In(OTf) 3 -mediated dehydrative annulation of b-ketothioamides with phenylglyoxal: one-pot access to diversely functionalized pyrrol-2-thiones Girijesh Kumar Verma, Gaurav Shukla, Anugula Nagaraju, Abhijeet Srivastava, Maya Shankar Singh ⇑ Department of Chemistry, Faculty of Science, Banaras Hindu University, Varanasi 221005, India article info Article history: Received 10 June 2014 Revised 16 July 2014 Accepted 16 July 2014 Available online 22 July 2014 This Letter is dedicated to Prof. Ganesh Pandey on the occasion of his 60th birthday Keywords: b-Ketothioamides Phenylglyoxal Indium triflate Pyrrol-2-thiones One-pot domino annulation abstract Indium triflate mediated first synthesis of diversely functionalized pyrrol-2-thiones has been developed by dehydrative annulation of b-ketothioamides with phenylglyoxal through the domino Knoevenagel condensation/cyclization cascade in one-pot. This new simple strategy not only utilizes readily accessible starting material, but also allows the construction of 5-membered azaheterocycle with one quaternary carbon center as a result of the formation of two new (C–C and C–N) bonds in a single operation. Ó 2014 Elsevier Ltd. All rights reserved. Pyrrol-2-ones represent important synthetic building blocks, which are found in a wide range of natural compounds with vari- ous biological activities. 1 5-Hydroxy-pyrrol-2-ones are among the well known nitrogen heterocycles, and are present as a structural motif in numerous natural and synthetic products. 2 Oteromycin, 3a talaroconvolutin, 3b and codinaeopsin 3c are a few examples of biologically active natural products containing the 5-hydroxy- pyrrol-2-one moiety. This class of compounds possesses interest- ing neuritogenic, 4 antimalarial 5 as well as antitumor 6 activities and pharmacological properties. 7 Further, they have been fre- quently utilized in the construction of alkaloids 8 and natural prod- ucts. 9 Because of their diverse biological properties, several elegant strategies for the synthesis of pyrrol-2-one derivatives have been developed. 10 However, no attention has been given to the synthesis of its 2-thione analogue and till date no direct report is available. Replacement of the carbonyl group with the thiocarbonyl group in 5-hydroxy-pyrrol-2-one may further enhance the biological activity as well as co-ordination properties. 11 Therefore, the devel- opment of synthetic methods for the synthesis of pyrrol-2-thione derivatives is highly desirable from both synthetic and medicinal standpoints. To develop a new synthetic strategy by improving resource effi- ciency, avoiding the use of toxic reagents, and reducing waste and byproducts is always a challenge to the synthetic chemist. Metal triflates are unique catalysts, which have been frequently utilized in various organic transformations and are of great interest. 12 There has been a considerable revival of interest in the use of cat- alysts like indium salts, because they are cheap and easily avail- able. In particular, In(OTf) 3 is a well-known mild Lewis acid catalyst, which has been marvellously exploited for a wide range of organic transformations. 13 In continuation of our ongoing research utilizing indium salts as catalyst, 14 for the development of new methodologies for various heterocyclic systems herein, we report a rapid and efficient one-pot synthesis of pyrrol-2- thiones via coupling of b-ketothioamides with phenylglyoxal catalyzed by In(OTf) 3 at room temperature. Ambiphilic synthons which hold both nucleophilic and electro- philic sites have a great potential in developing a novel synthetic strategy. Such simple polyfunctional chemical species are a-oxoke- tene acetals 15a–d and b-oxodithioesters, 15e,15f which have been efficiently utilized as useful intermediates in various organic syn- theses by our group. Importantly, the selection of synthons is highly crucial that governs the success of a protocol. As the b- oxodithioester variant, b-ketothioamides are also valuable and unique nucleophilic reagents in organic synthesis. http://dx.doi.org/10.1016/j.tetlet.2014.07.062 0040-4039/Ó 2014 Elsevier Ltd. All rights reserved. ⇑ Corresponding author. Fax: +91 542 2368127. E-mail address: mssinghbhu@yahoo.co.in (M.S. Singh). Tetrahedron Letters 55 (2014) 5182–5185 Contents lists available at ScienceDirect Tetrahedron Letters journal homepage: www.elsevier.com/locate/tetlet