G. Stavrakov, M. Keller, B. Breit
FULL PAPER
18 H), 3.57 (pdm, J = 10.6 Hz, 2 H), 3.75 (br. d, J = 10.6 Hz), 4.16
9.3 Hz, 2 H), 6.98 (mc, 4 H) ppm. 13C NMR (100 MHz, CDCl3):
(mc, 2 H), 4.39 (s, 2 H), 4.51 (AB, J = 12.3 Hz, 4 H), 7.10 (pdd, J δ = –4.5 (br. s, 4 C), 25.6 (br. s, 4 C), 26.5 (br. s, 2 C) 74.2 (br. s, 2
= 1.0, 7.9 Hz, 2 H), 7.18–7.24 (m, 14 H) ppm. 13C NMR C), 117.3 (2 C), 118.7 (2 C), 120.1 (2 C), 123.7 (2 C), 128.3 (2 C),
(100 MHz, CDCl3): δ = –4.6 (2 C), –3.5 (2 C), 18.2, 18.7, 25.8 (6 128.8 (2 C) ppm.
C), 70.5 (2 C), 73.8 (2 C), 74.8 (2 C), 83.1 (2 C), 114.9 (2 C), (120.2,
(9R,10R)-4,5,9,10-Tetrahydroxy-9,10-dihydrophenanthrene (2): A
121.7, 124.3, 127.9, 128.5, 128.9, 138.1, 141.1, 156.0, 22 C) ppm.
25 mL flask was loaded with (9R,10R)-9,10-bis[tert-butyl(dimeth-
yl)silyl]oxy-9,10-dihydrophenanthrene-4,5-diol (0.14g, 0.3 mmol.
1 equiv.), THF (5 mL), and TBAF·3H2O (1 g, 3 mmol, 10 equiv.).
The mixture was stirred at room temp. for 24 h, then quenched
with MeOH (3 mL), and concd. HCl (5 drops). Concentration and
flash-column chromatography (silica gel, EtOAc + 1% MeOH, Rf
= 0.28, petroleum ether/EtOAc, 1:2) afforded the tetraol 2 (0.07 g,
0.29 mmol, 95%) as a colourless solid; m.p. 87 °C (CH2Cl2). [α]2D4
((5R,6R,11R,12R)-11,12-Bis{[tert-butyl(dimethyl)silyl]oxy}-
5,6,11,12-tetrahydrophenanthro[4,5-efg][1,4]dioxocine-5,6-diyl)di-
methanol: A 25 mL flask was loaded with the benzyl ether (0.7 g,
0.95 mmol), EtOAc (6 mL), and Pd(OH)2 (10% on carbon, 0.1 g)
followed by vacuum – hydrogen exchange (6 times). The mixture
was stirred for 2 h, filtered through a pad of MgSO4 (EtOAc) and
concentrated to give 0.42 g (0.75 mmol, 79%) of the diol (Rf = 0.28,
petroleum ether/EtOAc, 1:2) as a colourless volatile oil which can
be crystallized from Et2O/petroleum ether (1:2) to give a colourless
1
= +106.7 (c = 0.15, MeOH). [α]2D4 = +120.5 (c = 0.2, CHCl3). H
NMR (300 MHz, [D4]MeOH): δ = 4.39 (s, 2 H), 6.95–7.03 (m, 2
H), 7.26–7.31 (m, 4 H) ppm. 1H NMR (300 MHz, CDCl3): δ =
4.51 (s, 2 H), 7.00 (pt, J = 4.8 Hz, 2 H), 7.34 (pd, J = 4.8 Hz, 4 H)
solid; m.p. 137 °C (Et2O/PE). [α]2D2 = –143.6 (c = 0.14, CHCl3). H
1
NMR (300 MHz, CDCl3): δ = 0.20 (s, 6 H), 0.32 (s, 6 H), 1.19 (s,
18 H), 2.72 (br. s, 2 H), 3.88 (pd, J = 10.0 Hz, 2 H), 4.06 (pd, J =
10.0 Hz, 2 H), 4.24 (br. s, 2 H), 4.62 (s, 2 H), 7.27 (pd, J = 7.8 Hz,
2 H), 7.47 (pt, J = 7.7 Hz, 2 H), 7.57 (pd, J = 7.5 Hz, 2 H) ppm.
13C NMR (100 MHz, CDCl3): δ = –4.6 (2 C), –3.5 (2 C), 18.7 (2
C), 26.6 (6 C), 62.8 (2 C), 74.6 (2 C), 83.8 (2 C), 120.6 (2 C),
121.4 (2 C), 124.1 (2 C), 129.2 (2 C), 141.3 (2 C), 155.4 (2 C) ppm.
