Citation: Chunhua Ma, Mengjiao Liu, Siyu Ouyang, Zhenwei Cui, Jingjing Bi, Yuqin Jiang, Zhiguo Zhang. Metal-free construction of diverse 1,2,4-triazolo[1,5-a]pyridines on water[J]. Chinese Chemical Letters, ;2025, 36(1): 109755. doi: 10.1016/j.cclet.2024.109755 shu

Metal-free construction of diverse 1,2,4-triazolo[1,5-a]pyridines on water

Chunhua Ma ^{a, *,} ,
Mengjiao Liu ^a ,
Siyu Ouyang ^a ,
Zhenwei Cui ^b ,
Jingjing Bi ^a ,
Yuqin Jiang ^{a, *,} ,
Zhiguo Zhang ^{a, *,}

a.
Collaborative Innovation Centre of Henan Province for Green Manufacturing of Fine Chemicals, Key Laboratory of Green Chemical Media and Reactions, Ministry of Education, Henan Engineering Research Centre of Chiral Hydroxyl Pharmaceutical, Henan Engineering Laboratory of Chemical Pharmaceutical and Biomedical Materials, School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang 453007, China
b.
Chongqing Aoshe Bio-chemical Co. Ltd., Chongqing 400000, China

2016007@htu.edu.cn

jiangyuqin@htu.edu.cn

zhangzg@htu.edu.cn

Received Date: 21 December 2023
Revised Date: 23 February 2024
Accepted Date: 5 March 2024
Available Online: 9 March 2024

Figures(6)

A transition-metal- and oxidant-free amination/cyclization reaction to access 1,2,4-triazolo[1,5-a]pyridines was realized in water by using amino diphenylphosphinate as amino source. A broad array of readily accessible N-(pyridyl)amides could be converted into the products featuring a diverse set of functional groups. The sustainable methodology was successfully applied to the late-stage functionalization of natural products and drugs.
- 1,2,4-Triazolo[1,5-a]pyridines,
- On water,
- N-(Pyridyl)amides,
- Cyclization,
- Metal-free
Sustainable synthetic practices, especially green solvents, transition-metal free, and strong oxidants-free strategies, are highly desired to medicinal chemistry and synthetic chemistry [1-4]. The sustainable construction of nitrogen-containing compounds is an enduring topic, owing to their value in drugs, bioactive compounds and functional materials [5-8]. As one of the most important triazole heterocycles, 1,2,4-trizaolo[1,5-α]pyridines are widely found in drug candidates and natural products (Fig. 1), such as glucose-lowering drug candidate LY3104607 [9], cancer immunotherapeutic/antifibrotic agent EW-7197 [10], anti-atopic dermatitis agent LEO 39652 [11], and prolylhydroxylase domain enzayme PHD-1 inhibitor Takeda-39 [12]. Hence, the construction of 1,2,4-trizaolo[1,5-α]pyridines in a sustainable fashion is highly desirable.

Figure 1

Figure 1. The bioactive molecules bearing the 1,2,4-trizaolo[1,5-α]pyridines fragment.

DownLoad: Full-Size Img PowerPoint

Several strategies have been developed to access this important heterocyclic moiety. In 2009, Nagasawa’s group reported a CuBr catalyzed oxidative coupling approach of nitrile with 2-aminopyridine to yield the 1,2,4-triazoles in 1,2-dichlorobenzene DCB (Scheme 1a) [13]. Afterwards, this catalytic system was reformed to the solid-supported heterogeneous catalytic systems by Zhao’s group and Cai’s group, respectively [14,15]. However, these strategies rely on the use of transition-metal catalyst and carcinogenic solvent DCB. Alternatively, N-(2-pyridyl)amidines could be converted into 1,2,4-triazolo[1,5-a]pyridines in the presence of stoichiometric amounts of external oxidants, such as phenyliodine(Ⅲ)bis(trifluoroacetate) PIFA [16], I₂ [17], isocyanuric chloride [18], in organic solvent (Scheme 1b). In 2019, Zhang’s group disclosed an electrochemical protocol to deliver the scaffold with ⁿBu₄NBr as the redox mediator in CH₃CN (Scheme 1c) [19]. The use of organic solvent will bring the cost increasing, environmental threat, toxicity issues, and safety hazard. While, water is a low cost, environmentally benign, nontoxic, and non-flammable alternative. Therefore, developing the reactions conducted in water represent a vibrant area of investigation both in industry and academia [20-47].

Scheme 1

Scheme 1. The synthesis of 1,2,4-triazolo[1,5-a]pyridines in water.

DownLoad: Full-Size Img PowerPoint

The amino diphenylphosphinate (DPPH) as amino source was successfully applied in various nitrogen insertion reactions [48-52]. However, aminations using DPPH conducted in water are rarely reported, and construction of the hetero-aromatic ring with DPPH is underdeveloped. With our continued interest in developing sustainable strategy to the construction and derivatization of privileged scaffolds [53-60], we herein report an additive-free procedure to access 1,2,4-triazolo[1,5-a]pyridines from the readily available N-(pyridyl)amides and amino diphenylphosphinate in water (Scheme 1d).

