Synthesis of Trifluoromethylthio Compounds from Sulfur Containing Precursors

Abstract

The trifluoromethylthio group (–SCF3) exhibits several distinctive physicochemical properties and can alter the molecular lipophilicity and other pharmacokinetic properties of functional molecules. Moreover, its potent electron‐withdrawing capability confers enhanced metabolic stability to functional molecules. Molecules containing trifluoromethylthio groups are extensively applied in the synthesis of pharmaceuticals or agrochemicals and have garnered significant attention in recent years. The synthetic routes to trifluoromethylthio groups primarily fall into two categories: direct introduction of –SCF3 into target molecules, and indirect construction of –SCF3 through the introduction of –CF3 into sulfur containing precursors. In this review, we delineate approaches developed over the past seven years for the indirect construction of SCF3 groups via electrophilic, nucleophilic, radical, or other types of reactions involving –CF3 groups and sulfur‐containing precursors. These reactions are classified into seven categories depending on the employed: thiols, disulfides, thiosulfates, sodium sulfinates, sulfonyl chlorides, sulfoxides, and other sulfur‐containing precursors.