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Organocatalytic diastereo- and atroposelective construction of N-N axially chiral pyrroles and indoles.

ABSTRACT: The construction of N-N axially chiral motifs is an important research topic, owing to their wide occurrence in natural products, pharmaceuticals and chiral ligands. One efficient method is the atroposelective dihydropyrimidin-4-one formation. We present herein a direct catalytic synthesis of N-N atropisomers with simultaneous creation of contiguous axial and central chirality by oxidative NHC (N-heterocyclic carbenes) catalyzed (3 + 3) cycloaddition. Using our method, we are able to synthesize structurally diverse N-N axially chiral pyrroles and indoles with vicinal central chirality or bearing a 2,3-dihydropyrimidin-4-one moiety in moderate to good yields and excellent enantioselectivities. Further synthetic transformations of the obtained axially chiral pyrroles and indoles derivative products are demonstrated. The reaction mechanism and the origin of enantioselectivity are understood through DFT calculations.

SUBMITTER: Wang SJ

PROVIDER: S-EPMC10789812 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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Organocatalytic diastereo- and atroposelective construction of N-N axially chiral pyrroles and indoles.

Wang Shao-Jie SJ Wang Xia X Xin Xiaolan X Zhang Shulei S Yang Hui H Wong Ming Wah MW Lu Shenci S

Nature communications 20240115 1

The construction of N-N axially chiral motifs is an important research topic, owing to their wide occurrence in natural products, pharmaceuticals and chiral ligands. One efficient method is the atroposelective dihydropyrimidin-4-one formation. We present herein a direct catalytic synthesis of N-N atropisomers with simultaneous creation of contiguous axial and central chirality by oxidative NHC (N-heterocyclic carbenes) catalyzed (3 + 3) cycloaddition. Using our method, we are able to synthesize ...[more]

PMID: 38225235

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