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raphy (hexanes/EtOAc = 4:1) provided 69 mg (84 %) of spiroketal 7
as colorless solid. M.p. 118–122 °C. H NMR (500 MHz, CDCl3): δ =
2.17 (td, J = 5.8, 13.5 Hz, 1 H, 3′-H), 2.35 (ddd, J = 2.8, 5.8, 13.5 Hz,
2.32 (ddd, J = 2.4, 5.8, 13.4 Hz, 1 H, 3′-H), 2.83 (ddd, J = 2.4, 5.8,
16.5 Hz, 1 H, 4′-H), 3.30 (mc, 1 H, 4′-H), 3.72, 3.73 (2 s, 3 H each,
OMe), 3.76 (q, J = 7.3 Hz, 1 H, 3-H), 3.80 (s, 3 H, OMe), 6.36, 6.68 (2
1
1 H, 3′-H), 2.79 (ddd, J = 2.8, 5.6, 16.5 Hz, 1 H, 4′-H), 3.26, 3.57 (AB d, J = 8.9 Hz, 1 H each, 5-H, 6-H), 6.70–6.75 (m, 2 H, Ar), 6.83 (t, J =
system, J = 16.8 Hz, 1 H each, 3-H), 3.29 (mc, 1 H, 4′-H), 3.76, 3.78,
3.79 (3 s, 3 H each, OMe), 6.35 (d, J = 8.9 Hz, 1 H, 5-H), 6.69–6.76
(m, 3 H, 6-H, Ar), 6.84 (t, J = 7.9 Hz, 1 H, Ar) ppm. 13C NMR (126 MHz,
CDCl3): δ = 21.8 (t, C-4′), 30.6 (t, C-3′), 40.1 (t, C-3), 55.5, 55.9, 56.6
(3 q, OMe), 102.8, 109.9 (2 d, C-5, C-6), 110.2 (s, C-2), 112.6 (d, Ar),
7.8 Hz, 1 H, Ar) ppm. 13C NMR (126 MHz, CDCl3): δ = 14.0 (q, Me),
21.6 (t, C-4′), 25.9 (t, C-3′), 45.0 (d, C-3), 55.4, 56.0, 56.6 (3 q, OMe),
103.1 (d, C-5), 110.2 (d, Ar), 111.7 (s, C-2), 112.5 (d, C-6), 120.2 (s,
Ar), 120.3, 121.0 (2 d, Ar), 122.8, 139.0, 142.1, 146.1, 148.4, 150.7 (6
s, Ar) ppm. cis/trans-12: IR (ATR): ν = 3000–2835 (C–H), 1735, 1605,
˜
114.0 (s, Ar), 120.5, 121.0 (2 d, Ar), 122.4, 138.9, 141.9, 147.3, 148.4, 1585, 1510, 1485, 1460 cm–1. HRMS (ESI-TOF): calcd. for [M + Na]+
150.4 (6 s, Ar) ppm. IR (ATR): ν = 3000–2835 (C–H), 1610, 1585, 365.1365, found 365.1375. C20H22O5 (342.4): calcd. C 70.16, H 6.48;
˜
1510, 1480, 1460, 1440 cm–1. HRMS (ESI-TOF): calcd. for [M + Na]+
351.1208, found 351.1224. C19H20O5 (328.4): calcd. C 69.50, H 6.14;
found C 69.54, H 6.23.
found C 70.14, H 6.51.
Acknowledgments
4-[3,6-Dimethoxy-2-(methoxymethoxy)phenyl]-1-[3-methoxy-2-
(methoxymethoxy)phenyl]pentan-3-one (11): To a cold (–78 °C) Financial support by Bayer HealthCare AG is gratefully acknowl-
solution of ketone 1 (87 mg, 0.20 mmol) in THF (5 mL) was added
dropwise LiHMDS (1.0 in THF/ethylbenzene, 0.40 mL, 0.40 mmol).
edged. We thank Dr. Cengiz Azap for preliminary experiments.
