Understanding the mechanism of CuI-catalyzed N–H carboxylation of heterocyclic rings with CO2 from a theoretical point of view

•The mechanism of copper catalyzed carboxylation of heterocyclic rings was studied by DFT.•The reaction mechanism relies on the identity of the heterocycles.•Two different reaction mechanisms for the carboxylation reaction were found.•The correlation between the pKa values and the N–H and CO2 activation energies was investigated.

The copper catalyzed carboxylation of heterocyclic rings has been studied with density functional theory. We find strong linear correlations between the pKa of the heterocycles and various steps in the reaction, including the initial copper-bound adduct and the barriers for N–H and CO2 activations. Using the mechanism proposed by Nolan, Cazin and coworkers, we find that the heterocycles fall into two groups (A and B) and we show that having a nitrogen atom adjacent to N–H in the ring (Group B) is important in lowering the barrier for the two key steps, that is, the N–H and CO2 activations. However our results for the heterocycles in Group A did not match up to the experimental results. In order to account fully for the observed experimental reactivity we have proposed an alternative mechanism involving promotion by base, i.e. the coordination of OH− to CuI before the N–H and CO2 activations to occur. This mechanism is the likely one to operate for Group A compounds, and is competitive with the mechanism proposed by Nolan and Cazin for Group B compounds.

Graphical abstractThe copper catalyzed carboxylation of heterocyclic rings using CO2 has been studied with density functional theory. The energy profile shows that a three coordinate Cu complex is more reactive toward CO2 activation than a two coordinate Cu complex.Figure optionsDownload full-size imageDownload as PowerPoint slide