SIOC 中文
ACS
Adv search

Acta Chimica Sinica >

0 3 - 3

DOI: https://doi.org/10.6023/A26070256

Communication

Photoredox/Nickel-Cocatalyzed Asymmetric C-N Couplings for Atroposelective Synthesis of Biaryl Anilines

  • Wu Ming-Xuan ,
  • Wu Yu-Xin ,
  • Zhang Hong-Hao ,
  • Chen Qun ,
  • Shi Feng
Expand
  • aSchool of Petrochemical Engineering, Institute of Functional Heterocycles, Changzhou University, Changzhou, Jiangsu 213164;
    bSchool of Chemistry and Molecular Engineering, Jiangsu Normal University, Xuzhou, Jiangsu 221116

Received date: 2026-07-20

  Online published: 2026-08-26

Supported by

National Natural Science Foundation of China (Nos. 22125104, 22571026).

Fold

Abstract

Axially chiral heterobiaryl anilines are privileged scaffolds widely embedded in natural products and bioactive molecules, and they serve as highly efficient chiral ligands or organocatalysts owing to their outstanding catalytic performance. As a result, the development of efficient asymmetric synthetic methods for these architectures has attracted intense attention. Photoredox/nickel dual catalysis has emerged as a versatile and mild platform for the construction of diverse C(sp2)-heteroatom bonds; however, its enantioselective variant remains extremely rare. Herein, we develop a single-electron-transfer (SET)-based photoredox/nickel dual catalytic system that accomplishes atroposelective C(sp2)-N bond formation between readily available arylamines and racemic heterobiaryl triflates. After systematic optimization of the reaction parameters, the desired axially chiral products were obtained in up to 98% yield and 86% enantiomeric excess (ee). The general procedure for this atroposelective C-N coupling is as follows: inside a nitrogen-filled glovebox, NiBr2(DME) (10 mol%) and chiral ligand (12 mol%) were combined with photocatalyst (2 mol%) in anhydrous toluene (3.0 mL) and stirred at room temperature for 30 min. Subsequently, racemic heterobiaryl triflates (0.1 mmol, 1.0 equiv.), arylamines (1.5 equiv.), N-tert-butylisopropylamine (1.5 equiv.), and ethyl acetate (3.0 mL) were added. The vial was sealed, brought out of the glovebox, and stirred under irradiation with 45 W blue LEDs at 0 oC for 12 h. After completion of the reaction, the mixture was concentrated in vacuo and purified by silica gel chromatography to afford the pure product. The substrate scope proved to be broad: a range of substituted anilines, heterocyclic arylamines, and structurally diverse heterobiaryl triflates were well tolerated. Mechanistic experiments demonstrated that the reaction operates through a SET pathway rather than an energy-transfer mechanism. This work not only provides a new strategy for photoredox/nickel dual-catalyzed asymmetric C(sp2)-N coupling but also opens an avenue for the enantioselective synthesis of axially chiral biaryl anilines.

Key words： Asymmetric C(sp2)-N bond coupling; Photoredox/Ni cocatalysis; (Hetero)Biaryl atropisomer; Axial chirality; Asymmetric catalysis

Cite this article

Wu Ming-Xuan , Wu Yu-Xin , Zhang Hong-Hao , Chen Qun , Shi Feng . Photoredox/Nickel-Cocatalyzed Asymmetric C-N Couplings for Atroposelective Synthesis of Biaryl Anilines[J]. Acta Chimica Sinica, 0 : 3 -3 . DOI: 10.6023/A26070256

