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Synthesis 2019; 51(07): 1516-1528
DOI: 10.1055/s-0037-1611714
short review
© Georg Thieme Verlag Stuttgart · New York

Synthetic Approaches to Nitro-Substituted Isoxazoles

Dmitry A. Vasilenko
a   Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 1–3, Moscow, 119991, Russian Federation   Email: elaver@med.chem.msu.ru
,
Kseniya N. Sedenkova
a   Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 1–3, Moscow, 119991, Russian Federation   Email: elaver@med.chem.msu.ru
b   IPhaC RAS, Severnyi Proezd, 1, Chernogolovka, Moscow Region, 142432, Russian Federation
,
Tamara S. Kuznetsova
a   Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 1–3, Moscow, 119991, Russian Federation   Email: elaver@med.chem.msu.ru
,
Elena B. Averina*
a   Department of Chemistry, Lomonosov Moscow State University, Leninskie Gory, 1–3, Moscow, 119991, Russian Federation   Email: elaver@med.chem.msu.ru
b   IPhaC RAS, Severnyi Proezd, 1, Chernogolovka, Moscow Region, 142432, Russian Federation
› Author AffiliationsWe thank the Russian Science Foundation, grant no. 17-15-01455 for financial support of this work.
Further Information

Publication History

Received: 22 October 2018

Accepted after revision: 22 November 2018

Publication Date:
27 February 2019 (online)

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Abstract

Nitro-substituted isoxazoles are of utmost interest both as versatile intermediates for targeted organic synthesis and as perspective bioactive compounds for drug development. Nevertheless, the existing approaches to them usually lack generality and strongly depend on the position of the nitro group and on the presence of other substituents in the isoxazole ring. This review provides the first systematization of all available data concerning synthetic approaches to 3-, 4-, and 5-nitroisoxazoles. There are a number of preparative approaches to 4-nitroisoxazoles based on classical heterocyclization reactions of nitro-substituted compounds and the nitration of isoxazoles. 3-Nitro- and, especially, 5-nitroisoxazoles are much less readily available. A few methods affording 3-nitroisoxazoles have been reported, often employing the heterocyclization of unsaturated compounds by treatment with sodium nitrite. The sole general preparative method for 5-nitroisoxazoles, containing a variety of functional groups, employs the heterocyclization of electrophilic alkenes by treatment with tetranitromethane activated with triethylamine.

1 Introduction

2 Synthesis of 4-Nitroisoxazoles

2.1 Nitration of Isoxazoles

2.2 Condensations of α-Nitro Ketones or Their Oximes

2.3 1,3-Dipolar Cycloaddition of Nitrile Oxides to Acetylenes and Their Synthetic Equivalents

2.4 Heterocyclization of Acetylene Derivatives by Treatment with Sodium Nitrite

2.5 Heterocyclization of Nitro Derivatives of 1,3-Diketones and Their Synthetic Equivalents

2.6 Miscellaneous Methods

3 Synthesis of 3-Nitroisoxazoles

3.1 Heterocyclization of Acetylene Derivatives or 1,3-Dihalogenoalkenes by Treatment with Sodium Nitrite

3.2 Heterocyclization of Morita–Baylis–Hillman Acetates by Treatment with Sodium Nitrite

3.3 1,3-Dipolar Cycloadditions

4 Synthesis of 5-Nitroisoxazoles

4.1 1,3-Dipolar Cycloadditions

4.2 Synthesis Using Polynitro Compounds

5 Conclusion

Key words

nitroisoxazoles - nitration - condensation - heterocyclization - cycloaddition - polynitro compounds