Switchable Regiodivergent Reductive Alkyl–Alkyl Coupling by Nickel Catalysis: Sorting Different Alkyl–Nickel Intermediates
Dr. Quan-Xing Zi
Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Guangming Advanced Research Institute, Shenzhen Grubbs Institute, Department of Chemistry, and Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen, Guangdong, 518055 P.R. China
Both authors contributed equally to this work.
Search for more papers by this authorDr. Lin Min
Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Guangming Advanced Research Institute, Shenzhen Grubbs Institute, Department of Chemistry, and Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen, Guangdong, 518055 P.R. China
Both authors contributed equally to this work.
Search for more papers by this authorHai-Wu Du
Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Guangming Advanced Research Institute, Shenzhen Grubbs Institute, Department of Chemistry, and Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen, Guangdong, 518055 P.R. China
Search for more papers by this authorDr. Qiong Yu
Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Guangming Advanced Research Institute, Shenzhen Grubbs Institute, Department of Chemistry, and Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen, Guangdong, 518055 P.R. China
Search for more papers by this authorProf. Dr. Yu-Long Li
College of Chemistry and Environmental Engineering, Key Laboratory of Green Catalysis of Higher Education Institutes of Sichuan, Sichuan University of Science and Engineering, Zigong, Sichuan, 643000 P.R. China
Search for more papers by this authorCorresponding Author
Prof. Dr. Wei Shu
Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Guangming Advanced Research Institute, Shenzhen Grubbs Institute, Department of Chemistry, and Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen, Guangdong, 518055 P.R. China
College of Chemistry and Environmental Engineering, Key Laboratory of Green Catalysis of Higher Education Institutes of Sichuan, Sichuan University of Science and Engineering, Zigong, Sichuan, 643000 P.R. China
E-mail: [email protected]
Search for more papers by this authorDr. Quan-Xing Zi
Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Guangming Advanced Research Institute, Shenzhen Grubbs Institute, Department of Chemistry, and Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen, Guangdong, 518055 P.R. China
Both authors contributed equally to this work.
Search for more papers by this authorDr. Lin Min
Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Guangming Advanced Research Institute, Shenzhen Grubbs Institute, Department of Chemistry, and Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen, Guangdong, 518055 P.R. China
Both authors contributed equally to this work.
Search for more papers by this authorHai-Wu Du
Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Guangming Advanced Research Institute, Shenzhen Grubbs Institute, Department of Chemistry, and Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen, Guangdong, 518055 P.R. China
Search for more papers by this authorDr. Qiong Yu
Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Guangming Advanced Research Institute, Shenzhen Grubbs Institute, Department of Chemistry, and Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen, Guangdong, 518055 P.R. China
Search for more papers by this authorProf. Dr. Yu-Long Li
College of Chemistry and Environmental Engineering, Key Laboratory of Green Catalysis of Higher Education Institutes of Sichuan, Sichuan University of Science and Engineering, Zigong, Sichuan, 643000 P.R. China
Search for more papers by this authorCorresponding Author
Prof. Dr. Wei Shu
Shenzhen Key Laboratory of Small Molecule Drug Discovery and Synthesis, Guangming Advanced Research Institute, Shenzhen Grubbs Institute, Department of Chemistry, and Guangdong Provincial Key Laboratory of Catalysis, Southern University of Science and Technology, Shenzhen, Guangdong, 518055 P.R. China
College of Chemistry and Environmental Engineering, Key Laboratory of Green Catalysis of Higher Education Institutes of Sichuan, Sichuan University of Science and Engineering, Zigong, Sichuan, 643000 P.R. China
E-mail: [email protected]
Search for more papers by this authorDedicated to the 60th anniversary of Sichuan University of Science and Engineering
Abstract
Site-selective and divergent functionalizations on saturated alkyl chain at specific unfunctionalized positions is a key challenge in organic chemistry and other related areas and offers unprecedented synthetic opportunities. Herein, a ligand-controlled Ni-catalyzed site-selective and divergent alkyl–alkyl reductive coupling between two different alkyl halides has been developed. Notably, the reaction finely tunes and recognizes thermodynamic favored α-aminoalkyl radicals over β-aminoalkyl radicals, and distal ipso-alkyl radicals to deliver chemo- and position-selective alkylation of unactivated α-H and β-H of amines under reductive conditions. Moreover, the reaction selectively functionalizes one alkyl chain over two migratable alkyl chains. By just switching the catalytic parameters, α- and β-alkylation of saturated C─H bonds, and ipso-alkyl-alkyl coupling allow for rapid access to three types of branched aliphatic amine architectures from identical starting materials.
Conflict of Interests
The authors declare no conflict of interest.
Open Research
Data Availability Statement
The data that support the findings of this study are available in the Supporting Information of this article.
Supporting Information
| Filename | Description |
|---|---|
| ange202507313-sup-0001-SuppMat.pdf45.2 MB | Supporting Information |
| ange202507313-sup-0002-SuppMat.zip487.2 KB | Supporting Information |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
References
- 1F. Lovering, J. Bikker, C. Humblet, J. Med. Chem. 2009, 52, 6752–6756.
