Ring opening of epoxides with NaHSO4: isolation of β-hydroxy sulfate esters and an effective synthesis for trans-diols

Article abstract of DOI:10.1016/j.tet.2008.11.092

Sodium hydrogen sulfate (NaHSO₄) was observed to be highly effective as a reagent or catalyst in the ring-opening reactions of epoxides under mild conditions. Reaction of epoxides with NaHSO₄ gave isolable β-hydroxy sulfate esters and vicinal diols. Experimenting with different epoxides, the study investigated the scope of the ring-opening reaction.

Full text of DOI:10.1016/j.tet.2008.11.092

Tetrahedron 65 (2009) 985–989
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Ring opening of epoxides with NaHSO4: isolation of b-hydroxy sulfate esters
and an effective synthesis for trans-diols
*
Huseyin Cavdar, Nurullah Saracoglu
Atatu¨rk University, Department of Chemistry, Erzurum 25240, Turkey
a r t i c l e i n f o
a b s t r a c t
Article history:
Sodium hydrogen sulfate (NaHSO4) was observed to be highly effective as a reagent or catalyst in the
ring-opening reactions of epoxides under mild conditions. Reaction of epoxides with NaHSO4 gave
Received 18 September 2008
Received in revised form 7 November 2008
Accepted 27 November 2008
Available online 3 December 2008
isolable
b-hydroxy sulfate esters and vicinal diols. Experimenting with different epoxides, the study
investigated the scope of the ring-opening reaction.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
supported sodium hydrogen sulfate (NaHSO4$SiO2) efficiently cat-
alyzes various reactions.14 In continuation of our work on the
epoxides, we also noticed that the epoxides underwent the ring-
opening reaction with sodium hydrogen sulfate. Herein, we report
our results on the ring opening of various epoxides with NaHSO4
under mild reaction conditions.
Epoxides are versatile organic tools as both building blocks and
synthetic intermediates. For instance, the ring opening of epoxides
with carbon and heteroatomic nucleophiles provides b-substituted
alcohols.1 One of the most important ring-opening reactions is the
conversion of epoxides to trans-1,2-diols (or vic-diols).2 This func-
tionality is usually a fundamental structural component for cycli-
tols, potential glycosidase inhibitors, which are receiving
considerable attention as chemotherapeutic applications against
diabetes, cancer, and viral infections.3 myo-Inositol (1) derivatives
play a central role in the cellular signal of various glycosidase en-
zymes (Fig. 1).4 Several multiply sulfated compounds have been
found in biologically active compounds and marine organisms.5 For
instance, sulfated sterols have exhibited effects such as anti-HIV,
antiviral activity, and inhibition of protein tyrosine kinases.6
Compound 2 isolated from Stilopus australis is the first sterol with
a 5-pregnen skeleton (Fig. 1).7
2. Results and discussions
Initially, we investigated the reaction of cyclohexene-epoxide
(3) and sodium bisulfate at room temperature in methylene chlo-
ride. The heterogeneous reaction of epoxide with NaHSO4 in
equivalent amounts gave a mixture of b-hydroxy sulfate ester 4 and
epoxide 3 (Scheme 1). When the reaction was repeated with
2 equiv of NaHSO4 under the same conditions, sulfate ester 4 was
obtained as the single reaction product characterized by 1H and 13
C
NMR spectroscopy. The NMR spectra of the product confirmed the
assumption that the presence of protons and carbons connected
Carbohydrate sulfates play an essential role in cellular com-
munication.8 Moreover, sulfate functionality comprises inter-
mediates in organic synthesis as powerful alkylating agents or
hydroxyl protecting groups.9 Despite the growing importance of
sulfate monoesters in biochemistry, the number of synthesis
methods is limited. Classical methods for sulfate synthesis include
the esterification of the parent alcohols with H2SO4 or choloro-
sulfonic acid.10 The most commonly used sulfating agents are
complexes of SO3 with pyridine, tertiary amine, or amides.11
Magnesium hydrogen sulfate (Mg(HSO4)2)12 and tetrabutyl-
ammonium bisulfate (Bu4NHSO4)13 are effective catalysts for the
hydrolysis of epoxides and aziridines under mild conditions. Silica-
the bisulfate (ddd at
and the alkoxy (a multiplet at
To add new members to these molecules potentially important
for biological processes, we undertook the synthesis of several
d
¼4.46 ppm, J¼9.0, 5.7, 3.7 Hz; ¼91.7 ppm)
d
d
¼4.04 ppm; ¼74.2 ppm) groups.
