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Synlett 2024; 35(10): 1185-1189
DOI: 10.1055/a-2253-4365
DOI: 10.1055/a-2253-4365
cluster
Thieme Chemistry Journals Awardees 2023
N-Heterocyclic Carbene Catalysis for Facile Access to Pentasubstituted 4H-Pyran Derivatives
We acknowledge financial support from the National Natural Science Foundation of China (22371058, 21961006, 32172459, 22371057, 22071036), the National Key Research and Development Program of China (2022YFD1700300), the Science and Technology Department of Guizhou Province (Qiankehejichu-ZK[2021]Key033), the Program of Introducing Talents of Discipline to Universities of China (111 Program, D20023) at Guizhou University, Frontiers Science Center for Asymmetric Synthesis and Medicinal Molecules, Department of Education, Guizhou Province [Qianjiaohe KY (2020)004], and Guizhou University (China), National Natural Science Fund for Excellent Young Scientists Fund Program (Overseas)the starting grant of Guizhou University [(2023)29].
Abstract
The synthesis of polysubstituted 4H-pyran derivatives has attracted considerable attention due to its wide application in agrochemicals, pharmaceuticals, and other functional molecules. We report an N-heterocyclic carbene-catalyzed [3+3] annulation reaction of β-ketone esters with enynals for rapid access to pentasubstituted 4H-pyran derivatives through a regioselective activation of the ynal. A series of 4H-pyran derivatives bearing various substituents were obtained in moderate to excellent yields. This method could find further applications in the synthesis of structurally diverse 4H-pyran-derived functional molecules from readily available starting materials.
Key words
N-heterocyclic carbene catalysis - organocatalysis - pyrans - regioselectivity - ketone esters - enynalsSupporting Information
- Supporting information for this article is available online at https://doi.org/10.1055/a-2253-4365.
- Supporting Information
Publication History
Received: 15 September 2023
Accepted after revision: 24 January 2024
Accepted Manuscript online:
24 January 2024
Article published online:
15 February 2024
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References and Notes
- 1a Kumar D, Reddy VB, Sharad S, Dube U, Kapur S. Eur. J. Med. Chem. 2009; 44: 3805
- 1b Nakhi A, Rahman MS, Archana S, Kishore R, Seerapu GP. K, Kumar KL, Haldar D, Pal M. Bioorg. Med. Chem. Lett. 2013; 23: 4195
- 1c Safaei-Ghomi J, Teymuri R, Shahbazi-Alavi H, Ziarati A. Chin. Chem. Lett. 2013; 24: 921
- 1d Reddy TN, Ravinder M, Bikshapathi R, Sujitha P, Kumar CG, Rao VJ. Med. Chem. Res. 2017; 26: 2832
- 1e Zheng X, Jiang Z, Li X, Zhang C, Li Z, Wu Y, Wang X, Zhang C, Luo H, Xu J, Wu D. Bioorg. Med. Chem. 2018; 26: 5934
- 1f Nguyen HT, Ha Truong M.-N, Le TV, Vo NT, Nguyen HD, Tran PH. ACS Omega 2022; 7: 17432
- 1g Mohamadpour F. J. Heterocycl. Chem. 2023; 60: 504
- 2a Goldmann S, Stoltefuss J. Angew. Chem. Int. Ed. 1991; 30: 1559
- 2b Pei C.-K, Jiang Y, Wei Y, Shi M. Angew. Chem. Int. Ed. 2012; 51: 11328
- 2c Ni C, Tong X. J. Am. Chem. Soc. 2016; 138: 7872
- 2d Yue Z, Li W, Liu L, Wang C, Zhang J. Adv. Synth. Catal. 2016; 358: 3015
- 2e Zhou W, Ni C, Chen J, Wang D, Tong X. Org. Lett. 2017; 19: 1890
- 3a Urbahns K, Horváth E, Stasch J.-P, Mauler F. Bioorg. Med. Chem. Lett. 2003; 13: 2637
- 3b de Souza Siqueira M, da Silva-Filho LC. Tetrahedron Lett. 2016; 57: 5050
- 4a List B. Chem. Rev. 2007; 107: 5413
- 4b Yamada S. Chem. Rev. 2018; 118: 11353
- 4c Krištofíková D, Modrocká V, Mečiarová M, Šebesta R. ChemSusChem 2020; 13: 2828
- 4d Lassaletta JM. Nat. Commun. 2020; 11: 3787
- 4e Han B, He X.-H, Liu Y.-Q, He G, Peng C, Li J.-L. Chem. Soc. Rev. 2021; 50: 1522
