Trisubstituted 2‑Trifluoromethyl Pyrrolidines via Catalytic Asymmetric Michael Addition/Reductive Cyclization
2015-12-17T01:56:59Z (GMT) by
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.