4-MeC6H4I-mediated efficient -tosyloxylation of ketones with oxone and p- toluenesulfonic acid in acetonitrile

Article abstract of DOI:10.1055/s-0029-1218370

Various alkyl aryl ketones, dialkyl ketones, and cycloheptanone were efficiently converted into the corresponding -tosyl-oxy ketones in good yields by using Oxone and p-toluenesulfonic acid monohydrate in the presence of p-iodotoluene in aceton

Full text of DOI:10.1055/s-0029-1218370

3360
LETTER
4-MeC6H4I-Mediated Efficient a-Tosyloxylation of Ketones with Oxone® and
p-Toluenesulfonic Acid in Acetonitrile
Efficient
a
-Tosylo
y
xylation of
K
u
etones mi Tanaka, 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 September 2009
the PhI-catalyzed and ion-supported PhI-catalyzed
Abstract: Various alkyl aryl ketones, dialkyl ketones, and cyclo-
heptanone were efficiently converted into the corresponding a-tosyl-
oxy ketones in good yields by using Oxone® and p-toluenesulfonic
acid monohydrate in the presence of p-iodotoluene in acetonitrile.
preparation of 3,4-dihydro-1H-2,1-benzothiazine 2,2-di-
oxides from N-methoxy-2-arylethanesulfonamides with
MCPBA.7d,e Among those reactions, the ArI-catalyzed
4-Methoxyacetophenone and 2-acetylthiophene bearing an elec- oxidative conversion of substrates with Oxone® is very
attractive5g,j,l,m,5q–s as Oxone® is an inorganic nonmetal ox-
tron-rich aromatic group could be also converted into the corre-
sponding a-tosyloxyketones smoothly in good yields with the
idant and is much less expensive than MCPBA. Here, as
present method. Here, p-iodotoluene works as catalyst and p-[(hy-
part of our study on the catalytic use of organo-
droxy)(tosyloxy)]iodotoluene is formed in situ as a reactive species
iodines(I) in organic synthesis,7 we would like to report
for the a-tosyloxylation of ketones. However, one equivalent of
the 4-MeC6H4I-mediated a-tosyloxylation of ketones with
Oxone® and p-toluenesulfonic acid monohydrate in aceto-
nitrile.
p-iodotoluene was required to obtain a-tosyloxyketones in good
yields and was recovered in 80–20% yields, depending on the reac-
tion conditions.
Key words: p-iodotoluene, Oxone®, a-tosyloxyketone, ketone,
p-toluenesulfonic acid, catalyst
Table 1 shows the effect of the amount of PhI on the yield
of a-tosyloxyacetophenone from the reaction of acetophe-
none with Oxone® and p-toluenesulfonic acid mono-
hydrate in chloroform at 60 °C. The yield of a-
tosyloxyacetophenone was extremely poor without PhI,
while good yield was obtained by using 1.0 equivalent of
PhI at 60 °C (entries 1–3). Moreover, the amounts of p-
toluenesulfonic acid monohydrate and Oxone® are impor-
tant. a-Tosyloxyacetophenone was obtained in good yield
when 3 or 5 equivalents of p-toluenesulfonic acid mono-
hydrate and 1.5 equivalents of Oxone® were used at 60 °C
(entries 3–8, and 14).
