Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000083.xml
Synlett
DOI: 10.1055/a-2538-1198
DOI: 10.1055/a-2538-1198
synpacts
Nickel-Catalyzed Deuteroalkylation Using Thianthrenium Salts
We would like to thank the National Key R&D Program of China (2022YFA1503200), the National Natural Science Foundation of China (Grants 22025104, 22171134, and 21972064), and the Fundamental Research Funds for the Central Universities (Grant 020514380254) for their financial support.
Abstract
Isotopically labeled compounds are essential in both organic and pharmaceutical chemistry. The standard methods for synthesizing such molecules often involve the use of deuterated building blocks, allowing the incorporation of functional groups and deuterium into the target molecule in one step. In this Synpacts article, we highlight our approach to accessing various a-deuterated alkyl thianthrenium (TT) salts through a pH-dependent hydrogen-isotope-exchange process using D2O as a cheap source of deuterium. Through the in situ formation of isotopically labeled alkyl halides, these TT salts exhibit exceptional compatibility with a range of nickel-catalyzed hydrodeuteroalkylations of nonactivated olefins and with nickel-catalyzed cross-electrophile coupling reactions with alkyl, alkenyl, and (het)aryl bromides. This technique has proven to be invaluable for accessing a range of deuterium-labeled compounds, particularly those of pharmaceutical significance.
Key words
deuteriation - thianthrenium salts - hydrodeuteroalkylation - nickel catalysis - metallaphotoredox reaction - pharmaceutical chemistryPublication History
Received: 11 December 2024
Accepted after revision: 12 February 2025
Accepted Manuscript online:
12 February 2025
Article published online:
20 June 2025
© 2025. Thieme. All rights reserved
Georg Thieme Verlag KG
Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany
-
References
- 1a Di Martino RM. C, Maxwell BD, Pirali T. Nat. Rev. Drug Discovery 2023; 22: 562
- 1b Pirali T, Serafini M, Cargnin S, Genazzani AA. J. Med. Chem. 2019; 62: 5276
- 2a Wood WW. J. Med. Chem. 2024; 67: 16991
- 2b Kopf S, Bourriquen F, Li W, Neumann H, Junge K, Beller M. Chem. Rev. 2022; 122: 6634
- 3 Schmidt C. Nat. Biotechnol. 2017; 35: 493
- 4 King B, Mesinkovska N, Mirmirani P, Bruce S, Kempers S, Guttman-Yassky E, Roberts JL, McMichael A, Colavincenzo M, Hamilton C, Braman V, Cassella JV. J. Am. Acad. Dermatol. 2022; 87: 306
- 5 Tang X, Bridson G, Ke J, Wu L, Erol H, Graham P, Lin CH, Braman V, Zhao H, Liu JF, Lin Z, Cheng C. J. Chromatogr., B 2014; 963: 1
- 6 Mullard A. Nat. Rev. Drug Discovery 2022; 21: 623
- 7a Pedras MS. C, To QH. J. Labelled Compd. Radiopharm. 2018; 61: 94
- 7b Bergare J, Kingston L, Guly DJ, Dolan J, Lewis RJ, Elmore CS. J. Labelled Compd. Radiopharm. 2020; 63: 434
