Mechanistic Aspects on [3+2] Cycloaddition (32CA) Reactions of Azides to Nitroolefins: A Computational and Kinetic Study

Author(s)

Kawamura, Meire Y. ; Alegre-Requena, Juan, V ; Barbosa, Thais M. ; Tormena, Claudio F. ; Paton, Robert S. ; Ferreira, Marco A. B.

• Document type: Journal article
• Source: CHEMISTRY-A EUROPEAN JOURNAL; v. 28, n. 69, p. 9-pg., 2022-10-19.

Abstract

[3+2] cycloadditions of nitroolefins have emerged as a selective and catalyst-free alternative for the synthesis of 1,2,3-triazoles from azides. We describe mechanistic studies into the cycloaddition/rearomatization reaction sequence. DFT calculations revealed a rate-limiting cycloaddition step proceeding via an asynchronous TS with high kinetic selectivity for the 1,5-triazole. Kinetic studies reveal a second-order rate law, and C-13 kinetic isotopic effects at natural abundance were measured with a significant normal effect at the conjugated olefinic centers of 1.0158 and 1.0216 at the alpha and beta-carbons of beta-nitrostyrene. Distortion/interaction-activation strain and energy decomposition analyses revealed that the major regioisomeric pathway benefits from an earlier and less-distorted TS, while intermolecular interaction terms dominate the preference for 1,5- over 1,4-cycloadducts. In addition, the major regioisomer also has more favorable electrostatic and dispersion terms. Additionally, while static DFT calculations suggest a concerted but highly asynchronous Ei-type HNO2 elimination mechanism, quasiclassical direct-dynamics calculations reveal the existence of a dynamic intermediate. (AU)

• FAPESP's process: 17/01754-0 - Experimental and theoretical studies on cycloaddition (3 + 2) reactions of azides to nitro-olefins
• Grantee: Meire Yasuko Kawamura
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 20/10246-0 - Nuclear magnetic resonance spectroscopy: from pulse sequences to structural assignments
• Grantee: Claudio Francisco Tormena
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 20/01255-6 - Application of statistical tools in catalysis for understanding and predicting organic reactions
• Grantee: Marco Antonio Barbosa Ferreira
• Support Opportunities: Regular Research Grants