Synlett 2016; 27(06): 888-892
DOI: 10.1055/s-0035-1561273
letter
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Flavonoid/Chromonoid–β-d-Ribofuranose Derivatives by Palladium-Catalyzed Cross-Coupling Reactions

Zoltán Kondor
a  Department of Organic Chemistry, University of Debrecen, Egyetem tér 1, 4032 Debrecen, Hungary   Email: konya.krisztina@science.unideb.hu
,
Dilver P. Fuentes
b  Institut für Chemie, Universität Rostock, Albert Einstein Str. 3a, 18059 Rostock, Germany
,
Christian Vogel
b  Institut für Chemie, Universität Rostock, Albert Einstein Str. 3a, 18059 Rostock, Germany
,
Tamás Patonay
a  Department of Organic Chemistry, University of Debrecen, Egyetem tér 1, 4032 Debrecen, Hungary   Email: konya.krisztina@science.unideb.hu
,
Krisztina Kónya*
a  Department of Organic Chemistry, University of Debrecen, Egyetem tér 1, 4032 Debrecen, Hungary   Email: konya.krisztina@science.unideb.hu
› Author Affiliations
Further Information

Publication History

Received: 29 June 2015

Accepted after revision: 02 November 2015

Publication Date:
23 December 2015 (online)


Dedicated to the memory of Professor Tamás Patonay.

Abstract

Structurally novel carbohydrate–flavone and –chromone derivatives with an unsaturated carbon bridge were synthesized by a phosphine-free palladium-catalyzed cross-coupling reaction.

