Highly Enantioselective Aza-Michael Reaction between Alkyl Amines and [beta]-Trifluoromethyl [beta]-Aryl Nitroolefins

The aza-Michael addition reaction is a vital transformation for the synthesis of functionalized chiral amines. Despite intensive research, enantioselective aza-Michael reactions with alkyl amines as the nitrogen donor have not been successful. We report the use of chiral N-heterocyclic carbenes (NHCs) as noncovalent organocatalysts to promote a highly selective aza-Michael reaction between primary alkyl amines and [beta]-trifluoromethyl [beta]-aryl nitroolefins. In contrast to classical conjugate-addition reactions, a strategy of HOMO-raising activation was used. Chiral trifluoromethylated amines were synthesized in high yield (up to 99%) with excellent enantioselectivity (up to 98%ee).