Synergistic Pd/Cu-catalyzed enantioselective Csp2–F bond alkylation of fluoro-1,3-dienes with aldimine esters

Abstract

AbstractDue to high bond dissociation energies of Csp2–F bonds, using fluorinated compounds in Csp2–Csp3 cross-coupling is difficult. Here the authors report a protocol for enantioselective Csp2–Csp3 coupling of dienyl fluorides with aldimine esters, enabled by synergistic copper and palladium catalysis. This reaction represents the first example of asymmetric Csp2–Csp3 cross-coupling involving an inert Csp2–F bond and provides expeditious access to chiral α-alkenyl α-amino acids with high enantioselectivity. Control experiments suggest that the Csp2–F bond activation occurs through a pathway involving PdH migratory insertion and subsequent allylic defluorination, rather than by direct oxidative addition of the Csp2–F bond to Pd(0). The detailed mechanism is further investigated by DFT calculation and the enantioselectivity is rationalized.