L. F. Tietze, C. Güntner, K. M. Gericke, I. Schuberth, G. Bunkoczi
FULL PAPER
15 min. Next, the reaction mixture was placed in a pre-warmed oil
bath at 65–70 °C and stirred for 105 min. The solvent was removed
under reduced pressure (20 mbar) and the slurry re-suspended in
diethyl ether, filtered through Celite, and the solvent evaporated in
vacuo (15 mbar). The crude product was distilled to give a cis/trans
temperature. The solvent was removed under reduced pressure and
the crude product was stored at –18 °C under argon overnight. The
solid formed was re-suspended in diethyl ether and filtered to af-
ford 23 (430 mg, 24%) as pale beige crystals. M.p. Ͼ 170 °C (dec.).
1H NMR (200 MHz, CDCl3): δ = 0.65 (t, J = 7.0 Hz, 3 H,
OCH2CH3), 2.61 (ddd, J = 14.5, 3.5, 1.0 Hz, 1 H, 3-Ha), 2.90 (dd,
mixture of 18 (33 g, 44%) as a colorless oil. B.p. 32–36 °C/
1
0.15 mbar. H NMR (300 MHz, CDCl3): δ = 1.22 (d, J = 7.1 Hz, J = 14.5, 3.5 Hz, 1 H, 3-Hb), 3.02 (dd, J = 9.0, 7.0 Hz, 1 H, OCHa-
3 H, 4-CH3), 1.27 (t, J = 7.1 Hz, 3 H, OCH2CH3), 2.97 (m, 1 H,
4-H), 3.47 (s, 3 H, OCH3), 3.61 (dq, J = 7.1, 1.0 Hz, 2 H,
HCH3), 3.42 (dd, J = 9.0, 7.0 Hz, 1 H, OCHHbCH3), 3.49 (s, 3 H,
OCH3), 3.55 (dd, J = 6.0, 3.0 Hz, 1 H, 4a-H), 3.85 (dd, J = 6.0,
OCH2CH3), 3.65 (m, 1 H, 3-H), 4.48 (m, 1 H, 2-H) ppm. 13C NMR 6.0 Hz, 9a-H), 3.92 (dd, J = 6.0, 1.0 Hz, 1 H, 1-H), 4.19 (q, J =
(75 MHz, CDCl3): δ = 11.6 (CH3), 15.2 (OCH2CH3), 51.8 (C-4), 3.0 Hz, 1 H, 4-H), 7.15 (dd, J = 8.0, 1.3 Hz, 1 H, 6-H), 7.40 (dd,
58.3 (OCH3), 65.8 (OCH2CH3), 77.5 (C-3), 92.8 (C-2), 206.7 (C-1)
ppm. MS (70 eV, EI): m/z (%) = 158.1 (4) [M+], 102.1 (80), 85.0
(80), 74.0 (100), 58.0 (42), 45.1 (32), 41.1 (30). HRMS: m/z (M+,
C8H14O3): calcd. 158.0943; found 158.0943.
J = 7.3, 1.7 Hz, 1 H, 8-H), 7.57 (dd, J = 8.0, 7.3 Hz, 1 H, 7-H),
11.81 (s, 1 H, OH) ppm. 13C NMR (75 MHz, CDCl3): δ = 14.2
(OCH2CH3), 43.7 (C-3), 51.3 (C-9a), 54.1 (C-4a), 59.3 (OCH3),
64.9 (OCH2CH3), 78.3 (C-4), 82.2 (C-1), 117.4 (C-8), 118.3 (C-10a),
122.4 (C-5), 137.0 (C-7), 138.1 (C-8a), 161.3 (C-5), 191.1 (C-9),
(1Z,3E)-4-Ethoxy-1-methoxy-2-(trimethylsilanyloxy)butadiene (21):
Triethylamine (23.2 mL, 166 mmol) and then, dropwise, TMSCl
(9.9 mL, 78 mmol) were added to a solution of cyclobutanone 17
(8.0 g, 55.5 mmol) in acetonitrile (40 mL). Next, the mixture was
placed in a pre-warmed oil bath at 60 °C and stirred for 14 h (TLC
control). The solvent was removed under reduced pressure
(20 mbar), the slurry was re-suspended in diethyl ether containing
2% triethylamine (re-suspension in n-hexane is also possible), fil-
tered through Celite, and the solvent removed under reduced pres-
sure (20 mbar). The crude product was distilled (avoiding overheat-
ing) to give 21 (9.5 g, 79%) as a slightly reddish oil. B.p. 44–48 °C/
0.30 mbar. 1H NMR (300 MHz, CDCl3): δ = 0.20 [s, 9 H, Si-
(CH3)3], 1.27 (t, J = 7.0 Hz, 3 H, OCH2CH3), 3.53 (s, 3 H, OCH3),
3.74 (q, J = 7.0 Hz, 2 H, OCH2CH3), 5.21 (d, J = 12.2 Hz, 1 H, 3-
H), 5.47 (s, 1 H, 1-H), 6.51 (d, J = 12.2 Hz, 1 H, 4-H) ppm. 13C
NMR (75 MHz, CDCl3): δ = 0.20 [Si(CH3)3], 14.7 (OCH2CH3),
56.3 (OCH3), 65.3 (OCH2CH3), 101.5 (C-3), 103.5(C-1), 132.8 (C-
2), 145.3 (C-4) ppm. MS (70 eV, EI): m/z (%) = 216 (5) [M+,
C10H6O3Si], 201 (5), 189 (3), 157 (5), 133 (50), 99 (8), 89 (12), 73
(100).
