Efficient One-Pot Synthesis of 2-Aryldihydrobenzofuran

Chongfeng Pan; Zhixiong Ma; Jie Yu; Zuhui Zhang; Ailing Hui; Zhiyong Wang

doi:10.1055/s-2005-871940

LETTER

Efficient One-Pot Synthesis of 2-Aryldihydrobenzofuran

Chongfeng Pan, Zhixiong Ma, Jie Yu, Zuhui Zhang, Ailing Hui, Zhiyong Wang*
Hefei National Laboratory for Physical Science at Microscale and Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, P. R. China
Fax: +86(551)3603185; e-Mail: zwang3@ustc.edu.cn;

Abstract

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Abstract

A series of 2-aryldihydrobenzofuran derivatives were successfully synthesized from the corresponding carbonyl compounds and (2-bromobenzyl)trimethylsilane by the one-pot benzylation-substitution procedure.

Key words

one-pot synthesis - 2-aryldihydrobenzofuran - benzylation - intramolecular Ullmann coupling - chemoselectivity

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References

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11

General Procedure for the One-Pot Synthesis of 2-Aryldihydrobenzofuran. Aldehyde (1 mmol) and BTMS (3 mmol) were dissolved in THF (4 mL), then 0.15 mL TBAF solution (1 M in THF) was added in one portion. The mixture was stirred at 35-40 °C for 30 min. After adding another 1 mmol of anhyd TBAF to the system, the solvent was evaporated under high vacuum. Then the residue was redissolved in 6 mL toluene. Under the nitrogen atmosphere, NaH (2 mmol) was added to the system with stirring. After stirring at 35-40 °C for 30 min, CuCl (5 mg) was added. The system was refluxed for 6-8 h, and then cooled to r.t. After being transferred to a 100 mL separatory funnel, the reaction mixture was diluted with 60 mL Et₂O. The organic layer was washed with 2 M HCl (5 mL), H₂O (10 mL) and brine (5 mL), then dried (anhyd MgSO₄). After evaporation of the solvent, the residue was purified by chromatography on silica gel to give the product. In the cases of 1g, 1j and 1k, the toluene was evaporated after the completion of the reaction and the mixture was directly purified by chromatography on silica gel.
Compound 1a: ¹H NMR (300 MHz, CDCl₃): δ = 7.34 (s, 4 H), 7.20-7.15 (m, 2 H), 6.92-6.86 (m, 2 H), 5.73 (dd, J = 8.1, 9.4 Hz, 1 H), 3.63 (dd, J = 9.4, 15.6 Hz, 1 H), 3.16 (dd, J = 8.1, 15.6 Hz, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 159.50, 140.63, 133.79, 128.87, 128.40, 127.23, 126.20, 124.99, 120.94, 109.50, 83.28, 38.50. IR (film): ν = 3051, 2926, 1720, 1599, 1492, 1479, 1462, 1232 cm^-1. HRMS: m/z calcd for C₁₄H₁₁O³⁵Cl: 230.0499; found: 230.0490.
Compound 1b: ¹H NMR (300 MHz, CDCl₃): δ = 7.30 (d, J = 8.1 Hz, 2 H), 7.22-7.13 (m, 4 H), 6.90-6.84 (m, 2 H), 5.72 (dd, J = 8.9, 8.8 Hz, 1 H), 3.60 (dd, J = 8.9, 15.6 Hz, 1 H), 3.16 (dd, J = 8.8, 15.6 Hz, 1 H), 2.35 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 159.75, 139.02, 137.91, 129.41, 128.28, 126.75, 125.96, 124.95, 120.68, 109.47, 84.17, 38.46, 21.29. IR (film): ν = 3031, 2921, 1716, 1596, 1516, 1480, 1462, 1232 cm^-1. HRMS: m/z calcd for C₁₅H₁₄O: 210.1048; found: 210.1054.
