Hypervalent iodine in synthesis. 78. Direct α-hydroxylation of ketones using [hydroxy(tosyloxy)iodo]benzene in dimethyl sulfoxide-water

Article abstract of DOI:10.1081/SCC-120004082

Ketones react with [hydroxy(tosyloxy)iodo]benzene in dimethyl sulfoxide-water to afford α-hydroxyketones under neutral conditions and in good yields.

Full text of DOI:10.1081/SCC-120004082

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HYPERVALENT IODINE IN SYNTHESIS. 78.
DIRECT α-HYDROXYLATION OF KETONES USING
[HYDROXY(TOSYLOXY)- IODO]BENZENE IN DIMETHYL
SULFOXIDE–WATER
Yuan-Yuan Xie a & Zhen-Chu Chen b
a Department of Chemistry, Zhejiang University (Xi-Xi Campus), Hangzhou, 310028, P.R.
China
b Department of Chemistry, Zhejiang University (Xi-Xi Campus), Hangzhou, 310028, P.R.
China
Version of record first published: 17 Oct 2011.
To cite this article: Yuan-Yuan Xie & Zhen-Chu Chen (2002): HYPERVALENT IODINE IN SYNTHESIS. 78. DIRECT α-
HYDROXYLATION OF KETONES USING [HYDROXY(TOSYLOXY)- IODO]BENZENE IN DIMETHYL SULFOXIDE–WATER, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry, 32:12, 1875-1879
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SYNTHETIC COMMUNICATIONS, 32(12), 1875–1879 (2002)
HYPERVALENT IODINE
IN SYNTHESIS. 78. DIRECT
a-HYDROXYLATION OF KETONES
USING [HYDROXY(TOSYLOXY)-
IODO]BENZENE IN DIMETHYL
SULFOXIDE–WATER
*
Yuan-Yuan Xie and Zhen-Chu Chen
Department of Chemistry, Zhejiang University
(Xi-Xi Campus), Hangzhou, 310028, P.R. China
ABSTRACT
Ketones react with [hydroxy(tosyloxy)iodo]benzene in
dimethyl sulfoxide–water to afford ꢀ-hydroxyketones under
neutral conditions and in good yields.
The conversion of enolizable ketones to their corresponding ꢀ-hydro-
xyderivatives is an important synthetic transformation and has received a
great deal of attention.[1] Recently, there has been considerable interest in
the development of direct methods for the synthesis of ꢀ-hydroxyketones
using nontoxic hypervalent iodine reagents, which involve (a) ketones react
with iodobenzene diacetate in the presence of potassium hydroxide in
methanol to give ꢀ-hydroxyketone dimethyl acetals and hydrolysis of
the dimethyl acetals yield the ꢀ-hydroxyketones;[2] (b) enol silyl ethers of
*Corresponding author.
1875
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1876
XIE AND CHEN
acetophenones are oxidized using the system iodosobenzene/boron trifluor-
ide etherate/water in methylene chloride at ꢀ40ꢁC;[3] (c) ketones react with
[bis(trifluoroacetoxy)]iodobenzene and trifluoroacetic acid in CH3CN/H2O
under acidic conditions.[4]
In connection with our programs to utilize hypervalent iodine com-
pounds in organic synthesis, we wish to report a convenient method of
conversion of ketones to the corresponding ꢀ-hydroxyketones through
treatment of ketones with [hydroxy(tosyloxy)iodo]benzene (HTIB, 2) in
dimethyl sulfoxide–water under neural conditions. It is known that enoliz-
able ketones react with HTIB in acetonitrile to give ꢀ-tosyloxylketones.[5]
We have now found that the reaction, when carried out in dimethyl sulf-
oxide–water, affords only ꢀ-hydroxyketones in good yields without the for-
mation of ꢀ-tosyloxyketones. In fact, simle stirring the mixture of ketones
and HTIB in DMSO–H2O at room temperature for 8 h gave, after work up
and isolation, the desired ꢀ-hydroxyketones (Scheme 1). The results are
summarized Table 1.
We found that the variation of the ratio of water to DMSO from 5/100
to 15/100 does not significantly alter the final yields (Entries 1,2,3). The
reaction was found to be general and applicable to aromatic or hetero-
aromatic ketones. Several aromatic ketones containing various substituents.
Such as para-chloro, para-methyl, para-methoxy were successfully reacted.
However, aliphatic ketones, such as cyclohexanone or 3-pentanone under
similar reaction conditions did not give corresponding ꢀ-hydroxyketones.
We observed under similar reaction conditions the ꢀ-tosyloxyaceto-
phenone does not be converted into ꢀ-hydroxyacetophenone. So, we believe
the ꢀ-tosyloxyketones are not probably the intermediates of the reaction. A
reasonable pathway (Scheme 2) for the ꢀ-hydroxylation involves an initial
ligand exchange by the enolic form of the ketones (1) with a tosyloxy ligand
of [hydroxy(tosyloxy)iodo] benzene to give intermediate A. Step A to 3 can
occur through displacement of the hypervalent iodine moiety by water to
yield the ꢀ-hydroxyketone (3).
Scheme 1.

