Published as part of the Cluster Iterative Synthesis
Abstract
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 Introduction
2 Insertion Reactions
2.1 Transamidation/Transpeptidation
2.2 Transesterification
2.3 Transthioesterification
2.4 Aminyl Radical Cascade
2.5 Iterative Synthesis of Lactones
2.6 Successive Ring Expansion of β-Ketoesters and Lactams
3 Pericyclic Reactions
3.1 Sulfur-Mediated Rearrangements
3.2 Nitrogen-Mediated Rearrangements
4 Fragmentation Reactions
5 Conclusions and Future Outlook
Key words
ring expansion - ring enlargement - rearrangements - macrocycles - medium-sized rings - iterative synthesis