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Synlett 2021; 32(07): 733-737
DOI: 10.1055/a-1294-0158
DOI: 10.1055/a-1294-0158
letter
Late-Stage Alkylation of N-Containing Heteroarenes Enabled by Homolysis of Alkyl-1,4-dihydropyridines under Blue LED Irradiation
Financial support for this work was provided by the China Postdoctoral Science Foundation (2017M622747).
Abstract
Alkylated heteroarenes are widely found in bioactive molecules and pharmaceuticals. Therefore, there is great interest in developing a chemoselective alkylation of heteroarenes under mild conditions, particularly during a late-stage functionalization step for the purpose of rapid derivatization. Herein, we introduce an efficient visible-light-promoted C–H alkylation of nitrogen-containing heteroarenes by using C4-alkyl 1,4-dihydropyridines (DHPs) as radical precursors at ambient temperatures. A broad scope of heteroarenes, such as 4-hydroxyquinazoline and its derivatives, including those bearing electron-donating or electron-withdrawing groups, can be successfully alkylated in good yields by using various C4-alkyl DHPs.
Supporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-1294-0158.
- Supporting Information
Publikationsverlauf
Eingereicht: 01. September 2020
Angenommen nach Revision: 20. Oktober 2020
Accepted Manuscript online:
20. Oktober 2020
Artikel online veröffentlicht:
27. November 2020
© 2020. Thieme. All rights reserved
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References and Notes
- 1 Smith BR, Eastman CM, Njardarson JT. J. Med. Chem. 2014; 57: 9764
- 2 Fache F, Schulz E, Tommasino ML, Lemaire M. Chem. Rev. 2000; 100: 2159
- 3 Cernak T, Dykstra KD, Tyagarajan S, Vachal P, Krska SW. Chem. Soc. Rev. 2016; 45: 546
- 4 Felpin F.-X, Sengupta S. Chem. Soc. Rev. 2019; 48: 1150
- 5 Wang W, Lorion MM, Shah J, Kapdi AR, Ackermann L. Angew. Chem. Int. Ed. 2018; 57: 14700
- 6 Wei Y, Hu P, Zhang M, Su W. Chem. Rev. 2017; 117: 8864
- 7 Proctor RS. J, Phipps RJ. Angew. Chem. Int. Ed. 2019; 58: 13666
- 8 Caron S, Dugger RW, Ruggeri SG, Ragan JA, Brown Ripin DH. Chem. Rev. 2006; 106: 2943
- 9 Tewari N, Dwivedi N, Tripathi RP. Tetrahedron Lett. 2004; 45: 9011
- 10 Lee JH. Tetrahedron Lett. 2005; 46: 7329
- 11 Rekunge DS, Khatri CK, Chaturbhuj GU. Tetrahedron Lett. 2017; 58: 1240
- 12 Santos VG, Godoi MN, Regiani T, Gama FH. S, Coelho MB, de Souza RO. M. A, Eberlin MN, Garden SJ. Chem. Eur. J. 2014; 20: 12808
- 13 Li G, Chen R, Wu L, Fu Q, Zhang X, Tang Z. Angew. Chem. Int. Ed. 2013; 52: 8432
- 14 Huang W, Cheng X. Synlett 2017; 28: 148
- 15 Wang P.-Z, Chen J.-R, Xiao W.-J. Org. Biomol. Chem. 2019; 17: 6936
- 16 Lai S, Ren X, Zhao J, Tang Z, Li G. Tetrahedron Lett. 2016; 57: 2957
