Deaminative Chlorination of Aminoheterocycles

  • 10.26434/chemrxiv.14262671
  • posted-content
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 NH<sub>2</sub> groups in aminoheterocycles to be conceived as masked modification handles; with the aid of a simple pyrylium reagent and a cheap chloride source, C(sp<sup>2</sup>)‒NH<sub>2</sub> can be converted into C(sp<sup>2</sup>)‒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 NH<sub>2</sub> 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.

Review

A Large Step Forward For Late Stage Functionalization

A simple but effective replacement for the Sandmeyer reaction. The avoidance of diazonium salts, copper, and the general functional group tolerability make this deamination reaction extremely valuable for late stage functionalization strategies. Initial testing in-house would...