Palladium/Amino Acid Co-catalyzed Atroposelective C–H Olefination to Access Tetra-Ortho-Substituted Atropisomers Featuring 2,2′-Difluoro-1-biaryl Scaffolds

Abstract

Despite the great advancement in atroposelective synthesis in the past decades, the enantioselective synthesis of 2,2'-difluoro-1-biaryls is unprecedented. Herein, a palladium and chiral amino acid catalyzed atroposelective C-H olefination to construct the axially chiral 2,2'-difluoro-1-biaryls is reported. A variety of polyfluoro-substituted biaryls were forged under mild conditions in good yields with excellent enantioselectivity (up to 99% ee). The potential application was demonstrated by a gram-scale synthesis and synthetic transformations.