Stereoselective synthesis of sulfur-containing β-enaminonitrile derivatives through electrochemical Csp3–H bond oxidative functionalization of acetonitrile

Abstract

Incorporation of nitrile groups into fine chemicals is of particular interest through C(sp3)–H bonds activation of alkyl nitriles in the synthetic chemistry due to the highly efficient atom economy. However, the direct α-functionalization of alkyl nitriles is usually limited to its enolate chemistry. Here we report an electro-oxidative C(sp3)–H bond functionalization of acetonitrile with aromatic/aliphatic mercaptans for the synthesis of sulfur-containing β-enaminonitrile derivatives. These tetrasubstituted olefin products are stereoselectively synthesized and the stereoselectivity is enhanced in the presence of a phosphine oxide catalyst. With iodide as a redox catalyst, activation of C(sp3)–H bond to produce cyanomethyl radicals proceeds smoothly at a decreased anodic potential, and thus highly chemoselective formation of C–S bonds and enamines is achieved. Importantly, the process is carried out at ambient temperature and can be easily scaled up.Direct α-functionalization of acetonitrile, a bulk chemical, is usually limited to its enolate chemistry. Here, the authors show an electro-oxidative C(sp3)–H bond functionalization of acetonitrile with thiols to afford tetrasubstituted olefins with high stereoselectivity.