SYNTHESIS
August 1998
1159
(4aS*,9aS*)-8,9a-Bis(tert-butoxymethyl)-7-hydroxy-2,3,4a,5,6-pen-
tamethyl-4,4a,9,9a-tetrahydro-1H-xanthene-1,4-dione (13B): orange
liquid.
We thank the Ministère de la Recherche et de l’Enseignement
Supérieur (MRES) for financial support and Ciba-Geigy (Marly,
Switzerland) for the elemental analyses. The authors are greatly
indebted to Prof. H. Stoeckli-Evans, University of Neuchâtel, for car-
rying out the X-ray structural determination of 12A. We are very
grateful to Prof. P. Renaud for helpful comments.
1H NMR (CDCl3, 500 MHz): δ = 8.51 (s, 1H, OH); 4.69 (AB, JAB
=
12.0 Hz, 2H, C(8)-CH2O); 3.38 (AB, JAB = 8.6 Hz, 2H, C(9a)-CH2O);
3.38 (d, J = 16.0 Hz, 1H, C(9)H2); 2.17 (d, J = 16.0 Hz, 1H, C(9)H2);
2.08 (s, 3H, C(6)-CH3); 1.95 (s, 3H, C(5)-CH3); 1.94 (q, J = 1.1 Hz,
3H, CH3); 1.91 (q, J = 1.1 Hz, 3H, CH3); 1.40 (s, 3H, C(4a)-CH3);
1.36 (s, 9H, CH3); 1.00 (s, 9H, CH3).
(1) Krause, M.; Hoffman, H. M. R. Tetrahedron Lett. 1990, 31,
6629.
(2) Subramanian, R. S.; Balasubramanian, K. K. Tetrahedron Lett.
1989, 30, 2297.
(3) Salomon, R. G.; Lal, K.; Mazza, S. M.; Zarate, E. A.; Youngs,
W. J. J. Am. Chem. Soc. 1988, 110, 5213.
(4) Takasaki, M.; Konoshima, T.; Kozuka, M.; Haruna, M.; Ito, K.;
Yoshida, S. Chem. Pharm. Bull. 1994, 42, 2177.
(5) Kokumai, M.; Konoshima, T.; Kozuka, M. J. Nat. Prod. 1991,
54, 1082.
13C NMR (CDCl3, 125.77 MHz): δ = 198.8 (s, CO); 193.9 (s, CO);
148.6 (s); 144.5 (s); 142.4 (s); 142.0 (s); 124.9 (s); 123.7 (s); 116.1
(s); 111.3 (s); 79.1 (s, C(4a)); 75.3 (s); 73.6 (s); 64.8 (t, C(9a)-CH2O);
60.1 (t, C(8)-CH2O); 48.0 (s, C(9a)); 27.3 (q, CH3); 26.7 (q, CH3);
24.6 (t, C(9)); 14.9 (q, CH3); 13.2 (q,CH3); 11.9 (q, CH3); 11.6 (q,
CH3).
CI-MS (CH4): m/z (%) = 473 (100, M+), 416 (43), 359 (17), 343 (7),
327 (4), 299 (3), 271 (1).
C28H40O6
(472.62)
calcd
found
C
71.16
71.41
H
8.53
8.71
(6) Xu, R.; Snyder, J. K.; Nakanishi, K. J. Am. Chem. Soc. 1984,
106, 734.
(7) Salomon, R. G.; Mazza, S. M.; Lal, K. J. Org. Chem. 1989, 54,
1562.
(8) Chiba, K.; Sonoyama, J.; Tada, M. J. Chem. Soc., Chem. Com-
mun. 1995, 1381.
(9) Koser, S.; Hoffman, H. M. R. Heterocycles 1994, 37, 661.
(10) Appendino, G.; Cravotto, G.; Toma, L.; Annunziata, R.; Pal-
misano, G. J. Org. Chem. 1994, 59, 5556.
(11) Majewski, M.; Irvine, N. M.; Bantle, G. W. J. Org. Chem. 1994,
59, 6697.
