Amine synthesis via iron-catalysed reductive coupling of nitroarenes with alkyl halides
(Hetero)Aryl amines, an important class of organic molecules in medicinal chemistry, are most commonly synthesized from anilines, which are in turn synthesized by hydrogenation of nitroarenes. Amine synthesis directly from nitroarenes is attractive due to improved step economy and functional group c...
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| Format: | Online |
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Nature Publishing Group
2016
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4990657/ |
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pubmed-4990657 |
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pubmed-49906572016-09-01 Amine synthesis via iron-catalysed reductive coupling of nitroarenes with alkyl halides Cheung, Chi Wai Hu, Xile Article (Hetero)Aryl amines, an important class of organic molecules in medicinal chemistry, are most commonly synthesized from anilines, which are in turn synthesized by hydrogenation of nitroarenes. Amine synthesis directly from nitroarenes is attractive due to improved step economy and functional group compatibility. Despite these potential advantages, there is yet no general method for the synthesis of (hetero)aryl amines by carbon–nitrogen cross-coupling of nitroarenes. Here we report the reductive coupling of nitroarenes with alkyl halides to yield (hetero)aryl amines. A simple iron catalyst enables the coupling with numerous primary, secondary and tertiary alkyl halides. Broad scope and high functional group tolerance are demonstrated. Mechanistic study suggests that nitrosoarenes and alkyl radicals are involved as intermediates. This new C–N coupling method provides general and step-economical access to aryl amines. Nature Publishing Group 2016-08-12 /pmc/articles/PMC4990657/ /pubmed/27515391 http://dx.doi.org/10.1038/ncomms12494 Text en Copyright © 2016, The Author(s) http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Cheung, Chi Wai Hu, Xile |
| spellingShingle |
Cheung, Chi Wai Hu, Xile Amine synthesis via iron-catalysed reductive coupling of nitroarenes with alkyl halides |
| author_facet |
Cheung, Chi Wai Hu, Xile |
| author_sort |
Cheung, Chi Wai |
| title |
Amine synthesis via iron-catalysed reductive coupling of nitroarenes with alkyl halides |
| title_short |
Amine synthesis via iron-catalysed reductive coupling of nitroarenes with alkyl halides |
| title_full |
Amine synthesis via iron-catalysed reductive coupling of nitroarenes with alkyl halides |
| title_fullStr |
Amine synthesis via iron-catalysed reductive coupling of nitroarenes with alkyl halides |
| title_full_unstemmed |
Amine synthesis via iron-catalysed reductive coupling of nitroarenes with alkyl halides |
| title_sort |
amine synthesis via iron-catalysed reductive coupling of nitroarenes with alkyl halides |
| description |
(Hetero)Aryl amines, an important class of organic molecules in medicinal chemistry, are most commonly synthesized from anilines, which are in turn synthesized by hydrogenation of nitroarenes. Amine synthesis directly from nitroarenes is attractive due to improved step economy and functional group compatibility. Despite these potential advantages, there is yet no general method for the synthesis of (hetero)aryl amines by carbon–nitrogen cross-coupling of nitroarenes. Here we report the reductive coupling of nitroarenes with alkyl halides to yield (hetero)aryl amines. A simple iron catalyst enables the coupling with numerous primary, secondary and tertiary alkyl halides. Broad scope and high functional group tolerance are demonstrated. Mechanistic study suggests that nitrosoarenes and alkyl radicals are involved as intermediates. This new C–N coupling method provides general and step-economical access to aryl amines. |
| publisher |
Nature Publishing Group |
| publishDate |
2016 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4990657/ |
| _version_ |
1613630359984930816 |