1972
J. L. Jeffrey, R. Sarpong / Tetrahedron Letters 50 (2009) 1969–1972
Tetrahedron 2001, 57, 4849–4854; (e) Li, W. W.; Ding, L. S.; Li, B. G.; Chien, Y.
With 9 in hand, a variety of Lewis and Bronsted acids were
Z. Phytochemistry 1996, 42, 1163–1165; (f) Tanaka, T.; Ito, T.; Nakaya, K.;
Iinuma, M.; Riswan, S. Phytochemistry 2000, 54, 63–69; (g) Coggon, P.; Janes, N.
F.; King, T. J.; Wallwork, S. C. J. Chem. Soc. 1965, 406–408; (h) Ito, T.; Tanaka, T.;
Iinuma, M.; Iliya, I.; Nakaya, K.; Ali, Z.; Takahashi, Y.; Sawa, R.; Shirataki, Y.;
Murata, J.; Darnaedi, D. Tetrahedron 2003, 59, 5347–5363; (i) Supudompol, B.;
Likhitwitayawuid, K.; Houghton, P. J. Phytochemistry 2004, 65, 2589–2594; (j)
Sahadin, ; Hakim, E. H.; Juliawaty, L. D.; Syah, Y. M.; bin Din, L.; Ghisalberti, E.
L.; Latip, J.; Said, I. M.; Achmad, S. A. Z. Naturforsch., C: Biosci. 2005, 60, 723–727;
(k) Ito, T.; Tanaka, T.; Iinuma, M.; Nakaya, K.; Takahashi, Y.; Sawa, R.; Murata, J.;
Darnaedi, D. J. Nat. Prod. 2004, 67, 932–937.
tested in an effort to form 10 via our proposed Nazarov-type cycli-
zation (Scheme 2). We found success with the treatment of 9 with
FeCl3Á6H2O (1 equiv) in CH2Cl2 to yield diene 1517 in 38% yield as a
maroon solid (Scheme 4). Although 10 was not observed, pentalene
15 could presumably have formed via the intermediacy of 10,
which was likely oxidized under the reaction conditions. Alterna-
tively, 15 may have resulted directly from 9 via a cyclodehydroge-
nation in keeping with the precedent of Kovacic.18 Slow
evaporation of a CH2Cl2 solution of 15 yielded X-ray quality crys-
tals, which confirmed the connectivity of 15 (Fig. 3). Attempts to
reduce 15, as well as the exo- and endocyclic double bonds of 9,
are ongoing.
7. (a) Snyder, S. A.; Zografos, A. L.; Lin, Y. Angew. Chem., Int. Ed. 2007, 46, 8186–
8191; b Snyder, S. A.; Breazzano, S. P.; Ross, A. G.; Lin, Y.; Zografos, A. L. J. Am.
Chem., Int. Ed. 2006, 45, 7609–7611.
8. Anstead, G. M.; Ensign, J. L.; Peterson, C. S.; Katzenellenbogen, J. A. J. Org. Chem.
1989, 54, 1485–1491.
9. (a) Nazarov, I. N.; Zaretskaya, I. I. Bull. Acad. Sci. U.R.S.S., Classe sci. chim. 1942,
200–209; For a review of the Nazarov cyclization, see: (b) Habermas, K. L.;
Denmark, S. E.; Jones, T. K. Org. React. 1994, 45, 1–158.
In conclusion, we have demonstrated a novel palladium-cata-
lyzed cascade reaction, which assembles the carbon framework
of several resveratrol-derived natural products. Starting from two
readily accessible building blocks, we have synthesized potential
precursors to a large family of natural products, including quadran-
gularin A, parthenocissin A, and pallidol. Studies on the functional-
ization of these compounds and completion of the total syntheses
of a series of resveratrol-based natural products are underway and
will be reported in due course.
