3846
J. Nanclares et al. / Tetrahedron Letters 49 (2008) 3844–3847
7. Badger, G.; Carruthers, W.; Cook, J. J. Chem. Soc. 1949, 1768–1771.
For identification purposes, 2,3-dihydro-4-methoxy-1H-
8. Imanzadeh, G.; Zamanloo, M.; Eskandari, H.; Shayesteh, K. J.
Chem. Res. 2006, 151–153; Experimental procedure: NBS (1.8 g,
10 mmol), neutral Al2O3 (8.2 g, flame dried), and 2-methoxynaph-
thalene (954 mg, 6 mmol) were mixed in a mortar until a uniform
color was perceived. The mixture was transferred to a round-
bottomed flask and then heated to 90 °C for one hour. Extraction
with CH2Cl2 followed by solvent evaporation afforded 1-bromo-2-
methoxynaphthalene (5) (1.4 g, 98%).
phenalen-1-one (4-methoxyperinaphthanone, 6) was
obtained using the above mentioned procedure for com-
pound 1 without adding DDQ and purified by column
chromatography using CH2Cl2 as an eluent (54% yield).14
The product slowly decomposed to 1 in open air atmo-
sphere at 30 °C.
In summary, we have developed a five-step synthesis of
9. Experimental procedure: A 100 mL three-necked round-bottomed
flask equipped with a condenser was charged with PdCl2 (161.6 mg,
0.72 mmol), tri-o-tolylphosphine (895 mg, 2.94 mmol), 1-bromo-2-
methoxynaphthalene (3.4 g, 14.5 mmol) and DMF (50 mL). The
mixture was refluxed under nitrogen for 6 h at 160 °C. DMF was
removed under vacuum and the crude mixture subjected to column
chromatography (n-hexane–diethyl ether is 9:1) to give an (E,Z)-
mixture of ethyl 3-(2-methoxy-1-naphthyl)acrylate (4) as a brown oil.
(68%, (E):(Z) ratio is 7:3); (E)-diastereomer: 1H NMR (C3D6O,
500.13 MHz) d 8.33 (d, J = 16.2 Hz, H-3), 8.18 (d, J = 8.6 Hz, H-80),
8.00 (d, J = 9.2 Hz, H-40), 7.86 (d, J = 8.1 Hz, H-50), 7.59 (dd, J = 8.6,
8.5 Hz, H-70), 7.51 (d, J = 9.2 Hz, H-30), 7.42 (dd, J = 8.5, 8.1 Hz,
H-60), 6.75 (d, J = 16.2 Hz, H-2), 4.27 (q, J = 7.2 Hz, –OCH2CH3),
4.07 (s, –OCH3), 1.33 (t, J = 7.2 Hz, –OCH2CH3); 13C NMR (C3D6O,
125.75 MHz) d 167.8 (C-1), 158.0 (C-20), 137.8 (C-3), 133.5 (C-8a0),
132.7 (C-40), 130.0 (C-4a0), 129.6 (C-50), 128.4 (C-70), 124.7 (C-60),
124.0 (C-2), 123.6 (C-80), 116.8 (C-10), 114.0 (C-30), 60.7 (–OCH2-
CH3), 56.7 (–OCH3), 14.7 (–OCH2CH3). HREIMS m/z 256.111221
(calcd for C16H16O3, 256.109945).
4-methoxy-1H-phenalen-1-one
(4-methoxyperinaphthe-
none, 1) starting from 2-methoxynaphthalene in a 36% glo-
bal yield. The use of a Heck–Fujiwara coupling and the
one-pot cyclization procedure significantly improved the
previously reported methods. Further studies focusing on
the use of 1 in the synthesis of natural phenylphenalenones
or structural analogs are currently underway.
Acknowledgments
We thank Sybille Lorenz for mass spectrometric analy-
ses, E. Wheeler for editorial assistance, and professors J.
