Sustainable Three-Component Synthesis of Isothioureas from Isocyanides, Thiosulfonates, and Amines

Multiple applications of isothioureas as fine chemicals (or their precursors) are known, but a general sustainable method for their synthesis was hitherto unavailable. We report a novel general approach towards S‐alkyl and S‐aryl isothioureas through a copper(I)‐catalyzed three‐component reaction between amines, isocyanides, and thiosulfonates. The formal synthesis of a superpotent sweetener further illustrates the applicability of our method. Safety first! A direct synthesis of isothioureas by a copper‐catalyzed three‐component reaction from readily available substrates (see scheme) avoids the toxic, flammable, and highly reactive reagents required in classical approaches. The reaction also enables the straightforward synthesis of S‐aryl isothioureas, which are difficult to obtain by other methods.