Compound 1c: ¹H NMR (300 MHz, CDCl₃): δ = 7.34 (d, J = 8.8 Hz, 2 H), 7.20-7.13 (m, 2 H), 6.91-6.83 (m, 4 H), 5.70 (dd, J = 8.8, 8.9 Hz, 1 H), 3.81 (s, 3 H), 3.58 (dd, J = 8.9, 15.6 Hz, 1 H), 3.16 (dd, J = 8.8, 15.6 Hz, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 159.67, 159.58, 133.97, 128.29, 127.46, 126.80, 124.93, 120.66, 114.11, 109.46, 84.10, 55.42, 38.43. IR (film): ν = 2914, 2843, 1613, 1516, 1460, 1301, 1248, 1029, 829 cm^-1. HRMS: m/z calcd for C₁₅H₁₄O₂: 226.0997; found: 226.1008.
Compound 1d: ¹H NMR (300 MHz, CDCl₃): δ = 7.43 (m, 1 H), 7.26 (m, 1 H), 7.16-7.14 (m, 2 H), 6.94-6.85 (m, 4 H), 6.04 (dd, J = 7.7, 9.5 Hz, 1 H), 3.86 (s, 3 H), 3.58 (dd, J = 9.5, 15.8 Hz, 1 H), 3.16 (dd, J = 7.7, 15.8 Hz, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 159.84, 156.06, 130.79, 128.69, 128.04, 127.00, 125.82, 125.05, 120.64, 120.62, 110.37, 109.40, 79.47, 55.46, 37.61. IR (film): ν = 3050, 2937, 2837, 1598, 1492, 1480, 1462, 1235 cm^-1. HRMS: m/z calcd for C₁₅H₁₄O₂: 226.0997; found: 226.0995.
Compound 1e: ¹H NMR (300 MHz, CDCl₃): δ = 7.20-7.16 (m, 2 H), 6.90-6.78 (m, 5 H), 5.95 (s, 2 H), 5.66 (dd, J = 8.7, 8.8 Hz, 1 H), 3.86 (s, 3 H), 3.58 (dd, J = 8.8, 15.7 Hz, 1 H), 3.19 (dd, J = 8.7, 15.7 Hz, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 159.55, 148.06, 147.53, 135.87, 128.31, 126.56, 124.92, 120.74, 119.65, 109.44, 108.26, 106.43, 101.20, 84.10, 38.42. IR (film): ν = 3032, 2897, 2778, 1597, 1504, 1480, 1461, 1444, 1232 cm^-1. HRMS: m/z calcd for C₁₅H₁₂O₃: 240.0789; found: 240.0782.
Compound 1f: ¹H NMR (300 MHz, CDCl₃): δ = 7.34 (dd, J = 1.9, 6.7 Hz, 2 H), 7.22-7.12 (m, 2 H), 7.03 (dd, J = 1.9, 6.7 Hz, 2 H), 6.91-6.83 (m, 2 H), 5.71 (dd, J = 8.8, 8.9 Hz, 1 H), 5.18 (s, 2 H), 3.59 (dd, J = 8.9, 15.6 Hz, 1 H), 3.47 (s, 3 H), 3.21 (dd, J = 8.8, 15.6 Hz, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 159.60, 157.11, 135.21, 128.60, 127.33, 126.67, 124.87, 120.63, 116.80, 109.39, 94.39, 83.86, 55.99, 38.27. IR (film): ν = 2954, 2826, 1611, 1513, 1480, 1461, 1232, 1152, 1003 cm^-1. HRMS: m/z calcd for C₁₆H₁₆O₃: 256.1103; found: 256.1091.
Compound 1g: ¹H NMR (300 MHz, CDCl₃): δ = 7.29 (dd, J = 1.9, 8.7 Hz, 2 H), 7.20-7.12 (m, 2 H), 6.89-6.81 (m, 2 H), 6.73 (dd, J = 1.9, 8.7 Hz, 2 H), 5.67 (dd, J = 8.9, 8.9 Hz, 1 H), 3.54 (dd, J = 8.9, 15.7 Hz, 1 H), 3.26 (dd, J = 8.9, 15.7 Hz, 1 H), 2.95 (s, 6 H). ¹³C NMR (75 MHz, CDCl₃): δ = 159.76, 150.70, 129.15, 128.16, 127.37, 127.19, 124.84, 120.40, 112.59, 109.42, 84.67, 40.68, 38.00. IR (film): ν = 3030, 2888, 2803, 1615, 1524, 1479, 1460, 1353, 1232 cm^-1. HRMS: m/z calcd for C₁₆H₁₇NO: 239.1351; found: 239.1352.