The use of hypervalent iodines in organic synthesis has
been studied widely.1 Especially, (diacetoxyiodo)benzene
and [(hydroxy)(tosyloxy)iodo]benzene (Koser’s reagent)
are the most popular and useful trivalent iodine reagents
for organic synthesis because they are good alternatives to
toxic heavy-metal oxidants.2 Among them, [(hydroxy)(to-
syloxy)iodo]benzene is a highly efficient and sole reagent
for the direct a-tosyloxylation of ketones.3a,b a-Tosyloxy-
ketones are very important strategic precursors for the
preparation of various heteroaromatics, such as thiazoles,
imidazoles, oxazoles, selenazoles, pyrazoles, and benzo-
furans.3 Therefore, we have been studying the synthetic
uses of [(hydroxy)(tosyloxy)iodo]arenes, 1-(arenesulfo-
nyloxy)benziodoxolones, and poly[4-(hydroxy)(tosyl-
oxy)iodo]styrenes for the construction of thiazoles,
imidazoles, imidazo[1.2-a]pyridines, and 2,1-benzothia-
zines.4 On the other hand, the ArI-catalyzed oxidative
conversion of substrates, such as ketones, hydroquinones,
and alcohols, with m-chloroperbenzoic acid (MCPBA) or
Oxone® has become very popular5 because it is a metal-
free oxidative reaction and thus conforms to environmen-
tally benign organic synthesis. Recently, we also reported
an efficient means to prepare various [(hydroxy)(sulfonyl-
oxy)iodo]arenes directly from iodoarenes with MCPBA
and sulfonic acids at room temperature;6 the PhI-cata-
lyzed, polymer-supported PhI-catalyzed, and ion-support-
ed PhI-catalyzed a-tosyloxylation of ketones with
MCPBA and p-toluenesulfonic acid monohydrate;7a–c and
Then, the effect of iodoarenes, such as PhI, 4-ClC6H4I, 3-
HO2CC6H4I, 4-HO2CC6H4I, and 4-MeC6H4I, was studied
at 60 °C as shown in entries 3 and 9–12, and PhI and 4-
MeC6H4I showed the best reactivity among these iodoar-
enes to provide a-tosyloxyacetophenone in high yield. Fi-
nally, the effect of solvent was studied. Acetonitrile was a
slightly better solvent than chloroform, while 1,2-dichlo-
roethane and ethyl acetate were not good solvents (entries
12–18). Instead of p-toluenesulfonic acid monohydrate,
the a-sulfonyloxylation of acetophenone with 5 and 3
equivalents of p-chlorobenzenesulfonic acid and DL-cam-
phorsulfonic acid with Oxone® (1.5 equiv) in acetonitrile
at 60 °C was carried out to form the corresponding a-sul-
fonyloxyacetophenones in good yields, respectively, as
shown in Table 2.
Based on these results, various ketones, such as alkyl aryl
ketones, dialkyl ketones, and cycloheptanone, were treat-
ed with Oxone® and p-toluenesulfonic acid monohydrate
in the presence of 4-MeC6H4I in acetonitrile to provide the
corresponding a-tosyloxyketones in good yields,8 as
shown in Table 3.8
SYNLETT 2009, No. 20, pp 3360–3364
x
x
.x
x
.2
0
0
9
