Enantioselective nucleophilic difluoromethylation of aromatic aldehydes with Me(3)SiCF(2)SO(2)Ph and PhSO(2)CF(2)H reagents catalyzed by chiral quaternary ammonium salts

BACKGROUND: Although the nucleophilic difluoromethylation of aldehydes, ketones, and imines has been realized with PhSO(2)CF(2)H and related reagents, there are still no reports on the enantioselective nucleophilic reactions. RESULTS: With a chiral quaternary ammonium salt as the catalyst and KOH as the base, we describe the first enantioselective difluoromethylation of aromatic aldehydes with PhSO(2)CF(2)H or Me(3)SiCF(2)SO(2)Ph. The enantioselectivity is substrate-dependent and for 2-chlorinated benzaldehyde an ee up to 64% was obtained. CONCLUSION: These results provide some insights into the enantioselective nucleophilic difluoromethylation chemistry, which will stimulate further progress in this field.