Improved and environmentally friendly large-scale preparation of cyclohexadienyl-, cycloheptadienyl sulfone and enantiopure epoxy cycloheptyl sulfones

Article abstract of DOI:10.1055/s-2004-822318

Kilogram-scale amounts of cycloheptadienyl phenylsulfone and cyclohexadienyl phenylsulfone were prepared by one operation in 5 stages with over 50% yield and requiring no purification. A practical and efficient method for the Jacobsen asymmetric epoxidati

Full text of DOI:10.1055/s-2004-822318

PRACTICAL SYNTHETIC PROCEDURES
1895
Improved and Environmentally Friendly Large-Scale Preparation of
Cyclohexadienyl-, Cycloheptadienyl Sulfone and Enantiopure Epoxy
Cycloheptyl Sulfones
Preparation of
C
a
ycloheptad
e
ienyl Sulfo
s
ne and its
i
E
nanti
k
opure
E
poxides Park, Eduardo Torres, Philip L. Fuchs*
Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, USA
E-mail: pfuchs@purdue.edu
PSP
Received 28 January 2004
No24
Abstract: Kilogram-scale amounts of cycloheptadienyl phenylsulfone and cyclohexadienyl phenylsulfone were prepared by one operation
in 5 stages with over 50% yield and requiring no purification. A practical and efficient method for the Jacobsen asymmetric epoxidation of
1,3-cycloheptadienyl sulfone is described. The reported method is suitable for large-scale synthesis, does not use halogenated solvents nor
does it require chromatography
Key words: vinyl sulfone, cycloheptadienyl, cyclohexadienyl, bromination, pyridinium salt, Jacobsen epoxidation
SO2Ph
SO2Ph
OH OH
5-15% Jacobsen Cat.
O
R
R
R
10% P3NO
n
n
Any desired stereopentad
buffered NaOCl
1 (n=2)
2 (n=1)
3 (n=2)
4 (n=1)
CH2Cl2, 0 o
C
Scheme 1
As a part of our program to develop short and scalable Synthesis of 1
syntheses of polypropionate containing natural products,
it became essential to develop efficient preparations of The synthesis of diene 1 begins with commercially avail-
dienes 1 and 2 and the enantiopure epoxides 3 and 4 de- able cycloheptanone 5, which is heated in toluene for 24
rived from them (Scheme 1).1 In 2002, Meyers developed hours with thiophenol in the presence of Montmorillonite
an improved method for the preparation of 1 and 2; al- KSF5 using a Dean–Stark trap to give the vinyl sulfide 6
though this method was highly satisfactory for generation (Scheme 2). Among various kinds of acid catalysts6 and
of hundred gram quantities of diene 1, and 2, it still was solvents tested, the best condition was 10 wt% of Mont-
unsuitable for the multi-kilogram scale.2 In 1997, Hente- morillonite KSF in 4 M toluene which gives 93% of the
mann found that Jacobsen asymmetric epoxidation (JAE) desired vinyl sulfide 6 and 7% of thioketal. The KSF cat-
of cyclohexadienyl and cycloheptadienyl sulfones 1 and 2 alyst is removed by filtration through a celite pad to gen-
gave the enantiopure epoxides 3 and 4 in good yield and erate a light yellow toluene solution, which is used
outstanding ee. Additionally, one could obtain either ep- directly in the next step.
oxide enantiomer by application of the appropriate com-
The original bromination method employed 1 equivalent
mercially available enantiomeric catalyst.3,4 A major
of NBS in CH2Cl2 cooled in an ice bath. The reaction was
drawback of the JAE was scalability of the reaction. The
excellent, but NBS is relatively expensive and use of ha-
development of an optimized process for the preparation
logenated solvents should be avoided due to their cost and
toxicity. The new bromination condition using H2O2–
of diene 1, 2 and epoxide 3 is now at hand.
