2696
E. Chevenier et al.
LETTER
The cooled solution was worked up in the usual way with
CHCl3 to afford a solid product, which was triturated with
Et2O and filtered to give 4 (79 mg, 37%) as an orange solid.
Mp 268–269 °C (CHCl3). IR (neat): 3411, 1649, 1620, 1602
cm–1. 1H NMR (300 MHz, CDCl3): d = 3.62 (s, 3 H), 3.89 (s,
3 H), 3.90 (s, 3 H), 3.98 (s, 3 H), 4.04 (s, 3 H), 5.16 (s, 2 H),
6.32 (d, J = 2.2 Hz, 1 H), 6.52 (d, J = 2.2 Hz, 1 H), 6.57 (d,
J = 2.2 Hz, 1 H), 6.70 (d, J = 2.2 Hz, 1 H), 6.98 (s, 1 H), 7.65
(s, 1 H). 13C NMR (75.4 MHz, CDCl3): d = 55.5 (CH3), 55.6
(CH3), 56.3 (CH3), 56.4 (CH3), 59.1 (CH3), 73.6 (CH2), 96.9
(CH), 97.9 (CH), 99.6 (CH), 99.8 (CH), 100.8 (CH), 104.4
(C), 108.2 (C), 109.7 (C), 112.4 (C), 119.7 (CH), 137.5 (C),
140.4 (C), 141.8 (C), 152.0 (C), 157.2 (C), 159.8 (C), 161.0
(C), 161.7 (C), 161.8 (C), 163.9 (C), 183.8 (C). MS (DCI,
NH3 + isobutane): m/z (%) = 477 (100) [MH+]. HRMS: m/z
calcd for C27H24O8: 476.1471. Found: 476.1479 (M+).
Xanthone 4 was identical in all respects with the material
prepared earlier2 through the homo-Fries route.
References
(1) (a) Edwards, R. L.; Fawcett, V.; Maitland, D. J.; Nettleton,
R.; Shields, L.; Whalley, A. J. S. J. Chem. Soc., Chem.
Commun. 1991, 1009. (b) Gimbert, Y.; Chevenier, E.;
Greene, A. E.; Massardier, C.; Piettre, A. EP 014025514,
2001.
(2) Piettre, A.; Chevenier, E.; Massardier, C.; Gimbert, Y.;
Greene, A. E. Org. Lett. 2002, 4, 3139.
(3) (a) Kjaer, D.; Kjaer, A.; Risbjerg, E. J. Chem. Soc., Perkin
Trans. 1 1983, 2815. (b) Kjaer, A.; Kjaer, D. Acta. Chem.
Scand. B 1982, 36, 417. (c) To the best of our knowledge,
bikaverin is the only natural product prepared to date
through the use of this chemistry.
(4) Crystal data for 8: C21H12O3 monoclinic. P21/n; a = 7.729 (1)
Å, b = 8.127 (3) Å, c = 23.067 (3) Å; b = 95.95 (1)°;
V = 1441.1 (5) Å3; D = 1.44 gcm–3; m = 0.96 cm–1;
l = 0.71073 Å. 2qmax = 48°. 2501 measured reflections, 2440
independent reflections; 220 parameters. Reflections/
parameters ratio: 6.8; R [I>1.1s(I)] = 5.8%; wR [all
data] = 5.8%. G. O. F. (all data) = 1.54. Full lists of
fractional atomic co-ordinates, bond lengths and angles, and
thermal parameters have been deposited with the Cambridge
Crystallographic Data Centre as supplementary publication
no. CCDC-247512.
(5) (a) Chiarello, J.; Joullié, M. Tetrahedron 1988, 44, 41.
(b) Barrett, A. G. M.; Moris, T. M.; Barton, D. H. R. J.
Chem. Soc., Perkin Trans. 1 1980, 2272.
(6) (a) Hauser, F. M.; Rhee, R. Synthesis 1977, 245.
(b) Hauser, F. M.; Rhee, R. P. J. Org. Chem. 1977, 42, 4155.
(c) Hauser, F. M.; Rhee, R. J. Am. Chem. Soc. 1977, 99,
4533.
(16) (a) Although acetonaphthone 17a was known,16b the
reported yield was only 3.5%. Therefore, a new route was
developed (Scheme 8, R = H; 30% overall yield).
Acetonaphthone 17b16c could be prepared through a route
analogous to that used for the preparation of acetonaphthone
15b (Scheme 5, N-methoxy-N-methylacetamide replaces
12); however, a route analogous to that used for 17a proved
superior (Scheme 8, R = OMe; 52% overall yield).
