Cycloadditions under Microwave Irradiation Conditions: Methods and Applications

Abstract

Microwave irradiation has been applied with success to cycloaddition reactions. The special characteristics of such irradiation entails the use of new methodologies, including equipment, glassware, solvents, and solid supports. All of these aspects are described in this review. Under classical heating conditions, these reactions usually require long reaction times, high temperatures, and/or Lewis acid catalysts, resulting in partial or total decomposition of sensitive compounds. This is a particularly significant problem in the synthesis of natural products. These problems have been conveniently overcome by the use of microwave irradiation. The short reaction time associated with microwave activation avoids decomposition of reagents and products, and prevents polymerization of the diene or dienophile. Heterocyclic compounds have been synthesized by cycloaddition reactions, or have been observed to react as dienes and dipoles under microwave irradiation conditions. Even those heterocyclic systems that are very reluctant to participate in cycloaddition reactions, such as pyrazoles, can be induced to react under microwave irradiation conditions. The application of this method to the chemistry of [60]fullerene has permitted derivatization of this system while avoiding the problems of polycycloaddition and cycloreversion. In most cases, spectacular accelerations and great improvements in yields and reaction conditions are observed. Finally, in some cases, changes in the chemo-, regio-, or stereoselectivity have been observed. These changes have been connected with the absolute hardness of the transition state, with the harder state being favored under microwave irradiation conditions. Microwave chemistry thus opens new possibilities for modifying the result of competitive reactions by considering the relative hardness of the transition states.