Synergistic Pd/Cu-catalyzed enantioselective Csp2–F bond alkylation of fluoro-1,3-dienes with aldimine esters
Huimin Yu, Qinglong Zhang, Weiwei Zi
Abstract
Abstract 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.