M. Aurrecoechea and B. Figadere for useful comments.
This research was financially supported by Universidad
de Antioquia (Programa de Sostenibilidad), Universidad
Nacional de Colombia (grant 2010100516), and the Max-
10. Experimental procedure: A balloon filled with hydrogen was fitted to a
25 mL round-bottomed flask charged with the catalyst (1 g) and a
solution of 4 (2.2 g, 14 mmol) in MeOH (10 mL). The mixture was
stirred at 25 °C for 24 h, the catalyst filtered and the solvent
evaporated. Ethyl 3-(2-methoxy-1-naphthyl)propanoate (3): White
powder, 1H NMR (C3D6O, 500.13 MHz) d 8.01 (d, J = 8.6 Hz, H-80),
7.84 (d, J = 8.1 Hz, H-50), 7.83 (d, J = 9.0 Hz, H-40), 7.50 (dd, J = 8.6,
8.5 Hz, H-70), 7.42 (d, J = 9.0 Hz, H-30), 7.34 (dd, J = 8.5, 8.1 Hz,
H-60), 4.10 (q, J = 7.2 Hz, –OCH2CH3), 3.98 (s, –OCH3), 3.38 (t,
J = 8.2 Hz, H-3), 2.54 (t, J = 8.2 Hz, H-2), 1.20 (t, J = 7.2 Hz,
–OCH2CH3); 13C NMR (C3D6O, 125.75 MHz) d 173.2 (C-1), 155.5
(C-20), 133.4 (C-8a0), 130.2 (C-4a0), 129.4 (C-50), 129.0 (C-40), 127.3
(C-70), 124.0 (C-60), 123.5 (C-80), 122.1 (C-10), 114.1 (C-30), 60.6
(–OCH2CH3), 56.7 (–OCH3), 34.8 (C-2), 21.3 (C-3), 14.5 (–OCH2-
CH3). HREIMS m/z 258.124791 (calcd for C16H18O3, 258.125595).
11. (a) Laundon, B.; Morrison, G. A.; Brooks, J. S. J. Chem. Soc. C 1971,
36–40; (b) Elwood, J. J. Org. Chem. 1973, 38, 2425–2430; (c) Schlomp,
G.; Kirste, B.; Hass, C. J. Am. Chem. Soc. 1983, 105, 7375–7383.
12. Sarvani, H. M.; Sharghi, H. Helv. Chim. Acta 2005, 88, 2282–2287.
13. Experimental procedure: To a 50 mL round-bottomed flask charged
with 2 (242 mg, 1 mmol) was added SOCl2 (1 mL). After gas evolution
had ceased, the flask was air-dried and the SOCl2 addition repeated
three times. The product was dissolved in CH2Cl2 (25 mL) and AlCl3
(400 mg) was added in one portion (the solution turns red). DDQ
(304 mg, 1.3 equiv) was added after 10 min and the mixture main-
tained at 30 °C for 15 min. Finally, silica gel (5 g) was added and the
mixture was dried at 30 °C. Column chromatography (1:1 n-hexane–
CH2Cl2) afforded 4-methoxy-1H-phenalen-1-one (4-methoxyperi-
naphthenone, 1) (134 mg, 64%): Orange powder, 1H NMR (C3D6O,
500.13 MHz) d 8.50 (d, J = 7.5 Hz, H-9), 8.30 (d, J = 7.9 Hz, H-7),
8.25 (d, J = 9.2 Hz, H-6), 8.25 (d, J = 10.0 Hz, H-3), 7.72 (dd, J = 7.5,
7.9 Hz, H-8), 7.60 (d, J = 9.2 Hz, H-5), 6.58 (d, J = 10.0 Hz, H-2),
4.17 (s, –OCH3); 13C NMR (C3D6O, 125.75 MHz) d 184.7 (C-1),
159.9 (C-4), 140.0 (C-3), 135.9 (C-6), 135.6 (C-7), 131.3 (C-9), 130.1
(C-9a), 129.0 (C-6a), 127.9 (C-2), 125.7 (C-8), 124.4 (C-9 b), 114.9
(C-5), 113.8 (C-3a), 57.1 (–OCH3). HREIMS m/z 210.067280 (calcd
for C14H10O2, 210.068080).
