Synergistic Pd/Cu-catalyzed enantioselective Csp(2)–F bond alkylation of fluoro-1,3-dienes with aldimine esters

Due to high bond dissociation energies of Csp(2)–F bonds, using fluorinated compounds in Csp(2)–Csp(3) cross-coupling is difficult. Here the authors report a protocol for enantioselective Csp(2)–Csp(3) coupling of dienyl fluorides with aldimine esters, enabled by synergistic copper and palladium catalysis. This reaction represents the first example of asymmetric Csp(2)–Csp(3) cross-coupling involving an inert Csp(2)–F bond and provides expeditious access to chiral α-alkenyl α-amino acids with high enantioselectivity. Control experiments suggest that the Csp(2)–F bond activation occurs through a pathway involving PdH migratory insertion and subsequent allylic defluorination, rather than by direct oxidative addition of the Csp(2)–F bond to Pd(0). The detailed mechanism is further investigated by DFT calculation and the enantioselectivity is rationalized.