Discovery of zinc-bound dithiolates for C(sp3)–S couplings of alkyl iodides: a radical solution to nucleophilic substitution

Abstract

The nucleophilic (thio)etherification of haloalkanes with O/S nucleophiles, known as Williamson (thio)etherification, is a prominent approach for synthesizing alkyl (thio)ethers. However, the reaction generally requires an elevated temperature and is primarily applicable to primary alkyl halides. Here, we develop a new class of bench-stable zinc dithiolates as thiolating reagents that oriented the radical functionalization of various alkyl iodides at room temperature to address the long-standing challenges associated with nucleophilic substitution. The base-free reactions proceed with excellent chemo-selectivity and broad functional group tolerance. Mechanistic studies reveal that these efficient C(sp³)–S couplings proceed through a synergistic single electron transfer (SET) of zinc dithiolates with diazonium salts and subsequent halogen atom transfer (XAT) between aryl radicals and alkyl iodides.