Iodine-mediated α-sulfonyloxylation of alkyl aryl ketones with oxone and sulfonic acids

Article abstract of DOI:10.1055/s-0032-1318199

Alkyl aryl ketones are converted into the corresponding α-sulfonyloxyketones, in moderate to excellent yields, via a novel procedure that utilizes Oxone, p-toluenesulfonic acid or methanesulfonic acid and molecular iodine in a mixture of aceton

Full text of DOI:10.1055/s-0032-1318199

PAPER
▌791
®
paper
Iodine-Mediated α-Sulfonyloxylation of Alkyl Aryl Ketones with Oxone and
Sulfonic Acids
Iodine-Mediated α-Sulfonyloxylation
Hiroki Kikui, Katsuhiko Moriyama, Hideo Togo*
Graduate School of Science, Chiba University, Yayoi-cho 1-33, Inage-ku, Chiba 263-8522, Japan
E-mail: togo@faculty.chiba-u.jp
Received: 25.12.2012; Accepted after revision: 20.01.2013
mCPBA7 or Oxone®,8 the iodobenzene-catalyzed α-tosyl-
Abstract: Alkyl aryl ketones are converted into the corresponding
oxylation of ketones with Oxone® and p-toluenesulfonic
α-sulfonyloxyketones, in moderate to excellent yields, via a novel
acid,9 and the iodoarene-mediated α-tosyloxylation of ke-
tones with mCPBA and p-toluenesulfonic acid,10 were
procedure that utilizes Oxone®, p-toluenesulfonic acid or methane-
sulfonic acid and molecular iodine in a mixture of acetonitrile and
2,2,2-trifluoroethanol. The yield is found to be dependent on the na- successfully carried out. In all the above reactions, the key
ture of the ketone. A mechanism is proposed in which the key inter-
mediates are an α-iodoketone and a subsequently formed α-
iodosylketone. The latter reacts with the sulfonic acid to afford the
α-sulfonyloxyketone product.
reagent was [(hydroxy)(tosyloxy)iodo]benzene, formed
in situ, which enabled the α-tosyloxylation of the ketones.
In comparison with mCPBA, Oxone® is a very attractive
reagent for the iodoarene-catalyzed oxidative conversion
of substrates3h,i,l,m,p–r because it is an inorganic, non-tran-
sition metal oxidant, and is less expensive than mCPBA.
In continuation of our research on the use of molecular io-
dine (I2) for organic synthesis,11 we herein report the mo-
lecular iodine mediated α-sulfonyloxylation of ketones
with Oxone® and p-toluenesulfonic acid or methanesul-
fonic acid in a mixture of acetonitrile and 2,2,2-trifluoro-
ethanol.
Key words: α-sulfonyloxyketones, Oxone®, molecular iodine, p-
toluenesulfonic acid, methanesulfonic acid
α-Sulfonyloxyketones are very important precursors for
the construction of various heteroaromatics, including
thiazoles, imidazoles, imidazo[1,2-a]pyridines, oxazoles,
selenazoles, pyrazoles, and benzofurans.1 [(Hydroxy)(tos-
yloxy)iodo]benzene (HTIB) is the sole reagent for the di-
rect α-sulfonyloxylation of ketones.1a,b We have
previously studied the synthetic uses of [(hydroxy)(tosyl-
oxy)iodo]arenes, 1-(arenesulfonyloxy)benziodoxolones,
and poly[4-(hydroxy)(tosyloxy)iodo]styrenes (PS-HTIB)
for the α-tosyloxylation of ketones and the construction of
thiazoles, imidazoles, and imidazo[1,2-a]pyridines.2 On
the other hand, the oxidative conversion of substrates such
as ketones, hydroquinones, alkenes, alcohols, and amides,
with m-chloroperbenzoic acid (mCPBA) or Oxone®
(2KHSO5·KHSO4·K2SO4), catalyzed by aryl iodides, has
become very popular3 since the procedure employed rep-
resents a metal-free oxidative reaction, and trivalent io-
dides such as (diacetoxy)iodoarenes, are formed in situ.
Using these methods, environmentally benign organic
syntheses have been carried out smoothly. Previously, we
reported an efficient procedure for the direct preparation
of various [(hydroxy)(sulfonyloxy)iodo]arenes from io-
doarenes with sulfonic acids and mCPBA.4 Based on this
method, the iodobenzene-catalyzed, polymer-supported
iodobenzene-catalyzed, and ion-supported iodobenzene-
catalyzed α-tosyloxylations of ketones with mCPBA and
p-toluenesulfonic acid (PTSA),5 the iodobenzene-cata-
lyzed and ion-supported iodobenzene-catalyzed prepara-
tion of 3,4-dihydro-1H-2,1-benzothiazine 2,2-dioxides
from N-methoxy-2-arylethanesulfonamides with mCPBA,6
the iodobenzene-catalyzed preparation of oxazoles with
The results of the α-sulfonyloxylation of acetophenone
with Oxone® and p-toluenesulfonic acid, methanesulfonic
acid, or ethanesulfonic acid in a mixture of acetonitrile
and 2,2,2-trifluoroethanol are shown in Table 1. Thus,
acetonitrile or 2,2,2-trifluoroethanol by themselves were
not good solvents for the present α-tosyloxylation (Table
1, entries 3 and 4). However, a mixture of acetonitrile and
2,2,2-trifluoroethanol (1:1) proved to be favorable solvent
system, due to the moderate acidity and the solubility of
the substrate and Oxone® (Table 1, entry 2). No reaction
occurred in the absence of Oxone®, even after a long reac-
tion time at 60 °C, whilst the use of two equivalents of
Oxone® were required to give the α-tosyloxyacetophe-
none in good yield (Table 1, entry 2). On the other hand,
when the α-tosyloxylation of acetophenone with p-tolu-
enesulfonic acid, in the absence and presence of molecu-
lar iodine (0.1 equiv, 0.7 equiv, and 1.0 equiv) in a
mixture of acetonitrile and 2,2,2-trifluoroethanol, was
carried out at 60 °C, α-tosyloxyacetophenone was not ob-
tained when molecular iodine was not present (Table 1,
entry 6); the best yield (79%) was obtained in the presence
of 0.7 equivalents of molecular iodine (Table 1, entries 2,
7 and 8). The potassium iodide (KI) mediated α-tosylox-
ylation of acetophenone did not proceed as efficiently
(Table 1, entry 9), whilst the potassium bromide (KBr)
mediated α-tosyloxylation of acetophenone provided α-
bromoacetophenone in 78% yield, instead of the desired
α-tosyloxyacetophenone (Table 1, entry 10). Moreover,
when methanesulfonic acid and ethanesulfonic acid were
used under the same conditions, α-methanesulfonyloxy-
acetophenone and α-ethanesulfonyloxyacetophenone
SYNTHESIS 2013, 45, 0791–0797
Advanced online publication: 19.02.2013
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0032-1318199; Art ID: SS-2012-F0972-OP
© Georg Thieme Verlag Stuttgart · New York

