Novel α-tosyloxylation of ketones catalyzed by the in situ generated hypoiodous acid from alkyl iodide

Article abstract of DOI:10.1016/j.tetlet.2014.08.093

Using a catalytic amount of 1-iodopropane, a novel and efficient procedure has been developed for direct preparation of α-tosyloxyketones from ketones. In this protocol, 1-iodopropane is first oxidized into iodosylpropane, which decomposes to form the key

Full text of DOI:10.1016/j.tetlet.2014.08.093

Tetrahedron Letters 55 (2014) 5851–5854
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Novel
a-tosyloxylation of ketones catalyzed by the in situ generated
hypoiodous acid from alkyl iodide
⇑
Bijun Zhang, Liuquan Han, Jiantao Hu, Jie Yan
College of Chemical Engineering, Zhejiang University of Technology, Hangzhou 310032, Zhejiang, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
Using a catalytic amount of 1-iodopropane, a novel and efficient procedure has been developed for direct
Received 3 August 2014
Revised 15 August 2014
Accepted 22 August 2014
Available online 29 August 2014
preparation of
iodosylpropane, which decomposes to form the key catalyst hypoiodous acid. With this method, not only
-tosyloxyketones, but also other -sulfonyloxyketones have been prepared in moderate to good yields,
a-tosyloxyketones from ketones. In this protocol, 1-iodopropane is first oxidized into
a
a
which extends the application of alkyl substituted hypervalent iodine reagents in organic synthesis.
Ó 2014 Elsevier Ltd. All rights reserved.
Keywords:
a-Tosyloxylation
Hypoiodous acid
1-Iodopropane
Iodosylalkane
Introduction
oxidatively assisted nucleophilic substitution of iodine.1a–c The
hypervalent iodine compounds, despite their lack of stability, have
The hypervalent iodine compounds, ArIL1L2, with one aryl and
two heteroatom ligands are versatile reagents for the oxidation
and functionalization of organic compounds.1 Due to that hyperva-
lent iodine reagents are nonmetallic oxidants, they avoid the issues
of toxicity of many transition metals commonly involved in such
processes. Among them, [hydroxyl(tosyloxy)]iodobenzene (Koser’s
reagent, HTIB) is the most popular and useful reagent for the direct
found several synthetic applications. Reich and Peake first demon-
strated that the elimination proceeds with syn-stereochemistry
and have also proposed iodosylalkanes as reactive intermediates
in the reaction.8 Knapp et al. applied iodosyl elimination to prepare
unsaturated oxazolidinone, the key intermediate in the synthesis of
valienamine.9 Della and Head developed a convenient procedure for
the preparation of bridgehead fluorides by the reaction of 1-iodo-
norbornanes with xenon difluoride.10 Burton and co-workers
utilized the oxidative deiodination reaction to synthesize steroidal
products.11 However, in comparison with aryl substituted
hypervalent iodine reagents, these applications are rather limited.
Therefore, to extend alkyl substituted hypervalent iodine reagent
applications in organic synthesis, and explore their new reactions,
especially the catalytic reactions, which is still desired. Asensio
et al. reported an oxidation of iodomethane with dimethyldioxirane
in 1999, with the in situ generated active hypoiodous acid, they
successfully synthesized iodohydrin in good yields.12 This is an
interesting and convenient method for the formation of the active
hypoiodous acid, in order to extend its application, we have investi-
gated some novel reactions, and found that when catalytic amounts
of alkyl iodides and suitable oxidants are used, the in situ generated
a
-tosyloxylation of ketones.2 The prepared
a-tosyloxyketones are
important strategic precursors for the construction of various het-
eroaromatics such as thiazoles, oxazoles, selenazoles, imidazoles,
pyrazoles, benzofurans, and lactones.3 In recent years, the catalytic
utilization of hypervalent iodine reagents is increasing in impor-
tance, with growing interest in the development of environmentally
benign synthetic transformations.4 With iodobenzene as catalyst,
Togo and co-workers have reported several methods for the direct
a
-tosyloxylation of ketones.5 They have also investigated new pro-
cedures using molecular iodine in place of catalyst iodobenzene.6
Similarly, on utilization of a catalytic amount of ammonium iodide,
we have just successfully synthesized
a-tosyloxyketones from
ketones.7
Derivatives of hypervalent iodine with an alkyl substituent at
iodine, RIL1L2, generally are highly unstable and can exist only as
short-lived reactive intermediates in the oxidations of alkyliodides,
which afford either elimination products or the products of
active hypoiodous acid can improve some reactions, such as
a-
tosyloxylation of ketones, sulfonyloxylactonization of alkenoic acid,
synthesis of isoxazolines from aldoximes and alkenes, and acetox-
yselenenylation of alkenes. Herein, we wish to report a novel and
efficient
a-tosyloxylation of ketones using a catalytic amount of
⇑
Corresponding author. Fax: +86 (571)88320238.
