Deaminative Chlorination of Aminoheterocycles

Selective modification of heteroatom-containing aromatic structures is in high demand as it permits rapid evaluation of molecular complexity in advanced intermediates. Inspired by the remarkable selectivity of deaminases in Nature, herein we present a simple methodology that enables the NH₂ groups in aminoheterocycles to be conceived as masked modification handles; with the aid of a simple pyrylium reagent and a cheap chloride source, C(sp²)‒NH₂ can be converted into C(sp²)‒Cl bonds. The method is characterized by its remarkable substrate scope and wide functional group tolerance, allowing the modification of >20 different classes of heteroaromatic motifs (5- and 6-membered heterocycles), bearing numerous sensitive motifs. The facile conversion of NH₂ into Cl in a late-stage fashion enables practitioners to apply Sandmeyer- and Vilsmeier-type transforms without the burden of explosive and unsafe diazonium salts, stoichiometric transition metals, or highly oxidizing and unselective chlorinating agents.