which are important building blocks for biologically active compounds.