Dual role of benzophenone enables a fast and scalable C-4 selective alkylation of pyridines in flow.

ABSTRACT: The efficient C-4 selective modification of pyridines is a major challenge for the synthetic community. Current strategies are plagued with at least one drawback regarding functional group-tolerant electronic activation of the heteroarene, mild generation of the required alkyl radicals, regioselectivity, safety and/or scalability. Herein, we describe a fast, safe and scalable flow process which allows preparation of said C-4 alkylated pyridines. The process involves a photochemical hydrogen atom transfer (HAT) event to generate the carbon-centered radicals needed to alkylate the C-2 blocked pyridine. In a two-step streamlined flow process, this light-mediated alkylation step is combined with a nearly instantaneous inline removal of the blocking group. Notably, cheap benzophenone plays a du

SUBMITTER: Sanjose-Orduna J 

PROVIDER: S-EPMC9629060 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature