A practical and general amidation method from isocyanates enabled by flow technology

William J. Kerr, Jason Williams, Stuart Leach, David Lindsay

Research output: Contribution to journalArticle

7 Citations (Scopus)
10 Downloads (Pure)

Abstract

The addition of carbon nucleophiles to isocyanates represents a conceptually flexible and efficient approach to the preparation of amides. This general synthetic strategy has, however, been relatively underutilized, due to narrow substrate tolerance, and the requirement for less favourable reaction conditions. Herein, we disclose a high‐yielding, mass efficient, and scalable method with appreciable functional group tolerance for the formation of amides by reaction of Grignard reagents with isocyanates. Through the application of flow chemistry, and the use of sub‐stoichiometric amounts of CuBr2, this process has been developed to encompass a broad range of substrates, including reactants found to be incompatible with previously published protocols.
Original languageEnglish
Pages (from-to)12126-12130
Number of pages5
JournalAngewandte Chemie International Edition
Volume57
Issue number37
Early online date18 Jul 2018
DOIs
Publication statusPublished - 10 Sep 2018

Fingerprint

Isocyanates
Amides
Nucleophiles
Substrates
Functional groups
Carbon

Keywords

  • amides
  • C-C coupling
  • synthetic methods
  • Grignard reaction
  • flow chemistry

Cite this

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A practical and general amidation method from isocyanates enabled by flow technology. / Kerr, William J.; Williams, Jason; Leach, Stuart; Lindsay, David.

In: Angewandte Chemie International Edition, Vol. 57, No. 37, 10.09.2018, p. 12126-12130.

Research output: Contribution to journalArticle

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AU - Williams, Jason

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AB - The addition of carbon nucleophiles to isocyanates represents a conceptually flexible and efficient approach to the preparation of amides. This general synthetic strategy has, however, been relatively underutilized, due to narrow substrate tolerance, and the requirement for less favourable reaction conditions. Herein, we disclose a high‐yielding, mass efficient, and scalable method with appreciable functional group tolerance for the formation of amides by reaction of Grignard reagents with isocyanates. Through the application of flow chemistry, and the use of sub‐stoichiometric amounts of CuBr2, this process has been developed to encompass a broad range of substrates, including reactants found to be incompatible with previously published protocols.

KW - amides

KW - C-C coupling

KW - synthetic methods

KW - Grignard reaction

KW - flow chemistry

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