We carried out the study with N-(pyridin-2-yl)benzamide (1a) and amino diphenylphosphinate (2) as the substrates. The first model reaction was conducted in DMF at 100 ℃ under N₂ atmosphere, affording the desired product 3a in 74% yield (Table 1, entry 1). Firstly, the effects of the base were investigated (entries 2–6). The use of Et₃N, K₂CO₃, NaH, NaOH, or KOH retarded the reaction. Green solvents H₂O, polyethyleneglycol (PEG400), ethylene glycol (EG), cyclopentyl methyl ether (CPME), 2-MeTHF, or dimethyl carbonate (DMC) were then evaluated (entries 7–12). It was found that H₂O (87%, entry 7) outperformed other green solvents (63%−82%, entries 8–12) in terms of the yield. Changing the reaction atmosphere from N₂ to air or O₂ has no adverse effect on the reaction efficiency (entries 13 and 14), indicating that the transformation is insensitive to O₂. Thus, the optimized conditions were identified as follows: 1a (0.2 mmol), 2 (2 equiv.), H₂O (3 mL) as a solvent, at 100 ℃ under N₂ atmosphere.

Table 1

Table 1. Optimization of reaction conditions.^a

DownLoad: CSV

With the optimal cyclization conditions at hand, the scope of the reaction was firstly investigated by variation of the R¹ group in N-(pyridyl)amide 1a (Scheme 2). The result indicated that a variety of substitutions on the aromatic moiety were well tolerated regardless of their electronic properties or steric properties. For example, both electron-donating (Me, Et, OMe) and electron-withdrawing (F, Cl, Br) substitutions on para-, meta-, or ortho-positions of the phenyl group were well compatible, affording the desired products 3b-3k in 51%−98% yields. Moreover, the N-(pyridyl)amides 1l and 1m bearing the valuable pharmacophores (acetyl and phenoxy group) reacted smoothly to give the desired products 3l and 3m. Unfortunately, N-(pyridyl)amide with nitro substitution was not compatible to the standard conditions. With R¹ being heteroaromatic rings (1n-1o), the reactions uneventfully afforded the corresponding products 3n-3o in 51% and 40% yields. Importantly, the substrates 1p-1t, with R¹ being an alkyl, also turned out competent, retrieving the cyclized products 3p-3t in 19%−74% yields. Moreover, the structure of product 3a was confirmed by the X-ray single crystal diffraction studies.

Scheme 2

Scheme 2. Scope of the phenyl ring in N-(pyridyl)amide. Reaction conditions: 1 (0.2 mmol), 2 (2 equiv.), H₂O (3 mL), 100 ℃, 10 h, N₂. Isolated yields were given.

DownLoad: Full-Size Img PowerPoint

We next turned our attention to study the effects of substitutions on the pyridine moiety (Scheme 3). Electron-donating groups on the different position of pyridine ring, such as 4-Me, 4-Et, 4-MeO-, 5-Me, 6-Me, 3-Me, and 3-MeO were amenable to the standard protocols, giving the desired products 3u-3aa in 48%−96% yields. Furthermore, the substrates 1ab-1ag with electron-withdrawing substituents (4-F, 4-Cl, 4-Br, 4-pH, 4-CF₃, 5-Br) also proceeded smoothly and afforded the anticipated products 3ab-3ag in moderate to good yields. To our delight, the products 3ah-3aj were also delivered in 60%−93% yields when there were substituents both on the pyridine ring and aryl ring.

Scheme 3

Scheme 3. Scope of the pyridine ring in N-(pyridyl)amide. Reaction conditions: 1 (0.2 mmol), 2 (2 equiv.), H₂O (3 mL), 100 ℃, 10 h, N₂. Isolated yields were given.

DownLoad: Full-Size Img PowerPoint

To highlight the usefulness of this sustainable strategy in medicinal chemistry, we conducted the late-stage modification of valuable natural products and pharmaceuticals (Scheme 4). The N-(pyridyl)amides derived from levulinic acid (1ak) and elaidic acid (1al) reacted efficiently to produce the products 3ak-3al in 34% and 62% yields, respectively. Furthermore, the method could also be successfully applied in the functionalization of nonsteroidal anti-inflammatory drug (lbuprofen, 1am), lipid regulators (gemfibrozil, 1an), and cholagogues (dehydrocholic acid, 1ao). The value of these current methods was further displayed by a scale-up synthesis which afforded the desired product in 70% yield (see Supporting information for details).

Scheme 4

Scheme 4. The late-stage modification of natural products and drugs. Reaction conditions: 1 (0.2 mmol), 2 (2 equiv.), H₂O (3 mL), 100 ℃, 10 h, N₂. Isolated yields were given.

DownLoad: Full-Size Img PowerPoint

Considering that amino diphenylphosphinate is a typical electrophilic amination reagent widely used in the regioselectivity N—N coupling reaction [61-65], a plausible mechanism for the amination/cyclization reaction is depicted in Scheme 5. Initially, the pyridine in 1 attacks amino diphenylphosphinate 2, generating the N-aminopyridinium phospate salt 4, which exists in three resonance forms 4a-4c. The amino group attacks the carbonyl group intramolecularly to afford diphenylphosphinic acid 5 (detected by HRMS) and 6. Then, intermediate 6 underwent dehydration with the aid of acid 5 to give the final product 3 [66,67].

Scheme 5

Scheme 5. The proposed mechanism.

DownLoad: Full-Size Img PowerPoint

In summary, we have developed a green and high yielding strategy for the amination/cyclization of N-(pyridyl)amides to access the 1,2,4-triazolo[1,5-a]pyridines in water. The transition metal- and oxidant-free protocol demonstrates broad substrate scope and exceptional functional group tolerance. The utility of this protocol is also highlighted in late-stage modification of several natural products and drugs. Accordingly, we anticipate that this sustainable protocol will be of great utility to the pharmaceutical chemistry as well as many other fields.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Acknowledgments

We acknowledge the financial support from the National Natural Science Foundation of China (No. 82003585), the Program for Science & Technology Innovation Talents in Universities of Henan Province (No. 24HASTIT069), the Technical Innovation Team of Henan Normal University (No. 2022TD03), the Special Project for Fundamental Research in University of Henan Province (No. 23ZX009), the Henan Science and Technology Program (No. 232102310364), the Key Project of Henan Educational Committee (No. 22A150041), Excellent Youth Foundation of Henan Scientific Committee (No. 222300420012), the Young Core Instructor Training Program of Xinyang Agriculture and Forestry University (2023).