d
b-hydroxy sulfate ester analogs. We modulated the ring size and
skeleton structure of molecules containing an epoxide. In a similar
manner, the concerned sulfate esters 5–7 were synthesized with
O
OH
HO
HO
OH
OH
OH
HO3SO
OH
1
2
* Corresponding author. Tel.: þ90 442 2314425; fax: þ90 442 2360948.
E-mail address: nsarac@atauni.edu.tr (N. Saracoglu).
Figure 1. Samples for cyclitol and sulfate monoester.
0040-4020/$ – see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2008.11.092

986
H. Cavdar, N. Saracoglu / Tetrahedron 65 (2009) 985–989
OH
out with the excess of NaHSO4. Due to the solubility problem, the
NaHSO4
O
reaction mixture was solved with methanol, which hydrolyzes the
formed di-sulfate ester to the corresponding tetrole, and then fil-
trated over filter paper. The crude product was characterized by
being acetylated with acetic anhydride–pyridine. Since bisepoxide
11 has two epoxide units, two trans-hydroxylation products (or
hydroxyl sulfate ester) can be expected. The 1H and 13C NMR
spectra of the acetylation product yielded only one hydroxylation
product 14,17 instead of two symmetrical products contrary to our
expectations. We assumed that the steric hindrance role of the first
added sulfate group was effective in the observed regioselectivity.
The other bisepoxides 12 and 13 were also transformed into the
corresponding products 15 and 1618 under similar reaction condi-
tions (Scheme 4). The molecule obtained from 13 is a half-acetyl-
ation product.
CH2Cl2
rt, 24h
70%
OSO3H
3
4
9
OH
2
H
syn
OH
OSO3H
OSO3H
OH
OSO3H
1
H
endo
3
5
6
7
Scheme 1. Ring opening of epoxides with NaHSO4: obtained hydroxy sulfate ester.
the appropriate epoxides using the same strategy (Scheme 1). The
regiochemical formation of the opening products 4–6 could be
understood on the basis of the usual stereoelectronic factors that
favor a trans-diaxial opening mode. However, sulfate ester 7 is
a Wagner–Meerwein-type product. The formation of 7 may well
proceed via a non-classic carbocation intermediate.2c It is not
possible to explain the product by the classic addition of hydrogen
sulfate. The configurations of hydroxyl and sulfate in 7 were de-
termined from the coupling constants of the relevant protons. The
long-range coupling constant (J¼1.5 Hz) between 7syn-H and
2endo-H in molecule 7 (M or W orientation) confirms the exo po-
sition of the sulfate. The large coupling constants (J¼12.7 Hz) for
the geminal 3 and 30 protons are in agreement with the proposed
structures.
1) NaHSO4
CH2Cl2, rt, 24h
AcO
AcO
OAc
OAc
then MeOH
O
O
O
O
2) Ac2O/Pyridine
62%
11
14
1) NaHSO4
CH2Cl2, rt, 24h
then MeOH
AcO
AcO
OAc
OAc
2) Ac2O/Pyridine
53%
12
15
We observed that these sulfate esters were unstable in workup
conditions and purification steps. Therefore, we turned our atten-
tion to the hydrolysis of the hydrogen sulfate group. 2-Hydroxy-
cyclohexyl hydrogen sulfate (4) selected as a test molecule was
treated with water or wet CH2Cl2. After workup, trans-cyclohexane-
1,2-diol (8)15 was obtained as the sole product (Scheme 2). Due to
the instability of the sulfate esters toward water, we also in-
vestigated the catalytic activity of NaHSO4 for the ring-opening
reaction of epoxide 3 in water medium. Reaction of 3 was carried
out in wet CH2Cl2 in the presence of catalytic NaHSO4 (0.10 mmol)
and it gave trans-diol 8 as the sole product.
