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Synlett 2002(6): 0927-0930
DOI: 10.1055/s-2002-31932
LETTER
© Georg Thieme Verlag Stuttgart · New York

Nickel-Catalyzed Tandem Reaction to Asymmetric Synthesis of Chiral Phthalides

Jian-Guang Lei, Ran Hong, Shen-Gang Yuan, Guo-Qiang Lin*
Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai, 200032, P. R. China
Fax: +86(21)64166263; e-Mail: lingq@pub.sioc.ac.cn;
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Publication History

Received 1 April 2002
Publication Date:
07 February 2007 (online)

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Abstract

Nickel-catalyzed tandem (addition-cyclization) reaction was developed to the enantioselective synthesis of optically active phthalides. The choice of bidentate ligand in this nickel-catalyzed reaction was critical to the formation of the phthalides in good yield and high ee value.

Key words

phthalides - nickel-catalyzed - bidentate - enantioselective - tandem reaction

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Hong, R.; Lei, J.-Q., unpublished works.

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General procedure: The substrates (0.2 mmol), NiCl2(PPh3)2 (0.04 mmol), (S)-BINAP (0.04 mmol), Zn (0.6 mmol) and 2 mL of toluene were added to an oven-dried 10 mL flask and flushed with argon. The reaction mixture was stirred at 90 °C for desired time. TLC detected the reaction progress. When the reaction was complete, the mixture was quenched with 5 mL of 2% HCl(aq) and diluted by 5 mL of CH2Cl2 and stirred for 1 hour at room temperature, then the organic layer was separated and the water layer was exacted with CH2Cl2 (3 × 20 mL).The combined organic extracts were washed with NaHCO3(aq) and brine, dried over anhydrous Na2SO4, filtered and evaporated the solvent, the residue was purified on silica gel (EtOAc-petroleum ether = 1:3) by column chromatography.

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2a.[α]D 20 -8.7 (0.61, CHCl3) for 72%ee; 1H NMR (300 MHz, CDCl3) δ 3.60 (s, 3 H), 3.66 (s, 3 H), 3.88 (s, 3 H), 3.92 (s, 3 H), 3.93 (s, 3 H), 3.97 (s, 3 H), 6.16 (s, 1 H), 6.87 (s, PhH, 1 H), 7.27 (s, PhH, 1 H); EIMS (m/z, %): 518 (M+ + 2, 6.66), 517 (M+ + 1, 25.80), 516 (M+, 100), 457 (8.30), 389 (11.32), 321 (16.95), 195 (26.04), 181(21.74); FT-IR(KBr): 2941, 1765, 1613, 1583, 1561, 1479, 1102, 474 cm-1; Anal. calcd for C20H21O8I: C, 46.53; H, 4.10. Found: C, 46.53; H, 4.13. HPLC (Chiral cel AD, hexane-iPrOH = 80:20, flow rate = 0.7 mL/min) tR = 11.44 min(minor), tR = 12.67 min(major).

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3a. [α]D 20 -26 (0.06, CHCl3) for 17%ee; 1H NMR (300 MHz, CDCl3) δ 3.55 (s, 3 H), 3.82 (s, 6 H), 3.84 (s, 3 H), 3.93 (s, 3 H), 3.96 (s, 3 H), 3.97 (s, 3 H), 6.29(s, 1 H), 6.49 (s, PhH, 2 H), 7.21 (s, PhH, 1 H); EIMS (m/z, %) : 391 (M+ + 1, 27.02), 390 (M+, 100), 375(14.71), 359 (19.84), 315 (11.76), 331 (18.01), 195 (21.02), 181 (8.71); FT-IR (KBr): 2942, 2840, 1762, 1595, 1508, 1479, 1236, 1128, 1106 cm-1; Anal. calcd for C20H22O8: C, 61.53; H, 5.68. Found: C, 61.64; H, 5.82. HPLC (Chiral cel AD, hexane-iPrOH = 70:30, flow rate = 0.7 mL/min) tR = 11.38 min(minor), tR = 13.47 min(major).

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2b.[α]D 20 -0.4 (1.85, CHCl3) for 98%ee; 1H NMR (300 MHz, CDCl3) δ 3.65 (s, 3 H), 3.71 (s, 3 H), 3.89 (s, 3 H), 3.90 (s, 3 H), 5.96 (d, J = 0.009 Hz, PhH, 1 H), 6.42 (d, J = 0.01 Hz, PhH, 1 H), 6.66 (d, J = 0.006 Hz, PhH, 1 H), 6.88 (s, 1 H), 6.98 (d, J = 0.006 Hz, PhH, 1 H); EIMS (m/z, %): 457 (M+ + 1, 22.80), 456 (M+, 100), 329 (27.06), 291 (39.26), 227 (8.12), 193 (18.15), 165 (27.23), 151 (17.28); FT-IR (KBr): 3068, 2963, 2936, 2837, 1753, 1625, 1589, 1569, 1450, 1272, 1036, 492 cm-1. HPLC (Chiral cel AD, hexane-iPrOH = 95:5, flow rate = 0.8 mL/min) tR = 35.85 min(minor), tR = 40.37 min(major).