Advanced online publication: 27.11.2009
DOI: 10.1055/s-0029-1218370; Art ID: U10009ST
© Georg Thieme Verlag Stuttgart · New York

LETTER
Efficient a-Tosyloxylation of Ketones
3361
Table 3 4-MeC6H4I-Mediated a-Tosyloxylation of Ketones with
Table 1 ArI-Mediated a-Tosyloxylation of Acetophenone with
Oxone® and PTSA·H2O
Oxone® and PTSA·H2O
4-MeC6H4I (1.0 equiv)
ArI, Oxone® (1.5 equiv)
O
Oxone® (1.5 equiv)
O
O
O
p-TsOH⋅H2O
4-TsOH⋅H2O (x equiv)
R2
OTs
Ph
Me
R2
Ph
CHCl3 or MeCN,
5 h, 60 °C
R1
R1
MeCN, 60 °C
OTs
Entry ArI (equiv)
PTSA·H2O (equiv) Yield (%)
Entry
Product
x
Time (h) Yield (%)
1
2
–
3.0
3.0
3.0
0
A
A
A
A
A
A
A
A
A
A
A
A
A
A
B
B
C
D
4 (70)a
7 (82)a
82 (7)a
0 (95)a
14 (78)a
14 (80)a
70 (11)a
76 (6)a
17 (69)a
57 (86)a
4 (23)b
81 (21)a
82 (4)a
50 (43)a
84
O
1
2
5
3
5
5
94
95
PhI (0.5)
OTs
O
3
PhI (1.0)
4
PhI (1.0)b
3
4
5
3
3
4
100
76
5
PhI (1.0)b
1.0
2.0
3.0
3.0
3.0
3.0
3.0
3.0
5.0
5.0
5.0
5.0
5.0
5.0
OTs
O
Cl
6
PhI (1.0)b
PhI (1.0)b
5
6
5
3
2
24
92
83
7
8
PhI (1.0)c
OTs
O
O2N
O2N
9
4-ClC6H4I (1.0)
3-HO2CC6H4I (1.0)
4-HO2CC6H4I (1.0)
4-MeC6H4I (1.0)
4-MeC6H4I (1.0)d
PhI (1.0)d
7
8
5
3
3
6
100
96
10
11
12
13
14
15
16
17
18
OTs
O
9
10
5
3
1
5
99
83
OTs
O
Me
11
12
5
3
4
5
77
PhI (1.0)
52 (26)a
95 (1)a
33 (55)a
15 (62)a
OTs
O
4-MeC6H4I (1.0)
PhI (1.0)
MeO
Me
13
14
5
3
5
48
71
65
PhI (1.0)
OTs
Me
a Yield of starting material.
b Oxone® (1.1 equiv) was used.
c Oxone® (1.3 equiv) was used.
Me
O
15
16
5
3
3
24
90
84
d Reaction time was 3 h. A: CHCl3 (4 mL), B: MeCN (4 mL), C: DCE
(4 mL), D: MeCO2Et (4 mL).
OTs
O
O
Table 2 4-MeC6H4I-Mediated a-Sulfonyloxylation of Acetophe-
17
18
5
3
4
27
80
92
none with Oxone® and RSO3H·H2O
4-MeC6H4I
OTs
OTs
OTs
Oxone® (1.5 equiv)
RSO3H⋅H2O (x equiv)
O
O
19
20
5
3
4
24
100
92
Ph
Ph
Me
MeCN (4 mL), 60 °C
O3SR
S
Entry
R
x
Time (h)
Yield (%)
O
21
22
5
3
3
3
41
45
1
2
4-MeC6H4
5
3
5
5
94
95
O
O
3
4
5
3
2
22
72
82
4-ClC6H4
23
24
5
3
4
2
75
68
OTs
5
6
5
3
3
7
70
76
O
Synlett 2009, No. 20, 3360–3364 © Thieme Stuttgart · New York

3362
A. Tanaka, H. Togo
LETTER
Table 3 4-MeC6H4I-Mediated a-Tosyloxylation of Ketones with
OH
O
Oxone® and PTSA·H2O (continued)
R2
R2
4-MeC6H4I (1.0 equiv)
R1
R1
Oxone® (1.5 equiv)
O
O
4-TsOH⋅H2O (x equiv)
R2
OTs
R2
R1
R1
H2O
MeCN, 60 °C
O
TsO
+
O
R2
Entry
Product
x
Time (h) Yield (%)
R1
R2
R1
O
I
Me
25
26
5
3
0.5
2
89
43
OTs
OH2
OTs
O
OTs
A
27
28
5
3
2
1.5
77
56
OH
I
Me
I
Me
O
O
O
29
30
5
3
1.5
1
92
71
OTs
OEt
Me
I(V)
OTs
O
31
32
5
3
1.5
1
73
70
OMe
OTs
O
2KHSO4⋅KHSO4⋅K2SO4
2KHSO5⋅KHSO4⋅K2SO4,
p-TsOH⋅H2O
a
b
OTs
+
33
3
1
52
O
Scheme 1 Reaction mechanism for 4-MeC6H4I-mediated a-tosyl-
oxylation of ketones
OTs
enol form of ketone to provide a-tosyloxyketone via inter-
mediate A, together with the regeneration of 4-MeC6H4I.
a/b = 32:20
a Yield of p-methoxyphenol.
