N-Heterocyclic carbene (NHC)-catalyzed oxidative [3+2] annulation of dioxindoles and enals: mechanism, role of NHC, role of a mixture of bases with different strength, and origin of stereoselectivity.

Abstract

Over recent years, in-depth understanding of the mechanism of oxidative N-heterocyclic carbene (NHC) catalyzed reactions in the presence of a mild oxidant and the structure of key radical intermediates have been considered as an important challenge in organic chemistry. Furthermore, the role of using a mixture of bases with different strengths is unclear in NHC-catalyzed reactions. In this paper, the detailed competing oxidative mechanisms, origin of stereoselectivity, and role of the NHC-organocatalyst in the NHC-catalyzed reactions of dioxindoles with enals were studied using the density functional theory method. In addition, the roles of newly produced Brønsted acids of the applied bases, i.e.DBU·H+ and DABCO·H+, are examined. The computational results indicated that the oxidation of the Breslow intermediate by nitrobenzene (NB) occurs first through a hydrogen atom transfer (HAT) pathway from the Breslow intermediate, and then it is oxidized into acyl azolium by single electron transfer (SET). We found that the energy barrier of the proton transfer processes is remarkably reduced by the conjugated Brønsted acid of the weaker base in the solution. Further, the calculated results revealed that the NHC catalyst has different behavior before and after the oxidation of the Breslow intermediate in these reactions. Before oxidation, the nucleophilicity of R1 increased by adding R1 to NHC, while, after the oxidation process, the electrophilicity of R1 increases, and as a result the product of oxidation, α, β unsaturated acyl azolium, acts as an electrophile. This mechanistic study paves the way for the rational design of oxidative NHC-catalyzed reactions.