An effective and catalytic oxidation using recyclable fluorous IBX

Article abstract of DOI:10.1039/c0cc03149f

Oxidation of alcohols in the presence of a catalytic amount of fluorous IBX and Oxone as a co-oxidant resulted in the corresponding carbonyl compounds in good to high yields. The fluorous IBX is readily recovered as insoluble fluorous IBA from the reaction mixture by simple filtration, and can be reused without significant loss of the catalytic activity.

Full text of DOI:10.1039/c0cc03149f

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An effective and catalytic oxidation using recyclable fluorous IBXw
Tsuyoshi Miura,* Kosuke Nakashima, Norihiro Tada and Akichika Itoh
Received 10th August 2010, Accepted 17th November 2010
DOI: 10.1039/c0cc03149f
Oxidation of alcohols in the presence of a catalytic amount of
fluorous IBX and Oxone as a co-oxidant resulted in the
corresponding carbonyl compounds in good to high yields. The
fluorous IBX is readily recovered as insoluble fluorous IBA from
the reaction mixture by simple filtration, and can be reused
without significant loss of the catalytic activity.
o-Iodoxybenzoic acid (IBX) as
a
hypervalent iodine
compound has attracted a great deal of attention in organic
synthesis since its synthetic utility as an oxidant was reported
by Frigerio and Santagostino in 1994,1 because IBX is a mild,
selective, metal-free, and non-toxic oxidation reagent.2
However, IBX is a potentially shock- or heat-sensitive
explosive compound,3 and must be used in DMSO due to its
insolubility in common organic solvents.1 Also, 2-iodoso-
benzoic acid (IBA), a waste product from the oxidations of
IBX, often makes it difficult to separate the desired products
from the reaction mixture. To resolve these issues, modified
IBX,4 with reduced explosive property that can be used in
common solvents, and polymer support IBX,5 which can be
easily separated from the desired products, have been
reported. In addition, oxidation with catalytic IBX and
2-iodoxybenzenesulfonic acid (IBS), that are generated in situ
from 2-iodobenzoic acid and 2-iodobenzenesulfonic acid in the
presence of Oxone, has also been reported.6,7 Oxone also is an
environmentally safe reagent, and offers several significant
advantages such as stability, easy of transport, simple handling,
controllable addition, and nontoxic nature.6a,7
Scheme 1 Preparation of fluorous 2-iodobenzoic acid and fluorous
IBX.
hypervalent iodine organocatalyst with
a fluorous tag,
fluorous IBX. We describe a catalytic oxidation using reusable
fluorous IBX in the presence of Oxone as a co-oxidant and
Bu4NHSO4 as a phase-transfer catalyst in this report.
The fluorous iodobenzoic acid 4 and fluorous IBX 5 we
designed are prepared as shown in Scheme 1. Treatment of
5-hydroxy-2-iodobenzoic acid (1) with hydrochloric acid in
methanol affords methyl ester 2 in 90% yield. Ester 2 is
coupled with the fluorous tosylate in the presence of potassium
carbonate in acetonitrile to give the fluorous benzoate 3 in
98% yield. Fluorous IBX 5 is obtained in quantitative yield by
treatment of 4 with Oxone after hydrolysis of 3.
From a view point of green chemistry, development of a
metal-free process has been focused and a variety of organo-
catalysts, including IBX, have been developed.8 Along with
this, recovery of organocatalysts from the reaction mixture
and its recycling are highly desired, as most organocatalysts
are expensive and require more steps for synthesis. The
fluorous tag technique by fluorous solid-phase or fluorous–
organic solvent extraction is one of a recycling method, and
many groups have attempted recyclable reactions.9,10 Oxida-
tion of alcohols and phenols with fluorous hypervalent iodines
also have been reported.11 Furthermore, several groups have
reported recovery of catalyst with a fluorous tag only by
filtration due to its insolubility.12 This method is a better
protocol, which can recover without using expensive fluorous
solvents and fluorous silica gel.
First, we examined the activity of 5 for oxidation of alcohol,
and found that it smoothly oxidized alcohol 6a to the corre-
sponding ketone 7a in 79% yield (Scheme 2).
Next, we studied the catalytic oxidation with 5 generated
in situ from fluorous iodobenzoic acid 4 as a pre-catalyst in the
presence of Oxone. We optimized the reaction conditions for
the oxidation, and found that a better result was obtained with
a catalytic amount of Bu4NHSO4 in the nitromethane/water
solvent system (Table 1).6b
Table 2 shows the scope and limitation of the oxidation with
various alcohols (6a–6k) under the optimized reaction
With these perspectives, in order to recover and reuse IBA
as a waste, we have attempted the development of a novel
Gifu Pharmaceutical University, 1-25-4 Daigaku-nishi, Gifu 501-1196,
Japan. E-mail: miura@gifu-pu.ac.jp
w Electronic supplementary information (ESI) available: Experimental
procedures, characterization of new compounds and NMR spectra.
See DOI: 10.1039/c0cc03149f
Scheme 2 Oxidation using fluorous IBX.
c
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Chem. Commun., 2011, 47, 1875–1877 1875