Optimization of each individual step for the kilogram syn- NaBr–Na2WO4 was adopted due to its low toxicity, low
thesis of 1 and 2 has now been accomplished. The new op- cost, and high selectivity (Table 1).
timized syntheses are now one-operation procedures that
This condition combines Sel’s bromination7 and Noyori’s
involve 5 distinct stages but require no purification.
oxidation.8 Sodium tungstate (1 mol%), phenylphosphinic
acid, and tricaprylylmethylammonium hydrogensulfate9
as a phase transfer catalyst were used with 1 equivalent of
30% H2O2, 1 equivalent NaBr and 1 equivalent 2 M aque-
ous phosphoric acid (or 2 M sulfuric acid) to give a very
clean bromination.
SYNTHESIS 2004, No. 11, pp 1895–1900
x
x.
x
x
.
2
0
0
4
Advanced online publication: 30.03.2004
DOI: 10.1055/s-2004-822318; Art ID: Z01904SS
© Georg Thieme Verlag Stuttgart · New York

1896
T. Park et al.
PRACTICAL SYNTHETIC PROCEDURES
Scheme 2
Table 1 Bromination of 6
sulfide mixture to their corresponding sulfones. Although
this mixture could be chromatographed with care to obtain
pure sulfone 9, such a procedure was not acceptable on
large scale, and we sought a chemical protocol that would
rely upon a phase separation.
SPh
SPh
SPh
SPh
Br
Br
Br
Br
+
+
6
7
12
8
After removal of the aqueous layer from the oxidation
procedure, 0.8 equivalent of pyridine and water to make
the new aqueous layer (1 M) were added and stirred at
60 °C for 2 hours which completed the formation of pyri-
dinium salt 11 as well as dissolving it to produce a homo-
geneous aqueous phase (11 is only partially soluble at
25 °C, but soluble at 60 °C). The organic layer, which
contains most of impurities as well as the unwanted b-bro-
movinylsulfone 10 (unreactive with pyridine) was
removed (Scheme 3). The resulting aqueous pyridinium
salt solution 11 was cooled to room temperature to gener-
ate a white solid.
Reagent
NBS
Allyl (7)
15.3
Vinyl (8)
Dibromide (12)
1
1
1
0.9
0.5
0
Br2/Py
8.3
NaBr/Na2WO4
11.4a
a The ratio for a small scale reaction. At kilogram scale it was a 9:1
ratio.
Excess H2O2 did not oxidize the sulfide to sulfone. An in-
organic salt or metal chelating halide anion may deacti-
vate the tungstate catalyst. After removal of the aqueous
layer, the original procedure for Noyori’s oxidation of the
organic mixture proceeded to convert the allyl and vinyl
Reaction of the pyridinium salt 11 with Et3N in water gave
a significant amount of the side product 20 (6–10%). A re-
action using the lower pKa base, DABCO,TM seeded with
0.1 wt% of 1 at room temperature gave the desired white
water layer
SO2Ph
SO2Ph
SO2Ph
OH
SO2Ph
Br
pyridine
N+
Br -
base
+
water
n
n
n
9 + 10 (n=2)
17 + 18 (n=1)
n
> 98%
< 1-2%
11 (n=2)
19 (n=1)
1 (n=2)
2 (n=1)
20 (n=2)
21 (n=1)
toluene layer
SO2Ph
Br
+ etc
n
10 (n=2)
18 (n=1)
Scheme 3
Synthesis 2004, No. 11, 1895–1900 © Thieme Stuttgart · New York

PRACTICAL SYNTHETIC PROCEDURES
Cycloheptadienyl Sulfone and its Enantiopure Epoxides
1897
solid product in a clean reaction having less than 2% of the id product was filtered, washed with water, and dried to
side product 20. Without the seed, the reaction gave red- give the pure and pale yellow solid 2 in 98% purity by
dish oil, which requires subsequent recrystallization. Af- HPLC and 51% overall yield from cyclohexanone 13.
