Recent Progress in Electrochemical Late-Stage C(sp²)–H Functionalization

Dedication

Dedicated to Prof. Dr. Paul Knochel on the occasion of his 70^th birthday.

Abstract

Late-stage C–H functionalization has gained rapid development as a key approach in modern synthetic methodology, particularly for the transformation of structurally complex molecules. This strategy has reformed retrosynthetic logic and improved synthetic efficiency. C(sp²)–H functionalization, as a pivotal part in late-stage functionalization, has significantly promoted the development of medicinal chemistry. However, the latter often employ transition metal catalysts, in combination with stoichiometric amounts of chemical oxidants, which severely compromise their sustainability, functional group tolerance, and their extension to industrial applications. In sharp contrast, electrochemical late-stage C(sp²)–H functionalization has emerged as a more sustainable and environmentally friendly alternative, where electrons are used as clean redox agents. Therefore, this approach obviates the need for toxic chemical oxidants, enabling reactions to be operative under milder conditions, allowing for a wide scope of redox transformations. In this review, we highlight the recent progress in the electrochemical late-stage functionalization of C(sp²)–H bonds from 2019 to 2025, with particular focus on the formation of C(sp²)–C, C(sp²)–O, C(sp²)–N, and C(sp²)–P bonds.

Keywords

Electrochemistry - Late-stage functionalization - C–H activation - Transition-metal catalysis - Bioactive molecules

Publikationsverlauf

Eingereicht: 08. August 2025

Angenommen nach Revision: 23. September 2025

Artikel online veröffentlicht:
20. November 2025

• References

• 1 Faraday M. Ann Phys 1834; 109: 481-520
• 2 Kolbe H. J Prakt Chem 1847; 41: 137-139

