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

Due to high bond dissociation energies of C(sp2)-F bonds, using fluorinated compounds in C(sp2)-C(sp3) cross-coupling is difficult. Here the authors report a protocol for enantioselective C(sp2)-C(sp3) coupling of dienyl fluorides with aldimine esters, enabled by synergistic copper and palladium catalysis. 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 alpha-alkenyl alpha-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.

Automated summary

This study reports a protocol for enantioselective C(sp2)-C(sp3) coupling enabled by synergistic copper and palladium catalysis. It overcomes the challenge of high bond dissociation energies of C(sp2)-F bonds and provides access to chiral products with high enantioselectivity. The detailed mechanism of this reaction is investigated and the enantioselectivity is rationalized.