ter 36 hours, the mixture was quenched with 2 M HCl and
the solid product was filtered, washed with water, and
dried to give the pure and white solid 1 in 53% overall
yield from cycloheptanone 5. Purity was assayed at 98%
by HPLC
Preparation of 3
As seen in Scheme 1 the JAE was originally carried out in
CH2Cl2 with 5–15% catalyst, and 10% P3NO as co-cata-
lyst and buffered bleach as the oxidant. Using this meth-
od, the cost for preparation of 1 mole of the epoxide was
> $1000,10 without factoring in waste disposal. In 1998,
Synthesis of 2
The synthesis of 2 is very similar to the above procedure. Pietikäinen screened a series of carboxylate salts to be
Dean–Stark condensation of cyclohexanone 13 with used as additives in the Jacobsen epoxidation with H2O2
thiophenol in the presence of 10 wt% Montmorillonite used as an oxidant.11 Although H2O2 is inexpensive, rea-
KSF, followed by bromination using NaBr and catalytic sonably stable, readily available, and gives only water as
sodium tungstate gave a nearly 1:1 mixture of the allyl a by-product, it suffers from the oxidative destruction of
(15) and vinyl bromide (16). Meyers observed that a neat heterocyclic additives which accelerate the reaction, in-
1:1 mixture of the allyl bromide 15 and the vinyl bromide crease the yield, and stabilize the chiral (salen)Mn cata-
16 equilibrates to an approximately 9:1 thermodynamic lyst. Fortunately, Mansuy and coworkers discovered that
mixture with the allyl bromide 15 as the major product ammonium acetate acts as an efficient co-catalyst for the
(Scheme 4). The organic layer was concentrated in vacuo manganese porphyrin-catalyzed epoxidation of olefins,12
and placed at room temperature for 8 hours.
and Jacobsen has successfully employed unbuffered H2O2
in the presence of (salen)Mn(III) catalysts for the asym-
metric oxidation of sulfides.13 When Pietikäinen’s condi-
tions were applied to diene 1 during the course of this
work, the results were very encouraging. This method
worked for both the cyclohepta- and cyclohexadiene sys-
tems (1, 2), but still required 5–10% catalyst, halogenated
solvent and column chromatography. Although many of
the problems associated with the JAE of our parent dienes
have been worked out in this lab,14 these methods were not
optimal for large scale purposes. Preparation of 10 g of
any of the enantiopure epoxides was a grueling and ex-
pensive task. The development of an optimized process
for the preparation of epoxide 3 on scales up to 1 mole is
now a routine procedure.
The equilibrated mixture was diluted to 2 M with toluene
and oxidized with 30% H2O2 and catalytic sodium tung-
state to give the allylic sulfone 17. After removal of the
aqueous layer, 0.8 equivalent pyridine with water to 2 M
was added and stirred at room temperature for 1.5 hours.
In this case pyridinium salt 19 was soluble in water at
room temperature. The organic layer containing most of
impurities was removed (Scheme 3).
To the resulting aqueous pyridinium salt solution 19, 0.7
equivalent Et3N and 0.1 wt% of 2 as a seed were added in
an ice bath. In this series, Et3N was satisfactory instead of
DABCOTM as a base, and higher concentration (2 M) and
lower temperature (ice bath) gave a clean reaction. After
5 hours, the mixture was quenched with 2 M HCl, the sol-
Scheme 4
Synthesis 2004, No. 11, 1895–1900 © Thieme Stuttgart · New York

1898
T. Park et al.
PRACTICAL SYNTHETIC PROCEDURES
Initial studies sought to recover and recycle the catalyst in order to get high purity product. The new procedure sim-
order to alleviate the cost of the process. Using Pietikäin- plifies purification to a great extent. After work-up, the
en conditions, it was found that the catalyst could be re- crude product was dissolved in MeOH and left at low tem-
covered in 89% yield, but the turn over number (TON) perature overnight, which gave crystalline epoxy cyclo-
was reduced significantly. Thus a reaction using 5 mol% heptanyl sulfone 3 in 74% yield with >95% purity and
of the catalyst gave 68% yield with 98% ee, and 70% of >99% ee. The need for chromatography was eliminated.
the catalyst was recovered and reused. The second reac- 1H NMR and HPLC indicated purity higher than 95%, but
tion required 10 mol% of the recycled catalyst for the re- elemental analysis failed due to trace amounts of manga-
action to go to completion with comparable yield and ee nese that were still present even after recrystallization.
to the fresh catalyst initially used. Although the catalyst This metal does not affect the use of the epoxide in subse-
can be recovered a second time it was found that the cata- quent reactions.
lyst is completely inactive even when 100 mol% is used
SO2Ph
for the epoxidation.
