Pincer-Cobalt-Catalyzed α-Alkylation of Nitriles with Alcohols in Air

The catalytic α-alkylation of nitriles has been accomplished with excellent yields and selectivity using bis(imino)pyridine pincer complexes of the inexpensive base metal Co. In particular, the (^iPr2NNN)CoCl₂ (0.5 mol %) catalyzed α-alkylation of benzyl nitrile with benzyl alcohol resulted in a maximum of 99% yield of the α-alkylated nitrile with exclusive selectivity after 4 h of reaction in air at 140 °C in the presence of 30 mol % KO^tBu. The catalytic protocol was effective for the selective α-alkylation of a range of substrates in good yields. Systematic control experiments reveal the well-defined molecular nature of the catalytic system. Kinetic analysis using the initial-rate method indicated that the reaction demonstrated a first-order dependence of rate on the concentration of (^iPr2NNN)CoCl₂, KO^tBu, benzyl nitrile, and benzyl alcohol. Isotope labeling studies suggest a KIE of 2.6, which points to the possible involvement of C-H activation in the RDS. Not surprisingly, the β-hydride elimination from the pincer-Co benzyloxide appears to be the RDS as the catalyst traverses through a more favorable alcoholysis path as inferred from DFT studies. Gratifyingly, The experimental barrier of 33.3 kcal/mol calculated using the Eyring equation matches well with the corresponding barrier (ΔG₁₄₀^‡ = 31.2 kcal/mol) computed for rate-determining β-hydride elimination.