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D. C. Cole et al. / Bioorg. Med. Chem. Lett. 12 (2002) 1791–1793
Table 1. Oxidation of polystyrene bound sulfide
Oxidation
methoda
Reagent
%
Sulfideb
%
Sulfoxideb
%
Sulfoneb
A
B
C
D
E
F
H2O2
33
5
0
33
23
0
66
60
Trace
66
77
0
35
100
0
0
0
mCPBA, 1 equiv
mCPBA 2 equiv
NaIO4
tBHP
tBHP, pTSA
100
aOxidation method: (A) 30% hydrogen peroxide (10 equiv) in MeOH;
(B) mCPBA (1 equiv) in DCM;(C) mCPBA (2 equiv) in DCM;
(D) sodium periodate (10 equiv) in EtOH/water;(E) 70% tBHP
(10 equiv) in DCM;(F) 70% tBHP (10 equiv) with pTSA (1.5 equiv) in
DCM.
bPercentages were calculated by integration of the CH3 peak of the
cleaved products in the proton NMR spectrum (CDCl3) (RSCH3
2.14 ppm;RSOC H3 2.74 ppm;RSO 2CH3 2.99 ppm).
Scheme 2. Reagents and conditions: (a) 3-(methylthio) propionic acid,
DMAP, DIC;(b) 70% tBHP, pTSA, DCM;(c) (COCl) 2, Et3N, DCM.
Table 2. Isolated yields of aldehydes and ketones after oxidation
with polystyrene bound sulfoxide reagent
Having shown that polystyrene bound sulfides are effi-
ciently oxidized to sulfoxides with 70% tBHP in the
presence of pTSA, the next step was to prepare a poly-
styrene bound sulfoxide for use in the Swern oxidation.
Thus, as shown in Scheme 2, 3-methylsulfanyl propionic
acid was attached to hydroxymethyl polystyrene resin.
The resin bound sulfide 4 was then oxidized to the
sulfoxide 5.
Alcohol
Isolated yield (%)
3-Benzyloxybenzyl alcohol
Anisoin
a-Methyl-2-naphthylenemethanol
71
80
82
The sulfoxide reagent 5 was used to oxidize several test
alcohols under the standard conditions described below.
HPLC analysis6 of the reaction mixtures showed com-
plete conversion to the aldehyde or ketone with no trace
of alcohol remaining. The isolated yields of aldehydes
and ketones after flash chromatography are shown in
Table 2.
alcohol (1 equiv) in DCM. After stirring for 30 min,
triethylamine (6 equiv) was added and the mixture
allowed to warm to À40 ꢀC for 2 h, then filtered and
washed with DCM. The filtrate was concentrated and
the residue purified by flash chromatography over silica
gel with ethyl acetate and hexanes.
To test the recyclability of the polystyrene bound
reagent 5, a-methyl-2-naphthylenemethanol was
oxidized to 20-acetonaphthone using the standard
conditions. After the reaction the reduced resin was
washed and re-oxidized using tBHP and pTSA. The
resin was then reused to oxidize a-methyl-2-naphthyle-
nemethanol. Again HPLC analysis indicated complete
conversion to the ketone, which was obtained in 71%
isolated yield.
Sulfide Oxidation Study on Wang Polystyrene Resin
A
suspension of Wang Resin (PL-Wang resin,
1.7 mmol/g 150–300 mM, from Polymer Laboratories),
3-(methylthio) propionic acid (5 equiv) and DMAP
(1 equiv) in DCM/DMF (1:1) was treated with DIC
(5 equiv) and shaken overnight. The material was
washed with DMF/water (10:1) (50 mL), DMF (50 mL),
DCM (50 mL), MeOH (50 mL) and DCM (3Â50 mL).
The material was then dried under vacuum.
In conclusion, an inexpensive, readily synthesized,
recyclable, polystyrene bound sulfoxide reagent has
been developed which may be used in place of DMSO in
Swern oxidations. The reagent is easily removed by fil-
tration and can be recycled and reused.
The sulfide resin 1 was suspended in the appropriate
solvent and the reagents indicated in Table 1 added. The
mixture was shaken at room temperature overnight,
then washed as above and dried under vacuum.
General Procedure for Oxidation Using Polystyrene
Bound Sulfoxide Resin
The polystyrene bound sulfoxide reagent 5 (2 equiv) was
suspended in DCM and cooled to À50 to À60 ꢀC. Oxa-
lyl chloride (2 equiv of a 2 M solution in DCM) was
added dropwise, followed after 15 min by a solution of
The oxidized resin 2 was treated with DCM/TFA for
30 min, then filtered and the filtrate concentrated. The
residue was analyzed by NMR to determine the extent
of oxidation.
Cole, Derek C
