A regio- and stereoselectivity and molecular mechanism study on the addition reactions of morpholine and m-CPBA to 9α-hydroxyparthenolide using DFT calculations

The chemoselectivity and stereospecificity of the addition of the morpholine and the meta-chloroperoxybenzoic acid  ( m-CPBA) onto 9α-hydroxyparthenolide were studied using Density Functional Theory (DFT) calculations with the B3LYP/6-311+G(d,p) computational level within the Molecular Electron Density Theory (MEDT), to demonstrate the key role of the Global Electron Density Transfer (GEDT) and to examine the polar character of these reactions. This work is divided into two parts; the first part concerns the reaction between the morpholine and the 9α-hydroxyparthenolide. The second part deals with the epoxidation of the 9α-hydroxyparthenolide by m-CPBA followed by the addition of the morpholine to the major product resulting from the epoxidation step. The obtained results show that the reaction between the morpholine and the 9α-hydroxyparthenolide takes place on the double bond C 3 =C 4 . On the other hand, when 9α-hydroxyparthenolide is attacked by m-CPBA, the epoxidation reaction is carried out on the double bond C 1 =C 2 .