Synergistic Pd/Cu-Catalyzed Enantioselective Csp2–F Bond Alkylation of Fluoro-1,3-Dienes with Aldimine Esters

Abstract

Due to the high energies of Csp2–F bonds, employing fluorinated compounds for Csp2–Csp3 coupling has been an unsolved challenge. In this work, we report an efficient protocol for enantioselective Csp2–Csp3 cross-coupling of dienyl fluorides with aldimine esters, which was enabled by a synergistic Cu/Pd 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 was further investigated by DFT calculation and the enantioselectivity was rationalized.