IntraMolecular Diels-Alder Reactions of Vinylarenes and Alkynyl Arenes (the IMDAV Reaction)

This comprehensive review summarizes the published literature data concerning the intramolecular Diels-Alder reactions of vinylarenes (the IMDAV reaction) and alkynyl arenes from 1970 to 2019, and covers mainly intramolecular [4+2] cycloaddition reactions of vinyl- or acetylene-substituted furans, thiophenes, pyrroles, indoles, imidazoles, benzenes, and naphthalenes, in which the unsaturated substituent is linked directly to an arene moiety. The selected area of the Diels-Alder reaction differs from other forms of [4+2] cycloadditions due to the uniqueness of the diene fragment, which, along with an exocyclic multiple bond, includes the double bond of an aromatic or heteroaromatic nucleus in its system. Thus, during the formation of the [4+2] cycloaddition intermediate, the aromaticity of furan, thiophene and even benzene rings is broken, leading, as a rule, to the formation of heterocyclic structures rarely accessible by other methods, in contrast to the majority of intermolecular Diels-Alder reactions, with the highest degree of chemo-, regio-, and diastereoselectivity. Therefore, the IMDAV approach is often used for the synthesis of naturally occurring and bioactive molecules, which are also discussed in this review alongside other applications of this reaction. Whenever possible, we have tried to avoid examples of radical, photochemical, oxidative, precious-metal-complex-catalyzed cyclizations and other types of formal [4+2] cycloadditions, focusing on thermal Diels-Alder reactions in the first step, according to the classical mechanism. The second stage of the process, aromatization, is unique for many initial substrates, and hence considerable attention in this overview is given to the detailed description of the reaction mechanisms.

Automated summary

This review summarizes the literature on intramolecular Diels-Alder reactions of vinylarenes and alkynyl arenes from 1970 to 2019, covering mainly [4+2] cycloaddition reactions of vinyl- or acetylene-substituted furans, thiophenes, pyrroles, indoles, imidazoles, benzenes, and naphthalenes. The unique nature of the diene fragment in this type of intramolecular Diels-Alder reaction leads to the formation of heterocyclic structures with high selectivity. The review also highlights the detailed description of reaction mechanisms, particularly focusing on the thermal Diels-Alder reactions and subsequent aromatization process.