Application of Carbohydrates with Methylene or Vinyl Groups in Heck–Mizoroki Cross-Coupling Reactions with O-Heterocycles

Dedicated to the memory of Prof. Tamás Patonay

Abstract

Structurally novel carbohydrate–O-heterocycle derivatives linked by various unsaturated carbon bridges were synthesized by palladium-catalyzed cross-coupling reactions.

Key words

carbohydrate–heterocycle conjugates - Heck–Mizoroki reaction - flavones - chromones - aurones - palladium catalysis

• References and Notes

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• 6 (5E)-5,6-Dideoxy-1,2-O-(1-methylethylidene)-6-(4-oxo-2-phenyl-4H-chromen-7-yl)-α-d-xylo-hex-5-enofuranose (4a); Typical Jeffery Procedure A mixture of flavone 1a (150 mg, 0.5 mmol), vinylfuranose 3 (93 mg, 0.5 mmol), TBAB (322 mg, 1 mmol), K₂CO₃ (104 mg, 0.75 mmol), and Pd(OAc)₂ (7 mg, 6 mol%) was stirred in anhyd DMF (10 mL) at 100 °C for 3 h. The solvent was then removed under reduced pressure and the crude product was purified by column chromatography [silica gel (60–120 mesh), hexane–EtOAc (1:2)] to give a white solid; yield: 160 mg (79%); mp 198–200 °C. IR (KBr): 1013, 1076, 1164, 1375, 1431, 1451, 1627, 2933, 2987, 3423 cm⁻¹. ¹H NMR (360 MHz, CDCl₃): δ = 7.81–7.73 (m, 3 H), 7.54–7.39 (m, 3 H), 7.22 (s, 1 H), 7.15 (d, J = 8.3 Hz, 1 H), 6.74 (d, J = 16.1 Hz, 1 H), 6.68 (s, 1 H), 6.43 (dd, J = 16.0, 5.7 Hz, 1 H), 6.10 (d, J = 3.6 Hz, 1 H), 4.89 (d, J = 5.2 Hz, 1 H), 4.71 (d, J = 3.6 Hz, 1 H), 4.38 (s, 1 H), 1.57 (s, 3 H), 1.38 (s, 3 H). ¹³C NMR (90 MHz, CDCl₃): δ = 178.3, 163.6, 156.1, 142.5, 131.9, 131.4, 131.2, 129.1, 128.2, 126.3, 125.5, 123.5, 122.4, 115.3, 111.8, 107.2, 105.0, 85.4, 81.3, 76.7, 27.0, 26.3. Anal. Calcd for C₂₄H₂₂O₆: C, 70.93; H, 5.46. Found: C, 70.97; H, 5.48. (5E)-5,6-Dideoxy-1,2-O-(1-methylethylidene)-6-(2-oxo-2H-chromen-6-yl)-α-d-xylo-hex-5-enofuranose (9) Eluent: hexane–EtOAc (1:1). White solid; yield: 143 mg (86%); mp 143–144 °C. IR (KBr): 821, 1004, 1075, 1100, 1164, 1215, 1719, 2935, 2985, 3438 cm⁻¹. ¹H NMR (360 MHz, CDCl₃): δ = 7.62 (d, J = 9.2 Hz, 1 H), 7.54 (d, J = 8.4 Hz, 1 H), 7.41 (s, 1 H), 7.19 (d, J = 8.4 Hz, 1 H), 6.81 (d, J = 16.1 Hz, 1 H), 6.37 (d, J = 9.5 Hz, 1 H), 6.29 (dd, J = 16.0, 5.6 Hz, 1 H), 6.09–5.97 (m, 1 H), 4.88 (s, 1 H), 4.70–4.56 (m, 1 H), 4.24 (s, 1 H), 1.55 (s, 3 H), 1.35 (s, 3 H). ¹³C NMR (90 MHz, CDCl₃): δ = 160.9, 153.4, 143.5, 133.2, 132.0, 129.9, 125.8, 123.9, 118.9, 117.2, 116.9, 111.9, 104.7, 85.2, 81.0, 76.4, 26.9, 26.3. Anal. Calcd for C₁₈H₁₈O₆: C, 65.45; H, 5.49. Found: C, 65.48; H, 5.54. (5E)-6-[(2Z)-2-Benzylidene-3-oxo-2,3-dihydro-1-benzofuran-5-yl]-5,6-dideoxy-1,2-O-(1-methylethylidene)-α-d-xylo-hex-5-enofuranose (11) Eluent: hexane–EtOAc (3:2). Yellow solid; yield: 96 mg (47%); mp 206–208 °C. IR (KBr): 1016, 1074, 1163, 1485, 1613, 1649, 1707, 2932, 2988, 3403 cm⁻¹. ¹H NMR (360 MHz, CDCl₃): δ = 7.92–7.83 (m, 2 H), 7.74 (d, J = 1.9 Hz, 1 H), 7.61 (dd, J = 8.6, 2.1 Hz, 1 H), 7.48–7.37 (m, 3 H), 7.20 (d, J = 8.5 Hz, 1 H), 6.87–6.76 (m, 2 H), 6.25 (dd, J = 16.0, 5.7 Hz, 1 H), 6.04 (d, J = 3.9 Hz, 1 H), 4.91–4.86 (m, 1 H), 4.64 (d, J = 3.7 Hz, 1 H), 4.23 (d, J = 2.9 Hz, 1 H), 1.55 (s, 3 H), 1.35 (s, 3 H). ¹³C NMR (90 MHz, CDCl₃): δ = 184.6, 165.7, 147.3, 135.4, 132.5, 132.3, 131.7, 130.2, 129.0, 123.3, 122.2, 121.9, 113.7, 113.1, 112.0, 104.8, 85.3, 81.0, 76.5, 26.9, 26.3. Anal. Calcd for C₂₄H₂₂O₆: C, 70.93; H, 5.46. Found: C, 70.98; H, 5.49. (5E)-5,6-Dideoxy-1,2-O-(1-methylethylidene)-6-(4-oxo-3,4-dihydro-2H-chromen-7-yl)-α-d-xylo-hex-5-enofuranose (5a); Typical Jeffery* Procedure A mixture of chromanone 2a (150 mg, 0.5 mmol), vinylfuranose 3 (93 mg, 0.5 mmol), TBAB (322 mg, 1 mmol), HCO₂Na (51 mg, 0.75 mmol), and Pd(OAc)₂ (7 mg, 6 mol%) in THF (10 mL) was stirred at 100 °C for 1 h. The solvent was then removed under reduced pressure and the crude product was purified by column chromatography [silica gel (60–120 mesh), hexane–EtOAc (3:1)] to give a pale-yellow solid; yield: 15 mg (79%); mp 145–150°C. IR (KBr): 1018, 1076, 1163, 1215, 1256, 1434, 1612, 1684, 2926, 3399 cm⁻¹. ¹H NMR (360 MHz, CDCl₃): δ = 7.83 (d, J = 8.2 Hz, 1 H), 7.07 (dd, J = 8.2, 1.3 Hz, 1 H), 6.96 (s, 1 H), 6.80 (d, J = 16.0 Hz, 1 H), 6.37 (dd, J = 16.1, 5.4 Hz, 1 H), 6.01 (d, J = 3.7 Hz, 1 H), 4.92–4.87 (m, 1 H), 4.62 (d, J = 3.6 Hz, 1 H), 4.53 (t, J = 6.4 Hz, 2 H), 4.21 (d, J = 2.6 Hz, 1 H), 2.80 (d, J = 6.4 Hz, 2 H), 1.54 (s, 3 H), 1.35 (s, 3 H). ¹³C NMR (90 MHz, CDCl₃): δ = 191.5, 162.2, 144.0, 133.0, 127.7, 126.3, 120.8, 119.7, 115.9, 112.1, 104.8, 85.2, 80.7, 76.4, 67.2, 37.8, 26.9, 26.3. Anal. Calcd for C₁₈H₂₀O₆: C, 65.05; H, 6.07. Found: C, 65.08; H, 6.10. 7-[(E)-2-{(3aR,5R,6R,6aR)-5-[(4R)-2,2-Dimethyl-1,3-dioxolan-4-yl]-6-hydroxy-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-yl}vinyl]-2-phenyl-4H-chromen-4-one (13) Eluent: hexane–EtOAc (1:1). White solid; yield: 141 mg (56%); mp 177–178 °C. IR (KBr): 1069, 1164, 1216, 1373, 1431, 1608, 1623, 1640, 2986, 3451 cm⁻¹. ¹H NMR (400 MHz, CDCl₃): δ = 8.18 (d, J = 8.2 Hz, 1 H), 7.96–7.88 (m, 2 H), 7.60–7.50 (m, 3 H), 7.47 (d, J = 8.3 Hz, 1 H), 7.06 (d, J = 16.0 Hz, 1 H), 6.81 (s, 1 H), 6.39 (d, J = 15.9 Hz, 1 H), 5.93 (d, J = 3.7 Hz, 1 H), 4.40 (d, J = 3.6 Hz, 1 H), 4.25–4.15 (m, 1 H), 4.06–3.97 (m, 3 H), 3.15 (s, 1 H), 1.66 (s, 3 H), 1.45 (s, 3 H), 1.39 (s, 3 H), 1.31 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 178.1, 163.5, 156.7, 142.1, 131.8, 131.7, 130.1, 129.9, 129.1, 126.3, 126.1, 123.4, 123.3, 115.9, 113.4, 109.7, 107.8, 103.8, 83.8, 81.6, 80.7, 73.9, 26.8, 26.7, 26.6, 25.4. Anal. Calcd for C₂₉H₃₀O₈: C, 68.76; H, 5.97. Found: C, 68.80; H, 6.01. 