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DOI: 10.1055/s-0037-1611500
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© Georg Thieme Verlag Stuttgart · New York

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

Thomas C. Stephens
,
University of York, Department of Chemistry, York, YO10 5DD, UK   Email: william.unsworth@york.ac.uk
› Author Affiliations
The authors wish to thank the Leverhulme Trust (for an Early Career Fellowship, ECF-2015-013, for W. P. U.), the University of York (T. C. S. and W. P. U.), and the EPSRC (for a contribution to the DTA studentship for T. C. S., 1792616) for funding.
Further Information

Publication History

Received: 04 March 2019

Accepted after revision: 26 March 2019

Publication Date:
12 April 2019 (eFirst)

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

 
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