Supplementary materials

Supplementary material associated with this article can be found, in the online version, at doi:10.1016/j.cclet.2024.109755.

References
1. [1]
  M.C. Bryan, B. Dillon, L.G. Hamann, et al., J. Med. Chem. 56 (2013) 6007–6021. doi: 10.1021/jm400250p
2. [2]
  J.Y. Chen, J. Huang, K. Sun, W.M. He, Org. Chem. Front. 9 (2022) 1152–1164. doi: 10.1039/D1QO01504D
3. [3]
  Y. Lang, C.J. Li, H. Zeng, Org. Chem. Front. 8 (2021) 3594–3613. doi: 10.1039/d1qo00359c
4. [4]
  X.Y. Yuan, F.L. Zeng, H.L. Zhu, et al., Org. Chem. Front. 7 (2020) 1884–1889. doi: 10.1039/d0qo00222d
5. [5]
  E. Vitaku, D.T. Smith, J.T. Njardarson, J. Med. Chem. 57 (2014) 10257–10274. doi: 10.1021/jm501100b
6. [6]
  C. Ma, Q. Li, M. Zhao, et al., J. Med. Chem. 64 (2021) 16242–16270. doi: 10.1021/acs.jmedchem.1c01559
7. [7]
  L.D. Pennington, D.T. Moustakas, J. Med. Chem. 60 (2017) 3552–3579. doi: 10.1021/acs.jmedchem.6b01807
8. [8]
  M.N.R. Ashfold, J.P. Goss, B.L. Green, et al., Chem. Rev. 120 (2020) 5745–5794. doi: 10.1021/acs.chemrev.9b00518
9. [9]
  C. Hamdouchi, P. Maiti, A.M. Warshawsky, et al., J. Med. Chem. 61 (2018) 934–945. doi: 10.1021/acs.jmedchem.7b01411
10. [10]
  C.H. Jin, M. Krishnaiah, D. Sreenu, et al., J. Med. Chem. 57 (2014) 4213–4238. doi: 10.1021/jm500115w
11. [11]
  J. Larsen, M. Lambert, H. Pettersson, et al., J. Med. Chem. 63 (2020) 14502–14521. doi: 10.1021/acs.jmedchem.0c00797
12. [12]
  S. Ahmed, A. Ayscough, G.R. Barker, et al., J. Med. Chem. 60 (2017) 5663–5672. doi: 10.1021/acs.jmedchem.7b00352
13. [13]
  S. Ueda, H. Nagasawa, J. Am. Chem. Soc. 131 (2009) 15080–15081. doi: 10.1021/ja905056z
14. [14]
  X. Meng, C. Yu, P. Zhao, RSC Adv. 4 (2014) 8612–8616. doi: 10.1039/c3ra47029f
15. [15]
  J. Xia, X. Huang, M. Cai, Synthesis 51 (2019) 2014–2022. doi: 10.1055/s-0037-1611712
16. [16]
  Z. Zheng, S. Ma, L. Tang, et al., J. Org. Chem. 79 (2014) 4687–4693. doi: 10.1021/jo500298j
17. [17]
  L. Song, X. Tian, Z. Lv, et al., J. Org. Chem. 80 (2015) 7219–7225. doi: 10.1021/acs.joc.5b01183
18. [18]
  A. Bhatt, R.K. Singh, B.K. Sarma, R. Kant, Tetrahedron Lett. 60 (2019) 151026. doi: 10.1016/j.tetlet.2019.151026
19. [19]
  Y. Li, Z. Ye, N. Chen, Z. Chen, F. Zhang, Green Chem. 21 (2019) 4035–4039. doi: 10.1039/c9gc01895f
20. [20]
  B. Li, P.H. Dixneuf, Chem. Soc. Rev. 42 (2013) 5744–5767. doi: 10.1039/c3cs60020c
21. [21]
  M. Cortes-Clerget, J. Yu, J.R.A. Kincaid, et al., Chem. Sci. 12 (2021) 4237–4266. doi: 10.1039/d0sc06000c
22. [22]
  W.T. Ouyang, F. Xiao, L.J. Ou, W.M. He, Curr. Opin. Green Sust. 40 (2023) 100760. doi: 10.1016/j.cogsc.2023.100760
23. [23]
  L.Y. Xie, S. Peng, F. Liu, et al., ACS Sustain. Chem. Eng. 7 (2019) 7193–7199. doi: 10.1021/acssuschemeng.9b00200
24. [24]
  S. Peng, Y.X. Song, J.Y. He, et al., Chin. Chem. Lett. 30 (2019) 2287–2290. doi: 10.1016/j.cclet.2019.08.002
25. [25]
  L.Y. Xie, S. Peng, J.X. Tan, et al., ACS Sustain. Chem. Eng. 6 (2018) 16976–16981. doi: 10.1021/acssuschemeng.8b04339
26. [26]
  L.Y. Xie, Y.J. Li, J. Qu, et al., Green Chem. 19 (2017) 5642–5646. doi: 10.1039/C7GC02304A
27. [27]
  S.S. Zhu, L. Zuo, Y. Liu, B. Yu, Green Chem. 24 (2022) 8725–8732. doi: 10.1039/d2gc02950b
28. [28]
  L. Tang, Y. Ouyang, K. Sun, B. Yu, RSC Adv. 12 (2022) 19736–19740. doi: 10.1039/d2ra03467k
29. [29]
  X.Y. Li, Y. Liu, X.L. Chen, et al., Green Chem. 22 (2020) 4445–4449. doi: 10.1039/c9gc04445k
30. [30]
  F. Li, L. Lu, J. Ma, Org. Chem. Front. 2 (2015) 1589–1597. doi: 10.1039/C5QO00255A
31. [31]