References

[1] For selected reviews, see: (a) Wang, Q.; Gu, Q.; You, S.-L. Acta Chim. Sinica 2019, 77, 690 (in Chinese). (王强, 顾庆, 游书力, 化学学报, 2019, 77, 690.) (b) Zhang, S.; Liao, G.; Shi, B.-F. Chin. J. Org. Chem., 2019, 39, 1522 (in Chinese). (张硕, 廖港, 史炳锋, 有机化学, 2019, 39, 1522.) (c) Bao, X.; Rodriguez, J.; Bonne, D. Angew. Chem., Int. Ed. 2020, 59, 12623. (d) Carmona, J. A.; Rodríguez-Franco, C.; Fernández, R.; Hornillos, V.; Lassaletta, J. M. Chem. Soc. Rev. 2021, 50, 2968. (e) Cheng, J. K.; Xiang, S.-H.; Li, S.; Ye, L.; Tan, B. Chem. Rev. 2021, 121, 4805. (f) Liu, C.-X.; Zhang, W.-W.; Yin, S.-Y.; Gu, Q.; You, S.-L. J. Am. Chem. Soc. 2021, 143, 14025. (g) Zhang, X.; Zhao, K.; Gu, Z. Acc. Chem. Res. 2022, 55, 1620. (h) Qin, W.; Liu, Y.; Yan, H. Acc. Chem. Res. 2022, 55, 2780. (i) Feng, J.; Lu, C.-J.; Liu, R.-R. Acc. Chem. Res. 2023, 56, 2537. (j) Xiang, S.-H.; Ding, W.-Y.; Wang, Y.-B.; Tan, B. Nat. Catal. 2024, 7, 483.
[2] For selected examples, see: (a) Cheng, D.-J.; Yan, L.; Tian, S.-K.; Wu, M.-Y.; Wang, L.-X.; Fan, Z.-L.; Zheng, S.-C.; Liu, X.-Y.; Tan, B. Angew. Chem., Int. Ed. 2014, 53, 3684. (b) Chen, Y.-H.; Qi, L.-W.; Fang, F.; Tan, B. Angew. Chem., Int. Ed. 2017, 56, 16308. (c) Qi, L.-W.; Mao, J.-H.; Zhang, J.; Tan, B. Nat. Chem. 2018, 10, 58. (d) Qi, L.-W.; Li, S.; Xiang, S.-H.; Wang, J.; Tan, B. Nat. Catal.2019, 2, 314. (e) Lu, S.; Ng, S. V. H.; Lovato, K.; Ong, J.-Y.; Poh, S. B.; Ng, X. Q.; Kürti, L.; Zhao, Y. Nat. Commun. 2019, 10, 3061. (f) Lu, S.; Poh, S. B.; Rong, Z.-Q.; Zhao, Y. Org. Lett. 2019, 21, 6169. (g) ang, G.; Guo, D.; Meng, D.; Wang, J. Nat. Commun. 2019, 10, 3062. (h) Zhang, L.; Shen, J.; Wu, S.; Zhong, G.; Wang, Y.-B.; Tan, B. Angew. Chem., Int. Ed. 2020, 59, 23077. (i) Liu, W.; Jiang, Q.; Yang, X. Angew. Chem., Int. Ed. 2020, 59, 23598. (j) Wang, G.; Shi, Q.; Hu, W.; Chen, T.; Guo, Y.; Hu, Z.; Gong, M.; Guo, J.; Wei, D.; Fu, Z.; et al. Nat. Commun. 2020, 11, 946. (k) Cen, S.; Huang, N.; Lian, D.; Shen, A.; Zhao, M.-X.; Zhang, Z. Nat. Commun. 2022, 13, 4735. (l) Hong, X.; Guo, J.; Liu, J.; Cao, W.; Wei, C.; Zhang, Y.; Zhang, X.; Fu, Z. Sci. China: Chem. 2022, 65, 905. (m) Cai, Y.; Zhao, Y.; Tang, K.; Zhang, H.; Mo, X.; Chen, J.; Huang, Y. Nat. Commun. 2024, 15, 496. (n) Gou, B.-B.; Shen, W.-J.; Gao, Y.-J.; Gu, Q.; You, S.-L. Angew. Chem., Int. Ed. 2025, 64, e202502131.
[3] For selected reviews, see: (a) Lu, C.-J.; Xu, Q.; Feng, J.; Liu, R.-R. Angew. Chem., Int. Ed. 2023, 62, e202216863. (b) Feng, J.; Xi, L.-L.; Lu, C.-J.; Liu, R.-R. Chem. Soc. Rev. 2024, 53, 9560.