Supporting Information

 
  • References

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  • 16 Flavone–Ribose Derivatives: General Procedures Conditions A (Jeffery’s Conditions): A stirred mixture of bromoflavone 1a or 1b (75 mg, 0.249 mmol), allyl derivative 2a or 2b (0.249 mmol, 1.0 equiv), K2CO3 (52 mg, 0.375 mmol, 1.5 equiv), KCl (19 mg, 0.250 mmol, 1.0 equiv), TBAB (162 mg, 0.500 mmol, 2.0 equiv), 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. Condition B (Classic Mizoroki–Heck Conditions): A stirred mixture of bromoflavone 1a or 1b (75 mg, 0.249 mmol), allyl derivative 2a (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. 7-[(1E)-3-{(2S,3S,4R,5R)-3,4-Bis(benzyloxy)-5-[(benzyloxy)-methyl]tetrahydrofuran-2-yl}prop-1-en-1-yl]-2-phenyl-4H-chromen-4-one (3a) White crystals; mp 126–127 °C; yield (conditions A): 147 mg (89%); yield (conditions B): 104 mg (63%). IR (KBr): 2922, 2903, 2856, 1639, 1624, 1450, 1372, 1101, 697 cm–1. 1H NMR (360 MHz, CDCl3): δ = 2.45–2.63 (m, 2 H), 3.52 (m, 2 H), 3.66 (t, J = 6.1 Hz, 1 H), 3.93 (t, J = 4.6 Hz, 1 H), 4.21 (m, 2 H), 4.42–4.64 (m, 6 H), 6.44 (s, 2 H), 6.80 (s, 1 H), 7.29 (m, 15 H), 7.39 (s, 1 H), 7.52 (m, 4 H), 7.90 (m, 2 H), 8.10 (d, J = 8.2 Hz, 1 H). 13C NMR (90 MHz, CDCl3): δ = 36.7, 70.3, 71.7, 72.0, 73.3, 79.8, 80.0, 81.6, 107.6, 114.9, 122.5, 123.1, 125.6, 126.2, 127.4, 127.6, 127.7, 128.0, 128.1, 128.3, 128.9, 130.5, 130.7, 131.4, 131.8, 137.7, 138.0, 143.2, 156.5, 163.2, 178.1. Anal. Calcd for C44H40O6: C, 79.50; H, 6.06. Found: C, 79.54; H, 6.10. 6-[(1E)-3-{(2S,3S,4R,5R)-3,4-Bis(benzyloxy)-5-[(benzyloxy)-methyl]tetrahydrofuran-2-yl}prop-1-en-1-yl]-2-phenyl-4H-chromen-4-one (4a) White crystals; mp 89–90 °C; yield (conditions A): 152 mg (92%). IR (KBr): 3029, 2875, 1639, 1614, 1451, 1360, 1097, 731, 697 cm–1. 1H NMR (360 MHz, CDCl3): δ = 2.52–2.59 (m, 2 H), 3.52 (m, 2 H), 3.66 (t, J = 5.8 Hz, 1 H), 3.91 (t, J = 4.6 Hz, 1 H), 4.15–4.22 (m, 2 H), 4.43–4.62 (m, 6 H), 6.25–6.34 (m, 1 H), 6.37–6.48 (m, 1 H), 6.79 (s, 1 H), 7.28 (m, 14 H), 7.43 (t, J = 6.6 Hz, 1 H), 7.50 (m, 4 H), 7.59 (d, J = 6.6 Hz, 1 H), 7.90 (m, 2 H), 8.08 (s, 1 H). 13C NMR (90 MHz, CDCl3): δ = 36.7, 70.2, 71.7, 71.9, 73.3, 77.1, 79.8, 80.1, 81.3, 107.3, 118.1, 122.6, 123.7, 126.1, 127.4, 127.6, 127.6, 127.7, 127.9, 128.2, 128.7, 128.9, 130.5, 131.0, 131.4, 131.6, 134.7, 137.6, 137.7, 138.7, 155.2, 163.1, 178.2. Anal. Calcd for C44H40O6: C, 79.50; H, 6.06. Found: C, 79.55; H, 6.08. 6-[(1E)-3-{(2S,4S,5R)-4-(Benzyloxy)-5-[(benzyloxy)methyl]-tetrahydrofuran-2-yl}prop-1-en-1-yl]-2-phenyl-4H-chromen-4-one (4b) White crystals; mp 82–83 °C; yield (conditions A): 104 mg (75%). IR (KBr): 3059, 3030, 2902, 2876, 1650, 1615, 1453, 1360, 1097, 741, 698 cm–1. 