10. Brand, K.; Krey, W. J. Prakt. Chem. 1925, 110, 10–25.
11. 7: To a solution of p-iodoanisole (0.100 g, 0.427 mmol), Pd(PPh3)2Cl2 (0.015 g,
0.0214 mmol), and CuI (0.0081 g, 0.0427 mmol) in Et3 N (5 mL) under N2 was
added ethynylbenzene 14 (0.0970 g, 0.598 mmol). The solution was stirred at
rt for 18 h. The solvent was removed in vacuo and the crude brown residue was
purified by flash chromatography (6:1 hexanes/EtOAc) to give 0.113 g (99%
yield) of 7 as a colorless oil. Rf 0.52 (2:1 hexanes/EtOAc); 1H NMR (400 MHz,
CDCl3) d 7.46 (d, J = 8.8 Hz, 2H), 6.86 (d, J = 8.8 Hz, 2H), 6.67 (s, 2H), 6.43 (s, 1H),
3.80 (s, 3H), 3.77 (m, 6H); 13C NMR (125 MHz, CDCl3) d 160.72, 159.88, 133.32,
125.07, 115.36, 114.20, 110.37, 109.37, 103.12, 101.74, 89.18, 88.28, 81.78,
55.62; IR (film) mmax 3002, 2957, 2935, 2837, 2216, 1650, 1588, 1511, 1452,
1419, 1357, 1347, 1290, 1248, 1205, 1156, 1121, 1064, 1031 cmÀ1; HRMS (ESI)
m/z 269.1178 [(M+H)+; calcd for [C17H17O3]+: 269.1172].
Acknowledgments
The authors are grateful to UC Berkeley and the NIH (NIGMS
GM84906-01) for generous financial support. We would also like
to thank Dr. Antonio DiPasquale for obtaining the X-ray structures
of 9 and 15.
12. Ramirez, F.; Desai, N. B.; McKelvie, N. J. Am. Chem. Soc. 1962, 84, 1745–1747.
13. (a) Corey, E. J.; Fuchs, P. L. Tetrahedron Lett. 1972, 13, 3769–3772; For a review
of alkyne synthesis using phosphorous compounds, see: (b) Eymery, F.; Iorga,
B.; Savignac, P. Synthesis 2000, 185–213.
14. Nakamura, H.; Kuroda, H.; Saito, H.; Suzuki, R.; Yamori, T.; Maruyama, K.; Haga,
T. Chem. Med. Chem. 2006, 1, 729–740.
15. (a) Sonogashira, K.; Tohda, Y.; Hagihara, N. Tetrahedron Lett. 1975, 4467–4470;
For a review of organopalladium chemistry in organic synthesis, see: (b)
Sonogashira, K. Synthesis 2002, 1, 493–529.
Supplementary data
16. Compound 9: To a flame-dried Schlenk tube containing Pd(OAc)2 (0.007 g,
Experimental details and characterization data for all new
compounds; X-ray structures of 9 and 15, structure refinement
details, tables of atomic coordinates, thermal parameters, bond
lengths, and bond angles. This material is available upon request
from the authors. Crystallographic data (excluding structure fac-
tors) for the structures in this paper have been deposited with
the Cambridge Crystallographic Data Centre as supplementary
publication nos. 718629 and 718630. Copies of the data can be
obtained, free of charge, on application to CCDC, 12 Union Road,
Cambridge CB2 1EZ, UK, (fax: +44-(0)1223-336033 or e-mail: de-
posit@ccdc.cam.ac.Uk). Supplementary data associated with this
article can be found, in the online version, at doi:10.1016/
0.031 mmol) and triphenylphosphine (0.016 g, 0.062 mmol) was added
a
solution of bromide 6 (0.050 g, 0.154 mmol), tolane 7 (0.081 g, 0.301 mmol),
and N,N-diisopropylethylamine (DIPEA) (0.08 mL, 0.461 mmol) in DMF (1 mL)
via syringe. The combined reaction mixture was evacuated, backfilled with N2
(Â3), sealed, and heated in an oil bath at 135 °C for 15 h. The reaction mixture
was allowed to cool to rt, diluted with Et2O (10 mL), and washed with 1%
aqueous HCl (3 Â 5 mL). The combined aqueous washings were reextracted
with Et2O (2 Â 5 mL). The combined organic extracts were washed with 1%
aqueous HCl (5 mL), brine (2 Â 5 mL), dried over MgSO4, filtered, and
concentrated in vacuo to afford a dark red residue. The crude product was
purified by flash chromatography (12:1 hexanes/EtOAc) to afford 0.0437 g
(53% yield) of 9 as a bright red solid. Rf 0.70 (1:1 hexanes/EtOAc); 1H NMR
(400 MHz, CDCl3) d 7.48 (d, J = 8.5 Hz, 2H), 7.07 (d, J = 8.5 Hz, 3H), 7.03 (s, 1H),
6.99 (s, 1H), 6.92 (d, J = 5.0 Hz, 2H), 6.79 (m, 2H), 6.41 (m, 2H), 6.37 (m, 1H),
6.29 (s, 1H), 3.84 (s, 3H), 3.77 (s, 3H), 3.70 (m, 3H), 3.62 (s, 6H), 3.59 (s, 3H); 13C
NMR (125 MHz, CDCl3)
d 160.15, 159.44, 159.27, 158.44, 158.33, 141.19,
140.64, 139.63, 138.90, 137.95, 137.40, 132.47, 131.38, 131.10, 129.46, 127.90,
124.58, 124.43, 113.98, 113.96, 113.44, 112.44, 109.82, 108.49, 102.04, 99.70,
99.58, 99.03, 55.83, 55.66, 55.64, 55.55, 55.42, 55.32; IR (film) mmax 2998, 2936,
References and notes
2836, 1591, 1559, 1540, 1509, 1462, 1421, 1282, 1247, 1203, 1174, 1153, 1105,
1065 cmÀ1; HRMS (ESI) m/z 536.2198 [(M+); calcd for [C34H32O6]+: 536.2199];
mp 158–159 °C.