792
H. Kikui et al.
PAPER
Table 2 α-Sulfonyloxylation of Ketones with Iodine, Oxone® and-
Sulfonic Acids
were obtained in fair to good yields (Table 1, entries 11
and 12).
I2 (0.7 equiv)
O
O
Table 1 α-Sulfonyloxylation of Acetophenone with Iodine, Oxone®
and Sulfonic Acids
Oxone® (2.0 equiv)
R3SO3H (3.0 equiv)
R2
R2
O3SR3
I2 (0.7 equiv)
Oxone® (2.0 equiv)
O
O
MeCN–CF3CH2OH
(1:1, 6 mL), 24 h, 60 °C
R1
R1
RSO3H (3.0 equiv)
Entry
R1
R2
R3
Time (h) Yield (%)
O3SR
MeCN–CF3CH2OH
(1:1, 6 mL), 24 h, 60 °C
1
2
3
4
5
6
7
8
Cl
H
p-MeC6H4
p-MeC6H4
p-MeC6H4
p-MeC6H4
p-MeC6H4
p-MeC6H4
p-MeC6H4
p-MeC6H4
24
24
24
10
19
24
24
24
88
51
97
42
63
67
90
58
Entry
R
Yield (%)
Br
H
1a
2
p-MeC6H4
p-MeC6H4
p-MeC6H4
p-MeC6H4
p-MeC6H4
p-MeC6H4
p-MeC6H4
p-MeC6H4
p-MeC6H4
p-MeC6H4
Me
41
NO2
Me
Ph
H
H
79
H
3b
4c
18
H
48
Me
Me
Me
5d
6e
64
Cl
0 (37)j
45
Me
7f
O
O
8g
9h
10i
11
12
51
9
10
11
p-MeC6H4
p-MeC6H4
p-MeC6H4
24
24
6
44
52
54
6
57
0 (78)k
78
S
Et
62
O
a Oxone® (1.1 equiv) was used.
b CF3CH2OH (6 mL) was used as the solvent.
c MeCN (6 mL) was used as the solvent.
d p-TsOH (1.0 equiv) was used.
e I2 was not used.
12
13
14
15
16
17a
18
19
Cl
H
Me
Me
Me
Me
Me
Me
Me
Me
24
24
24
24
24
24
24
24
98
51
58
48
47
66
90
79
f I2 (0.1 equiv) was used.
Br
H
g I2 (1.0 equiv) was used.
h KI (0.7 equiv) was used instead of I2.
i KBr (0.7 equiv) was used instead of I2.
j Yield of recovered acetophenone.
k Yield of α-bromoacetophenone.
NO2
Me
Ph
H
H
H
H
Me
Me
Me
Having optimized the reaction conditions, the molecular
iodine mediated α-tosyloxylation of various acetophe-
none derivatives, including p-chloro-, p-bromo-, p-nitro-,
p-methyl-, and p-phenylacetophenone with p-toluenesul-
fonic acid and Oxone®, was carried out to give the corre-
sponding α-tosyloxyketones in moderate to excellent
yields, as shown in Table 2 (entries 1–5). The same treat-
ment of propiophenone, p-chloropropiophenone, and p-
methylpropiophenone also provided the corresponding α-
tosyloxypropiophenones in good to moderate yields (Ta-
ble 2, entries 6–8). The reactions of nonanophenone, 2-
acetylthiophene, and 2-acetylnaphthalene, with p-tolu-
enesulfonic acid and Oxone® in the presence of molecular
iodine in acetonitrile–2,2,2-trifluoroethanol at 60 °C, fur-
nished the corresponding α-tosyloxyketones in moderate
yields (Table 2, entries 9–11), despite the fact that the
starting ketones were almost completely consumed. Next,
Cl
Me
O
20a
21
Me
Me
Me
10
24
8
47
36
46
6
O
S
O
22a
a I2 (1.0 equiv) and MeSO3H (5.0 equiv) were used in a mixture of
MeCN–CF3CH2OH (1:2, 6 mL).
Synthesis 2013, 45, 791–797
© Georg Thieme Verlag Stuttgart · New York

PAPER
Iodine-Mediated α-Sulfonyloxylation
793
the molecular iodine mediated α-methanesulfonyloxyl-
ation of various acetophenone and propiophenone deriva-
tives with methanesulfonic acid and Oxone®, under the
optimized conditions, provided the corresponding α-
methanesulfonyloxyketones in moderate to excellent
yields (Table 2, entries 12–19). The reactions of nonaphe-
none, 2-acetylthiophene, and 2-acetylnaphthalene with
methanesulfonic acid and Oxone® in the presence of mo-
lecular iodine in acetonitrile–2,2,2-trifluoroethanol under
the same conditions provided the corresponding α-methane-
sulfonyloxyketones in moderate yields (Table 2, entries
20–22). Overall, the yields of the α-sulfonyloxyketones
with p-toluenesulfonic acid were slightly higher than
those with methanesulfonic acid. As p-toluenesulfonic
acid is a stronger acid than methanesulfonic acid, it prob-
ably promoted enolization of the ketone substrates more
efficiently.