  B. Lin, X. Zhang, C.Y. Zhou, C.M. Che, Org. Chem. Front. 8 (2021) 1216–1222. doi: 10.1039/d0qo01266a
32. [32]
  X. Liu, W.Z. Dong, Y. Li, et al., Org. Chem. Front. 10 (2023) 355–362. doi: 10.1039/d2qo01541b
33. [33]
  D. Ye, R. Huang, H. Zhu, L.H. Zou, D. Wang, Org. Chem. Front. 6 (2019) 62–69. doi: 10.1039/c8qo00941d
34. [34]
  Z. Zhang, L. Ji, X. Liu, et al., Org. Chem. Front. 9 (2022) 5154–5159. doi: 10.1039/d2qo01081j
35. [35]
  J.K. Laha, A. Gupta, U. Gulati, et al., Org. Chem. Front. 9 (2022) 6902–6908. doi: 10.1039/d2qo01465c
36. [36]
  M.A. Morozova, M.S. Yusubov, B. Kratochvil, et al., Org. Chem. Front. 4 (2017) 978–985. doi: 10.1039/C6QO00787B
37. [37]
  W. Shi, C. Yang, L. Guo, W. Xia, Org. Chem. Front. 9 (2022) 6513–6519. doi: 10.1039/d2qo01424f
38. [38]
  S. Liu, Y. Zhou, Y. Sui, H. Liu, H. Zhou, Org. Chem. Front. 4 (2017) 2175–2178. doi: 10.1039/C7QO00604G
39. [39]
  J. Zhen, Y. Li, H. Yuan, et al., Org. Chem. Front. 10 (2023) 404–409. doi: 10.1039/d2qo01429g
40. [40]
  S. Xu, P. Wu, W. Zhang, Org. Biomol. Chem. 14 (2016) 11389–11395. doi: 10.1039/C6OB02200F
41. [41]
  M. Liu, F. Zhou, Z. Jia, C.J. Li, Org. Chem. Front. 1 (2014) 161–166. doi: 10.1039/c3qo00063j
42. [42]
  S. Liu, P. Zhang, Y. Zhang, et al., Org. Chem. Front. 8 (2021) 5858–5865. doi: 10.1039/d1qo01068a
43. [43]
  H.X. Song, Q.Y. Han, C.L. Zhao, C.P. Zhang, Green Chem. 20 (2018) 1662–1731. doi: 10.1039/c8gc00078f
44. [44]
  P. Norcott, C. Spielman, C.S.P. McErlean, Green Chem. 14 (2012) 605–609. doi: 10.1039/c2gc16259h
45. [45]
  J. Tomasek, J. Schatz, Green Chem. 15 (2013) 2317–2338. doi: 10.1039/c3gc41042k
46. [46]
  D.N. Kommi, P.S. Jadhavar, D. Kumar, A.K. Chakraborti, Green Chem. 15 (2013) 798–810. doi: 10.1039/c3gc37004f
47. [47]
  Y.H. Lu, Z.T. Zhang, H.Y. Wu, et al., Chin. Chem. Lett. 34 (2023) 108036. doi: 10.1016/j.cclet.2022.108036
48. [48]
  S. Laulhé, S.S. Gori, M.H. Nantz, J. Org. Chem. 77 (2012) 9334–9337. doi: 10.1021/jo301133y
49. [49]
  J.A. Smulik, E. Vedejs, Org. Lett. 5 (2003) 4187–4190. doi: 10.1021/ol035629w
50. [50]
  A. Armstrong, R.D.C. Pullin, C.R. Jenner, J.N. Scutt, J. Org. Chem. 75 (2010) 3499–3502. doi: 10.1021/jo100407s
51. [51]
  A. Armstrong, C.A. Baxter, S.G. Lamont, A.R. Pape, R. Wincewicz, Org. Lett. 9 (2007) 351–353. doi: 10.1021/ol062852v
52. [52]
  M. Ong, M. Arnold, A.W. Walz, J.M. Wahl, Org. Lett. 24 (2022) 6171–6175. doi: 10.1021/acs.orglett.2c02361
53. [53]
  C. Ma, Z. Feng, J. Li, et al., Org. Chem. Front. 8 (2021) 3286–3291. doi: 10.1039/d1qo00064k
54. [54]
  C.H. Ma, L. Zhao, X. He, Y.Q. Jiang, B. Yu, Org. Chem. Front. 9 (2022) 1445–1450. doi: 10.1039/d1qo01870a
55. [55]
  C.H. Ma, M. Chen, Z.W. Feng, et al., New J. Chem. 45 (2021) 9302–9314. doi: 10.1039/d1nj00704a
56. [56]
  C.H. Ma, Y. Ji, J. Zhao, et al., Chin. J. Catal. 43 (2022) 571–583. doi: 10.1016/S1872-2067(21)63917-7
57. [57]
  C. Ma, Y. Tian, J. Wang, et al., Org. Lett. 24 (2022) 8265–8270. doi: 10.1021/acs.orglett.2c02949
58. [58]
  C. Ma, H. Meng, J. Li, et al., Chin. J. Chem. 40 (2022) 2655–2662. doi: 10.1002/cjoc.202200386
59. [59]
  Y.Q. Jiang, J. Li, Z.W. Feng, et al., Adv. Synth. Catal. 362 (2020) 2609–2614. doi: 10.1002/adsc.202000233
60. [60]
  C. Ma, X. Li, X. Chen, et al., Org. Lett. 25 (2023) 8016–8021. doi: 10.1021/acs.orglett.3c03193
61. [61]
  W. Klötzer, H. Baldinger, E.M. Karpitschka, J. Knoflach, Synthesis 1982 (1982) 592–595. doi: 10.1055/s-1982-29875
62. [62]
  M. Fernández, R. Alonso, Org. Lett. 5 (2003) 2461–2464. doi: 10.1021/ol034696n
63. [63]
  A.G. Draffan, B. Frey, B. Pool, et al., ACS Med. Chem. Lett. 5 (2014) 679–684. doi: 10.1021/ml500077j