Practically, when the reaction of p-iodotoluene and p-tol-
uenesulfonic acid monohydrate with Oxone® was carried
out in acetonitrile at room temperature, [hydroxy](tosyl-
oxy)iodo]toluene was obtained in 32% yield. However, 4-
MeC6H4I(I) may be partly further oxidized to 4-
MeC6H4I(V), which is not applicable to the a-tosyloxyla-
tion of ketones, at the present conditions. Generally, 4-
MeC6H4I was recovered in 80–20% yields depending on
the reaction conditions and substrates, and this is probably
the reason why 4-MeC6H4I could not be recovered quan-
titatively.
Especially, 4-methoxyacetophenone and 2-acetyl-
thiophene bearing an electron-rich aromatic group reacted
with Oxone® and p-toluenesulfonic acid monohydrate in
the presence of 4-MeC6H4I in acetonitrile to provide the
corresponding a-tosyloxyketones in good yields (entries
11, 19, and 20), although the treatment of 4-methoxyace-
tophenone and 2-acetylthiophene with the PhI-catalyzed
MCPBA and p-toluenesulfonic acid monohydrate system
gave the corresponding a-tosyloxyketones in 27% and
47% yields, respectively.7a,b Thus, the present system is
much more effective than the PhI-catalyzed MCPBA and
p-toluenesulfonic acid monohydrate system to give the
corresponding a-tosyloxyketones from ketones. Ethyl
benzoylacetate and methyl acetoacetate gave the corre-
sponding a-tosyloxy products in good yields, respectively
(entries 29–32). In unsymmetrical methyl ketones, a-tosyl-
oxylation at the alkyl group is favored over that at the me-
thyl group (entry 33). 4-MeC6H4-mediated formation of
a-tosyloxyketones from ketones is shown in Scheme 1. 4-
MeC6H4I is oxidized by Oxone® in the presence of p-tol-
uenesulfonic acid monohydrate to generate [(hydroxy)(to-
syloxy)iodo]toluene in situ, which then reacts with the
In conclusion, various a-tosyloxyketones were prepared
in good yields from the reaction of ketones with Oxone®
and p-toluenesulfonic acid monohydrate in the presence
of 4-MeC6H4I in acetonitrile. The a-sulfonyloxylation of
acetophenone was also achieved with Oxone® and p-chlo-
robenzenesulfonic acid and DL-camphorsulfonic acid in
the presence of 4-MeC6H4I. In view of the synthetic utility
of a-tosyloxyketones for the preparation of various het-
erocyclic compounds, we believe that the present a-tosyl-
oxylation method is very useful due to the simplicity of
operation and isolation of the product, and the fact that
[(hydroxy)(tosyloxy)]iodobenzene is not required. Fur-
thermore, Oxone® is an inorganic nonmetal oxidant and is
much less expensive than MCPBA.
Synlett 2009, No. 20, 3360–3364 © Thieme Stuttgart · New York

LETTER
Efficient a-Tosyloxylation of Ketones
3363
(5) Reviews: (a) Ochiai, M.; Miyamoto, K. Eur. J. Org. Chem.
2008, 4229. (b) Dohi, T.; Kita, Y. Chem. Commun. 2009,
2073. (c) Uyanik, M.; Ishihara, K. Chem. Commun. 2009,
2086. Papers: (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.;
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.;
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.
Acknowledgment
Financial support of a Grant-in-Aid for Scientific Research
(No.20550033) from the Ministry of Education, Science, Sports and
Culture of Japan is gratefully acknowledged.
References and Notes
(1) Varvoglis, A. Hypervalent Iodine in Organic Synthesis;
Academic Press: San Diego, 1997.
