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CC BY-NC-ND 4.0 · Synlett
DOI: 10.1055/s-0042-1751566
DOI: 10.1055/s-0042-1751566
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Isotopic Labeling
Late-Stage C–H Deuteration of Organic Compounds via Ligand-Enabled Palladium-Catalyzed Hydrogen Isotope Exchange
We thank Kiel University for generous support. This project has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (Grant No. 946044).
Abstract
Over the past years our lab has established a research program towards the late-stage introduction of deuterium into organic molecules using Pd-catalyzed reversible C–H activation as a means to affect hydrogen isotope exchange. Through catalyst design, including the introduction of novel ligand scaffolds, as well as the use of strategically chosen optimization and screening approaches, e.g., exploiting microscopic reversibility by first optimizing de-deuteration processes or using a multi-substrate screening approach, our studies have resulted in a number of synthetically useful labelling protocols and are described herein from a personal perspective.
1 Introduction
2 β-C(sp3)–H Deuteration of Free Carboxylic Acids
3 Nondirected C–H Deuteration of Arenes
4 Nondirected C–H Deuteration of Heteroarenes
5 Conclusion
Publication History
Received: 05 December 2023
Accepted after revision: 15 January 2024
Article published online:
22 March 2024
© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)
Georg Thieme Verlag KG
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References
- 1a Atzrodt J, Derdau V, Fey T, Zimmermann J. Angew. Chem. Int. Ed. 2007; 46: 7744
- 1b Mutlib AE. Chem. Res. Toxicol. 2008; 21: 1672
- 1c Valero M, Derdau V. J. Labelled Compd. Radiopharm. 2020; 63: 266
- 1d Jansen-van Vuuren RD, Jedlovčnik L, Košmrlj J, Massey TE, Derdau V. ACS Omega 2022; 7: 41840
- 1e Di Martino RM. C, Maxwell BD, Pirali T. Nat. Rev. Drug Discovery 2023; 22: 562
- 2a Wiberg KB. Chem. Rev. 1955; 55: 713
- 2b Bell RP. Chem. Soc. Rev. 1974; 3: 513
- 2c Scheiner S, Čuma M. J. Am. Chem. Soc. 1996; 118: 1511
- 2d Simmons EM, Hartwig JF. Angew. Chem. Int. Ed. 2012; 51: 3066
- 3a Stokvis E, Rosing H, Beijnen JH. Rapid Commun. Mass Spectrom. 2005; 19: 401
- 3b Atzrodt J, Derdau V. J. Labelled Compd. Radiopharm. 2010; 53: 674
- 3c Damont A, Legrand A, Cao C, Fenaille F, Tabet J.-C. Mass Spectrom. Rev. 2023; 42: 1300
- 4a Marathe PH, Shyu WC, Humphreys WG. Curr. Pharm. Des. 2004; 10: 2991
- 4b Gant TG. J. Med. Chem. 2014; 57: 3595
- 4c Elmore CS, Bragg RA. Bioorg. Med. Chem. Lett. 2015; 25: 167
- 5 Isin EM, Elmore CS, Nilsson GN, Thompson RA, Weidolf L. Chem. Res. Toxicol. 2012; 25: 532
- 6 Pirali T, Serafini M, Cargnin S, Genazzani AA. J. Med. Chem. 2019; 62: 5276
- 7a Mullard A. Nat. Rev. Drug Discovery 2017; 16: 305