64. [64]
  A. Armstrong, R.D.C. Pullin, C.R. Jenner, et al., Tetrahedron: Asymmetry 25 (2014) 74–86. doi: 10.1016/j.tetasy.2013.11.008
65. [65]
  J.S.W. Klötzer, J. Raneburger, Org. Synth. 64 (1986) 96. doi: 10.15227/orgsyn.064.0096
66. [66]
  H. Hikawa, M. Imani, H. Suzuki, Y. Yokoyama, I. Azumaya, RSC Adv. 4 (2014) 3768–3773. doi: 10.1039/C3RA46749J
67. [67]
  A.K. Sharma, P. Sharma, P. Mehara, P. Das, Chem. Eng. J. 471 (2023) 144666. doi: 10.1016/j.cej.2023.144666
1. [1]
  M.C. Bryan, B. Dillon, L.G. Hamann, et al., J. Med. Chem. 56 (2013) 6007–6021. doi: 10.1021/jm400250p
2. [2]
  J.Y. Chen, J. Huang, K. Sun, W.M. He, Org. Chem. Front. 9 (2022) 1152–1164. doi: 10.1039/D1QO01504D
3. [3]
  Y. Lang, C.J. Li, H. Zeng, Org. Chem. Front. 8 (2021) 3594–3613. doi: 10.1039/d1qo00359c
4. [4]
  X.Y. Yuan, F.L. Zeng, H.L. Zhu, et al., Org. Chem. Front. 7 (2020) 1884–1889. doi: 10.1039/d0qo00222d
5. [5]
  E. Vitaku, D.T. Smith, J.T. Njardarson, J. Med. Chem. 57 (2014) 10257–10274. doi: 10.1021/jm501100b
6. [6]
  C. Ma, Q. Li, M. Zhao, et al., J. Med. Chem. 64 (2021) 16242–16270. doi: 10.1021/acs.jmedchem.1c01559
7. [7]
  L.D. Pennington, D.T. Moustakas, J. Med. Chem. 60 (2017) 3552–3579. doi: 10.1021/acs.jmedchem.6b01807
8. [8]
  M.N.R. Ashfold, J.P. Goss, B.L. Green, et al., Chem. Rev. 120 (2020) 5745–5794. doi: 10.1021/acs.chemrev.9b00518
9. [9]
  C. Hamdouchi, P. Maiti, A.M. Warshawsky, et al., J. Med. Chem. 61 (2018) 934–945. doi: 10.1021/acs.jmedchem.7b01411
10. [10]
  C.H. Jin, M. Krishnaiah, D. Sreenu, et al., J. Med. Chem. 57 (2014) 4213–4238. doi: 10.1021/jm500115w
11. [11]
  J. Larsen, M. Lambert, H. Pettersson, et al., J. Med. Chem. 63 (2020) 14502–14521. doi: 10.1021/acs.jmedchem.0c00797
12. [12]
  S. Ahmed, A. Ayscough, G.R. Barker, et al., J. Med. Chem. 60 (2017) 5663–5672. doi: 10.1021/acs.jmedchem.7b00352
13. [13]
  S. Ueda, H. Nagasawa, J. Am. Chem. Soc. 131 (2009) 15080–15081. doi: 10.1021/ja905056z
14. [14]
  X. Meng, C. Yu, P. Zhao, RSC Adv. 4 (2014) 8612–8616. doi: 10.1039/c3ra47029f
15. [15]
  J. Xia, X. Huang, M. Cai, Synthesis 51 (2019) 2014–2022. doi: 10.1055/s-0037-1611712
16. [16]
  Z. Zheng, S. Ma, L. Tang, et al., J. Org. Chem. 79 (2014) 4687–4693. doi: 10.1021/jo500298j
17. [17]
  L. Song, X. Tian, Z. Lv, et al., J. Org. Chem. 80 (2015) 7219–7225. doi: 10.1021/acs.joc.5b01183
18. [18]
  A. Bhatt, R.K. Singh, B.K. Sarma, R. Kant, Tetrahedron Lett. 60 (2019) 151026. doi: 10.1016/j.tetlet.2019.151026
19. [19]
  Y. Li, Z. Ye, N. Chen, Z. Chen, F. Zhang, Green Chem. 21 (2019) 4035–4039. doi: 10.1039/c9gc01895f
20. [20]
  B. Li, P.H. Dixneuf, Chem. Soc. Rev. 42 (2013) 5744–5767. doi: 10.1039/c3cs60020c
21. [21]
  M. Cortes-Clerget, J. Yu, J.R.A. Kincaid, et al., Chem. Sci. 12 (2021) 4237–4266. doi: 10.1039/d0sc06000c
22. [22]
  W.T. Ouyang, F. Xiao, L.J. Ou, W.M. He, Curr. Opin. Green Sust. 40 (2023) 100760. doi: 10.1016/j.cogsc.2023.100760
23. [23]
  L.Y. Xie, S. Peng, F. Liu, et al., ACS Sustain. Chem. Eng. 7 (2019) 7193–7199. doi: 10.1021/acssuschemeng.9b00200
24. [24]
  S. Peng, Y.X. Song, J.Y. He, et al., Chin. Chem. Lett. 30 (2019) 2287–2290. doi: 10.1016/j.cclet.2019.08.002
25. [25]
  L.Y. Xie, S. Peng, J.X. Tan, et al., ACS Sustain. Chem. Eng. 6 (2018) 16976–16981. doi: 10.1021/acssuschemeng.8b04339
26. [26]
  L.Y. Xie, Y.J. Li, J. Qu, et al., Green Chem. 19 (2017) 5642–5646. doi: 10.1039/C7GC02304A
27. [27]
  S.S. Zhu, L. Zuo, Y. Liu, B. Yu, Green Chem. 24 (2022) 8725–8732. doi: 10.1039/d2gc02950b
28. [28]