(2) Reviews: (a) Moriarty, R. M.; Vaid, R. K. Synthesis 1990,
431. (b) Stang, P. J. Angew. Chem., Int. Ed. Engl. 1992, 31,
274. (c) Prakash, O.; Saini, N.; Sharma, P. K. Synlett 1994,
221. (d) Kitamura, T. Yuki Gosei Kagaku Kyokaishi 1995,
53, 893. (e) Stang, P. J.; Zhdankin, V. V. Chem. Rev. 1996,
96, 1123. (f) Umemoto, T. Chem. Rev. 1996, 96, 1757.
(g) Kita, Y.; Takada, T.; Tohma, H. Pure Appl. Chem. 1996,
68, 627. (h) Togo, H.; Hoshina, Y.; Nogami, G.; Yokoyama,
M. Yuki Gosei Kagaku Kyokaishi 1997, 55, 90.
(i) Varvoglis, A. Tetrahedron 1997, 53, 1179. (j) Zhdankin,
V. V. Rev. Heteroat. Chem. 1997, 17, 133. (k) Muraki, T.;
Togo, H.; Yokoyama, M. Rev. Heteroat. Chem. 1997, 17,
213. (l) Kitamura, T.; Fujiwara, Y. Org. Prep. Proced. Int.
1997, 29, 409. (m) Varvoglis, A.; Spyroudis, S. Synlett
1998, 221. (n) Zhdankin, V. V.; Stang, P. J. Tetrahedron
1998, 54, 10927. (o) Moriarty, R. M.; Prakash, O. Adv.
Heterocycl. Chem. 1998, 69, 1. (p) Togo, H.; Katohgi, M.
Synlett 2001, 565. (q) Zhdankin, V. V.; Stang, P. J. Chem.
Rev. 2002, 102, 2523. (r) Richardson, R. D.; Wirth, T.
Angew. Chem. Int. Ed. 2006, 45, 4402. (s) Ladziata, U.;
Zhdankin, V. Synlett 2007, 527.
(6) Yamamoto, Y.; Togo, H. Synlett 2005, 2486.
(7) (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. (d) Moroda, A.; Togo, H.
Synthesis 2008, 1257. (e) Ishiwata, Y.; Togo, H.
(3) Reviews: (a) Moriarty, R. M.; Vaid, R. K.; Koser, G. F.
Synlett 1990, 365. (b) Koser, G. F. Aldrichimica Acta 2001,
34, 89. (c) Papers: 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.
Tetrahedron Lett. 2009, 50, 5354.
(8) Typical Procedure for 4-MeC6H4I-Mediated
a-Tosyloxylation of Ketone with Oxone® and
p-Toluenesulfonic Acid Monohydrate
To a solution of acetophenone (120 mg, 1 mmol) in MeCN
(4 mL) were added p-iodotoluene (218 mg, 1.0 mmol),
PTSA·H2O (951 mg, 5 mmol), and Oxone® (249 mg, 1.5
mmol). The mixture was stirred for 5 h at 60 °C under an
argon atmosphere. After the reaction, the reaction mixture
was poured into sat. aq NaHCO3 solution and extracted with
CHCl3 (3 × 20 mL). The organic layer was dried over
Na2SO4. After removal of the solvent under reduced
pressure, a-tosyloxyacetophenone was obtained as a crude
state. Pure a-tosyloxyacetophenone was obtained in 94%
yield by short flash column chromatography on silica gel
(EtOAc–hexane = 1:4).
(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.
a-Tosyloxyacetophenone
Mp 90 °C (lit.3h 90–91 °C). IR (KBr): 1180, 1360, 1715 cm–1.
1H NMR (400 MHz, CDCl3): d = 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).
(4) 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.
a-Tosyloxy-p-methylacetophenone
Mp 105 °C (lit.9 82–83 °C). IR (KBr): 1170, 1350, 1700 cm–1.
1H NMR (400 MHz, CDCl3): d = 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).
a-Tosyloxy-p-chloroacetophenone
Mp 123 °C (lit.9 125 °C). IR (KBr): 1190, 1360, 1710 cm–1.
1H NMR (400 MHz, CDCl3): d = 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).
