MEDT analysis of mechanism and selectivities in non-catalyzed and lewis acid-catalyzed diels–alder reactions between R-carvone and isoprene

Within the context of Molecular Electronic Density Theory (MEDT), this study investigates the Diels–Alder reaction among isoprene ( 2 ) and R-carvone ( 1R ) applying DFT simulations, with and without Lewis acid (LA) catalysis. The results show that carvone ( 1R ) acts as an electrophile and isoprene ( 2 ) as a nucleophile in a polar process. LA catalysis increases the electrophilicity of carvone, thereby improving the reactivity and selectivity of the reaction by reducing the activation Gibbs free energy. Parr functions reveal that the C 5 =C 6 double bond is more reactive than the C 9 =C 10 double bond, indicating chemoselectivity. The examination of the Electron Localization Function (ELF) reveals high regio- and stereoselectivity, indicating an asynchronous mechanism for the LA-catalyzed DA reaction. Furthermore, it is suggested that cycloadduct 3 has great anti-HIV potential because it exhibits lower binding energies than azidothymidine (AZT) in the docking studies of cycloadducts 3 and 4 amongst a primary HIV-1protein (1A8O plus 5W4Q).