1. For a review of domino reactions in organic synthesis, see: (a) Tietze, L. F.
Chem. Rev. 1996, 96, 115–136; For a review of the Heck reaction in modern
synthesis and
a
list of several examples of palladium-catalyzed cascade
17. Compound 15: To a solution of 9 (0.0171 g, 0.0319 mmol) in CH2Cl2 (1 mL) was
added FeCl3Á6H2O (0.009 g, 0.0319 mmol). The reaction mixture was stirred at
rt for 18 h, diluted with CH2Cl2 (5 mL), washed with water (3 mL), brine (5 mL),
dried over MgSO4, filtered, and concentrated in vacuo. The resulting residue
was purified by flash chromatography (9:1 hexanes/EtOAc) to give 0.0065 g
(38% yield) of 15 as a maroon solid. Rf 0.50 (1:1 hexanes/EtOAc); 1H NMR
(400 MHz, CDCl3) d 7.52 (d, J = 8.8 Hz, 4H), 6.91 (d, J = 8.8 Hz, 4H), 6.37 (d,
J = 2.0 Hz, 2H), 5.95 (d, J = 2.0 Hz, 2H), 3.85 (s, 6H), 3.64 (s, 6H), 3.52 (s, 6H); 13C
reactions, see: (b) De Meijere, A.; Meyer, F. E. Angew. Chem., Int. Ed. Engl.
1994, 33, 2379–2411.
2. Takaoka, M. Proc. Imp. Acad. Tokyo 1940, 16, 405–407.
3. Langcake, P.; Pryce, R. J. Physiol. Plant Pathol. 1976, 9, 77–86.
4. Jang, M.; Cai, L.; Udeani, G. O.; Slowing, K. V.; Thomas, C. F.; Beecher, C. W. W.;
Fong, H. H. S.; Farnsworth, N. R.; Kinghorn, A. D.; Mehta, R. G.; Moon, R. C.;
Pezzuto, J. M. Science 1997, 275, 218–220.
5. Valenzano, D. R.; Terzibasi, E.; Genade, T.; Cattaneo, A.; Domenici, L.; Cellerino,
A. Curr. Biol. 2006, 16, 296–300.
6. (a) Ohyama, M.; Tanaka, T.; Iinuma, M. Phytochemistry 1995, 38, 733–740; (b)
Ohyama, M.; Tanaka, T.; Iinuma, M. Chem. Pharm. Bull. 1994, 42, 2117–2120; (c)
Adesanya, S. A.; Nia, R.; Martin, T. M.; Boukamcha, N.; Montagnac, A.; Pais, M. J.
Nat. Prod. 1999, 62, 1694–1695; (d) Luo, H.-F.; Zhang, L.-P.; Hu, C.-Q.
NMR (125 MHz, CDCl3) d 161.71, 159.61, 156.22, 146.79, 142.30, 140.10,
139.14, 130.78, 128.11, 118.08, 112.79, 101.68, 98.47, 97.19, 69.72, 55.57,
55.47, 55.45, 53.98; IR (film) mmax 2927, 1596, 1508, 1462, 1390, 1360, 1246,
1200, 1151, 1085 cmÀ1; HRMS (ESI) m/z 534.2035 [(M+); calcd for [C34H30O6]+:
534.2042]; mp 242–243 °C.
18. Kovacic, P.; Jones, M. B. Chem. Rev. 1987, 87, 357–379.