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2c. [α]D 20 -33 (0.22, CHCl3) for 81% ee; 1H NMR (300 MHz, CDCl3) δ 3.65 (s, 3 H), 3.72 (s, 3 H), 3.90 (s, 3 H), 3.91 (s, 3 H), 5.97 (d, J = 2.71 Hz, PhH, 1 H), 6.48 (d, J = 2.71 Hz, PhH, 1 H), 6.67 (d, J = 1.81 Hz, PhH, 1 H), 6.92 (s, 1 H), 6.99 (d, J = 1.83 Hz, PhH, 1 H); EIMS (m/z, %): 410 (M+ + 1, 97.77), 408 (M+ - 1, 98.20), 329 (39.36), 245 (47.35), 243 (52.18), 193 (42.89), 165(100), 151 (21.29); FT-IR (KBr): 2972, 2941, 2842, 1765, 1628, 1592, 1504, 1463, 1229, 1207, 607 cm-1; Anal. calcd for C18H17O6Br: C, 52.83; H, 4.19. Found: C,52.82; H,4.49. HPLC (Chiral cel OJ, hexane-iPrOH = 90:10, flow rate = 0.7 mL/min) tR = 15.59 min(major), tR = 21.32 min(minor).

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2d. [α]D 20 -33 (0.38, CHCl3) for 43%ee; 1H NMR (300 MHz, CDCl3) δ 3.61 (s, 3 H), 3.67 (s, 3 H), 3.89 (s, 3 H), 3.93 (s, 3 H), 3.93 (s, 3 H), 3.96 (s, 3 H), 6.17 (s, 1 H), 6.90 (s, PhH, 1 H), 7.22 (s, PhH, 1 H); EIMS (m/z, %): 471 (M+ + 2, 23.49), 470 (M+ + 1,100), 469 (M+, 83.60), 468 (M+ - 1, 99.52), 389 (17.06), 275 (18.06), 273 (19.33), 195 (61.66); FT-IR (KBr): 3030, 2941, 2830, 1761, 1617, 1588, 1567, 1479, 1245, 1201, 587 cm-1; Anal. calcd for C20H21O8Br: C, 51.19; H, 4.51.Found: C, 50.99; H, 4.36. HPLC (Chiral cel AD, hexane-iPrOH = 80:20, flow rate = 0.7 mL/min) tR = 10.46min(minor), tR = 11.61min(major).

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2e. [α]D 20 -48 (0.07, CHCl3) for 71%ee; 1H NMR (300 MHz, CDCl3) δ 3.53 (s, 3 H), 3.84 (s, 3 H), 3.88(s, 3 H), 3.95 (s, 3 H), 6.58 (d, J = 8.44 Hz, PhH, 1 H), 6.78 (d, J = 8.66 Hz, PhH, 1 H), 6.88 (s, 1 H), 7.13 (d, J = 8.23 Hz, PhH, 1 H), 7.69 (d, J = 8.25 Hz, PhH, 1 H); EIMS (m/z, %): 457 (M+ + 1,22.80), 456 (M+, 100), 397 (15.16), 329 (23.85), 330 (10.84), 298 (11.27), 291 (19.73), 165 (22.55); FT-IR (KBr): 3051, 2980, 1765, 1580, 1483, 1203, 1116, 539 cm-1; HPLC (Chiral cel AD, hexane-iPrOH = 70:30, flow rate = 0.5 mL/min) tR = 41.25 min(minor), tR = 48.31 min(major).

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2f. 61% ee; 1H NMR (300 MHz, CDCl3) δ 3.75 (s, 3 H), 3.93 (s, 3 H), 6.37 (dd, J 1 = 1.07 Hz, J 2 = 1.39 Hz, PhH, 1 H), 6.81 (dd, J 1 = 1.23 Hz, J 2 = 1.25 Hz, PhH, 1 H), 6.97 (s, 1 H), 7.18 (m, PhH, 2 H), 7.55 (t, J = 1.95, 3.47 Hz, PhH, 2 H); EIMS (m/z, %): 397 (M+ + 1,22.66), 396 (M+, 100), 270 (27.30), 269 (82.24), 261 (59.73), 237 (19.36), 139 (18.82), 135 (46.37); FT-IR (KBr): 3005, 2968, 2940, 2838, 1764, 1609, 1568, 1492, 500 cm-1; Anal. calcd for C16H13O4I: C, 48.51; H, 3.31. Found: C,48.93; H, 3.77. HPLC (Chiral cel AD, hexane-iPrOH = 80:20, flow rate = 0.7 mL/min) tR = 13.92 min(minor), tR = 16.47 min(major).