Unveiling the Electronic Effects of Lewis and Brønsted Base Catalysts in Diels-Alder Reactions

The Lewis (LB) and Brønsted (BB) base-catalyzed Diels-Alder (DA) reactions have been investigated within Molecular Electron Density Theory (MEDT). To this end, the polar DA reaction of 3-hydroxy-2-pyrone (HOPy) with N-methylmaleimide (NMM) in the presence of Et₃N, and the ionic DA reaction of anion OPy^- with NMM have been studied. DFT-based reactivity indices indicate that the species formed by the earlier interaction between HOPy and Et₃N, and anion OPy^- are supernucleophile species, accounting for the strong catalytic effects of Et₃N (LB) and NaH (BB). The LB-catalyzed DA reaction features an activation enthalpy of only 4.1 kcal·mol^-1, whereas the transition-state structures (TSs) for the BB-catalyzed DA reaction lie below the reactants. The high global electron density transfer (GEDT) computed at the high asynchronous TSs, 0.39 e (LB) and 0.45 e (BB), accounts for the high polar and low activation energies. Relative Interacting Atomic Energy (RIAE) analysis reveals the strong stabilization of the electrophilic NMM via the high GEDT, a behavior analogous to that found in Lewis acid-catalyzed DA reactions. These behaviors unify the acid/base-catalyzed DA reactions within a unique concept based on the strong stabilization of the electrophilic ethylene resulting of the GEDT at the TSs.