SO2Ph
1 % Jacobsen Cat.*
There seemed to be a reasonable amount of active catalyst
O
after the first epoxidation, so it appeared feasible to lower
1 eq NH4OAc
the amount of catalyst used in the reaction without ad-
1
3
6 eq H2O2
>70 % yield
versely affecting the outcome of the epoxidation. It was
found that the catalyst can be lowered to 1 mol% without
significant loss of yield or ee, but the reaction time was
overly long. This problem was overcome by using 100
mol% of NH4OAc; other possible co-catalysts were
screened at various temperatures but none were as effi-
cient as NH4OAc. This modification combined with the 1
mol% catalyst loading, made it possible to run the reaction
in a reasonable time period with excellent results, but ac-
tive catalyst can no longer be recovered (Table 2).
0.2 M MeOH, 0 oC, 12 h
>99 % ee
* (R,R)-Mn cat.
(S,S)-Mn cat.
(S,S)-3
(R,R)-3
Scheme 5
In conclusion, an environmentally friendly and practical
method for cycloheptadienyl sulfone, cyclohexadienyl
sulfone, and the JAE of the cycloheptadienyl sulfone has
been successfully performed. This new method has low-
ered the cost of the production of epoxide 3 significantly;
it uses less catalyst, no halogenated solvents, and requires
only a final crystallization to get the desired product. This
procedure enables preparation of the epoxide in large
scales (> 200 g) and minimal costs. Application of this
process to cyclohexadienyl sulfone 2 was unsuccessful
due to substantial aromatization; further studies on this
substrate must be conducted.
Table 2 Effect of Lowering the Amount of Jacobsen Catalyst
Entry
Mol% of
catalyst
% Yield
(% ee)
Reaction
time (h)
1
2
3
4
5
6
7a
5
68 (98)
67 (98)
66 (96)
67 (95)
69 (95)
26 (95)
72(95)
8
4
8
3
10
15
24
48
12
Cyclohexanone (Aldrich), cycloheptanone (Aldrich), benzenethiol
(97%, Aldrich), Montmorillonite KSF (Aldrich), NaBr, sodium
tungstate, phenyl phosphonic acid, DABCOTM, and Et3N were all
used as received. Melting points were obtained on a capillary melt-
ing point apparatus and are uncorrected. Optical rotations were car-
ried out in CHCl3.
2
1
0.5
1
2-(Phenylsulfonyl)-1,3-cycloheptadiene (1); Typical Procedure
To a 12 L 3-neck round bottom flask equipped with a mechanical
stirrer, heating mantle, Dean–Stark trap and condenser, were added
cycloheptanone 5 (1.0 kg, 8.92 mol), benzenthiol (1.06 kg, 1.05
equiv), and 10 wt% Montmorillonite KSF (100 g) in toluene (2.2 L)
and the mixture was heated at reflux for 24 hours. After the reaction
was complete, the resulting vinyl sulfide mixture 6 was cooled to r.t.
and then filtered through Celite® (100 g) and the pad was washed
with toluene (2.2 L).
a Using 1 mol equiv NH4OAc.
It was necessary to find a solvent system that would min-
imize waste disposal costs and at the same time accommo-
date the environment. Various non-halogenated solvents
were screened to determine the best compromise of cost,
ease of use, and ease of disposal. It was found that the re-
action worked best at a concentration of 0.2 M in MeOH.
This result had two major benefits: 1) it was possible to
observe the reaction go to completion, since the reaction
began dark brown and gradually turned pale yellow, 2) ha-
logenated solvents were eliminated from this procedure,
thus making this a ‘greener’ process.