1) NaHSO4
OAc
O
O
CH2Cl2, rt, 24h
then MeOH
HO
HO
2) Ac2O/Pyridine
67%
OAc
16
13
Scheme 4. Ring opening of syn- and anti-bisepoxides 11–13 and obtained products
14–16.
After the successful formation of the mono-sulfate esters and
diols from the rigid carbocyclic mono- or bisepoxides and epoxide
in a bicyclic framework, we further investigated the ring-opening
activity of sodium hydrogen sulfate toward benzylic epoxides such
as stilbene oxide and styrene oxide. If this trend continues, the
formation of sulfate ester or diol can be expected to occur. There-
fore, trans-stilbene oxide (17) was firstly treated with an equivalent
amount of NaHSO4 in methylene chloride at room temperature.
Following the chromatography on silica gel, 2,2-diphenylacetalde-
hyde (19),19 a pinacol-type rearrangement product, was obtained as
the single reaction product, instead of sulfate ester 20 or diol 21, the
possible expected ring-opening products (Scheme 5). As can be
understood, the formation of this product involves the formation of
a carbenium ion intermediate 18a or sodium alcoholate 18b that
subsequently rearranges through a 1,2-phenyl shift to produce the
carbonyl compound. The driving force behind the rearrangement of
benzylic epoxide to pinacol product might be the formation of
H2O
OH
OH
OH
NaHSO4 (cat.)
98%
or
O
H2O
CH2Cl2
76%
OSO3H
wet CH2Cl2
95%
4
8
3
Scheme 2. Hydrolysis of sulfate ester 4 and epoxide 3.
Additionally, the ring opening of 1,2,3,4-tetrahydronaph-
thalene-2,3-epoxide (9) with 2 equiv of NaHSO4 was performed
and a mixture of the diol and mono-sulfate ester was obtained. The
concerned sulfate ester was attempted to be purified by crystalli-
zation. Yet, the desired mono-sulfate ester could not be isolated.
Therefore, the reaction mixture was hydrolyzed to yield the diol
1016 with water (Scheme 3).
-
HSO4
HO3SO
or
OH
OH
NaHSO4
O
NaHSO4
Ph
Ph
ONa
Ph
ONa
O
Ph
Ph
Ph
CH2Cl2
rt, 24h
then H2O
84%
CH2Cl2
17
rt, 30min
9
10
18b
18a
67%
Ph shift
-NaHSO4
Scheme 3.
OSO3H
OH
O
H
Ph
19
or
Ph
Ph
Ph
Ph
Ph
The observed results encouraged us to examine the ring-open-
ing reactions of bisepoxides with sodium hydrogen sulfate, for
which syn- and anti-bisepoxides 11–13 were selected (Scheme 4).
Thus, the ring-opening reaction of syn-bisepoxide 11 was carried
OH
20
OH
21
Scheme 5.

H. Cavdar, N. Saracoglu / Tetrahedron 65 (2009) 985–989
987
a more stable benzylic carbocation in which the positive charge can
be delocalized on the phenyl.
white crystals (350 mg, 70%, mp 194–195 ꢀC). 1H NMR (200 MHz,
CDCl3)
d
4.46 (ddd, J¼9.0, 5.8, 3.7 Hz, CHOSO3H, 1H), 4.26 (m, OH,
Finally, we studied the reaction of styrene oxide (22) with
NaHSO4, which was performed by treating epoxide 22 with excess
NaHSO4 in methylene chloride for 15 min (Scheme 6). Surprisingly,
chromatography of the crude product provided 1,3-dioxolane de-
rivative 23, which is known in the literature and whose constitu-
tion was elucidated by NMR spectroscopy.20 We assume that the
1,3-dioxolane derivative 23 is formed by the acetalization of the
initially formed 2-phenylacetaldehyde (24) and 1-phenylethane-
1,2-diol (25) under the given reaction conditions. Two possible
approaches can be postulated for the outcome of this final exper-
iment. Firstly, epoxide 22 hydrolyzes to give its parent diole 25,
which undergoes the pinacol rearrangement product 24 and then,
aldehyde 24 is caught with diol 25 to give dioxolane 23. Secondly,
the epoxide gives both hydrolysis and semi-pinacol rearrangement
reactions, which undergoes acetal as in situ.
