PdII -Catalyzed Enantioselective C(sp3 )-H Activation/Cross-Coupling Reactions of Free Carboxylic Acids

Abstract

Pd^II -catalyzed enantioselective C(sp³ )-H cross-coupling of free carboxylic acids with organoborons has been realized using either mono-protected amino acid (MPAA) ligands or mono-protected aminoethyl amine (MPAAM) ligands. A diverse range of aryl- and vinyl-boron reagents can be used as coupling partners to provide chiral carboxylic acids. This reaction provides an alternative approach to the enantioselective synthesis of cyclopropanecarboxylic acids and cyclobutanecarboxylic acids containing α-chiral tertiary and quaternary stereocenters. The utility of this reaction was further demonstrated by converting the carboxylic acid into cyclopropyl amine without loss of optical activity.

Keywords: C−H activation; arylation; palladium; vinylation.