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Enantioselective synthesis of γ-chiral amides via copper-catalyzed reductive relay hydroaminocarbonylation.

ABSTRACT: Chiral amides are common and effective structural motifs found in many pharmaceuticals and biologically active molecules. Despite their importance, existing synthetic methods are predominantly employed for the synthesis of α-amides and β-amides. The synthesis of remote chiral amides, characterized by distal stereocenters, typically requires intricate synthetic steps conducted under demanding conditions. Here, we present a general procedure for the copper-catalyzed enantioselective synthesis of γ-chiral amides, employing a reductive relay hydroaminocarbonylation strategy with trisubstituted allylic benzoates and hydroxylamine electrophiles. This approach demonstrates a wide substrate scope with excellent enantioselectivity and regioselectivity, thus providing access to challenging enantioenriched γ-chiral amides.

SUBMITTER: Yuan Y

PROVIDER: S-EPMC11306323 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature

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Enantioselective synthesis of γ-chiral amides via copper-catalyzed reductive relay hydroaminocarbonylation.

Yuan Yang Y Zhang Youcan Y Wu Xiao-Feng XF

Nature communications 20240807 1

Chiral amides are common and effective structural motifs found in many pharmaceuticals and biologically active molecules. Despite their importance, existing synthetic methods are predominantly employed for the synthesis of α-amides and β-amides. The synthesis of remote chiral amides, characterized by distal stereocenters, typically requires intricate synthetic steps conducted under demanding conditions. Here, we present a general procedure for the copper-catalyzed enantioselective synthesis of γ ...[more]

PMID: 39112513

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