Organocatalysis in Conjugate Amine Additions. Synthesis of β-Amino Acid Derivatives

摘要

Organocatalysis is an area of intense investigation. Spectacular advances have been made in the past decade using organocatalysts to prepare chiral building blocks. In this context, enamine and iminium ion intermediates derived from chiral amines as well as substrate and/or reagent activation through hydrogen bonds have been employed in enantioselective transformations. In a majority of reactions of the latter class, a thiourea motif has played a key role. Conjugate addition of nitrogen nucleophiles to unsaturated carboxylic acid derivatives provides rapid access to β-amino acids, an important class of compounds. There are reported examples of conjugate nitrogen nucleophile addition using organocatalysts. However, H-bond activation has played a limited role in enantioselective conjugate addition of heteroatom nucleophiles. In continuation of our program on the synthesis of β-amino acids, we have been interested in the development of simple and novel organocatalysts which in combination with appropriate acyclic systems would allow for the introduction of heteroatom nucleophiles. This work describes a highly efficient conjugate hydroxylamine addition to enoates that proceed with high levels of enantioselectivity using a bifunctional organocatalyst.