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General Light-Mediated, Highly Diastereoselective Piperidine Epimerization: From Most Accessible to Most Stable Stereoisomer.

ABSTRACT: We report a combined photocatalytic and hydrogen atom transfer (HAT) approach for the light-mediated epimerization of readily accessible piperidines to provide the more stable diastereomer with high selectivity. The generality of the transformation was explored for a large variety of di- to tetrasubstituted piperidines with aryl, alkyl, and carboxylic acid derivatives at multiple different sites. Piperidines without substitution on nitrogen as well as N-alkyl and aryl derivatives were effective epimerization substrates. The observed diastereoselectivities correlate with the calculated relative stabilities of the isomers. Demonstration of reaction reversibility, luminescence quenching, deuterium labeling studies, and quantum yield measurements provide information about the mechanism.

SUBMITTER: Shen Z

PROVIDER: S-EPMC7855822 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature

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General Light-Mediated, Highly Diastereoselective Piperidine Epimerization: From Most Accessible to Most Stable Stereoisomer.

Shen Zican Z Walker Morgan M MM Chen Shuming S Parada Giovanny A GA Chu Duc M DM Dongbang Sun S Mayer James M JM Houk K N KN Ellman Jonathan A JA

Journal of the American Chemical Society 20201229 1

We report a combined photocatalytic and hydrogen atom transfer (HAT) approach for the light-mediated epimerization of readily accessible piperidines to provide the more stable diastereomer with high selectivity. The generality of the transformation was explored for a large variety of di- to tetrasubstituted piperidines with aryl, alkyl, and carboxylic acid derivatives at multiple different sites. Piperidines without substitution on nitrogen as well as <i>N</i>-alkyl and aryl derivatives were eff ...[more]

PMID: 33373212

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