202.0 (C-2, C-10) ppm. IR (KBr): ν = 2934, 1727, 1706, 1645, 1454,
˜
1331, 1258, 1240, 1137, 1102, 1018 cm–1. UV (CHCl3): λmax (log ε)
= 194.0 (4.182), 229.0 (4.323), 262.0 (3.698), 346.0 (3.700) ppm.
MS (70 eV, EI): m/z (%) = 318.1 (32) [M+], 288.1 (18), 240.1 (56),
218.1 (40), 173.1 (34), 159.1 (12), 144.1 (44), 102.1 (28), 89.1 (100),
72.0 (32), 61.0 (62), 45.0 (22). HRMS: m/z (M+, C17H18O6): calcd.
318.1103; found 318.1103.
(1SR,4SR,4aRS,9aSR)-4-Ethoxy-5-hydroxy-1-methoxy-3-methyl-2-
oxo-3,4,4a,9a-tetrahydro-1H-9,10-anthraquinone (24): Diene 22
(213 mg, 0.93 mmol) was added at 0 °C to a solution of juglone
(13; 64 mg, 0.37 mmol) in DCM (4.9 mL) and the reaction left to
warm to room temperature over 2 h while stirring. The solvent was
removed under reduced pressure and the crude product was stored
at –18 °C under argon overnight. The solid formed was re-sus-
pended in diethyl ether and filtered to afford 24 (47 mg, 38%) as
pale-yellow crystals. M.p. Ͼ 150 °C (dec.). 1H NMR (200 MHz,
CDCl3): δ = 0.48 (t, J = 7.0 Hz, 3 H, OCH2CH3),1.16 (d, J =
6.9 Hz, 3 H, CH3), 2.71 (m, 1 H, 3-H), 2.82 (dq, J = 9.4, 7.0 Hz,
1 H, OCHaHCH3), 3.21 (dq, J = 9.4, 7.0 Hz, 1 H, OCHHbCH3),
3.56 (s, 1 H, OCH3), 3.59 (m, 1 H, 4a-H), 3.92 (m, 1 H, 1-H), 3.94
(m, 1 H, 1a-H), 4.07 (br. t, J = 2.6 Hz, 1 H, 4-H), 7.18 (dd, J =
8.4, 0.9 Hz, 1 H, 6-H), 7.46 (dd, J = 7.5, 0.9 Hz, 1 H, 8-H), 7.62
(dd, J = 8.4, 7.5 Hz, 1 H, 7-H), 12.01 (s, 1 H, OH) ppm. 13C NMR
(75 MHz, CDCl3): δ = 10.18 (CH3), 14.27 (OCH2CH3), 48.96 (C-
3), 51.46 (C-9a), 55.82 (C-4a), 59.65 (OCH3), 69.81 (OCH2CH3),
82.89 (C-1), 84.95 (C-4), 191.30 (C-9), 117.52 (C-8), 117.75 (C-10a),
122.28 (C-6), 137.57 (C-7), 138.07 (C-8a), 161.62 (C-5), 202,76,
(1Z,3E)-4-Ethoxy-1-methoxy-3-methyl-2-(trimethylsilanyloxy)buta-
diene (22): Triethylamine (36.7 mL, 263 mmol) and then, dropwise,
TMSCl (15.7 mL, 124 mmol) were added to a solution of cyclobut-
anone 18 (13.8 g, 87 mmol) in acetonitrile (63 mL). Next, the mix-
ture was placed in a pre-warmed oil bath at 65 °C and stirred for
2.5 h (TLC control). The solvent was removed under reduced pres-
sure (20 mbar), the slurry was re-suspended in diethyl ether con-
taining 2% triethylamine (re-suspension in n-hexane is also pos-
sible), filtered through Celite, and the solvent removed under re-
duced pressure (20 mbar). The crude product was distilled (avoid-
ing overheating) to give 22 (15 g, 75%) as a slightly reddish oil.
