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Reductive Transamination of Pyridinium Salts to N-Aryl Piperidines.

ABSTRACT: Saturated N-heterocycles are found in numerous bioactive natural products and are prevalent in pharmaceuticals and agrochemicals. While there are many methods for their synthesis, each has its limitations, such as scope and functional group tolerance. Herein, we describe a rhodium-catalyzed transfer hydrogenation of pyridinium salts to access N-(hetero)aryl piperidines. The reaction proceeds via a reductive transamination process, involving the initial formation of a dihydropyridine intermediate via reduction of the pyridinium ion with HCOOH, which is intercepted by water and then hydrolyzed. Subsequent reductive amination with an exogenous (hetero)aryl amine affords an N-(hetero)aryl piperidine. This reductive transamination method thus allows for access of N-(hetero)aryl piperidines from readily available pyridine derivatives, expanding the toolbox of dearomatization and skeletal editing.

SUBMITTER: Chen Z

PROVIDER: S-EPMC11232014 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature

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Reductive Transamination of Pyridinium Salts to N-Aryl Piperidines.

Chen Zhenyu Z Song Geyang G Qi Leiming L Gunasekar Ramachandran R Aïssa Christophe C Robertson Craig C Steiner Alexander A Xue Dong D Xiao Jianliang J

The Journal of organic chemistry 20240613 13

Saturated N-heterocycles are found in numerous bioactive natural products and are prevalent in pharmaceuticals and agrochemicals. While there are many methods for their synthesis, each has its limitations, such as scope and functional group tolerance. Herein, we describe a rhodium-catalyzed transfer hydrogenation of pyridinium salts to access N-(hetero)aryl piperidines. The reaction proceeds via a reductive transamination process, involving the initial formation of a dihydropyridine intermediate ...[more]

PMID: 38872240

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