The solution was transferred to a 22 L 3-neck round bottom flask
equipped with a mechanical stirrer, addition funnel, thermometer,
and water bath, NaBr (918 g, 1.0 equiv), 2 M H3PO4 solution (4.46
L, 1.0 equiv), 1 M aq Na2WO4·2H2O (89 mL, 0.01 equiv), and 1 M
aq PhPO(OH)2 (89 mL, 0.01 equiv) were added and stirred in the
water bath for 30 min. With vigorous stirring, 30 wt% H2O2 (857
mL, 1.0 equiv) was slowly added with the addition funnel for 3 h.
The reaction temperature was maintained below 25 °C and the bath
temperature was kept in the range of 15–18 °C. After one more hour
of stirring, the aqueous layer was removed, and the organic layer
Purification of the final product was originally a very dif-
ficult task. It usually required 2 large silica gel columns in
Synthesis 2004, No. 11, 1895–1900 © Thieme Stuttgart · New York

PRACTICAL SYNTHETIC PROCEDURES
Cycloheptadienyl Sulfone and its Enantiopure Epoxides
1899
was washed with 2 M Na2SO3 (1 L) and 2 M H3PO4 (1 L) to give a
crude mixture of 7 and 8 (9:1 ratio).
and the aqueous solution was washed with EtOAc (2 × 1 L) and
then with hexane (1 L) to give an aqueous solution of 19.
To the mixture solution of 7 and 8, were added 1 M aq
Na2WO4·2H2O (89 mL, 0.01 equiv), 1 M aq PhPO(OH)2 (89 mL,
0.01 equiv), PTC (0.5 M solution in toluene, 180 mL, 0.01 equiv)
and stirred in the water bath for 30 min. H2O2 (30 wt%, 1.7 L, 2.0
equiv) was added slowly with an addition funnel for 2.5 h. After
stirring vigorously in the water bath for 15 h, brine (1 L) was added
and stirred for 1 min. The aqueous layer was removed.
After stirring in an ice bath for 30 min, to the aqueous solution of
19, were added Et3N (990 mL, 0.7 equiv ), and 0.1 wt% 1,3-cyclo-
hexadienophenylsulfone (1 g) as a seed. After stirring for 5 h, 2 N
HCl (3.5 L) was added, and it was filtered through a glass filter. The
solid product was washed with water (2 L) and dried by forcing air
through the filter cake for 24 h to give a pure and pale yellow solid
(2, 1.1 kg, 51% yield over 5 steps from cyclohexanone, 98% purity
by HPLC); mp 58–60 °C (lit.2 58–61 °C, lit.15 60–63 °C).
1H NMR (300 MHz, CDCl3): d = 2.10 (m, 2 H), 2.40 (m, 2 H), 5.90
(m, 1 H), 6.15 (m, 1 H), 6.95 (m, 1 H), 7.50–7.70 (m, 3 H), 7.80–
8.00 (m, 2 H).
To the toluene solution of 9 and 10, were added pyridine (580 mL,
0.8 equiv) and water (8.92 L) and with stirring, heated up from r.t.
to 60 °C for 2 h. After removal of the organic layer, the aqueous lay-
er was washed with EtOAc (2 × 1 L) and then with hexane (1 L)
while the solution temperature was maintained at about 60 °C. To
remove the insoluble solid, the warm aqueous layer was filtered
through a small glass filter into a 22 L 3-neck round bottom flask,
equipped with a mechanical stirrer. Cooling to r.t. gave a white solid
suspension of 11.
13C NMR (75 MHz, CDCl3): d = 20.71, 22.23, 118.39, 127.66,
129.08, 129.95, 133.16, 134.75, 138.64, 139.84.
(2-Phenylsulfonyl)-8-oxabicyclo[5.1.0]oct-2-ene (3); Typical
Procedure
To the white solid suspension of 11 were added 0.1 wt% of the solid
product 1 (1 g) and 1,4-diazabicyclo[2.2.2]octane (DABCOTM, 701
g, 0.7 equiv). After stirring for 36 h at r.t., 2 N HCl (4.0 L) was add-
ed, filtered through a large glass filter and rinsed with water (5 L).
It was dried with an air stream and under vacuum to give a pure and
white solid (1, 1.11 kg, 53% yield over 5 steps from cyclohep-
tanone, 98% purity by HPLC); mp 61–62 °C (lit.2 57–58 °C).
