Catalytic asymmetric reactions of isoxazole derivatives: organocatalysis, metal catalysis and phase-transfer catalysis.

Isoxazoles are versatile N,O-containing five-membered heterocyclic building blocks widely utilized in the construction of chiral pharmaceutical intermediates. Over the past two decades, tremendous progress has been made in their catalytic asymmetric transformations, which can be categorized into three types: organocatalysis, transition-metal catalysis and chiral phase-transfer catalysis, yet a systematic review covering all these systems remains absent. This paper summarizes diverse reactions involving substrates such as nitroalkenylisoxazoles and aminoisoxazoles, including asymmetric Michael addition, cycloaddition, cascade addition, ring contraction and hydrofunctionalization. It elaborates on reaction parameters, substrate compatibility, stereocontrol mechanisms and synthetic practicability of each catalytic system and compares the respective merits and drawbacks of the three catalytic categories. This review identifies the existing limitations in this research field and puts forward prospects for future development, providing a theoretical reference for the exploration of novel asymmetric catalytic reactions based on isoxazole scaffolds.