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HYPERVALENT IODINE IN SYNTHESIS. 78
Table 1. Synthesis of ꢀ-Hydroxyketones (3a)
1877
Yieldb
(%)
M.P.c
(ꢁC)
Lit. M.P.
(ꢁC)
Entry
R1
R2
Product
1
C6H5
C6H5
C6H5
p-CH3C6H4
p-CH3OC6H4
p-ClC6H4
p-BrC6H4
C6H5
H
H
H
H
H
H
H
CH3
C6H5
3a
3a
3a
3b
3c
3d
3e
3f
59
80–82
86–87[3]
[3]
2d
3e
4
–826080 86–87
–826080 86–87
[3]
65
46
69
63
43
39
81–83
99–101
118–120122.4
134–136
Oil
89–90[6]
5
6
7
8
100[7]
[8]
136.6[8]
Oil[9]
129[10]
9
C6H5
3g
126–128
10
H
3h
58
79–81
82–83[3]
a. Reaction was carried out in DMSO (10ml) and H 2O (0.5 ml) at room temperature
for 8 h.
b. Isolated yield based on ketone.
c. Melting points were uncorrected.
d. DMSO : H2O ¼ 10: 1.0.
e. DMSO : H2O ¼ 10: 1.5.
Scheme 2.

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1878
XIE AND CHEN
In conclusion, we have provided a new, effective method for synthesis
of ꢀ-hydroxyketones under neutral conditions. It has some advantages over
previous methods, such as simple procedure, neutral reaction conditions and
good yields.
EXPERIMENTAL SECTION
IR spectra were recorded as KBr pellets on VECTOR-22 Infrared
Spectrophotometer. 1H-NMR spectra were recorded on BRUCKER-
400 Hz Spectrometer using CDCl3 as the solvent with TMS as an internal
standard.
Typical Procedure for Synthesis of
2-Hydroxy-1-phenyl Ethanone (3a)
Acetophenone (0.12 g, 1 mmol) and HTIB (0.47 g, 1.2 mmol) were
added successively with efficient stirring to dimethyl sulfoxide (10ml)–
water (0.5 ml). The reaction mixture was stirred at room temperature for
eight hours. Then, the reaction mixture was poured into ice-water and
extracted with ether (3 ꢂ 15 ml); the extracts were washed with water
(2 ꢂ 5 ml) and dried with anhydrous magnesium sulfate. After removal
of the solvent under reduced pressure, the crude product was purified by
preparative TLC (ether/petroleum ether ¼ 1 : 1.5) to obtain 3a (0.08 g, 59%
yield) as white solide.
Spectroscopic Data
3a: IR (cmꢀ1) 3432 (O-H), 1683 (C¼O). 1H-NMR, ppm: ꢁ 2.90(s, 1H),
4.90(s, 2H), 7.50–7.95 m, 5H).
3b: IR (cmꢀ1) 3432 (O-H), 1680(C ¼O). 1H-NMR, ppm: ꢁ 2.44 (s, 3H),
3.31 (s, 1H), 4.86 (s, 2H), 7.30–7.84 (q, 4H).
3c: IR (cmꢀ1) 3418 (O-H), 1673 (C¼O). 1H-NMR, ppm: ꢁ 3.42 (s, 1H),
3.89 (s, 3H), 4.83 (s, 2H), 6.97–7.92 (q, 4H).
3d: IR (cmꢀ1) 3426 (O-H), 1680(C ¼O). 1H-NMR, ppm: ꢁ 3.45 (s, 1H),
4.86 (s, 2H), 7.48–7.88 (q, 4H).
3e: IR (cmꢀ1) 3426 (O-H), 1682 (C¼O). 1H-NMR, ppm: ꢁ 3.28 (s, 1H),
4.86 (s, 2H), 7.65–7.81 (q, 4H).
1
3f: IR (cmꢀ1) 3447 (O-H), 1684 (C¼O). H-NMR, ppm: ꢁ 1.45–1.47
(d, 3H), 3.84 (s, 1H), 5.15–5.20(q, 1H), 7.49–7.95 (m, 5H).

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HYPERVALENT IODINE IN SYNTHESIS. 78
1879
3g: IR (cmꢀ1) 3419 (O-H), 1718 (C¼O). 1H-NMR, ppm: ꢁ 3.90(s, 1H),
5.97 (s, 1H), 7.27–7.93 (m, 10H).
3h: IR (cmꢀ1) 3425 (O-H), 1680(C ¼O). 1H-NMR, ppm: ꢁ 2.82 (s, 1H),
4.75 (s, 2H), 6.60–7.64 (m, 3H).
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Received in the Netherlands April 6, 2001