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G. A. Kraus et al. / Tetrahedron Letters 50 (2009) 5303–5304
O
References and notes
1. K2CO3, 6, DMF
2. Jones oxidation
OH
LAH
O
OMe
1. Lin, Y.-L.; Chang, Y.-Y.; Kuo, Y.-H.; Shiao, M.-S. J. Nat. Prod. 2002, 65, 745–
747.
5
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G. M. J. Nat. Prod. 2006, 69, 323–327.
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Kittakoop, P. J. Nat. Prod. 2007, 70, 795–801.
O
CO2H
OH
7
8
(NH4)2S2O8
Ag+
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Nat. Prod. 2008, 71, 1938–1941; MacNeil, S. L.; Gray, M.; Gusev, D. G.; Briggs, L.
E.; Snieckus, V. J. Org. Chem. 2008, 73, 9710–9719.
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Org. Biomol. Chem. 2004, 2, 570–577.
3
Scheme 1. Synthesis of 3.
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2001, 42, 6899–6902.
8. Togo, H.; Katohgi, M. Synlett 2001, 565.
9. Togo, H.; Aoki, M.; Kuramochi, T.; Yokoyama, M. Perkin Trans. 1 1993, 2417.
10. Barton, D. H. R.; Bridon, D.; Zard, S. Z. Tetrahedron 1989, 45, 2615–2626.
11. Barton, D. H. R.; Bridon, D.; Zard, S. Z. Tetrahedron 1987, 43, 5307–5314.
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14. DeKimpe, Norbert, private communication.
15. To a stirred solution of acid 8 (16 mg, 0.053 mmol) in 6 mL of 30% aq CH3CN
under argon was added silver nitrate (0.3 equiv). The mixture was heated to
65 °C and a solution of ammonium persulfate (1.3 equiv) in 2 mL of 30% aq
CH3CN was added dropwise for 20 min. The mixture was then stirred at 70 °C
for 3 h. The mixture was cooled to 65 °C. An additional amount of silver nitrate
(0.3 equiv) was added and a solution of ammonium persulfate (1.3 equiv) in
2 mL of 30% aq CH3CN was added dropwise for 20 min. After an additional 3 h
at 70 °C, the reaction mixture was cooled to rt and extracted with
dichloromethane. The organic extracts were washed with brine, dried over
Na2SO4, and evaporated in vacuo. The residue was purified using flash
chromatography on silica gel (1:1 hexanes:ethyl acetate) to obtain 3 (5.5 mg,
40% yield).
identifiable product. We also tried using potassium persulfate in-
stead of ammonium persulfate; however, it provided only a 13%
yield of 3. The conditions of DeKimpe,14 wherein both the silver
salt and the persulfate were added in two portions,15 afforded 3
in 40% isolated yield. This constitutes a 25% overall yield of Bauhi-
noxepin J. The identity of synthetic Bauhinoxepin J (3) was con-
firmed by comparison of our 1H NMR, 13C NMR, LRMS, and HRMS
data with the published spectra.
This represents the first total synthesis of quinone 3. This syn-
thesis features the first intramolecular radical addition to a qui-
none. This flexible and direct synthetic pathway will facilitate
further biological evaluation of this little studied class of natural
products.
IR (thin film): 2915, 2849, 1661, 1607, 1582, 1488, 1463, 1380, 1228,
Acknowledgment
1193 cmÀ1 1H NMR (300 MHz, CDCl3) d 7.22–7.25 (m, 2H), 7.13–7.17 (m,
.
2H), 5.90 (s, 1H), 3.83 (s, 3H), 3.06–3.09 (m, 2H), 2.81–2.85 (m, 2H). 13C NMR
(100 MHz, CDCl3) d 182.8, 181.9, 158.9, 155.7, 152.9, 133.2, 129.6, 128.0, 126.0,
123.7, 121.2, 105.4, 56.7, 29.9, 26.5; LRMS (EI): m/z 256 (M+, 100%), 241, 115,
69; HRMS (EI) calcd for C15H12O4: 256.0736, found: 256.0740.
We thank the Department of Chemistry at Iowa State University
for partial support of this work.