Convenient oxidation of benzylic and allylic halides to aldehydes and ketones

Article abstract of DOI:10.1016/j.tetlet.2008.04.124

Benzylic and allylic halides were conveniently oxidized to aldehydes and ketones by pyridine N-oxide in the presence of silver oxide under mild conditions.

Full text of DOI:10.1016/j.tetlet.2008.04.124

Tetrahedron Letters 49 (2008) 4147–4148
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Tetrahedron Letters
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Convenient oxidation of benzylic and allylic halides to aldehydes and ketones
David X. Chen, Chi M. Ho, Q. Y. Rudy Wu, Peter R. Wu, Freeman M. Wong, Weiming Wu *
Department of Chemistry and Biochemistry, San Francisco State University, San Francisco, CA 94132, United States
a r t i c l e i n f o
a b s t r a c t
Article history:
Benzylic and allylic halides were conveniently oxidized to aldehydes and ketones by pyridine N-oxide in
the presence of silver oxide under mild conditions.
Received 6 March 2008
Revised 10 April 2008
Accepted 22 April 2008
Available online 24 April 2008
Ó 2008 Elsevier Ltd. All rights reserved.
1
. Introduction
HO—
H
H
H
H
R
X•••••Ag O
2
Aldehydes and ketones, especially aromatic and a,b-unsaturated
N+
N+
—O
H
R
O
carbonyl compounds, are important classes of chemicals. Methods
for direct conversion of halides to carbonyl compounds have been
1
,2
reviewed. Dimethyl sulfoxide (DMSO) is often employed as the
3
,4
3,4
oxygen donor. However, high temperature is usually required.
+
5
–7
Oxidations involving amine oxides have also been reported.
In
R
O
N
our attempt to modify carbohydrates with benzylic halides, we
have found that pyridine N-oxide can effectively and conveniently
oxidize benzylic and allylic halides to aromatic and a,b-unsaturated
Scheme 1.
carbonyl compounds, respectively, in the presence of silver oxide
(
the resulting mixture was filtered through a thin layer of Celite.
Concentration of the filtrate gave essentially pure product in quan-
Ag
2
O) under mild conditions.8
,9
1
0
The reactions were carried out in acetonitrile (toluene and
titative yield. Further purification, when desired, consisted of
filtering the crude product through a short column of silica gel
with methylene chloride as the solvent. Pyridine by-product was
removed by initial washing of the loaded column with hexane.
The percent yields shown in Table 1 refer to the isolated yields of
the purified products and are generally good.
The above results have demonstrated that pyridine N-oxide is
an efficient oxidizing agent for the conversion of benzylic and
allylic halides to aromatic and a,b-unsaturated aldehydes and
ketones, respectively. The reaction can be applied to benzylic
halides with both electron-donating and -withdrawing substi-
tuents. The reaction described here is thus a useful and convenient
alternative to existing methods for oxidation of benzylic and allylic
halides to conjugated carbonyl compounds.
tetrahydrofuran gave much lower yield). The reaction mechanism
should be identical to that proposed for the reaction with DMSO
and base, as shown in Scheme 1.1 Half equivalent of silver oxide
was utilized to facilitate the reaction. Silver oxide assists the
heterolysis of the carbon–halogen bond in the substitution reac-
tion with pyridine N-oxide. The resulting hydroxide ion from the
reaction between silver oxide and halogen then functions as the
base in the elimination reaction to produce the carbonyl group.
When DMSO was employed instead of pyridine N-oxide as the
source of oxygen, the reaction did not go to completion while
giving a mixture of products.
,8
For most bromides, the reactions were conveniently carried out
at room temperature. The reaction was complete in a few hours
but was stirred overnight for convenience. For chlorides and some
benzyl bromides with very strong electron-withdrawing substitu-
ents, slightly elevated temperature (50 °C) was required (Table 1,
entries 4–7 and 12–15). For some chlorides, only partial conversion
was observed (entries 13 and 14). The substituent effects indicate a
2
. Experimental
All reagents were obtained from commercial sources and used
without further purification. The reactions were run in a nitrogen
atmosphere.
S
N
1-like mechanism for the first step in the reaction pathway.
The reaction workup was very simple. Upon completion of the
reaction, sodium sulfate or magnesium sulfate was added and
2
.1 Typical experimental procedure
Silver oxide (0.68 g, 2.93 mmol) was added to a solution of
benzyl bromide (1.00 g, 5.85 mmol) and pyridine N-oxide (0.56 g,
5.85 mmol) in acetonitrile (10 mL) in a round-bottomed flask.
*
Corresponding author. Tel.: +1 415 338 1436; fax: +1 415 338 2384.
E-mail address: wuw@sfsu.edu (W. Wu).
0
040-4039/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2008.04.124