1H NMR (300 MHz, CDCl3): d = 1.85 (m, 2 H), 2.31 (m, 2 H), 2.56
(q, J = 5.8 Hz, 2 H), 6.03 (m, 2 H), 7.28 (t, J = 5.5 Hz, 1 H), 7.46–
7.64 (m, 3 H), 7.84–7.90 (m, 2 H).
A 22 L 3-neck round bottom flask equipped with a mechanical stir-
rer, 1 L pressure equalizing addition funnel and thermometer was
charged with diene 1 (307.7 g, 1.3 mol). The solid was then com-
pletely dissolved with MeOH (6.5 L). NH4OAc (100.9 g, 1.3 mol)
was then added to the solution and the temperature lowered to 0 °C.
Mechanical stirring was commenced (ca 600 rpm), it is necessary to
ensure that all the NH4OAc is dissolved before proceeding further.
The Jacobsen Mn catalyst (8.3 g, 0.01 mol) was then added and the
solution immediately turned brown (due to the catalyst). If the R,R-
Jacobsen catalyst is used the product obtained is the S,S-epoxide, if
the S,S-catalyst is used the product obtained is the R,R-epoxide
(Scheme 5). H2O2 (30 wt%, 797 mL, 6 equiv) was slowly added
over a period of 2 h at 0 °C. It is crucial that the temperature of the
reaction remains below 5 °C, thus slow addition of the H2O2 was
carefully monitored. The reaction was then left stirring vigorously
for an additional 14 h and the temperature allowed to slowly rise to
25 °C. Dimethyl sulfide (573 mL) was slowly added to quench any
unreacted peroxide and left stirring for 1 h. Brine (12 L) was then
added to the solution and sludge formed on the walls of the flask.
The aqueous mixture was decanted, and extracted with EtOAc (3 ×
1 L). The sludge (ca 167 g) was dissolved in EtOAc (2 L) and both
the combined organic extracts and the dissolved sludge were put to-
gether and dried over Na2SO4 (500 g). The organic mixture was then
concentrated via rotary evaporation and redissolved in MeOH (3 L).
The solution was placed in a –20 °C freezer and allowed to recrys-
tallize overnight. The resulting crystals were collected on a large
fritted glass filter (large pore) and rinsed with Et2O (250 mL), and
air-dried for 1 h. The mother liquor was concentrated and the entire
recrystallization process was repeated twice. The first batch of crys-
tals gave ca 64% yield of the desired epoxide as an off-white solid.
Recrystallization of the second crop took between 18–24 hours. The
combined yield after two recrystallizations was 78% with a >
99%ee and > 95% purity as assessed by HPLC (5.0 cm × 4.6 mm
ChiralPak AD, hexanes–i-PrOH (90:10), 1 mL/min, UV detector:
230 nm, tR S,S-epoxide: 8.4 min, tR R,R-epoxide: 5.2 min.
13C NMR (75 MHz, CDCl3): d = 24.55, 30.53, 31.02, 118.94,
127.67, 128.97, 132.93, 138.04, 139.16, 140.02, 141.87.
2-(Phenylsulfonyl)-1,3-cyclohexadiene (2); Typical Procedure
To a 12 L 3-neck round bottom flask equipped with a mechanical
stirrer, heating mantle, Dean–Stark trap and condenser, were added
cyclohexanone 13 (1.0 kg, 10.18 mol), benzenthiol (1.12 kg, 1.05
equiv), and 10 wt% Montmorillonite KSF (100 g) in toluene (2.5 L)
and refluxed for 24 h. After the reaction, the resulting vinyl sulfide
mixture 14 was cooled to r.t. and then filtered through a Celite® (100
g) pad and the pad was washed with toluene (2.5 L).