Compound 1h: ¹H NMR (300 MHz, CDCl₃): δ = 7.92-6.91 (m, 11 H), 6.45 (dd, J = 1.9, 8.7 Hz, 2 H), 5.67 (dd, J = 8.1, 9.5 Hz, 1 H), 3.87 (dd, J = 9.5, 15.6 Hz, 1 H), 3.26 (dd, J = 8.1, 15.6 Hz, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 159.78, 137.57, 134.07, 129.97, 129.18, 128.42, 126.53, 126.38, 125.82, 125.60, 125.25, 123.28, 122.78, 120.93, 109.71, 109.58, 81.96, 38.23. IR (film): ν = 3051, 2926, 1713, 1596, 1510, 1480, 1460, 1325, 1234 cm^-1. HRMS: m/z calcd for C₁₈H₁₄O: 246.1048; found: 246.1056.
Compound 1i: ¹H NMR (300 MHz, CDCl₃): δ = 7.43 (dd, J = 0.7, 1.8 Hz, 1 H), 7.26-7.12 (m, 2 H), 6.89-6.80 (m, 2 H), 6.42 (d, J = 3.3 Hz, 1 H), 6.37 (dd, J = 1.8, 3.3 Hz, 1 H), 5.74 (t, J = 8.9 Hz, 1 H), 3.50 (d, J = 8.9 Hz, 2 H). ¹³C NMR (75 MHz, CDCl₃): δ = 159.00, 153.07, 143.23, 128.32, 126.29, 124.80, 120.80, 110.45, 109.65, 108.42, 77.02, 34.26. IR (film): ν = 3055, 2957, 2927, 1714, 1597, 1480, 1462, 1234 cm^-1. HRMS: m/z calcd for C₁₂H₁₀O₂: 186.0683; found: 186.0680.
Compound 1j: ¹H NMR (300 MHz, CDCl₃): δ = 8.61 (d, J = 5.9 Hz, 2 H), 7.36 (d, J = 5.9 Hz, 2 H), 7.22-7.17 (m, 2 H), 6.94-6.89 (m, 2 H), 5.77 (dd, J = 7.7, 9.8 Hz, 1 H), 3.73 (dd, J = 9.8, 15.5 Hz, 1 H), 3.15 (dd, J = 7.7, 15.5 Hz, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 159.31, 151.13, 150.12, 128.51, 125.51, 125.03, 121.21, 120.35, 109.55, 81.93, 38.11. IR (film): ν = 3031, 2918, 1597, 1561, 1480, 1462, 1412, 1233 cm^-1. HRMS: m/z calcd for: C₁₃H₁₁NO: 197.0880; found: 197.0884.
Compound 1k: ¹H NMR (300 MHz, CDCl₃): δ = 8.66 (s, 1 H), 8.58 (d, J = 3.7 Hz, 1 H), 7.75 (d, J = 7.9 Hz, 1 H), 7.31 (dd, J = 3.7, 7.9 Hz, 1 H), 7.22-7.16 (m, 2 H), 6.94-6.88 (m, 2 H), 5.79 (dd, J = 8.2, 9.1 Hz, 1 H), 3.69 (dd, J = 9.1, 15.6 Hz, 1 H), 3.15 (dd, J = 8.2, 15.6 Hz, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 159.28, 149.40, 147.57, 137.55, 133.39, 128.51, 125.84, 124.97, 123.64, 121.08, 109.51, 81.56, 38.21. IR (film): ν = 3034, 2919, 1597, 1578, 1479, 1462, 1427, 1326, 1232 cm^-1. HRMS: m/z calcd for C₁₃H₁₁NO: 197.0880; found: 197.0873.
Compound 1l: ¹H NMR (300 MHz, CDCl₃): δ = 7.47 (m, 4 H), 7.33-7.15 (m, 8 H), 6.97-6.86 (m, 2 H), 3.92 (s, 2 H). ¹³C NMR (75 MHz, CDCl₃): δ = 158.74, 145.49, 128.40, 138.37, 127.48, 126.37, 126.11, 124.84, 120.91, 109.69, 92.48, 44.46. IR (film): ν = 3057, 1596, 1480, 1461, 1447, 1240 cm^-1. HRMS: m/z calcd for C₂₀H₁₆O: 272.1205; found: 272.1212.
Compound 1m: ¹H NMR (300 MHz, CDCl₃): δ = 8.04 (d, J = 8.3 Hz, 2 H), 7.47 (d, J = 8.3 Hz, 2 H), 7.17 (m, 2 H), 6.90 (m, 2 H), 5.80 (dd, J = 8.0, 9.6 Hz, 1 H), 3.91 (s, 3 H), 3.68 (dd, J = 9.6, 15.6 Hz, 1 H), 3.17 (dd, J = 8.0, 15.6 Hz, 1 H). ¹³C NMR (75 MHz, CDCl₃): δ = 166.83, 159.55, 147.27, 130.06, 129.79, 128.43, 126.05, 125.62, 125.00, 121.01, 83.31, 52.18, 38.52. IR (film): ν = 2925, 1715, 1595, 1478, 1441, 1281 cm^-1. HRMS: m/z calcd for C₁₆H₁₄O₃: 254.0946; found: 254.0941.

12 Hosomi A. Shirahata A. Sakurai H. Tetrahedron Lett. 1978, 19: 3043