Copper-Catalyzed\nα‑Alkylation of Aryl\nAcetonitriles with Benzyl Alcohols

A highly efficient, <i>in situ</i> formed CuCl<sub>2</sub>/TMEDA catalytic system (TMEDA\n= <i>N</i>,<i>N</i>,<i>N</i>′,<i>N</i>′-tetramethylethylene-diamine)\nfor the cross-coupling reaction of aryl acetonitriles with benzyl\nalcohols is reported. This user-friendly protocol, employing a low\ncatalyst loading and a catalytic amount of base, leads to the synthesis\nof α-alkylated nitriles in up to 99% yield. Experimental mechanistic\ninvestigations reveal that the key step of this transformation is\nthe C(sp<sup>3</sup>)–H functionalization of the alcohol, taking\nplace <i>via</i> a hydrogen atom abstraction, with the simultaneous\nformation of copper-hydride species. Detailed density functional theory\nstudies shed light on all reaction steps, confirming the catalytic\npathway proposed on the basis of the experimental findings.