DFT investigation of solvent, substituent, and catalysis effects on the intramolecular Diels-Alder reaction.

In this study, we report on a DFT investigation of two intramolecular Diels-Alder furan reactions. Optimizations of the studied structures, TS and IRC calculations, were carried out at B3LYP/6-31G(d) level. We have studied the effect of substituent, solvent and Lewis acid catalyst on cyclization-retrocyclization equilibria, activation energies, and stability of the desired products. The analysis of orbital coefficients, IRC curves, and Wiberg indices have proved that both reactions are under orbital control. We have found that for the reaction I (2↔4 + 5), where R = H, the exo attack is favored by hydrogen bond interaction, while for R = t-Bu, the steric hindrance leads to the endo attack. For the reaction II (3 → 6 + 7), the t-Bu-substituted products are the most stable ones. At another level, we have found that it is recommended to use polar organic solvents as DMSO with Lewis acid catalyst BF3. The latest leads to accelerate the reaction II with stabilization of the desired products.