Nickel-Catalyzed Cross-Coupling Reactions of 4-Mesylcoumarins with Aryl Halides: Facile Synthesis of 4-Substituted Coumarins

Abstract

A new and efficient nickel-catalyzed cross-coupling reaction between 4-mesylcoumarins and aryl halides was developed to give a number of 4-arylcoumarins in good yield under mild conditions. Unlike the previously reported coupling examples, this new method allows the direct cross-coupling of 4-mesylcoumarins with aryl- or vinyl halides in the NiCl₂(PPh₃)₂/PPh₃/Zn/toluene system. This has greatly facilitated the synthesis of biologically useful 4-substituted coumarins.

Key words

coumarin - aryl halide - nickel-catalyzed - homocoupling - cross-coupling

References

• 1a Soine TO. J. Pharm. Sci.  1964,  53:  231 
• 1b Chen CH. Fox JL. Proc. Int. Conf. Lasers  1987,  995 
• 1c Edelson RL. Sci. Am.  1988,  August:  68 
• 1d Dini A. Ramundo E. Saturnino P. Scimone A. Stagno d’Alcontres I. Boll. Soc. Ital. Biol. Sper.  1992,  68:  453 
• 1e Hoult JR. Paya M. Gen. Pharmacol.  1996,  27:  713 
• 1f Rocha L. Marston A. Kaplan M. Stoeckli-Evans H. Thull U. Testa B. Hostettmann K. Phytochemistry  1994,  36:  1381 
• 1g Levine C. Hiasa H. Marians KJ. Biochim. Biophys. Acta  1998,  29:  1400 
• 1h Vlietinck AJ. De Bruyne T. Apers S. Pieters LA. Planta Med.  1998,  64:  97 
• 1i Murakami A. Gao G. Omura M. Yano M. Ito C. Furukawa H. Takahashi D. Koshimizu K. Ohigashi H. Bioorg. Med. Chem. Lett.  2000,  10:  59 
• 1j Raboin J.-C. Beley M. Kirsch G. Tetrahedron Lett.  2000,  41:  1175 
• For reviews, see:
• 2a Egan D. Okennedy R. Moran E. Cox D. Prosser E. Thornes RD. Drug Metab. Rev.  1990,  22:  503 
• 2b Pineo GF. Hull RD. Drug Safety  1993,  9:  263 
• 2c Murray RDH. Nat. Prod. Rep.  1995,  12:  477 
• 2d Trivedi KN. Rao SSM. Mistry SV. Desai SM. J. Indian Chem. Soc.  2001,  78:  579 
• 3a Awasthi AK. Tewari RS. Synthesis  1986,  1061 
• 3b Sato K. Inour S. Kobayashi T. Ota T. Tazaki M. J. Chem. Soc., Perkin Trans. 1  1987,  1753 
• 3c Desouza MD. Joshi V. Indian J. Heterocycl. Chem.  1993,  3:  93 
• 3d Ivanova DI. Eremin SV. Shvets VI. Tetrahedron  1996,  52:  9581 
• 3e Lee YR. Kim BS. Wang HC. Tetrahedron  1998,  54:  12215 
• 3f De la Hoz A. Moreno A. Vazquez E. Synlett  1999,  608 
• 3g Yavari I. Adib M. Hojabri L. Tetrahedron  2001,  57:  7537 
• 3h Gonzalez-Gomez JC. Santana L. Uriarte E. Synthesis  2002,  43 
• 3i Bose DS. Rudradas AP. Babu MH. Tetrahedron Lett.  2002,  43:  9195 
• 3j Song AM. Wang XB. Lam KS. Tetrahedron Lett.  2003,  44:  1755 
• 3k Kaye PT. Musa MA. Synth. Commun.  2003,  33:  1755 
• 3l Pave G. Chalard P. Viaud-Massuard MC. Synlett  2003,  987 
• 3m Fringuelli F. Piermatti O. Pizzo F. Synthesis  2003,  2331 
• 3n Selles P. Mueller U. Org. Lett.  2004,  6:  277 
• 3o Kontogiorgis CA. Hadjipavlou-Litina DJ. Bioorg. Med. Chem. Lett.  2004,  14:  611 
• 4 Kadnikov DV. Larock RC. Org. Lett.  2000,  2:  3643 
• 5 Boland GM. Donnelly DMX. Finet J.-P. Rea MD. J. Chem. Soc., Perkin Trans. 1  1996,  2591 
• 6 Yao M.-L. Deng M.-Z. Heteroat. Chem.  2000,  11:  380 
• 7 Wu J. Liao Y. Yang Z. J. Org. Chem.  2001,  66:  3642 
• 8 Wu J. Yang Z. J. Org. Chem.  2001,  66:  7875 
• 9 Saleem R. Faizi S. Deeba F. Siddiqui BS. Qazi MH. Planta Med.  1997,  63:  454 
• 10 Lin G.-Q. Hong R. J. Org. Chem.  2001,  66:  2877 
• 11 Pharkphoom P. Hiroshi N. Wanchai DE. Planta Med.  1998,  64:  774 
• 12 Lei J.-G. Lin G.-Q. Chin. J. Chem.  2002,  20:  1263 
• 13a Percec V. Bae J.-Y. Zhao M. Hill DH. J. Org. Chem.  1995,  60:  176 
• 13b Percec V. Bae J.-Y. Hill DH. J. Org. Chem.  1995,  60:  1060 
• 13c Percec V. Bae J.-Y. Zhao M. Hill DH. J. Org. Chem.  1995,  60:  1066 
• 13d Percec V. Golding GM. Smidrkal J. Weichold O. J. Org. Chem.  2004,  69:  3447 

