Barbier Continuous Flow Preparation and Reactions of Carbamoyllithiums for Nucleophilic Amidation

Maximilian A. Ganiek; Matthias R. Becker; Guillaume Berionni; Hendrik Zipse; Paul Knochel

doi:10.1002/chem.201702593

Barbier Continuous Flow Preparation and Reactions of Carbamoyllithiums for Nucleophilic Amidation

Maximilian A. Ganiek, Matthias R. Becker, Guillaume Berionni, Hendrik Zipse, Paul Knochel

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

Abstract

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.

Original language	English
Pages (from-to)	10280-10284
Number of pages	5
Journal	Chemistry - A European Journal
Volume	23
Issue number	43
DOIs	https://doi.org/10.1002/chem.201702593
Publication status	Published - 1 Aug 2017
Externally published	Yes

Keywords

acidity
amidation
Barbier reaction
flow chemistry
lithiation

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10.1002/chem.201702593

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abstract = "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.",

keywords = "acidity, amidation, Barbier reaction, flow chemistry, lithiation",

author = "Ganiek, {Maximilian A.} and Becker, {Matthias R.} and Guillaume Berionni and Hendrik Zipse and Paul Knochel",

note = "Funding Information: We thank the Deutsche Forschungsgemeinschaft (SFB 749, B2 and C6) for financial and Vapoutec Ltd. for technical support. M.A.G. thanks the German Academic Scholarship Foundation for a fellowship. Publisher Copyright: {\textcopyright} 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Copyright: Copyright 2017 Elsevier B.V., All rights reserved.",

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doi = "10.1002/chem.201702593",

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AU - Ganiek, Maximilian A.

AU - Becker, Matthias R.

AU - Berionni, Guillaume

AU - Zipse, Hendrik

AU - Knochel, Paul

N1 - Funding Information: We thank the Deutsche Forschungsgemeinschaft (SFB 749, B2 and C6) for financial and Vapoutec Ltd. for technical support. M.A.G. thanks the German Academic Scholarship Foundation for a fellowship. Publisher Copyright: © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Copyright: Copyright 2017 Elsevier B.V., All rights reserved.

PY - 2017/8/1

Y1 - 2017/8/1

N2 - 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.

AB - 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.

KW - acidity

KW - amidation

KW - Barbier reaction

KW - flow chemistry

KW - lithiation

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DO - 10.1002/chem.201702593

M3 - Article

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JO - Chemistry - A European Journal

JF - Chemistry - A European Journal

IS - 43

ER -

Barbier Continuous Flow Preparation and Reactions of Carbamoyllithiums for Nucleophilic Amidation

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Keywords

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