1H), 3.57–3.52 (m, CHOH, 1H), 2.33–2.30 (m, CH2, 1H), 2.10–2.03
(m, CH2, 1H), 1.80–1.69 (m, CH2, 2H), 1.41–1.25 (m, CH2, 4H); 13C
NMR (50 MHz, CDCl3)
d 91.7, 74.2, 35.4, 33.1, 26.0, 25.5; IR (CH2Cl2,
cmꢁ1) 3391, 2936, 2862, 1453, 1392, 1191, 1075, 992, 910. Anal.
Calcd for C6H12O5S: C, 36.73; H, 6.16; S, 16.34. Found: C, 36.92; H,
6.13; S, 16.47.
4.1.2. trans-(1R(S),6R(S))-6-Hydroxycyclohex-3-enyl hydrogen
sulfate (5)
Product
5 was obtained from 1,4-cyclohexadiene-epoxide
(150 mg, 1.56 mmol) and NaHSO4 (375 mg, 3.12 mmol) as described
for the preparation of 4 in 24 h. The residue (290 mg) was crys-
tallized from CH2Cl2/hexane: white crystals 5 (225 mg, 74%, mp
126–127 ꢀC). 1H NMR (400 MHz, CDCl3)
d 5.56–5.51 (m, ]CH, 2H),
4.80 (ddd, J¼14.8, 9.5, 6.2 Hz, CHOSO3H, 1H), 3.99 (ddd, J¼15.0, 9.6,
6.3 Hz, CHOH, 1H), 2.87–2.81 (m, CH2, 1H), 2.63–2.57 (m, CH2, 1H),
2.43–2.35 (m, CH2, 1H), 2.21–2.07 (m, CH2 and OH, 3H); 13C NMR
Ph
NaHSO4
O
(100 MHz, CDCl3)
d 124.5, 123.5, 86.2, 69.1, 34.1, 31.7; IR (CH2Cl2,
O
cmꢁ1) 3256, 2928, 1399, 1195, 1067, 996, 969, 894. Anal. Calcd for
C6H10O5S: C, 37.11; H, 5.19; S,16.51. Found: C, 37.35; H, 5.05; S,16.30.
Ph
H
CH2Cl2
rt, 15min
48%
O
23
Ph
22
4.1.3. trans-(1R(S),8R(S),Z)-8-Hydroxycyclooct-4-enyl hydrogen
sulfate (6)
Product
6
was obtained from 1,5-cyclooctadiene-epoxide
(580 mg, 4.82 mmol) as de-
OH
Ph
+
(300 mg, 2.41 mmol) and NaHSO4
OH
O
Ph
scribed for the preparation of 4 in 24 h. The residue (510 mg) was
crystallized from CH2Cl2/hexane: white crystals 6 (380 mg, 70%,
24
25
Scheme 6.
mp 115–116 ꢀC). 1H NMR (400 MHz, CDCl3)
d 5.62–5.56 (m, ]CH,
2H), 4.89–4.84 (m, CHOSO3H, 1H), 4.04 (ddd, J¼12.5, 8.5, 3.7 Hz,
CHOH, 1H), 3.31 (m, OH, 2H), 2.52–2.36 (m, CH2, 2H), 2.25–2.16
(m, CH2, 4H), 2.15–2.00 (m, CH2, 1H), 1.78–1.71 (m, CH2, 1H); 13C
3. Conclusion
NMR (100 MHz, CDCl3)
d 129.0,128.5, 91.3, 72.1, 31.9, 30.1, 23.3,
In conclusion, we have described sodium hydrogen sulfate as
a highly effective reagent for ring-opening reactions of epoxides.
This unknown behavior of NaHSO4 toward monocarbocyclic ep-
oxides provides a facile and convenient route for the synthesis of
23.2; IR (CH2Cl2, cmꢁ1) 3405, 2936, 1723, 1187, 1058, 890, 734.