- 2F. Lovering, MedChemComm 2013, 4, 515.
- 3R. Jana, T. P. Pathak, M. S. Sigman, Chem. Rev. 2011, 111, 1417–1492.
- 4C. Cheng, J. F. Hartwig, Chem. Rev. 2015, 115, 8946–8975.
- 5P. Ruiz-Castillo, S. L. Buchwald, Chem. Rev. 2016, 116, 12564–12649.
- 6G. C. Fu, ACS Cent. Sci. 2017, 3, 692–700.
- 7J. Choi, G. C. Fu, Science 2017, 356, eaaf7230.
- 8Z. Chen, M.-Y. Rong, J. Nie, X.-F. Zhu, B.-F. Shi, J.-A. Ma, Chem. Soc. Rev. 2019, 48, 4921–4942.
- 9R. Y. Liu, S. L. Buchwald, Acc. Chem. Res. 2020, 53, 1229–1243.
- 10B. Baruah, M. L. Deb, Eur. J. Org. Chem. 2021, 2021, 5756–5766.
- 11R. Kranthikumar, Organometallics 2022, 41, 667–679.
- 12J. H. Docherty, T. M. Lister, G. McArthur, M. T. Findlay, P. Domingo-Legarda, J. Kenyon, S. Choudhary, I. Larrosa, Chem. Rev. 2023, 123, 7692–7760.
- 13I. F. Yu, J. W. Wilson, J. F. Hartwig, Chem. Rev. 2023, 123, 11619–11663.
- 14G. Cahiez, A. Moyeux, Chem. Rev. 2010, 110, 1435–1462.
- 15Y. P. Budiman, R. N. Perutz, P. G. Steel, U. Radius, T. B. Marder, Chem. Rev. 2024, 124, 4822–4862.
- 16C. Le, Y. Liang, R. W. Evans, X. Li, D. W. C. MacMillan, Nature 2017, 547, 79–83.
- 17R. T. Smith, X. Zhang, J. A. Rincón, J. Agejas, C. Mateos, M. Barberis, S. García-Cerrada, O. De Frutos, D. W. C. MacMillan, J. Am. Chem. Soc. 2018, 140, 17433–17438.
- 18L. Yang, Z. Qiu, J. Wu, J. Zhao, T. Shen, X. Huang, Z.-Q. Liu, Org. Lett. 2021, 23, 3207–3210.
- 19S. Dongbang, Organometallics 2024, 43, 1662–1681.
- 20H. Xu, C. Zhao, Q. Qian, W. Deng, H. Gong, Chem. Sci. 2013, 4, 4022–4029.
- 21Y. Peng, L. Luo, C.-S. Yan, J.-J. Zhang, Y.-W. Wang, J. Org. Chem. 2013, 78, 10960–10967.
- 22J.-H. Liu, C.-T. Yang, X.-Y. Lu, Z.-Q. Zhang, L. Xu, M. Cui, X. Lu, B. Xiao, Y. Fu, L. Liu, Chem. - Eur. J. 2014, 20, 15334–15338.
- 23W. Xue, H. Xu, Z. Liang, Q. Qian, H. Gong, Org. Lett. 2014, 16, 4984–4987.
- 24X. Wang, Y. Dai, H. Gong, Top. Curr. Chem. 2016, 374, 43.
- 25Y. Li, Y. Li, L. Peng, D. Wu, L. Zhu, G. Yin, Chem. Sci. 2020, 11, 10461–10464.
- 26D. A. Everson, D. J. Weix, J. Org. Chem. 2014, 79, 4793–4798.
- 27C. E. I. Knappke, S. Grupe, D. Gärtner, M. Corpet, C. Gosmini, A. Jacobi von Wangelin, Chem. - Eur. J. 2014, 20, 6828–6842.
- 28J. Liu, Y. Ye, J. L. Sessler, H. Gong, Acc. Chem. Res. 2020, 53, 1833–1845.
- 29W.-T. Zhao, J.-X. Zhang, B.-H. Chen, W. Shu, Nat. Commun. 2023, 14, 2938.
- 30W.-T. Zhao, W. Shu, Sci. Adv. 2023, 9, eadg9898.
- 31L.-X. You, L. Tian, C.-L. Guo, S.-X. Li, Y.-C. Liu, Y.-L. Li, W. Shu, Sci. China Chem. 2025, 68, https://doi.org/10.1007/s11426-024-2438-x.
- 32M. R. Prinsell, D. A. Everson, D. J. Weix, Chem. Commun. 2010, 46, 5743.
- 33X. Yu, T. Yang, S. Wang, H. Xu, H. Gong, Org. Lett. 2011, 13, 2138–2141.
- 34Y. Dai, F. Wu, Z. Zang, H. You, H. Gong, Chem. - Eur. J. 2012, 18, 808–812.