Synlett 2009, No. 20, 3360–3364 © Thieme Stuttgart · New York

3364
A. Tanaka, H. Togo
LETTER
a-Tosyloxy-p-nitroacetophenone
3-Tosyloxy-2-octanone
Mp 137 °C (lit.9 130–131 °C). IR (KBr): 1180, 1340, 1710
cm–1. 1H NMR (400 MHz, CDCl3): d = 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).
Oil. IR (neat): 1180, 1360, 1600, 1740 cm–1. 1H NMR (400
MHz, CDCl3): d = 0.80 (t, J = 7.3 Hz, 3 H), 1.00–1.30 (m, 6
H), 1.54–1.78 (m, 2 H), 2.23 (s, 3 H), 2.48 (s, 3 H), 4.58 (dd,
J = 8.4, 4.6 Hz, 1 H), 7.36 (d, J = 8.7 Hz, 2 H), 7.81 (d,
J = 8.7 Hz, 2 H). 13C NMR (400 MHz, CDCl3): d = 13.91,
21.97, 22.35, 24.17, 26.01, 31.00, 31.52, 84.62, 128.13,
130.07. 132.98, 145.48, 205.78. HRMS–FAB: m/z calcd for
C15H23O4S [M + 1]: 299.1317; found: 299.1315.
2-Thienyl (Tosyloxy)methyl Ketone
a-Tosyloxypropiophenone
Mp 68 °C (lit.9 68–69 °C). IR (KBr): 1170, 1370, 1700 cm–1.
1H NMR (400 MHz, CDCl3): d = 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).
Mp 92–93 °C (lit.3i 94–96 °C). IR (KBr): 1685, 1370, 1180,
730 cm–1. 1H NMR (400 MHz, CDCl3): d = 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).
a-(Tosyloxy)octyl Phenyl Ketone
Mp 59–61 °C (lit.4d 59–61 °C). IR (neat): 1180, 1340, 1700
cm–1. 1H NMR (400 MHz, CDCl3): d = 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).
a-Tosyloxy-p-methoxyacetophenone
Mp 131–132 °C. IR (KBr): 1684, 1376, 1171 cm–1. 1H NMR
(400 MHz, CDCl3): d = 2.45 (s, 3 H), 3.88 (s, 3 H), 5.20 (s,
2 H), 6.93 (d, J = 8.5 Hz, 2 H), 7.34 (d, J = 8.8 Hz, 2 H), 7.83
(d, J = 8.8 Hz, 2 H), 7.85 (d, J = 8.5 Hz, 2 H). 13C NMR (400
MHz, CDCl3): d = 30.89, 55.55, 69.77, 114.11, 125.88,
128.15, 129.87, 130.43, 133.52, 144.70, 163.52, 189.17.
ESI-HRMS: m/z calcd for C16H16O5SNa [M + Na]:
343.0611; found: 343.0602.
a-Tosyloxy-3-pentanone
Mp 45–46 °C (lit.3k 43–44 °C). IR (neat): 1190, 1360, 1720
cm–1. 1H NMR (400 MHz, CDCl3): d = 1.03 (t, J = 7.3 Hz, 3
H), 1.35 (d, J = 7.0 Hz, 3 H), 2.47 (s, 3 H), 2.60 (m, 2 H),
4.80 (q, J = 7.0 Hz, 1 H), 7.37 (d, J = 8.0 Hz, 2 H), 7.81 (d,
J = 8.0 Hz, 2 H).
a-Tosyloxy-6-undecanone
a-Tosyloxy-m-nitroacetophenone
Mp 72 °C (lit.4d 72 °C). IR (neat): 1190, 1380, 1720 cm–1. 1H
NMR (400 MHz, CDCl3): d = 0.70–0.80 (m, 3 H), 0.86–1.75
(m, 15 H), 2.46 (s, 3 H), 2.51 (t, J = 7.5 Hz, 2 H), 4.64 (dd,
J = 8.0, 4.6 Hz, 1 H), 7.36 (d, J = 8.0 Hz, 2 H), 7.80 (d,
J = 8.0 Hz, 2 H).
