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Reductive Hydroxymethylation of 4-Heteroarylpyridines.

ABSTRACT: The activation of pyridinium salts with electron-withdrawing heterocycles enables an iridium-catalyzed reductive hydroxymethylation reaction to proceed smoothly, facilitating the preparation of useful 3D heteroaryl-substituted functionalized piperidines. The methodology is used to prepare 3-hydroxymethylated analogues of pharmaceutical agents. Mechanistically, formaldehyde acts as both a hydride donor and the electrophile, leading to the formation of two new carbon-hydrogen bonds and one new carbon-carbon bond under relatively mild conditions.

SUBMITTER: Hepburn HB

PROVIDER: S-EPMC7754387 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Reductive Hydroxymethylation of 4-Heteroarylpyridines.

Hepburn Hamish B HB Donohoe Timothy J TJ

Chemistry (Weinheim an der Bergstrasse, Germany) 20200130 9

The activation of pyridinium salts with electron-withdrawing heterocycles enables an iridium-catalyzed reductive hydroxymethylation reaction to proceed smoothly, facilitating the preparation of useful 3D heteroaryl-substituted functionalized piperidines. The methodology is used to prepare 3-hydroxymethylated analogues of pharmaceutical agents. Mechanistically, formaldehyde acts as both a hydride donor and the electrophile, leading to the formation of two new carbon-hydrogen bonds and one new car ...[more]

PMID: 31917881

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