- 8 Tanaka T, Koga Y, Honda Y, Tsuruta A, Matsunaga N, Koyanagi S, Ohdo S, Yazaki R, Ohshima T. Nat. Synth. 2022; 1: 824
- 9a Yang X, Wang J, Pei M, Wang S, Shang R, Wei X. Org. Lett. 2024; 26: 10934
- 9b Du Z, Gong W, Yuan S, Ren Y, Huang C, Zeng X. Org. Lett. 2024; 26: 11062
- 9c Pan S, Sk MS, Sanyal B, Roy L, Samanta R. ACS Catal. 2024; 18419
- 9d Tewari S, Klask N, Ritter T. J. Am. Chem. Soc. 2024; 146: 27282
- 9e Kaiser D, Klose I, Oost R, Neuhaus J, Maulide N. Chem. Rev. 2019; 119: 8701
- 9f Lou J, Wang Q, Wu P, Wang H, Zhou Y.-G, Yu Z. Chem. Soc. Rev. 2020; 49: 4307
- 9g Meng H, Liu M.-S, Shu W. Chem. Sci. 2022; 13: 13690
- 9h Campos PR. O, Alberto EE. Chem. Rec. 2024; 24: e202400139
- 9i Jin Z, Yu T, Wang H, Jia P, Huang Y. Org. Chem. Front. 2024; 11: 6573
- 9j Kim MJ, Targos K, Holst DE, Wang DJ, Wickens ZK. Angew. Chem. Int. Ed. 2024; 63: e202314904
- 10a Cai Y, Roy TK, Zähringer TJ. B, Lansbergen B, Kerzig C, Ritter T. J. Am. Chem. Soc. 2024; 146: 30474
- 10b Sau S, Takizawa S, Kim HY, Oh K. Org. Lett. 2024; 26: 8821
- 10c Fu Q.-Q, Liang Y, Sun X.-X, Chu X.-Q, Xu H, Zhou X, Rao W, Shen Z.-L. Org. Lett. 2024; 26: 8577
- 10d Guo G, Ma J, Dong Y, Wu Q, Lv J, Shi Y, Yang D. Org. Lett. 2024; 26: 8382
- 10e Wu Q, Li X, Ma J, Shi Y, Lv J, Yang D. Org. Lett. 2024; 26: 7949
- 11 Li J, Chen J, Sang R, Ham W.-S, Plutschack MB, Berger F, Chabbra S, Schnegg A, Genicot C, Ritter T. Nat. Chem. 2020; 12: 56
- 12 Ni S, Yan J, Tewari S, Reijerse EJ, Ritter T, Cornella J. J. Am. Chem. Soc. 2023; 145: 9988
- 13 Zhao D, Petzold R, Yan J, Muri D, Ritter T. Nature 2021; 600: 444
- 14a Chen C, Wang M, Lu H, Zhao B, Shi Z. Angew. Chem. Int. Ed. 2021; 60: 21756
- 14b Chen C, Wang Z.-J, Lu H, Zhao Y, Shi Z. Nat. Commun. 2021; 12: 4526
- 15a Ban K, Imai K, Oyama S, Tokunaga J, Ikeda Y, Uchiyama H, Kadota K, Tozuka Y, Akai S, Sawama Y. Angew. Chem. Int. Ed. 2023; 62: e202311058
- 15b Lv H, Liu J, Qin L.-Z, Sun H, Wang J, Zhu S.-S, Duan X, Yuan X, Qiu J.-K, Guo K. Green Chem. 2024; 26: 7414
- 15c Jia H, Ritter T. Angew. Chem. Int. Ed. 2022; 61: e202208978
- 15d Bai Z, Lansbergen B, Ritter T. J. Am. Chem. Soc. 2023; 145: 25954
- 15e Ma H, Li Y, Wang P, Ye J, Zhang J, Liu G, Wu J. Org. Chem. Front. 2023; 10: 866
- 15f Guo C, Wang X, Ding Q, Wu J. J. Org. Chem. 2024; 89: 9672
- 15g Jia H, Häring AP, Berger F, Zhang L, Ritter T. J. Am. Chem. Soc. 2021; 143: 7623
- 15h Kong X, Chen Y, Liu Q, Wang W, Zhang S, Zhang Q, Chen X, Xu Y.-Q, Cao Z.-Y. Org. Lett. 2023; 25: 581
- 15i Luo M, Zhu S, Yang C, Guo L, Xia W. Org. Lett. 2024; 26: 4388
- 16a Lo JC, Gui J, Yabe Y, Pan C.-M, Baran PS. Nature 2014; 516: 343
- 16b Crossley SW. M, Obradors C, Martinez RM, Shenvi RA. Chem. Rev. 2016; 116: 8912