The solution 14 was transferred to a 22 L 3-neck round bottom flask
equipped with a mechanical stirrer, addition funnel, thermometer,
and water bath. NaBr (1.04 kg, 1.0 equiv), 2 M H3PO4 solution (5.1
L, 1.0 equiv), Na2WO4·2H2O (33.5 g, 0.01 equiv), and PhPO(OH)2
(16 g, 0.01 equiv) were added and stirred in the water bath for 20
min. With vigorous stirring, 30 wt% H2O2 (978 mL, 1.0 equiv) was
slowly added with the addition funnel for 3 h while maintaining the
reaction temperature below 20 °C. The organic layer was concen-
trated by removing 80% of the toluene with rotary evaporator and
the concentrated solution then kept at r.t. for 8 h to allow equilibra-
tion to 15.
The concentrated solution was diluted with toluene (5 L) in a 22 L
3-neck round bottom flask, equipped with a mechanical stirrer, ad-
dition funnel, thermometer, and water bath. After adding
Na2WO4·2H2O (33.5 g, 0.01 equiv), PhPO(OH)2 (16.0 g, 0.01
equiv), PTC (0.5 M solution in toluene, 200 mL, 0.01 equiv ), and
water (500 mL), 30% H2O2 (1957 mL, 2.0 equiv) was added slowly
with the addition funnel for 2 h, while maintaining the reaction mix-
ture temperature below 30 °C. After stirring vigorously in a 25 °C
bath for 3 h, brine (1 L) was added and stirred for 1 min. The aque-
ous layer was removed to give crude solution of 17.
(1S,7S)-(2-Phenylsulfonyl)-8-oxabicyclo[5.1.0]oct-2-ene (3)
[a]D25 +68 (c = 18.5 mg/mL, CHCl3).
1H NMR (300 MHz, CDCl3): d = 7.88–1.94 (m, 2 H), 7.50–7.68 (m,
3 H), 7.37–7.42 (m, 1 H), 3.68–3.71 (dd, J = 1.22 Hz, J = 4.15 Hz,
1 H), 3.41–3.48 (m, 1 H), 2.49–2.63 (m, 1 H), 2.20–2.33 (m, 1 H),
1.95–2.18 (m, 2 H), 1.52–1.72 (m, 2 H).
13C NMR (75 MHz, CDCl3): d = 146.82, 139.87, 138.73, 133.50,
129.30, 128.08, 59.62, 51.23, 30.76, 29.03, 21.06.
To the crude toluene solution of 17 was added deionized water (5.0
L) and then pyridine (563 g, 0.7 equiv) was added dropwise for 30
min. After stirring at r.t. for 1.5 h, the organic layer was removed
LRMS (CI): m/z = 251 [M + H], 233 (base peak).
HRMS: m/z calcd for C13H14O3S: 251.0742; found: 251.0741.
Synthesis 2004, No. 11, 1895–1900 © Thieme Stuttgart · New York

1900
T. Park et al.
PRACTICAL SYNTHETIC PROCEDURES
(6) Polyaniline-sulfuric acid salt gave a similar result to
Montmorillonite KSF: Palaniappan, S.; Narender, P.;
Saravanan, C.; Rao, V. J. Synlett 2003, 1793.
(7) Sels, B.; Vos, D.; Buntinx, M.; Pierard, F.; Mesmaeker, A.
K.; Jacobs, P. Nature (London) 1999, 400, 855.
(8) Sato, K.; Hyodo, M.; Aoki, M.; Zheng, X.; Noyori, R.
Tetrahedron 2001, 57, 2469.
Acknowledgment
We thank Karl Wood and Arlene Rothwell for mass spectral data
and Daniel Lee for elemental analysis. E. T. wishes to thank Pfizer,
Inc. for a fellowship. We also wish to thank Dr. Douglas Lantrip for
his technical assistance and help with the HPLC, and Dr. In Chul
Kim for helpful discussions.
(9) Prepared from Aliquat 336 (Aldrich) according to Noyori’s
procedure.8
References
(10) Based on prices from Aldrich catalog, including reagents
necessary for purification.
(11) Pietikäinen, P. Tetrahedron 1998, 54, 4319.
(12) Thellend, A.; Battioni, P.; Mansuy, D. J. Chem. Soc., Chem.
Commun. 1994, 1035.
(13) Palucki, M.; Hanson, P.; Jacobsen, E. N. Tetrahedron Lett.
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