M. Serdar G €u ltekin et al. / Tetrahedron: Asymmetry 15 (2004) 453–456
455
O
O
3.3. CCL hydrolysis of (± ±)anti)2,3)dioxabicyclo)
2.2.2]oct)7)en)5)ol 8a
O
O
[
HO
OCOCH
3
(
+)-8b
(-)-8a
To a stirred solution of 500 mg (± ±-8a in 5 mL vinyl
acetate, 10 mg of CCL was added in one portion and the
reaction mixture stirred at 20 °C (TLC monitoring±. The
reaction mixture was filtered and the vinyl acetate
evaporated under reduced pressure. The products ()±-8a
and (+±-8b were purified by preparative TLC (EtOAc/
hexane 1:1±.
Thiourea
AcCl
Thiourea
AcCl
OAc
OAc
OAc
AcO
OAc
OAc
(
+)-9
(-)-9
3.3.1. (1S,4S,5S±)2,3)dioxabicyclo[2.2.2]oct)7)en)5)yl ace)
tate 8b. Colorless liquid (279 mg, 42% yield±; 72% ee
OsO
4
, NMO
OsO , NMO
4
20
NH
3
, CH OH
3
NH , CH OH
½a ¼ +16.9 (c 0.1, MeOH±; m
max
(liquid film± 2953,
3
3
D
ꢀ
1
1
727, 1450, 1385, 1250, 1094, 962 cm ; d
H
(400 MHz,
OH
OH
CDCl ± 6.75 (1H, dt, J ¼ 8.2, 1.3Hz±, 5.95 (1H, br t,
3
HO
HO
OH
HO
OH
OH
J ¼ 8.2 Hz±; 5.20 (1H, ddd, J ¼ 7.8, 4.5, 2.3Hz±, 4.70
(1H, m±, 4.60 (1H, m±, 2.65 (1H, ddd, J ¼ 14.2, 7.8,
OH
3
.8 Hz±, 1.95 (3H, 3±, 1.40 (1H, dm, J ¼ 14.2 Hz±; d
C
OH
(63MHz, CDCl ± 171.2, 135.1, 129.8, 71.1, 65.8, 32.8,
3
(
+)-proto-quercitol 10
(
-)-proto-quercitol 10
22.0±.
After the successful isolation and characterization of the
bicyclic endoperoxides (+±-8b and ()±-8a, they were
submitted to the selective reduction of the peroxide
linkages with thiourea under very mild conditions. Since
it is only the oxygen–oxygen bond that breaks, the
configuration at all three carbon atoms is preserved. For
further characterization, the formed diols were con-
3.3.2. (1R,4R,5R±)2,3)dioxabicyclo[2.2.2]oct)7)en)5)ol 8a.
Colorless prisms (235 mg, 47% yield±, mp 105–106°C
11
20
(lit. 106–107 °C ±; 91% ee ½a ¼ )23.3 (c 0.2, MeOH±;
D
d
H
(250 MHz, CDCl ± 6.71 (1H, ddd, J ¼ 8.2, 6.1,
3
1.8 Hz±, 6.48–6.42 (1H, m±, 4.64–4.55 (2H, m±, 4.28–4.20
(1H, m±, 2.50 (1H, ddd, J ¼ 14.0, 7.9, 3.6 Hz±, 1.75 (1H,
br d±, 1.24 (1H, dm, J ¼ 14.0 Hz±; d (63MHz, CDCl ±
C
3
14
verted into the corresponding acetates. OsO
4
oxidation
134.8, 129.0, 73.0, 70.8, 62.5, 35.0.
of the double bonds in (+±-9 and ()±-9 followed by the
ammonolysis of acetate groups resulted in the formation
of ()±-proto-quercitol and (+±-proto-quercitol 10,
3.4. ()±)proto)Quercitol 10 and (+±)proto)quercitol 10
These were synthesized starting from the triacetates (+±-
11;12;15
respectively.
9
ture.
and ()±-9, respectively, as described in the litera-
11;13;15
3. Experimental
3
.1. General
(1R,2R,5R±-()±-2,5-bis(acetyloxy±cyclohex-3-en-1-yl
20
acetate 9 ½a ¼ )4.8 (c 0.3, MeOH±.
D
(1S,2S,5S±-(+±-2,5-bis(acetyloxy±cyclohex-3-en-1-yl
Melting points are uncorrected. Infrared spectra were
obtained from KBr pellets on a Mattson 1000 FT-IR
20
acetate 9 ½a ¼ +3.8 (c 0.3, MeOH±.
D
1
13
20
D
12
12
spectrophotometer. The H and C NMR spectra were
recorded on Brucker 400 and 250 MHz spectrometers.
Apparent splittings are given in all cases. Optical rota-
tions were measured in a 1 dm cell using a Bellingham
and Stanley P20 polarimeter at 20 °C. PLE (pig liver
esterase± was purchased from Sigma as a suspension in
ammonium sulfate solution (3.2 mol/L±. CCL (lipase,
typeVII, from Candida cylindracea±, PPL (lipase, type II,
from porcine pancreas±, and HLE (horse liver esterase±
were purchased from Aldrich. Column chromatography
was performed on silica gel (60 mesh, Merck±. TLC was
carried out on Merck 0.2-mm silica gel 60 F254 analytical
aluminum plates.
()±-proto-quercitol 10 ½a ¼ )18.0 (c 0.2, H O±, lit.
2
20
½a ¼ )25.1 (c 1, H O±.
D
2
2
D
0
(+±-proto-quercitol 11 ½a ¼ +23.2 (c 0.2, H O±, lit.
2
20
½a ¼ +25.3( c 2, H O±.
2
D
Acknowledgements
The authors are indebted to the Department of Chem-
istry (Middle East Technical University± and the State
Planning Organizations of Turkey (DPT, Grant Nr.
2002K-120540-18, and 2002K-120540-04± as well as the
Turkish Academy of Sciences (TUBA± for the financial
support of this work. Furthermore, M.S.G. would like
to thank to the Scientific and Technical Research
Council of Turkey (TUBITAK± for a post-doctoral
grant.
3
.2. 2,3)Dioxabicyclo[2.2.2]oct)7)en)5)yl hydroperoxide 6
13
This was synthesized as described in the literature.