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

Abstract

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.