O
OH
R2
R2
R1
R1
O
S
O
S
I2
I
O
OK
HOO
OK
– HOI
O
O
KHSO4
Oxone® = 2KHSO5⋅KHSO4⋅K2SO4
O
R2
R1
I
Oxone®
O
O
R3SO3H
– HOI
R2
R2
R1
R1
O
I
OSO2R3
To uncover the present reaction mechanism, α-iodoaceto-
phenone was treated with Oxone® and p-toluenesulfonic
acid in a mixture of acetonitrile and 2,2,2-trifluoroethanol,
using similar conditions to those applied previously, to
generate α-tosyloxyacetophenone in 99% yield (Equation
1). In this reaction, α-tosyloxyacetophenone was not
formed in the absence of Oxone®. On the other hand, sim-
ilar treatment of α-bromoacetophenone did not afford α-
tosyloxyacetophenone, and instead α-bromoacetophe-
none was recovered, quantitatively. It is well known that
Oxone® is a powerful oxidant; iodoarenes and perfluo-
roiodoalkanes (monovalent iodine)12 are oxidized into tri-
valent iodine species by Oxone®. Therefore, we believe
the present α-sulfonyloxylation reaction proceeds through
the α-iodination of the enol form of the ketone with a hy-
Scheme 1 A plausible reaction mechanism
In conclusion, α-sulfonyloxyketones have been prepared
in moderate to excellent yields via the reactions of alkyl
aryl ketones with Oxone® and p-toluenesulfonic acid or
methanesulfonic acid in the presence of molecular iodine
in a mixture of acetonitrile and 2,2,2-trifluoroethanol. The
present procedure for the α-sulfonyloxylation of ketones
does not require [(hydroxy)(tosyloxy)iodo]benzene, or re-
lated reagents, and the reaction mechanism is not the same
as that when [(hydroxy)(tosyloxy)iodo]benzene is in-
volved. We believe that the described method for the α-
sulfonyloxylation is very attractive and opens new possi-
bilities in the reactions of alkyl iodides with Oxone®, and
further synthetic studies on these reactions are underway
in our laboratory.
–
poiodite–sulfate species (i.e., IOSO3 ), formed from the
reaction of molecular iodine with Oxone®. Once the α-io-
doketone is formed, it is smoothly oxidized into an α-io-
dosylketone, a very reactive intermediate, which reacts
rapidly with the sulfonic acid to produce the correspond-
ing α-sulfonyloxyketone (Scheme 1). When iodoethane
was treated with Oxone® in the presence of p-toluenesul-
fonic acid in a mixture of acetonitrile and 2,2,2-trifluoro-
ethanol, ethyl p-toluenesulfonate was obtained in 60%
yield, as shown in Equation 2, whereas ethyl p-toluenesul-
fonate was not formed from the reaction of iodoethane
and p-toluenesulfonic acid in the absence of Oxone®.
Melting points were determined with a Yamato MP-21 melting
point apparatus. IR spectra were measured with a JASCO FT/IR-
1
4100 spectrophotometer. H and 13C NMR spectra were obtained
with JEOL JNM-ECS400 and JEOL JNM-ECA500 spectrometers.
Chemical shifts (δ) are expressed in ppm downfield from TMS.
Mass spectra were recorded on JMS T100GCV and Thermo LTQ
Orbitrap XL spectrometers. Merck silica gel 60F254 was used for
TLC, and column chromatography was carried out with silica gel 60
from Kanto Kagaku Co.
α-Tosyloxylation; Typical Procedure
To a soln of acetophenone (120 mg, 1 mmol) in MeCN–CF3CH2OH
(1:1, 6 mL) were added I2 (178 mg, 0.7 mmol), p-TsOH·H2O (571
mg, 3.0 mmol), and Oxone® (2.73 g, 2.0 mmol). The mixture was
stirred for 24 h at 60 °C under an Ar atm. After the reaction was
complete, the mixture was added to sat. aq NaHCO3 soln (10 mL)
and brine (10 mL), and extracted with CHCl3 (3 × 20 mL). The com-
bined organic layer was dried over Na2SO4. After removal of the
solvent under reduced pressure, the residue was purified by short
flash column chromatography on silica gel (EtOAc–hexane, 1:2) to
give α-tosyloxyacetophenone in 79% yield.
O
O
Oxone® (1.1 equiv)
p-TsOH (3.0 equiv)
X
OTs
MeCN–CF3CH2OH
(1:1, 3 mL), 18 h, 60 °C
X = I
99%
0%
X = Br
Equation 1
α-Methanesulfonyloxylation; Typical Procedure
Oxone® (1.1 equiv)
To a soln of acetophenone (120 mg, 1 mmol) in MeCN–CF3CH2OH
(1:1, 6 mL) were added I2 (178 mg, 0.7 mmol), MsOH (288 mg, 3.0
mmol), and Oxone® (2.73 g, 2.0 mmol). The mixture was stirred for
24 h at 60 °C under an Ar atm. After the reaction was complete, the
mixture was added to sat. aq NaHCO3 soln (10 mL) and brine (10
mL), and extracted with CHCl3 (3 × 20 mL). The combined organic
p-TsOH (3.0 equiv)
I
Et
TsO Et
60%
MeCN–CF3CH2OH
(1:1, 3 mL), 18 h, 60 °C
Equation 2
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 791–797

794
H. Kikui et al.
PAPER
layer was dried over Na2SO4. After removal of the solvent under
reduced pressure, the residue was purified by short flash column
chromatography on silica gel (EtOAc–hexane, 1:2) to give α-methane-
sulfonyloxyacetophenone in 78% yield.
α-Tosyloxy-p-methylacetophenone
Yield: 127.8 mg (42%); white solid; mp 105 °C (Lit.14 82–83 °C).
IR (KBr): 1170, 1350, 1700 cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.41 (s, 3 H), 2.45 (s, 3 H), 5.24
(s, 2 H), 7.26 (d, J = 8.1 Hz, 2 H), 7.35 (d, J = 8.2 Hz, 2 H), 7.74 (d,
J = 8.1 Hz, 2 H), 7.86 (d, J = 8.2 Hz, 2 H).
α-Tosyloxyacetophenone
Yield: 229.2 mg (79%); white solid; mp 90 °C (Lit.1h 90–91 °C).