E-mail address: jieyan87@zjut.edu.cn (J. Yan).
1-iodopropane together with a stoichiometric m-chloroperbenzoic
http://dx.doi.org/10.1016/j.tetlet.2014.08.093
0040-4039/Ó 2014 Elsevier Ltd. All rights reserved.

5852
B. Zhang et al. / Tetrahedron Letters 55 (2014) 5851–5854
O
acid as the terminal oxidant, and to our knowledge this method has
not been reported before.
OH
O
mCPBA
Ph
Ph
I
Ph
Discussion and results
At first, 1-iodopentane was selected as representative of alkyl
O
HOI
iodides to attempt the novel
1-iodopentane was absent,
a
a
-tosyloxylation of ketones. When
mixture of acetophenone with
I
O
Ph
p-toluenesulfonic acid monohydrate (TsOHÁH2O) and oxidant
m-chloroperbenzoic acid (mCPBA) was stirred at room tempera-
ture for a long time, no desired product was detected, and the
substrate acetophenone was recovered quantitatively. After adding
RI O
mCPBA
RI
Scheme 1. Proposed mechanism for the
TsOH
O
OTs
Ph
a catalytic amount of 1-iodopentane in the mixture, the
oxylation of ketones occurred smoothly and the desired product
-tosyloxyacetophenone was obtained in good yield. According
a-tosyl-
a
-tosyloxylation of ketone.
a
to the key action of 1-iodopentane in the catalytic reaction, a
plausible reaction pathway is hypothesized (Scheme 1). Thus,
1-iodopentane is first oxidized by mCPBA into the corresponding
iodosylpentane, which is highly unstable and decomposes at once
to form hypoiodous acid.12 Acetophenone then reacts with the
O
O
O
HOI
TsOH
I
OTs
Ph
Ph
TsOH
Ph
mCPBA
in situ generated active hypoiodous acid to afford
none,13 which is easily changed to
-iodosylacetophenone by the
continuing oxidation of mCPBA. Finally, the reactive hypervalent
iodine intermediate -iodosylacetophenone is rapidly transformed
into -tosyloxyacetophenone by a nucleophilic substitution of
a-iodoacetophe-
a
X
O
a
a
OTs
Ph
Scheme 2.
TsOHÁH2O or attacked by TsOH to form a similar structure of
Koser’s reagent and subsequent reductive elimination to form the
corresponding product.
Table 1
Optimization of the a-tosyloxylation of acetophenone
O
O
RI, Oxidant, TsOH
Solvent, r.t
OTs
Entry
Solvent
Oxidant (equiv)
RI (equiv)
TsOH (equiv)
Time (h)
Yielda (%)
1
2
3
4
5
6
7
8
9
CH3OH
EtOAc
THF
EtOH
MeCN
CH2Cl2
DMF
CF3CH2OH
mCPBA (1.2)
mCPBA (1.2)
mCPBA (1.2)
mCPBA (1.2)
mCPBA (1.2)
mCPBA (1.2)
mCPBA (1.2)
mCPBA (1.2)
mCPBA (1.2)
mCPBA (1.2)
mCPBA (1.2)
mCPBA (1.2)
mCPBA (1.2)
mCPBA (1.2)
Oxone (1.2)
NaBO3.4H2O (1.2)
mCPBA (1.5)
mCPBA (2.0)
