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Barbier Continuous Flow Preparation and Reactions of Carbamoyllithiums for Nucleophilic Amidation
Author(s) -
Ganiek Maximilian A.,
Becker Matthias R.,
Berionni Guillaume,
Zipse Hendrik,
Knochel Paul
Publication year - 2017
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201702593
Subject(s) - nucleophile , continuous flow , chemistry , combinatorial chemistry , flow (mathematics) , mathematics , organic chemistry , catalysis , biochemical engineering , engineering , geometry
An ambient temperature continuous flow method for nucleophilic amidation and thioamidation is described. Deprotonation of formamides by lithium diisopropylamine (LDA) affords carbamoyllithium intermediates that are quenched in situ with various electrophiles such as ketones, allyl bromides, Weinreb and morpholino amides. The nature of the reactive lithium intermediates and the thermodynamics of the metalation were further investigated by ab initio calculations and kinetic experiments.