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Synlett 2016; 27(04): 626-630
DOI: 10.1055/s-0035-1561274
DOI: 10.1055/s-0035-1561274
letter
A Facile Synthesis of Benzofuro[2,3-c]quinolines via a Multicomponent Reaction and Staudinger–Aza-Wittig–Dehydroaromatization Sequence
Weitere Informationen
Publikationsverlauf
Received: 16. September 2015
Accepted after revision: 08. November 2015
Publikationsdatum:
09. Dezember 2015 (online)
![](https://www.thieme-connect.de/media/synlett/201604/lookinside/thumbnails/st-2015-w0733-l_10-1055_s-0035-1561274-1.jpg)
Abstract
An iodine-mediated pyridinium ylide assisted multicomponent reaction for the synthesis of tetrahydrobenzofurans through a halogenation–SN2 displacement–Michael addition–cyclization sequence was developed and its further use in the preparation of benzofuro[2,3-c]quinolines through subsequent Staudinger–aza-Wittig–dehydroaromatization reactions was also investigated.
Supporting Information
- Supporting information for this article is available online at http://dx.doi.org/10.1055/s-0035-1561274.
- Supporting Information
-
References and Notes
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- 17 General Procedure for the Preparation of Tetrahydrobenzofurans 4 Iodine (0.761 g, 3 mmol) was added to a stirred solution of acetophenone 1 (3 mmol) in pyridine (3 mL) at r.t. After 30 min of stirring under reflux conditions, compound 2 (3 mmol), 3 (3 mmol), and Et3N (1 mL, 7.5 mmol) were added sequentially, followed by MeCN (10 mL). The reaction was vigorously stirred at refluxing temperature under argon atmosphere conditions. Progress of the reaction was monitored by TLC. Once completed, the reaction mixture was cooled to r.t. and quenched with H2O (15 mL), extracted with CH2Cl2 (30 mL). The combined organic extracts were washed with H2O and brine and dried (Na2SO4). After evaporating the solvent under reduced pressure, the residue was purified on silica gel with PE–EtOAc as eluent to give tetrahydrobenzofurans 4. Analytical Data for Compound 4a Yield 915 mg (85%); white crystals; mp 111–112 °C. IR (KBr): 2972, 2918, 2882, 2133, 1702, 1650, 1633, 1564, 1465, 1439, 1402, 776 cm–1. 1H NMR (400 MHz, CDCl3): δ = 7.85 (d, J = 8.0 Hz, 2 H, ArH), 7.63–7.48 (m, 1 H, ArH), 7.47–7.44 (m, 2 H, ArH), 7.34–7.30 (m, 1 H, ArH), 7.17–7.13 (m, 3 H, ArH), 5.76 (d, J = 5.2 Hz, 1 H, CH), 4.82 (d, J = 5.2 Hz, 1 H, CH), 2.68 (t, J = 5.2 Hz, 2 H, CH2), 2.38–2.34 (m, 2 H, CH2), 2.16–2.13 (m, 2 H, CH2) ppm. 13C NMR (100 MHz, CDCl3): δ = 194.1, 192.7, 177.7, 137.5, 134.0, 133.7, 131.9, 128.9, 128.8, 128.7, 128.6, 125.2, 118.4, 115.1, 90.2, 43.3, 36.7, 23.9, 21.6 ppm. LC–MS: m/z = 359. Anal. Calcd for C21H17N3O3: C, 70.18; H, 4.77; N, 11.69. Found: C, 70.23; H, 4.65; N, 11.82.
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- 19 General Procedure for the Preparation of 7 To a stirred solution of tetrahydrobenzofuran 4 (1 mmol) in CH2Cl2 (5 mL) was added dropwise Ph3P (0.26 g, 1 mmol) in CH2Cl2 (5 mL) at r.t. After the reaction mixture was stirred for 2 h at r.t. and then for 3–8 h under reflux conditions (monitored by TLC). Once completed, the solvent was removed under reduced pressure, and the residual was recrystallized from CH2Cl2–PE to give benzofuro[2,3-c]quinoline 7. Analytical Data for Compound 7a Yield 250 mg (80%); white crystals; mp 166–167 °C. IR (KBr): 2988, 2868, 1679, 1580, 1556, 1518, 1446, 1399, 1190, 771, 729, 690 cm–1. 1H NMR (400 MHz, CDCl3): δ = 9.50–9.47 (m, 1 H, ArH), 8.38–8.24 (m, 3 H, ArH), 7.76–7.50 (m, 5 H, ArH), 3.19 (t, J = 8.4 Hz, 2 H, CH2), 2.76 (t, J = 8.4 Hz, 2 H, CH2), 2.38–2.32 (m, 2 H, CH2) ppm. 13C NMR (100 MHz, CDCl3): δ = 193.3, 171.9, 146.5, 145.1, 143.7, 135.7, 129.7, 129.5, 128.9, 128.5, 128.3, 127.6, 126.4, 122.7, 118.2, 38.6, 24.2, 21.9 ppm. LC–MS: m/z = 313. Anal. Calcd for C21H15NO2: C, 80.49; H, 4.83; N, 4.47. Found: C, 80.41; H, 4.97; N, 4.59.
- 20 Crystallographic data of compound 7j in this manuscript have been deposited with the Cambridge Crystallographic Data Centre as supplementary publication number CCDC 1416029. Copies of the data can be obtained, free of charge, on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax: +44(1223)336033 or e-mail: deposit@ccdc.cam.ac.uk].
Representative works for the synthesis of dihydrofurans:
The reports of this system are relatively rare, see:
Molecular iodine was selected for the reason that its halogenation conditions were more suitable in one pot for the formation of ylide than other common halogenation reagents such as NBS, NIS, and Br2. For reviews over synthetic applications of molecular iodine, see: