Enantioselective Enolate Protonation with Chiral Anilines: Scope, Structural Requirements, and Mechanistic Implications

High enantioselectivity has been demonstrated in the protonation of N,N-diisopropyl amides (Table 1, entries 1−4, 7, and 10−13) derived from certain β,γ unsaturated acids. Depending on double bond geometry and the degree of substitution at the γ-carbon, γ-protonation can be a competing reaction in the case of the aliphatic substrates 12, 14b, 14d, and 18. The evidence is most consistent with a mechanism that involves proton transfer from 1a to a mixed aggregate consisting of enolate 4a and the lithiated amide 5, but direct proton transfer from 1a to the enolate is not ruled out.