mCPBA (2.5)
mCPBA (2.0)
mCPBA (2.0)
mCPBA (2.0)
mCPBA (2.0)
mCPBA (2.0)
mCPBA (2.0)
mCPBA (2.0)
mCPBA (2.0)
mCPBA (2.0)
mCPBA (2.0)
mCPBA (2.0)
mCPBA (2.0)
mCPBA (2.0)
CH3(CH2)4I (0.2)
CH3(CH2)4I (0.2)
CH3(CH2)4I (0.2)
CH3(CH2)4I (0.2)
CH3(CH2)4I (0.2)
CH3(CH2)4I (0.2)
CH3(CH2)4I (0.2)
CH3(CH2)4I (0.2)
CH3(CH2)4I (0.2)
CH3(CH2)4I (0.2)
CH3(CH2)4I (0.2)
CH3(CH2)4I (0.2)
CH3(CH2)4I (0.2)
CH3(CH2)4I (0.2)
CH3(CH2)4I (0.2)
CH3(CH2)4I (0.2)
CH3(CH2)4I (0.2)
CH3(CH2)4I (0.2)
CH3(CH2)4I (0.2)
CH3(CH2)4I (0.2)
CH3(CH2)4I (0.2)
CH3(CH2)5I (0.2)
CH3(CH2)3I (0.2)
CH3CHICH3 (0.2)
CH3(CH2)2I (0.2)
CH3(CH2)9I (0.2)
CH3(CH2)2I (0.1)
CH3(CH2)2I (0.25)
CH3(CH2)2I (0.3)
—
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.0
2.5
3.0
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
2.5
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
12
6
12
29
34
19
44
43
17
45
54
54
57
54
53
49
22
24
63
66
61
72
72
70
72
76
79
63
72
82
83
0
MeCN–CF3CH2OH (1:1)
MeCN–CF3CH2OH (6:4)
MeCN–CF3CH2OH (7:3)
MeCN–CF3CH2OH (8:2)
MeCN–CF3CH2OH (9:1)
MeCN–CF3CH2OH (2:8)
MeCN–CF3CH2OH (7:3)
MeCN–CF3CH2OH (7:3)
MeCN–CF3CH2OH (7:3)
MeCN–CF3CH2OH (7:3)
MeCN–CF3CH2OH (7:3)
MeCN–CF3CH2OH (7:3)
MeCN–CF3CH2OH (7:3)
MeCN–CF3CH2OH (7:3)
MeCN–CF3CH2OH (7:3)
MeCN–CF3CH2OH (7:3)
MeCN–CF3CH2OH (7:3)
MeCN–CF3CH2OH (7:3)
MeCN–CF3CH2OH (7:3)
MeCN–CF3CH2OH (7:3)
MeCN–CF3CH2OH (7:3)
MeCN–CF3CH2OH (7:3)
MeCN–CF3CH2OH (7:3)
MeCN–CF3CH2OH (7:3)
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
CH3(CH2)2I (0.25)
CH3(CH2)2I (0.25)
77
84
24
a
Isolated yields.

B. Zhang et al. / Tetrahedron Letters 55 (2014) 5851–5854
5853
Table 2
Preparation of
a-sulfonyloxyketones 2
(2.0 equiv)
(2.5 equiv)
2
mCPBA
O
RSO H
3
O
R
2
CH CH CH I (0.25 equiv)
3
2
R
R
2
1
R
1
MeCN-TFE (7:3), r.t.
OSO R
2
1
2
Entry
1
Substrate
RSO3Ha
Product
Time (h)
12
Yieldb (%)
O
O
SO3H
OTs
82
(TsOH)
1a
O
2a
O
O
OTs
2
3
4
TsOH
8
8
8
90
88
81
O2
N
N
O2
N
1b
1c
2b
2c
O
O2
O
2
N
OTs
TsOH
TsOH
O
O
O
OTs
Cl
Br
1d
Cl
Br
2d
O
OTs
OTs
5
6
TsOH
TsOH
TsOH
TsOH
TsOH
TsOH
8
10
8
80
80
81
72
69
68
1e
2e
O
O
1f
2f
O
O
O
O
OTs
OTs
7
1g
2g
8
12
8
1h
2h
O
O
OTs
9
Cl
Cl
1i
2i
O
O
OTs
10
14
1j
2j
O
O
S
S
OTs
11
12
TsOH
TsOH
16
12
27
93
1k
2k
O
O
O
O
OTs
1l
2l
O
O
OC2H5
OC2H5
13
TsOH
12
73
1m
OTs
O
2m
SO H
3
OSO Ph
2
14
15
16
17
1a
1a
1a
1e
1a
8
8
65
56
51
52
47
2n
O
O
Cl
SO3H
Cl
OSO
2
2o
OSO2Me
MeSO3H
MeSO3H
8
2p
O
OSO2Me
8
2q
O
OCs
18
(+)-Camphorsulfonic acid (CsOH)
10
2r
a
Ts, p-Me–C6H4SO2; Cs, (+)-10-camphorylsulfonyl.
