Aryl sulfides are extremely useful reactants in synthetic organic chemistry. Moreover, aryl sulfide moiety is ubiquitous in natural products and bioactive molecules. These include several pharmaceuticals and drug candidates, exhibiting anti-Alzheimer, antiviral, antiinflammatory, and antidepressant activities. Among the existing methods for the preparation of aryl sulfides, the most general and widely used is the transition metal-catalyzed C–S cross-coupling. Despite their high versatility, the inherent drawbacks of the transition metal catalyzed cross-couplings, especially in the context of pharmaceutical applications, are high price of the catalysts and possible contamination of products with trace metal residues.<br/>In this context, we have developed a metal-free arylation of thiols using diaryliodonium salts as aryl transfer reagents. The method enables the C–S bond formation under mild and experimentally simple conditions. The reaction allows for the synthesis of aryl sulfides containing a broad range of aryl groups from aryl, heteroaryl, and alkyl thiols. In particular, pharmaceutically relevant moieties, such as benzazoles, thiazole, 2-thiazoline, and 1,3,4-oxadiazole can be incorporated into the products. The mechanism of the reaction was studied by DFT calculations, demonstrating that it follows the inner sphere pathway involving the incipient formation of Ar<sub>2</sub>I(SR) intermediate, followed by the reductive elimination.

Synthesis of aryl sulfides by metal-free arylation of thiols with diaryliodonium salts

ACS Spring 2022

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