SIOC 中文
ACS
Adv search

Acta Chimica Sinica >

0 26040116 - 26040116

DOI: https://doi.org/10.6023/A26040116

Article

Cobalt-Catalyzed Synthesis of Anilines from Cyclohexenones via Dehydrogenative Amination Strategy

  • Xu Qiaoliang ,
  • An Guanghui ,
  • Li Guangming
Expand
  • School of Chemistry and Materials Science, Heilongjiang University, Harbin 150080, China

Received date: 2026-04-09

  Online published: 2026-05-19

Supported by

Name of Foundation (No. UNPYSCT-2017124).

Fold

Abstract

Anilines and their derivatives play pivotal roles in the advancement of medicinal chemistry, life sciences, and advanced materials. Beyond conventional synthetic approaches to anilines, including nitration/reduction, C-N cross-coupling, and arene C-H amination, dehydrogenative amination has emerged as a highly efficient strategy for constructing aniline-based compounds. However, current dehydrogenative amination approaches for aniline synthesis inevitably require elevated temperatures, precious metal catalysts, stoichiometric oxidants, or additional energy input. Therefore, the development of green, sustainable, and mild-condition protocols for aniline synthesis remains a formidable challenge. In this study, we have developed a green and sustainable dehydrogenative amination of cyclohexenones for aniline synthesis using O2 as the oxidant and inexpensive CoCl2•6H2O as the catalyst under ambient temperature. This method eliminates the need for precious metal catalysts, features mild reaction conditions, simple operation, and environmental friendliness, while exhibiting excellent substrate generality to afford target products in high yields. Furthermore, the plausible mechanistic pathway of this dehydrogenative amination was elucidated through X-ray photoelectron spectroscopy (XPS) and high-resolution mass spectrometry (HRMS) analysis. The practical synthetic potential of this methodology was subsequently demonstrated through late-stage functionalization of drug molecules, laying a solid foundation for its broader application in organic synthesis. The experimental procedure is as follows: To a 15 mL reaction tube equipped with a magnetic stir bar was added CoCl2•6H2O (4.8 mg, 4 mol%), DABCO (168.0 mg, 3.0 equiv.), cyclohexenone 1 (0.5 mmol, 1.0 equiv.), amine 2 (1.2 mmol, 2.4 equiv.), CH3CN (1.5 mL), and CF3SO3H (18 µL, 40 mol%). The tube was evacuated and backfilled with O2 three times. The reaction mixture was stirred at room temperature for 24 h. Subsequently, the mixture was diluted with saturated aqueous NaHCO3 (25 mL) and extracted with ethyl acetate (3 × 30 mL). The combined organic layers were washed with brine (15 mL), dried over anhydrous Na2SO4, and concentrated to give the crude product, which was purified by silica gel column chromatography to afford the desired product.

Key words： C-N bond construction; dehydrogenative amination; cobalt catalysis; aniline synthesis; green oxidant

Cite this article

Xu Qiaoliang , An Guanghui , Li Guangming . Cobalt-Catalyzed Synthesis of Anilines from Cyclohexenones via Dehydrogenative Amination Strategy[J]. Acta Chimica Sinica, 0 : 26040116 -26040116 . DOI: 10.6023/A26040116