1H NMR (360 MHz, CDCl3): δ = 1.67–1.80 (m, 2 H), 2.43–2.61 (m, 2 H), 3.46–3.59 (m, 2 H), 4.00–4.04 (m, 1 H), 4.15–4.17 (m, 1 H), 4.23–4.29 (m, 1 H), 4.50 (s, 2 H), 4.56 (s, 2 H), 6.29–6.36 (m, 1 H), 6.49–6.53 (m, 1 H), 6.79 (s, 1 H), 7.31 (m, 8 H), 7.45 (m, 4 H), 7.67 (d, J = 8.7 Hz, 1 H), 7.89 (m, 2 H), 8.12 (d, J = 7.2 Hz, 1 H). 13C NMR (90 MHz, CDCl3): δ = 37.6, 38.6, 70.9, 73.3, 73.3, 78.1, 81.0, 83.5, 107.3, 118.1, 122.5, 123.7, 126.1, 127.5, 128.1, 128.2, 128.7, 128.9, 130.4, 131.2, 131.5, 131.6, 134.8, 138.0, 138.1, 155.2, 163.1, 178.3. Anal. Calcd for C37H34O5: C, 79.55; H, 6.13; H, 6.06. Found: C, 79.57; H, 6.09. 3-[(1E)-3-{(2S,3S,4R,5R)-3,4-Bis(benzyloxy)-5-[(benzyloxy)-methyl]tetrahydrofuran-2-yl}prop-1-en-1-yl]-2-phenyl-4H-chromen-4-one (6a) Colorless oil; yield (conditions A): 55 mg (40%). IR (KBr): 3059, 3027, 2919, 2896, 2880, 1648, 1631, 1612, 1467, 1396, 1104, 762, 696 cm–1. 1H NMR (360 MHz, CDCl3): δ = 2.33–2.43 (m, 2 H), 3.52 (m, 2 H), 3.69 (t, J = 5.4 Hz, 1 H), 3.87 (t, J = 5.2 Hz, 1 H), 4.15 (m, 2 H), 4.48–4.57 (m, 6 H), 6.10 (d, J = 15.8 Hz, 1 H), 6.91 (m, 1 H), 7.24 (m, 15 H), 7.44 (m, 6 H), 7.64 (m, 2 H), 8.26 (d, J = 7.6 Hz, 1 H). 13C NMR (100 MHz, CDCl3): δ = 28.7, 70.5, 72.2, 73.4, 77.8, 77.9, 81.4, 81.5, 81.9, 118.0, 119.6, 123.0, 124.9, 125.8, 127.6, 127.7, 127.9, 128.1, 128.3, 128.4, 128.6, 129.9, 130.4, 131.4, 133.2, 133.6, 138.1, 138.3, 156.2, 162.4, 177.9. Anal. Calcd for C44H40O6: C, 79.50; H, 6.06. Found: C, 79.55; H, 6.09. 3-[(1E)-3-{(2S,4S,5R)-4-(Benzyloxy)-5-[(benzyloxy)-methyl]tetrahydrofuran-2-yl}prop-1-en-1-yl]-2-phenyl-4H-chromen-4-one (6b) Colorless oil; yield (conditions A): 29 mg (21%). IR (KBr): 2954, 2923, 2853, 1637, 1465, 1315, 1097, 758, 696 cm–1. 1H NMR (360 MHz, CDCl3): δ = 1.61–1.68 (m, 1 H), 2.06 (dd, J = 13.1, 4.9 Hz, 1 H), 2.31–2.52 (m, 2 H), 3.41–3.55 (m, 2 H), 3.99–4.01 (m, 1 H), 4.08–4.10 (m, 1 H), 4.16–4.19 (m, 1 H), 4.49 (s, 2 H), 4.54 (s, 2 H), 6.16 (d, J = 15.8 Hz, 1 H), 6.79–6.84 (m, 1 H), 7.29 (m, 8 H), 7.38 (m, 5 H), 7.47 (m, 2 H), 7.56 (m, 3 H), 8.26 (d, J = 8.1 Hz, 1 H). 13C NMR (90 MHz, CDCl3): δ = 37.5, 39.9, 70.9, 71.0, 73.3, 78.2, 81.2, 83.4, 117.7, 117.9, 123.1, 123.5, 124.9, 126.2, 126.3, 127.6, 128.3, 129.0, 129.7, 130.4, 133.2, 133.3, 138.2, 155.5, 162.0, 177.5. Anal. Calcd for C37H34O5: C, 79.55; H, 6.13; H, 6.06. Found: C, 79.58; H, 6.15. Chromone–Ribose Derivatives; General Procedure A stirred mixture of bromochromone 8a or 8b (56 mg, 0.249 mmol), allyl derivative 2a or 2b (0.249 mmol, 1.0 equiv), K2CO3 (52 mg, 0.375 mmol, 1.5 equiv), KCl (19 mg, 0.250 mmol, 1.0 equiv), TBAB (162 mg, 0.500 mmol, 2.0 equiv), and Pd(OAc)2 (4 mg, 0.015 mmol, 6 mol%) in dry 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. 