[4] For selected reviews, see: (a) Hartwig, J. F. Nature 2008, 455, 314. (b) Ruiz-Castillo, P.; Buchwald, S. L. Chem. Rev. 2016, 116, 12564.
[5] For selected examples, see: (a) Ramírez-López, P.; Ros, A.; Romero-Arenas, A.; Iglesias-Sigüenza, J.; Fernández, R.; Lassaletta, J. M. J. Am. Chem. Soc. 2016, 138, 12053. (b) Wang, X.; Liu, W.-G.; Liu, L.-T.; Yang, X.-D.; Niu, S.; Tung, C.-H.; Wu, L.-Z.; Cong, H. Org. Lett. 2021, 23, 5485. (c) Zhang, K.; Oestreich, M. J. Am. Chem. Soc. 2025, 147, 32329.
[6] For selected reviews, see: (a) Bhunia, S.; Pawar, G. G.; Kumar, S. V.; Jiang, Y.; Ma, D. Angew. Chem., Int. Ed. 2017, 56, 16136. (b) Cai, Q.; Zhou, W. Chin. J. Chem. 2020, 38, 879.
[7] For selected examples, see: (a) Thönnißen, V.; Westphäling, J.; Atodiresei, I. L.; Patureau, F. W. Chem. - Eur. J. 2024, 30, e202304378. (b) Ishida, M.; Adachi, R.; Kobayashi, K.; Yamamoto, Y.; Kawahara, C.; Yamada, T.; Aoyama, H.; Kanomata, K.; Akai, S.; Lam, P. Y. S.; et al. Chem. Commun. 2024, 60, 678.
[8] Peng X.; Rahim A.; Peng W.; Jiang F.; Gu Z.; Wen S. Chem.Rev. 2023, 123, 1364.
[9] For selected examples, see: (a) Zhao, K.; Duan, L.; Xu, S.; Jiang, J.; Fu, Y.; Gu, Z. Chem 2018, 4, 599. (b) Xu, S.; Zhao, K.; Gu, Z. Adv. Synth. Catal. 2018, 360, 3877. (c) Yang, H.; Sun, X.; Chen, Z.; Jiang, C.; Duan, L.; Zhao, J.; Gu, Z. Angew. Chem., Int. Ed. 2025, 64, e202416839. (d) Li, Q.; Zhang, M.; Zhan, S.; Gu, Z. Org. Lett. 2019, 21, 6374. (e) Liu, Y.; Ma, Y.; Liu, P.-Z.; Shen, C.; Cen, S.; Zhu, Y.-Y.; Peng, Q.; Zhang, Z. Angew. Chem., Int. Ed. 2026, 65, e202514745. (f) Yihuo, A.; Pu, M.; Tan, Z.; Liao, J.; Tan, J.; Zhou, Q.-L.; Liu, X.; Feng, X. Sci. China: Chem. 2024, 67, 2694.
[10] For selected examples, see: (a) Li, L.-J.; He, Y.; Yang, Y.; Guo, J.; Lu, Z.; Wang, C.; Zhu, S.; Zhu, S.-F. CCS Chem. 2024, 6, 537. (b) Tasker, S. Z.; Standley, E. A.; Jamison, T. F. Nature 2014, 509, 299. (c) Poremba, K. E.; Dibrell, S. E.; Reisman, S. E. ACS Catal. 2020, 10, 8237 (d) Xue, W.; Jia, X.; Wang, X.; Tao, X.; Yin, Z.; Gong, H. Chem. Soc. Rev. 2021, 50, 4162. (e) Zhu, S.; Zhao, X.; Li, H.; Chu, L. Chem. Soc. Rev. 2021, 50, 10836.
