Hetero-Diels-Alder Reaction Transition Structures: Reactivity, Stereoselectivity, Catalysis, Solvent Effects, and the exo-Lone-Pair Effect

Transition structures for the Diels-Alder reactions of butadiene with formaldehyde, thioformaldehyde, formaldimine, N-methylformaldimine, diazene, nitrosyl hydride, singlet oxygen, BH₃-coordinated formaldehyde and formaldimine, and protonated formaldimine have been located with ab initio molecular orbital calculations using the 3-21G basis set. Activation energies have been evaluated with MP2/6-31G* calculations on these geometries. Formaldehyde and the imines are predicted to be comparable in reactivity to ethylene, whereas the other dienophiles are predicted to be more reactive. Transition structures with the nitrogen lone pair(s) in the endo position are less stable than the corresponding transition structures with exo lone pairs. Formaldimine, cis-diazene, and nitrosyl hydride are predicted to favor the transition structures with the imino hydrogens endo by 4.9, 11.6, and 8.1 kcal/mol, respectively. The exo-lone-pair preference of formaldimine is 4.1 kcal/mol at high levels of theory (up to MP4SDTQ/6-31G*//6-31G*). These preferences result from electrostatic repulsions between the heteroatom lone pairs and the butadiene π electrons when the lone pairs are endo. The partial CO and CN bonds in the uncatalyzed Diels-Alder transition structures are shorter than the forming CC bonds, while the partial CS bond is significantly longer. These relationships reflect the normal single bond lengths in the products. Protonation and BH₃ coordination, used to model strong and weak Lewis acid catalysis, respectively, cause lower activation energies and less symmetrical transition structures. BH₃ has a preference for the exo position in the transition structures. The effect of BH₃ coordination on the activation energy is more pronounced for the aldehyde than the imine. The influence of solvent on the transition structure is assessed with a solvent cavity model.