AN EXPEDIENT APPROACH FOR THE SYNTHESIS OF 1-ALKYL-4-PROPIONYLPYRROLIDIN-2-ONES Fatma Saa ˆdi, Khaoula Jebali, Aı ¨cha Arfaoui, and Hassen Amri Laboratory of Selective Organic Synthesis and Biological Activity, Faculty of Science, El Manar University, Tunis, Tunisia GRAPHICAL ABSTRACT Abstract A simple and useful tandem addition–cyclization reaction of primary amines on a prepared a-functionalized propylvinyl ketone 3 in methanol at reflux is a promising route for the synthesis of a new family of 1-alkyl-4-propionylpyrrolidin-2-ones 4. [Supplementary materials are available for this article. Go to the publisher’s online edition of Synthetic Communications 1 for the following free supplemental resource(s): Full experimental and spectral details.] Keywords Primary amines; 4-propionylpyrrolidin-2-ones; propylvinyl ketone INTRODUCTION The Michael addition reaction, discovered more than a century ago, [1] is one of the most important organic reactions leading to the formation of a new carbon– carbon and carbon–heteroatom bonds. These reactions include nucleophilic reagents (donors) and activated a, b-unsaturated molecules (acceptors) [2] recognized for their great ability to react with various nucleophiles. Aside from single acceptors, we verify that some homologous a-functionalized enones 3 [3–10] are of considerable importance in organic synthesis and can act as intermediates in the synthesis of a wide range of biologically active compounds [11] to skeletal pyrrolidin-2-ones derivatives [12] and c-butyrolactams. [13,14] Because of the growing importance of some N-heterocyclic five-membered rings in the development of synthetic intermediates in medicinal chem- istry and their usefulness as pharmacological molecules, much attention has been focused on their synthesis and especially that of c-lactams. [15–18] In this article, we describe an efficient alternative for the preparation of a new family of 1-alkyl-4- propionylpyrrolidin-2-ones 4 following a tandem Michael-type reaction of primary Received January 21, 2013. Address correspondence to Hassen Amri, Laboratory of Selective Organic Synthesis and Biological Activity, Faculty of Science, El Manar University, 2092 Tunis, Tunisia. E-mail: hassen.amri@fst.rnu.tn Synthetic Communications 1 , 44: 42–48, 2014 Copyright # Taylor & Francis Group, LLC ISSN: 0039-7911 print=1532-2432 online DOI: 10.1080/00397911.2013.786091 42 Downloaded by [Prof. Hassen Amri] at 14:19 22 October 2013