Synthesis of 4-Heteroaryl-Substituted Coumarins by Suzuki Cross-Coupling Reactions

Irina P. Beletskaya; Olga G. Ganina; Alexey V. Tsvetkov; Alexey Yu Fedorov; Jean-Pierre Finet

doi:10.1055/s-2004-835636

LETTER

Synthesis of 4-Heteroaryl-Substituted Coumarins by Suzuki Cross-Coupling Reactions

Irina P. Beletskaya*^a, Olga G. Ganina^a,b, Alexey V. Tsvetkov^a, Alexey Yu. Fedorov^b, Jean-Pierre Finet^c
^a Department of Chemistry, Moscow State Lomonosov University, Vorobyevy Gory, 119992 Moscow, Russia
^b Department of Chemistry, Nizhny Novgorod State University, 23 Gagarin Avenue, 603950 Nizhny Novgorod, Russia
Fax: +7(95)9393618; e-Mail: beletska@org.chem.msu.ru;
^c UMR 6517 CNRS, Universités d’Aix-Marseille 1 et 3, Faculté des Sciences Saint-Jérôme, 13397 Marseille Cedex 20, France

Abstract

Alle Artikel dieser Rubrik

Abstract

Palladium-catalyzed coupling of 4-trifluoromethylsulfonyloxycoumarins 1a-d with heteroarylboronic acids 2a-d under the Suzuki reaction conditions affords 4-heteroaryl-substituted coumarins in good to excellent yields.

Key words

coumarin - heteroarylboronic acids - neoflavonoid derivatives - palladium catalyst - tubulin

Volltext

Referenzen

References

<A NAME="RG29104ST-1A">1a</A> Cao S.-G. Wu X.-H. Sim K.-Y. Tan BHK. Vittal JJ. Pereira JT. Goh S.-H. Helv. Chim. Acta 1998, 81: 1404

<A NAME="RG29104ST-1B">1b</A> Ito A. Chai H.-B. Shin YG. García R. Mejía M. Gao Q. Fairchild CR. Lane KE. Menendez AT. Farnsworth NR. Cordell GA. Pezzuto JM. Kinghorn AD. Tetrahedron 2000, 56: 6401

<A NAME="RG29104ST-1C">1c</A> Guilet D. Seraphin D. Rondeau D. Richomme P. Bruneton J. Phytochemistry 2001, 58: 571

<A NAME="RG29104ST-1D">1d</A> Chaturvedula VSP. Schilling JK. Kingston DGI. J. Nat. Prod. 2002, 65: 965

<A NAME="RG29104ST-1E">1e</A> Jenett-Siems K. Kohler I. Kraft C. Beyer G. Melzig MF. Eich E. Pharmazie 2002, 57: 351

<A NAME="RG29104ST-2">2</A> Itoigawa M. Ito C. Tan HT.-W. Kuchide M. Tokuda H. Nishino H. Furukawa H. Cancer Lett. 2001, 169: 15

<A NAME="RG29104ST-3">3</A> Bailly C. Bal C. Barbier P. Combes S. Finet J.-P. Hildebrand M.-P. Peyrot V. Wattez N. J. Med. Chem. 2003, 46: 5437

<A NAME="RG29104ST-4A">4a</A> Jordan MA. Curr. Med. Chem.: Anti-Cancer Agents 2002, 2: 1

<A NAME="RG29104ST-4B">4b</A> Jordan A. Hadfield JA. Lawrence NJ. McGown AT. Med. Res. Rev. 1998, 18: 259

<A NAME="RG29104ST-4C">4c</A> Hamel E. Med. Res. Rev. 1996, 16: 207

<A NAME="RG29104ST-5A">5a</A> Pettit GR. Singh SB. Boyd MR. Hamel E. Pettit RK. Schmidt JM. Hogan F. J. Med. Chem. 1995, 38: 1666