¨
Planck-Institut fur Chemische Okologie.
¨
References and notes
´
1. (a) Luis, J. G.; Echeverri, F.; Quinones, W.; Brito, I.; Lopez, M.;
˜
Torres, F.; Cardona, G.; Aguiar, Z.; Pelaez, C.; Rojas, M. J. Org.
Chem. 1993, 58, 4306–4308; (b) Kamo, T.; Kato, N.; Hirai, N.; Tsuda,
M.; Fujioka, D.; Ohigashi, H. Biosci. Biotechnol. Biochem. 1998, 62,
95–101; (c) Kamo, T.; Hirai, H.; Iwami, K.; Fujioka, D.; Ohigashi, H.
Tetrahedron 2001, 57, 7649–7656; (d) Opitz, S.; Otalvaro, F.;
Echeverri, F.; Quinones, W.; Schneider, B. Nat. Prod. Lett. 2002,
16, 335–338; (e) Otalvaro, F.; Go¨rls, G.; Ho¨lscher, D.; Schmitt, B.;
Echeverri, F.; Quinones, W.; Schneider, B. Phytochemistry 2002, 60,
61–66; (f) Otalvaro, F.; Nanclares, J.; Vasquez, E.; Quinones, W.;
˜
´
˜
´
˜
´
´
Echeverri, F.; Arango, R.; Schneider, B. J. Nat. Prod. 2007, 70, 887–
890.
2. (a) Cooke, R. G.; Edwards, J. M. Prog. Chem. Org. Nat. Prod. 1980,
40, 153–190; (b) Ho¨lscher, D.; Schneider, B. Phytochemistry 1999, 50,
155–161; (c) Ho¨lscher, D.; Schneider, B. J. Nat. Prod. 2000, 63, 1027–
1028; (d) Opitz, S.; Ho¨lscher, D.; Oldham, N. J.; Bartram, S.;
Schneider, B. J. Nat. Prod. 2002, 65, 1122–1130; (e) Ho¨lscher, D.;
Schneider, B. Phytochemistry 2005, 66, 59–64.
3. (a) Quinones, W.; Escobar, G.; Echeverri, F.; Torres, F.; Rosero, Y.;
˜
Arango, V.; Cardona, G.; Gallego, G. Molecules 2000, 5, 974–980; (b)
Ortega, R.; Martınez, S.; Saugar, J.; Izquierdo, L.; Abad, T.; Luis, J.;
Pinero, J.; Valladares, B.; Rivas, L. Antimicrob. Agents Chemother.
2004, 48, 1534–1540; (c) Lazzaro, A.; Corominas, M.; Martı, C.;
Flors, C.; Izquierdo, L.; Grillo, T.; Luis, J.; Nonell, S. Photochem.
Photobiol. Sci. 2004, 3, 706–710. See also Refs.1b, 1c and 1f.
´
˜
´
4. (a) Cooke, R.; Dagley, I. Aust. J. Chem. 1978, 31, 193–197; (b)
´
Otalvaro, F.; Quinones, W.; Echeverri, F.; Schneider, B. J. Labelled.
˜
Compd. Radiopharm. 2004, 47, 147–159. See also Ref. 2a.
5. (a) Cooke, R.; Dagley, I. Aust. J. Chem. 1979, 32, 1841–1847; (b)
Takikawa, H.; Yoshida, M.; Mori, K. Biosci. Biotechnol. Biochem.
1999, 63, 1834–1836.
14. Experimental procedure: 2,3-Dihydro-4-methoxy-1H-phenalen-1-one
(4-methoxyperinaphthanone, 6) was synthesized from 2 (92 mg) by
treatment with SOCl2 (3 ꢂ 0.5 mL), dissolving the residue in CH2Cl2
6. (a) Cooke, G.; Johnson, B.; Segal, W. Aust. J. Chem. 1958, 11, 230–
235. For a review, see: (b) Reid, D. H. Quart. Rev. 1965, 19, 274–
302.