A theoretical study on aza-Michael additions

In this paper, we investigate aza-Michael additions, which are key-reactions in organic synthesis, from the theoretical point of view on a representative database collecting weak, medium and strong electrophiles. The full mechanism is studied in detail, focusing on the various elementary steps (creation of the C-N bond, proton transfer) and on the catalytic role of the amine reagent, through a comprehensive sampling of the potential energy surface. The computed activations barriers are then discussed in relation with the available experimental electrophilicity values. Furthermore, in order to unravel the main physico-chemical factors governing the reaction, charge transfers and descriptors from conceptual density functional theory are followed along the reaction path, casting light on the reactivity principles that are verified, and finally affording a unified view of these important chemical processes.