New chiral bis(diphenylphospholane) ligands: design, synthesis, and application to catalytic enantioselective aldol reaction to ketones

Abstract

New chiral bidentate diphenylphospholanes were designed targeting a catalytic enantioselective aldol reaction to ketones. Ligands 5l and 5m having cis-2-butenyl and cyclopropyl groups at the linker part, respectively, were identified as effective chiral ligands for a CuF-catalyzed enantioselective aldol reaction to ketones. Catalysts prepared from CuF·3PPh 3·2EtOH and these ligands produced ketone aldol products with up to 66% ee, which is promising particularly for this extremely difficult and important catalytic enantioselective carbon–carbon bond forming reaction. The enantioselectivity was strongly dependent on the linker structure. Construction of a deep chiral pocket around the copper metal with stable bidentate chelation is the key to meaningful enantioinduction.