LAUSR

In this work, the possible reaction mechanisms and the role of N-heterocyclic carbene (NHC) catalysts in the umpolung reaction of imines to generate 2-substituted indole-3-acetic acid derivatives were investigated by density functional theory (DFT). Two different NHCs (named A-NHC and B-NHC) were studied as model catalysts. Calculations revealed that the whole reaction includes four steps: (1) the formation of a key aza-Breslow intermediate, (2) an intramolecular 1,4-addition, (3) a second 1,2-proton transfer, and (4) the desorption of the NHC to give 2-substituted indole-3-acetic acid derivatives. Furthermore, the nucleophilic attack of the NHC on the imine carbon or β-carbon of the α,β-unsaturated ester is the rate-limiting step that determines which intermediate is formed (the aza-Breslow or deoxy-Breslow intermediate). Analysis of the global reaction index indicates that NHCs play a vital role in the polarity reversal of an imine carbon atom or a β-carbon from the α,β-unsaturated ester. This strengthens the nucleophilicity of an imine carbon or a β-carbon from the α,β-unsaturated ester as a Lewis base. In addition, B-NHC has a slightly higher nucleophilicity value, which makes the reactivity of B-NHC slightly better than that of A-NHC. The theoretical results obtained not only rationalize the experimental observations well but also provide important insight into the mechanistic details of the reaction.