Non-catalytic regioselective synthesis of <i>trans</i> bis-pyrrolo isoxazole cycloadducts in water

Majhool, Alhussein Arkan; Khalaf, Assad Abbas; Hasan, Iman Sabeeh; Kumar, Ranvijay; Kaushal, Sandeep; Badru, Rahul

doi:10.1039/d3su00396e

RSC Sustain.

2024

DOI: 10.1039/d3su00396e

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Non-catalytic regioselective synthesis of trans bis-pyrrolo isoxazole cycloadducts in water

Alhussein Arkan Majhool,

Assad Abbas Khalaf,

Iman Sabeeh Hasan

et al.

Abstract: In the present work, pyrrolo isoxazoles have been synthesized by a one-pot, facile, and non-catalytic process, conducted at low temperature and under aqueous conditions. It can be counted as a step towards sustainable and green synthetic chemistry.

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Mechanisms and Origins of Regio- and Stereoselectivities in NHC-Catalyzed [3 + 3] Annulation of α-Bromoenals and 5-Aminoisoxazoles: A DFT Study

Zhang,

2024

J. Org. Chem.

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Density functional theory (DFT) calculations were conducted to explore the mechanisms and origins of regio-and stereoselectivities underlying the [3 + 3] annulation reaction between α-bromoenals and 5-aminoisoxazoles with N-heterocyclic carbene (NHC) as the catalyst. The reaction occurs in nine steps:(1) nucleophilic addition of NHC to α-bromoenal, (2) Breslow intermediate formation through 1,2-proton transfer, (3) debromination, (4) α,β-unsaturated acyl azolium intermediate formation via 1,3-proton transfer, (5) addition of α,β-unsaturated acyl azolium intermediate to 5-aminoisoxazole, (6) deprotonation, (7) protonation, (8) ring closure, and (9) elimination of NHC. For the fifth step, 1,2-addition suggested in the experiment was not supported by our results. Instead, we found that Michael addition is energetically the most feasible pathway and the stereocontrolling step that preferentially provides the S-configuration product. DFT-computed results and experimental findings agree well. Analysis of distortion/interaction reveals that lower distortion energy leads to stability of the transition state corresponding to the Sconfiguration product. Global reactivity index analysis indicates that the behavior of the NHC catalyst differs significantly before and after the Breslow intermediate debromination. Before debromination, the nucleophilicity of α-bromoenal is enhanced by addition to NHC. However, after debromination, the α,β-unsaturated acyl azole generates and acts as an electrophilic reagent.

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Mechanisms and Origins of Regio- and Stereoselectivities in NHC-Catalyzed [3 + 3] Annulation of α-Bromoenals and 5-Aminoisoxazoles: A DFT Study

Zhang,

2024

J. Org. Chem.

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Non-catalytic regioselective synthesis of trans bis-pyrrolo isoxazole cycloadducts in water

Abstract: In the present work, pyrrolo isoxazoles have been synthesized by a one-pot, facile, and non-catalytic process, conducted at low temperature and under aqueous conditions. It can be counted as a step towards sustainable and green synthetic chemistry.

Cited by 1 publication

References 39 publications

Mechanisms and Origins of Regio- and Stereoselectivities in NHC-Catalyzed [3 + 3] Annulation of α-Bromoenals and 5-Aminoisoxazoles: A DFT Study

Mechanisms and Origins of Regio- and Stereoselectivities in NHC-Catalyzed [3 + 3] Annulation of α-Bromoenals and 5-Aminoisoxazoles: A DFT Study

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