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

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.

Automated summary

This study reports a novel method for the enantioselective synthesis of axially chiral 2,2' difluoro-1-biaryls using a palladium and chiral amino acid catalyzed atroposelective C-H olefination. The results demonstrate that a variety of polyfluoro-substituted biaryls can be efficiently synthesized under mild conditions with excellent enantioselectivity.