Enantioselective Cyanation/Brook Rearrangement/C-Acylation Reactions of Acylsilanes Catalyzed by Chiral Metal Alkoxides

Abstract

New catalytic enantioselective cyanation/1,2-Brook rearrangement/C-acylation reactions of acylsilanes (4) with cyanoformate esters (7) are described. The products of the reaction are fully substituted malonic acid derivatives (8). Catalysts for this transformation were discovered via a directed candidate screen of 96 metal−ligand complexes. Optimization of a (salen)aluminum complex revealed significant remote electronic effects and concentration effects. The scope of the reaction was investigated by using a number of aryl acylsilanes and cyanoformate esters. Chemoselective reduction of the reaction products (8) afforded new enantioenriched α-hydroxy-α-aryl-β-amino acid derivatives (32−34) and β-lactams (35 and 36). This reaction provides a simple method for the construction of new nitrogen-containing enantioenriched chiral building blocks.