Bis(trifluoromethylthio)carbene as a toolbox for versatile carbene transformations

Abstract

Abstract Carbenes are highly valued for their broad utility across diverse fields, and their chemistry has consequently been the subject of extensive research. Taming the high reactivity of these divalent carbon intermediates to achieve controllable selectivity for diverse transformations remains a fundamental challenge. This often necessitates bespoke, fine-tuned conditions for each reaction type, limiting generality and efficiency. Here, we report the rational design of a versatile, electrophilic carbene—bis(trifluoromethylthio)carbene (:C(SCF 3 ) 2 )—generated from a scalable reagent (BrCH(SCF 3 ) 2 , >30 g/batch). We show that this single carbene species efficiently mediates nearly all classic free carbene reactions, including cyclopropanation, skeletal editing, X–H insertion, sulfur ylide-based [2,3]-σ rearrangement/1,2-migration, and nitrogen ylide-initiated [4+1] cyclization, under one set of mild conditions with high chemoselectivity. This versatility may be attributed to the synergistic design of the –SCF 3 substituent, which concurrently provides strong electron withdrawal, a polarizable sulfur atom, and a bulky trifluoromethyl group. Our work establishes a unified synthetic platform that extends beyond specific reaction development, suggesting a potential paradigm for controlling reactive intermediates through rational substituent design, which may help streamline the synthesis of functional molecules.