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

Thomas C. Stephens; William P. Unsworth

doi:10.1055/s-0037-1611500

Synlett, Table of Contents

Synlett 2020; 31(02): 133-146
DOI: 10.1055/s-0037-1611500

account

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

Thomas C. Stephens

,

William P. Unsworth *

University of York, Department of Chemistry, York, YO10 5DD, UK Email: william.unsworth@york.ac.uk

› Author Affiliations

Abstract

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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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References

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