Enantio- and Diastereoselective De Novo Synthesis of 3-Substituted Proline Derivatives via Cooperative Photoredox/Brønsted Acid Catalysis and Epimerization

Chao Che; Yi-Nan Lu; Chun-Jiang Wang

doi:10.1021/jacs.2c12995

Enantio- and Diastereoselective De Novo Synthesis of 3-Substituted Proline Derivatives via Cooperative Photoredox/Brønsted Acid Catalysis and Epimerization

J Am Chem Soc. 2023 Feb 8;145(5):2779-2786. doi: 10.1021/jacs.2c12995. Epub 2023 Jan 27.

Authors

Chao Che¹, Yi-Nan Lu¹, Chun-Jiang Wang^{1

2}

Affiliations

¹ College of Chemistry and Molecular Sciences, Wuhan University, Wuhan 430072, China.
² State Key Laboratory of Elemento-organic Chemistry, Nankai University, Tianjin 300071, China.

PMID: 36706215
DOI: 10.1021/jacs.2c12995

Abstract

Herein, a novel strategy for the catalytic asymmetric synthesis of enantioenriched 3-cis- and 3-trans-substituted prolines has been successfully established via an unprecedented cascade radical addition/cyclization enabled by synergistic photoredox/Brønsted acid catalysis and subsequent base-assisted epimerization. The current protocol provides a unique de novo access to all four stereoisomers of 3-substituted prolines which are not readily achieved via currently established methods. This methodology could be further extended to the asymmetric synthesis of the full complement of stereoisomers of 3-substituted pipecolinic acids.