IR (KBr): 1180, 1360, 1715 cm–1.
13C NMR (100 MHz, CDCl3): δ = 21.68, 21.77, 69.85, 128.07,
128.14, 129.57, 129.87, 131.24, 132.62, 135.23, 135.28, 189.80.
1H NMR (400 MHz, CDCl3): δ = 2.45 (s, 3 H), 5.27 (s, 2 H), 7.35
(d, J = 8.5 Hz, 2 H), 7.47 (t, J = 8.2 Hz, 2 H), 7.61 (t, J = 8.2 Hz, 1
H), 7.84 (d, J = 8.2 Hz, 2 H), 7.85 (d, J = 8.2 Hz, 2 H).
α-Tosyloxy-p-phenylacetophenone
Yield: 230.6 mg (63%); pale yellow solid; mp 139 °C (Lit.16 137–
138 °C).
13C NMR (100 MHz, CDCl3): δ = 21.78, 70.01, 128.09, 128.24,
IR (neat): 1171, 1372, 1702 cm–1.
129.01, 130.00, 132.72, 133.86, 134.29, 145.39, 190.39.
1H NMR (500 MHz, CDCl3): δ = 2.45 (s, 3 H), 5.29 (s, 2 H), 7.35
(d, J = 8.0 Hz, 2 H), 7.42 (t, J = 7.3 Hz, 1 H), 7.48 (t, J = 7.3 Hz, 2
H), 7.61 (d, J = 6.9 Hz, 2 H), 7.69 (d, J = 8.6 Hz, 2 H), 7.87 (d,
J = 8.4 Hz, 2 H), 7.92 (d, J = 8.9 Hz, 2 H).
13C NMR (125 MHz, CDCl3): δ = 21.69, 69.96, 127.26, 127.48,
128.15, 128.54, 128.62, 129.02, 129.90, 132.40, 132.62, 139.43,
145.29, 146.89, 189.91.
α-Methanesulfonyloxyacetophenone
Yield: 166.7 mg (78%); white solid; mp 78 °C (Lit.13 77–78 °C).
IR (neat): 1174, 1348, 1708 cm–1.
1H NMR (400 MHz, CDCl3): δ = 3.29 (s, 3 H), 5.52 (s, 2 H), 7.52
(t, J = 7.9 Hz, 2 H), 7.65 (t, J = 7.6 Hz, 1 H), 7.89 (d, J = 8.4 Hz, 2
H).
13C NMR (125 MHz, CDCl3): δ = 39.26, 70.21, 127.77, 129.09,
133.41, 134.49, 191.10.
α-Tosyloxypropiophenone
Yield: 203.9 mg (67%); white solid; mp 68 °C (Lit.14 68–69 °C).
α-Ethanesulfonyloxyacetophenone
Yield: 141.4 mg (62%); white solid; mp 64–65 °C.
IR (neat): 1163, 1343, 1702 cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.55 (t, J = 7.4 Hz, 3 H), 3.39 (q,
J = 7.5 Hz, 2 H), 5.49 (s, 2 H), 7.51 (t, J = 7.9 Hz, 2 H), 7.64 (t,
J = 7.6 Hz, 1 H), 7.89 (d, J = 7.1 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 8.13, 46.54, 69.67, 127.75,
129.01, 133.50, 134.36, 191.05.
IR (KBr): 1170, 1370, 1700 cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.60 (d, J = 7.0 Hz, 3 H), 2.41 (s,
3 H), 5.79 (q, J = 7.0 Hz, 1 H), 7.29 (d, J = 8.1 Hz, 2 H), 7.46 (t,
J = 7.2 Hz, 2 H), 7.59 (t, J = 7.2 Hz, 1 H), 7.75 (d, J = 7.2 Hz, 2 H),
7.88 (d, J = 8.1 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 18.84, 21.74, 128.04, 128.84,
129.85, 133.51, 133.77, 133.93, 143.48, 143.69, 145.10, 194.93.
α-Tosyloxy-p-chloropropiophenone
HRMS–FAB: m/z [M]+ calcd for C10H12O4S: 228.0456; found:
228.0451.
Yield: 304.0 mg (90%); white solid; mp 89 °C (Lit.17 94–96 °C).
IR (neat): 1176, 1359, 1695 cm–1.
α-Tosyloxy-p-chloroacetophenone
1H NMR (500 MHz, CDCl3): δ = 1.58 (d, J = 6.9 Hz, 3 H), 2.42 (s,
3 H), 5.68 (q, J = 6.9 Hz, 1 H), 7.28 (d, J = 8.1 Hz, 2 H), 7.42 (d,
J = 8.6 Hz, 2 H), 7.74 (d, J = 8.4 Hz, 2 H), 7.84 (d, J = 8.6 Hz, 2 H).
Yield: 285.0 mg (88%); white solid; mp 123 °C (Lit.14 125 °C).
IR (KBr): 1190, 1360, 1710 cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.46 (s, 3 H), 5.21 (s, 2 H), 7.35
(d, J = 8.4 Hz, 2 H), 7.45 (d, J = 8.6 Hz, 2 H), 7.80 (d, J = 8.6 Hz,
2 H), 7.84 (d, J = 8.4 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 21.67, 69.81, 128.11, 129.25,
129.47, 129.92, 132.06, 132.46, 140.75, 145.41, 189.46.
13C NMR (125 MHz, CDCl3): δ = 18.54, 21.62, 77.44, 127.90,
129.07, 129.79, 130.20, 131.93, 133.27, 140.37, 145.17, 193.83.
α-Tosyloxy-p-methylpropiophenone
Yield: 185.4 mg (58%); white solid; mp 83–84 °C (Lit.18 88–89 °C).
IR (neat): 1176, 1363, 1693 cm–1.
α-Tosyloxy-p-bromoacetophenone
Yield: 187.6 mg (51%); white solid; mp 129–131 °C (Lit.15 131–
132 °C).
IR (neat): 1175, 1360, 1701 cm–1.
1H NMR (500 MHz, CDCl3): δ = 2.45 (s, 3 H), 5.20 (s, 2 H), 7.35
(d, J = 8.0 Hz, 2H), 7.62 (d, J = 8.9 Hz, 2 H), 7.71 (d, J = 8.9 Hz, 2
H), 7.84 (d, J = 8.3 Hz, 2 H).