<A NAME="RG29104ST-5B">5b</A> Gaukroger K. Hadfield JA. Hepworth LA. Lawrence NG. McGown AT. J. Org. Chem. 2001, 66: 8135

<A NAME="RG29104ST-6A">6a</A> Boyle FT. Costello GF. Chem. Soc. Rev. 1998, 27: 251

<A NAME="RG29104ST-6B">6b</A> Chang YC. Nair MG. Nitiss JL. J. Nat. Prod. 1995, 58: 1901

<A NAME="RG29104ST-6C">6c</A> Dixon RA. Ferreira D. Phytochemistry 2002, 60: 205

<A NAME="RG29104ST-7A">7a</A> Jones GH. Mackenzie JBD. Robertson A. Whalley WB. J. Chem. Soc. 1949, 562

<A NAME="RG29104ST-7B">7b</A> Barton DHR. Donnelly DMX. Finet J.-P. Guiry PJ. J. Chem. Soc., Perkin Trans. 1 1992, 1365

<A NAME="RG29104ST-7C">7c</A> Combes S. Finet J.-P. Siri D. J. Chem. Soc., Perkin Trans. 1 2002, 38

<A NAME="RG29104ST-8A">8a</A> Boland GM. Donnelly DMX. Finet J.-P. Rea MD. J. Chem. Soc., Perkin Trans. 1 1996, 2591

<A NAME="RG29104ST-8B">8b</A> Donnelly DMX. Finet J.-P. Guiry PJ. Rea MD. Synth. Commun. 1999, 29: 2719

<A NAME="RG29104ST-9A">9a</A> Wattanasin S. Synth. Commun. 1988, 18: 1919

<A NAME="RG29104ST-9B">9b</A> Schio L. Chatreaux F. Klich M. Tetrahedron Lett. 2000, 41: 1543

<A NAME="RG29104ST-10">10</A> Wu J. Liao Y. Yang Z. J. Org. Chem. 2001, 66: 3642

<A NAME="RG29104ST-11A">11a</A> Miyaura N. Suzuki A. Chem. Rev. 1995, 95: 2457

<A NAME="RG29104ST-11B">11b</A> Suzuki A. J. Organomet. Chem. 1999, 576: 147

<A NAME="RG29104ST-11C">11c</A> Hassan J. Sevignon M. Gozzi C. Schultz E. Lemaire M. Chem. Rev. 2002, 102: 1359

<A NAME="RG29104ST-11D">11d</A> Kotha S. Lahiri K. Kashinath D. Tetrahedron 2002, 58: 9633

General Procedure: A mixture of 4-trifluoromethyl-sulfonyloxycoumarin (0.15-0.4 mmol, 1 equiv), heteroarylboronic acid (1.3 equiv), K₃PO₄ (3.00 equiv), Bu₄NBr (0.1 equiv) and PdCl₂(dppf) (0.05 equiv) in dry MeCN (1-2 mL), under argon atmosphere, was heated at reflux until the 4-trifluoromethylsulfonyloxycoumarin was completely consumed (0.5-3 h, monitored by TLC). The mixture was diluted with H₂O and extracted with CH₂Cl₂. The organic layer was dried (Na₂SO₄), and after distillation of the solvent, the residue was purified by column chromatography on silica gel (EtOAc-petroleum ether = 3:2) to give the corresponding products.

The heteroarylboronic acids 2a-c were obtained from Lancaster and used as received. The 2,4-dibenzyloxy-3,5-pyrimidylboronic acid (2d) was prepared by the procedure of:

<A NAME="RG29104ST-13A">13a</A> Schinazi RF. Prusoff W. Tetrahedron Lett. 1978, 19: 4981

<A NAME="RG29104ST-13B">13b</A> Schinazi RF. Prusoff W. J. Org. Chem. 1985, 50: 841 ; it can also be obtained from Khimmed (Kashirskoe avenue, 115230 Moscow, Russia)

