Epoxidation of Chalcone Derivatives under Visible-Light Irradiation: An Organophotoredox Catalytic Approach

Abstract

Epoxidation of α,β-unsaturated ketones under visible-light irradiation constitutes a significant chemical transformation with potential applications in the synthesis of epoxypropane derivatives. An organophotoredox catalytic system is herein reported to facilitate efficient aerobic epoxidation. This protocol enables the conversion of α,β-unsaturated ketones into their corresponding epoxy products with moderate to high yields under benign reaction conditions. The methodology demonstrates broad functional-group compatibility, providing a reliable and direct route to a variety of functionalized epoxypropane compounds. Additionally, the absence of heavy metals in this strategy renders it particularly suitable for the pharmaceutical industry, offering a new avenue for the synthesis of epichlorohydrin drugs.

Key words

organophotocatalysis - epoxidation - epoxy ketones - enones - phenanthraquinone - medicinal chemistry

Publikationsverlauf

Eingereicht: 23. Juli 2024

Angenommen nach Revision: 07. Oktober 2024

Accepted Manuscript online:
07. Oktober 2024

Artikel online veröffentlicht:
29. Oktober 2024

• References and Notes

• 1a Wipf P, Coish PD. G. J. Org. Chem. 1999; 64: 5053
• 1b Sekizawa R, Ikeno S, Nakamura H, Naganawa H, Matsui S, Iinuma H, Takeuchi T. J. Nat. Prod. 2002; 65: 1491
• 1c Tuladhar A, Rein KS. ACS Med. Chem. Lett. 2018; 9: 318

For selected reviews on the synthesis of epoxides, see:
• 2a Chawla R, Singh AK, Yadav LD. S. RSC Adv. 2013; 3: 11385
• 2b Zhu Y, Wang Q, Cornwall RG, Shi Y. Chem. Rev. 2014; 114: 8199
• 2c Moschona F, Savvopoulou I, Tsitopoulou M, Tataraki D, Rassias G. Catalysts 2020; 10: 1117
• 2d Pellissier H. Synthesis 2020; 52: 3837

