Mechanisms of cascade reactions between N-methylindole and sulfonylazides via Huisgen cycloaddition: A theoretical investigation

•The mechanisms for cascade reactions between N-methylindole and sulfonylazides via Huisgen cycloaddition were proposed.•Two possible reaction pathways I and II were found for these Huisgen cycloaddition reactions.•The gaseous environment and solvent play crucial roles in determining the product.

The mechanisms of three cascade reactions between N-methylindole and sulfonylazides via Huisgen cycloaddition were investigated using density functional theory, and the polarized continuum model (PCM) was applied to simulate the solvent effects. Fukui functions and dual descriptor have been employed to assess the atomic reactivity. With respect to these three reactions, each has two possible reaction pathways (I and II). The calculated results show that singlet O2 plays a crucial role in the oxidative dehydrogenation process in the first reaction between 2-imine indole and p-tosylazide (TsN3), when the reaction occurs without O2 but with N2, two pathways via the processes of breaking two covalent bonds, followed by 1,2-H shift and N2 removal (or by N2 removal and 1,2-H shift) exist. Water molecule plays an important role in the H-shift process in the third reaction of the methyl substituted N-methylindole with TsN3. Our results demonstrated that these reactions can take place at certain condition, in good agreement with the experimental observation. The understanding of the competitive pathways for Huisgen cycloaddition of N-methylindole and sulfonylazides can provide valuable insights into related reactions.

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