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.