Water-Mediated Rhenium-Catalyzed Photodeoxygenation of Polyfunctional Organic N-Oxides

Dedication

Dedicated to Professor Paul Knochel on the occasion of his 70th birthday.

Abstract

The oxidation of N-heterocycles is key to their functionalization as it enhances their reactivity in the ortho position. However, an efficient post-reduction is often required to access the targeted compound. Here, an air-stable rhenium(I)-based photocatalyst enables the fast deoxygenation of N-heterocyclic and alkyl N-oxides, avoiding sacrificial oxophilic reagents. We demonstrate that adding H₂O dramatically accelerates the reaction rate. The system tolerates air contamination, is scalable, and shows a high functional group tolerance toward other reducible functions (free alcohol, carboxylic acid, ester, nitrile, halogen, etc.) and light-sensitive N-heterocycles.

Keywords

Pyridine N-oxides - Photocatalysis - Reduction - Synthetic methodology - Rhenium catalysis

Publication History

Received: 02 June 2025

Accepted after revision: 03 July 2025

Accepted Manuscript online:
03 July 2025

Article published online:
07 August 2025

• References

• 1a Vitaku E, Smith DT, Njardarson JT. J Med Chem 2014; 57: 10257
• 1b Ameta KL, Kant R, Penoni A, Maspero A, Scapinello L. N-Heterocycles. Singapore: Springer; 2022
• 1c Walsh CT. Tetrahedron Lett 2015; 56: 3075
• 2a Wang D, Désaubry L, Li G, Huang M, Zheng S. Adv Synth Catal 2020; 363: 2
• 2b Singha K, Habib I, Hossain M. ChemistrySelect 2022; 7: e202203537
• 2c Habib I, Singha K, Hossain M. ChemistrySelect 2023; 8: e202204099
• 2d Yan G, Borah AJ, Yang M. Adv Synth Catal 2014; 356: 2375
• 2e Youssif S. ARKIVOC 2001; 2001: 242
• 2f Bull JA, Mousseau JJ, Pelletier G, Charette AB. Chem Rev 2012; 112: 2642
• 2g Ochiai E. J Org Chem 2002; 18: 534
• 3 Zhang L, Wang Y. Synthesis 2015; 47: 289
• 4 For a recent review of deoxygenation methods, see the introduction of: Ryu HK, Song YD, Lee JH. Org Chem Front 2024; 11: 2249
• 5 Howard E, Olszewski WF. J Am Chem Soc 2002; 81: 1483
• 6 Kokatla HP, Thomson PF, Bae S, Doddi VR, Lakshman MK. J Org Chem 2011; 76: 7842
• 7a Lecroq W, Schleinitz J, Billoue M. et al. ChemPhysChem 2021; 22: 1237
• 7b Chandrasekhar S, Reddy CR, Rao RJ, Rao JM. Synlett 2002; 2002: 349
• 8 Spence GG, Taylor EC, Buchardt O. Chem Rev 1970; 70: 231
• 9a Kim KD, Lee JH. Org Lett 2018; 20: 7712
• 9b An JH, Kim KD, Lee JH. J Org Chem 2021; 86: 2876
• 10 Kim SH, An JH, Lee JH. Org Biomol Chem 2021; 19: 3735
• 11 Prier CK, Rankic DA, MacMillan DW. Chem Rev 2013; 113: 5322
• 12 Konev MO, Cardinale L, Jacobi von Wangelin A. Org Lett 2020; 22: 1316
• 13 Kjellberg M, Ohleier A, Thuéry P, Nicolas E, Anthore-Dalion L, Cantat T. Chem Sci 2021; 12: 10266
• 14 Hawecker J, Lehn JM, Ziessel R. Helv Chim Acta 2004; 69: 1990
• 15 See ESI for details on the new setup and its validation.
• 16 Brandl F, Bergwinkl S, Allacher C, Dick B. Chem Eur J 2020; 26: 7946
• 17a Ishida H, Tanaka K, Tanaka T. Organometallics 2002; 6: 181
• 17b Collomb-Dunand-Sauthier M-N, Deronzier A, Ziessel R. Inorg Chem 2002; 33: 2961
• 17c Kuramochi Y, Ishitani O, Ishida H. Coord Chem Rev 2018; 373: 333
• 18 Prat D, Wells A, Hayler J. et al. Green Chem 2016; 18: 288
• 19 Degradation of 4-phenyl pyridine was observed in the absence of water under prolonged irradiation with cool white LEDs.
• 20 Shvydkiv O, Gallagher S, Nolan K, Oelgemoller M. Org Lett 2010; 12: 5170
• 21a Hawecker J, Lehn J-M, Ziessel R. J Chem Soc, Chem Commun 1983; 536
• 21b Yam VW-W, Lau VC-Y, Cheung K-K. Organometallics 2002; 14: 2749
• 22a Sullivan BP, Bolinger CM, Conrad D, Vining WJ, Meyer TJ. J Chem Soc, Chem Commun 1985; 1414
• 22b Deeba R, Chardon-Noblat S, Costentin C. Chem Sci 2021; 12: 12726
• 22c Deeba R, Chardon-Noblat S, Costentin C. ACS Catal 2023; 13: 8262
• 23 A working paper unveiling key mechanistic features and using advanced spectroscopic techniques is available as a preprint: El Moqaouil Z, Kjellberg M, Leibl W. et al. ChemRxiv 2025
• 24a https://kessil.com 2024 (accessed: 09/07/2024)
• 24b Balayeva NO, Zheng N, Dillert R, Bahnemann DW. ACS Catal 2019; 9: 10694
• 24c Barker TJ, Jarvo ER. J Am Chem Soc 2009; 131: 15598
• 24d Chen S, Wan Q, Badu-Tawiah AK. Angew Chem Int Ed 2016; 55: 9345
• 24e Creencia EC, Kosaka M, Muramatsu T, Kobayashi M, Iizuka T, Horaguchi T. J Heterocycl Chem 2009; 46: 1309
• 24f Kanyiva KS, Nakao Y, Hiyama T. Angew Chem Int Ed 2007; 46: 8872
• 24g Korsager S, Taaning RH, Skrydstrup T. J Am Chem Soc 2013; 135: 2891
• 24h Lüthy M, Darmency V, Renaud P. Eur J Org Chem 2010; 2011: 547
• 24i Ma C, Zhao CQ, Xu XT. et al. Org Lett 2019; 21: 2464
• 24j Matsuda N, Hirano K, Satoh T, Miura M. Angew Chem Int Ed 2012; 51: 3642
• 24k Murray RW, Iyanar K, Chen J, Wearing JT. Tetrahedron Lett 1996; 37: 805
• 24l Qian B, Zhang Z, Chen S, Yang S, Wang H, Niu Y. Synthesis 2022; 54: 3999
• 24m Spectral Database for Organic Compounds (SDBS) https://sdbs.db.aist.go.jp/ National Institute of Advanced Industrial Science and Technology, (accessed: 29/07/2024)
• 24n Smieja JM, Kubiak CP. Inorg Chem 2010; 49: 9283
• 24o Szafran M, Koput J, Dega-Szafran Z, Katrusiak A. J Mol Struct 2006; 797: 66
• 24p Zhang M, Liu S, Li H. et al. Chem Eur J 2019; 25: 12620