Anal. Calcd for C8H14O5S: C, 43.23; H, 6.35; S, 14.43. Found: C,
42.99; H, 6.23; S, 14.30.
isolable
b
-hydroxy sulfate esters or trans-1,2-diols. Furthermore,
4.1.4. 9(R(S))-Hydroxy-1,2,3,4-tetrahydro-1,4-methanonaphthalen-
2(R(S))-yl sulfate (7)
Product 7 was obtained from benzonorbornadiene-epoxide
(110 mg, 0.69 mmol) and NaHSO4 (167 mg, 1.39 mmol) as described
for the preparation of 4 in 24 h. The residue (120 mg) was crystal-
lized from CH2Cl2/hexane: yellow crystals 7 (127 mg, 83%, mp 186–
the ring-opening reactions of the epoxide with a bicyclic skeleton
and the benzylic epoxides with NaHSO4 are exposed to Wagner–
Meerwein and pinacol rearrangement. Using epoxides and sodium
hydrogen sulfate, the present study not only includes advantages
such as experimental convenience and mild conditions, but it also
creates opportunities for the synthesis of potentially important
molecules for biological processes such as sulfate esters and
cyclitols.
187 ꢀC). 1H NMR (400 MHz, CDCl3)
d
7.30 (d, J¼7.0 Hz, C6H4, 1H),
7.26–7.17 (m, C6H4, 3H), 5.01 (ddd, J¼3.9, 3.2, 1.5 Hz, CHOSO3H,
1H), 4.39 (m, CH, 1H), 4.10–4.09 (m, CHOH, 1H), 3.78–3.77 (m, CH,
1H), 2.74 (dd, J¼12.7, 3.9 Hz, A part of AX system, CH2, 1H), 1.58 (m,
OH, 1H), 1.55 (ddd, J¼12.7, 3.2, 1.5 Hz, X part of AX system, CH2, 1H);
4. Experimental section
4.1. General methods
13C NMR (100 MHz, CDCl3)
d 146.9, 135.9, 129.0, 127.6, 124.4, 120.8,
84.4, 74.2, 56.0, 43.1, 36.0; IR (CH2Cl2, cmꢁ1) 3410, 2924, 2853, 1720,
1465, 1332, 1210, 1188, 1078, 1015, 750. Anal. Calcd for C11H12O5S: C,
51.55; H, 4.72; S, 12.51. Found: C, 51.75; H, 4.70; S, 12.38.
Melting points were determined on Buchi 539 capillary melting
apparatus. Infrared spectra were recorded on a Mattson 1000 FT-IR
spectrophotometer. 1H NMR and 13C NMR spectra were recorded on
200 (50) and 400 (100) MHz Varian spectrometer and are reported
4.1.5. Hydrolysis of 4 to trans-(1R(S),2R(S))-cyclohexane-
1,2-diol (8)
in d units with SiMe4 as internal standard. Elemental analyses were
carried out on a Leco CHNS-932 instrument.
(A) trans-(1R(S),2R(S))-2-Hydroxycyclohexyl hydrogen sulfate (4)
(100 mg, 0.51 mmol) and 10 mL of water were stirred for 5 min
at room temperature. Water was evaporated at 60 ꢀC under
reduced pressure. The residue was dissolved in 30 mL of CH2Cl2
and then dried (Na2SO4). Diol 8 crystallized from CH2Cl2/hex-
ane: white solid (58 mg, 98%, mp 107–108 ꢀC, lit.15a mp 144–
145 ꢀC, lit.15d mp 107.5–108.5 ꢀC).
