Citation: Changming Li, Hongdan Zhu, Can-Can Bao, Yongjia Lin, Bing-Tao Guan, Qian Peng. Mechanistic insights for Aryl dilithium base enables the acylation of unactivated C_sp3–H[J]. Chinese Chemical Letters, ;2025, 36(9): 110809. doi: 10.1016/j.cclet.2024.110809 shu

Mechanistic insights for Aryl dilithium base enables the acylation of unactivated C_sp3–H

Changming Li ^a ,
Hongdan Zhu ^a ,
Can-Can Bao ^a ,
Yongjia Lin ^a ,
Bing-Tao Guan ^c ,
Qian Peng ^{a, b, *,}

a.
State Key Laboratory of Elemento-Organic Chemistry, Frontiers Science Center for New Organic Matter, Tianjin Key Laboratory of Biosensing and Molecular Recognition, College of Chemistry, Nankai University, Tianjin 300071, China
b.
Haihe Laboratory of Sustainable Chemical Transformation, Tianjin 300192, China
c.
Department of Chemistry, Fudan University, Shanghai 200438, China

^☆

^th

qpeng@nankai.edu.cn

Received Date: 14 October 2024
Revised Date: 18 December 2024
Accepted Date: 26 December 2024
Available Online: 27 December 2024

Figures(7)

