Synthesis of Mannich type products via a three-component coupling reaction

The reactions of alkyl nitriles, acetyl chloride, aldehydes and beta-ketoesters or simple ketones was studied for the one-pot synthesis of beta-acetamido carbonyl compounds. It was observed that the reaction proceeds in the absence of Lewis acids. However, a Lewis acid catalyzes the reaction and several were tested. It was found that whereas Cu(OTf)(2) is suitable for the coupling of beta-ketoesters with aldehydes, Sc(OTf)(3) is the best for ketones. A possible mechanism is proposed based on the isolation and characterization of an intermediate. (C) 2005 Elsevier Ltd. All rights reserved.