(b) Yang, N. C.; Lin, L. C.; Shani, S.; Yang, S. S. J. Org.
Chem. 1969, 34, 1845. (c) Dodd, J. H.; Garigipati, R. S.;
Weinreb, S. M. J. Org. Chem. 1982, 47, 4045.
R
R
MeO2C
CO2Me
(7) For an excellent review of modern methods for the synthesis
of naphthalenes, see: de Koning, C. B.; Rousseau, A. L.; van
Otterlo, W. A. L. Tetrahedron 2003, 59, 7.
(8) Graham, S. L.; Scholz, T. H. J. Org. Chem. 1991, 56, 4260.
(9) For similar transformations, see: Lewis, C. N.; Spargo, P. L.;
Staunton, J. Synthesis 1986, 944.
(10) Weinreb amides are superior to acid chlorides for this type
of reaction. See: Carpenter, T. A.; Evans, G. E.; Leeper, F.
J.; Staunton, J.; Wilkinson, M. R. J. Chem. Soc., Perkin
Trans. 1 1984, 1043; see also ref. 6c.
(11) Matsumoto, N.; Nakashima, T.; Isshiki, K.; Kuboki, H.;
Hirano, S.-I.; Kumagai, H.; Yoshioka, T.; Ishizuka, M.;
Takeuchi, T. J. Antibiotics 2001, 54, 285.
CH2(CO2Me)2
Pyridine, TiCl4
O
R
R
O
OH
R
1. MeSO3H
2. MeLi, TMSCl
R
17a, R = H
b, R = OMe
Scheme 8
(17) Crystal data for 18d: C26H22O7 triclinic. P-1; a = 10.404 (3)
Å, b = 11.124 (3) Å, c = 15.392 (6) Å; a = 67.91 (2)°, b =
77.29 (2)°, g = 66.97 (2)°. V = 1513.5 (9) Å3; D = 1.49 gcm–3;
m = 1.97 cm–1, l = 0.56083 Å; 2qmax = 35.7°. 3863 measured
reflections, 3863 independent reflections. 424 parameters.
Reflections/parameters ratio: 5; R [I>2s(I)] = 9.7%; wR [all
data] = 9.9%. G. O. F. = 2.22. The poor resolution is due to
problems associated with severely disordered CHCl3
molecules in the asymmetric cell and desolvation (capillary
tube). Full lists of fractional atomic co-ordinates, bond
lengths and angles, and thermal parameters have been
deposited with the Cambridge Crystallographic Data Centre
as supplementary publication no. CCDC-247513.
(12) Roush, W. R.; Murphy, M. J. Org. Chem. 1992, 57, 6622.
(13) (a) Rubottom, G. M.; Kim, C. J. Org. Chem. 1983, 48, 1550.
(b) Cooke, M. P. J. Org. Chem. 1986, 51, 951.
(14) Shi, J.; Zhang, X.; Neckers, D. C. J. Org. Chem. 1992, 57,
4418.
(15) Procedure for the Preparation of 4 – Polycondensation of
11 and 15b: To a stirred suspension of pentane-washed NaH
(79 mg, 3.29 mmol, from a 60% dispersion in mineral oil) in
anhyd THF (2.5 mL) under argon at 0 °C was added
dropwise a solution of 15b (130 mg, 0.45 mmol) in THF (5.0
mL). The mixture was stirred at 25 °C for 1 h before the
addition of a solution of homophthalate 11 (204 mg, 0.76
mmol) in THF (3.5 mL). The resultant mixture was stirred at
25 °C for 2 h and then heated at 80 °C for 20 h (pressure
tube). The solution was cooled and aq HCl (6 N) was added,
and the resultant mixture was extracted with CHCl3. After
the usual workup, the product was flash chromatographed
(SiO2, EtOAc in pentane, 30–50%) to give a mixture of 4 and
16 (12% and 25%, respectively, NMR), which was heated in
H2O–toluene 5:1 (12 mL) at 180 °C for 16 h (pressure tube).
(18) This procedure for accessing the o-quinone methides was
found to be more convenient than that previously used2
based on Saegusa dehydrosilylation.
(19) The corresponding unprotected derivatives 19b–d (R1,
R2 = H, OH) could also be secured in moderate yield through
treatment of the xanthones 18b–d with boron tribromide
prior to reduction–hydrolysis.
Synlett 2004, No. 15, 2693–2696 © Thieme Stuttgart · New York