LETTER
Total Synthesis of Linear Furocoumarins
569
(24) Benzofuran 4: Compound 2 (2 mmol) was added to an aq
soln of 2 M NaOH (15 mL) and stirred at r.t. for 30 min
under an N2 atmosphere. After cooling to 0 °C, the resultant
solution was added dropwise to a well-stirred aq solution of
3 M H2SO4 (25 mL) at 0 °C. The reaction was stirred at r.t.
for about 4 h until the reaction was complete. The solution
was extracted with EtOAc and the organic phase was dried
over anhyd Na2SO4. After removal of the solvent, the residue
was purified by flash chromatography on silica gel to afford
the desired compound 4.28 Mp 54–55 °C. IR (KBr): 3423,
3122, 1602, 1446, 1132, 837 cm–1. 1H NMR (400 MHz,
CDCl3): d = 7.52 (d, J = 2.2 Hz, 1 H), 7.42 (d, J = 8.5 Hz, 1
H), 7.00 (m, 1 H), 6.79 (dd, J = 8.5 Hz, J = 2.2 Hz, 1 H), 6.69
(dd, J = 2.2 Hz, J = 0.9 Hz, 1 H), 5.16 (br s, 1 H). EI-MS:
m/z (%) = 134 (M+, 100), 105(30), 78 (35), 51 (15). Anal.
Calcd for C8H6O2: C, 71.64; H, 4.51. Found: C, 71.57; H,
4.52.
(25) 5b–f; General Procedure: To a mixture of 4 and an
appropriate b-ketoester (ratio 1:1.2), an excess of MsOH
(0.5 mL per mmol of 4) was slowly added, and stirred at 0 °C
for 30 min. Stirring was continued at r.t. until the reaction
was complete (monitored by TLC). The resulting mixture
was poured into ice-water, stirred for 1 h at r.t., extracted
with EtOAc, the organic phase was dried over anhyd
Na2SO4, and then concentrated in vacuo. The residue was
purified by flash chromatography over silica gel (PE–
acetone) to afford the title compounds 5b–f.
References and Notes
(1) Bethea, D.; Fullmer, B.; Syed, S.; Seltzer, G.; Tiano, J.;
Rischko, C.; Gillespie, L.; Brown, D.; Gasparro, F. P. J.
Dermatol. Sci. 1999, 19, 78.
(2) (a) Grundmann, K. M.; Ludwig, R.; Zollner, T. M.;
Ochsendorf, F.; Thaci, D.; Boehncke, W. H.; Krutmann, J.;
Kaufmann, R.; Podda, M. J. Am. Acad. Dermatol. 2004, 50,
734. (b) Grimes, P. E. Clin. Dermatol. 1997, 15, 921.
(c) Petering, H.; Breuer, C.; Herbst, R.; Kapp, A.; Werfel, T.
J. Am. Acad. Dermatol. 2004, 50, 68.
(3) (a) Diederen, P. V. M. M.; Weelden, H.; Sanders, C. J. G.;
Toonstra, J.; Vloten, W. A. J. Am. Acad. Dermatol. 2003, 48,
215. (b) Miolo, G.; Tomanin, R.; Rossi, A. D.; Dall, A. F.;
Zacchello, F.; Scarpa, M. J. Photochem. Photobiol. B 1994,
26, 241. (c) Lage, C.; Pádula, M.; Alencar, T. A. M.;
Gonçalves, S. R. F.; Vidal, L. S.; Cabral-Neto, J.; Leitão, A.
C. Mutat. Res. Rev. Mutat. Res. 2003, 544, 143.
(4) Cimino, G. D.; Gamper, H. B.; Isaacs, S. T.; Hearst, J. E.
Ann. Rev. Biochem. 1985, 54, 1151.
(5) Edelson, R. L. Arch. Dermatol. 1999, 135, 600.
(6) (a) Goupil, J. J. French Patent 2:698,270, 1994. (b)Goaster,
J. L. French Patent 2:691,629, 1993.
(7) Wiesmann, A.; Weller, A.; Lischka, G.; Klingebiel, T.;
Kanz, L.; Einsele, H. Bone Marrow Transplant 1999, 23,
151.
(8) Kaufman, K. D.; Erb, D. J.; Blok, T. M.; Carlson, R. W.;
Knoechel, D. J.; McBride, L.; Zeitlow, T. J. Heterocycl.
Chem. 1982, 19, 1051.
(9) Nore, P.; Honkanen, E. J. Heterocycl. Chem. 1980, 17, 985.
(10) Macleod, J. K.; Worth, B. R. Tetrahedron Lett. 1972, 237.
(11) (a) Esse, R. C.; Christensen, B. E. J. Org. Chem. 1960, 25,
1565. (b) Abu-Shady, H.; Hassib, S. T.; Amin, K. M.; Farag,
A. E. Egypt. J. Pharm. Sci. 1990, 31, 453.
5b Yield: 72%; mp 186–187 °C (acetone) (lit.29 185–186
°C). IR (KBr): 3161, 1724, 1631, 1385, 746 cm–1. 1H NMR
(400 MHz, CDCl3): d = 7.82 (s, 1 H), 7.69 (d, J = 2.4 Hz,
1 H), 7.48 (d, J = 0.4 Hz, 1 H), 6.86 (dd, J = 2.4 Hz, J = 0.4
Hz, 1 H), 6.27 (s, 1 H), 2.51 (s, 3 H). EI-MS: m/z (%) = 200
(M+, 100), 172 (70), 171 (75), 144 (10), 115 (25).
