Trisubstituted 2‑Trifluoromethyl Pyrrolidines via Catalytic Asymmetric Michael Addition/Reductive Cyclization

The stereoselective synthesis of trisubstituted 2-trifluoromethyl pyrrolidines by asymmetric Michael addition/hydrogenative cyclization is described. The direct organocatalytic addition of 1,1,1-trifluoro­methyl­ketones to nitroolefins proceeds under mild reaction conditions and low catalyst loadings to provide Michael adducts in high yield with excellent diastereo- and enantioselectivity. Catalytic hydrogenation of the Michael adducts stereoselectively generates 2-tri­fluoro­methylated pyrrolidines bearing three contiguous stereocenters. A stereospecific route to epimeric 2-tri­fluoro­methyl pyrrolidines from a common intermediate is described.