1,3-Dipolar cycloaddition of nitrile imines with alpha,beta-unsaturated lactones, thiolactones and lactams: synthesis of ring-fused pyrazoles

Abstract

1,3-Dipolar cycloaddition of nitrile imines with alpha,beta-unsaturated five- and six-membered lactones, thiolactones and lactams gave ring-fused pyrazoles. Regioisomeric mixtures have been obtained with the 5-substituted pyrazole as the major cycloadduct. Only with the five-membered lactone the major product was the 4-acyl derivative. Computational studies, the use of the topological analysis of the Fukui functions and the potential energy surfaces (PES) theory allowed a theoretical description of the local reactivity in agreement with the observed high regiochemistry and with the role of the heteroatom adjacent to the carbonyl group. (C) 2012 Elsevier Ltd. All rights reserved.