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

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.

SUBMITTER: Corbett MT

PROVIDER: S-EPMC4011570 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature

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

Corbett Michael T MT Corbett Michael T MT Xu Qihai Q Johnson Jeffrey S JS

Organic letters 20140418 9

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 ...[more]

PMID: 24746344

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