References

[1] (a) Zare, E. N.; Makvandi, P.; Ashtari, B.; Rossi, F.; Motahari, A.; Perale, G. J. Med. Chem. 2020, 63, 1. (b) Karthikeyan, L.; Rithisa, B.; Min, S.; Hong, H.; Kang, H.; Thangam, R.; Vivek, R. Chem. Eng. J. 2024, 493, 152530. (c) Guan, A.-Y.; Liu, C.-L.; Huang, G.; Li, H.-C.; Hao, S.-L.; Xu, Y.; Li, Z.-N. J. Agric. Food Chem. 2013, 61, 11929. (d) Blakemore, D. C.; Castro, L.; Churcher, I.; Rees, D. C.; Et., A. Thomas, A. W.; Wilson, D. M.; Wood, A. Nat. Chem. 2018, 10, 383. (e) Baker, C. O.; Huang, X.; Nelson, W.; Kaner, R. B. Chem. Soc. Rev. 2017, 46, 1510. (f) Peng, H.; Chen, S.; Yan, B. Acta Chim. Sinica 2024, 82, 797 (in Chinese). (彭红超,陈胜,阎斌,化学学报,2024, 82, 797.) (g) Luo, X.; Jiao, N. Acta Chim. Sinica 2020, 78, 758 (in Chinese). (罗潇,焦宁,化学学报,2020, 78, 758) (h) Jiang, M.; Yu, Z.; Yang, L.; Wang, F.; Cao, W.; Liu, X.; Feng, X. Angew. Chem. Int. Ed. 2025, 64, e202500756. (i) Tan, J.; Su, H.; Chen, M.; Xiao, F.; Yang, L.; Feng, X.; Feng, L.-W.; Liu, X. ACS Catal. 2025, 15, 9633. (j) Chang, X.; Zhang, F.; Zhu, S.; Yang, Z.; Feng, X.; Liu, Y. Nat. Commun. 2023, 14, 3876. (k) Qing, B.; Yang, Z.; Wu, Z.; Zhang, Z.; Zhou, Y.; Yan, X.; Liu, Y.; Feng, X. J. Am. Chem. Soc. 2025, 147, 7729. (l) Sang, X.; Xu, W.; Zhou, Y.; Chen, M.; Lin, L.; Ji, M.; Wang, F.; Dong, S.; Feng, X. Sci. China Chem. 2025, 68, 5007. (m) Hou, Z.; Yan, H.; Song, J.; Xu, H. Chin. J. Chem. 2018, 36, 909. (n) Chen, T.; Liu, H.; Wang, Z.; Liu, J.; Chen, N.; Xu, H. Angew. Chem. Int. Ed. 2026, 65, e9433561. (o) Wang, Q.; Ren, Z.; Zhang, K.; Zhou, D.; Fan, J. Acta Chim. Sinica 2026, 84, 248 (in Chinese). (汪庆辉,任正,张凯,周东营,樊健,化学学报,2026, 84, 248.) (p) Zhao, H.; Ponnam, D.; Li, Y.; Li, M.; Yang, J.; Chen, J.; Fan, B. Acta Chim. Sinica 2026, 84, 293 (in Chinese). (赵红艳,Ponnam Devendara,李亚彤,李明珠,杨晶雯,陈景超,樊保敏,化学学报,2026, 84, 293.) (q) Zhang, M.; Zhang, Y.; Qin, J.; Feng, X.; Li, X.; Chang, T.; Yang, H. Acta Chim. Sinica 2025, 83, 132 (in Chinese). (张蒙茜,张玉莹,秦家轩,冯霄,李雪艳,畅通,杨海英,化学学报,2025, 83, 132.)
[2] (a) Wang J.; Wang Z.; He W.; Ye, L. Chin. J. Org. Chem.2024, 44, 1786.(b) Wang, Y.; He, L.; Tan, Y.; Zhang, Z.; Xu, Y.; Ding, R.; Jiang, J.; He, W.Adv. Sci. 2026, 13, e15993.(c) Gui, Q.-W.; Teng, F.; Yu, P.; Wu, Y.-F.; Nong, Z.-B.; Yang, L.-X.; Chen, X.; Yang, T.-B.; He, W.-M. Chin. J. Catal. 2023, 44, 111.(d) Song, H.-Y.; Jiang, J.; Wu, C.; Hou, J.-C.; Lu, Y.-H.; Wang, K.-L.; Yang, T.-B.; He, W.-M. Green Chem. 2023, 25, 3292. (e) Fan, X.; Zhao, Y.; Liu, L.; Wang, H. Chin. J. Chem. 2023, 41, 1589. (f) Pan, Y.; Liu, W.; Huang, L.; Huang, J.; Feng, H. Chin. J. Chem. 2025, 43, 3597. (g) Zhou, F.; Luo, Y.; Xue, Z.; Nie, T.; Huang, X.; Xiong, Y.; Lu, J.; Lei, B.; Yang, L.; Wei, S.; Cong, X.; Hao, N. Chin. J. Chem. 2026, 44, 1766. (h) Xie, H.; Cheng, Y.; An, G. Chin. J. Org. Chem. 2026, 46, 475. (i) Cheng, Y.; Zhang, X.; An, G.; Li, G.; Yang, Z. Chin. Chem. Lett. 2023, 34, 107625. (j) Cheng, Y.; Yu, S.; He, Y.; An, G.; Li, G.; Yang, Z. Chem. Sci. 2021, 12, 3216. (k) Liang, C.; Cheng, Y.; Wang, C.; Zong, Y.; Xu, Q.; Lv, X.; Wang, J.; An, G. Chin. Chem. Lett. 2026 doi:10.1016/j.cclet.2026.112869.
[3] McGrath N. A.; Brichacek M.; Njardarson, J. T. J. Chem. Educ.2010, 87, 1348.
[4] (a) Song L.-R.; Fan Z.; Zhang, A. Org. Biomol. Chem.2019, 17, 1351.(b) Roscales S.; Csáky, A. G. Chem. Soc. Rev.2020, 49, 5159.