4.1.1. trans-(1R(S),2R(S))-2-Hydroxycyclohexyl hydrogen sulfate (4)
To a solution of cyclohexene-epoxide (3) (250 mg, 2.6 mmol) in
10 mL of CH2Cl2 was added 615 mg NaHSO4 (5.12 mmol) at room
temperature. The reaction was completed in 24 h as verified by
TLC. Then, the reaction mixture was filtered over filter paper and
the solvent was concentrated under reduced pressure. The crude
product 4 (450 mg, 90%) was recrystallized from CH2Cl2/hexane as
(B) trans-(1R(S),2R(S))-2-Hydroxycyclohexyl hydrogen sulfate (4)
(100 mg, 0.51 mmol) and 2 mL of CH2Cl2 and 20 mL of water

988
H. Cavdar, N. Saracoglu / Tetrahedron 65 (2009) 985–989
were stirred for 30 min at room temperature. The solvent was
(1.50 g) and Ac2O (0.60 g) at 1 day. Then, the mixture was cooled to
0 ꢀC and poured into a cold solution (1%, 100 mL) of HCl. The
mixture was extracted with CH2Cl2 (3ꢂ50 mL). The combined or-
ganic layer was washed with NaHCO3 (5%, 100 mL) and water
(100 mL), and then dried over Na2SO4. After the solvent was
evaporated, tetra acetate 15 was recrystallized from CH2Cl2/hexane
as white crystals (275 mg, 53%, mp 138–139 ꢀC). The yield of 15 was
calculated as a total according to anti-bisepoxide 12. 1H NMR
evaporated under reduced pressure. The residue was dissolved
in 30 mL of CH2Cl2 and then dried (Na2SO4). Diol 8 was
obtained as white solid (56 mg, 95%).
(C) A solution of cyclohexene-epoxide (3) (100 mg, 1.02 mmol) and
13 mg NaHSO4 (0.10 mmol) in 2 mL of CH2Cl2 and 20 mL of
water was stirred for 24 h at room temperature. Then, the re-
action mixture was filtered over filter paper and the solvent
was concentrated under reduced pressure. The crude product 8
(110 mg, 93%) was dissolved in 30 mL of CH2Cl2 and then dried
(Na2SO4). Diol 8 was obtained as white solid (90 mg, 76%). 1H
(400 MHz, CDCl3)
d
4.96–4.92 (m, OCH, 4H), 2.38 (dt, J¼12.5, 4.2 Hz,
A part of AX system, CH2, 2H), 2.02 (s, OAc, 12H), 1.57 (br d,
J¼12.5 Hz, X part of AX system, CH2, 2H); 13C NMR (100 MHz,
CDCl3)
d
170.1, 70.4, 32.0, 21.1; IR (CH2Cl2, cmꢁ1) 1727, 1373, 1235,
NMR (200 MHz, CDCl3)
d 3.34 (m, CHOH, 2H), 3.24 (m, OH, 2H),
1.98–1.86 (m, CH2, 2H), 1.71–1.69 (m, CH2, 2H), 1.26–1.24 (m,
1059, 919, 749. Anal. Calcd for C14H20O8: C, 53.16; H, 6.37. Found: C,
53.34; H, 6.32.
CH2, 4H); 13C NMR (50 MHz, CDCl3)
d 77.8, 34.9, 25.3; IR
(CH2Cl2, cmꢁ1) 3290, 2859, 1446, 1352, 1254, 1210, 1073, 1044,
928, 857. Anal. Calcd for C6H12O2: C, 62.04; H, 10.41. Found: C,
61.88; H, 10.32.
4.1.9. trans,trans-(1R(S),2R(S),3S(R),4S(R))-2,3-Dihydroxy-
cyclohexane-1,4-diyl diacetate (16)
To a stirred solution of syn-bisepoxide 23 (185 mg,1.65 mmol) in
CH2Cl2 (10 mL) was added 1190 mg NaHSO4 (9.91 mmol) at room
temperature. After the mixture was stirred for 24 h, 15 mL of
methanol was added, the reaction mixture was filtered over filter
paper, and the solvent was concentrated under reduced pressure.
Then, the crude product (215 mg) was acetylated in pyridine
(1.50 g) and Ac2O (0.60 g) at 1 day. Then, the mixture was cooled to
0 ꢀC and poured into a cold solution (1%, 100 mL) of HCl. The
mixture was extracted with CH2Cl2 (3ꢂ50 mL). The combined or-
ganic layer was washed with NaHCO3 (5%, 100 mL) and water
(100 mL), and then dried over Na2SO4. After the solvent was
evaporated, tetra acetate 16 was recrystallized from CH2Cl2/hexane
as pale yellow crystals (256 mg, 67%, mp 114–115 ꢀC, lit.18 mp 115–
116 ꢀC). The yield of 16 was calculated as a total according to anti-
4.1.6. trans-(2R(S),3R(S))-1,2,3,4-Tetrahydronaphthalene-
2,3-diol (10)
To a solution of 1,2,3,4-tetrahydronaphthalene-2,3-epoxide (9)
(80 mg, 0.55 mmol) in 10 mL of CH2Cl2 was added 264 mg NaHSO4
(2.18 mmol) at room temperature. The mixture was stirred for 24 h
and 2 mL of water was added to the mixture. Then, the reaction
mixture was filtered over filter paper, the solvent was dried
(Na2SO4), and concentrated under reduced pressure. The crude
product 10 (75 mg, 84%) was recrystallized from CH2Cl2/hexane as
white crystals (45 mg, 50%, mp 161–162 ꢀC, lit.16 mp 157–159 ꢀC).