1H NMR (500 MHz, CDCl3): δ = 1.58 (d, J = 6.9 Hz, 3 H), 2.40 (s,
3 H), 2.41 (s, 3 H), 5.77 (q, J = 7.0 Hz, 1 H), 7.26 (t, J = 8.2 Hz, 4
H), 7.76 (d, J = 7.3 Hz, 2 H), 7.78 (d, J = 8.3 Hz, 2 H).
13C NMR (125 MHz, CDCl3): δ = 18.81, 21.62, 21.72, 77.33,
127.93, 128.85, 129.43, 129.72, 131.11, 133.50, 144.89, 144.93,
194.27.
α-(Tosyloxy)octyl Phenyl Ketone
13C NMR (100 MHz, CDCl3): δ = 21.70, 69.77, 128.13, 129.52,
129.93, 132.26, 132.46, 145.43, 189.68.
Yield: 176.2 mg (44%); white solid; mp 59–61 °C (Lit.2d 59–61 °C).
IR (neat): 1180, 1340, 1700 cm–1.
α-Tosyloxy-p-nitroacetophenone
1H NMR (400 MHz, CDCl3): δ = 0.86 (t, J = 6.9 Hz, 3 H), 1.20–
1.43 (m, 10 H), 1.84–1.91 (m, 2 H), 2.40 (s, 3 H), 5.59 (dd, J = 8.2,
4.8 Hz, 1 H), 7.24 (d, J = 8.0 Hz, 2 H), 7.45 (t, J = 7.5 Hz, 2 H),
7.59 (t, J = 7.5 Hz, 1 H), 7.74 (d, J = 8.2 Hz, 2 H), 7.86 (d, J = 8.2
Hz, 2 H).
13C NMR (125 MHz, CDCl3): δ = 14.00, 21.58, 22.53, 24.96, 28.75,
28.86, 31.58, 32.67, 81.39, 128.01, 128.61, 128.68, 129.65, 133.20,
133.71, 134.04, 144.91, 195.02.
Yield: 324.8 mg (97%); yellow solid; mp 137 °C (Lit.14 130–
131 °C).
IR (KBr): 1180, 1340, 1710 cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.47 (s, 3 H), 5.25 (s, 2 H), 7.37
(d, J = 8.3 Hz, 2 H), 7.83 (d, J = 8.3 Hz, 2 H), 8.03 (d, J = 8.9 Hz,
2 H), 8.32 (d, J = 8.9 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 21.83, 70.04, 117.70, 124.17,
128.26, 129.45, 130.15, 132.32, 138.29, 145.81, 189.87.
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Iodine-Mediated α-Sulfonyloxylation
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α-Thienyl (Tosyloxy)methyl Ketone
13C NMR (125 MHz, CDCl3): δ = 39.24, 70.20, 127.26, 127.64,
128.38, 128.61, 129.04, 132.05, 139.32, 147.17, 190.66.
Yield: 154.2 mg (52%); light brown solid; mp 92–93 °C (Lit.1i 94–
96 °C).
α-Methanesulfonyloxypropiophenone
IR (KBr): 730, 1180, 1370, 1685 cm–1.
Yield: 150.5 mg (66%); white solid; mp 64 °C (Lit.14 68–69 °C).
1H NMR (400 MHz, CDCl3): δ = 2.45 (s, 3 H), 5.09 (s, 2 H), 7.16
(dd, J = 5.0, 3.9 Hz, 1 H), 7.35 (d, J = 8.1 Hz, 2 H), 7.73 (dd,
J = 5.0, 1.0 Hz, 1 H), 7.79 (dd, J = 3.9, 1.0 Hz, 1 H), 7.85 (d,
J = 8.1 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 21.66, 69.87, 128.17, 128.46,
129.94, 132.38, 133.13, 135.12, 140.12, 145.43, 183.64.
IR (neat): 1178, 1362, 1702 cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.67 (d, J = 7.1 Hz, 3 H), 3.14 (s,
3 H), 6.05 (q, J = 7.1 Hz, 1 H), 7.51 (t, J = 7.9 Hz, 2 H), 7.64 (t,
J = 7.5 Hz, 1 H), 7.94 (d, J = 7.3 Hz, 2 H).
13C NMR (125 MHz, CDCl3): δ = 18.69, 39.38, 77.11, 128.58,
128.97, 133.63, 134.14, 195.26.
α-Naphthalen-2-yl (Tosyloxy)ethanone
Yield: 182.3 mg (54%); white solid; mp 118–120 °C (Lit.16 118–
119 °C).
IR (neat): 1176, 1367, 1699 cm–1.
α-Methanesulfonyloxy-p-chloropropiophenone
Yield: 236.3 mg (90%); white solid; mp 88–89 °C.
IR (neat): 1177, 1360, 1695 cm–1.
1H NMR (400 MHz, CDCl3): δ = 1.66 (d, J = 7.1 Hz, 3 H), 3.14 (s,
3 H), 5.97 (d, J = 7.0 Hz, 1 H), 7.49 (d, J = 8.7 Hz, 2 H), 7.89 (d,
J = 8.9 Hz, 2 H).
1H NMR (500 MHz, CDCl3): δ = 2.44 (s, 3 H), 5.39 (s, 2 H), 7.33
(d, J = 8.0 Hz, 2 H), 7.57 (t, J = 6.9 Hz, 1 H), 7.63 (t, J = 6.9 Hz, 1
H), 7.87 (d, J = 8.3 Hz, 2 H), 7.87–7.90 (m, 3 H), 7.94 (d, J = 7.8
Hz, 1 H), 8.34 (s, 1 H).
13C NMR (125 MHz, CDCl3): δ = 18.54, 39.38, 76.78, 129.35,
13C NMR (125 MHz, CDCl3): δ = 21.67, 70.00, 123.26, 127.16,
127.86, 128.16, 128.89, 129.13, 129.61, 129.90, 129.99, 131.09,
132.27, 132.68, 135.95, 145.28, 190.27.
