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).National Natural Science Foundation of China [21372013, 21572004]; Shenzhen Peacock Program [KQTD201103]; MOE within the Program for New Century Excellent Talents in UniversitySCI(E)EIPubMedARTICLEhuangyong@pkusz.edu.cn5115414-154185