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

William P. Unsworth; Richard J K Taylor

doi:10.1055/s-0035-1562095

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

William P. Unsworth^*, Richard J K Taylor

^*Corresponding author for this work

Chemistry

Research output: Contribution to journal › Article › peer-review

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

Original language	English
Pages (from-to)	2051-2064
Number of pages	14
Journal	Synlett
Volume	27
Issue number	14
Early online date	10 May 2016
DOIs	https://doi.org/10.1055/s-0035-1562095
Publication status	E-pub ahead of print - 10 May 2016

Bibliographical note

© 2016, Georg Thieme Verlag. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details

Keywords

cavidine
evodiamine
N-acyliminium ions
N-heterocycles
natural products
spirocycles
‘upenamide

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10.1055/s-0035-1562095

SYNLETT account DIA FINAL version after review
© 2016, Georg Thieme Verlag. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details
Accepted author manuscript, 1.15 MB

Cite this

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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 {\textquoteleft}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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N2 - 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

AB - 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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KW - natural products

KW - spirocycles

KW - ‘upenamide

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

Abstract

Bibliographical note

Keywords

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