  L. Tang, Y. Ouyang, K. Sun, B. Yu, RSC Adv. 12 (2022) 19736–19740. doi: 10.1039/d2ra03467k
29. [29]
  X.Y. Li, Y. Liu, X.L. Chen, et al., Green Chem. 22 (2020) 4445–4449. doi: 10.1039/c9gc04445k
30. [30]
  F. Li, L. Lu, J. Ma, Org. Chem. Front. 2 (2015) 1589–1597. doi: 10.1039/C5QO00255A
31. [31]
  B. Lin, X. Zhang, C.Y. Zhou, C.M. Che, Org. Chem. Front. 8 (2021) 1216–1222. doi: 10.1039/d0qo01266a
32. [32]
  X. Liu, W.Z. Dong, Y. Li, et al., Org. Chem. Front. 10 (2023) 355–362. doi: 10.1039/d2qo01541b
33. [33]
  D. Ye, R. Huang, H. Zhu, L.H. Zou, D. Wang, Org. Chem. Front. 6 (2019) 62–69. doi: 10.1039/c8qo00941d
34. [34]
  Z. Zhang, L. Ji, X. Liu, et al., Org. Chem. Front. 9 (2022) 5154–5159. doi: 10.1039/d2qo01081j
35. [35]
  J.K. Laha, A. Gupta, U. Gulati, et al., Org. Chem. Front. 9 (2022) 6902–6908. doi: 10.1039/d2qo01465c
36. [36]
  M.A. Morozova, M.S. Yusubov, B. Kratochvil, et al., Org. Chem. Front. 4 (2017) 978–985. doi: 10.1039/C6QO00787B
37. [37]
  W. Shi, C. Yang, L. Guo, W. Xia, Org. Chem. Front. 9 (2022) 6513–6519. doi: 10.1039/d2qo01424f
38. [38]
  S. Liu, Y. Zhou, Y. Sui, H. Liu, H. Zhou, Org. Chem. Front. 4 (2017) 2175–2178. doi: 10.1039/C7QO00604G
39. [39]
  J. Zhen, Y. Li, H. Yuan, et al., Org. Chem. Front. 10 (2023) 404–409. doi: 10.1039/d2qo01429g
40. [40]
  S. Xu, P. Wu, W. Zhang, Org. Biomol. Chem. 14 (2016) 11389–11395. doi: 10.1039/C6OB02200F
41. [41]
  M. Liu, F. Zhou, Z. Jia, C.J. Li, Org. Chem. Front. 1 (2014) 161–166. doi: 10.1039/c3qo00063j
42. [42]
  S. Liu, P. Zhang, Y. Zhang, et al., Org. Chem. Front. 8 (2021) 5858–5865. doi: 10.1039/d1qo01068a
43. [43]
  H.X. Song, Q.Y. Han, C.L. Zhao, C.P. Zhang, Green Chem. 20 (2018) 1662–1731. doi: 10.1039/c8gc00078f
44. [44]
  P. Norcott, C. Spielman, C.S.P. McErlean, Green Chem. 14 (2012) 605–609. doi: 10.1039/c2gc16259h
45. [45]
  J. Tomasek, J. Schatz, Green Chem. 15 (2013) 2317–2338. doi: 10.1039/c3gc41042k
46. [46]
  D.N. Kommi, P.S. Jadhavar, D. Kumar, A.K. Chakraborti, Green Chem. 15 (2013) 798–810. doi: 10.1039/c3gc37004f
47. [47]
  Y.H. Lu, Z.T. Zhang, H.Y. Wu, et al., Chin. Chem. Lett. 34 (2023) 108036. doi: 10.1016/j.cclet.2022.108036
48. [48]
  S. Laulhé, S.S. Gori, M.H. Nantz, J. Org. Chem. 77 (2012) 9334–9337. doi: 10.1021/jo301133y
49. [49]
  J.A. Smulik, E. Vedejs, Org. Lett. 5 (2003) 4187–4190. doi: 10.1021/ol035629w
50. [50]
  A. Armstrong, R.D.C. Pullin, C.R. Jenner, J.N. Scutt, J. Org. Chem. 75 (2010) 3499–3502. doi: 10.1021/jo100407s
51. [51]
  A. Armstrong, C.A. Baxter, S.G. Lamont, A.R. Pape, R. Wincewicz, Org. Lett. 9 (2007) 351–353. doi: 10.1021/ol062852v
52. [52]
  M. Ong, M. Arnold, A.W. Walz, J.M. Wahl, Org. Lett. 24 (2022) 6171–6175. doi: 10.1021/acs.orglett.2c02361
53. [53]
  C. Ma, Z. Feng, J. Li, et al., Org. Chem. Front. 8 (2021) 3286–3291. doi: 10.1039/d1qo00064k
54. [54]
  C.H. Ma, L. Zhao, X. He, Y.Q. Jiang, B. Yu, Org. Chem. Front. 9 (2022) 1445–1450. doi: 10.1039/d1qo01870a
55. [55]
  C.H. Ma, M. Chen, Z.W. Feng, et al., New J. Chem. 45 (2021) 9302–9314. doi: 10.1039/d1nj00704a
56. [56]
  C.H. Ma, Y. Ji, J. Zhao, et al., Chin. J. Catal. 43 (2022) 571–583. doi: 10.1016/S1872-2067(21)63917-7
57. [57]
  C. Ma, Y. Tian, J. Wang, et al., Org. Lett. 24 (2022) 8265–8270. doi: 10.1021/acs.orglett.2c02949
58. [58]
  C. Ma, H. Meng, J. Li, et al., Chin. J. Chem. 40 (2022) 2655–2662. doi: 10.1002/cjoc.202200386
59. [59]
  Y.Q. Jiang, J. Li, Z.W. Feng, et al., Adv. Synth. Catal. 362 (2020) 2609–2614. doi: 10.1002/adsc.202000233
60. [60]
