Multicomponent synthesis of α-branched amines using organozinc reagents generated from alkyl bromides

The use of alkylzinc bromides in the multicomponent Mannich reaction is described. Heteroleptic organozinc compounds were obtained in THF or 2-MeTHF by direct insertion of zinc dust into the C–Br bond of alkyl bromides. It was found that the presence of a stoichiometric amount of LiCl was essential...

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Main Authors: Baptiste Leroux, Alexis Beaufils, Federico Banchini, Olivier Jackowski, Alejandro Perez-Luna, Fabrice Chemla, Marc Presset, Erwan Le Gall
Format: Article
Language:English
Published: Beilstein-Institut 2024-11-01
Series:Beilstein Journal of Organic Chemistry
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Online Access:https://doi.org/10.3762/bjoc.20.239
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author Baptiste Leroux
Alexis Beaufils
Federico Banchini
Olivier Jackowski
Alejandro Perez-Luna
Fabrice Chemla
Marc Presset
Erwan Le Gall
author_facet Baptiste Leroux
Alexis Beaufils
Federico Banchini
Olivier Jackowski
Alejandro Perez-Luna
Fabrice Chemla
Marc Presset
Erwan Le Gall
author_sort Baptiste Leroux
collection DOAJ
description The use of alkylzinc bromides in the multicomponent Mannich reaction is described. Heteroleptic organozinc compounds were obtained in THF or 2-MeTHF by direct insertion of zinc dust into the C–Br bond of alkyl bromides. It was found that the presence of a stoichiometric amount of LiCl was essential for the efficiency of the subsequent three-component coupling with aldehydes and amines. A variety of primary, secondary, and tertiary organozinc reagents as well as secondary amines and aromatic aldehydes could be used for the straightforward preparation of α-branched amines. Interestingly, whereas previously reported work describing the preparation and reaction of organozinc iodides in acetonitrile showed higher reactivity of secondary organozinc reagents over primary ones, reactions in THF in the presence of LiCl led to opposite results, with higher reactivity of primary organozinc reagents.
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spelling doaj-art-4b7b21f253ac485da4a8fbcb65eacfa92024-12-02T08:46:11ZengBeilstein-InstitutBeilstein Journal of Organic Chemistry1860-53972024-11-012012834283910.3762/bjoc.20.2391860-5397-20-239Multicomponent synthesis of α-branched amines using organozinc reagents generated from alkyl bromidesBaptiste Leroux0Alexis Beaufils1Federico Banchini2Olivier Jackowski3Alejandro Perez-Luna4Fabrice Chemla5Marc Presset6Erwan Le Gall7Univ Paris-Est Créteil, CNRS, ICMPE, UMR 7182, 2 rue Henri Dunant, 94320 Thiais, France Univ Paris-Est Créteil, CNRS, ICMPE, UMR 7182, 2 rue Henri Dunant, 94320 Thiais, France Sorbonne Université, CNRS, Institut Parisien de Chimie Moléculaire, IPCM, 75005 Paris, France Sorbonne Université, CNRS, Institut Parisien de Chimie Moléculaire, IPCM, 75005 Paris, France Sorbonne Université, CNRS, Institut Parisien de Chimie Moléculaire, IPCM, 75005 Paris, France Sorbonne Université, CNRS, Institut Parisien de Chimie Moléculaire, IPCM, 75005 Paris, France Univ Paris-Est Créteil, CNRS, ICMPE, UMR 7182, 2 rue Henri Dunant, 94320 Thiais, France Univ Paris-Est Créteil, CNRS, ICMPE, UMR 7182, 2 rue Henri Dunant, 94320 Thiais, France The use of alkylzinc bromides in the multicomponent Mannich reaction is described. Heteroleptic organozinc compounds were obtained in THF or 2-MeTHF by direct insertion of zinc dust into the C–Br bond of alkyl bromides. It was found that the presence of a stoichiometric amount of LiCl was essential for the efficiency of the subsequent three-component coupling with aldehydes and amines. A variety of primary, secondary, and tertiary organozinc reagents as well as secondary amines and aromatic aldehydes could be used for the straightforward preparation of α-branched amines. Interestingly, whereas previously reported work describing the preparation and reaction of organozinc iodides in acetonitrile showed higher reactivity of secondary organozinc reagents over primary ones, reactions in THF in the presence of LiCl led to opposite results, with higher reactivity of primary organozinc reagents.https://doi.org/10.3762/bjoc.20.239alkyl bromidesbranched aminesmannich reactionmulticomponent reactionzinc
spellingShingle Baptiste Leroux
Alexis Beaufils
Federico Banchini
Olivier Jackowski
Alejandro Perez-Luna
Fabrice Chemla
Marc Presset
Erwan Le Gall
Multicomponent synthesis of α-branched amines using organozinc reagents generated from alkyl bromides
Beilstein Journal of Organic Chemistry
alkyl bromides
branched amines
mannich reaction
multicomponent reaction
zinc
title Multicomponent synthesis of α-branched amines using organozinc reagents generated from alkyl bromides
title_full Multicomponent synthesis of α-branched amines using organozinc reagents generated from alkyl bromides
title_fullStr Multicomponent synthesis of α-branched amines using organozinc reagents generated from alkyl bromides
title_full_unstemmed Multicomponent synthesis of α-branched amines using organozinc reagents generated from alkyl bromides
title_short Multicomponent synthesis of α-branched amines using organozinc reagents generated from alkyl bromides
title_sort multicomponent synthesis of α branched amines using organozinc reagents generated from alkyl bromides
topic alkyl bromides
branched amines
mannich reaction
multicomponent reaction
zinc
url https://doi.org/10.3762/bjoc.20.239
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