C30H46O6Si2 (558.85): calcd. C 64.48, H 8.30; found C 64.70, H
8.24.
1
ppm. H NMR (300 MHz, [D6]acetone): δ = 2.8 (br. s, 2 H), 4.21
(s, 2 H), 6.86 (pdd, J = 1.4, 8.0 Hz, 2 H), 7.13 (pt, J = 7.5 Hz, 2
H), 7.28 (pdd, J = 1.2, 8.0 Hz, 2 H) ppm. 13C NMR (125 MHz,
[D4]MeOH): δ = 74.7 (2 C), 116.8 (2 C), 119.5 (2 C), 121.6 (2 C),
129.0 (2 C), 140.8 (2 C), 156.7 (2 C) ppm. 13C NMR (100 MHz,
[D6]acetone): δ = 74.0 (2 C), 117.5 (2 C), 117.9 (2 C), 119.5 (2 C),
129.3 (2 C), 141.8 (2 C), 153.1 (2 C) ppm. HRMS (C14H12O4):
calcd. 244.0735 found 244.0742. Enantiomeric excess of 2 was de-
termined after derivatization to the corresponding dimethyl ether
2a.
{[(5S,6S,11R,12R)-5,6-Bis(iodomethyl)-5,6,11,12-tetrahydrophenan-
thro[4,5-efg][1,4]dioxocine-11,12-diyl]bis(oxy)}bis[tert-butyl(di-
methyl)silane] (14): A dried 25 mL flask was loaded with tri-
phenylphosphane (0.184 g, 0.7 mmol), imidazole (0.143 g,
2.1 mmol) and CH2Cl2 (3 mL). The clear solution was cooled to
0 °C, and to it was added I2 (0.178 g, 0.7 mmol). The mixture was
stirred for 10 min at room temperature with formation of a yellow
precipitate. The iodine compound was stabilized by addition of 2-
methyl-2-butene (0.37 mL). To the mixture was added a solution
of the diol (0.185 g, 0.33 mmol, 1 equiv.) in CH2Cl2 (3 mL). After
stirring at room temp. for 1 h, the reaction was quenched with
water (20 mL), and extracted with Et2O (2 times 50 mL). The or-
ganic phase was washed with satd. aq. Na2S2O3 (20 mL), diluted
H2O2 (10 mL), water (20 mL), dried (MgSO4), concentrated, and
filtered through a pad of silica gel (CH2Cl2; Rf = 0.88, petroleum
ether/EtOAc, 4:1). Concentration and crystallization (MeOH) af-
forded the desired bis-iodide 14 (0.216 g, 28 mmol, 84%) as colour-
less crystals; m.p. 151 °C (MeOH). [α]2D6 = –66.2 (c = 0.14, CHCl3).
1H NMR (300 MHz, CDCl3): δ = 0.07 (s, 6 H), 0.18 (s, 6 H), 1.05
(s, 18 H), 3.27 (pdm, J = 10.0 Hz, 2 H), 3.53 (pd, J = 9.9 Hz, 2 H),
3.97–4.10 (m, 2 H), 4.47 (s, 2 H), 7.37 (pt, J = 7.8 Hz, 2 H), 7.46
(pd, J = 6.8 Hz, 2 H), 7.52 (pdd, J = 1.0, 7.9 Hz, 2 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = –4.6 (2 C), –3.6 (2 C), 25.8, 26.1,
26.6 (6 C), 72.2 (2 C), 74.6, 85.4 (2 C), 120.9 (2 C), 121.4 (2 C),
124.1 (2 C), 129.1 (2 C), 141.3 (2 C), 155.1 (2 C) ppm.
