The enantioselective Mannich-type reaction of an enolate or an enolate anion equivalent with aldimines constitutes a useful method for the preparation of chiral b-amino carbonyl compounds, which are the precursors of biologically important compounds such as b-lactams and b-amino acids. The development of chiral catalysts for the asymmetric Mannichtype reaction has attracted the attention of synthetic organic chemists.[1] Although stoichiometric amounts of chiral acid were employed initially, [2] a number of enantioselective catalysts such as chiral Lewis acid catalysts [3] and chiral base catalysts [4] have been developed lately. In addition to metal-based chiral catalysts, [5] the use of small organic molecules as catalysts to promote asymmetric reactions has emerged as a new frontier in reaction methodology.[6] Accordingly, l-proline derivatives [7] and peptide derivatives [8] have been developed as catalysts for the Mannich-type reactions. We previously reported that Mannich-type reactions [9] and the aza-Diels-Alder reaction [10] proceed smoothly in the presence of a catalytic amount of a strong Brønsted acid. We thus postulated that the use of a chiral Brønsted acid, in which the proton is surrounded by bulky substituents, may lead to effective asymmetric induction. We report herein an enantioselective Mannich-type reaction of silyl enolates with aldimines catalyzed by a chiral metal-free Brønsted acid. [11,12] First, treatment of aldimine 1 a (Scheme 1, R 1 = Ph) and ketene silyl acetal 2 (3.0 equiv) with 0.3 equivalents of the chiral phosphate 4 a [13,14,15] (which is readily prepared from (R)-BINOL; Scheme 2) in toluene at À78 8C led to a smooth Mannich-type reaction to give 3 a (R 1 = Ph). However, no enantioselectivity was observed (Table 1, entry 1), as deterScheme 1. Mannich-type reaction of aldimines 1 and ketene silyl acetals 2 to form b-aminoesters 3.

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The enantioselective Mannich-type reaction of an enolate or an enolate anion equivalent with aldimines constitutes a useful method for the preparation of chiral b-amino carbonyl compounds, which are the precursors of biologically important compounds such as b-lactams and b-amino acids. The development of chiral catalysts for the asymmetric Mannichtype reaction has attracted the attention of synthetic organic chemists.[1] Although stoichiometric amounts of chiral acid were employed initially, [2] a number of enantioselective catalysts such as chiral Lewis acid catalysts [3] and chiral base catalysts [4] have been developed lately. In addition to metal-based chiral catalysts, [5] the use of small organic molecules as catalysts to promote asymmetric reactions has emerged as a new frontier in reaction methodology.[6] Accordingly, l-proline derivatives [7] and peptide derivatives [8] have been developed as catalysts for the Mannich-type reactions. We previously reported that Mannich-type reactions [9] and the aza-Diels-Alder reaction [10] proceed smoothly in the presence of a catalytic amount of a strong Brønsted acid. We thus postulated that the use of a chiral Brønsted acid, in which the proton is surrounded by bulky substituents, may lead to effective asymmetric induction. We report herein an enantioselective Mannich-type reaction of silyl enolates with aldimines catalyzed by a chiral metal-free Brønsted acid. [11,12] First, treatment of aldimine 1 a (Scheme 1, R 1 = Ph) and ketene silyl acetal 2 (3.0 equiv) with 0.3 equivalents of the chiral phosphate 4 a [13,14,15] (which is readily prepared from (R)-BINOL; Scheme 2) in toluene at À78 8C led to a smooth Mannich-type reaction to give 3 a (R 1 = Ph). However, no enantioselectivity was observed (Table 1, entry 1), as deterScheme 1. Mannich-type reaction of aldimines 1 and ketene silyl acetals 2 to form b-aminoesters 3.

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