- 7b DeWitt SH, Maryanoff BE. Biochemistry 2018; 57: 472
- 9a Atzrodt J, Derdau V, Kerr WJ, Reid M. Angew. Chem. Int. Ed. 2018; 57: 3022
- 9b Yang H, Hesk D. J. Labelled Compd. Radiopharm. 2020; 63: 296
- 9c Prakash G, Paul N, Oliver GA, Werz DB, Maiti D. Chem. Soc. Rev. 2022; 51: 3123
- 9d Kang Q.-K, Shi H. Synlett 2022; 33: 329
- 9e Kopf S, Bourriquen F, Li W, Neumann H, Junge K, Beller M. Chem. Rev. 2022; 122: 6634
- 10a Junk T, Catallo WJ. Chem. Soc. Rev. 1997; 26: 401
- 10b Lockley WJ. S, Heys JR. J. Labelled Compd. Radiopharm. 2010; 53: 635
- 10c Li W, Rabeah J, Bourriquen F, Yang D, Kreyenschulte C, Rockstroh N, Lund H, Bartling S, Surkus A.-E, Junge K, Brückner A, Lei A, Beller M. Nat. Chem. 2022; 14: 334
- 11a Kuhl N, Hopkinson MN, Wencel-Delord J, Glorius F. Angew. Chem. Int. Ed. 2012; 51: 10236
- 11b Hartwig JF, Larsen MA. ACS Cent. Sci. 2016; 2: 281
- 11c Wedi P, van Gemmeren M. Angew. Chem. Int. Ed. 2018; 57: 13016
- 11d Mondal A, Wedi P, van Gemmeren M. The Non-directed Distal C(sp2)–H Functionalization of Arenes. In Remote C–H Bond Functionalizations: Methods and Strategies in Organic Synthesis. Maiti D, Guin S. Wiley-VCH; Weinheim: 2021: 191-219
- 11e Kaltenberger S, van Gemmeren M. Acc. Chem. Res. 2023; 56: 2459
- 12a Ranjan P, Pillitteri S, van de Eycken EV, Sharma UK. Green Chem. 2020; 22: 7725
- 12b Zhou R, Ma L, Yang X, Cao J. Org. Chem. Front. 2021; 8: 426
- 12c Li N, Li Y, Wu X, Zhu C, Xie J. Chem. Soc. Rev. 2022; 51: 6291
- 13 Goossen LJ, Rodríguez N, Goossen K. Angew. Chem. Int. Ed. 2008; 47: 3100
- 14a Giri R, Maugel N, Li J.-J, Wang D.-H, Breazzano SP, Saunders LB, Yu J.-Q. J. Am. Chem. Soc. 2007; 129: 3510
- 14b He J, Wasa M, Chan KS. L, Shao Q, Yu J.-Q. Chem. Rev. 2017; 117: 8754
- 14c Uttry A, van Gemmeren M. Synlett 2018; 29: 1937
- 14d Uttry A, van Gemmeren M. Synthesis 2020; 52: 479
- 14e Das J, Mal DK, Maji S, Maiti D. ACS Catal. 2021; 11: 4205
- 14f Das A, Maji B. Chem. Asian J. 2021; 16: 397
- 15a Lockley WJ. S. J. Labelled Compd. Radiopharm. 1984; 21: 45
- 15b Piola L, Fernández-Salas JA, Manzini S, Nolan SP. Org. Biomol. Chem. 2014; 12: 8683
- 15c Garreau AL, Zhou H, Young MC. Org. Lett. 2019; 21: 7044
- 15d Müller V, Weck R, Derdau V, Ackermann L. ChemCatChem 2020; 12: 100
- 15e Kramer M, Watts D, Vedernikov AN. Organometallics 2020; 39: 4102
- 16 Ma S, Villa G, Thuy-Boun PS, Homs A, Yu J.-Q. Angew. Chem. Int. Ed. 2014; 53: 734
- 17 Sajiki H, Aoki F, Esaki H, Maegawa T, Hirota K. Org. Lett. 2004; 6: 1485
- 18 Yamada T, Park K, Yasukawa N, Morita K, Monguchi Y, Sawama Y, Sajiki H. Adv. Synth. Catal. 2016; 358: 3277
- 19 Zhao D, Luo H, Chen B, Chen W, Zhang G, Yu Y. J. Org. Chem. 2018; 83: 7860
- 20a Ghosh KK, Uttry A, Mondal A, Ghiringhelli F, Wedi P, van Gemmeren M. Angew. Chem. Int. Ed. 2020; 59: 12848
