Lewis acid-catalyzed Diels–Alder cycloaddition of 2,5-dimethylfuran and ethylene: a density functional theory investigation

Density functional theory calculations with the M06-2X exchange–correlation functional have been performed to explore the Diels–Alder reaction between 2,5-DMF and ethylene as well as to compare the uncatalyzed reaction to the one catalyzed by the AlCl3 Lewis acid. The uncatalyzed reaction corresponds to a normal electron-demand (NED) mechanism where ethylene is an electron acceptor and 2,5-DMF plays the role of electron donor. This reaction presents a low polar character, its kinetics is little impacted by the solvent dielectric constant, and the formation of the two new σ bonds occurs through a one-step synchronous process. When the LA interacts with ethylene, forming a π-complex, it enhances its acceptor character, further favoring the NED mechanism, which is accompanied by a reduction of the free energy of the transition state. On the other hand, when AlCl3 is complexed by 2,5-DMF, the inverse electron-demand (IED) mechanism is favored, with ethylene playing the role of the donor. Within both NED and IED mechanism, the LA-catalyzed reaction takes place via a one-step asynchronous process. In addition, it is highly polar, so that the activation barrier decreases with the solvent polarity. Moreover, the calculations have evidenced that the LA forms stable complexes with any of the reactants so that the gain on the activation barrier amounts to 9–12 kcal mol−1 for the NED mechanism and to 3–9 kcal mol−1 for the IED one and that the formation of Al2Cl6 dimers impacts the different equilibria. Finally, the decrease of the activation barrier goes in pair with the reduction of the HOMO–LUMO gap, with the greatest decrease recorded when the LA interacts with ethylene according to the NED mechanism.