- 17 Zhang H.-H, Yu S. J. Org. Chem. 2017; 82: 9995
- 18 Gu F, Huang W, Liu X, Chen W, Cheng X. Adv. Synth. Catal. 2018; 360: 925
- 19 Verrier C, Alandini N, Pezzetta C, Moliterno M, Buzzetti L, Hepburn HB, Vega-Peñaloza A, Silvi M, Melchiorre P. ACS Catal. 2018; 8: 1062
- 20 van Leeuwen T, Buzzetti L, Perego LA, Melchiorre P. Angew. Chem. Int. Ed. 2019; 58: 4953
- 21 Nakajima K, Nojima S, Nishibayashi Y. Angew. Chem. Int. Ed. 2016; 55: 14106
- 22 Nakajima K, Nojima S, Sakata K, Nishibayashi Y. ChemCatChem 2016; 8: 1028
- 23 Gutiérrez-Bonet Á, Tellis JC, Matsui JK, Vara BA. ACS Catal. 2016; 6: 8004
- 24 Buzzetti L, Prieto A, Roy SR, Melchiorre P. Angew. Chem. Int. Ed. 2017; 56: 15039
- 25 Badir SO, Dumoulin A, Matsui JK, Molander GA. Angew. Chem. Int. Ed. 2018; 57: 6610
- 26 Phelan JP, Lang SB, Sim J, Berritt S, Peat AJ, Billings K, Fan L, Molander GA. J. Am. Chem. Soc. 2019; 141: 3723
- 27 Gutiérrez-Bonet Á, Remeur C, Matsui JK, Molander GA. J. Am. Chem. Soc. 2017; 139: 12251
- 28 Zhang H.-H, Zhao J.-J, Yu S. J. Am. Chem. Soc. 2018; 140: 16914
- 29 Wang Q, Duan J, Tang P, Chen G, He G. Sci. China Chem. 2020; 63: 1613
- 30 Chen X, Ye F, Luo X, Liu X, Zhao J, Wang S, Zhou Q, Chen G, Wang P. J. Am. Chem. Soc. 2019; 141: 18230
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Cyclohexylation of Quinine; Typical Procedure
A solution of quinine (1j; 0.2 mmol, 1.0 equiv) and DHP 2c (0.3 mmol, 1.5 equiv) in degassed TFE (2.0 mL) was bubbled with Ar for 15 min. TFA (22 μL, 0.30 mmol, 1.5 equiv) was added from a microsyringe, and the tube was sealed and irradiated by four 10 W blue LEDs at rt for 4 h. The cap then was removed and the mixture was stirred for another 4 h. After completion, the reaction was quenched by addition of Et3N (69 μL, 0.50 mmol, 10 equiv) and concentrated. The crude mixture was purified by column chromatography (silica gel) to give 4u as a white solid; yield: 61.8 mg (76%).
1H NMR (500 MHz, CDCl3): δ = 12.44 (s, 1 H), 8.17 (d, J = 9.3 Hz, 1 H), 7.89 (s, 1 H), 7.36 (dd, J = 9.3, 2.3 Hz, 1 H), 7.17 (d, J = 2.5 Hz, 1 H), 6.24 (s, 1 H), 5.57 (ddd, J = 17.1, 10.5, 6.7 Hz, 1 H), 5.09–5.00 (m, 2 H), 4.17 (d, J = 11.8 Hz, 1 H), 3.84 (s, 3 H), 3.56–3.46 (m, 1 H), 3.34–3.22 (m, 2 H), 3.12 (dq, J = 16.0, 5.2 Hz, 1 H), 3.08–3.00 (m, 1 H), 2.71 (s, 1 H), 2.17 (d, J = 11.9 Hz, 1 H), 2.12–2.03 (m, 3 H), 1.98 (d, J = 11.2 Hz, 1 H), 1.85 (dt, J = 30.7, 14.1 Hz, 5 H), 1.63 (qd, J = 12.4, 3.3 Hz, 1 H), 1.58–1.41 (m, 3 H), 1.31 (ddd, J = 13.1, 8.6, 3.2 Hz, 2 H). 13C NMR (125 MHz, CDCl3): δ = 160.9, 160.1, 154.1, 137.1, 134.4, 126.7, 125.2, 124.3, 117.7, 117.7, 100.3, 66.6, 60.6, 59.9, 56.7, 54.8, 43.9, 43.0, 37.1, 32.8, 32.0, 26.9, 25.9, 25.9, 24.2, 21.2.