- 20b Ghiringhelli F, Uttry A, Ghosh KK, van Gemmeren M. Angew. Chem. Int. Ed. 2020; 59: 23127
- 21 Uttry A, Mal S, van Gemmeren M. J. Am. Chem. Soc. 2021; 143: 10895
- 22a Engle KM, Wang D.-H, Yu J.-Q. J. Am. Chem. Soc. 2010; 132: 14137
- 22b Shen P.-X, Hu L, Shao Q, Hong K, Yu J.-Q. J. Am. Chem. Soc. 2018; 140: 6545
- 22c Hu L, Shen P.-X, Shao Q, Hong K, Qiao JX, Yu J.-Q. Angew. Chem. Int. Ed. 2019; 58: 2134
- 22d Shao Q, Wu K, Zhuang Z, Quian S, Yu J.-Q. Acc. Chem. Res. 2020; 53: 833
- 23 Pitzer L, Schäfers F, Glorius F. Angew. Chem. Int. Ed. 2019; 58: 8572
- 24a Colomer I, Chamberlain AE. R, Haughey MB, Donohoe TJ. Nat. Rev. Chem. 2017; 1: 0088
- 24b Sinha SK, Bhattacharya T, Maiti D. React. Chem. Eng. 2019; 4: 244
- 24c Bhattacharya T, Ghosh A, Maiti D. Chem. Sci. 2021; 12: 3857
- 25a Clayden J. Synlett 1998; 810
- 25b Betson MS, Clayden J, Helliwell M, Johnson P, Lai LW, Pink JH, Stimson CC, Vassiliou N, Westlund N, Yasin SA, Youssef LH. Org. Biomol. Chem. 2006; 4: 424
- 25c Engle KM. Pure Appl. Chem. 2016; 88: 119
- 25d Bisz E, Piontek A, Dziuk B, Szostak R, Szostak M. J. Org. Chem. 2018; 83: 3159
- 25e Salazar CA, Gair JJ, Flesch KN, Guzei IA, Lewis JC, Stahl SS. Angew. Chem. Int. Ed. 2020; 59: 10873
- 25f Tóth BL, Monory A, Egyed O, Domján A, Bényei A, Szathury B, Novák Z, Stirling A. Chem. Sci. 2021; 12: 5152
- 26a Wang P, Verma P, Xia G, Shi J, Qiao JX, Tao S, Cheng PT. W, Poss MA, Farmer ME, Yeung K.-S, Yu J.-Q. Nature 2017; 551: 489
- 26b Chen H, Wedi P, Meyer T, Tavakoli G, van Gemmeren M. Angew. Chem. Int. Ed. 2018; 57: 2497
- 26c Chen H, Mondal A, Wedi P, van Gemmeren M. ACS Catal. 2019; 9: 1979
- 26d Mondal A, Chen H, Flämig L, Wedi P, van Gemmeren M. J. Am. Chem. Soc. 2019; 141: 18662
- 26e Chen H, Farizyan M, Ghiringhelli F, van Gemmeren M. Angew. Chem. Int. Ed. 2020; 59: 12213
- 26f Mondal A, van Gemmeren M. Angew. Chem. Int. Ed. 2021; 61: 742
- 26g Wedi P, Farizyan M, Bergander K, Mück-Lichtenfeld C, van Gemmeren M. Angew. Chem. Int. Ed. 2021; 60: 15641
- 26h Farizyan M, de Jesus R, Dey J, van Gemmeren M. Chem. Sci. 2023; 14: 4357
- 27a Hickman AJ, Villalobos JM, Sanford MS. Organometallics 2009; 28: 5316
- 27b Emmert MH, Gary JB, Villalobos JM, Sanford MS. Angew. Chem. Int. Ed. 2010; 49: 5884
- 27c Rhinehart JL, Manbeck KA, Buzak SK, Lippa GM, Brennessel WW, Goldberg KI, Jones WD. Organometallics 2012; 31: 1943
- 27d Martin J, Eyselein J, Grams S, Harder S. ACS Catal. 2020; 10: 7792
- 27e Corpas J, Viereck P, Chirik PJ. ACS Catal. 2020; 10: 8640
- 27f Smith JD, Durrant G, Ess DH, Gelfand BS, Piers WE. Chem. Sci. 2020; 11: 10705
- 28 Yu RP, Hesk D, Rivera N, Pelczer I, Chirik PJ. Nature 2016; 529: 195
- 29 Zarate C, Yang H, Bezdek MJ, Hesk D, Chirik PJ. J. Am. Chem. Soc. 2019; 141: 5034
- 30 Garhwal S, Kaushansky A, Fridman N, Shimon LJ. W, de Ruiter G. J. Am. Chem. Soc. 2020; 142: 17131
