On the Catalytic Effects of the Thiazolium Salt in the Oxa-Diel-Alder Reaction between Benzaldehyde and Danishefsky’s Diene: A Molecular Electron Density Theory Study

The oxa-Diels-Alder (ODA) reaction of benzaldehyde with the Danishefsky diene in the presence of [thiazolium][Cl] salt, as a model of an ionic liquid, has been studied within Molecular Electron Density Theory (MEDT) at the M06-2X/6-311G(d,p) computational level. The formation of two hydrogen bonds (HBs) between thiazolium cation and the carbonyl oxygen of benzaldehyde modifies neither the electrophilic character of benzaldehyde nor its electronic structure substantially but accelerates the reaction considerably. This ODA reaction presents activation energy of 4.5 kcal·mol-1; the formation of the only one observed dihydropyranone being strong exothermic by -28.8 kcal·mol-1. The presence of [thiazolium][Cl] salt decreases the activation Gibbs free energy of the ODA reaction between benzaldehyde and Danishefsky diene by 5.9 kcal·mol-1. This ODA reaction presents total para regioselectivity and high endo stereoselectivity. This ODA reaction takes place through a high asynchronous polar transition state structure (TS) associated with a non-concerted two-stage one-step mechanism. ELF analysis of para/endo TSs associated with the ODA reactions in the absence and the presence of [thiazolium][Cl] salt shows that the formation of the HBs at the TSs does not modify their electronic structure substantially. This MEDT study makes it possible to conclude that the acceleration found in the ODA reaction of benzaldehyde with Danishefsky diene in ILs is a consequence of an increase of the global electron density transfer at TS3-pn, resulting from the HB formation, and the greater strength of the HBs at the polar TS3-pn than at the benzaldehyde:[thiazolium][Cl] complex, more than an increase of the electrophilic character of the latter.