Work

Regioselective and site-divergent synthesis of tetrahydropyridines by controlled reductive-oxidative dearomative hydroarylation of pyridinium salts

Year: 2025

Type: article

Abstract: Tetrahydropyridine skeletons serve as ubiquitous structural motifs which are predominant in natural products, bioactive and drug molecules. Thus, the development of efficient and general synthetic methods for the synthesis of tetrahydropyridine frameworks with different substitutions has attracted great attention from the community. Moreover, the control of regioselectivity and site-divergency remains an unmet challenge. Herein, we report a regioselective and site-divergent reductive hydroarylation of pyridinium salts with aryl nucleophiles, enabling direct access to diverse tetrahydropyridine derivatives with aryl substitution at different positions under mild conditions. Mechanistic studies support that the reaction underwent a CoH-mediated double-reduction process of pyridinium salts. Tetrahydropyridines are vital scaffolds, yet regio- and site-selective assembly is hard. This work delivers a mild CoH-mediated reductive hydroarylation of pyridinium salts, enabling site-divergent arylation to access diverse tetrahydropyridines.

Source: Nature Communications

DOI: 10.1038/s41467-025-65735-7

Authors: Xing-Fu Wei, Shan Wang, Yu-Long Li, Qiong Yu, Wei Shu

Institutions: Southern University of Science and Technology, Sichuan University of Science and Engineering

Language: English

Topic: Radical Photochemical Reactions

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

Open Access status: gold

Estimated APC paid: $6,990