- 31 Farizyan M, Mondal A, Mal S, Deufel F, van Gemmeren M. J. Am. Chem. Soc. 2021; 143: 16370
- 32 Britton L, Docherty JH, Sklyaruk J, Cooney J, Nichol GS, Dominey AP, Thomas SP. Chem. Sci. 2022; 13: 10291
- 33a Yang H, Zarate C, Palmer WN, Rivera N, Hesk D, Chirik PJ. ACS Catal. 2018; 8: 10210
- 33b Bouzouita D, Asensio JM, Pfeifer V, Palazzolo A, Lecante P, Pieters G, Feuillastre S, Tricard S, Chaudret B. Nanoscale 2020; 12: 15736
- 34a Lotz MD, Camasso NM, Canty AJ, Sanford MS. Organometallics 2017; 36: 165
- 34b Li E.-C, Hu G.-Q, Zhu Y.-X, Zhang H.-H, Shen K, Hang X.-C, Zhang C, Huang W. Org. Lett. 2019; 21: 6745
- 34c Hu G.-Q, Bai J.-W, Li E.-C, Liu K.-H, Sheng F.-F, Zhang H.-H. Org. Lett. 2021; 23: 1554
- 34d Tlahuext-Aca A, Hartwig JF. ACS Catal. 2021; 11: 1119
- 34e Sheng F.-F, Li E.-C, Bai J.-W, Wang C.-X, Hu G.-Q, Liu K.-H, Sun Z.-Y, Shen K, Zhang H.-H. Org. Biomol. Chem. 2022; 20: 1176
- 35a Mai VH, Gadzhiev OB, Ignatov SK, Nikonov GI. Catal. Sci. Technol. 2019; 9: 3398
- 35b Pfeifer V, Certiat M, Bouzouita D, Palazzolo A, Garcia-Argote S, Marcon E, Buisson D.-A, Lesot P, Maron L, Chaudret B, Tricard S, Del Rosal I, Poteau R, Feuillastre S, Pieters G. Chem. Eur. J. 2020; 26: 4988
- 36a Gomtsyan A. Chem. Heterocycl. Compd. 2012; 48: 7
- 36b Taylor RD, MacCoss M, Lawson AD. G. J. Med. Chem. 2014; 57: 5845
- 36c Vitaku E, Smith DT, Njardarson JT. J. Med. Chem. 2014; 57: 10257
- 37a Teja C, Kolb S, Colonna P, Grover J, Kumar Lahiri G, Pieters G, Werz DB, Maiti D. ChemRxiv 2023; preprint DOI: DOI: 10.26434/chemrxiv-2023-mk6js.
- 37b Yun SJ, Kim J, Kang E, Jung H, Kim HT, Kim M, Joo JM. ACS Catal. 2023; 13: 4042
- 38 Fogel MS, Koide K. Org. Process Res. Dev. 2023; 27: 1235
- 39a Gao X, Kagan HB. Chirality 1998; 10: 120
- 39b Satyanarayana T, Kagan HB. Adv. Synth. Catal. 2005; 347: 737
- 40 Gennari C, Ceccarelli S, Piarulli U, Montalbetti CA. G. N, Jackson RF. W. J. Org. Chem. 1998; 63: 5312
- 41 Dey J, Kaltenberger S, van Gemmeren M. Angew. Chem. Int. Ed. 2024; 63: e202404421
- 42a Ying C.-H, Yan S.-B, Duan W.-L. Org. Lett. 2014; 16: 500
- 42b Morja MI, Chauhan PM, Chikhalia KH. Res. Chem. Intermed. 2021; 47: 4513
- 43a Zhuang Z, Yu C.-B, Chen G, Wu Q.-F, Hsiao Y, Joe CL, Qiao JX, Poss MA, Yu J.-Q. J. Am. Chem. Soc. 2018; 140: 10363
- 43b Zhuang Z, Yu J.-Q. J. Am. Chem. Soc. 2020; 142: 12015
- 43c Zhuang Z, Herron AN, Yu J.-Q. Angew. Chem. Int. Ed. 2021; 60: 16382
- 43d Zhuang Z, Liu S, Cheng J.-T, Yeung K.-S, Qiao JX, Meanwell NA, Yu J.-Q. Angew. Chem. Int. Ed. 2022; 61: e202207354
- 44a Chen G, Gong W, Zhuang Z, Andrä MS, Chen Y.-Q, Hong X, Yang Y.-F, Liu T, Houk KN, Yu J.-Q. Science 2016; 353: 1023
- 44b Andrä MS, Schifferer L, Pollok CH, Merten C, Gooßen LJ, Yu J.-Q. Chem. Eur. J. 2019; 25: 8503