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

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