130.02, 131.89, 140.74, 194.14.
HRMS–FAB: m/z [M]+ calcd for C10H11ClO4S: 262.0067; found:
262.0061.
α-Methanesulfonyloxy-p-chloroacetophenone
α-Methanesulfonyloxy-p-methylpropiophenone
Yield: 243.9 mg (98%); white solid; mp 109–110 °C (Lit.14 125 °C).
Yield: 190.5 mg (79%); white solid; mp 86–88 °C.
IR (neat): 1170, 1344, 1698 cm–1.
IR (neat): 1174, 1359, 1690 cm–1.
1H NMR (400 MHz, CDCl3): δ = 3.29 (s, 3 H), 5.47 (s, 2 H), 7.50
(d, J = 8.7 Hz, 2 H), 7.84 (d, J = 8.7 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 39.23, 69.88, 129.20, 129.49,
1H NMR (400 MHz, CDCl3): δ = 1.66 (d, J = 7.1 Hz, 3 H), 2.43 (s,
3 H), 3.13 (s, 3 H), 6.03 (q, J = 7.1 Hz, 1 H), 7.31 (d, J = 8.0 Hz, 2
H), 7.84 (d, J = 8.2 Hz, 2 H).
13C NMR (125 MHz, CDCl3): δ = 18.84, 21.73, 39.40, 77.13,
131.75, 141.12, 190.04.
128.73, 129.68, 131.07, 145.30, 194.78.
HRMS–FAB: m/z [M]+ calcd for C11H14O4S: 242.0613; found:
242.0606.
α-Methanesulfonyloxy-p-bromoacetophenone
Yield: 147.5 mg (51%); white solid; mp 119–120 °C (Lit.19 106 °C).
IR (neat): 1171, 1344, 1699 cm–1.
1H NMR (400 MHz, CDCl3): δ = 3.28 (s, 3 H), 5.46 (s, 2 H), 7.67
(d, J = 8.9 Hz, 2 H), 7.76 (d, J = 8.7 Hz, 2 H).
13C NMR (125 MHz, CDCl3): δ = 39.24, 69.84, 129.24, 129.87,
α-(Methanesulfonyloxy)octyl Phenyl Ketone
Yield: 151.7 mg (47%); white solid; mp 53–54 °C.
IR (neat): 1176, 1357, 1701 cm–1.
1H NMR (500 MHz, CDCl3): δ = 0.86 (t, J = 7.0 Hz, 3 H), 1.25–
1.38 (m, 8 H), 1.51 (quin, J = 7.4 Hz, 2 H), 1.84–1.96 (m, 2 H), 3.13
(s, 3 H), 5.92 (dd, J = 8.6, 4.0 Hz, 1 H), 7.51 (t, J = 7.7 Hz, 2 H),
7.64 (t, J = 7.5 Hz, 1 H), 7.92 (d, J = 7.2 Hz, 2 H).
13C NMR (125 MHz, CDCl3): δ = 14.02, 22.55, 25.04, 28.89, 31.62,
32.49, 39.30, 81.25, 128.48, 129.01, 134.11, 195.34.
132.15, 132.48, 190.26.
α-Methanesulfonyloxy-p-nitroacetophenone
Yield: 150.5 mg (58%); yellow solid; mp 123–124 °C (Lit.13 123 °C).
IR (neat): 1173, 1356, 1708 cm–1.
1H NMR (400 MHz, CDCl3): δ = 3.30 (s, 3 H), 5.51 (s, 2 H), 8.08
(d, J = 9.2 Hz, 2 H), 8.38 (d, J = 9.2 Hz, 2 H).
13C NMR (125 MHz, CDCl3): δ = 39.23, 69.85, 124.28, 129.05,
137.83, 151.02, 190.05.
HRMS–FAB: m/z [M]+ calcd for C16H24O4S: 312.1395; found:
312.1390.
α-Thienyl (Methanesulfonyloxy)methyl Ketone
Yield: 79.9 mg (36%); yellow solid; mp 83–84 °C.
IR (neat): 1176, 1365, 1674 cm–1.
1H NMR (500 MHz, CDCl3): δ = 3.27 (s, 3 H), 5.38 (s, 2 H), 7.20
(dd, J = 5.2, 4.0 Hz, 1 H), 7.76–7.79 (m, 2 H).
13C NMR (125 MHz, CDCl3): δ = 39.16, 69.68, 128.60, 132.59,
135.25, 139.46, 184.23.
HRMS–FAB: m/z [M]+ calcd for C7H8O4S2: 219.9864; found:
α-Methanesulfonyloxy-p-methylacetophenone
Yield: 110.1 mg (48%); white solid; mp 88–89 °C (Lit.13 87 °C).
IR (neat): 1175, 1346, 1707 cm–1.
1H NMR (400 MHz, CDCl3): δ = 2.44 (s, 3 H), 3.28 (s, 3 H), 5.49
(s, 2 H), 7.31 (t, J = 7.9 Hz, 2 H), 7.79 (d, J = 8.4 Hz, 2 H).
13C NMR (100 MHz, CDCl3): δ = 21.78, 39.21, 70.17, 127.86,
129.73, 130.94, 145.61, 190.68.
219.9858.
α-Methanesulfonyloxy-p-phenylacetophenone
Yield: 136.0 mg (47%); pale yellow solid; mp 141–142 °C (Lit.20
141–142 °C).
IR (neat): 1167, 1359, 1699 cm–1.
α-Naphthalen-2-yl (Methanesulfonyloxy)ethanone
Yield: 113.8 mg (46%); white solid; mp 90–94 °C (Lit.21 105–
106 °C).
1H NMR (500 MHz, CDCl3): δ = 3.30 (s, 3 H), 5.54 (s, 2 H), 7.49
(t, J = 6.9 Hz, 1 H), 7.43 (t, J = 7.3 Hz, 2 H), 7.63 (d, J = 7.4 Hz, 2
H), 7.73 (d, J = 8.6 Hz, 2 H), 7.97 (d, J = 8.3 Hz, 2 H).
IR (neat): 1169, 1357, 1711 cm–1.
© Georg Thieme Verlag Stuttgart · New York
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H. Kikui et al.
