Nitrone chemistry: a versatile gateway to diverse heterocycles

Abstract

Nitrones (azomethine N-oxides) are among the most versatile intermediates in organic synthesis, enabling the efficient construction of heterocyclic frameworks that underpin advances in medicinal chemistry, materials science, and chemical biology. Over the past few years, transition-metal-catalyzed strategies have delivered remarkable control over regio- and stereoselectivity, yet their cost and limitations in substrate scope have encouraged the search for alternatives. In this context, transition-metal-free protocols, including [3 + 2], [2 + 2] and [4 + 2] cycloadditions, have emerged as sustainable and economical approaches. Complementing these methods, new developments such as asymmetric click reactions, deoxygenative cyclizations, silylacetate-promoted addition reactions, photoredox catalysis, and self-oxidative cyclizations further broaden the synthetic toolbox, enabling access to structurally complex and biologically relevant scaffolds. By integrating these diverse methodologies, nitrone chemistry continues to evolve as a dynamic platform for heterocycle construction. This review highlights recent synthetic strategies for nitrone-derived heterocycles reported from 2021 to 2025, critically evaluating their advantages and limitations while outlining promising directions toward greener, more versatile, and practically useful methodologies.