6-{(E)-2-[(2R,3R,4S,5R,6S)-4,5-Bis(benzyloxy)-6-methoxy-3-(2-naphthylmethoxy)tetrahydro-2H-pyran-2-yl]vinyl}-2-phenyl-4H-chromen-4-one (15b) Eluent: hexane–EtOAc (3:1). White solid; yield: 245 mg (86%); mp 159–163 °C. IR (KBr): 696, 736, 1042, 1077, 1357, 1451, 1616, 1648, 2908, 3030 cm⁻¹. ¹H NMR (360 MHz, CDCl₃): δ = 8.14 (s, 1 H), 7.91 (d, J = 7.6 Hz, 1 H), 7.30 (m, 23 H), 6.84 (s, 1 H), 6.73 (d, J = 15.9 Hz, 1 H), 6.15 (dd, J = 15.9, 6.8 Hz, 1 H), 4.64 (m, 7 H), 4.25 (t, J = 8.2 Hz, 1 H), 4.06 (t, J = 9.3 Hz, 1 H), 3.58 (dd, J = 9.5, 3.5 Hz, 1 H), 3.38 (m, 4 H). ¹³C NMR (90 MHz, CDCl₃): δ = 178.2, 163.3, 155.6, 138.7, 138.1, 133.8, 133.4, 133.1, 132.9, 131.7, 131.6, 131.4, 131.3, 129.0, 128.4, 128.0, 127.8, 127.6, 127.0, 126.3, 125.9, 125.8, 123.8, 123.3, 118.3, 107.5, 98.2, 82.0, 79.9, 75.9, 75.3, 73.4, 71.1, 55.3. Anal. Calcd for C₄₈H₄₂O₇: C, 78.88; H, 5.79. Found: C, 78.93; H, 5.81. 7-{(E)-2-[(2R,3R,4S,5R)-4,5-Bis(benzyloxy)-3-[(4-methoxybenzyl)oxy]-6-(phenylsulfanyl)tetrahydro-2H-pyran-2-yl]vinyl}-2-phenyl-4H-chromen-4-one (17a) Eluent: hexane–EtOAc (2:1).White solid; yield: 136 mg (70%); mp 139–140 °C. IR (KBr): 1028, 1067, 1251, 1369, 1430, 1450, 1608, 1649, 2901, 3005 cm⁻¹. ¹H NMR (360 MHz, CDCl₃): δ = 8.17 (s, 1 H), 7.93 (m, 2 H), 7.24 (m, 20 H), 7.12 (d, J = 8.6 Hz, 2 H), 6.74 (m, 4 H), 6.31 (dd, J = 16.0, 6.0 Hz, 1 H), 4.74 (m, 6 H), 4.53 (d, J = 10.9 Hz, 1 H), 3.96 (dd, J = 8.5, 6.1 Hz, 1 H), 3.72 (t, J = 8.9 Hz, 1 H), 3.68 (s, 3 H), 3.52 (t, J = 9.3 Hz, 1 H), 3.40 (t, J = 9.3, 1 H). ¹³C NMR (90 MHz, CDCl₃): δ = 178.0, 163.4, 159.4, 156.5, 142.3, 138.2, 137.9, 133.5, 132.1, 131.7, 131.6, 130.9, 129.9–127.7, 126.2, 125.9, 123.4, 123.1, 115.7, 113.8, 107.7, 87.7, 86.5, 81.1, 80.9, 79.21, 76.0, 75.5, 74.9, 55.1. Anal. Calcd for C₅₀H₄₄O₇S: C, 76.12; H, 5.62. Found: C, 76.16; H, 5.66. 6-{(Z)-[(3aR,5S,6aR)-5-[(4R)-2,2-Dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyldihydrofuro[2,3-d][1,3]dioxol-6(5H)-ylidene]methyl}-2-phenyl-4H-chromen-4-one [(Z)-19b] Eluent: hexane–EtOAc (3:1). White solid; yield: 88 mg (37%); mp 114–116 °C. IR (KBr): 1019, 1068, 1354, 1371, 1381, 1453, 1613, 1646, 2933, 2987 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 8.30 (s, 1 H), 8.03 (d, J = 8.7 Hz, 1 H), 7.95–7.88 (m), 7.60 (d, J = 8.7 Hz, 1 H), 7.53 (m, 3 H), 7.12 (s, 1 H), 6.82 (s, 1 H), 5.87 (d, J = 3.7 Hz, 1 H), 5.13 (d, J = 2.7 Hz, 1 H), 4.80 (d, J = 6.1 Hz, 1 H), 4.18–4.01 (m, 3 H), 1.60 (s, 3 H), 1.49 (s, 3 H), 1.47 (s, 3 H), 1.44 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 178.2, 163.5, 155.7, 140.3, 134.1, 133.4, 131.8, 131.7, 129.1, 126.7, 126.4, 125.9, 123.9, 118.5, 112.7, 110.1, 107.6, 105.2, 80.8, 79.1, 77.5, 67.4, 27.5, 27.3, 26.9, 25.7. Anal. Calcd for C₂₈H₂₈O₇: C, 70.58; H, 5.92. Found: C, 70.60; H, 5.94. 