Copper-Catalyzed α-Alkylation of Aryl Acetonitriles with Benzyl Alcohols.

A highly efficient, formed CuCl/TMEDA catalytic system (TMEDA = ,,','-tetramethylethylene-diamine) for the cross-coupling reaction of aryl acetonitriles with benzyl alcohols is reported. This user-friendly protocol, employing a low catalyst loading and a catalytic amount of base, leads to the synthesis of α-alkylated nitriles in up to 99% yield. Experimental mechanistic investigations reveal that the key step of this transformation is the C(sp)-H functionalization of the alcohol, taking place a hydrogen atom abstraction, with the simultaneous formation of copper-hydride species. Detailed density functional theory studies shed light on all reaction steps, confirming the catalytic pathway proposed on the basis of the experimental findings.