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

Due 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.