Theoretical Studies of the Lithiation of Enamines

In order to probe the origin of regioselectivity of the lithiation of enamines with alkyllithium reagents in hydrocarbon solvents, ab initio calculations were carried out on the reactions of lithium hydride and methyllithium with a series of vinylamines at the 3-21G level. The calculations indicate that the reactions occur via a cyclic transition state in which the base attacks the acidic proton in an almost collinear (anion-proton-base angle = 155-166°) fashion regardless of the ring size. A favorable transition state involves the achievement of both the stereoelectronic requirement for deprotonation and stabilizing coordination of the lithium cation with the base, the nitrogen of the enamine, and the developing anionic center. The rates of deprotonation are dependent upon favorable Li⁺ coordination, not anion stability. There is good qualitative accord with experimental deprotonation preferences and with ¹³C spectral changes upon coordination of n-BuLi with the enamines.