Diels–Alder Polar Reactions of Azaheterocycles: A Theoretical and Experimental Study

Abstract

A number of azaheterocycles (pyridines, pyrroles and indoles) have been properly functionalized so that they can act as dienophiles in cycloaddition Diels–Alder processes. This work analyzed the reactive behavior of these molecules through mechanistic analysis and the regioselectivity of the process using computational calculation tools. Based on this knowledge, a study was conducted on the influences of reaction variables, in particular solvent, catalyst and microwave irradiation, to achieve favorable changes—shorter reaction times, more acceptable temperatures and better yields. Theoretical calculations allowed the development of predictive approaches, which were later experimentally corroborated. This analysis allowed us to make reasonable assumptions related to reaction mechanisms, which allowed—through the analysis of corresponding transition states—us to consider such reactions at the boundary between pericyclic and polar processes.