Carbene-catalysed reductive coupling of nitrobenzyl bromides and activated ketones or imines via single-electron-transfer process
Benzyl bromides and related molecules are among the most common substrates in organic synthesis. They are typically used as electrophiles in nucleophilic substitution reactions. These molecules can also be activated via single-electron-transfer (SET) process for radical reactions. Representative rec...
| Main Authors: | , , , , , , , |
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| Format: | Journal Article |
| Language: | English |
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2017
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| Online Access: | https://hdl.handle.net/10356/83912 http://hdl.handle.net/10220/42863 |
| _version_ | 1811678007546347520 |
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| author | Li, Bao-Sheng Wang, Yuhuang Proctor, Rupert S. J. Zhang, Yuexia Webster, Richard D. Yang, Song Song, Bao-An Chi, Robin Yonggui |
| author2 | School of Physical and Mathematical Sciences |
| author_facet | School of Physical and Mathematical Sciences Li, Bao-Sheng Wang, Yuhuang Proctor, Rupert S. J. Zhang, Yuexia Webster, Richard D. Yang, Song Song, Bao-An Chi, Robin Yonggui |
| author_sort | Li, Bao-Sheng |
| collection | NTU |
| description | Benzyl bromides and related molecules are among the most common substrates in organic synthesis. They are typically used as electrophiles in nucleophilic substitution reactions. These molecules can also be activated via single-electron-transfer (SET) process for radical reactions. Representative recent progress includes α-carbon benzylation of ketones and aldehydes via photoredox catalysis. Here we disclose the generation of (nitro)benzyl radicals via N-heterocyclic carbene (NHC) catalysis under reductive conditions. The radical intermediates generated via NHC catalysis undergo formal 1,2-addition with ketones to eventually afford tertiary alcohol products. The overall process constitutes a formal polarity-inversion of benzyl bromide, allowing a direct coupling of two initially electrophilic carbons. Our study provides a new carbene-catalysed reaction mode that should enable unconventional transformation of (nitro)benzyl bromides under mild organocatalytic conditions. |
| first_indexed | 2024-10-01T02:46:25Z |
| format | Journal Article |
| id | ntu-10356/83912 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T02:46:25Z |
| publishDate | 2017 |
| record_format | dspace |
| spelling | ntu-10356/839122023-02-28T19:54:55Z Carbene-catalysed reductive coupling of nitrobenzyl bromides and activated ketones or imines via single-electron-transfer process Li, Bao-Sheng Wang, Yuhuang Proctor, Rupert S. J. Zhang, Yuexia Webster, Richard D. Yang, Song Song, Bao-An Chi, Robin Yonggui School of Physical and Mathematical Sciences Science::Chemistry Synthetic Chemistry Methodology Organocatalysis Benzyl bromides and related molecules are among the most common substrates in organic synthesis. They are typically used as electrophiles in nucleophilic substitution reactions. These molecules can also be activated via single-electron-transfer (SET) process for radical reactions. Representative recent progress includes α-carbon benzylation of ketones and aldehydes via photoredox catalysis. Here we disclose the generation of (nitro)benzyl radicals via N-heterocyclic carbene (NHC) catalysis under reductive conditions. The radical intermediates generated via NHC catalysis undergo formal 1,2-addition with ketones to eventually afford tertiary alcohol products. The overall process constitutes a formal polarity-inversion of benzyl bromide, allowing a direct coupling of two initially electrophilic carbons. Our study provides a new carbene-catalysed reaction mode that should enable unconventional transformation of (nitro)benzyl bromides under mild organocatalytic conditions. Economic Development Board (EDB) Ministry of Education (MOE) Nanyang Technological University National Research Foundation (NRF) Published version We acknowledge support by Singapore National Research Foundation (NRF), Ministry of Education, Singapore Economic Development Board (EDB), GlaxoSmithKline (GSK) and Nanyang Technological University (NTU); and China’s National Key program for Basic Research (No. 2010CB 126105), Thousand Talent Plan, National Natural Science Foundation of China (No.21132003; No. 21472028), the Returned Oversea Student Science and Technology Activity Program of Guizhou Province, The Guizhou Science and Technology Department’s Key Program and Guizhou University 2017-07-14T04:49:30Z 2019-12-06T15:34:27Z 2017-07-14T04:49:30Z 2019-12-06T15:34:27Z 2016 Journal Article Li, B., Wang, Y., Proctor, R. S. J., Zhang, Y., Webster, R. D., Yang, S., Song, B. & Chi, R. Y. (2016). Carbene-catalysed reductive coupling of nitrobenzyl bromides and activated ketones or imines via single-electron-transfer process. Nature Communications, 7, 12933-. https://dx.doi.org/10.1038/ncomms12933 2041-1723 https://hdl.handle.net/10356/83912 http://hdl.handle.net/10220/42863 10.1038/ncomms12933 27671606 7 12933 en Nature Communications © 2016 The Author(s). 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/ application/pdf |
| spellingShingle | Science::Chemistry Synthetic Chemistry Methodology Organocatalysis Li, Bao-Sheng Wang, Yuhuang Proctor, Rupert S. J. Zhang, Yuexia Webster, Richard D. Yang, Song Song, Bao-An Chi, Robin Yonggui Carbene-catalysed reductive coupling of nitrobenzyl bromides and activated ketones or imines via single-electron-transfer process |
| title | Carbene-catalysed reductive coupling of nitrobenzyl bromides and activated ketones or imines via single-electron-transfer process |
| title_full | Carbene-catalysed reductive coupling of nitrobenzyl bromides and activated ketones or imines via single-electron-transfer process |
| title_fullStr | Carbene-catalysed reductive coupling of nitrobenzyl bromides and activated ketones or imines via single-electron-transfer process |
| title_full_unstemmed | Carbene-catalysed reductive coupling of nitrobenzyl bromides and activated ketones or imines via single-electron-transfer process |
| title_short | Carbene-catalysed reductive coupling of nitrobenzyl bromides and activated ketones or imines via single-electron-transfer process |
| title_sort | carbene catalysed reductive coupling of nitrobenzyl bromides and activated ketones or imines via single electron transfer process |
| topic | Science::Chemistry Synthetic Chemistry Methodology Organocatalysis |
| url | https://hdl.handle.net/10356/83912 http://hdl.handle.net/10220/42863 |
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