Recent advances in the application of the isoxazoline route to aldols in the synthesis of natural products

Abstract

Covering: 2000 to 2024

The cycloaddition of nitrile oxides with olefins (NOC), followed by reductive cleavage of the resulting isoxazolines, has been widely recognised as a convenient and powerful synthetic strategy for constructing the aldol motif in natural product synthesis. Different modes of NOC (intermolecular, fused and bridged intramolecular) enable the synthesis of diverse isoxazoline products, which can be converted into highly substituted cyclic and acyclic aldol frameworks. This review examines the advances in this field over the past 25 years. More than 50 total syntheses are discussed, encompassing various classes of natural compounds, including macrolides, alkaloids, terpenoids, steroids, pseudosugars, sulfolipids and some others. Moreover, the basic aspects of this methodology are outlined, including methods for the generation of nitrile oxides and isoxazoline ring cleavage, as well as stereochemical models for intramolecular nitrile oxide cycloaddition.