  C. Ma, X. Li, X. Chen, et al., Org. Lett. 25 (2023) 8016–8021. doi: 10.1021/acs.orglett.3c03193
61. [61]
  W. Klötzer, H. Baldinger, E.M. Karpitschka, J. Knoflach, Synthesis 1982 (1982) 592–595. doi: 10.1055/s-1982-29875
62. [62]
  M. Fernández, R. Alonso, Org. Lett. 5 (2003) 2461–2464. doi: 10.1021/ol034696n
63. [63]
  A.G. Draffan, B. Frey, B. Pool, et al., ACS Med. Chem. Lett. 5 (2014) 679–684. doi: 10.1021/ml500077j
64. [64]
  A. Armstrong, R.D.C. Pullin, C.R. Jenner, et al., Tetrahedron: Asymmetry 25 (2014) 74–86. doi: 10.1016/j.tetasy.2013.11.008
65. [65]
  J.S.W. Klötzer, J. Raneburger, Org. Synth. 64 (1986) 96. doi: 10.15227/orgsyn.064.0096
66. [66]
  H. Hikawa, M. Imani, H. Suzuki, Y. Yokoyama, I. Azumaya, RSC Adv. 4 (2014) 3768–3773. doi: 10.1039/C3RA46749J
67. [67]
  A.K. Sharma, P. Sharma, P. Mehara, P. Das, Chem. Eng. J. 471 (2023) 144666. doi: 10.1016/j.cej.2023.144666
1. [1]
  Tong Li , Leping Pan , Yan Zhang , Jihu Su , Kai Li , Kuiliang Li , Hu Chen , Qi Sun , Zhiyong Wang . Electrochemical construction of 2,5-diaryloxazoles via N–H and C(sp³)-H functionalization. Chinese Chemical Letters, 2024, 35(4): 108897-. doi: 10.1016/j.cclet.2023.108897
2. [2]
  Jianhui Yin , Wenjing Huang , Changyong Guo , Chao Liu , Fei Gao , Honggang Hu . Tryptophan-specific peptide modification through metal-free photoinduced N-H alkylation employing N-aryl glycines. Chinese Chemical Letters, 2024, 35(6): 109244-. doi: 10.1016/j.cclet.2023.109244
3. [3]
  Guoju Guo , Xufeng Li , Jie Ma , Yongjia Shi , Jian Lv , Daoshan Yang . Photocatalyst/metal-free sequential C–N/C–S bond formation: Synthesis of S-arylisothioureas via photoinduced EDA complex activation. Chinese Chemical Letters, 2024, 35(11): 110024-. doi: 10.1016/j.cclet.2024.110024
4. [4]
  Bofei JIA , Zhihao LIU , Zongyuan GAO , Shuai ZHOU , Mengxiang WU , Qian ZHANG , Xiamei ZHANG , Shuzhong CHEN , Xiaohan YANG , Yahong LI . Cu(Ⅱ) and Cu(Ⅰ) complexes based on derivatives of imidazo[1,5-a]pyridine: Synthesis, structures, in situ metal-ligand reactions, and catalytic activity. Chinese Journal of Inorganic Chemistry, 2025, 41(5): 1020-1036. doi: 10.11862/CJIC.20240317
5. [5]
  Xiaodan Wang , Yingnan Liu , Zhibin Liu , Zhongjian Li , Tao Zhang , Yi Cheng , Lecheng Lei , Bin Yang , Yang Hou . Highly efficient electrosynthesis of H₂O₂ in acidic electrolyte on metal-free heteroatoms co-doped carbon nanosheets and simultaneously promoting Fenton process. Chinese Chemical Letters, 2024, 35(7): 108926-. doi: 10.1016/j.cclet.2023.108926
6. [6]
  Jie Li , Huida Qian , Deyang Pan , Wenjing Wang , Daliang Zhu , Zhongxue Fang . Efficient Synthesis of Anethaldehyde Induced by Visible Light. University Chemistry, 2024, 39(4): 343-350. doi: 10.3866/PKU.DXHX202310076
7. [7]
  Yaping Zhang , Wei Zhou , Mingchun Gao , Tianqi Liu , Bingxin Liu , Chang-Hua Ding , Bin Xu . Oxidative cyclization of allyl compounds and isocyanide: A facile entry to polysubstituted 2-cyanopyrroles. Chinese Chemical Letters, 2024, 35(4): 108836-. doi: 10.1016/j.cclet.2023.108836
8. [8]
  Hai-Yang Song , Jun Jiang , Yu-Hang Song , Min-Hang Zhou , Chao Wu , Xiang Chen , Wei-Min He . Supporting-electrolyte-free electrochemical [2 + 2 + 1] annulation of benzo[d]isothiazole 1,1-dioxides, N-arylglycines and paraformaldehyde. Chinese Chemical Letters, 2024, 35(6): 109246-. doi: 10.1016/j.cclet.2023.109246
9. [9]
