Synergistic copper-aminocatalysis for direct tertiary 𝜶-alkylation of ketones with electron-deficient alkanes
In this study, a novel approach for the tertiary α-alkylation of ketones using alkanes with electron-deficient C─H bonds is presented, employing a synergistic catalytic system combining inexpensive copper salts with aminocatalysis. This methodology addresses the limitations of traditional alkylation...
| Main Authors: | , , , , , |
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| Other Authors: | |
| Format: | Journal Article |
| Language: | English |
| Published: |
2024
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| Online Access: | https://hdl.handle.net/10356/178845 |
| _version_ | 1826125285183979520 |
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| author | Shan, Qi-Chao Wu, You-Wei Chen, Mu-Xiang Zhao, Xuefei Loh, Teck-Peng Hu, Xu-Hong |
| author2 | School of Chemistry, Chemical Engineering and Biotechnology |
| author_facet | School of Chemistry, Chemical Engineering and Biotechnology Shan, Qi-Chao Wu, You-Wei Chen, Mu-Xiang Zhao, Xuefei Loh, Teck-Peng Hu, Xu-Hong |
| author_sort | Shan, Qi-Chao |
| collection | NTU |
| description | In this study, a novel approach for the tertiary α-alkylation of ketones using alkanes with electron-deficient C─H bonds is presented, employing a synergistic catalytic system combining inexpensive copper salts with aminocatalysis. This methodology addresses the limitations of traditional alkylation methods, such as the need for strong metallic bases, regioselectivity issues, and the risk of over alkylation, by providing a high reactivity and chemoselectivity without the necessity for pre-functionalized substrates. The dual catalytic strategy enables the direct functionalization of C(sp3)─H bonds, demonstrating remarkable selectivity in the presence of conventional C(sp3)─H bonds that are adjacent to heteroatoms or π systems, which are typically susceptible to single-electron transfer processes. The findings contribute to the advancement of alkylation techniques, offering a practical and efficient route for the construction of C(sp3)─C(sp3) bonds, and paving the way for further developments in the synthesis of complex organic molecules. |
| first_indexed | 2024-10-01T06:33:51Z |
| format | Journal Article |
| id | ntu-10356/178845 |
| institution | Nanyang Technological University |
| language | English |
| last_indexed | 2024-10-01T06:33:51Z |
| publishDate | 2024 |
| record_format | dspace |
| spelling | ntu-10356/1788452024-07-12T15:31:46Z Synergistic copper-aminocatalysis for direct tertiary 𝜶-alkylation of ketones with electron-deficient alkanes Shan, Qi-Chao Wu, You-Wei Chen, Mu-Xiang Zhao, Xuefei Loh, Teck-Peng Hu, Xu-Hong School of Chemistry, Chemical Engineering and Biotechnology Chemistry Ketones Tertiary alkylation In this study, a novel approach for the tertiary α-alkylation of ketones using alkanes with electron-deficient C─H bonds is presented, employing a synergistic catalytic system combining inexpensive copper salts with aminocatalysis. This methodology addresses the limitations of traditional alkylation methods, such as the need for strong metallic bases, regioselectivity issues, and the risk of over alkylation, by providing a high reactivity and chemoselectivity without the necessity for pre-functionalized substrates. The dual catalytic strategy enables the direct functionalization of C(sp3)─H bonds, demonstrating remarkable selectivity in the presence of conventional C(sp3)─H bonds that are adjacent to heteroatoms or π systems, which are typically susceptible to single-electron transfer processes. The findings contribute to the advancement of alkylation techniques, offering a practical and efficient route for the construction of C(sp3)─C(sp3) bonds, and paving the way for further developments in the synthesis of complex organic molecules. Agency for Science, Technology and Research (A*STAR) Nanyang Technological University Published version The authors gratefully acknowledge funding from the National Natural Science Foundation of China (21702106) and the Natural Science Foundation of Jiangsu Province (BK20221310). T.P.L. thanks the Distinguished University Professor grant (Nanyang Technological University) and the Agency for Science, Technology, and Research (A*STAR) under its MTC Individual Research grant (M21K2c0114) and RIE2025 MTC Programmatic Fund (M22K9b0049) for financial support. 2024-07-09T01:25:43Z 2024-07-09T01:25:43Z 2024 Journal Article Shan, Q., Wu, Y., Chen, M., Zhao, X., Loh, T. & Hu, X. (2024). Synergistic copper-aminocatalysis for direct tertiary 𝜶-alkylation of ketones with electron-deficient alkanes. Advanced Science, e2402255-. https://dx.doi.org/10.1002/advs.202402255 2198-3844 https://hdl.handle.net/10356/178845 10.1002/advs.202402255 38885363 2-s2.0-85196090578 e2402255 en M21K2c0114 M22K9b0049 Advanced Science © 2024 The Author(s). Advanced Science published by Wiley-VCH GmbH. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. application/pdf |
| spellingShingle | Chemistry Ketones Tertiary alkylation Shan, Qi-Chao Wu, You-Wei Chen, Mu-Xiang Zhao, Xuefei Loh, Teck-Peng Hu, Xu-Hong Synergistic copper-aminocatalysis for direct tertiary 𝜶-alkylation of ketones with electron-deficient alkanes |
| title | Synergistic copper-aminocatalysis for direct tertiary 𝜶-alkylation of ketones with electron-deficient alkanes |
| title_full | Synergistic copper-aminocatalysis for direct tertiary 𝜶-alkylation of ketones with electron-deficient alkanes |
| title_fullStr | Synergistic copper-aminocatalysis for direct tertiary 𝜶-alkylation of ketones with electron-deficient alkanes |
| title_full_unstemmed | Synergistic copper-aminocatalysis for direct tertiary 𝜶-alkylation of ketones with electron-deficient alkanes |
| title_short | Synergistic copper-aminocatalysis for direct tertiary 𝜶-alkylation of ketones with electron-deficient alkanes |
| title_sort | synergistic copper aminocatalysis for direct tertiary 𝜶 alkylation of ketones with electron deficient alkanes |
| topic | Chemistry Ketones Tertiary alkylation |
| url | https://hdl.handle.net/10356/178845 |
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