4
148
D. X. Chen et al. / Tetrahedron Letters 49 (2008) 4147–4148
Table 1
Reduction of benzylic and allylic halides with pyridine N-oxide in CH
3
CN
Entry
Substrate
Product
Temperature (°C)
Yield (isolated, %)
CHO
Br
R
R
1
2
3
4
5
6
7
R = H
R = p-Br
25
25
25
50
50
50
50
82
80
81
84
80
86
86
R = p-CO
2
CH
3
R = m-CN
R = p-CN
R = m-NO
R = p-NO
2
2
CHO
Br
Br
8
9
25
25
95
84
Br
O
CHO
CHO
1
0
1
25
25
85
85
Br
O
1
Cl
1
1
1
1
2
3
4
5
50
50
50
50
92
MeO
MeO
MeO
MeO
CHO
CHO
Cl
74a
75b
95
Cl
Cl
O N
2
O N
2
CHO
a
The yield is based on 71% converted starting material.
The yield is based on 50% converted starting material.
b
The resulting mixture was stirred overnight under nitrogen.
Sodium sulfate or magnesium sulfate was added to the reaction
and the resulting mixture was filtered through a thin layer of
Celite. The flask and funnel were rinsed with ethyl acetate. Concen-
tration of the combined filtrate gave a slightly yellow oil. The crude
product was loaded on a short column of silica gel, which was
eluted with hexane to remove pyridine by-product and then with
methylene chloride. The methylene chloride solution was concen-
trated to yield a clear oil (0.51 g, 82%). The product was identified
by comparison of its NMR spectrum to that of an authentic
References and notes
1.
For a review on direct conversion of halides to aldehydes and ketones, see:
Smith, M. B.; March, J. March’s Advanced Organic Chemistry. Reactions,
Mechanisms, and Structure, 5th ed.; Wiley: New York, 2001; pp 1535–1536.
2. For another review on direct conversion of halides to aldehydes and ketones
see: Larock, R. C. Comprehensive Organic Transformations; Wiley: New York,
1999. pp 1222–1223.
3.
Kornblum, N.; Jones, W. J.; Anderson, G. J. J. Am. Chem. Soc. 1959, 81, 4113–
4114.
4. Nace, H. R.; Monagle, J. J. J. Org. Chem. 1959, 24, 1792–1793.
5.
6.
7.
8.
(a) Franzen, V.; Otto, S. Chem. Ber. 1961, 94, 1360–1363; (b) Franzen, V. Org.
Synth. Coll. Vol. V 1955, 872–874.
Suzuki, S.; Onoshi, T.; Fujita, Y.; Misawa, H.; Otera, J. Bull. Chem. Soc. Jpn. 1986,
1
0
sample.
5
9, 3287–3288.
Mukaiyama, S.; Inanaga, J.; Yamagauchi, M. Bull. Chem. Soc. Jpn. 1981, 54, 2221–
222.
Acknowledgments
2
Alkaline decomposition of pyridinimium salts have been discussed: (a) Ochiai,
E.; Katada, M.; Naito, T. J. Pharm. Soc. Jpn. 1944, 64, 210–214; (b) Katritsky, A. R.
J. Chem. Soc. 1956, 2404–2408; (c) Feely, W.; Lehn, W. L.; Boekelheide, V. J. Org.
Chem. 1957, 22, 1135; (d) Silwa, H.; Tartar, A. J. Org. Chem. 1976, 41, 160–
This investigation was supported by the National Institutes of
Health, MBRS SCORE Program—Grant #5 S06 GM52588 and by a
grant from the Center for Computing for Life Sciences at SFSU.
Mr. Q. Y. R. Wu was supported by Project SEED of the American
Chemical Society. We are indebted to Mr. Wee Tam at SFSU for
obtaining the NMR spectra. The NMR facility was funded by the
National Science Foundation (DUE-9451624 and DBI 0521342).
We thank Dr. Ihsan Erden (SFSU) for helpful discussions.
163.
9. Microwave-assisted reactions of substituted benzyl bromide with pyridine N-
oxide have been reported, but the yields were poor for some bromides: Barbry,
D.; Champagne, P. Tetrahedron Lett. 1996, 37, 7725–7726.
1
0. All products have NMR spectra identical to those of authentic samples. They
can be found in: The Aldrich Library of 13C and
1
H FT-NMR Spectra; Pouchert, C.
J., Behnke, J., Eds.; Aldrich: Milwaukee, 1992.