5c Yield: 70%; mp 170–171 °C. IR (KBr): 3122, 2972,
1716, 1629, 1583, 1130 cm–1. 1H NMR (400 MHz, CDCl3):
d = 7.86 (s, 1 H), 7.69 (d, J = 2.4 Hz, 1 H), 7.49 (d, J = 0.8
Hz, 1 H), 6.84 (dd, J = 2.4 Hz, J = 0.8 Hz, 1 H), 6.28 (t,
J = 1.2 Hz, 1 H), 2.89 (dq, J = 7.2 Hz, J = 1.2 Hz, 2 H), 1.38
(t, J = 7.2 Hz, 3 H). EI-MS: m/z (%) = 214 (M+, 75), 185
(30), 171 (100), 115 (15). Anal. Calcd for C13H10O3: C,
72.89; H, 4.71. Found: C, 72.97; H, 4.65.
(12) Zubia, E.; Luis, F. R.; Massanet, G. M.; Collado, I. G.
Tetrahedron 1992, 48, 4239.
(13) (a) Ahluwalia, V. K.; Prakash, C.; Bala, S. Monatsh. Chem.
1980, 111, 877. (b) Aquila, B. M. Tetrahedron Lett. 1997,
38, 2795.
(14) Hayakawa, K.; Yodo, M.; Ohsuki, S.; Kanematsu, K. J. Am.
Chem. Soc. 1984, 106, 6735.
5d Yield: 65%; mp 127–128 °C (lit.30 128–129 °C). IR
(KBr): 3112, 2955, 1708, 1630, 1576, 1161, 1112 cm–1. 1H
NMR (300 MHz, CDCl3): d = 7.84 (s, 1 H), 7.68 (d, J = 2.4
Hz, 1 H), 7.47 (s, 1 H), 6.84 (d, J = 2.4 Hz, 1 H), 6.25 (s, 1
H), 2.81 (t, J = 7.6 Hz, 2 H), 1.79 (m, 2 H), 1.08 (t, J = 7.6
Hz, 3 H). EI-MS: m/z (%) = 228 (M+, 100), 200(35), 185
(70), 171 (70), 115 (20).
5e Yield: 67%; mp 142–143 °C. IR (KBr): 3101, 1731,
1628, 1581, 1450, 1283, 1151 cm–1. 1H NMR (400 MHz,
CDCl3): d = 7.97 (q, J = 1.9 Hz, 1 H), 7.75 (d, J = 2.2 Hz, 1
H), 7.56 (d, J = 0.5 Hz, 1 H), 6.90 (dd, J = 2.2 Hz, J = 0.8
Hz, 1 H), 6.79 (s, 1 H). EI-MS: m/z (%) = 254 (M+, 90), 226
(100), 198 (20), 169 (20). Anal. Calcd for C12H5F3O3: C,
56.71; H, 1.98. Found: C, 56.67; H, 2.10.
5f Yield: 58%; mp 177–178 °C. IR (KBr): 3128, 3124,
1722, 1626, 1568, 1375, 1149 cm–1. 1H NMR (300 MHz,
CDCl3): d = 7.68 (s, 1 H), 7.67 (br s, 1 H), 7.57–7.47 (m,
6 H), 6.76 (dd, J = 2.2 Hz, J = 1.0 Hz, 1 H), 6.34 (s, 1 H).
EI-MS: m/z (%) = 262 (M+, 90), 234 (100), 205 (35), 176
(30), 76 (20). Anal. Calcd for C17H10O3: C, 77.85; H, 3.84.
Found: C, 77.94; H, 3.92.
(15) (a) Mal, D.; Bandhyopadhyay, M.; Datta, K.; Murty, K. V.
S. N. Tetrahedron 1998, 54, 7525. (b) Mal, D.; Murty, K. V.
S. N.; Datta, K. Tetrahedron Lett. 1994, 35, 9617.
(16) Herndon, J. W.; Zhang, Y.; Wang, H.; Wang, K.
Tetrahedron Lett. 2000, 41, 8687.
(17) Nicolaou, K. C.; Snyder, S. A.; Bigot, A.; Pfefferkorn, J. A.
Angew. Chem. Int. Ed. 2000, 39, 1093.
(18) (a) Roshchin, A. I.; Kel’chevski, S. M.; Bumagin, N. A. J.
Organomet. Chem. 1998, 560, 163. (b) Youn, S. W.; Eom,
J. I. Org. Lett. 2005, 7, 3355.
(19) Bellur, E.; Freifeld, I.; Langer, P. Tetrahedron Lett. 2005,
46, 2185.
(20) Tsai, T.; Wang, E.; Huang, K.; Li, S.; Wang, Y.; Lin, Y.;
Chen, Y. Heterocycles 2004, 63, 1771.
(21) Majumdar, K. C.; Basu, P. K.; Mukhopadhyay, P. P.
Tetrahedron 2005, 61, 10603.
(22) (a) Ballini, R.; Petrini, M. Tetrahedron 2004, 60, 1017.
(b) Van Tamelen, E. E.; Thiede, R. J. J. Am. Chem. Soc.
1952, 74, 2615. (c) Kornblum, N.; Erickson, A. S.; Kelly,
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3861.
(26) Psoralen 5a: A mixture of ZnCl2 (210 mg, 1.5 mmol), ethyl
propiolate (0.5 mL, 5 mmol), and compound 4 (134 mg, 1.0
mmol) was heated at 90 °C for 3 h under a N2 atmosphere.
After cooling to r.t., 5% HCl (25 mL) was added to the
resultant mixture, which was then extracted with EtOAc
(23) Dauzonne, D.; Royer, R. Synthesis 1984, 1054.
Synlett 2006, No. 4, 567–570 © Thieme Stuttgart · New York