DFT Investigation of the Stereoselectivity of the Lewis-Acid-Catalyzed Diels-Alder Reaction between 2,5-Dimethylfuran and Acrolein

Density functional theory (DFT) has been enacted to study the Diels-Alder reaction between 2,5-dimethylfuran (2,5-DMF), a direct product of biomass transformation, and acrolein and to analyze its thermodynamics, kinetics, and mechanism when catalyzed by a Lewis acid (LA), in comparison to the uncatalyzed reaction. The uncatalyzed reaction occurs via a typical one-step asynchronous process, corresponding to a normal electron demand (NED) mechanism, where acrolein is an electrophile whereas 2,5-DMF is a nucleophile. The small endo selectivity in solvents of low dielectric constants is replaced by a small exo selectivity in solvents with larger dielectric constants, such as DMSO. In the catalyzed process, the LA interacts with acrolein, forming a O-LA coordinating bond, that enhances its electron-acceptor character, further favoring the NED mechanism and reducing the activation energy. When AlCl₃ and GaCl₃ catalyze the reaction, the bond formations of both the endo and exo pathways occur via a two-step asynchronous process. Thus, these processes involve the formation of two transition states and a stable intermediate. The second transition state is the critical one and it dictates the increase of the exo selectivity, in comparison to the uncatalyzed reaction. The DFT calculations have also unraveled that the LA plays additional roles, i.e. it forms stable complexes with the carbonyl group of acrolein while AlCl₃ and GaCl₃ form dimers, which also impact the different equilibria.