[11] For selected reviews, see: (a) Tellis, J. C.; Kelly, C. B.; Primer, D. N.; Jouffroy, M.; Patel, N. R.; Molander, G. A. Acc. Chem. Res. 2016, 49, 1429. (b) Twilton, J.; Le, C.; Zhang, P.; Shaw, M. H.; Evans, R. W.; MacMillan, D. W. C. The merger of transition metal and photocatalysis. Nat. Rev. Chem. 2017, 1, 0052. (c) Zhang, H.-H.; Chen, H.; Zhu, C.; Yu, S. Sci. China: Chem. 2020, 63, 637. (d) Zhu, C.; Yue, H.; Chu, L.; Rueping, M. Chem. Sci. 2020, 11, 4051. (e) Lu, F.-D.; Chen, J.; Jiang, X.; Chen, J.-R.; Lu, L.-Q.; Xiao, W.-J. Chem. Soc. Rev. 2021, 50, 12808. (f) Xu, L.; Wang, F.; Chen, F.; Zhu, S.; Chu, L. Chin. J. Org. Chem., 2022, 42, 1 (in Chinese). (徐磊, 王方, 陈凡, 朱圣卿, 储玲玲, 有机化学, 2022, 42, 1.) (g) Wang, X.; Xu, S.; Ping, Y.; Kong, W. Chin. J. Org. Chem., 2025, 45, 383 (in Chinese). (王晓琴, 许盛, 平媛媛, 孔望清, 有机化学, 2025, 45, 383.) (h) Gao, G.; Li, Z.; Li, Y.; Lu, X. Chin. J. Org. Chem., 2025, 45, 1905 (in Chinese). (高根伟, 李震, 李炎, 陆熹, 有机化学, 2025, 45, 1905.) (i) Li, G.; Li, T.; Luo, L.; Tan, Y.; Lu, Z. Org. Chem. Front. 2025, 12, 4530.
[12] For selected reviews, see: (a) Zhu, C.; Yue, H.; Jia, J.; Rueping, M. Angew. Chem., Int. Ed. 2021, 60, 17810. (b) Song, Ge.; Xue, D. Chin. J. Org. Chem., 2022, 42, 2275 (in Chinese). (宋戈洋, 薛东, 有机化学, 2022, 42, 2275.) (c) Zhu, S.; Li, H.; Li, Y.; Huang, Z.; Chu, L. Org. Chem. Front. 2023, 10, 548. (d) Luo, H.; Feng, Y.; Lin, L. ChemCatChem 2023, 15, e202300303. (e) Arora, R.; Samokhin, P.; Lautens, M. Angew. Chem., Int. Ed. 2025, 64, e202500929.
[13] For selected examples, see: (a) Terrett, J. A.; Cuthbertson, J. D.; Shurtleff, V. W.; MacMillan, D. W. C. Nature 2015, 524, 330. (b) Corcoran, E. B.; Pirnot, M. T.; Lin, S.; Dreher, S. D.; DiRocco, D. A.; Davies, I. W.; Buchwald, S. L.; MacMillan, D. W. C. Science 2016, 353, 279. (c) Kim, T.; McCarver, S. J.; Lee, C.; MacMillan, D. W. C. Angew. Chem., Int. Ed. 2018, 57, 3488. (d) Qi, Z.-H.; Ma, J. ACS Catal. 2018, 8, 1456. (e) Kudisch, M.; Lim, C.-H.; Thordarson, P.; Miyake, G. M. J. Am. Chem. Soc. 2019, 141, 19479. (f) Bradley, R. D.; McManus, B. D.; Yam, J. G.; Carta, V.; Bahamonde, A. Angew. Chem., Int. Ed. 2023, 62, e202310753. (g) Zhu, D.-L.; Li, J.; Young, D. J.; Wang, Y.; Li, H.-X. Org. Chem. Front. 2023, 10, 3612. (h) Delgado, J. A. C.; Tian, Y.-M.; Marcon, M.; König, B.; Paixão, M. W. J. Am. Chem. Soc. 2023, 145, 26452. (i) Niyogi, S.; Mondal, A.; Nandy, M.; Pal, S.; Khatua, A.; Bisai, A. Org. Lett. 2024, 26, 8643. (j) Zhu, D.-L.; Jiang, S.; Wu, Q.; Wang, H.; Li, H.-Y.; Li, H.-X. Org. Lett. 2021, 23, 8327. (k) He, X.; Zhang, Y.-Y.; Shou, J.-Y.; Chu, L.; Qing, F.-L. Org. Lett. 2024, 26, 6782.
