Enantioselective enolate protonation: Matching chiral aniline and substrate acidity

A comparison of chiral anilines 1a-f in the asymmetric protonation of enola te 15 shows that the optimum Delta pK(a) value (chiral acid vs protonated e nolate) for the highest enantioselectivity is ca. 3 (Table 2). An extension of this concept to amino acid enolates was possible, and le was found to g ive the best enantioselectivity (85% ee) with the alanine-derived N-lithioe nolate 5a (Table 3). Changes in aniline pK(a) due to variation of substitue nts at the aniline nitrogen were evaluated briefly, but these changes did n ot show consistent trends in the enantioselectivity vs pK(a).