A Practical and General Amidation Method from Isocyanates Enabled by Flow Technology. Issue 37 (17th August 2018)

• Record Type: Journal Article
• Authors: Williams, Jason D.; Kerr, William J.; Leach, Stuart G.; Lindsay, David M.
• Is Part Of: Angewandte Chemie international edition. Volume 57:Issue 37(2018)
• Page Start: 12126
• Page End: 12130
• Publication Date: 2018-08-17
• Subjects: amides -- C−C coupling -- flow chemistry -- Grignard reaction -- synthetic methods; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201807393
• Languages: English
• ISSNs: 1433-7851

Abstract

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 owing 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 substoichiometric amounts of CuBr2, this process has been developed to encompass a broad range of substrates, including reactants found to be incompatible with previously published procedures. Abstract : Isocyanates represent a reactive and mass‐efficient synthon for amide bond formation, yet their use with stoichiometric organometallic reagents has, in the past, been hindered by side product formation. A straightforward and widely applicable procedure that is enabled by continuous flow now allows the coupling of sp 2 and sp 3 carbon fragments with a wide range of isocyanates.