[5] (a) Ma D.; Zhang Y.; Yao J.; Wu S.; Tao, F. J. Am. Chem. Soc.1998, 120, 12459.(b) Creutz, S. E.; Lotito, K. J.; Fu, G. C.; Peters, J. C. Science 2012, 338, 647.(c) Luo, Y.; Li, Y.; Wu, B.; Wang, G.; Wu, J.; Zhang, S.-Y.; Houk, K. N.; Shen, Q. Nature 2025, 646, 1105.(d) Ma D.; Cai, Q. Acc. Chem. Res.2008, 41, 1450.(e) Monnier, F.; Taillefer, M. Catalytic Angew. Chem. Int. Ed. 2009, 48, 6954.(f) Sambiagio, C.; Marsden, S. P.; Blacker, A. J.; McGowan, P. C. Chem. Soc. Rev. 2014, 43, 352. (g) Cai, Q.; Zhou, W. Chin. J. Chem. 2020, 38, 879.
[6] (a) Paul, F.; Patt, J.; J. Am. Chem. Soc. 1994, 116, 5969. (b) Wolfe, J. P.; Wagaw, S.; Marcoux, J.-F.; Buchwald, S. L. Acc. Chem. Res. 1998, 31, 805. (c) Hartwig, J. F. Acc. Chem. Res. 1998, 31, 852. (d) Dorel, R.; Grugel, C. P.; Haydl, A. M. Angew. Chem. Int. Ed. 2019, 58, 17118.
[7] (a) Dominic M. T. Chan. Tetrahedron Lett.1996, 37, 9013.(b) Lam P. Y. S.; Deudon S.; Averill K. M.; Li R.; He M. Y.; DeShong P.; Clark, C. G. J. Am. Chem. Soc.2000, 122, 7600.(c) West, M. J.; Fyfe, J. W. B.; Vantourout, J. C.; Watson, A. J. B. Chem. Rev. 2019, 119, 12491.
[8] (a) Paudyal M. P.; Adebesin A. M.; Burt S. R.; Ess D. H.; Ma Z.; Kürti L.; Falck J. R. Science2016, 353, 1144.(b) Margrey K. A.; Levens A.; Nicewicz, D. A. Angew. Chem. Int. Ed.2017, 56, 15644.(c) Park, Y.; Kim, Y.; Chang, S. Chem. Rev. 2017, 117, 9247.(d) Ruffoni, A.; Juliá, F.; Svejstrup, T. D.; McMillan, A. J.; Douglas, J. J.; Leonori, D. Nat. Chem. 2019, 11, 426. (e) Hou, Z.-W.; Yan, H.; Song, J.; Xu, H.-C. Green Chem. 2023, 25, 7959. (f) Ma, C.-R.; Huang, G.-W.; Xu, H.; Wang, Z.-L.; Li, Z.-H.; Liu, J.; Yang, Y.; Li, G.; Dang, Y.; Wang, F. Nat. Catal. 2024, 7, 636. (g) Stewart, G.; Alvarez, E. M.; Rapala, C.; Sklar, J. H.; Kalow, J. A.; Malapit, C. A. Nat. Synth. 2025, 5, 55. (h) Chen, T.; Xiong, P.; Xu, H. Angew. Chem. Int. Ed. 2025, 64, e202513864.
[9] Izawa, Y., Pun D.; Stahl S. S. Science2011, 333, 209.
[10] Hajra A.; Wei Y.; Yoshikai N. Org. Lett.2012, 14, 5488.
[11] Girard S. A.; Hu X.; Knauber T.; Zhou F.; Simon M.-O.; Deng G.-J.; Li C.-J. Org. Lett.2012, 14, 5606.
[12] Xie Y.; Liu S.; Liu Y.; Wen Y.; Deng G.-J. Org. Lett.2012, 14, 1692.
[13] Jie X.; Shang Y.; Chen Z.-N.; Zhang X.; Zhuang W.; Su W. Nat. Commun.2018, 9, 5002.
[14] Dighe S. U.; Juliá S.; F.; Luridiana A.; Douglas J. J.; Leonori D. Nature2020, 584, 75.
[15] Tao S.-K.; Chen S.-Y.; Feng M.-L.; Xu J.-Q.; Yuan M.-L.; Fu H.-Y.; Li R.-X.; Chen H.; Zheng X.-L.; Yu X.-Q. Org. Lett.2022, 24, 1011.
[16] Zhao X.; Liu, Z. Angew. Chem. Int. Ed.2025, 64, e202505252.
[17] Bongso A.; Roswanda R.; Syah, Y. M. RSC Adv.2022, 12, 15885.
[18] Castellino N. J.; Montgomery A. P.; Danon J. J.; Kassiou M. Chem. Rev.2023, 123, 8127.
[19] Dutta U.; Maiti S.; Bhattacharya T.; Maiti D. Science2021, 372, eabd5992.
[20] (a) Varala R.; Seema V.; Alam M. M.; Amanullah M.; Prasad, B. D. Curr. Org. Chem.2024, 28, 1307.(b) Barham J. P.; John M. P.; Murphy, J. A. J. Am. Chem. Soc.2016, 138, 15482.(c) McKinney, T. M.; Geske, D. H. J. Am. Chem. Soc. 1965, 87, 3013.(d) Zheng, Z.-R.; Evans, D. H.; Nelsen, S. F. J. Org. Chem. 2000, 65, 1793. (e) Kim, D.; Scranton, A. B.; Stansbury, J. W. J. Appl. Polym. Sci. 2009, 114, 1535.
[21] (a) Chuang T. J.; Brundle C. R.; Rice, D. W. Surf. Sci.1976, 59, 413.(b) Ivanova, T.; Naumkin, A.; Sidorov, A.; Eremenko, I.; Kiskin, M. J. Electron Spectrosc. Relat. Phenom. 2007, 156, 200.
Options
Outlines

/

〈 〉