trans-4-tert-Butyldimethylsiloxy-l-proline displays a greater catalytic activity than the parent proline without compromising the enantioselectivity, which widens the substrate scope in the a-aminoxylation of carbonyl compounds, as well as O-nitrosoaldol/Michael, and Mannich reactions.Keywords: asymmetric synthesis; Mannich reaction; organic catalysis; oxidation; proline Organic catalyst-mediated asymmetric reactions [1] represent a rapidly developing field of research and numerous impressive results have appeared recently following the discovery of the proline-catalyzed aldol reaction, which is the intermolecular variant of the Hajos-Parrish À Eder-Sauer À Wiechert reaction, [2] reported by List, Lerner and Barbas in 2000.[3] Among several organic catalysts developed for asymmetric reactions, proline has occupied a central role. It has been successfully employed not only in the aldol, [3,4] but also in Mannich, [5] Michael, [6] a-amination, [7] and a-aminoxylation [8] reactions. Several modifications of proline catalyst such as the substitution of the carboxylic acid moiety of proline with an amide or tetrazole function have been performed to improve the enantioselectivity and reactivity. Substituted proline amides have been employed in the aldol reaction to improve the enantioselectivity, [9] while 5-pyrrolidin-2-yltetrazole was found to be a more reactive organic catalyst than proline in aldol, [10] a-aminoxylation [11] and O-nitroso-aldol/Michael [12] reactions as reported by Yamamoto et al. and in the Mannich reaction by Ley et al. [13] During our study of proline-catalyzed a-aminoxylations of aldehydes, [8 g] the reproducibility of the reaction was poor, especially at low catalyst loading, owing to the poor solubility of proline in the organic solvent. After intensive investigations, reproducible results were obtained using ultrasound irradiation of a DMF suspension of proline.[8g] This solubility problem prompted us to find a more soluble catalyst, which led us to try trans-4-tert-butyldimethylsiloxy-l-proline (1), easily prepared from commercially available trans-4-hydroxy-l-proline in large quantities [14] (Figure 1). The proline catalyst 1 not only provides reproducible results, but also accelerates the reaction dramatically with a reduced amount of the catalyst, promoting reactions that cannot be catalyzed by proline itself. As the catalyst 1 possesses a higher reactivity than the parent proline, its superiority to proline will be discussed in this paper.First of all, the reactivity of the catalyst 1 was investigated in the a-aminoxylation of cyclohexanone in the presence of 30 mol % of the catalyst [Eq. (1)]. The increase in the solubility of 1 in organic solvents greatly widens the choice of possible reaction medium (Table 1). For instance, the reaction scarcely proceeded in CH 2 Cl 2 and THF in the presence of proline owing to its poor solubility, while these solvents can be employed in the reaction with 1, affording the product in moderate yield (entries 1 and 2), although DMF is the ...