Selected Physical Data:
4-(3′-Quinolyl)-5,6,7-trimethoxycoumarin ( 3c): white needles; mp 155 °C. ¹H NMR: δ = 3.23, 3.77 and 3.95 (9 H, s, OCH₃), 6.16 (1 H, s, H-3), 6.75 (1 H, s, H-8), 7.62 (1 H, td, J = 7.4 and 1.1 Hz, H-5′), 7.78 (1 H, td, J = 7.4 and 1.5 Hz, H-6′), 7.88 (1 H, d, J = 8.3 Hz, H-7′), 8.13 (1 H, d, J = 2.2 Hz, H-8′), 8.18 (1 H, d, J = 8.3 Hz, H-4′), 8.89 (1 H, d, J = 2.2 Hz, H-2′). ¹³C NMR: δ = 56.4, 60.8 and 61.1 (OCH₃), 96.4, 106.7, 115.0, 127.0, 127.3, 128.0, 129.1, 130.1, 132.3, 133.2, 139.2, 147.0, 149.5, 150.8, 151.7, 151.9, 157.4, 160.2. MS: m/z (%) = 363 (100) [M⁺], 348 (56), 332 (10), 320 (14), 277 (12), 262 (13).
4-(2′-Furyl)-5,6,7-trimethoxycoumarin ( 4c): yellow needles; mp 116 °C; ¹H NMR: δ = 3.62, 3.83 and 3.92 (9 H, s, OCH₃), 6.35 (1 H, s, H-3), 6.51 (1 H, dd, J = 3.4 and 1.5 Hz, H-4′), 6.69 (1 H, s, H-8), 6.74 (1 H, d, J = 3.4 Hz, H-5′), 7.56 (1 H, d, J = 1.5 Hz, H-3′). ¹³C NMR: δ = 56.2, 61.1 and 61.8 (OCH₃), 96.3, 105.8, 111.4, 112.0, 113.4, 139.4, 142.9, 143.7, 149.9, 150.8, 151.8, 156.8, 160.6. MS: m/z (%) = 302 (100) [M⁺], 287 (18), 274 (20), 259 (100), 231 (13), 216 (23), 201 (19).
4-(4′-Methoxy-3′-pyridinyl)-5,6,7-trimethoxycoumarin ( 5c): white needles; mp 164 °C. ¹H NMR: δ = 3.31, 3.80, 3.93 and 3.98 (12 H, s, OCH₃), 6.05 (1 H, s, H-3), 6.72 (1 H, s, H-8), 7.77 (1 H, dd, J = 8.6 and 0.9 Hz, H-5′), 7.59 (1 H, dd, J = 8.8 and 2.5 Hz, H-6′), 8.14 (1 H, d, J = 2.5 Hz, H-2′). ¹³C NMR: δ = 53.5, 56.2, 60.8 and 61.0 (OCH₃), 96.4, 106.9, 107.6, 109.3, 114.3, 127.8, 138.6, 139.4, 144.5, 150.8, 151.7, 156.9, 160.2 (C2), 164.0 (C4′). MS: m/z (%) = 343 (100) [M⁺], 328 (54), 315 (8), 300(15), 257 (8).
4-(2′,4′-Dibenzyloxy-3′,5′-pyrimidinyl)-5,6,7-trimethoxycoumarin ( 6c): white needles; mp 139 °C. ¹H NMR: δ = 3.31, 3.63, and 3.89 (9 H, s, OCH₃), 5.48 (4 H, s, CH₂), 6.06 (1 H, s, H-3), 6.67 (1 H, s, H-8), 7.11-7.49 (10 H, m, ArH), 8.15 (1 H, s, H-6′). ¹³C NMR: δ = 56.3, 60.8 and 61.1 (OCH₃), 68.4 and 69.4 (CH₂), 96.2, 107.1, 114.4, 115.3, 127.2, 127.9, 128.0, 128.1, 128.3, 128.4, 135.6, 136.3, 139.0, 147.3, 150.7, 151.2, 154.4, 156.8, 160.3, 164.8, 167.9.