- 4f García Mancheño O, Waser M. Eur. J. Org. Chem. 2023; 26: e202200950
- 5a Enders D, Niemeier O, Henseler A. Chem. Rev. 2007; 107: 5606
- 5b Grossmann A, Enders D. Angew. Chem. Int. Ed. 2012; 51: 314
- 5c Hopkinson MN, Richter C, Schedler M, Glorius F. Nature 2014; 510: 485
- 5d Flanigan DM, Romanov-Michailidis F, White NA, Rovis T. Chem. Rev. 2015; 115: 9307
- 5e Menon RS, Biju AT, Nair V. Beilstein J. Org. Chem. 2016; 12: 444
- 5f Zhang C, Hooper JF, Lupton DW. ACS Catal. 2017; 7: 2583
- 5g Barik S, Biju AT. Chem. Commun. 2020; 56: 15484
- 5h Chen K.-Q, Sheng H, Liu Q, Shao P.-L, Chen X.-Y. Sci. China Chem. 2020; 64: 7
- 5i Ishii T, Nagao K, Ohmiya H. Chem. Sci. 2020; 11: 5630
- 5j Chen X.-Y, Gao Z.-H, Ye S. Acc. Chem. Res. 2020; 53: 690
- 5k Dai L, Ye S. Chin. Chem. Lett. 2021; 32: 660
- 5l Liu K, Schwenzer M, Studer A. ACS Catal. 2022; 12: 11984
- 5m Das TK, Biju AT. Prog. Heterocycl. Chem. 2019; 31: 1
- 6a Ma D, Qiu Y, Dai J, Fu C, Ma S. Org. Lett. 2014; 16: 4742
- 6b Hu Y, Li S, Wang Z, Yao Y, Li T, Yu C, Yao C. J. Org. Chem. 2018; 83: 3361
- 6c Lu F, Chen Y, Song X, Yu C, Li T, Zhang K, Yao C. J. Org. Chem. 2022; 87: 6902
- 6d Shi B, Jin F, Lv Q, Zhou X, Liao Z, Yu C, Zhang K, Yao C. Org. Biomol. Chem. 2023; 21: 5775
- 7 CCDC 2304296 contains the supplementary crystallographic data for compound 5. The data can be obtained free of charge from The Cambridge Crystallographic Data Centre via www.ccdc.cam.ac.uk/structures.
- 8 4H-Pyrans 3a–i and 4a–n; General Procedure Under a N2, the appropriate 1 (0.12 mmol) and 2 (0.10 mmol) together with NHC (0.02 mmol), K2CO3 (0.15 mmol), and DQ (0.15 mmol) were dissolved in anhyd THF (1.0 mL), and then EtOH (100 μL) was added. The mixture was stirred for 48 h at r.t. and then purified by column chromatography (silica gel). 5-Ethyl 3-Methyl 2-(2-ethoxy-2-oxoethyl)-4,6-diphenyl-4H-pyran-3,5-dicarboxylate (3a) Yellow oil; yield: 36.8 mg, 84%. 1H NMR (400 MHz, CDCl3): δ = 7.45–7.34 (m, 7 H), 7.30 (t, J = 7.5 Hz, 2 H), 7.24–7.19 (m, 1 H), 4.93 (s, 1 H), 4.20 (q, J = 7.1 Hz, 2 H), 4.00–3.82 (m, 4 H), 3.66 (s, 3 H), 1.26 (t, J = 7.1 Hz, 3 H), 0.89 (t, J = 7.1 Hz, 3 H). 13C NMR (101 MHz, CDCl3): δ = 168.8, 166.4, 166.3, 156.9, 155.2, 144.5, 133.8, 129.8, 128.9 (2 C), 128.4 (2 C), 128.4 (2 C), 127.9 (2 C), 127.0, 110.4, 109.6, 61.3, 60.5, 51.8, 39.2, 38.3, 14.2, 13.6. HRMS (ESI): m/z [M + Na]+ calcd for C26H26NaO7: 473.1570; found: 473.1562. 3-Ethyl 5-Methyl 6-(2-ethoxy-2-oxoethyl)-2,4-diphenyl-3,4-dihydro-2H-pyran-3,5-dicarboxylate (5) 10% Pd/C (50 mg) was added to a solution of 3a (443.96 μmol, 200 mg) in EtOH (20.0 mL) under a N2 atmosphere. The suspension was degassed in vacuum and purged with H2 (balloon) several times. The mixture was stirred at r.t. for 24 h and then filtered through Celite, which was washed with EtOH (3 × 10 mL). The combined organic solution was concentrated under reduced pressure to afford a crude product that was purified by flash chromatography (silica gel) to give a colorless solid; yield: 159.1 mg (79%); mp 117–118 °C. 1H NMR (400 MHz, CDCl3): δ = 7.39–7.26 (m, 5 H), 7.24–7.11 (m, 5 H), 5.30 (d, J = 2.6 Hz, 1 H), 4.49 (d, J = 7.9 Hz, 1 H), 4.39 (d, J = 16.6 Hz, 1 H), 4.23–4.12 (m, 2 H), 3.60 (dd, J = 16.6, 0.8 Hz, 1 H), 3.48 (q, J = 7.1 Hz, 2 H), 3.42 (dd, J = 8.0, 2.7 Hz, 1 H), 3.37 (s, 3 H), 1.27 (t, J = 7.1 Hz, 3 H), 0.65 (t, J = 7.1 Hz, 3 H). 13C NMR (101 MHz, CDCl3): δ = 169.4, 168.3, 167.7, 160.7, 140.6, 137.4, 128.4 (2 C), 128.1 (2 C), 128.1 (2 C), 127.3, 126.6, 125.6 (2 C), 106.7, 78.0, 60.9, 59.8, 52.2, 51.0, 42.2, 39.1, 14.2, 13.5. HRMS (ESI): m/z [M + Na]+ calcd for C26H28NaO7: 475.1727; found: 475.1732.