Unusual Stability of N-Methylmaleimide Cycloadducts: Characterization of Isobenzofuran Retro-Diels-Alder Reactions

Article abstract of DOI:10.1021/jo00076a032

Many years ago Diels and Thiele noted the unusual stability of maleic anhydride cycloadducts and employed this feature in scavenging anthracene generated in a retro-<4 + 2> reaction.N-methylmaleimide, although nearly identical to maleic anhydride in rates of Diels-Alder reactions, forms even more stable cycloadducts.The rate constants for the four reactions that characterize the furan/N-methylmaleimide system were measured under the conditions used by Lee and Herndon to study the furan/maleic anhydride system.Comparison of the two dienophiles indicates thatN-methylmaleimide adducts are ca. 3 kcal*mol^-1 more stable than the corresponding exo- and endo-maleic anhydride adducts.Somewhat larger (ca. 4 +/- 0.5 kcal*mol^-1) differences in stability were found for the cycloadducts of the much more reactive diene isobenzofuran.N-Methylmaleimide is used as a diene scavenger to obtain rate constants for retro-Diels-Alder reactions of isobenzofuran adducts with maleic anhydride and some substituted analogs.The rates of retro-Diels-Alder reactions of substituted N-methylmaleimide adducts were also determined by an alternative method.The substituents examined enhance the rates of exo retro-Diels-Alder reactions by factors of 15-40, while endo adduct retro-Diels-Alder rates are only slightly affected.Calculations were done at the MP2/6-31G^*//HF/6-31G^* level to compare the heats of hydrogenation of maleic anhydride and maleimide.The reduction of maleimide is calculated to be 2.5 kcal*mol^-1 more exergonic, supporting the experimental observations.