Photoredox-catalyzed branch-selective pyridylation of alkenes for the expedient synthesis of Triprolidine

Abstract

Alkenylpyridines are important pharmaceutical cores as well as versatile building blocks in organic synthesis. Heck reaction represents one of the most powerful platform for the construction of aryl-substituted alkenes, nevertheless, examples for Heck type coupling of alkenes with pyridines, particularly with branched selectivity, remain elusive. Here we report a catalytic, branch-selective pyridylation of alkenes via a sulfinate assisted photoredox catalysis. This reaction proceeds through a sequential radical addition/coupling/elimination, by utilizing readily available sodium sulfinates as reusable radical precursors as well as traceless elimination groups. This versatile protocol allows for the installation of important vinylpyridines with complete branched selectivity under mild conditions. Furthermore, this catalytic manifold is successfully applied to the expedient synthesis of Triprolidine.

Alkenylpyridines are versatile building blocks for the synthesis of drugs and other complex molecular structures. Here, the authors show a branch-selective pyridylation of alkenes via sulfinate-assisted photoredox catalysis and showcase its utility in an expedient synthesis of Triprolidine.