(9R,10R)-4,5-Dimethoxy-9,10-dihydrophenanthrene-9,10-diol (2a):
A 10 mL flask was loaded with tetraol 2 (0.018 g, 0.074 mmol),
acetone (3 mL), K2CO3 (0.2 g), and MeI (0.1 g, 0.05 mL,
0.74 mmol). The reaction mixture was heated to reflux for 6 h,
filtered, and concentrated. Purification via flash-column
chromatography (silica, PE/EE, 1:1, Rf = 0.65) afforded 0.01 g
(0.036 mmol, 48%) of the diol 2a as a yellow solid; m.p. 103 °C
(PE/EE). [α]3D2 = +109.7 (c = 0.3, MeOH). [α]3D2 = +160.0 (c = 0.3,
CHCl3); eeϾ99% {determined by chiral HPLC analysis using a
Chiralpak-OD-H column, 250 mmϫ4.6 mm, n-heptane/2-propa-
nol (95:5), 1 mL/min, 35 °C, 270 nm, tR [(P)-enantiomer] =
30.7 min, tR [(M)-enantiomer] = 47.3 min}. 1H NMR (300 MHz,
CDCl3): δ = 2.69 (br. s, 2 H), 3.90 (s, 6 H), 4.46 (s, 2 H), 6.99 (pd,
J = 8.2 Hz, 2 H), 7.25 (pd, J = 7.1 Hz, 2 H), 7.3 (pt, J = 7.8 Hz, 2
1
H) ppm. H NMR (300 MHz, [D4]MeOH): δ = 3.84 (s, 6 H), 4.87
(s, 2 H), 6.99 (d, J = 9.2 Hz, 2 H), 7.25–7.33 (m, 4 H) ppm. 13C
NMR (100 MHz, CDCl3): δ = 56.1 (2 C), 74.6 (2 C), (111.7, 115.6,
119.4, 129.1, 129.3, 10 C), 156.5 (2 C) ppm. 13C NMR (100 MHz,
[D4]MeOH): δ = 56.4 (2 C), 74.8 (2 C), (112.4, 141.5 116.9, 120.7,
129.4, 10 C), 157.7 (2 C) ppm. HRMS(C16H16O4): calcd. 272.10486
found 272.10480.
Acknowledgments
(9R,10R)-9,10-Bis{[tert-butyl(dimethyl)silyl]oxy}-9,10-dihydrophen-
anthrene-4,5-diol: A dried 50 mL flask was loaded under an atmo-
sphere of argon with bis-iodide 14 (0.19 g, 0.24 mmol), EtOH
(20 mL), and Zn powder (0.65 g, 10 mmol). The suspension was
refluxed for 2 h, cooled to room temp., diluted with Et2O (20 mL),
and filtered. The filtrate was washed with satd. aq. Na2S2O4, dried
(MgSO4), filtered and concentrated. Flash-column chromatog-
raphy (silica gel, petroleum ether/EtOAc, 4:1, Rf = 0.68) furnished
the desired bis-phenol (0.1 g, 0.23 mmol, 96%) as a yellow oil.
This work was supported by the Fonds der Chemischen Industrie,
and the Alfried Krupp Award for young university teachers of the
Krupp foundation (to BB). We thank Jürgen Leonhardt for techni-
cal and Gerd Fehrenbach for analytical assistance.
[1] a) T. Takeuchi, T. Hara, H. Naganawa, M. Okada, M. Ham-
ada, H. Umezaw, S. Gomi, M. Sezaki, S. Kondo, J. Antibiot.
1988, 41, 807; b) T. Oki, M. Konishi, K. Tomatsu, K. Tomita,
K. Saitoh, M. Tsunakawa, M. Nishio, T. Miyaki, H. Kawagu-
chi, J. Antibiot. 1988, 41, 1701; c) J. Rohr, R. Thiericke, Nat.
Prod. Rep. 1992, 9, 103.
1
[α]2D6 = –109.1 (c = 1, CHCl3). [α]2D6 = –154.5 (c = 1, MeOH). H
NMR (500 MHz, [D8]toluene, 360 K): δ = –0.16 (s, 6 H), 0.06 (s, 6
H), 0.76 (s, 9 H), 4.68 (s, 2 H), 6.12 (br. s, 2 H), 6.63 (pd, J =
5732
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Eur. J. Org. Chem. 2007, 5726–5733