1H NMR (200 MHz, CDCl3) 7.18–7.10 (m, AA0BB0 system, C6H4, 4H),
d
3.94–3.83 (m, CHOH, 2H), 3.18 (ddd, J¼5.5, 3.8, 1.7 Hz, A part of AB
bisepoxide 13. 1H NMR (400 MHz, CDCl3)
OCH, 2H), 3.45–3.43 (m, CHOH, 2H), 2.07 (s, OAc, 6H), 1.80–1.71 (m,
d
5.25 (br d, J¼5.9 Hz,
system, CH2, 2H), 2.95–2.75 (m, B part of AB system, CH2 and OH,
4H); 13C NMR (50 MHz, CDCl3)
d 135.8, 130.8, 128.3, 74.3, 38.8; IR
(CH2Cl2, cmꢁ1) 3368, 2925, 1721, 1493, 1172, 1064, 745. Anal. Calcd
for C10H12O2: C, 73.15; H, 7.37. Found: C, 73.40; H, 7.30.
CH2, 4H); 13C NMR (100 MHz, CDCl3)
d 170.3, 76.5, 71.6, 24.0, 21.3; IR
(CH2Cl2, cmꢁ1) 3522, 2925, 2846, 1747, 1599, 1459, 1432, 1371, 1245,
1172, 1125, 1056. Anal. Calcd for C10H16O6: C, 51.72; H, 6.94. Found:
C, 52.01; H, 7.00.
4.1.7. trans,trans-(1S(R),2S(R),4S(R),5S(R))-Cyclohexane-1,2,4,5-
tetrayl tetra acetate (14)
To a stirred solution of syn-bisepoxide 11 (140 mg,1.25 mmol) in
a CH2Cl2 (10 mL) was added 900 mg NaHSO4 (7.50 mmol) at room
temperature. After the mixture was stirred for 24 h, 15 mL of
methanol was added, the reaction mixture was filtered over filter
paper, and the solvent was concentrated under reduced pressure.
Then, the crude product (170 mg) was acetylated in pyridine
(1.00 g) and Ac2O (0.50 g) at 1 day. Then, the mixture was cooled to
0 ꢀC and poured into a cold solution (1%, 100 mL) of HCl. The
mixture was extracted with CH2Cl2 (3ꢂ50 mL). The combined or-
ganic layer was washed with NaHCO3 (5%, 100 mL) and water
(100 mL), and then dried over Na2SO4. After the solvent was
evaporated, tetra acetate 14 was recrystallized from CH2Cl2/hexane
as pale yellow crystals (245 mg, 62%, mp 147–148 ꢀC, lit.17 mp 144–
145 ꢀC). The yield of 14 was calculated as a total according to syn-
4.1.10. 2,2-Diphenylacetaldehyde (19)
A solution of trans-stilbene oxide (17) (280 mg, 1.42 mmol) and
NaHSO4 (171 mg,1.42 mmol) in 10 mL of CH2Cl2 was stirred at room
temperature for 30 min. Then, the reaction mixture was filtered
over filter paper and the solvent was concentrated under reduced
pressure. The residue (275 mg) was submitted to column chro-
matography on silica gel (25 g) eluting with ethyl acetate/hexane
(2%). Elution gave 2,2-diphenylacetaldehyde (19) as colorless liquid
(188 mg, 67%). 1H NMR (200 MHz, CDCl3)
d
9.87 (d, J¼2.5 Hz, CHO,
1H), 7.43–7.22 (m, C6H5, 10H), 4.91 (d, J¼2.5 Hz, CH, 1H); 13C NMR
(50 MHz, CDCl3)
d 200.4, 138.4, 131.1, 131.0, 129.6, 66.1; IR (CH2Cl2,
cmꢁ1) 3061, 3029, 2896, 2721, 1954, 1885, 1809, 1724, 1657, 1599,
1494, 1451, 1389, 1279, 1177, 1079, 950. Anal. Calcd for C14H12O: C,
85.68; H, 6.16. Found: C, 85.35; H, 6.10.
