Amide Groups Switch Selectivity: C–H Trifluoromethylation of α,β-Unsaturated Amides and Subsequent Asymmetric Transformation

The first direct
C–H β-trifluoromethylation of unsubstituted
or α-alkyl-substituted α,β-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)-β-trifluoromethyl
(CF3) α,β-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.