Mp 129–130 °C. IR (KBr): 1615, 1375, 1348, 1188 cm–1. 1H
NMR (400 MHz, CDCl3): d = 2.46 (s, 3 H), 5.25 (s, 2 H),
7.37 (d, J = 8.0 Hz, 2 H), 7.72 (t, J = 8.0 Hz, 1 H), 7.84 (d,
J = 8.0 Hz, 2 H), 8.21 (dt, J = 8.0, 1.2 Hz, 1 H), 8.46 (dt,
J = 8.0, 1.2 Hz, 1 H), 8.63 (t, J = 1.2 Hz, 1 H). 13C NMR (400
MHz, CDCl3): d = 30.38, 69.87, 123.05, 128.15, 128.25,
130.03, 130.25, 132.35, 133.72, 135.29, 144.70, 145.88,
188.82. ESI-HRMS: m/z calcd for C15H13O6NSNa [M + Na]:
358.0356; found: 358.0347.
a-Tosyloxycycloheptanone
Oil. IR (neat): 1190, 1590, 1720 cm–1. 1H NMR (400 MHz,
CDCl3): d = 1.48–1.95 (m, 8 H), 2.42–2.63 (m, 5 H), 4.98 (t,
J = 5.1 Hz, 1 H), 7.35 (d, J = 8.0 Hz, 2 H), 7.83 (d, J = 8.0
Hz, 2 H). 13C NMR (400 MHz, CDCl3): d = 21.36, 22.30,
24.77, 27.45, 30.93, 39.98, 83.75, 127.61, 129.51, 133.00,
144.66, 206.05. HRMS–FAB: m/z calcd for C14H19O4S [M +
1]: 283.1004; found: 283.0986.
2,4,6-Trimethylphenyl (Tosyloxy)methyl Ketone
Mp 58 °C. IR (neat): 1191, 1377, 1608 cm–1. 1H NMR (400
MHz, CDCl3): d = 2.12 (s, 6 H), 2.27 (s, 3 H), 2.45 (s, 3 H),
4.84 (s, 2 H), 6.81 (s, 2 H), 7.33 (d, J = 8.0 Hz, 2 H), 7.87 (d,
J = 8.0 Hz, 2 H). 13C NMR (400 MHz, CDCl3): d = 18.96,
21.08, 21.65, 72.28, 128.05, 128.61. 129.81, 132.70, 133.83,
134.70, 139.82, 145.19, 201.17. Elemental Analysis: Calcd
for C18H20O4S. C 65.04, H 6.06%. Found: C 64.70, H 5.90%.
2-Furyl (Tosyloxy)methyl Ketone
Methyl a-Tosyloxyacetoacetate
Oil. IR (neat): 1180, 1320, 1720 cm–1. 1H NMR (400 MHz,
CDCl3): d = 2.30 (s, 3 H), 2.48 (s, 3 H), 3.71 (s, 3 H), 5.20
(s, 1 H), 7.38 (d, J = 8.5 Hz, 2 H), 7.83 (d, J = 8.5 Hz, 2 H).
13C NMR(400 MHz, CDCl3): d = 21.66, 26.53, 53.27, 80.34,
128.18, 129.98, 132.02, 145.90, 163.86, 196.98. HRMS–
FAB: m/z calcd for C12H15O6S [M + 1]: 287.0589; found:
287.0596.
Mp 63–64 °C (lit.3h 65–67 °C). IR (KBr): 1695, 1370, 1170,
810, 750 cm–1. 1H NMR (400 MHz, CDCl3): d = 2.45 (s, 3
H), 5.09 (s, 2 H), 6.58 (dd, J = 3.7, 1.7 Hz, 1 H), 7.33 (dd,
J = 3.7, 0.7 Hz, 1 H), 7.36 (d, J = 8.2 Hz, 2 H), 7.61 (dd,
J = 1.7, 0.7 Hz, 1 H), 7.86 (d, J = 8.2 Hz, 2 H).
