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Asymmetric synthesis of ?-branched amines via rhodium-catalyzed reductive amination.

ABSTRACT: Amines bearing ?-stereocenters are highly important structural motifs in many biologically active compounds. However, reported enantioselective syntheses of these molecules are indirect and often require multiple steps. Herein, we report a general asymmetric route for the one-pot synthesis of chiral ?-branched amines through the highly enantioselective isomerization of allylamines, followed by enamine exchange and subsequent chemoselective reduction. This protocol is suitable for establishing various tertiary stereocenters, including those containing dialkyl, diaryl, cyclic, trifluoromethyl, difluoromethyl, and silyl substituents, which allows for a rapid and modular synthesis of many chiral ?-branched amines. To demonstrate the synthetic utility, Terikalant and Tolterodine are synthesized using this method with high levels of enantioselectivity.

SUBMITTER: Wu Z

PROVIDER: S-EPMC5864842 | biostudies-other | 2018 Mar

REPOSITORIES: biostudies-other

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Asymmetric synthesis of γ-branched amines via rhodium-catalyzed reductive amination.

Wu Zhao Z Laffoon Summer D SD Hull Kami L KL

Nature communications 20180322 1

Amines bearing γ-stereocenters are highly important structural motifs in many biologically active compounds. However, reported enantioselective syntheses of these molecules are indirect and often require multiple steps. Herein, we report a general asymmetric route for the one-pot synthesis of chiral γ-branched amines through the highly enantioselective isomerization of allylamines, followed by enamine exchange and subsequent chemoselective reduction. This protocol is suitable for establishing va ...[more]

PMID: 29567989

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