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Table 1 Optimization of reaction conditions
Table 2 Oxidation of alcohols using fluorous organocatalyst
Entry Product
Oxone (equiv.) Time/h Yielda (%)
Yielda (%)
7a
5c
8
6ab
Entry
Solvent
Time/h
1
1
1
1
8
10
24
88
75
78
1
2
3
4
5
6
DMSO
H2O
EtOAc
1,4-Dioxane
MeCN
MeNO2
60
78
60
71
34
81
8
8c
70c
38c
36c
60
0
4
0
0
23c
30c
38
44
59
88
99
16c
20c
0
2
3
35
37
0
7d
8d,e
MeNO2–H2O
MeNO2–H2O
12
0
a
b
Isolated yield. Recovered yields of starting material 6a. Deter-
e
mined by H NMR. Bu4NHSO4 (0.1 equiv.) was added. Fluorous
c
1
d
IBX 5 was used as the catalyst instead of 4.
4b
2
1
20
12
84
condition as mentioned above.13 Secondary alcohols are
smoothly oxidized by the catalytic oxidative system to afford
the corresponding ketones in good to high yields (entries 1–5).
Aliphatic primary alcohols also are oxidized to the corre-
sponding carboxylic acids in high yields (entries 6–8). On the
other hand, a variety of benzylic alcohols are converted to
the corresponding aldehydes in moderate to high yields
(entries 9–11).6b
5
70c
6
1.5
1.5
8
92
91
The second objective of our project is recovery of fluorous
IBA 9, a precursor of 5. Fortunately, the recovery of 914 could
be carried out only by filtration (65–100%) from the reaction
mixture, not by the fluorous solid phase and fluorous–organic
solvent extraction technique, due to its insolubility. In each
reuse, the recovered 5, without further purification, retains its
catalytic activity for five cycles (Table 3).
7b
12
Although the structure of 9 could not be identified by NMR
measurement due to its insolubility in any organic solvents
and water, we could detect 9 by high resolution mass
spectra. Therefore, we assume that this reaction with 5
proceeds in a similar manner to those of the catalytic IBX
oxidations (Scheme 3).6,7 Fluorous iodobenzoic acid 4 is
converted to 5, active species of oxidizing alcohol, by
oxidation with tetra-n-butylammonium oxone through 9.
Fluorous IBX 5 is regenerated by re-oxidation with tetra-n-
butylammonium oxone.
8
1.5
12
20
92
77
9d,e
1
10d
1
1
12
4
86
In conclusion, novel fluorous IBX 5, generated in situ from
pre-catalyst 4, efficiently works as a catalyst for oxidation of
various alcohols to the corresponding carbonyl compounds in
good to high yields. The organocatalyst 5 can be regenerated
in situ from fluorous IBA 9, which is readily recovered only
by simple filtration, in the presence of Oxone. The
catalytic activity of 5, regenerated from recovered 9,
does not change significantly up to five times. Further
application to the other oxidation is currently in progress in
our laboratory.
11d
49f
a
b
Isolated yield. 0.2 equiv. of catalyst 4 was used. Determined by
c
1H NMR. MeNO2 was used as the reaction solvent. Bu4NHSO4
f
was not added. p-Methoxybenzyl alcohol (6k) was recovered in 36%
d
e
yield.
c
1876 Chem. Commun., 2011, 47, 1875–1877
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Table 3 Recycling and reuse of the fluorous catalyst by filtration
5 (a) M. Mulbaier and A. Giannis, Angew. Chem., Int. Ed., 2001, 40,
¨
4393–4394; (b) G. Sorg, A. Mengel, G. Jung and J. Rademann,
Angew. Chem., Int. Ed., 2001, 40, 4395–4397; (c) N. N. Reed,
M. Delgado, K. Hereford, B. Clapham and K. D. Janda, Bioorg.
Med. Chem. Lett., 2002, 12, 2047–2049; (d) Z. Lei, C. Denecker,
S. Jegasothy, D. C. Sherrington, N. K. H. Slater and
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(e) W.-J. Chung, D.-K. Kim and Y.-S. Lee, Synlett, 2005,
2175–2178; (f) Z. Q. Lei, H. C. Ma, Z. Zhang and Y. X. Yang,
React. Funct. Polym., 2006, 66, 840.
6 For catalytic IBX, see: (a) A. P. Thottumkara, M. S. Bowsher and
T. K. Vinod, Org. Lett., 2005, 7, 2933–2936; (b) A. Schulze and
A. Giannis, Synthesis, 2006, 257–260.
7 For catalytic IBS, see: M. Uyanik, M. Akakura and K. Ishihara,
J. Am. Chem. Soc., 2009, 131, 251–262.
8 For selected reviews on organocatalysts, see: (a) P. I. Dalko and
L. Moisan, Angew. Chem., Int. Ed., 2004, 43, 5138–5175;
(b) H. Pellissier, Tetrahedron, 2007, 63, 9267–9331;