7-[(1E)-3-{(2S,3S,4R,5R)-3,4-Bis(benzyloxy)-5-[(benzyl­oxy)methyl]tetrahydrofuran-2-yl}prop-1-en-1-yl]-4H-chromen-4-one (9a) Colorless oil; yield: 115 mg (79%). IR (KBr): 3063, 3029, 2901, 2865, 1654, 1621, 1430, 1127, 1027, 736, 698 cm–1. 1H NMR (360 MHz, CDCl3): δ = 2.43–2.57 (m, 2 H), 3.50 (m, 2 H), 3.61–3.66 (m, 1 H), 3.90 (m, 1 H), 4.19 (m, 2 H), 4.44–4.62 (m, 6 H), 6.24 (d, J = 5.9 Hz, 1 H), 6.38 (m, 2 H), 7.27 (m, 17 H), 7.72 (d, J = 5.9 Hz, 1 H), 8.05 (d, J = 8.2 Hz, 1 H). 13C NMR (90 MHz, CDCl3): δ = 36.5, 70.1, 71.5, 71.7, 73.2, 76.8, 79.7, 79.9, 81.4, 112.7, 114.8, 122.8, 123.2, 125.5, 127.3, 127.4, 127.5, 127.6, 127.8, 127.9, 128.1, 130.4, 137.5, 137.6, 137.8, 137.9, 143.0, 155.0, 156.6, 177.0. Anal. Calcd for C38H36O6: C, 77.53; H, 6.16. Found: C, 77.58; H, 6.19. 3-[(1E)-3-{(2S,3S,4R,5R)-3,4-Bis(benzyloxy)-5-[(benzyl­oxy)methyl]tetrahydrofuran-2-yl}prop-1-en-1-yl]-4H-chromen-4-one (12a) Colorless oil; yield: 73 mg (50%). IR (KBr): 3063, 3029, 2901, 2865, 1654, 1621, 1430, 1127, 1027, 736, 698 cm–1. 1H NMR (360 MHz, CDCl3): δ = 2.16–2.56 (m, 2 H), 3.53 (m, 2 H), 3.68 (t, J = 5.6 Hz, 1 H), 3.89 (t, J = 4.9 Hz, 1 H), 4.16 (m, 2 H), 4.48–4.61 (m, 6 H), 6.32 (d, J = 15.8 Hz, 1 H), 6.47 (m, 1 H), 7.28 (m, 15 H), 7.40 (m, 2 H), 7.64 (t, J = 7.2 Hz, 1 H), 7.76 (s, 1 H), 8.24 (d, J = 7.9 Hz, 1 H). 13C NMR (100 MHz, CDCl3): δ = 37.4, 70.3, 71.7, 72.0, 73.3, 77.1, 79.3, 80.5, 81.2, 117.9, 121.9, 122.4, 124.0, 124.9, 126.1, 127.5, 127.6, 127.8, 128.0, 128.3, 128.4, 128.9, 133.3, 137.8, 138.1, 151.9, 155.8, 176.4. Anal. Calcd for C38H36O6: C, 77.53; H, 6.16. Found: C, 77.58; H, 6.18. 3-[(2E)-3-{(2S,3S,4R,5R)-3,4-Bis(benzyloxy)-5-[(benzyloxy)methyl]tetrahydrofuran-2-yl}prop-2-en-1-yl]-4H-chromen-4-one (13a) Colorless oil; yield: 26 mg (18%). IR (KBr): 2924, 2856, 1718, 1646, 1609, 1464, 1126, 1100, 751, 698 cm–1. 1H NMR (360 MHz, CDCl3): δ = 3.22 (m, 2 H), 3.51–3.52 (m, 2 H), 3.66 (t, J = 6.1 Hz, 1 H), 3.91 (t, J = 4.9 Hz, 1 H), 4.00–4.21 (m, 2 H), 4.44–4.61 (m, 6 H), 5.56 (dd, J = 15.3, 7.3 Hz, 1 H), 5.94 (dt, J = 15.3, 6.8 Hz, 1 H), 7.28 (m, 15 H), 7.35 (m, 2 H), 7.65 (m, 2 H), 8.22 (d, J = 7.2 Hz, 1 H). 13C NMR (100 MHz, CDCl3): δ = 29.8, 70.4, 72.0, 72.2, 73.5, 77.5, 81.4, 81.5, 81.6, 118.1, 123.0, 123.8, 125.0, 126.0, 127.7, 127.8, 127.8, 128.0, 128.1, 128.3, 128.4, 130.2, 131.5, 133.5, 138.0, 138.9, 152.8, 156.5, 177.5. Anal. Calcd for C38H36O6: C, 77.53; H, 6.16. Found: C, 77.55; H, 6.19.