Journal of Organic Chemistry vol:79 pages:12148-12158
Ab initio calculations are reported for the
reaction of methyl boronic ester with organolithium reagents
with α-leaving groups. The best calculations rely on density
functional theory prediction of structures and coupled-cluster
theory calculation of accurate potential energies. The results
provide strong confirmation of the feasibility of a two-step
mechanism with rapid initial formation of a boron−ate complex followed by slower migration of methyl from boron to carbon with loss of the leaving group. The calculated free energy of activation is consistent with observed kinetic behavior, and the calculations provide a framework for exploring substituent and other effects on reactivity. Obtaining reasonable agreement with experiment in this way is not trivial and requires careful treatment of level of theory (density functional theory calculations tend to yield inaccurate results), of conformational complexity, especially for the ate complexes, and of the nature of the microscopic model of reactants and solvent. The methodological challenges and possible pitfalls, many of which are relevant more broadly to computational modeling of organic reaction mechanisms, are discussed in detail.