Isolated yield.
b
To identify above mechanism, we have focused our attention on
the key intermediate -iodoacetophenone due to that other inter-
mediates iodosylpentane and -iodosylacetophenone are highly
unstable1a–c and difficult to be determined by NMR and normal
physical methods. Firstly, -iodosylacetophenone was prepared
by the reaction of acetophenone with hypoiodous acid.13 Then
the prepared
-iodoacetophenone was treated with TsOHÁH2O
and mCPBA for several hours, the desired -tosyloxyacetophenone
in situ generated hypervalent iodine intermediate
tophenone may be responsible for the reaction.
a
-iodosylace-
a
a
In light of successful formation of a-tosyloxyacetophenone, the
reaction conditions were optimized, the results are summarized in
Table 1. When acetophenone was treated with 2.0 equiv of
TsOHÁH2O and 1.2 equiv of mCPBA in the presence of 0.2 equiv of
1-iodopentane in several organic solvents at room temperature
for 12 h, the reaction usually gave poor yields (entries 1–8). Utili-
zation of a mixture solvent of acetonitrile and 2,2,2-trifluoroetha-
nol (MeCN–CF3CH2OH), the yield increased and the mixture
a
a
a
was obtained in a good yield (86%); however, in the absence of
mCPBA, no product was detected (Scheme 2). Therefore, the

5854
B. Zhang et al. / Tetrahedron Letters 55 (2014) 5851–5854
solvent MeCN–CF3CH2OH (7:3) was proved to be the favorable sol-
vent system for the reaction (entries 9–14). Other oxidants, such as
OxoneÒand NaBO3Á4H2O normally led to rather poor yields (entries
15 and 16). The amounts of mCPBA and TsOH were also checked,
the results showed that 2.0 equiv of mCPBA and 2.5 equiv of
TsOHÁH2O were suitable for the reaction (entries 17–21). A series
of alkyl iodides were active in the reaction, in which 1-iodopropane
was the most effective one, and 0.25 equiv of it was the best choice
for the reaction (entries 22–29). However, in the absence of alkyl
iodide, no product was observed (entry 30). The suitable reaction
time should be 12 h (entries 28, 31, and 32).
a-sulfonyloxyketones. Furthermore, the use of alkyl iodide in the
catalytic reactions will extend the scope of alkyl substituted hyper-
valent iodine reagents in organic synthesis.
Acknowledgment
Financial support from the Natural Science Foundation of China
(Project 21072176) is greatly appreciated.
References and notes
With the optimal conditions in hand, in order to assess the
scope of this method, a series of ketones were investigated to react
with mCPBA and TsOHÁH2O in the presence of 1-iodopropane in
MeCN–CF3CH2OH (7:3), a good result was obtained (Table 2).14
As shown in Table 2, the reaction was compatible with most of
the studied alkyl aryl ketones except 2-acetylthiophene (1k) and
1. (a) Varvoglis, A. Tetrahedron 1997, 53, 1179; (b) Stang, P. J.; Zhdankin, V. V.
Chem. Rev. 1996, 96, 1123; (c) Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2002, 102,
2523; (d) Zhdankin, V. V.; Stang, P. J. Chem. Rev. 2008, 108, 5299; (e) Kirschning,
A. Eur. J. Org. Chem. 1998, 11, 2267; (f) Ochiai, M. J. Organomet. Chem. 2000, 611,
494; (g) Okuyama, T. Acc. Chem. Res. 2002, 35, 12; (h) Zhdankin, V. V.; Stang, P. J.
Tetrahedron 1998, 54, 10927; (i) Grushin, V. V. Chem. Soc. Rev. 2000, 29, 315.
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Aldrichim. Acta 2001, 34, 89.
3. (a) Koser, G. F.; Wettach, R. H.; Smith, C. S. J. Org. Chem. 1980, 45, 1543; (b)
Moriarty, R. M.; Vaid, R. K.; Duncan, M. P.; Levy, S. G.; Prakash, O.; Goyal, S.
Synthesis 1992, 845; (c) Prakash, O.; Goyal, S. Synthesis 1992, 629; (d) Prakash,
O.; Saini, N.; Sharma, P. K. Synlett 1994, 221; (e) Lee, J. C.; Choi, J. H. Synlett
2001, 234; (f) Koser, G. F.; Relenyi, A. G.; Kalos, A. N.; Rebrovic, L.; Wettach, R.
H. J. Org. Chem. 1982, 47, 2487.
4. (a) Ochiai, M.; Takeuchi, Y.; Katayama, T.; Sueda, T.; Miyamoto, K. J. Am. Chem.
Soc. 2005, 127, 12244; (b) Dohi, T.; Maruyama, A.; Yoshimura, M.; Morimoto,
K.; Tohma, H.; Kita, Y. Angew. Chem. Int. Ed. 2005, 44, 6193; (c) Dohi, T.;
Maruyama, A.; Minamitsuji, Y.; Takenaga, N.; Kita, Y. Chem. Commun. 2007,
1224; (d) Richardson, R. D.; Wirth, T. Angew. Chem. Int. Ed. 2006, 45, 4402; (e)
Dohi, T.; Minamitsuji, Y.; Maruyama, A.; Hirose, S.; Kita, Y. Org. Lett. 2008, 10,
3559; (f) Ochiai, M. Chem. Rec. 2007, 7, 13; (g) Uyanik, M.; Ishihara, K. Chem.