For selected reviews on the epoxidation of alkenes, see:
• 3a Bentley PA, Bergeron S, Cappi MW, Hibbs DE, Hursthouse MB, Nugent TC, Pulido R, Roberts SM, Wu LE. Chem. Commun. 1997; 739
• 3b De Faveri G, Ilyashenko G, Watkinson M. Chem. Soc. Rev. 2011; 40: 1722
• 3c Ujwaldev SM, Sindhu KS, Thankachan AP, Anilkumar G. Tetrahedron 2016; 72: 6175
• 3d Verma S, Joshi A, De SR, Jat JL. New J. Chem. 2022; 46: 2005
• 4a Liu P, Liu Y, Wong EL.-M, Xiang S, Che C.-M. Chem. Sci. 2011; 2: 2187
• 4b Zhang J, Wang H, Ren S, Zhang W, Liu Y. Youji Huaxue 2015; 35: 2650
• 4c Wang W, Sun Q, Xu D, Xia C, Sun W. ChemCatChem 2017; 9: 420
• 4d He Q, Pu M.-P, Jiang Z, Wang H, Feng X, Liu X. J. Am. Chem. Soc. 2023; 145: 15611
• 5a Punniyamurthy T, Velusamy S, Iqbal J. Chem. Rev. 2005; 105: 2329
• 5b Campbell AN, Stahl SS. Acc. Chem. Res. 2012; 45: 851
• 5c Liang Y.-F, Jiao N. Acc. Chem. Res. 2017; 50: 1640
• 5d Bates JS, Johnson MR, Khamespanah F, Root TW, Stahl SS. Chem. Rev. 2023; 123: 6233
• 6a Clark JH. Green Chem. 1999; 1: 1
• 6b Podgoršek A, Zupan M, Iskra J. Angew. Chem. Int. Ed. 2009; 48: 8424
• 6c Xie P, Xue C, Luo J, Shi S, Du D. Green Chem. 2021; 23: 5936
• 6d Yamamoto Y, Kodama S, Nomoto A, Ogawa A. Org. Biomol. Chem. 2022; 20: 9503
• 7a Prier CK, Rankic DA, MacMillan DW. C. Chem. Rev. 2013; 113: 5322
• 7b Skubi KL, Blum TR, Yoon TP. Chem. Rev. 2016; 116: 10035
• 7c Marzo L, Pagire SK, Reiser O, König B. Angew. Chem. Int. Ed. 2018; 57: 10034
• 7d Hong B.-C, Indurmuddam RR. Org. Biomol. Chem. 2024; 22: 3799
• 8a Tada N, Okubo H, Miura T, Itoh A. Synlett. 2009; 3024
• 8b Bian G, Jiang P, Wang F, Shen Y, Jiang K, Liu L, Zhang W. New J. Chem. 2018; 42: 85
• 8c Graml A, König B. ChemPhotoChem 2020; 5: 362
• 8d Hosseini-Sarvari M, Bazyar Z. ChemistrySelect 2020; 5: 8853
• 9 Zhang Y, Yang X, Tang H, Liang D, Wu J, Huang D. Green Chem. 2020; 22: 22
• 10 Wu Y, Zhou G, Meng Q, Tang X, Liu G, Yin H, Zhao J, Yang F, Yu Z, Luo Y. J. Org. Chem. 2018; 83: 13051
• 11a Xie P, Du D, Xue C, Shi S. Catal. Res. 2022; 2: 13
• 11b Li H.-L, Yan C.-P, Qi J.-S, Zhang S, Guo D.-Q, Gu W.-C, Wu Y.-M, Wu Y, Zhou N. Front. Pharmacol. 2023; 14: 1277395
• 11c Rani P, Chahal S, Singh R, Sindhu J. Top. Curr. Chem. 2024; 382: 13
• 11d Thomas R. J. Test. Eval. 2024; 52: JTE20230603
• 12 Xie P, Shi S, Hu X, Xue C, Du D. ChemistrySelect 2021; 6: 3922
• 13a Xie P, Xue C, Du D, Shi S. Org. Biomol. Chem. 2021; 19: 6781
• 13b Wang Z, Fei G, Shi S, Liu M, Li P, Xie P. Mol. Catal. 2024; 564: 114334
• 14 Xie P, Xue C, Shi S, Du D. ChemSusChem 2021; 14: 2689
• 15 Abiko Y, Nakai Y, Luong NC, Bianco CL, Fukuto JM, Kumagai Y. Chem. Res. Toxicol. 2019; 32: 551
• 16a Hay JM. Reactive Free Radicals . Academic Press; London: 1974
• 16b Parsons AF. An Introduction to Free Radical Chemistry . Blackwell Science; Oxford: 2000
• 16c Perkins MJ. Radical Chemistry: The Fundamentals . Oxford; Oxford University Press: 2000
• 17 Photocatalytic Synthesis of Epoxy Ketones: General Procedure A mixture of the appropriate chalcone (0.5 mmol), 9,10-phenanthraquinone (0.025 mmol, 5 mol%), PhCHO (0.6 mmol, 1.2 equiv), NaOAc (0.5 mmol, 1.0 equiv), and acetone (1.0 mL) was added to a quartz tube, which was placed in a photochemical reactor. The mixture was then stirred at r.t. (25 °C) under air for 8 h with irradiation by blue LEDs (5 W). The residue was purified by flash column chromatography (silica gel, EtOAc–PE). Phenyl(3-phenyloxiran-2-yl)methanone (2a) Prepared by the general procedure and isolated by flash column chromatography [silica gel, PE–EtOAc (20:1)] as a white solid; yield: 101.9 mg (91%), R_f = 0.35. ¹H NMR (400 MHz, CDCl₃): δ = 9.33 (s, 2 H), 8.10 (t, J = 7.9 Hz, 1 H), 7.82 (t, J = 7.6 Hz, 2 H), 7.56 (d, J = 5.6 Hz, 5 H), 5.50 (s, 1 H), 4.30 (s, 1 H). ¹³C NMR (101 MHz, CDCl₃): δ = 195.2, 137.5, 134.1, 129.5, 127.6, 124.9, 123.1, 119.0, 61.2.