Organic Letters 2014-05-02

Trisubstituted 2-trifluoromethyl pyrrolidines via catalytic asymmetric Michael addition/reductive cyclization.

Michael T Corbett, Qihai Xu, Jeffrey S Johnson

Index: Org. Lett. 16(9) , 2362-5, (2014)

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Abstract

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.