  Junjun Huang , Ran Chen , Yajian Huang , Hang Zhang , Anran Zheng , Qing Xiao , Dan Wu , Ruxia Duan , Zhi Zhou , Fei He , Wei Yi . Discovery of an enantiopure N-[2-hydroxy-3-phenyl piperazine propyl]-aromatic carboxamide derivative as highly selective α_1D/1A-adrenoceptor antagonist and homology modelling. Chinese Chemical Letters, 2024, 35(11): 109594-. doi: 10.1016/j.cclet.2024.109594
10. [10]
  Chunxiu Yu , Zelin Wu , Hongle Shi , Lingyun Gu , Kexin Chen , Chuan-Shu He , Yang Liu , Heng Zhang , Peng Zhou , Zhaokun Xiong , Bo Lai . Insights into the electron transfer mechanisms of peroxydisulfate activation by modified metal-free acetylene black for degradation of sulfisoxazole. Chinese Chemical Letters, 2024, 35(8): 109334-. doi: 10.1016/j.cclet.2023.109334
11. [11]
  Lang Gao , Cen Zhou , Rui Wang , Feng Lan , Bohang An , Xiaozhou Huang , Xiao Zhang . Unveiling inverse vulcanized polymers as metal-free, visible-light-driven photocatalysts for cross-coupling reactions. Chinese Chemical Letters, 2024, 35(4): 108832-. doi: 10.1016/j.cclet.2023.108832
12. [12]
  Xiuwen Xu , Quan Zhou , Yacong Wang , Yunjie He , Qiang Wang , Yuan Wang , Bing Chen . Expanding the toolbox of metal-free organic halide perovskite for X-ray detection. Chinese Chemical Letters, 2024, 35(9): 109272-. doi: 10.1016/j.cclet.2023.109272
13. [13]
  Kexin Yin , Jingren Yang , Yanwei Li , Qian Li , Xing Xu . Metal-free diatomaceous carbon-based catalyst for ultrafast and anti-interference Fenton-like oxidation. Chinese Chemical Letters, 2024, 35(12): 109847-. doi: 10.1016/j.cclet.2024.109847
14. [14]
  Ke Zhang , Sheng Zuo , Pengyuan You , Tong Ru , Fen-Er Chen . Palladium-catalyzed stereoselective decarboxylative [4 + 2] cyclization of 2-methylidenetrimethylene carbonates with pyrrolidone-derived enones: Straightforward access to chiral tetrahydropyran-fused spiro-pyrrolidine-2,3-diones. Chinese Chemical Letters, 2024, 35(6): 109157-. doi: 10.1016/j.cclet.2023.109157
15. [15]
  Huaixiang Yang , Miao-Miao Li , Aijun Zhang , Jiefei Guo , Yongqi Yu , Wei Ding . Visible-light-induced photocatalyst- and metal-free radical phosphinoyloximation of alkenes with tert-butyl nitrite as bifunctional reagent. Chinese Chemical Letters, 2025, 36(3): 110425-. doi: 10.1016/j.cclet.2024.110425
16. [16]
  Qiang Feng , Jindong Hao , Ya Hu , Rong Fu , Wei Wei , Dong Yi . Photocatalytic multi-component synthesis of ester-containing quinoxalin-2(1H)-ones using water as the hydrogen donor. Chinese Chemical Letters, 2025, 36(6): 110582-. doi: 10.1016/j.cclet.2024.110582
17. [17]
  Boqiang Wang , Yongzhuo Xu , Jiajia Wang , Muyang Yang , Guo-Jun Deng , Wen Shao . Transition-metal free trifluoromethylimination of alkenes enabled by direct activation of N-unprotected ketimines. Chinese Chemical Letters, 2024, 35(9): 109502-. doi: 10.1016/j.cclet.2024.109502
18. [18]
  Tao Zhou , Jing Zhou , Yunyun Liu , Jie-Ping Wan , Fen-Er Chen . Transition metal-free tunable synthesis of 3-(trifluoromethylthio) and 3-trifluoromethylsulfinyl chromones via domino C–H functionalization and chromone annulation of enaminones. Chinese Chemical Letters, 2024, 35(11): 109683-. doi: 10.1016/j.cclet.2024.109683
19. [19]
  Zhaodong WANG . In situ synthesis, crystal structure, and magnetic characterization of a trinuclear copper complex based on a multi-substituted imidazo[1,5-a]pyrazine scaffold. Chinese Journal of Inorganic Chemistry, 2025, 41(3): 597-604. doi: 10.11862/CJIC.20240268
20. [20]
  Zhiqiang Wang , Yajie Gao , Tianjun Wang , Wei Chen , Zefeng Ren , Xueming Yang , Chuanyao Zhou . Photocatalyzed oxidation of water on oxygen pretreated rutile TiO₂(110). Chinese Chemical Letters, 2025, 36(4): 110602-. doi: 10.1016/j.cclet.2024.110602