PAPER
1H NMR (400 MHz, CDCl3): δ = 3.32 (s, 3 H), 5.65 (s, 2 H), 7.60
(t, J = 7.1 Hz, 1 H), 7.66 (t, J = 7.0 Hz, 1 H), 7.90 (d, J = 8.2 Hz, 1
H), 7.95 (s, 2 H), 7.98 (d, J = 8.5 Hz, 1 H), 8.40 (s, 1 H).
13C NMR (100 MHz, CDCl3): δ = 39.23, 70.24, 122.95, 127.30,
127.91, 129.11, 129.26, 129.62, 129.76, 130.73, 132.28, 136.05,
191.01.
Akakura, M.; Ishihara, K. J. Am. Chem. Soc. 2009, 131, 251.
(n) Miyamoto, K.; Sei, Y.; Yamaguchi, K.; Ochiai, M.
J. Am. Chem. Soc. 2009, 131, 1382. (o) Ojha, L. R.;
Kudugunti, S.; Maddukuri, P. P.; Kommareddy, A.; Gunna,
M. R.; Dokuparthi, P.; Gottam, H. B.; Botha, K. K.; Parapati,
D. R.; Vinod, T. K. Synlett 2009, 117. (p) Dohi, T.;
Minamitsuji, Y.; Maruyama, A.; Hirose, S.; Kita, Y. Org.
Lett. 2008, 10, 3559. (q) Uyanik, M.; Fukatsu, R.; Ishihara,
K. Org. Lett. 2009, 11, 3470. (r) Uyanik, M.; Yasui, T.;
Ishihara, K. Bioorg. Med. Chem. Lett. 2009, 19, 3848.
(s) Yakura, T.; Tian, Y.; Yamauchi, Y.; Omoto, M.; Konishi,
T. Chem. Pharm. Bull. 2009, 57, 252. (t) Dohi, H.;
Takenaga, N.; Fukushima, K.; Uchiyama, T.; Kato, D.;
Shiro, M.; Fujioka, H.; Kita, Y. Chem. Commun. 2010, 46,
7697. (u) Zagulyaeva, A. A.; Banek, C. T.; Yusubov, M. S.;
Zhdankin, V. V. Org. Lett. 2010, 12, 4644. (v) Thottumkara,
P. P.; Vinod, T. K. Org. Lett. 2010, 12, 5640. (w) Miura, T.;
Nakashima, K.; Tada, N.; Itoh, A. Chem. Commun. 2011, 47,
1875. (x) Yu, Z.; Ju, X.; Wang, J.; Yu, W. Synthesis 2011,
860.
Acknowledgment
Financial support in the form of a Grant-in-Aid for Scientific Re-
search (No. 20550033) from the Ministry of Education, Culture,
Sports, Science, and Technology, Japan, and the Iodine Research
Project, Chiba University are gratefully acknowledged.
References
(1) (a) Review: Moriarty, R. M.; Vaid, R. K.; Koser, G. F.
Synlett 1990, 365. (b) Review: Koser, G. F. Aldrichimica
Acta 2001, 34, 89. (c) Prakash, O.; Saini, N.; Sharma, P. K.
Heterocycles 1994, 38, 409. (d) Neilands, O.; Karele, B.
J. Org. Chem. USSR 1970, 6, 885. (e) Koser, G. F.; Wettach,
R. H.; Troup, J. M.; Frenz, B. A. J. Org. Chem. 1976, 41,
3609. (f) Koser, G. F.; Wettach, R. H. J. Org. Chem. 1977,
42, 1476. (g) Koser, G. F.; Wettach, R. H.; Smith, C. S. J.
Org. Chem. 1980, 45, 1543. (h) Koser, G. F.; Relenyi, A. G.;
Kalos, A. N.; Rebrovic, L.; Wettach, R. H. J. Org. Chem.
1982, 47, 2487. (i) Moriarty, R. M.; Penmasta, R.; Awasthi,
A. K.; Epa, W. R.; Prakash, I. J. Org. Chem. 1989, 54, 1101.
(j) Moriarty, R. M.; Vaid, R. K.; Hopkins, T. E.; Vaid, B. K.;
Prakash, O. Tetrahedron Lett. 1990, 31, 201. (k) Tuncay, A.;
Dustman, J. A.; Fisher, G.; Tuncay, C. I. Tetrahedron Lett.
1992, 33, 7647. (l) Moriarty, R. M.; Vaid, B. K.; Duncan, M.
P.; Levy, S. G.; Prakash, O.; Goyal, S. Synthesis 1992, 845.
(m) Prakash, O.; Goyal, S. Synthesis 1992, 629. (n) Prakash,
O.; Rani, N.; Goyal, S. J. Chem. Soc., Perkin Trans. 1 1992,
707. (o) Prakash, O.; Saini, N.; Sharma, P. K. Synlett 1994,
221. (p) Vrama, R. S.; Kumar, D.; Liesen, P. J. J. Chem.
Soc., Perkin Trans. 1 1998, 4093. (q) Lee, J. C.; Choi, J.-H.
Synlett 2001, 234. (r) Lai, P.; Taylor, M. S. Synthesis 2010,
1449.
(2) Monomer reagents: (a) Muraki, T.; Togo, H.; Yokoyama, M.
J. Org. Chem. 1999, 64, 2883. (b) Nabana, T.; Togo, H.
J. Org. Chem. 2002, 67, 4362. (c) Misu, Y.; Togo, H. Org.
Biomol. Chem. 2003, 1, 1342. (d) Ueno, M.; Nabana, T.;
Togo, H. J. Org. Chem. 2003, 68, 6424. Polymer reagents:
(e) Abe, S.; Sakuratani, K.; Togo, H. Synlett 2001, 22.
(f) Abe, S.; Sakuratani, K.; Togo, H. J. Org. Chem. 2001, 66,
6174. (g) Sakuratani, K.; Togo, H. ARKIVOC 2003, (vi), 11.
(h) Ueno, M.; Togo, H. Synthesis 2004, 2673.
(3) (a) Review: Ochiai, M.; Miyamoto, K. Eur. J. Org. Chem.
