Convenient one-pot synthesis of trans-1,2-diaryloxiranes from the direct coupling of benzyl halides

Article abstract of DOI:10.1016/j.tetlet.2010.10.075

trans-1,2-Diaryloxiranes were conveniently prepared in an one-pot reaction by the direct coupling of benzyl halides in the presence of silver oxide and DMSO under mild conditions.

Full text of DOI:10.1016/j.tetlet.2010.10.075

Tetrahedron Letters 51 (2010) 6649–6650
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Convenient one-pot synthesis of trans-1,2-diaryloxiranes from the direct
coupling of benzyl halides
⇑
Freeman M. Wong, Yee Man Chan, David X. Chen, 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:
trans-1,2-Diaryloxiranes were conveniently prepared in an one-pot reaction by the direct coupling of
benzyl halides in the presence of silver oxide and DMSO under mild conditions.
Ó 2010 Elsevier Ltd. All rights reserved.
Received 22 September 2010
Revised 6 October 2010
Accepted 12 October 2010
Available online 19 October 2010
1. Introduction
tion intermediate. The reaction does not work with benzyl bromide
derivatives with strong electron-withdrawing groups such as nitro
Epoxides or oxiranes are an important class of chemicals and
their reactions and synthesis have been extensively discussed.1–3
In this Letter, we present an unusual direct coupling reaction of
benzyl halides to form symmetrically substituted trans-1,2-diary-
loxiranes in the presence of silver oxide (Ag2O) and DMSO under
or cyano groups.
The reactions were conveniently carried out by stirring the
reaction mixture overnight at room temperature. Upon completion
of the reaction, the resulting mixture was centrifuged, decanted,
and concentrated to give the epoxides as reasonably pure crude
products. The epoxides were further purified through flash chro-
matography using hexane (or a hexane/methylene chloride mix-
ture) as solvent. As shown in Table 1, the epoxides were
obtained in moderate yield. All epoxides were identified as the
trans-isomer by their NMR spectra.5
The above results have demonstrated that benzyl bromide
derivatives can be directly coupled to form trans-epoxide. The
one-pot reaction is conveniently carried out and can be of interest
if symmetrically substituted 1,2-diaryloxiranes are desired.
mild conditions.
R
Br
DMSO, Ag2O
O
R
R
Previously we reported a convenient method for the conversion
of benzyl halides into aldehydes and ketones in the presence of
Ag2O and pyridine N-oxide.4 When DMSO was employed instead
of pyridine N-oxide as the source of oxygen, it was noted that
the reaction with benzyl bromide gave a mixture of products.4
An epoxide, trans-stilbene oxide, was isolated from the product
mixture. Further experiments with DMSO as the solvent have led
to the development of the current method. The overall reaction in-
volves the unusual coupling of the benzylic carbon to form the
trans-1,2-diaryloxirane as the main product.
The reactions were carried out in DMSO. One equivalent of sil-
ver oxide was utilized to facilitate the reaction. Silver oxide pre-
sumably assists the heterolysis of the carbon–halogen bond and
also functions as a base. The reaction mechanism is yet to be illus-
trated and awaits further investigation. However, a small amount
of cross-coupling product was isolated when p-chlorobenzalde-
hyde was added to the reaction of benzyl bromide with silver oxide
and DMSO, indicating possible involvement of aldehyde as a reac-
2. Experimental details
All reagents were obtained from commercial sources and used
without further purification.
2.1. Typical experimental procedure
Silver oxide (0.68 g, 2.9 mmol) was added to a solution of ben-
zyl bromide (0.50 g, 2.9 mmol) in anhydrous DMSO (5 mL) in a
Table 1
Coupling of benzyl bromide derivatives to epoxides
Entry
Benzyl bromide derivatives
Yield (isolated) (%)
1
2
3
7
4
5
6
R = H
R = p-Br
R = o-Cl
R = 2-Cl-4-F
R = p-CO2CH3
R = m-CO2CH3
R = p-CF3
48
43
48
52
58
57
48
⇑
Corresponding author. Tel.: +1 415 338 1436; fax: +1 415 338 2384.
E-mail address: wuw@sfsu.edu (W. Wu).
0040-4039/$ - see front matter Ó 2010 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2010.10.075

6650
F. M. Wong et al. / Tetrahedron Letters 51 (2010) 6649–6650
round-bottommed flask. The resulting mixture was stirred over-
night under nitrogen. The reaction mixture was centrifuged, dec-
anted, and concentrated to give the crude product. The product
was purified by flash chromatography using hexane as the solvent
(0.14 g, 48%). The product was identified to be trans-stilbene oxide
by comparison of its NMR spectrum and melting point to that of an
authentic sample.5
oratory. We are indebted to Professor Ihsan Erden (SFSU) for help-
ful discussions.
References and notes
1. Smith, M. B.; March, J. March’s Advanced Organic Chemistry. Reactions,
Mechanisms and Structure, 5th ed.; Wiley: NewYork, 2001.
2. Erden, I. Monocyclic Oxiranes and Oxirenes In Comprehensive Heterocyclic
Chemistry II; Katritzky, A. R., Rees, C. W., Scriven, E. F. V., Eds.; Pergamon: New
York, 1997; Vol. 1A, Ch. 1.03,.
3. Erden, I. Oxiranes and Oxirenes: Fused Ring Derivatives In Comprehensive
Heterocyclic Chemistry II; Katritzky, A. R., Rees, C. W., Scriven, E. F. V., Eds.;
Pergamon: New York, 1997; Vol. 1A, Ch. 1.04,.
Acknowledgments
This investigation was supported by the National Institutes of
Health, MBRS SCORE Program—Grant #5 S06 GM52588. The NMR
facility was funded by the National Science Foundation (DUE-
9451624 and DBI 0521342). Initial experiments were carried out
by Chi M. Ho, Q. Y. Rudy Wu, Peter R. Wu, and Lili Wong in our lab-
4. Chen, D. X.; Ho, C. M.; Wu, Q. Y. R.; Wu, P. R.; Wong, F. M.; Wu, W. Tetrahedron
Lett. 2008, 49, 4147–4148.
5. Pouchert, C. J.; Behnke, J. The Aldrich Library of 13C and 1H FT-NMR Spectra;
Aldrich: Milwaukee, 1992.