14

General Procedure for the Synthesis of 7: To an oven-dried Schlenk flask (25 mL) was charged 4-coumarin compound 3 (0.5 mmol), NiCl_{2 (}PPh₃)₂ (0.2 equiv), PPh₃ (0.4 equiv), zinc dust (2.2 mmol) and dry toluene (3 mL) under argon. The resulting mixture was heated to 90 °C. The aryl halide 5 (0.6 mmol) was then added dropwise through micro-syringe pump over 3 h. After the addition, the reaction mixture was stirred at the same temperature until completion. The reaction mixture was cooled down to r.t., quenched with 5% HCl and diluted by CH₂Cl₂. The mixture was stirred vigorously at r.t. until the solution was clear. The organic layer was separated and the water layer was extracted with CH₂Cl₂ (3 × 10 mL). The combined organic layer was washed with sat. aq NaHCO₃, brine, and dried over Na₂SO₄. The solution was concentrated under vacuum; the obtained residue was purified by silica column chromato-graphy to give the corresponding cross-coupling product 7 (selected characterization data of 7 are listed as follows).

15

Compound 7c. ¹H NMR (300 MHz, CDCl₃): d = 9.69 (s, 1 H), 7.86 (m, 1 H), 7.54 (m, 1 H), 7.45 (m, 1 H), 7.22-7.16 (m, 2 H), 7.01 (m, 1 H), 6.40 (s, 1 H), 4.05 (s, 3 H), 3.70 (s, 3 H). MS (EI): m/z (%) = 310 (71) [M⁺], 295 (100). IR (KBr): 3088, 2947, 2837, 2733, 1729, 1695, 1683, 1604, 1584, 1566 cm^-1. Anal. Calcd for C₁₈H₁₄O₅: C, 69.67; H, 4.55. Found: C, 69.86; H, 4.57.

16

Compound 7f. ¹H NMR (300 MHz, CDCl₃): d = 8.08 (d, J = 2.1 Hz, 1 H), 7.64 (s, 1 H), 7.54 (d, J = 7.5 Hz, 1 H), 7.51 (d, J = 7.5 Hz, 1 H), 7.42-7.21 (m, 4 H), 6.45 (d, J = 2.1 Hz, 1 H), 3.93 (s, 3 H). ¹³C NMR (75.5 MHz, CDCl₃): d = 175.12, 160.67, 157.84, 154.08, 153.90, 151.45, 148.05, 132.41, 127.02, 124.91, 124.52, 120.90, 120.03, 118.95, 117.70, 117.45, 105.45, 56.28. MS (EI): m/z (%) = 320 (4) [M⁺], 292 (10.00). IR (KBr): 3078, 2963, 1720, 1649, 1610, 1488, 1446, 1334, 1271 cm^-1. HRMS: m/z calcd for C₁₉H₁₂O₅: 320.0685; found: 320.0734.

17

Compound 7h. ¹H NMR (300 MHz, CDCl₃): δ = 8.05 (s, 1 H), 7.65 (s, 1 H), 7.55-7.30 (m, 4 H), 7.11 (s, 1 H), 6.42 (s, 1 H), 3.94 (s, 3 H), 2.34 (s, 3 H). ¹³C NMR (75.5 MHz, CDCl₃): δ = 174.84, 160.58, 157.73, 153.66, 151.79, 151.20, 147.65, 133.95, 133.21, 126.31, 124.64, 120.69, 119.76, 118.46, 117.47, 116.90, 105.26, 59.01, 20.91. MS (EI): m/z (%) = 335 (18) [M⁺ + 1], 334 (78) [M⁺], 333 (21) [M⁺ - 1], 306 (100). IR (KBr): 3078, 2959, 2929, 2498, 1719, 1698, 1646, 1618, 1568, 1488, 821 cm^-1. HRMS: m/z calcd for C₂₀H₁₄O₅: 334.0841; found: 334.0874.

18

Compound 7j. ¹H NMR (300 MHz, CDCl₃): δ = 9.70 (s, 1 H), 7.54-7.30 (m, 5 H), 6.80 (s, 1 H), 6.39 (d, J = 15 Hz, 2 H). MS (EI): m/z (%) = 312 (71) [M⁺], 269 (100). IR (KBr): 3075, 2913, 2861, 1725, 1682, 1610, 1571, 1504, 1482, 1440, 1369, 1268, 1253 cm^-1. HRMS: m/z calcd for C₁₇H₉FO₅: 312.0434; found: 312.0385.

19

Compound 7m. ¹H NMR (300 MHz, CDCl₃): δ = 10.16 (s, 1 H), 8.09 (d, J = 9.0 Hz, 2 H), 7.89 (d, J = 9.0 Hz, 2 H), 7.74-7.58 (m, 4 H), 7.37 (d, J = 9.3 Hz, 1 H), 7.16 (d, J = 8.7 Hz, 1 H), 6.51 (s, CH, 1 H). MS (EI): m/z (%) = 301 (20) [M⁺ + 1], 300 (91) [M⁺], 272 (100). IR (KBr): 1733, 1631, 1601, 1549, 1500, 1470, 1375, 1209 cm^-1. HRMS: m/z calcd for C₂₀H₁₂O₃: 300.0786; found: 300.0809.