Synlett 2016; 27(14): 2051-2064
DOI: 10.1055/s-0035-1562095
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© Georg Thieme Verlag Stuttgart · New York

Direct Imine Acylation: A Versatile Method for the Synthesis of Nitrogen-Containing Heterocycles, Spirocycles and Natural Products

William P. Unsworth*
Department of Chemistry, University of York, Heslington, York, YO10 5DD, UK   Email: william.unsworth@york.ac.uk   Email: richard.taylor@york.ac.uk
,
Richard J. K. Taylor*
Department of Chemistry, University of York, Heslington, York, YO10 5DD, UK   Email: william.unsworth@york.ac.uk   Email: richard.taylor@york.ac.uk
› Author Affiliations
Further Information

Publication History

Accepted: 25 February 2016

Accepted after revision: 25 March 2016

Publication Date:
10 May 2016 (online)


Abstract

Diverse nitrogen-containing heterocyclic compounds can be synthesised by the N-acylation of imines using functionalised carboxylic acids (Direct Imine Acylation, DIA). The carboxylic acids are activated in situ using the coupling agent propylphosphonic acid anhydride (T3P), before reacting with the imine coupling partner to generate N-acyl­iminium ions in situ, that can then be trapped by oxygen-, nitrogen-, sulfur- or carbon-based nucleophiles built into the carboxylic acid. This versatile, convergent method has been used to generate a wide range of products, including aromatic and aliphatic heterocycles, β-lactams, azaspirocycles and natural products.

1 Introduction

2 DIA in the Total Synthesis of ‘Upenamide

3 DIA with Benzoic Acid Derivatives

4 DIA with Aliphatic Carboxylic Acids

5 DIA in the Synthesis of β-Lactams

6 DIA in the Synthesis of Azaspirocycles

7 Mechanistic Studies

8 Conclusion

 
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