Iodide-mediated electrochemical cyclization and desulfurization of N-substituted 3-aminoprop-2-enethioamides.

Abstract

The synthesis of 5-aminoisothiazoles typically relies on toxic oxidants, transition metals, or harsh conditions. A green electrochemical method that enables the oxidative cyclization of readily available N-substituted 3-aminoprop-2-enethioamides (generated in situ from isothiocyanates and β-enamines) under constant current without the need for external chemical oxidants is reported herein. A broad range of 5-aminoisothiazoles are obtained in moderate to good yields (up to 85%, 30 examples) with high atom economy. Remarkably, when nucleophiles (e.g., alcohols, water, and TMSN₃) are present, the reaction switches to desulfurization, affording imidates, amides, or tetrazoles in good yields. Mechanistic studies support an anodic oxidation of iodide to iodine, which triggers cyclization and desulfurization. This work provides a mild and sustainable alternative to classical isothiazole synthesis and offers a tunable desulfurization platform.