LAUSR

Macrocycles and medium-sized rings have important applications in several scientific fields but can be challenging to make using traditional end-to-end cyclization reactions. Ring-expansion methods represent a useful alternative and offer numerous practical benefits. In this Account, we discuss the current state of the art of ring-expansion strategies that have been applied consecutively. Such methods have the power to expedite the design and synthesis of functionalized macro­cycles via the selective, iterative insertion of smaller fragments into ring-enlarged products.1 Introduction2 Insertion Reactions2.1 Transamidation/Transpeptidation2.2 Transesterification2.3 Transthioesterification2.4 Aminyl Radical Cascade2.5 Iterative Synthesis of Lactones2.6 Successive Ring Expansion of β-Ketoesters and Lactams3 Pericyclic Reactions3.1 Sulfur-Mediated Rearrangements3.2 Nitrogen-Mediated Rearrangements4 Fragmentation Reactions5 Conclusions and Future Outlook