Regioselective C–H Thioarylation of Electron-Rich Arenes by Iron(III) Triflimide Catalysis

A mild and regioselective method for the preparation of unsymmetrical biaryl sulfides using iron­(III) catalysis is described. Activation of N-(arylthio)­succinimides using the powerful Lewis acid iron­(III) triflimide allowed the efficient thiolation of a range of arenes, including anisoles, phenols, acetanilides, and N-heterocycles. The method was applicable for the late-stage thiolation of tyrosine and tryptophan derivatives and was used as the key step for the synthesis of pharmaceutically relevant biaryl sulfur-containing compounds such as the antibiotic dapsone and the antidepressant vortioxetine. Kinetic studies revealed that while N-(arylthio)­succinimides bearing electron-deficient arenes underwent thioarylation catalyzed entirely by iron­(III) triflimide, N-(arylthio)­succinimides with electron-rich arenes displayed an autocatalytic mechanism promoted by the Lewis basic product.