bisepoxide 11. 1H NMR (200 MHz, CDCl3)
2.11–2.01 (m, CH2, 4H), 2.06 (s, OAc,12H); 13C NMR (50 MHz, CDCl3)
171.6, 71.2, 32.2, 22.9; IR (CH2Cl2, cmꢁ1) 2966, 1741, 1441, 1370,
d 5.08–5.04 (m, OCH, 4H),
4.1.11. trans-(2S(R),4S(R))-2-Benzyl-4-phenyl-1,3-dioxolane (23)
A solution of styrene oxide (22) (150 mg, 1.25 mmol) and
NaHSO4 (300 mg, 2.50 mmol) in 10 mL of CH2Cl2 was stirred at
room temperature for 15 min. Then, the reaction mixture was fil-
tered over filter paper and the solvent was concentrated under
reduced pressure. The residue (210 mg) was subjected to column
chromatography on silica gel (25 g) eluting with ethyl acetate/
hexane (2%). Elution gave trans-(2S(R),4S(R))-2-benzyl-4-phenyl-
1,3-dioxolane (23) as colorless liquid (140 mg, 48%, lit.20a mp 42 ꢀC,
d
1233, 1182, 1030, 974, 934. Anal. Calcd for C14H20O8: C, 53.16; H,
6.37. Found: C, 53.01; H, 6.15.
4.1.8. trans,trans-(1R(S),2R(S),4S(R),5S(R))-Cyclohexane-1,2,4,5-
tetrayl tetra acetate (15)
To a stirred solution of anti-bisepoxide 12 (185 mg, 1.65 mmol)
in CH2Cl2 (10 mL) was added 1190 mg NaHSO4 (9.91 mmol) at room
temperature. After the mixture was stirred for 24 h, 15 mL of
methanol was added, the reaction mixture was filtered over filter
paper, and the solvent was concentrated under reduced pressure.
Then, the crude product (200 mg) was acetylated in pyridine
lit.20d mp 33–34 ꢀC). 1H NMR (400 MHz, CDCl3)
d 7.36–7.25 (m,
C6H5, 10H), 5.30 (t, J¼4.6 Hz, OCH, 1H), 5.01 (t, J¼6.8 Hz, OCH, 1H),
4.17 (dd, J¼7.7, 6.8 Hz, A part of AX system, CH2, 1H), 3.69 (dd, J¼7.7,
6.8 Hz, X part of AX system, CH2, 1H), 3.15 (dd, J¼13.9, 4.6 Hz, A part

H. Cavdar, N. Saracoglu / Tetrahedron 65 (2009) 985–989
989
7. Prinsep, M. R.; Blunt, J. W.; Munro, M. H. G. J. Nat. Prod. 1989, 52, 657–659.
of AB system, CH2, 1H), 3.11 (dd, J¼13.9, 4.6 Hz, B part of AB system,
CH2, 1H); 13C NMR (100 MHz, CDCl3)
139.6, 136.2, 130.2, 128.7,
128.6, 128.4, 126.6, 126.6, 105.6, 78.7, 72.2, 41.0; IR (CH2Cl2, cmꢁ1
2924, 1495, 1455, 1134, 1080, 1028, 754, 698. Anal. Calcd for
C16H16O2: C, 79.97; H, 6.71. Found: C, 79.69; H, 6.51.
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d
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Acknowledgements
The authors thank the Department of Chemistry and Atatu¨rk
University for financial support of this work.
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Supplementary data
Supplementary data includes experimental procedures and 1H
and 13C NMR spectra of compounds. Supplementary data associ-
ated with this article can be found in the online version, at
doi:10.1016/j.tet.2008.11.092.
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