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Asymmetric C(sp(3))–H functionalization of unactivated alkylarenes such as toluene enabled by chiral Brønsted base catalysts
Benzylic functionalisation of unactivated alkylarenes remains as a significant challenge in asymmetric catalysis due to their less reactive nature. Here, we show development of catalytic asymmetric C(sp(3))–H functionalization of unactivated alkylarenes such as toluene with imines. The reactions pro...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9814754/ https://www.ncbi.nlm.nih.gov/pubmed/36697525 http://dx.doi.org/10.1038/s42004-021-00459-5 |
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author | Hirata, Tsubasa Sato, Io Yamashita, Yasuhiro Kobayashi, Shū |
author_facet | Hirata, Tsubasa Sato, Io Yamashita, Yasuhiro Kobayashi, Shū |
author_sort | Hirata, Tsubasa |
collection | PubMed |
description | Benzylic functionalisation of unactivated alkylarenes remains as a significant challenge in asymmetric catalysis due to their less reactive nature. Here, we show development of catalytic asymmetric C(sp(3))–H functionalization of unactivated alkylarenes such as toluene with imines. The reactions proceeded smoothly under proton-transfer conditions using a chiral, strong Brønsted base catalyst system. A chiral Brønsted base prepared from an alkylpotassium and a chiral amine ligand was found to effectively form a promising asymmetric environment around a benzyl anion. Optimization of the reaction conditions revealed that the use of the alkaline metal amide, potassium hexamethyldisilazide (KHMDS), as an additive was most effective, and enantioselective and atom economical carbon–carbon bond-forming reactions at the benzylic positions of unactivated alkylarenes was achieved without using any transition-metal catalyst. |
format | Online Article Text |
id | pubmed-9814754 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-98147542023-01-10 Asymmetric C(sp(3))–H functionalization of unactivated alkylarenes such as toluene enabled by chiral Brønsted base catalysts Hirata, Tsubasa Sato, Io Yamashita, Yasuhiro Kobayashi, Shū Commun Chem Article Benzylic functionalisation of unactivated alkylarenes remains as a significant challenge in asymmetric catalysis due to their less reactive nature. Here, we show development of catalytic asymmetric C(sp(3))–H functionalization of unactivated alkylarenes such as toluene with imines. The reactions proceeded smoothly under proton-transfer conditions using a chiral, strong Brønsted base catalyst system. A chiral Brønsted base prepared from an alkylpotassium and a chiral amine ligand was found to effectively form a promising asymmetric environment around a benzyl anion. Optimization of the reaction conditions revealed that the use of the alkaline metal amide, potassium hexamethyldisilazide (KHMDS), as an additive was most effective, and enantioselective and atom economical carbon–carbon bond-forming reactions at the benzylic positions of unactivated alkylarenes was achieved without using any transition-metal catalyst. Nature Publishing Group UK 2021-03-16 /pmc/articles/PMC9814754/ /pubmed/36697525 http://dx.doi.org/10.1038/s42004-021-00459-5 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Hirata, Tsubasa Sato, Io Yamashita, Yasuhiro Kobayashi, Shū Asymmetric C(sp(3))–H functionalization of unactivated alkylarenes such as toluene enabled by chiral Brønsted base catalysts |
title | Asymmetric C(sp(3))–H functionalization of unactivated alkylarenes such as toluene enabled by chiral Brønsted base catalysts |
title_full | Asymmetric C(sp(3))–H functionalization of unactivated alkylarenes such as toluene enabled by chiral Brønsted base catalysts |
title_fullStr | Asymmetric C(sp(3))–H functionalization of unactivated alkylarenes such as toluene enabled by chiral Brønsted base catalysts |
title_full_unstemmed | Asymmetric C(sp(3))–H functionalization of unactivated alkylarenes such as toluene enabled by chiral Brønsted base catalysts |
title_short | Asymmetric C(sp(3))–H functionalization of unactivated alkylarenes such as toluene enabled by chiral Brønsted base catalysts |
title_sort | asymmetric c(sp(3))–h functionalization of unactivated alkylarenes such as toluene enabled by chiral brønsted base catalysts |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9814754/ https://www.ncbi.nlm.nih.gov/pubmed/36697525 http://dx.doi.org/10.1038/s42004-021-00459-5 |
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