Computational Insight into the Mechanism of Ruthenium(II)-Catalyzed α‑Alkylation of Arylmethyl Nitriles Using Alcohols

The ruthenium­(II)-catalyzed α-alkylation reaction of arylmethyl nitriles (phenylacetonitrile) using alcohols (ethanol) in toluene has been extensively investigated by means of SMD-M06-2X/6-311G­(d,p)-LANL2dz (LAnL2dz for Ru, 6-311G­(d,p) for other atoms) calculations. Detailed mechanistic schemes have been proposed and discussed. The catalytically active Ru­(II) complex was generated by the base-induced KCl elimination from the catalyst precursor [(PNP^Ph)­RuHCl­(CO)]. The overall Ru­(II) catalytic cycle consists of three basic processes: (1) ethanol-to-aldehyde transformation catalyzed by the 16-electron unsaturated ruthenium pincer catalyst; (2) a 16-electron unsaturated ruthenium pincer catalyst catalyzed condensation reaction of arylmethyl nitrile with aldehyde, which leads to PhC­(CN)=CHCH₃; (3) hydrogenation of PhC­(CN)=CHCH₃, which leads to the formation of the α-alkylated arylmethyl nitrile product (PhCH­(CH₂CH₃)­CN). The DFT results revealed that the rate-determining barrier of the overall reaction was 23.9 kcal/mol of the H-transfer step in the third process. The reaction of PhC­(CN)=CHCH₃ with the dihydride Ru complex, which is generated in the ethanol-to-aldehyde transformation process, is the more preferable hydrogenation mechanism than hydrogenation of vinyl nitrile–Ru complex by H₂. Using alcohol as the reactant not only fulfills the requirement of the borrowing-H strategy but also lowers the barriers of the H-migration steps.