Ethyl a-Tosyloxybenzoylacetate
Oil. IR (neat): 1440, 1590, 1690 cm–1. 1H NMR (400 MHz,
CDCl3): d = 1.18 (t, J = 7.0 Hz, 3 H), 2.85 (s, 3 H), 4.18 (m,
2 H), 5.59 (s, 1 H), 7.30 (d, J = 8.4 Hz, 2 H), 7.46 (t, J = 7.5
Hz, 2 H), 7.61 (t, J = 7.5 Hz, 1 H), 7.79 (d, J = 8.5 Hz, 2 H),
7.93 (d, J = 8.5 Hz, 2 H). 13C NMR (400 MHz, CDCl3):
d = 13.75, 21.63, 62.80, 78.03, 128.24, 128.71, 129.34,
129.82, 132.34, 133.28, 134.36, 145.68, 164.12, 188.19.
HRMS–FAB: m/z calcd for C18H19O6S [M + 1]: 363.0902;
found: 363.0920.
a-(p-Chlorobenzenesulfonyloxy)acetophenone
Mp 96 °C (lit.10 97 °C). IR (KBr): 1180, 1540, 1700 cm–1. 1H
NMR (400 MHz, CDCl3): d = 5.36 (s, 2 H), 7.48 (t, J = 7.5
Hz, 2 H), 7.56 (d, J = 8.9 Hz, 2 H), 7.63 (t, J = 8.9 Hz, 1 H),
7.84 (d, J = 7.5 Hz, 2 H), 7.92 (d, J = 8.9 Hz, 2 H).
a-(Camphorsulfonyloxy)acetophenone
Oil (lit.11 60–61 °C). IR (neat): 1170, 1590, 1720 cm–1. 1H
NMR (400 MHz, CDCl3): d = 0.92 (s, 3 H), 1.14 (s, 3 H),
1.42–1.51 (m, 1 H), 1.74–1.85 (m, 1 H), 1.95 (d, J = 18.6 Hz,
1 H), 2.04–2.16 (m, 2 H), 2.36–2.55 (m, 2 H), 3.35 (d,
J = 15.3 Hz, 1 H), 3.82 (d, J = 15.3 Hz, 1 H), 5.53 (s, 2 H),
7.52 (t, J = 7.2 Hz, 2 H), 7.64 (t, J = 7.2 Hz, 1 H), 7.92 (d,
J = 7.2 Hz, 2 H).
1-Tosyloxy-2-octanone
Oil. IR (neat): 1180, 1360, 1590,1730 cm–1. 1H NMR (400
MHz, CDCl3): d = 0.87 (t, J = 7.0 Hz, 3 H), 1.20–1.32 (m, 6
H), 1.48–1.62 (m, 2 H), 2.45 (s, 3 H), 2.49 (t, J = 7.2 Hz, 2
H), 4.49 (s, 2 H), 7.37 (d, J = 8.0 Hz, 2 H), 7.82 (d, J = 8.0
Hz, 2 H). 13C NMR (400 MHz, CDCl3): d = 13.97, 21.68,
22.39, 22.76, 28.62, 31.43, 38.98, 71.78, 128.04, 130.00,
132.30, 145.44, 203.43. HRMS–FAB: m/z calcd for
C15H23O4S [M + 1]: 299.1317; found: 299.1295.
(9) Khanna, M. S.; Grag, C. P.; Kapoor, R. P. Tetrahedron Lett.
1992, 33, 1495.
(10) Lee, I.; Chung, S. Y.; Lee, H. W. J. Chem. Soc., Perkin
Trans. 2 1988, 975.
(11) Hatzigrigorious, E.; Varvoglis, A.; Christianopoulou, M.
J. Org. Chem. 1990, 55, 315.
Synlett 2009, No. 20, 3360–3364 © Thieme Stuttgart · New York

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