202.84 (C-2, C-10) ppm. IR (KBr): ν = 2979, 1724, 1642, 1454,
˜
1334, 1240, 1136, 1071 cm–1. UV (CHCl3): λmax (log ε) = 194.0
(8.136), 229.5 (8.250), 347.0 (7.645) ppm. MS (70 eV, EI): m/z (%)
= 332.3 (26) [M+], 302.3 (24), 284.2 (16), 254.2 (100), 218.2 (20),
158.2 (14), 89.1 (52), 61.0 (32), 45.0 (10). HRMS: m/z (M+,
C18H20O6): calcd. 332.1260; found 332.1260.
1
B.p. 40–42 °C/0.115 mbar. H NMR (300 MHz, CDCl3): δ = 0.17
[s, 9 H, Si(CH3)3], 1.24 (t, J = 7.0 Hz, 3 H, OCH2CH3), 1.60 (d, J
= 1.2 Hz, 3 H, CH3), 3.55 (s, 3 H, OCH3), 3.81 (q, J = 7.0 Hz, 2
H, OCH2CH3), 5.57 (s, 1 H, 1-H), 6.30 (d, J = 1.2 Hz, 1 H, 4-H)
ppm. 13C NMR (75 MHz, CDCl3): δ = 0.30 [Si(CH3)3], 9.33 (CH3),
15.32 (OCH2CH3), 59.43 (OCH3), 67.92 (OCH2CH3), 109.87 (C-
(1RS,4RS,4aRS,9aSR)-1-Ethoxy-4,5-dimethoxy-3-oxo-1,2,4a,9a-tetra-
hydro-4H-9,10-anthraquinone (25): Diene 21 (79 mg, 0.37 mmol)
was added to a solution of O-methyljuglone (11; 33 mg, 0.18 mmol)
in DCM (2.4 mL) and the reaction mixture stirred for 18 h under
reflux. The solvent was removed under reduced pressure and the
crude product was stored at –18 °C under argon overnight. The
solid formed was re-suspended in diethyl ether and filtered to af-
ford 25 (15 mg, 25%) as pale beige crystals. M.p. Ͼ 165 °C (dec.).
1H NMR (200 MHz, CDCl3): δ = 0.82 (t, J = 7.0 Hz, 3 H,
OCH2CH3), 2.60 (dd, J = 14.5, 3.5 Hz, 1 H, 2-Ha), 3.05 (dd, J =
14.5, 5.1 Hz, 1 H, 2-Hb), 3.15 (m, 1 H, OCHaHCH3), 3.42 (s, 3 H,
4-OCH3), 3.50 (m, 2 H, OCHHbCH3, 9a-H), 3.72 (dd, J = 6.0,
4.6 Hz, 4a-H), 3.85 (d, J = 4.6 Hz, 1 H, 4-H), 3.90 (s, 3 H, 5-
OCH3), 4.10 (m, 1 H, 1-H), 7.22 (dd, J = 7.5, 1.4 Hz, 1 H, 6-H),
3), 129.55 (C-1), 135.30 (C-2), 142.01 (C-4) ppm. IR (film): ν =
˜
3402, 2958, 2901, 2830, 1783, 1729, 1636, 1445, 1386, 1362, 1250,
1195, 1103, 1008, 994, 947, 956, 926 cm–1. UV (CHCl3): λmax (log ε)
= 258.5 (4.044) ppm. MS (70 eV, EI): m/z (%) = 230.1 (16) [M+],
186.1 (20), 143.0 (8), 133.0 (92), 73.0 (100), 69.0 (16), 45.0 (8).
HRMS: m/z (M+, C11H22O3Si): calcd. 230.1338; found 230.1338.
(1SR,4SR,4aRS,9aSR)-4-Ethoxy-5-hydroxy-1-methoxy-2-oxo-
3,4,4a,9a-tetrahydro-1H-9,10-anthraquinone (23): Diene 21 (2.5 g,
11.6 mmol) was added to a solution of 13 (1.0 g, 5.7 mmol) in
DCM (77 mL) and the reaction mixture stirred for 19 h at room
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© 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2005, 2459–2467