Deprotonation of β,β-disubstituted α,β-unsaturated amides - Mechanism and stereochemical consequences

A detailed study of the lithium dialkylamide induced deprotonation of β,β-disubstituted α,β-unsaturated amides is presented. The preferential γ-Z-deprotonation and stereochemical outcome of substituents on the γ-Z carbon atom are rationalized in terms of a cyclic eight-membered transition state, which is supported by DFT calculations. Analogous deprotonations on cyclohexylidenecarboxamides reveal a delicate balance of the preference for the eight-membered cyclic transition state with the effects of existing substituents on the ring and the intervention of a twist-boat transition state.Key words: dienolate, amide, deprotonation mechanism, transition state, enolization, regioselectivity, stereoselectivity.