Uncovering a general oxidation model of nitrogen-containing oxidant in N-heterocyclic carbene (NHC) catalyzed oxidative reactions of aldehydes

Abstract

Predicting how oxidants interact with reactive partners to alter the oxidation mechanism is a significant challenge in carbene catalysis. In this study, we investigated several examples to address this issue. Using density functional theory (DFT), we explored N-heterocyclic carbene (NHC)-catalyzed oxidative [2 + 4] annulations of aliphatic aldehydes with α,β-unsaturated ketones, focusing on the role of nitrogen-containing oxidant. Our computational results reveal that a hydrogen-bonding bridge framework, formed during oxidation, is crucial for facilitating π···π stacking interactions between the oxidant and the NHC catalyst. These interactions significantly lower the oxidation energy barrier, enabling a facile hydride transfer. This mechanism was validated across other reactions involving different nitrogen-containing oxidants. Frontier molecular orbital (FMO) analysis demonstrates how the NHC catalyst lowers the cycloaddition energy barrier by altering the orbital overlap from shoulder-to-head to head-to-head. Additionally, this elucidates the origin of stereoselectivity by highlighting energy differences between two reacting components at cycloaddition transition states. The nucleophilic index further predicts the preferred ketone attack site. This work advances our understanding of oxidation mechanisms involving nitrogen-containing oxidants and offers valuable insights for designing potent organic oxidants in organocatalytic oxidative reactions.