(12) Koser, S.; Hoffman, H. M. R. J. Org. Chem. 1993, 58, 6164.
(13) Wagner, H.-U.; Gompper, R. In The Chemistry of the Quinono-
id Compounds; Patai, S. Ed.; Wiley: New York, 1974; p 1145.
(14) For a recent review on hetero Diels–Alder reactions in organic
chemistry, see: Tietze, L. F.; Kettschau, G. Top. Curr. Chem.
1997, 189, 1.
(15) For reviews on the chemistry of quinone methides, see: Vecia-
na, J.; Martinez, A. D.; Armet, O. Rev. Chem. Intermed. 1988,
10, 35.
Volod'kin, A. A.; Ershov, V. V. Usp. Khim. 1988, 57, 595.
(16) Taing, M.; Moore, H. W. J. Org. Chem. 1996, 61, 329.
Bush, E. J.; Jones, D. W. J. Chem. Soc., Perkin Trans. 1 1996,
151.
According to the General Procedure (Table, Entry 2):
From 10 (500 mg, 1.85 mmol), MeOLi (71 mg, 1.85 mmol) at r.t. FC
(hexane/Et2O 1:1) gave 14A (366 mg, 73%) along with 14B (60 mg,
12%).
(4aS*,9aS*)-4a,8-Bis(benzyloxymethyl)-7-hydroxy-2,3,5,6,9a-penta-
methyl-4,4a,9,9a-tetrahydro-1H-xanthene-1,4-dione (14A): yellow oil.
1H NMR (CDCl3, 500 MHz): δ = 7.42 (s, 1H, OH); 7.34–7.18 (m, 10H,
10 arom H); 4.52 (AB, JAB = 11.9 Hz, 2H, OCH2Ph); 4.51 (s, 2H,
OCH2Ph); 4.50 (AB, JAB = 12.5 Hz, 2H, C(8)-CH2O); 3.77 (AB, JAB
=
10.4 Hz, 2H, C(4a)-CH2); 2.45 (AB, JAB = 16.6 Hz, 2H, C(9)H2); 2.27
(s, 3H, C(5)-CH3); 2.17 (s, 3H, C(6)-CH3); 1.97 (q, J = 1.1 Hz, 3H,
CH3); 1.92 (q, J = 1.1 Hz, 3H, CH3); 1.25 (s, 3H, C(9a)-CH3).
13C NMR (CDCl3, 125.77 MHz): δ = 199.7 (s, CO); 196.4 (s, CO);
148.6 (s); 143.4 (s); 142.9 (s); 142.8 (s); 137.2 (s); 136.7 (s); 128.6 (d,
=CH); 128.4 (d, =CH); 128.2 (d, =CH); 127.9 (d, =CH); 127.7 (d,
=CH); 125.7 (s); 124.1 (s); 115.7 (s); 112.0 (s); 85.3 (s, C(4a)); 73.7
(t, OCH2Ph); 73.3 (t, C(4a)-CH2O); 72.1 (t, OCH2Ph); 66.3 (t, C(8)-
CH2O); 48.7 (s, C(9a)); 33.8 (t, C(9)); 15.8 (q, C(9a)-CH3); 13.1 (q,
CH3); 13.0 (q, CH3); 12.2 (q, CH3); 11.8 (q, CH3).
CI-MS (CH4): m/z (%) = 541 (22, M+), 434 (67), 326 (100), 297 (4),
268 (19), 238 (7), 208 (34), 178 (3), 148 (8), 87 (10).
Eru, E.; Hawkes, G. E.; Utley, J. H. P.; Wyatt, P. B. Tetrahedron
1995, 51, 3033.
(17) Dean, F. M.; Matkin, D. A. J. Chem. Soc., Perkin Trans. I 1977,
2289.
C34H36O6
(540.65)
calcd
found
C
75.53
75.62
H
6.71
6.76
Smith, L. I.; Tess, R. W. H.; Ullyot, G. E. J. Am. Chem. Soc.
1944, 66, 1320.
(18) Dean, F. M.; Houghton, L. E. J. Chem. Soc. (C) 1968, 1060.