(c) S. Mukherjee, J. W. Yang, S. Hoffmann and B. List, Chem.
Rev., 2007, 107, 5471–5569; (d) A. Dondoni and A. Massi, Angew.
Chem., Int. Ed., 2008, 47, 4638–4660; (e) A. Lattanzi, Chem.
Commun., 2009, 1452–1463; (f) X. Liu, L. Lin and X. Feng, Chem.
Commun., 2009, 6145–6158.
Entry
Time/h
Yielda (%)
Cat. recoveryb
Initial
9
9
9
9
10
10
83
82
91
95
94
88
100
100
100
84
91
65
First reuse
Second reuse
Third reuse
Fourth reuse
Fifth reuse
a
b
Isolated yield. Determined by weight of recovered fluorous
IBA (9).
9 For a review on the fluorous tag technique, see (a) D. P. Curran,
Synlett, 2001, 1488–1496; (b) D. P. Curran, in The Handbook of
Fluorous Chemistry, ed. J. A. Gladysz, I. T. Horvath and
´
D. P. Curran, Wiley-VCH, Weinheim, 2004; (c) W. Thang and
D. P. Curran, Tetrahedron, 2006, 62, 11837–11865.
10 For a review on fluorous organocatalysts, see: W. Zhang and
C. Cai, Chem. Commun., 2008, 5686–5694; For other examples
of fluorous organocatalysts, see: (a) G. Pozzi, M. Cavazzini,
O. Holczknecht, S. Quici and I. Shepperson, Tetrahedron Lett.,
2004, 45, 4249–4251; (b) J. Legros, B. Crousse and D. Bonnet-
Delpon, J. Fluorine Chem., 2008, 129, 974–977; (c) D. Vuluga,
J. Legros, B. Crousse and D. Bonnet-Delpon, Chem.–Eur. J., 2010,
16, 1776–1779; (d) L. Wang, C. Cai, D. P. Curran and W. Zhang,
Synlett, 2010, 433–436; (e) T. Miura, K. Imai, M. Ina, N. Tada,
N. Imai and A. Itoh, Org. Lett., 2010, 12, 1620–1623.
11 (a) C. Rocaboy and J. A. Gladysz, Chem.–Eur. J., 2003, 9, 96–105;
(b) V. Tesevic and J. A. Gladysz, Green Chem., 2005, 7, 833–836;
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7433–7440.
12 (a) K. Ishihara, S. Kondo and H. Yamamoto, Synlett, 2001,
1371–1374; (b) M. Wende, R. Meier and J. A. Gladysz, J. Am. Chem.
Soc., 2001, 123, 11490–11491; (c) M. Wende and J. A. Gladysz,
J. Am. Chem. Soc., 2003, 125, 5861–5872; (d) K. Mikami, Y. Mikami,
H. Matsuzawa, Y. Matsumoto, J. Nishikido, F. Yamamoto and
H. Nakajima, Tetrahedron, 2002, 58, 4015–4021; (e) J. Bayardon,
O. Holczknecht, G. Pozzi and D. Sinou, Tetrahedron: Asymmetry,
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Tetrahedron: Asymmetry, 2007, 18, 2782–2786; (g) S. Goushi,
K. Funabiki, M. Ohta, K. Hatano and M. Matsui, Tetrahedron,
2007, 63, 4061–4066.
Scheme 3 Plausible mechanism of catalytic oxidation using fluorous
IBX.
This work was supported in part by Grants-in-Aid for
Scientific Research (C) (No. 22590007) from the Japan Society
for the Promotion of Science and Suzuken Memorial
Foundation.
13 A typical procedure of oxidation using fluorous organocatalyst 4 is
as follows: to a colorless solution of diphenylmethanol (6a, 100 mg,
0.543 mmol) and the organocatalyst 4 (39.3 mg, 0.054 mmol) in
MeNO2 (1.6 mL) and H2O (0.6 mL) were added Oxone (334 mg,
0.543 mmol) and Bu4NHSO4 (18.4 mg, 0.054 mmol) at room
temperature. The reaction mixture was stirred at 70 1C for 8 h,
and then cooled to room temperature. The precipitated fluorous
IBA (9) was filtered, and washed with water and ether. The
collected 9 was dried in vacuo, and was used in the next step
without further purification. The filtrate was extracted three times
with EtOAc. The EtOAc layers were combined, washed with brine,
dried over anhydrous MgSO4, and evaporated. The residue was
purified by flash column chromatography on silica gel with a 5 : 1
mixture of hexane and EtOAc to afford pure benzophenone
(7a, 86.4 mg, 87%).
Notes and references
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2008, 108, 5299–5358.
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´
(b) A. Ozanne, L. Pouysegu, D. Depernet, B. Francois and
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K. Senapati, Tetrahedron Lett., 2008, 49, 80–84.
14 Fluorous IBA (9) did not have the oxidative activity. Only 5% of
benzophenone (7a) was given when using a stoichiometric amount
of 9 in the presence of Bu4NHSO4 (0.1 equiv.) in MeNO2–H2O at
70 1C for 8 h.
c
This journal is The Royal Society of Chemistry 2011
Chem. Commun., 2011, 47, 1875–1877 1877