Mechanistic studies of the cleavage and transformation of unactivated C_sp3–H bonds are a significant field of chemistry. Overcoming the inherent low acidity of C–H bonds to activate the inert substrates is challenge under mild conditions. And their complex multi-step transformations may also hinder mechanistic understanding. Herein, we perform theoretical calculations and experimental studies to explore the C_sp3–H bonds activation and acylation mechanisms of toluene/thioether using the relatively weak base LDA. A synergistic "main and auxiliary" model was revealed involving dual lithium metal by LDA dimers, and the aryl dilithium species as an intermediate base can facilitate C_sp3–H activation. This model not only aids in understanding the acidity of unactivated C_sp3–H bonds and the nucleophilicity of their conjugate bases for their kinetic control through cooperative interactions, but also predicts unusual kinetic isotope effects (KIE) for newly designed 2-(methylthio)naphthalene that are experimentally validated. This research is expected to provide a crucial scenario for the cleavage and transformation of unactivated C_sp3–H bonds and the development of new functionalities for alkali metal reagents.
- Acylation of unactivated C_sp3–H bonds,
- Mechanistic studies,
- LDA dimers,
- Aryl dilithium base,
- Acidity and nucleophilicity,
- DFT calculations
1. [1]
  M. Bandini, F. Piccinelli, A. Melloni, Handbook of C–H Transformations: Applications in Organic Synthesis, 2005.
2. [2]
  J. Wencel-Delord, F. Glorius, Nat. Chem. 5 (2013) 369–375. doi: 10.1038/nchem.1607
3. [3]
  D.J. Abrams, P.A. Provencher, E.J. Sorensen, Chem. Soc. Rev. 47 (2018) 8925–8967. doi: 10.1039/c8cs00716k
4. [4]
  G. Prakash, N. Paul, G.A. Oliver, D.B. Werz, D. Maiti, Chem. Soc. Rev. 51 (2022) 3123–3163. doi: 10.1039/d0cs01496f
5. [5]
  X.S. Xue, P. Ji, B. Zhou, J.P. Cheng, Chem. Rev. 117 (2017) 8622–8648. doi: 10.1021/acs.chemrev.6b00664
6. [6]
  Y.R. Luo, Comprehensive Handbook of Chemical Bond Energies, CRC press, 2007.
7. [7]
  G. Wu, M. Huang, Chem. Rev. 106 (2006) 2596–2616. doi: 10.1021/cr040694k
8. [8]
  P. Knochel, G.A. Molander, Comprehensive Organic Synthesis. 2nd ed. Amsterdam: Elsevier, 2014.
9. [9]
  N.J. Gunsalus, A. Koppaka, S.H. Park, et al., Chem. Rev. 117 (2017) 8521–8573. doi: 10.1021/acs.chemrev.6b00739
10. [10]
  C. Shan, R. Bai, Y. Lan, Acta Phys. Chim. Sin. 35 (2019) 940–953. doi: 10.3866/pku.whxb201810052
11. [11]
  J. Han, L.L. Zeng, Q.Y. Fei, et al., Chin. Chem. Lett. 35 (2024) 109647.
12. [12]
  X. Wang, J. He, Y.N. Wang, et al., Chem. Rev. 124 (2024) 10192–10280. doi: 10.1021/acs.chemrev.4c00188
13. [13]
  W. Cui, Y. Li, X. Li, et al., Chin. Chem. Lett. 34 (2023) 107477.
14. [14]
  R. Vanjari, K.N. Singh, Chem. Soc. Rev. 44 (2015) 8062–8096.
15. [15]
  Y. Yamashita, H. Suzuki, I. Sato, T. Hirata, S. Kobayashi, Angew. Chem. Int. Ed. 57 (2018) 6896–6900. doi: 10.1002/anie.201711291
16. [16]
  G. Liu, P.J. Walsh, J. Mao, Org. Lett. 21 (2019) 8514–8518. doi: 10.1021/acs.orglett.9b02737
17. [17]
  D.D. Zhai, X.Y. Zhang, Y.F. Liu, L. Zheng, B.T. Guan, Angew. Chem. Int. Ed. 57 (2018) 1650–1653. doi: 10.1002/anie.201710128
18. [18]
  Y.F. Liu, L. Zheng, D.D. Zhai, X.Y. Zhang, B.T. Guan, Org. Lett. 21 (2019) 5351–5356. doi: 10.1021/acs.orglett.9b01994
19. [19]
  B. Guan, Z. Shi, Sci. Sin. Chim. 51 (2021) 201–212. doi: 10.1360/ssc-2020-0180
20. [20]
  X.Z. Ouyang Kunbing, Acta Chim. Sinica 71 (2013) 13–25.
21. [21]
  S.D. Robertson, M. Uzelac, R.E. Mulvey, Chem. Rev. 119 (2019) 8332–8405. doi: 10.1021/acs.chemrev.9b00047
22. [22]
  N. Davison, E. Lu, Dalton Trans. 52 (2023) 8172–8192. doi: 10.1039/d3dt00980g
23. [23]
  S. Chen, Z. Wang, S. Geng, et al., CCS Chem. 5 (2023) 1674–1685. doi: 10.31635/ccschem.022.202202234
24. [24]
  Y. Zhang, P. Du, Y. Ji, et al., Chem 9 (2023) 3623–3636.
25. [25]
  A. Greenberg, C.M. Breneman, J.F. Liebman, The Amide Linkage: Structural Significance in Chemistry, Biochemistry, and Materials Science, Wiley-Interscience, New York, 2000.
26. [26]
  D. Kaiser, A. Bauer, M. Lemmerer, N. Maulide, Chem. Soc. Rev. 47 (2018) 7899–7925. doi: 10.1039/c8cs00335a
27. [27]
  G. Li, S. Ma, M. Szostak, Trends Chem. 2 (2020) 914–928.
28. [28]
  S. Shi, S.P. Nolan, M. Szostak, Acc. Chem. Res. 51 (2018) 2589–2599. doi: 10.1021/acs.accounts.8b00410
29. [29]
  W.S. Bechara, G. Pelletier, A.B. Charette, Nat. Chem. 4 (2012) 228–234. doi: 10.1038/nchem.1268
30. [30]
  K.J. Xiao, A.E. Wang, Y.H. Huang, P.Q. Huang, Asian J. Org. Chem. 1 (2012) 130–132. doi: 10.1002/ajoc.201200066
31. [31]
  D.P. Wu, Q. He, D.H. Chen, J.L. Ye, P.Q. Huang, Chin. J. Chem. 37 (2019) 315–322. doi: 10.1002/cjoc.201900035
32. [32]
  W. Sun, L. Wang, Y. Hu, et al., Nat. Commun. 11 (2020) 3113.
33. [33]
  R.R. Fraser, M. Bresse, T.S. Mansour, J. Am. Chem. Soc. 105 (1983) 7790–7791. doi: 10.1021/ja00364a078
34. [34]
  J. Clayden, Organolithiums: Selectivity for Synthesis, Oxford, Elsevier, 2002, pp. pp9–109.
35. [35]
  J.D. Yang, X.S. Xue, P. Ji, X. Li, J.P. Cheng, Internet Bond-energy Databank (pKa and BDE): iBonD Home Page. http://ibond.nankai.edu.cn.
36. [36]
  F. Bordwell, D. Algrim, N.R. Vanier, J. Org. Chem. 42 (1977) 1817–1819. doi: 10.1021/jo00430a039
37. [37]
  K.B. Wiberg, H. Castejon, J. Am. Chem. Soc. 116 (1994) 10489–10497. doi: 10.1021/ja00102a016
38. [38]
  C.C. Bao, Y.L. Luo, H.Z. Du, B.T. Guan, Sci. China Chem. 64 (2021) 1349–1354. doi: 10.1007/s11426-021-1035-5
39. [39]
  C.C. Bao, H.Z. Du, Y.L. Luo, B.T. Guan, Commun. Chem. 4 (2021) 138–145.
40. [40]
  K.J. Singh, D.B. Collum, J. Am. Chem. Soc. 128 (2006) 13753–13760. doi: 10.1021/ja064655x
41. [41]
  R.F. Algera, L. Gupta, A.C. Hoepker, et al., J. Org. Chem. 82 (2017) 4513–4532. doi: 10.1021/acs.joc.6b03083
42. [42]
  J. Bigeleisen, M.G. Mayer, J. Chem. Phys. 15 (1947) 261–267. doi: 10.1063/1.1746492
43. [43]
  T. Lu, Q. Chen, J. Comput. Chem. 43 (2022) 539–555. doi: 10.1002/jcc.26812
44. [44]
  K. Chen, H. Zhu, Y. Li, et al., ACS Catal. 11 (2021) 13696–13705. doi: 10.1021/acscatal.1c04141
45. [45]
  K. Chen, H. Zhu, S. Liu, et al., J. Am. Chem. Soc. 145 (2023) 24877–24888.
46. [46]
  S. Zheng, H. Zhang, Q. Peng, Chin. Chem. Lett. 34 (2023) 108067.
47. [47]
  W. Liu, G. Hong, D. Dai, L. Li, M. Dolg, Theor. Chem. Acc. 96 (1997) 75–83.
48. [48]
  W. Liu, F. Wang, L. Li, J. Theor. Comput. Chem. 2 (2003) 257–272.
49. [49]
  Y. Zhang, B. Suo, Z. Wang, et al., J. Chem. Phys. 152 (2020) 064113.
50. [50]
  L.G. Zhuo, W. Liao, Z.X. Yu, Asian J. Org. Chem. 1 (2012) 336–345. doi: 10.1002/ajoc.201200103
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Mechanistic insights for Aryl dilithium base enables the acylation of unactivated Csp3–H

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通讯作者: 陈斌, bchen63@163.com

Mechanistic insights for Aryl dilithium base enables the acylation of unactivated C_sp3–H