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Continuous‐Flow Divergent Lithiation of 2,3‐Dihalopyridines: Deprotolithiation versus Halogen Dance
We describe herein the first halogen dance (HD) in continuous flow on 2‐chloro‐3‐bromopyridine by selectively trapping a (pyridin‐4‐yl)lithium species that is known to undergo the halogen‐dance process. In addition, this lithiated intermediate was trapped at lower temperature before the HD occurs. T...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10092453/ https://www.ncbi.nlm.nih.gov/pubmed/36200571 http://dx.doi.org/10.1002/chem.202202286 |
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author | Brégent, Thibaud Ivanova, Maria V. Poisson, Thomas Jubault, Philippe Legros, Julien |
author_facet | Brégent, Thibaud Ivanova, Maria V. Poisson, Thomas Jubault, Philippe Legros, Julien |
author_sort | Brégent, Thibaud |
collection | PubMed |
description | We describe herein the first halogen dance (HD) in continuous flow on 2‐chloro‐3‐bromopyridine by selectively trapping a (pyridin‐4‐yl)lithium species that is known to undergo the halogen‐dance process. In addition, this lithiated intermediate was trapped at lower temperature before the HD occurs. The HD process was extended to fluoro‐iodopyridines by using various electrophiles to afford 28 examples with yields ranging from 42 to 97 % with very short residence times. Finally, scale up of the reaction was demonstrated, affording a promising space‐time yield (STY) of 4.2 kg.h(−1).L(−1). |
format | Online Article Text |
id | pubmed-10092453 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-100924532023-04-13 Continuous‐Flow Divergent Lithiation of 2,3‐Dihalopyridines: Deprotolithiation versus Halogen Dance Brégent, Thibaud Ivanova, Maria V. Poisson, Thomas Jubault, Philippe Legros, Julien Chemistry Research Articles We describe herein the first halogen dance (HD) in continuous flow on 2‐chloro‐3‐bromopyridine by selectively trapping a (pyridin‐4‐yl)lithium species that is known to undergo the halogen‐dance process. In addition, this lithiated intermediate was trapped at lower temperature before the HD occurs. The HD process was extended to fluoro‐iodopyridines by using various electrophiles to afford 28 examples with yields ranging from 42 to 97 % with very short residence times. Finally, scale up of the reaction was demonstrated, affording a promising space‐time yield (STY) of 4.2 kg.h(−1).L(−1). John Wiley and Sons Inc. 2022-10-31 2022-12-20 /pmc/articles/PMC10092453/ /pubmed/36200571 http://dx.doi.org/10.1002/chem.202202286 Text en © 2022 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Research Articles Brégent, Thibaud Ivanova, Maria V. Poisson, Thomas Jubault, Philippe Legros, Julien Continuous‐Flow Divergent Lithiation of 2,3‐Dihalopyridines: Deprotolithiation versus Halogen Dance |
title | Continuous‐Flow Divergent Lithiation of 2,3‐Dihalopyridines: Deprotolithiation versus Halogen Dance |
title_full | Continuous‐Flow Divergent Lithiation of 2,3‐Dihalopyridines: Deprotolithiation versus Halogen Dance |
title_fullStr | Continuous‐Flow Divergent Lithiation of 2,3‐Dihalopyridines: Deprotolithiation versus Halogen Dance |
title_full_unstemmed | Continuous‐Flow Divergent Lithiation of 2,3‐Dihalopyridines: Deprotolithiation versus Halogen Dance |
title_short | Continuous‐Flow Divergent Lithiation of 2,3‐Dihalopyridines: Deprotolithiation versus Halogen Dance |
title_sort | continuous‐flow divergent lithiation of 2,3‐dihalopyridines: deprotolithiation versus halogen dance |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10092453/ https://www.ncbi.nlm.nih.gov/pubmed/36200571 http://dx.doi.org/10.1002/chem.202202286 |
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