The reactions of five‐membered cyclodiene derivatives with itaconic anhydride could proceed via four plausible pathways: two pathways involving initial Diels–Alder cycloaddition reactions followed by lactonization, and two pathways involving direct ring‐opening esterification reactions followed by intramolecular Diels–Alder cycloaddition, all to afford five‐ and six‐membered norbornene lactones, which are key intermediates in the synthesis of biologically interesting molecules as well as polymers such as polyelectrolytes. There are several regio‐, enantio‐, peri‐, and stereo‐chemical possibilities in these reactions, leading to several potential pathways, and these pathways are studied with density functional theory calculations in this work. The results reveal that the initial Diels–Alder reaction pathways have lower activation barriers than esterification reaction pathways. Generally, the activation barriers for the formation of S‐enantiomers are lower compared with the formation of R‐enantiomers. The reactions are stereo‐selective toward endo‐cycloadducts over exo‐cycloadducts, and this is as a result of steric interaction. The analysis of the electrophilic (Pk+) and nucleophilic (Pk−) Parr functions at the reactive centers shows that the cycloaddition will happen in such a way as to unite the atoms with the highest molecular orbital coefficients because this would lead to the greatest stabilization, and this is in good agreement with the energetic trends and the experimental outcome.

This work investigated theoretically, at the M06/6‐311++G(d,p) level of theory, the Diels–Alder reactions of furan with substituted alkynes to afford oxanorbornadienes and the subsequent [4 + 2] and [2 + 2 + 2] cycloaddition reactions leading to the formation of heterocyclic furans, deltacyclenes, and bicyclic oxanorbornadienes, which have high utility in the chemical and pharmaceutical industries. The results show that in the initial Diels–Alder reactions to afford oxanorbornadiene intermediates, reactions of alkynes bearing electron‐withdrawing substituents have lower activation barriers compared with those with electron‐donating substituents. In the [4 + 2] reactions of the oxanorbornadiene intermediates to form bicyclic oxanorbornadienes, oxanorbornadienes with electron‐donating groups favor addition across the unsubstituted olefinic bond, whereas those with electron‐withdrawing substituents favor addition across the substituted double bond, but in both cases, the exo stereoisomer is favored. The regioselectivity of the reactions are strictly dictated by the nature of substituent on oxanorbornadiene. The retrocleavage step, regardless of the addition sequence and nature of substituents, is the rate‐determining step. For the reactions of substituted oxanorbornadienes with furan along the [4 + 2] cycloaddition and the [2 + 2 + 2] cycloaddition (dimerization) of substituted oxanorbornadienes, we observed a decrease in activation barriers when electron‐withdrawing substituents are involved. The global electrophilicity indices (ω) and maximum electronic charge transfer (ΔNmax) computed for various oxanorbornadiene derivatives considered in this work is consistent with energetic trends and experimental outcomes. Perturbation molecular orbital theory was employed to rationalize the results.

The 1,3-dipolar cycloadditions of nitrones and nitrile oxides to N-vinylindole afford isoxazolidines and 5-indolyl-substituted isoxazolines which are structural components of a wide range of natural and pharmaceutically active compounds. In these reactions, there are several regio-, enantio-, and stereo-chemical possibilities, leading to several potential pathways, and these pathways are studied with density functional theory calculations at the M06/6-311G(d,p) level of theory. The results show that the electron-withdrawing substituents on the dipolarophile accelerate the (3 + 2) cycloaddition reactions of nitrones with N-vinylindole by lowering the activation barriers of the reaction. The (3 + 2) cycloaddition of electron-withdrawing and electron-donating substituted nitrones with N-vinylindole proceeds with the preferential formation of cis-stereoisomers, and this is due to the Z-configuration of the nitrone and the trans-periplanar orientation of the substituents and the indolyl group on the transition state. The reactions of nitrile oxides with N-vinylindole proceed regioselectively at the exocyclic double bond in the indole to form 5-indolyl-substituted-isoxazolines. It has been established that the (3 + 2) cycloaddition of electron-donating and electron-withdrawing substituted nitrones and nitrile oxides to N-vinylindole is not enantioselective. The global electrophilicity indices (ω) and maximum electronic charge transfer (ΔN max ) computed for various nitrones and nitrile oxides considered in this work are consistent with energetic trends and experimental outcomes. The analysis of the electrophilic (P k + ) and nucleophilic (P k −) Parr functions at the reactive centers shows that the cycloaddition will happen in such a way as to unite the atoms with the highest molecular orbital coefficients because this would lead to the greatest stabilization, and this is in good agreement with the energetic trends and the experimental outcome.