Issue 28, 2021

[2 + 2 + 1] Cycloaddition of N-tosylhydrazones, tert-butyl nitrite and alkenes: a general and practical access to isoxazolines

Abstract

N-Tosylhydrazones have proven to be versatile synthons over the past several decades. However, to our knowledge, the construction of isoxazolines based on N-tosylhydrazones has not been examined. Herein, we report the first demonstrations of [2 + 2 + 1] cycloaddition reactions that allow the facile synthesis of isoxazolines, employing N-tosylhydrazones, tert-butyl nitrite (TBN) and alkenes as reactants. This process represents a new type of cycloaddition reaction with a distinct mechanism that does not involve the participation of nitrile oxides. This approach is both general and practical and exhibits a wide substrate scope, nearly universal functional group compatibility, tolerance of moisture and air, the potential for functionalization of complex bioactive molecules and is readily scaled up. Both control experiments and theoretical calculations indicate that this transformation proceeds via the in situ generation of a nitronate from the coupling of N-tosylhydrazone and TBN, followed by cycloaddition with an alkene and subsequent elimination of a tert-butyloxy group to give the desired isoxazoline.

Graphical abstract: [2 + 2 + 1] Cycloaddition of N-tosylhydrazones, tert-butyl nitrite and alkenes: a general and practical access to isoxazolines

Supplementary files

Article information

Article type
Edge Article
Submitted
28 apr 2021
Accepted
19 iyn 2021
First published
22 iyn 2021
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2021,12, 9823-9830

[2 + 2 + 1] Cycloaddition of N-tosylhydrazones, tert-butyl nitrite and alkenes: a general and practical access to isoxazolines

L. Ma, F. Jin, X. Cheng, S. Tao, G. Jiang, X. Li, J. Yang, X. Bao and X. Wan, Chem. Sci., 2021, 12, 9823 DOI: 10.1039/D1SC02352G

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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