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Coupling of pseudoradical centers in the synthesis of oxazine fused-spiroindoline: a two-stage one-step double cyclization

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Abstract

In this research, a MEDT study was performed on the reaction of phenyl nitrile oxide (NO) with N-methyl-2-isocyanoethylindole (MICI), experimentally explored by Xu and coworkers. Based on their report, a step-wise double cyclization takes place on the nitrilium ion (NI) intermediate generated from the reaction of NO and MICI. The result of the CDFT analysis indicated that MICI acts as nucleophile toward NO. The results of the PES analysis suggested that the first step of the reaction leading to the formation of NI is the rate-determining step. Although Xu and coworkers proposed a step-wise mechanism with the formation of a zwitterionic intermediate for the double cyclization on NI, our results ruled out the formation of any stable zwitterionic intermediate. Indeed, this reaction proceeds via a two-stage one-step mechanism, in which the two new single bonds are formed in two stages but from one transition state. The ELF analysis suggested that while the first single bond is formed via the coupling of the pseudoradical centers located on the corresponding carbon atoms, the second single bond is formed from the polarization of the oxygen lone pair toward the carbon atom. IGMH analysis supported the two-stage one-step mechanism of the reaction.

Graphical abstract

A two-stage one-step mechanism is concluded for double cyclization of a nitrilium ion intermediate. The ELF analysis suggests that while the C-C bond is formed via the coupling of the pseudoradical centers, the C-O bond is formed from the polarization of the oxygen lone pair toward the carbon atom.

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Acknowledgment

The author is thankful to the Research Council and Office of Graduate Studies of Ayatollah Boroujerdi University for their financial support.

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  1. Chemistry Department, Faculty of Science, Ayatollah Boroujerdi University, Boroujerd, Iran

    Mousa Soleymani

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Soleymani, M. Coupling of pseudoradical centers in the synthesis of oxazine fused-spiroindoline: a two-stage one-step double cyclization. J Chem Sci 134, 99 (2022). https://doi.org/10.1007/s12039-022-02098-2

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