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Dual catalytic enantioselective desymmetrization of allene-tethered cyclohexanones.

ABSTRACT: The construction of enantioenriched azabicyclo[3.3.1]nonan-6-one heterocycles via an enantioselective desymmetrization of allene-linked cyclohexanones, enabled through a dual catalytic system, that provides synchronous activation of the cyclohexanone with a chiral prolinamide and the allene with a copper(i) co-catalyst to deliver the stereodefined bicyclic core, is described. Successful application to oxygen analogues was also achieved, thereby providing a new enantioselective synthetic entry to architecturally complex bicyclic ethereal frameworks. The mechanistic pathway and the origin of enantio- and diastereoselectivities has been uncovered using density functional theory (DFT) calculations.

SUBMITTER: Zhang L

PROVIDER: S-EPMC8159440 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

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Dual catalytic enantioselective desymmetrization of allene-tethered cyclohexanones.

Zhang Lin L Yamazaki Ken K Leitch Jamie A JA Manzano Ruben R Atkinson Victoria A M VAM Hamlin Trevor A TA Dixon Darren J DJ

Chemical science 20200624 28

The construction of enantioenriched azabicyclo[3.3.1]nonan-6-one heterocycles <i>via</i> an enantioselective desymmetrization of allene-linked cyclohexanones, enabled through a dual catalytic system, that provides synchronous activation of the cyclohexanone with a chiral prolinamide and the allene with a copper(i) co-catalyst to deliver the stereodefined bicyclic core, is described. Successful application to oxygen analogues was also achieved, thereby providing a new enantioselective synthetic e ...[more]

PMID: 34123026

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