Recent Advances on the Synthesis and Reactivity of Isoxazoles

Teresa   M.V.D.   Pinho e Melo

Abstract

Isoxazoles are a class of heterocyclic compounds having a remarkable number of applications and have been demonstrated to be very versatile building blocks in organic synthesis. The wide range of biological activities includes pharmacological properties such as hypoglycemic, analgesic, antiinflammatory, anti-bacterial and HIV-inhibitory activity. Some isoxazole derivatives display agrochemical properties namely herbicidal and soil fungicidal activity and have applications as pesticides and insecticides. Isoxazoles have also been used as dyes, electric insulating oils, high temperature lubricants and polyisoxazoles have applications as semicondutors. The key feature of these heterocycles is that they possess the typical properties of an aromatic system but contain a weak nitrogen-oxygen bond which under certain reaction conditions, particularly in reducing or basic conditions, is a potential site of ring cleavage. Thus, isoxazoles are very useful intermediates since the ring system stability allows the manipulation of substituents to give functionally complex derivatives, yet it is easily cleaved when necessary. The ring opening provides difunctionalized compounds, namely 1,3-dicarbonyl, enaminoketone, γ-amino alcohol, α,β- unsaturated oxime, β-hydroxy nitrile or β-hydroxy ketone compounds, so that isoxazoles can be considered masked forms of these synthetic units. Consequently, isoxazoles have become an important synthetic tool. The construction of the isoxazole ring can be achieved by several synthetic approaches. However, the two major routes to isoxazoles are the 1,3-dipolar cycloadditon of alkenes and alkynes with nitrile oxides and the reaction of hydroxylamine with a three-carbon atom component, such as 1,3-diketone or an α,β-unsaturated ketone. This review aims to provide coverage of the recent developments on the synthesis and reactivity of isoxazoles.

Keywords: cyclizationdehydration, cycloaddition, hydroxylamine, anti-inflammatory, boc-protected