Selected reviews:
• 3a Yoshida J-I, Shimizu A, Hayashi R. Chem Rev 2018; 118: 4702-4730
• 3b Francke R, Little RD. Chem Soc Rev 2014; 43: 2492-2521
• 3c Jutand A. Chem Rev 2008; 108: 2300-2347
• 3d Xiong P, Xu H-C. Acc Chem Res 2019; 52: 3339-3350
• 3e Yuan Y, Lei A. Acc Chem Res 2019; 52: 3309-3324
• 3f Ackermann L. Acc Chem Res 2020; 53: 84-104
• 3g Siu JC, Fu N, Lin S. Acc Chem Res 2020; 53: 547-560
• 3h Wang F, Stahl SS. Acc Chem Res 2020; 53: 561-574
• 3i Jiao K-J, Xing Y-K, Yang Q-L, Qiu H, Mei T-S. Acc Chem Res 2020; 53: 300-310
• 3j Wang Y, Dana S, Long H. et al. Chem Rev 2023; 123: 11269-11335
• 3k Davies HM, Du Bois J, Yu J-Q. Chem Soc Rev 2011; 40: 1855-1856
• 4 Zhu C, Ang NWJ, Meyer TH, Qiu Y, Ackermann L. ACS Cent Sci 2021; 7: 415-431
• 5 Guillemard L, Kaplaneris N, Ackermann L, Johansson MJ. Nat Rev Chem 2021; 5: 522-545
• 6a Davies HML, Morton D. ACS Cent Sci 2017; 3: 936-943
• 6b Chu JCK, Rovis T. Angew Chem Int Ed 2018; 57: 62-101
• 6c Börgel J, Ritter T. Chem 2020; 6: 1877-1887
• 7 Kärkäs MD. Chem Soc Rev 2018; 47: 5786-5865
• 8 Aynetdinova D, Callens MC, Hicks HB. et al. Chem Soc Rev 2021; 50: 5517-5563
• 9 Ma C, Zhao C-Q, Li Y-Q. et al. Chem Commun 2017; 53: 12189-12192
• 10 Yang Q-L, Li C-Z, Zhang L-W. et al. Organometallics 2019; 38: 1208-1212
• 11 Kuciński K, Simon H, Ackermann L. Chem Eur J 2022; 28: e202103837
• 12 Yang Q-L, Liu Y, Liang L, Li Z-H, Qu G-R, Guo H-M. J Org Chem 2022; 87: 6161-6178
• 13 Müller K, Faeh C, Diederich F. Science 2007; 317: 1881-1886
• 14 O'Brien AG, Maruyama A, Inokuma Y, Fujita M, Baran PS, Blackmond DG. Angew Chem Int Ed 2014; 53: 11868-11871
• 15 Qiu Y, Scheremetjew A, Finger LH, Ackermann L. Chem Eur J 2020; 26: 3241-3246
• 16 Qi J, Xu J, Ang H-T. et al. J Am Chem Soc 2023; 145: 24965-24971
• 17 Motornov V, Trienes S, Resta S. et al. Angew Chem Int Ed 2025; 64: e202504143
• 18 Yan H, Hou Z-W, Xu H-C. Angew Chem Int Ed 2019; 58: 4592-4595
• 19 Lai X-L, Shu X-M, Song J, Xu H-C. Angew Chem Int Ed 2020; 59: 10626-10632
• 20 Xu P, Chen P-Y, Xu H-C. Angew Chem Int Ed 2020; 59: 14275-14280
• 21 Wang K, Liu X, Yang S. et al. Org Lett 2022; 24: 3471-3476
• 22 Wan Q, Hou Z-W, Zhao X-R, Xie X, Wang L. Org Lett 2023; 25: 1008-1013
• 23a Shen T, Lambert TH. Science 2021; 371: 620-626
• 23b Shen T, Li Y-L, Ye K-Y, Lambert TH. Nature 2023; 614: 275-280
• 24 Niu L, Jiang C, Liang Y. et al. J Am Chem Soc 2020; 142: 17693-17702
• 25 Zheng Y-X, Gao Y, Xiong P, Xu H-C. Angew Chem Int Ed 2025; 64: e202423241
• 26 Ye X, Wang C, Zhang S. et al. ACS Catal 2020; 10: 11693-11699
• 27a Xu F, Li Y-J, Huang C, Xu H-C. ACS Catal 2018; 8: 3820-3824
• 27b Zeng L, Li H, Tang S. et al. ACS Catal 2018; 8: 5448-5453
• 27c Mei R, Sauermann N, Oliveira JCA, Ackermann L. J Am Chem Soc 2018; 140: 7913-7921
• 27d Yang Q-L, Xing Y-K, Wang X-Y. et al. J Am Chem Soc 2019; 141: 18970-18976
• 28 Stangier M, Messinis AM, Oliveira JCA, Yu H, Ackermann L. Nat Commun 2021; 12: 4736-4743
• 29 Chakrabarty S, Wang Y, Perkins JC, Narayan ARH. Chem Soc Rev 2020; 49: 8137-8155
• 30 So Y-H, Becker JY, Miller LL. J Chem Soc, Chem Commun 1975; 0: 262-263
• 31 Long H, Chen T-S, Song J, Zhu S, Xu H-C. Nat Commun 2022; 13: 3945-3951
• 32 Hou X, Kaplaneris N, Yuan B. et al. Chem Sci 2022; 13: 3461-3467
• 33 Hu X, Zhang G, Nie L, Kong T, Lei A. Nat Commun 2019; 10: 5467-5476
• 34 Alvarez EM, Stewart G, Ullah M, Lalisse R, Gutierrez O, Malapit CA. J Am Chem Soc 2024; 146: 3591-3597
• 35 Song C, Liu K, Wang Z. et al. Chem Sci 2019; 10: 7982-7987
• 36 Chen T-S, Xiong P, Xu H-C. Angew Chem Int Ed 2025; e202513864
• 37 Wu Z-J, Su F, Lin W. et al. Angew Chem Int Ed 2019; 58: 16770
• 38 Long H, Huang C, Zheng Y-T. et al. Nat Commun 2021; 12: 6629
• 39 Gou X-Y, Oliveira JCA, Chen S. et al. Chem Sci 2025; 16: 824-833