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Synlett 2004(13): 2364-2368  
DOI: 10.1055/s-2004-832818
LETTER
© Georg Thieme Verlag Stuttgart · New York

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

Jian-Guang Lei, Ming-Hua Xu, Guo-Qiang Lin*
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Rd., Shanghai 200032, P. R. China
Fax: +86(21)64166263; e-Mail: lingq@mail.sioc.ac.cn;
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Publikationsverlauf

Received 22 June 2004
Publikationsdatum:
24. September 2004 (online)

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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

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General Procedure for the Synthesis of 7: To an oven-dried Schlenk flask (25 mL) was charged 4-coumarin compound 3 (0.5 mmol), NiCl2 (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).

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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.

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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.

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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.

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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.

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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.