Amide groups switch selectivity: C-H trifluoromethylation of α,ß-unsaturated amides and subsequent asymmetric transformation.

ABSTRACT

The first direct C-H ß-trifluoromethylation of unsubstituted or α-alkyl-substituted α,ß-unsaturated carbonyl compounds under metal-free conditions was realized with excellent regio- and stereoselectivity as well as a very broad substrate scope. Both olefinic and allylic trifluoromethylation products are accessible with high selectivities by altering the substrate substitutions. The resultant olefinic products, namely (E)-ß-trifluoromethyl (CF3) α,ß-unsaturated hydroxamic acid derivatives, served as acceptors in organocatalytic asymmetric Michael addition reactions to give hydroxamic acid derivatives bearing a chiral CF3-substituted stereocenter with high enantioselectivities.