6-{(E)-[(3aR,5S,6aR)-5-[(4R)-2,2-Dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyldihydrofuro[2,3-d][1,3]dioxol-6(5H)-ylidene]methyl}-2-phenyl-4H-chromen-4-one [(E)-19b] Eluent: hexane–EtOAc (3:1); yield: 88 mg (37%); white solid; mp 200–206 °C. IR (KBr): 1042, 1207, 1355, 1370, 1381, 1454, 1609, 1646, 2932, 2987 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 8.17 (s, 1 H), 7.93 (d, J = 7.5 Hz, 2 H), 7.78 (d, J = 8.6 Hz, 1 H), 7.55 (m, 4 H), 6.94 (s, 1 H), 6.84 (s, 1 H), 5.93 (d, J = 4.4 Hz, 1 H), 5.52 (s, 1 H), 5.25–5.16 (m, 1 H), 4.11 (dd, J = 11.7, 6.1 Hz, 1 H), 3.88 (t, J = 7.5 Hz, 1 H), 3.59 (t, J = 7.7 Hz, 1 H), 1.52 (s, 3 H), 1.46 (s, 3 H), 1.37 (s, 3 H), 1.25 (s, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 178.0, 163.6, 155.6, 140.8, 133.8, 133.5, 131.8, 131.6, 129.1, 127.4, 126.4, 125.6, 124.0, 118.6, 113.2, 109.9, 107.7, 103.9, 83.0, 79.7, 77.2, 65.9, 28.0, 27.9, 26.1, 25.5. Anal. Calcd for C₂₈H₂₈O₇: C, 70.58; H, 5.92. Found: C, 70.61; H, 5.94. 7-{(E)-2-[(2R,3R,4S,5R,6S)-4,5-Bis(benzyloxy)-6-methoxy-3-(2-naphthylmethoxy)tetrahydro-2H-pyran-2-yl]vinyl}-2-phenyl-4H-chromen-4-one (15a); Typical Heck Procedure A stirred mixture of bromoflavone 1a (75 mg, 0.249 mmol), vinylpyranose 14 (0.249 mmol, 1.0 equiv), Et₃N (39 μL, 0.274 mmol, 1.1 equiv), Ph₃P (7 mg, 0.025 mmol, 10 mol%), and Pd(OAc)₂ (4 mg, 0.015 mmol, 6 mol%) in anhyd DMF (5 mL) was heated at 110 °C for 2 h under N₂. The mixture was cooled, silica gel was added, and the solvent was evaporated under reduced pressure. The residue was purified by column chromatography [silica gel, hexane–EtOAc (3:1)] to give a white solid; yield: 100 mg (70%); mp 151–153 °C. IR (KBr): 734, 1050, 1068, 1367, 1430, 1622, 1646, 2925, 3030, 3060 cm⁻¹. ¹H NMR (360 MHz, CDCl₃): δ = 8.06 (d, J = 8.2 Hz, 1 H), 7.90 (m, 2 H), 7.54 (m, 7 H), 7.22 (m, 15 H), 6.85 (s, 1 H), 6.68 (d, J = 15.9 Hz, 1 H), 6.20 (dd, J = 16.0, 6.5 Hz, 1 H), 4.64 (m, 7 H), 4.26 (t, J = 8.0 Hz, 1 H), 4.07 (t, J = 9.2 Hz, 1 H), 3.58 (dd, J = 9.6, 3.5 Hz, 1 H), 3.38 (m, 4 H). ¹³C NMR (90 MHz, CDCl₃): δ = 178.1, 163.4, 156.4, 142.4, 138.6, 138.1, 135.3, 133.1, 132.9, 131.7, 131.6, 130.9, 130.6, 129.0, 128.5, 128.1, 128.0, 127.7, 127.5, 127.1, 126.3, 126.0, 125.9, 125.8, 123.3, 123.0, 115.4, 107.6, 98.2, 81.9, 81.8, 79.9, 76.0, 75.4, 73.5, 70.8. Anal. Calcd for C₄₈H₄₂O₇: C, 78.88; H, 5.79. Found: C, 78.90; H, 5.80.
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