Abstract

Background: Azlactones, also known as oxazolones, are a class of versatile intermediates and are commonly used for the synthesis of various heterocyclic scaffolds and unnatural α-amino acids. In particular, because of their inherent multiple sites of reactivity, azlactones have recently attracted a great deal of research efforts from the synthetic community. By exploring different sites of reactivity, a variety of cycloaddition reactions have been developed to construct diverse synthetically and biologically important hetereocycles as well as α-amino acid derivatives bearing quaternary carbons. With the development of asymmetric catalysis, a range of catalytic asymmetric variants have also been developed by metal and organocatalysis to access various valuable enantioenriched molecules. However, to the best of our knowledge, there is still no comprehensive review devoted to this emerging topic to date.

Methods: We performed a systemic survey of azlactone-mediated cycloaddition reactions by SciFinder search. To calibrate the reasonable scope of this survey, we highlight the recent advances in the field of cycloaddition reactions of azlactones, and their applications to the construction of heterocycles according to the different types of reaction modes. Thus, thirty four leading papers were included in this review and accordingly organized by different sites of reactivity, including [2+3], [2+4], [2+8], and [3+2] cycloaddition reactions.

Conclusion: The results shown in this review confirmed the significance of such type of versatile intermediates. The discovery of new suitable reactive species and application of other catalytic modes can provide a fruitful platform for the development of new cycloadditions of azlactones.

Keywords: Azlactones, cycloaddition reactions, heterocycles, quaternary carbons, oxazolones, intermediate.

Graphical Abstract