Transition Metal-Free Difunctionalization of Sulfur Nucleophiles

Abstract

Efficient protocols for accessing iodo-implanted diaryl and aryl(vinyl) thioethers have been developed using iodonium salts as reactive electrophilic arylation and vinylation reagents. The reactions take place under transition metal-free, thiol-free, and external base-free conditions. A wide variety of functional groups are tolerated in the S-diarylation, leading to the regioselective late-stage application of several heterocycles and drug molecules under mild reaction conditions. A novel S-difunctionalization pathway was discovered using vinyliodonium salts, which proceeds under additive-free reaction conditions and grants excellent stereoselectivity in the synthesis of (aryl)vinyl thioethers. A one-pot strategy combining transition metal-free diarylation and subsequent reduction provided facile access to electron-rich thioanilines and direct synthesis of a potential drug candidate derivative. The retained iodo group allows a wide array of further synthetic transformations. Mechanistic insights were elucidated by isolating the key intermediate, and the relevant energy profile was substantiated by DFT calculations.