Origin of Product Selectivity in Yttrium-Catalyzed Benzylic C–H Alkylations of Alkylpyridines with Olefins: A DFT Study

DFT studies have been conducted for the direct benzylic C­(sp³)–H alkylation of alkylpyridines with olefins catalyzed by a cationic half-sandwich yttrium alkyl complex. It has been found that, in the case of 2-tert-butyl-6-methylpyridine, the successive insertion of two molecules of ethylene, achieving butylation, was the outcome of kinetics. However, the continuous insertion of the third ethylene for hexylation was unfavorable both kinetically and thermodynamically in comparison with C–H activation to release the butylation product, which is in agreement with experimental results. The energy decomposition analyses disclosed that the steric repulsion between the two ^tBu groups of pyridyl moieties made the C–H activation of the one-ethylene preinserted intermediate relatively unfavorable. In contrast, in the case of 2,6-lutidine, the resulting monoethylation intermediate via feasible ethylene insertion favorably promotes C–H activation of another molecule of 2,6-lutidine rather than undergoes successive ethylene insertion to give the monobutylation product because of the additional Y···N interaction between the metal and incoming 2,6-lutidine moiety to stabilize the C–H activation transition state. The subsequent ethylene insertion and C–H activation alternatively take place at the remaining α-methyl group and then at the resulting α-CH₂, finally yielding the multiethylation product. Interestingly, the Y-catalyzed C­(sp³)–H alkylation reactivity of alkylpyridines has been found to follow the order C_α–H (1°) > C_α′–H (2°) > C_α″–H (3°) > C_β–H (2°) > C_γ–H (1°). The calculations show a clear correlation between the energy barrier for C–H activation and the Y···N contacts of the corresponding transition state. The shorter the Y···N distance in the transition states, the lower the energy barrier for the C–H activation. Further analyses of charge population indicate that the NBO charge on the Y atom positively correlates well with the reactivity of the C–H bonds.