Commun. 2009, 2086; (h) Dohi, T.; Kita, Y. Chem. Commun. 2009, 2073; (i) Liu,
H.-G.; Tan, C.-H. Tetrahedron Lett. 2007, 48, 8220.
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; (d) Moroda, A.; Togo, H. Synthesis 2008, 1257; (e)
Ishiwata, Y.; Togo, H. Tetrahedron Lett. 2009, 50, 5354; (f) Suzuki, Y.; Togo, H.
Synthesis 2010, 2355; (g) Kawano, Y.; Togo, H. Tetrahedron 2009, 65, 6251; (h)
Tanaka, A.; Togo, H. Synlett 2009, 3360.
provided the corresponding
a-tosyloxyketones in good yields
(entries 1–11). It was also found that the groups on the benzene
ring, no matter whether they were electron-donating or electron-
withdrawing groups, did not influence on the yield. Due to the
hinder effect of the methyl group, propiophenone (1h) and
p-chloropropiophenone (1i) furnished the respective products in
somewhat lower yields compared with 1a and 1d. Acetone, an
aliphatic ketone, when treated under the same conditions, the
desired product was afforded with an excellent yield of 93% (entry
12). Ethyl acetoacetate, a b-dicarbonyl compound, was also active
in the reaction, and it gave the corresponding product in 73% yield
(entry 13). Other aromatic sulfonic acids, such as benzenesulfonic
acid and p-chlorobenzenesulfonic acid, can react with acetophe-
none and result in the corresponding products in moderate yields
(entries 14 and 15). Methanesulfonic acid and (+)-camphorsulfonic
acid, both aliphatic sulfonic acids were also active in the reaction
and the corresponding
moderate yields (entries 16–18). This result has extended its appli-
cation compared with previous reports in which the -sulfonyl-
a-sulfonyloxyketones were obtained in
6. (a) Tanaka, A.; Moriyama, K.; Togo, H. Synlett 2011, 1853; (b) Kikui, H.;
Moriyama, K.; Togo, H. Synthesis 2013, 45, 791.
7. Hu, J.-T.; Zhu, M.; Xu, Y.; Yan, J. Synthesis 2012, 44, 1226.
a
8. Reich, H. J.; Peake, S. L. J. Am. Chem. Soc. 1978, 100, 4888.
oxylation of ketones using iodobenzene and molecular iodine as
catalysts was only suitable for aromatic sulfonic acids, and when
an aliphatic sulfonic acid was used, the reaction usually got trace
amount of product.5,6
9. Knapp, S.; Naughton, A. B. J.; Dhar, T. G. M. Tetrahedron Lett. 1992, 33, 1025.
10. Della, E. W.; Head, N. J. J. Org. Chem. 1992, 57, 2850.
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Chem. 1996, 61, 6673.
12. Asensio, G.; Andreu, C.; Boix-Bernardini, C.; Mello, R.; Gonzalez-Nunez, M. E.
Org. Lett. 1999, 1, 2125.
13. Reddy, M. M.; Kumar, M. A.; Swamy, P.; Narender, N. Tetrahedron Lett. 2011, 52,
6554.
Conclusion
14. A typical procedure for
a-tosyloxylation of ketones: To a mixture solvent of
We have developed a novel and efficient process for the synthe-
sis of various a-tosyloxyketones in moderate to good yields by the
reaction of ketones with mCPBA and TsOHÁH2O in the presence of a
catalytic amount of 1-iodopropane in MeCN–CF3CH2OH (7:3) at
room temperature for several hours. This method has some advan-
tages such as mild reaction conditions and simple procedure,
MeCN–CF3CH2OH (7:3) (5 mL), ketone 1 (0.5 mmol), mCPBA (1.0 mmol), 1-
iodopropane (0.125 mmol) and TsOHÁH2O (1.25 mmol) were added. The
resulting solution was stirred at rt for several hours. After the reaction
completed, H2O (10 mL), satd aq Na2S2O3 (5 mL) and satd aq Na2CO3 (5 mL)
were added to the mixture, then it was extracted with CH2Cl2 (3 Â 10 mL). The
organic layer was dried over anhydrous Na2SO4, filtered, and the filtration was
concentrated under reduced pressure. The residue was then purified on a silica
gel plate (4:1 hexane–ethyl acetate) to furnish a-tosyloxyketones 2.
which suits to prepare not only a-tosyloxyketones, but also other