Deaminative Chlorination of Aminoheterocycles

Abstract

Selective modification of heteroatom-containing aromatic structures is\nin high demand as it permits rapid evaluation of molecular complexity in\nadvanced intermediates. Inspired by the remarkable selectivity of deaminases in\nNature, herein we present a simple methodology that enables the NH2\ngroups in aminoheterocycles to be conceived as masked modification handles; with\nthe aid of a simple pyrylium reagent and a cheap chloride source, C(sp2)‒NH2\ncan be converted into C(sp2)‒Cl bonds. The method is characterized\nby its remarkable substrate scope and wide functional group tolerance, allowing\nthe modification of >20 different classes of heteroaromatic motifs (5- and\n6-membered heterocycles), bearing numerous sensitive motifs. The facile conversion\nof NH2 into Cl in a late-stage fashion enables practitioners to\napply Sandmeyer- and Vilsmeier-type transforms without the burden of explosive\nand unsafe diazonium salts, stoichiometric transition metals, or highly\noxidizing and unselective chlorinating agents.