Oxidative Dearomatization of Pyridines

J Am Chem Soc. 2024 Jan 31;146(4):2358-2363. doi: 10.1021/jacs.3c13603. Epub 2024 Jan 17.

Abstract

Dearomatization of pyridines is a well-established synthetic approach to access piperidines. Although remarkably powerful, existing dearomatization processes have been limited to the hydrogenation or addition of carbon-based nucleophiles to activated pyridiniums. Here, we show that arenophile-mediated dearomatizations can be applied to pyridines to directly introduce heteroatom functionalities without prior substrate activation. The arenophile platform in combination with olefin oxidation chemistry provides access to dihydropyridine cis-diols and epoxides. These previously elusive compounds are now readily accessible and can be used for the downstream preparation of diversely functionalized piperidines.