2008, 4229. (b) Review: Dohi, T.; Kita, Y. Chem. Commun.
2009, 2073. (c) Review: Uyanik, M.; Ishihara, K. Chem.
Commun. 2009, 2086. (d) Ochiai, M.; Takeuchi, Y.;
Katayama, T.; Sueda, T.; Miyamoto, K. J. Am. Chem. Soc.
2005, 127, 12244. (e) Dohi, T.; Maruyama, A.; Yoshimura,
M.; Morimoto, K.; Tohma, H.; Kita, Y. Angew. Chem. Int.
Ed. 2005, 44, 6193. (f) Li, J.; Chan, P. W. H.; Che, C. Org.
Lett. 2005, 7, 5801. (g) Thottumkara, A. P.; Bowsher, M. S.;
Vinod, T. K. Org. Lett. 2005, 7, 2933. (h) Dohi, T.;
(4) Yamamoto, Y.; Togo, H. Synlett 2005, 2486.
(5) (a) Yamamoto, Y.; Togo, H. Synlett 2006, 798.
(b) Yamamoto, Y.; Kawano, Y.; Toy, P. H.; Togo, H.
Tetrahedron 2007, 63, 4680. (c) Akiike, J.; Yamamoto, Y.;
Togo, H. Synlett 2007, 2168.
(6) (a) Moroda, A.; Togo, H. Synthesis 2008, 1257. (b) Ishiwata,
Y.; Togo, H. Tetrahedron Lett. 2009, 50, 5354. (c) Suzuki,
Y.; Togo, H. Synthesis 2010, 2355.
(7) Kawano, Y.; Togo, H. Tetrahedron 2009, 65, 6251.
(8) Ishiwata, Y.; Togo, H. Tetrahedron 2009, 65, 10720.
(9) Tanaka, A.; Togo, H. Synlett 2009, 3360.
(10) Tanaka, A.; Moriyama, K.; Togo, H. Synlett 2011, 1853.
(11) (a) Review: Togo, H.; Iida, S. Synlett 2006, 2159.
(b) Review: Togo, H. J. Synth. Org. Chem. 2008, 66, 652.
(c) Mori, N.; Togo, H. Synlett 2004, 880. (d) Mori, N.; Togo,
H. Synlett 2005, 1456. (e) Mori, N.; Togo, H. Tetrahedron
2005, 61, 5915. (f) Ishihara, M.; Togo, H. Synlett 2006, 227.
(g) Iida, S.; Togo, H. Synlett 2006, 2633. (h) Ihihara, M.;
Togo, H. Tetrahedron 2007, 63, 1474. (i) Iida, S.; Togo, H.
Tetrahedron 2007, 63, 8274. (j) Iida, S.; Togo, H. Synlett
2007, 407. (k) Iida, S.; Togo, H. Synlett 2008, 1639. (l) Iida,
S.; Ohmura, R.; Togo, H. Tetrahedron 2009, 65, 6257.
(m) Suzuki, Y.; Moriyama, K.; Togo, H. Tetrahedron Lett.
2010, 51, 5950. (n) Ushijima, S.; Togo, H. Synlett 2010,
1562. (o) Ohmura, R.; Takahata, M.; Togo, H. Tetrahedron
Lett. 2010, 51, 4378. (p) Ushijima, S.; Togo, H. Synlett 2010,
1067. (q) Ushijima, S.; Moriyama, K.; Togo, H.
Tetrahedron 2011, 67, 958. (r) Ushijima, S.; Dohi, S.;
Moriyama, K.; Togo, H. Tetrahedron 2012, 68, 1436.
(s) Baba, H.; Moriyama, K.; Togo, H. Synlett 2012, 1175.
(t) Ushijima, S.; Moriyama, K.; Togo, H. Tetrahedron 2012,
68, 4701. (u) Ushijima, S.; Moriyama, K.; Togo, H.
Tetrahedron 2012, 68, 4588. (v) Dohi, S.; Moriyama, K.;
Togo, H. Tetrahedron 2012, 68, 6557.
(12) Zagulyaeva, A. A.; Yusubov, M. S.; Zhdankin, V. V. J. Org.
Chem. 2010, 75, 2119.
(13) Mahajan, U. S.; Akamanchi, K. G. Synlett 2008, 987.
(14) Khanna, M. S.; Grag, C. P.; Kapoor, R. P. Tetrahedron Lett.
1992, 33, 1495.
(15) Su, F.; Zhang, J. Z.; Jin, G. Y.; Qiu, T.; Zhao, D. J.; Jia, H.
B. J. Chem. Res. 2009, 741.
(16) Cho, B. T.; Yang, W. K.; Choi, O. K. J. Chem. Soc., Perkin
Trans. 1 2001, 1204.
Maruyama, A.; Minamitsuji, Y.; Takenaga, N.; Kita, Y.
Chem. Commun. 2007, 1224. (i) Richardson, R. D.; Page, T.
K.; Altermann, S.; Paradine, S. M.; French, A. N.; Wirth, T.
Synlett 2007, 538. (j) Yakura, T.; Konishi, T. Synlett 2007,
765. (k) Sheng, J.; Li, X.; Tang, M.; Gao, B.; Huang, G.
Synthesis 2007, 1165. (l) Chen, C.; Feng, X.; Zhang, G.;
Zhao, Q.; Huang, G. Synthesis 2008, 3205. (m) Uyanik, M.;
(17) Hodson, D.; Holt, G.; Wall, D. K. J. Chem. Soc. C 1970, 971.
(18) Moroda, A.; Togo, H. Tetrahedron 2006, 62, 12408.
(19) Kanna, M. S.; Grag, C. P.; Kapoor, R. P. Synlett 1992, 393.
Synthesis 2013, 45, 791–797
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Iodine-Mediated α-Sulfonyloxylation
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(20) Floyd, M. B.; Du, M. T.; Fabio, P. F.; Jacob, L. A.; Johnson,
(21) Lee, D. M.; Kwak, S. H.; Lee, K. I. Bull. Korean Chem. Soc.
2009, 30, 1317.
B. D. J. Org. Chem. 1985, 50, 5022.
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Synthesis 2013, 45, 791–797