Terrahedmn zyxwvutsrqponmlkjihgfedcbaZYX Vol. 50, No. 23, pp. 6935-6940, 1994 Copyright Q 1994 Elsevier Science Ltd Printedin Great Britain. All rights resewed 0040-4020/94 $7.00+0.00 0040-4020(94)EO327-P zyxwvutsrqponmlkjihgfedcbaZYXWVUTSRQPO Lipase-Catalyzed Aminolysis and Ammonolysis of p - ketoesters. Synthesis of Optically Active P-ketoamides. Maria Jestis Garcia, Francisca Rebolledo and Vicente Gotor* Deprtamento de Qufmica Orghica e Inorpanica, Facultad de Qufmica, Universidad de Ovkdo, 33071 Oviedo, Spain. AbstracL- Amino&is and ammonolysis reactions of bketoesters catalyzedby Candida antarctica lipase are very efficient methods for the preparation of /%keioamides. W hen racemic amines are used in these processes, the corresponding optically active B- ketoumides are obtainedwith moderate-high enantiomeric excesses. INTRODUCTION P_Ketoamides are highly versatile intermediates in organic synthesis,1 and for this reason it is always of current interest to find new and simple procedures for the preparation of these compounds. Several methods to achieve 3-oxoamides have been put forth. In general these processes involve specific reactions and low yields are achieved2 in many cases. Chemoselective transformations of diiunctional compounds is a critical problem in organic synthesis. Thus, when B-ketoesters (l), react with primary amines (2) at room temperature, enaminoesters (3) are mainly formed (Scheme I). and only in a few cases the selective preparation of the corresponding P-ketoamide is achieved. For instance, by using dimethylaminopyridine as catalyst it is possible to prepare 3-oxoamides if secondary amines are used as starting materials.3 In other cases, the aminolysis of b-ketoesters requires high temperatures and long reaction times and often low yields of p-ketoamides are obtained due to the competitive enaminoester formation.4 An interesting alternative is the room temperature aminolysis of the P-ketothioester derivatives,5 but these substrates are not so readily available.6 Scheme I 0 0 R3HN 0 R’ + R3NH2 - 6935