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A Practical and General Amidation Method from Isocyanates Enabled by Flow Technology
Author(s) -
Williams Jason D.,
Kerr William J.,
Leach Stuart G.,
Lindsay David M.
Publication year - 2018
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201807393
Subject(s) - nucleophile , reagent , functional group , combinatorial chemistry , substrate (aquarium) , flow chemistry , chemistry , reaction conditions , process (computing) , organic chemistry , computer science , catalysis , oceanography , operating system , geology , polymer
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 CuBr 2 , this process has been developed to encompass a broad range of substrates, including reactants found to be incompatible with previously published procedures.