Single-atom molecular editing: transformative advances in carbocyclic and heterocyclic frameworks.

Abstract

Single-atom editing has emerged as a transformative strategy in organic synthesis, enabling precise modification of carbocyclic and heterocyclic frameworks by selectively targeting single atoms. These frameworks are crucial backbones of pharmaceuticals, agrochemicals, and advanced materials, making this approach powerful for organic chemists. In drug discovery and natural product synthesis, single-atom editing diversifies molecular scaffolds and tailors molecular properties to enhance pharmacological activity. In heterocyclic synthesis, this approach enables controlled heteroatom substitution, addition or deletion in an unprecedented and highly selective manner compared to traditional methods. Recent advances in transition-metal catalysis, organocatalysis, photoredox catalysis, and heterocycle-to-heterocycle metamorphosis have expanded the versatility of single-atom editing, enabling the synthesis of various carbocyclic and heterocyclic compounds. Principally, this approach has been exploited to design new architectures that are not easily accessible by other methods and to establish major improvements in the synthesis of known scaffolds, providing more efficient and sustainable routes towards large-scale chemical synthesis. This review overviews recent advances, focusing on carbocyclic and heterocyclic frameworks, and is organized by key single-atom editing strategies, such as ring contractions, atom deletions, ring expansions, and atom insertions. The review highlights key transformations like Favorskii and Wolff rearrangements, alongside modern photochemical and transition-metal-catalyzed processes, to provide a broad overview of synthetic applications and inspire further advancements in targeted molecular edits.