Consecutive Ring-Expansion Reactions for the Iterative Assembly of Medium-Sized Rings and Macrocycles

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

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