M
The mixture was stirred at this temperature for 30 min. Then methyl
iodide (142 mg in 0.50 mL of THF, 1.00 mmol) was added. The
mixture was warmed up and stirred at room temperature for
30 min. Then satd. NH4Cl solution (aq.) and EtOAc were added. The
layers were separated, and the aqueous phase was extracted three
times with EtOAc. The combined organic layers were washed with
satd. NaCl solution (aq.), dried with MgSO4, filtered, and concen-
trated. Column chromatography (hexanes/EtOAc = 3:1) provided
83 mg (93 %) of 11 as pale yellow oil. 1H NMR (500 MHz, CDCl3):
δ = 1.35 (d, J = 6.7 Hz, 3 H, Me), 2.55 (mc, 2 H, 3-H), 2.90 (mc, 2 H,
4-H), 3.52, 3.54, 3.66, 3.78, 3.78 (5 s, 3 H each, OMe), 4.02 (q, J =
6.7 Hz, 1 H, 1-H), 5.00, 5.02 (AB system, JAB = 5.8 Hz, 1 H each,
OCH2), 5.08, 5.10 (AB system, JAB = 6.0 Hz, 1 H each, OCH2), 6.52,
6.74 (2 d, J = 9.2 Hz, 1 H each, Ar), 6.69–6.70 (m, 2 H, Ar), 6.91 (t,
J = 8.0 Hz, 1 H, Ar) ppm. 13C NMR (126 MHz, CDCl3): δ = 14.5 (q,
Me), 24.8 (t, C-4), 40.3 (t, C-3), 43.8 (t, C-1), 55.4, 55.5, 56.0, 57.3, 57.4
(5 q, OMe), 98.7, 99.1 (2 t, OCH2), 105.8, 110.0, 110.8, 121.9, 124.0
(5 d, Ar), 125.5, 135.9, 144.1, 144.7, 146.4, 151.4, 152.0 (7 s, Ar), 210.2
Keywords: Benzofuran · Ketals · Ketones · Pyran ·
Rubromycin · Spiro compounds
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(s, C-2) ppm. IR (ATR): ν = 2935–2780 (C–H), 1710 (C=O), 1585, 1485,
˜
1465, 1440 cm–1. HRMS (ESI-TOF): calcd. for [M + Na]+ 471.1995,
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63.78, H 7.06.
4,7,8′-Trimethoxy-3-methyl-3H-spiro[benzofuran-2,2′-
chroman] (12): To a cold (–25 °C) solution of 11 (225 mg,
0.50 mmol) in MeCN (10.0 mL) was added TfOH (25 μL of a freshly
prepared 2.2
M stock solution of TfOH in MeCN, 50 μM). The mixture
was warmed up to –15 °C over 15 min. Then satd. Na2CO3 solution
(aq. 1 mL), water, and EtOAc were sequentially added. The layers
were separated, and the aqueous phase was extracted three times
with EtOAc. The combined organic layers were washed with satd.
NaCl solution (aq.), dried with Na2SO4, filtered, and concentrated.
Column chromatography (hexanes/EtOAc = 8:1) provided 25 mg of
cis-12, 94 mg of trans-12 and 15 mg as mixed fraction of both
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1
products as colorless solids in a combined yield of 78 %. cis-12: H
NMR (500 MHz, CDCl3): δ = 1.51 (d, J = 7.2 Hz, 3 H, Me), 2.06 (mc,
1 H, 3′-H), 2.28 (ddd, J = 2.9, 5.7, 13.5 Hz, 1 H, 3′-H), 2.77 (ddd, J =
2.9, 5.7, 16.2 Hz, 1 H, 4′-H), 3.26 (mc, 1 H, 4′-H), 3.50 (q, J = 7.2 Hz,
1 H, 3-H), 3.76, 3.77, 3.80 (3 s, 3 H each, OMe), 6.36, 6.68 (2 d, J =
8.9 Hz, 1 H each, 5-H, 6-H), 6.71–6.75 (m, 2 H, Ar), 6.83 (t, J = 7.8 Hz,
1 H, Ar) ppm. 13C NMR (126 MHz, CDCl3): δ = 12.4 (q, Me), 21.7 (t,
C-4′), 30.3 (t, C-3′), 45.7 (d, C-3), 55.6, 56.4, 56.7 (3 q, OMe), 103.0
(d, C-5), 110.4 (s, C-2), 110.8 (d, Ar), 112.5 (d, C-6), 119.0 (s, Ar), 120.3,
121.1 (2 d, Ar), 122.7, 139.0, 142.4, 146.3, 148.6, 151.1 (6 s, Ar) ppm.
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1
trans-12: Melting range 125–135 °C. H NMR (500 MHz, CDCl3): δ =
1.32 (d, J = 7.3 Hz, 3 H, Me), 2.05 (td, J = 5.8, 13.4 Hz, 1 H, 3′-H),
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