Chandrasenan, K.; Thomson, R. H. J. Chem. Soc. (C) 1966, 123.
(19) Crozet, M. P.; Giraud, L.; Sabuco, J.-F.; Vanelle, P.; Barreau,
M. Tetrahedron Lett. 1991, 32, 4125.
(20) Chiba, K.; Tada, M. J. Chem. Soc., Chem. Commun. 1994, 2485.
Inoue, T.; Inoue, S.; Sato, K. Bull. Chem. Soc. Jpn. 1990, 63,
1647.
(4aS*,9aS*)-8,9a-Bis(benzyloxymethyl)-7-hydroxy-2,3,4a,5,6-pen-
tamethyl-4,4a,9,9a-tetrahydro-1H-xanthene-1,4-dione (14B): orange
liquid.
1H NMR (CDCl3, 500 MHz): δ = 7.52 (s, 1H, OH); 7.32–7.11 (m,
10H, 10 arom H); 4.72 (AB, JAB = 12.6 Hz, 2H, C(8)-CH2O); 4.59 (s,
2H, C(8)-CH2O-CH2); 4.35 (s, 2H, C(9a)CH2OCH2); 3.48 (AB, JAB
=
6.9 Hz, 2H, C(9a)-CH2O); 3.33 (d, J = 15.9 Hz, 1H, C(9)H2); 2.21 (d,
J = 15.9 Hz, 1H, C(9)H2); 2.10 (s, 3H, C(6)-CH3); 2.03 (q, J = 1.1 Hz,
3H, CH3); 1.98 (s, 3H, C(5)-CH3); 1.92 (q, J = 1.1 Hz, 3H, CH3); 1.37
(s, 3H, C(4a)-CH3).
Guindon, Y.; Frenette, R.; Fortin, R.; Rokach, J. J. Org. Chem.
1983, 48, 1357.
Mao, Y.; Boekelheide, V. Proc. Natl. Acad. Sci. USA 1980, 77,
1732.
13C NMR (CDCl3, 125.77 MHz): δ = 197.8 (s, CO); 194.4 (s, CO);
148.6 (s); 148.2 (s); 144.1 (s); 144.0 (s); 138.4 (s); 137.1 (s); 128.6 (d,
=CH); 128.3 (d, =CH); 128.1 (d, =CH); 127.9 (d, =CH); 127.6 (d,
=CH); 126.2 (s); 123.9 (s); 115.8 (s); 113.3 (s); 83.3 (s, C(4a)); 73.7
(t, C(9a)-CH2O); 73.5 (t, CH2OCH2Ph); 72.2 (t, CH2OCH2Ph); 66.6
(t, C(8)-CH2O); 54.7 (s, C(9a)); 25.1 (t, C(9)); 15.7 (q, C(4a)-CH3);
13.3 (q,CH3); 13.1 (q, CH3); 12.0 (q, C(5)-CH3); 11.7 (q, C(6)-CH3).
CI-MS (CH4): m/z (%) = 541 (11, M+), 511 (43), 481 (100), 390 (18),
299 (13), 269 (4), 239 (11), 209 (9), 105 (34), 53 (4).
(21) Seebach, D.; Wasmuth, D. Helv. Chim. Acta 1980, 63, 197.
(22) Appendino, G.; Cravotto, G.; Tagliapietra, S.; Ferraro, S.; Na-
no, G. M.; Palmisano, G. Helv. Chim. Acta 1991, 74, 1451.
Wolfrum, C.; Bohlmann, F. Liebigs Ann. Chem. 1989, 295.
(23) Fleming, I. Frontier Orbitals and Organic Chemical Reactions;
Wiley: London, 1976.
(24) Chen, X.; Hortelano, E. R.; Eliel, E. L.; Frye, S. V. J. Am. Chem.
Soc. 1992, 114, 1778.
C34H36O6
(540.65)
calcd
found
C
75.53
75.84
H
6.71
6.92
Reetz, M. T. Acc. Chem. Res. 1993, 26, 462.