[14] (a) Zhou, Q.-Q.; Lu, F.-D.; Liu, D.; Lu, L.-Q.; Xiao, W.-J. Org. Chem. Front. 2018, 5 (21), 3098. (b) Li, T.-Z.; Tian, C.-C.; Chen, W.; Zou, Z.-Y.; Yang, J.-L.; Liu, F.-X.; Li, X.; Zhang, H.-H.; Shi, F. Angew. Chem., Int. Ed. 2025, 64, e202516584. (c) Zhang, H.-H.; Yang, D.; Li, T.-Z.; Yang, J.-L.; Liu, F.-X.; Zou, Z.-Y.; Shi, F. ACS Catal. 2026, 16, 3873. (d) Liu, S.-J.; Yang, J.-L.; Li, T.-Z.; Zhang, H.-H.; Shi, F. Org. Lett. 2026, 28, 5786. (e) Xue, J.; Su, L.; Fang, W.; Gao, S.; Zheng, Q.; Liu, J. Angew. Chem., Int. Ed. 2026, 65, e202523823.
[15] For selected reviews, see: (a) Strieth-Kalthoff, F.; James, M. J.; Teders, M.; Pitzer, L.; Glorius, F. Chem. Soc. Rev. 2018, 47, 7190. (b) Zhou, Q.-Q.; Zou, Y.-Q.; Lu, L.-Q.; Xiao, W.-J. Angew. Chem., Int. Ed. 2019, 58, 1586. (c) Dutta, S.; Erchinger, J. E.; Strieth-Kalthoff, F.; Kleinmans, R.; Glorius, F. Chem. Soc. Rev. 2024, 53, 1068.
[16] For selected examples, see: (a) Ros, A.; Estepa, B.; Ramírez-López, P.; Álvarez, E.; Fernández, R.; Lassaletta, J. M. J. Am. Chem. Soc. 2013, 135, 15730. (b) Jiang, X.; Xiong, W.; Deng, S.; Lu, F.-D.; Jia, Y.; Yang, Q.; Xue, L.-Y.; Qi, X.; Tunge, J. A.; Lu, L.-Q.; Xiao, W.-J. Nat. Catal. 2022, 5, 788. (c) Xiong, W.; Jiang, X.; Wang, W.-C.; Cheng, Y.; Lu, L.-Q.; Gao, K.; Xiao, W.-J. J. Am. Chem. Soc. 2023, 145, 7983. (d) Chen, X.-W.; Li, C.; Gui, Y.-Y.; Yue, J.-P.; Zhou, Q.; Liao, L.-L.; Yang, J.-W.; Ye, J.-H.; Yu, D.-G. Angew. Chem., Int. Ed. 2024, 63, e202403401. (e) Sun, Y.-W.; Zhao, J.-H.; Yan, X.-Y.; Ji, C.-L.; Feng, H.; Gao, D.-W. Nat. Commun. 2024, 15, 10810. (f) Yang, Z.; Gu, X.; Han, L.-B.; Wang, J. ACS Catal. 2025, 15, 8268.
[17] For selected reviews, see: (a) Zhang, H.-H.; Shi, F. Acc. Chem. Res. 2022, 55, 2562. (b)Zhang, H.-H.; Li, T.-Z.; Liu, S.-J.; Shi, F. Angew. Chem., Int. Ed. 2024, 63, e202311053. (c) Bai, J.-Y.; Zhu, Z.-Q.; Liu, S.-Y.; Ai, Z.-Y.; Shi, F. Sci. China Chem. 2026, 69, DOI: 10.1007/s11426-026-3709-3.
[18] For recent examples, see: (a) Wang, N.-Y.; Gao, S.; Shu, Z.-D.; Cheng, B.-B.; Ma, C.; Zhang, Y.-C.; Shi, F. Sci. China Chem. 2025, 68, 3130. (b) Liu, S.-J.; Wang, X.; Yang, J.-X.; Ao, X.-S.; Ni, S.-F.; Zhang, Y.-C.; Shi, F. Nat. Commun. 2025, 16, 6605. (c) Liu, S.-Y.; Zhu, Z.-Q.; Chen, F.-X.; Feng, N.-N.; Ni, S.-F.; Shi, F. Chem. Sci. 2025, 16, 21394. (d) Gao, C.-H.; Yu, X.-Y.; Yao, B.-X.; Yu, H.-L.; Ni, S.-F.; Tan, W.; Shi, F. Nat. Commun. 2026, 17, 7473. (e) Wu, X.-Y.; Wang, C.-P.; Qiu, X.-D.; Tan, W.; Shi, F. Sci. China Chem. 2026, 69, DOI: 10.1007/s11426-026-3686-2.
[19] (a) Cheng, X.; Li, T.; Liu, Y.; Lu, Z. ACS Catal. 2021, 11, 11059. (b) Li, T.; Cheng, X.; Lu, J.; Wang, H.; Fang, Q.; Lu, Z. Chin. J. Chem. 2022, 40, 1033.
Options
Outlines

/

〈 〉