Asymmetric Synthesis of Isoxazol-5-ones and Isoxazolidin-5-ones

Abstract

Isoxazol-5-ones and isoxazolidin-5-ones represent two important classes of heterocycles, with several applications as bioactive compounds and as versatile building blocks for further transformations. Unlike the parent aromatic isoxazoles, the presence of one or two stereocenters in the ring renders their asymmetric construction particularly important. In this review, starting from the description of general features and differences between these two related compound families, we present an overview on the most important enantioselective synthesis strategies to access these heterocycles. Both chiral metal catalysts and organocatalysts have recently been successfully employed for this task and some of the most promising approaches will be discussed.1 Introduction2 Isoxazol-5-ones as Nucleophiles2.1 Isoxazol-5-ones as C-Nucleophiles2.2 Isoxazol-5-ones as N-Nucleophiles2.3 Isoxazol-5-ones as C-Nucleophiles in Cyclization Processes3 Asymmetric Construction of Isoxazolidin-5-ones3.1 Enantioselective α-Functionalizations of Isoxazolidin-5-ones4 Arylideneisoxazol-5-ones in Conjugated Addition5 Conclusions

Recent Advances in Selected Asymmetric Reactions Promoted by Chiral Catalysts: Cyclopropanations, Friedel–Crafts, Mannich, Michael and Other Zinc-Mediated Processes—An Update

“…Moreover, Michael additions performed in the presence of zinc ions also enjoy quite a lot of interest [70]. Currently, target materials in the asymmetric Michael addition reaction are very often isoxazole-5-ones and isoxazolidin-5-ones [71], and pyrazolones [72].…”

On the Brønsted acid-catalyzed aza-Michael reaction of isoxazol-5-ones to enones: reaction optimization, scope, mechanistic investigations and scale-up

“…31 Interestingly, although 4-arylidene isoxazol-5ones have been widely described as Michael acceptors, 32 the use of other 4-substitued isoxazol-5-ones as Michael donors is still sparse. 33 Moreover, most precedents involve the reactivity at the carbon at the 4-position of the heterocycle. 34,35 To the best of our knowledge only two studies have described the use of isoxazol-5-ones as aza-Michael donors, both presenting the regioselective 1,6-addition to para-quinone methides (Scheme 1A and B ).…”