S. J. Gharpure et al. / Tetrahedron Letters 49 (2008) 2974–2978
2977
1. BF3.OEt2
OMe
OMe
CH2Cl2, 0
º
C, 0.5 h
OH
+
2. Et3SiH, 0
ºC-r.t.
BnO
OH
OBn
OMe
OBn
1 h, 34%
BnO
O
12c
7f
5k
Scheme 5.
R1
R2
Acknowledgements
R1
R2
a or b
We thank DST, New Delhi, for the funding towards the
400 MHz NMR machine to the Department of Chemistry,
IIT-Madras under the IRPHA scheme and ESI-MS facility
under the FIST programme. We thank DST, New Delhi
(SR/S1/OC-03/2005), for the financial support. We are
grateful to CSIR, New Delhi, for the award of research
fellowships to A.M.S. and P.J.
R3
R3
R4
O
R4
O
equol, R = R4 = OH,
1
= R4 = OBn,
1
2:
5j:
R
R
R2 = R3 = H
2 = R3 = H
3: 3'-hydroxyequol, R1 = R2 = R4 = OH,
5i: R1 = R2 = R4 = OMe,
R3 = H
R3 = H
R
R
vestitol, R1 = OMe, R2 = H,
1 = OMe, R2 = H,
3 = R4 = OBn
4:
5k:
R
3 = R4 = OH
Scheme 6. Reagents, conditions and yields: (a) H2/10% Pd/C, EtOAc,
24 h, 83% (for 2), 87% (for 4); (b) pyridinium hydrochloride, 150 °C, 65%
(for 3).
References and notes
1. Harborne, J. B.; Baxter, H. In The Handbook of Natural Flavonoids;
Wiley: New York, 1999; Vol. 2 and references cited therein.
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1994; p 619.
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In conclusion, we have developed a general and concise
strategy for the synthesis of the isoflavan skeleton based on
a [4+2] cycloaddition of o-QMs with aryl-substituted enol
ethers followed by reductive removal of the acetal moiety.
We have also demonstrated that the isoflavans can be syn-
thesized in a single pot operation with reduction in the
overall reaction time with comparable efficiencies. Further,
the method is applied to the total syntheses of equol (2), 30-
hydroxyequol (3) and vestitol (4). The method developed is
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Representative experimental procedure: A solution of o-
acetoxymethylphenol 9a (183 mg, 1.10 mmol) and enol
ether 7b (900 mg, 5.50 mmol) in benzene (2 ml) at 80 °C
was stirred in a sealed tube under nitrogen for 26 h (TLC
monitoring). Evaporation of the benzene under reduced
pressure gave a brown oily residue which was purified by
silica gel column chromatography using ethyl acetate–hex-
anes (1:50) as eluent to give a diastereomeric mixture of
acetal 6b (156 mg, 52%) as a sticky solid.
To a cooled (0 °C), magnetically stirred solution of 6b
(58 mg, 0.22 mmol) and triethylsilane (0.15 ml, 0.93 mmol)
in dry CH2Cl2 (5 ml) was added BF3ꢀOEt2 (0.07 ml,
0.55 mmol) dropwise. The reaction mixture was then
allowed to warm to rt slowly over a period of 30 min.
The reaction mixture was quenched using saturated aq
NaHCO3 (2 ml) and extracted with ethyl acetate
(3 ꢁ 10 ml). The combined organic extracts were washed
with brine, dried (anhyd. Na2SO4) and filtered. Evapora-
tion of the solvent under reduced pressure and purification
of the residue by silica gel column chromatography using
ethyl acetate–hexanes (1:50) as eluent furnished isoflavan
5b (48 mg, 92%) as a white solid which was recrystallized
from boiling hexanes–CH2Cl2.
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