- 16c Lee BC, Liu C.-F, Lin LQ. H, Yap KZ, Song N, Ko C. HM, Chan PH, Koh MJ. Chem. Soc. Rev. 2023; 52: 2946
- 16d Hou X, Liu H, Huang H. Nat. Commun. 2024; 15: 1480
- 16e Li F, Luo Y, Ren J, Yuan Q, Yan D, Zhang W. Angew. Chem. Int. Ed. 2023; 62: e202309859
- 17a Wen J, Wang F, Zhang X. Chem. Soc. Rev. 2021; 50: 3211
- 17b Li Y, Liu D, Hu X, Zhang J.-Y, Zhu Q.-W, Men B, Gao G.-W, Chen P.-W, Tong Y.-Z, Chang Z, Li Z, Lu X, Fu Y. Nat. Synth. 2024; 3: 1134
- 17c Wang S.-C, Liu L, Duan M, Xie W, Han J, Xue Y, Wang Y, Wang X, Zhu S. J. Am. Chem. Soc. 2024; 146: 30626
- 17d Chen G, Tian D, Wang X, Zhang H.-J. ACS Catal. 2024; 14: 14928
- 18 Lu X, Xiao B, Zhang Z, Gong T, Su W, Yi J, Fu Y, Liu L. Nat. Commun. 2016; 7: 11129
- 19a Ehehalt LE, Beleh OM, Priest IC, Mouat JM, Olszewski AK, Ahern BN, Cruz AR, Chi BK, Castro AJ, Kang K, Wang J, Weix DJ. Chem. Rev. 2024; 124: 13397
- 19b Cheng L.-J, Mankad NP. Acc. Chem. Res. 2021; 54: 2261
- 19c Zhao C, Dong C, Ma W, Shi L, Liu D, Zhang X, Cui Z, Wang Z, Fu J. ACS Catal. 2024; 14: 14475
- 19d Pace AL, Xu F, Liu W, Lavagnino MN, MacMillan DW. C. J. Am. Chem. Soc. 2024; 146: 32925
- 19e Wang C, Dai Y.-H, Wang Z, Lu B, Cao W, Zhao J, Mei G, Yang Q, Guo J, Duan W.-L. J. Am. Chem. Soc. 2024; 146: 27843
- 19f Li X, Hu Y, Huang Z, Zhu S, Qing F.-L, Chu L. ACS Catal. 2024; 14: 15790
- 19g Xia H, Jiang X, Lin D, Zhang S, Yu Z, Wu X, Qu J, Chen Y. J. Am. Chem. Soc. 2024; 146: 28468
- 19h Chen S, Ding D, Yin L, Wang X, Krause JA, Liu W. J. Am. Chem. Soc. 2024; 146: 31982
- 19i Wang Z, Yin H, Fu GC. Nature 2018; 563: 379
- 19j Sun S.-Z, Börjesson M, Martin-Montero R, Martin R. J. Am. Chem. Soc. 2018; 140: 12765
- 19k Zhou F, Zhang Y, Xu X, Zhu S. Angew. Chem. Int. Ed. 2019; 58: 1754
- 19l Wang J.-W, Li Y, Nie W, Chang Z, Yu Z.-A, Zhao Y.-F, Lu X, Fu Y. Nat. Commun. 2021; 12: 1313
- 20 Dong Y, Shin K, Mai BK, Liu P, Buchwald SL. J. Am. Chem. Soc. 2022; 144: 16303
- 21a He F.-S, Ye S, Wu J. ACS Catal. 2019; 9: 8943
- 21b Sun S.-Z, Romano C, Martin R. J. Am. Chem. Soc. 2019; 141: 16197
- 21c Rodrigalvarez J, Wang H, Martin R. J. Am. Chem. Soc. 2023; 145: 3869
- 22 Zhang J, Jiao M, Lu Z, Lu H, Wang M, Shi Z. Angew. Chem. Int. Ed. 2024; 63: e202409862
- 23a Pflugfelder SC, de Paiva CS. Ophthalmology 2017; 124: S4
- 23b Sheppard JD, Kurata F, Epitropoulos AT, Krösser S, Vittitow JL. Am. J. Ophthalmol. 2023; 252: 265
- 24 Strutz F, Heeg M, Kochsiek T, Siemers G, Zeisberg M, Müller GA. Nephrol. Dial. Transplant. 2000; 15: 1535
- 25 Jiao M, Zhang J, Wang M, Lu H, Shi Z. Nat. Commun. 2024; 15: 5067
- 26 Wang F, Langley R, Gulten G, Dover LG, Besra GS, Jacobs WR. Jr, Sacchettini JC. J. Exp. Med. 2007; 204: 73
- 27 Grassi G. Curr. Med. Res. Opin. 2018; 34: 1635
- 28 Witte E.-C, Stach KI, Thiel M, Schmidt F, Stork H. DE 2149070, 1973
For selected examples, see: