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A. Ozanne-Beaudenon, S. Quideau / Tetrahedron Letters 47 (2006) 5869–5873
Table 1. Optimization of SIBX-mediated sulfoxidationa
O
S
S
SIBX
rt
1
2
Entry
SIBX (equiv)
Solvent
Toluene
Toluene/H2O (50:1)
Toluene
Toluene/H2O (50:1)
CH2Cl2/H2O (50:1)
EtOAc/H2O (50:1)
CH2Cl2/H2O (50:1)
CH2Cl2/H2O (50:1)
CTAB (mol %)
Time (h)
Yieldb (%)
1
2
3
4
5
6
7
8
1
1
1
1
1
1
5
0.5
0
0
72
72
40
2
0.5
2.5
24
96
No reaction
No reaction
72
93
20
20
20
20
20
20
89
86
91c
50d
a All reactions were run at rt using 0.2 mmol of 1 in ca. 5 mL of solvent and 1 equiv of SIBX, unless otherwise noted.
b Isolated yields.
c Reaction completed in 30 min; yield evaluated from NMR analysis of the reaction mixture.
d Reaction not completed after 96 h.
addition of a small amount of water was here found to
be highly beneficial for accelerating the reaction, which
presumably then takes place at the interior of reversed
micelles formed by CTAB acting as a surfactant.14–16
Thus, in a 50:1 toluene–water plus 20 mol % CTAB
reversed micellar medium, the same reaction led to 2
in 93% yield after only 2 h (Table 1, entry 4). Sulfoxida-
tion of 1 is even faster and completed in 30 min in
dichloromethane–water (50:1), but slows down in a
more polar solvent system such as ethyl acetate–water
(50:1) (Table 1, entries 5 and 6).
into sulfoxides 4 and 6 in 82% and 84% yields (Table 2,
entries 1 and 2). Oxidation of electron-poor sulfides such
as 7 and 9 furnished sulfoxides 8 and 10 in 74% and 76%
yields, but these reactions were much slower (Table 2,
entries 3 and 4). Diphenyldisulfide (not shown) was
refractory to any oxygenation. Also, SIBX expressed
the same shift of chemoselectivity than that previously
observed with IBX in the presence of catalytic amounts
of Et4N+Brꢀ in either dimethylsulfoxide–acetone or
chloroform–water.7 In our case, phenylthioethanol (11)
was converted into the corresponding sulfoxide 12 in
91% yield in the reversed micellar system (Table 2, entry
5), whereas it furnished aldehyde 13 in quantitative yield
in refluxing ethyl acetate (Table 2, entry 6).11
The selectivity of this oxygenation reaction was then put
to the test by adding an excess of SIBX, up to 5 equiv,
and by letting the reaction go for 24 h in the 50:1 dichlo-
romethane–water solvent system, still in the presence of
20 mol % of CTAB. Under such reaction conditions, 1
was cleanly converted into 2 in 91% yield (Table 1, entry
7). The only additional product was the corresponding
sulfone (not shown) that was observed in only 9% yield.
Both the presence of water and the acidity of the SIBX
formulation certainly help preventing overoxidation of
the sulfoxide into a sulfone. Indeed, both solvation by
water and protonation of the sulfoxide will decrease
the nucleophilicity of its sulfur atom, thereby lowering
its susceptibility to further oxygenation.17 Once the reac-
tion is completed, the insoluble white powder is removed
by filtration. It contains the k3-iodane iodosobenzoic
acid (IBA) generated as a result of the concomitant
reduction of IBX during the oxidation process. Since
IBA is also capable of oxidizing sulfides into sulf-
oxides,15 we then wanted to verify if less than stoichio-
metric amounts of SIBX could be enough to lead the
reaction to completion. The sulfoxidation of 1 using
0.5 equiv of SIBX proceeded initially quite rapidly but
then seemed to stop. After four days, 2 was obtained
in only 50% yield (Table 1, entry 8). Consequently, all
subsequent reactions were run using 1 equiv of SIBX.
Asymmetric sulfoxidation has previously been accom-
plished by Kita and co-workers with moderate to good
enantioselectivity (up to 72% ee) using the k5-iodane
PhIO2 (0.5 equiv) in a reversed micellar medium (i.e.,
toluene–water (50:1) plus 20 mol % CTAB) in the pres-
ence of 10 mol % of a chiral additive.15 We were there-
fore curious to examine the ability of SIBX to perform
such an asymmetric reaction under similar conditions.
Thus, we first evaluated the potential of various chiral
species to induce enantioselective oxidation of sulfide 3
(Table 3). Although the use of dichloromethane was
shown to increase the sulfoxidation rate of 1 (Table 1,
entry 4 vs 5), we chose to use the same solvent system
as the one used by Kita and co-workers (i.e., toluene–
water (50:1)) in this evaluation of chiral additives. The
best one thus tested was the tartaric acid derivative 14
(i.e., di(2-methoxybenzoyl)-L-tartaric acid) that led to
sulfoxide 4 in quantitative yield with a 28% ee in favor
of the S enantiomer (Table 3, entry 7). This tartaric acid
was also shown by Kita and co-workers as the most effi-
cient inductor of asymmetry among the chiral species
they used in concert with PhIO2 as the oxygen source.15
Interestingly, these authors postulated the in situ gener-
ation of some stereochemically-defined intermediate
from PhIO2 and 14 as the reactive species responsible
for the observed asymmetric oxygenation event.15 Such
an intermediate could indeed conceivably be formed
via nucleophilic addition of the carboxylic acid
Several other sulfides were then oxidized under our opti-
mized CTAB-induced reversed micellar conditions in
dichloromethane–water (50:1) (Table 2). Methyl p-tolyl-
sulfide (3) and diphenylsulfide (5) were rapidly converted