- 35K. Komeyama, T. Michiyuki, I. Osaka, ACS Catal. 2019, 9, 9285–9291.
- 36J. Wang, Y. Gong, D. Sun, H. Gong, Org. Chem. Front. 2021, 8, 2944–2948.
- 37J. Zhou, D. Wang, W. Xu, Z. Hu, T. Xu, J. Am. Chem. Soc. 2023, 145, 2081–2087.
- 38X.-X. Wang, X. Lu, Y. Li, J.-W. Wang, Y. Fu, Sci. China Chem. 2020, 63, 1586–1600.
- 39Y. He, J. Chen, X. Jiang, S. Zhu, Chin. J. Chem. 2022, 40, 651–661.
- 40Z. Zhang, S. Bera, C. Fan, X. Hu, J. Am. Chem. Soc. 2022, 144, 7015–7029.
- 41P.-F. Yang, W. Shu, Chem Catal 2023, 3, 100508.
- 42Z. Wang, H. Yin, G. C. Fu, Nature 2018, 563, 379–383.
- 43S. Bera, R. Mao, X. Hu, Nat. Chem. 2021, 13, 270–277.
- 44L. Shi, L.-L. Xing, W.-B. Hu, W. Shu, Angew. Chem. Int. Ed. 2021, 60, 1599–1604.
- 45S. Wang, J.-X. Zhang, T.-Y. Zhang, H. Meng, B.-H. Chen, W. Shu, Nat. Commun. 2021, 12, 2771.
- 46P.-F. Yang, L. Zhu, J.-X. Liang, H.-T. Zhao, J.-X. Zhang, X.-W. Zeng, Q. Ouyang, W. Shu, ACS Catal. 2022, 12, 5795–5805.
- 47P.-F. Yang, W. Shu, Angew. Chem. Int. Ed. 2022, 61, e202208018.
- 48F. Zhou, J. Zhu, Y. Zhang, S. Zhu, Angew. Chem. Int. Ed. 2018, 57, 4058–4062.
- 49D. Qian, X. Hu, Angew. Chem. Int. Ed. 2019, 58, 18519–18523.
- 50X.-X. Wang, Y.-T. Xu, Z.-L. Zhang, X. Lu, Y. Fu, Nat. Commun. 2022, 13, 1890.
- 51Z.-L. Zhang, Z. Li, Y.-T. Xu, L. Yu, J. Kuang, Y. Li, J.-W. Wang, C. Tian, X. Lu, Y. Fu, Angew. Chem. Int. Ed. 2023, 62, e202306381.
- 52Z. Li, B. Liu, C.-Y. Yao, G.-W. Gao, J.-Y. Zhang, Y.-Z. Tong, J.-X. Zhou, H.-K. Sun, Q. Liu, X. Lu, Y. Fu, J. Am. Chem. Soc. 2024, 146, 3405–3415.
- 53Y. Li, H. Pang, D. Wu, Z. Li, W. Wang, H. Wei, Y. Fu, G. Yin, Angew. Chem. Int. Ed. 2019, 58, 8872–8876.
- 54Y. Li, D. Wu, H.-G. Cheng, G. Yin, Angew. Chem. Int. Ed. 2020, 59, 7990–8003.
- 55D. Qian, S. Bera, X. Hu, J. Am. Chem. Soc. 2021, 143, 1959–1967.
- 56C. Ding, Y. Ren, C. Sun, J. Long, G. Yin, J. Am. Chem. Soc. 2021, 143, 20027–20034.
- 57J.-W. Wang, D.-G. Liu, Z. Chang, Z. Li, Y. Fu, X. Lu, Angew. Chem. Int. Ed. 2022, 61, e202205537.
- 58Y. Li, H. Wei, G. Yin, Tetrahedron Lett. 2022, 100, 153889.
- 59B. Liu, D. Liu, X. Rong, X. Lu, Y. Fu, Q. Liu, Angew. Chem. Int. Ed. 2023, 62, e202218544.
- 60C. Ding, Y. Ren, Y. Yu, G. Yin, Nat. Commun. 2023, 14, 7670.
- 61W.-T. Zhao, H. Meng, J.-N. Lin, W. Shu, Angew. Chem. Int. Ed. 2023, 62, e202215779.
- 62J. Rodrigalvarez, H. Wang, R. Martin, J. Am. Chem. Soc. 2023, 145, 3869–3874.
- 63Deposition numbers 2362543 (for 3o), 2362567 (for 4e) and 2362569 (for 5i) contain the supplementary crystallographic data for this paper. These data are provided free of charge by the joint Cambridge Crystallographic Data Centre and Fachinformationszentrum Karlsruhe Access Structures service.
- 64F. Chen, K. Chen, Y. Zhang, Y. He, Y.-M. Wang, S. Zhu, J. Am. Chem. Soc. 2017, 139, 13929–13935.
- 65L. Peng, Y. Li, Y. Li, W. Wang, H. Pang, G. Yin, ACS Catal. 2018, 8, 310–313.
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