DFT Investigation\nof the Stereoselectivity of the\nLewis-Acid-Catalyzed Diels–Alder Reaction between 2,5-Dimethylfuran\nand Acrolein

Density functional theory (DFT) has been enacted to study\nthe Diels–Alder\nreaction between 2,5-dimethylfuran (2,5-DMF), a direct product of\nbiomass transformation, and acrolein and to analyze its thermodynamics,\nkinetics, and mechanism when catalyzed by a Lewis acid (LA), in comparison\nto the uncatalyzed reaction. The uncatalyzed reaction occurs via a\ntypical one-step asynchronous process, corresponding to a normal electron\ndemand (NED) mechanism, where acrolein is an electrophile whereas\n2,5-DMF is a nucleophile. The small endo selectivity in solvents of\nlow dielectric constants is replaced by a small exo selectivity in\nsolvents with larger dielectric constants, such as DMSO. In the catalyzed\nprocess, the LA interacts with acrolein, forming a O-LA coordinating\nbond, that enhances its electron-acceptor character, further favoring\nthe NED mechanism and reducing the activation energy. When AlCl<sub>3</sub> and GaCl<sub>3</sub> catalyze the reaction, the bond formations\nof both the endo and exo pathways occur via a two-step asynchronous\nprocess. Thus, these processes involve the formation of two transition\nstates and a stable intermediate. The second transition state is the\ncritical one and it dictates the increase of the exo selectivity,\nin comparison to the uncatalyzed reaction. The DFT calculations have\nalso unraveled that the LA plays additional roles, i.e. it forms stable\ncomplexes with the carbonyl group of acrolein while AlCl<sub>3</sub> and GaCl<sub>3</sub> form dimers, which also impact the different\nequilibria.