Synthesis of stilbenes via homocoupling of aryl aldehyde tosylhydrazones

Article abstract of DOI:10.1016/S0040-4039(01)00859-0

Stilbenes are readily prepared in good yields via homocoupling of aryl aldehyde tosylhydrazones in the presence of lithium tert-butoxide and trimethyl borate under reflux in THF.

Full text of DOI:10.1016/S0040-4039(01)00859-0

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 42 (2001) 4759–4760
Synthesis of stilbenes via homocoupling of aryl aldehyde
tosylhydrazones
George W. Kabalka,* Zhongzhi Wu and Yuhong Ju
Departments of Chemistry and Radiology, The University of Tennessee, Knoxville, TN 37996-1600, USA
Received 3 May 2001; accepted 16 May 2001
Abstract—Stilbenes are readily prepared in good yields via homocoupling of aryl aldehyde tosylhydrazones in the presence of
lithium tert-butoxide and trimethyl borate under reflux in THF. © 2001 Elsevier Science Ltd. All rights reserved.
Stilbenes are important synthetic precursors to phenan-
threne alkaloids as well as enantiomerically pure 1,2-
diphenylethanes, 1,2-diamines, and diols. They also are
used as optical brighteners and therapeutic agents for
liver disorders. A number of methods have been devel-
oped for the preparation of stilbenes based on Wittig-
type reactions,1 reductive coupling of carbonyl
compounds,2 self-coupling of a-lithiated benzylic sul-
fones,3 and condensations of aldehyde tosylhydrazones
with stabilized carbanions.4 More recently, Katritsky
and co-workers reported a new procedure for the syn-
thesis of stilbenes via reaction of aldehyde tosylhydra-
zones with benzotriazole-stabilized carbanions.5
excellent yields of stilbenes (Table 1). It should be
noted that the successful reaction of the tosylhydrazone
of 4-nitrobenzaldehyde (entry 11) required refluxing in
DME. Interestingly, aryl aldehyde tosylhydrazones
containing electron-withdrawing functionality such as
the cyano and nitro groups afforded trans-stilbenes as
major products. These reactions proceeded relatively
slowly.
Although a detailed mechanistic study has not been
carried out, the reaction presumably proceeds via the
formation of an aryl carbene intermediate as shown
in Scheme 2. Trimethyl borate reacts with the lith-
ium tosylate (which precipitates from the reaction
mixture) and thus prevents the tosylate from reacting
with the aryl carbene intermediate. In fact, benzyl
4-methylphenylsulfone has been observed in the reac-
tion of all aryl aldehyde tosylhydrazones with lith-
ium tert-buto2xide in the absence of trimethyl borate,
which led to the low yields of stilbenes. In order to
confirm the existence of a carbene intermediate, 4-
methylstyrene was added to a mixture of 4-methylben-
zaldehyde tosylhydrazone, lithium t-butoxide and
trimethyl borate to trap the carbene intermediate. As
expected, 1,2-di-(4-methylphenyl)cyclopropane was iso-
lated. Stoichiometric quantities of lithium tert-butoxide
and trimethyl borate are required to produce high
yields of stilbenes.
During our investigation of the alkylation of aryl alde-
hyde tosylhydrazones with trialkylboranes and alkyl-
boron chlorides,6 we discovered that reactions involving
alkylboron chlorides produced stilbenes rather than
alkylation products. To our knowledge, the formation
of stilbenes via homocoupling of aryl aldehyde tosylhy-
drazone has not been reported. Since this method pro-
vides
a simple and inexpensive method for the
preparing stilbenes, we investigated the reaction in the
presence of various boron compounds. It was found
that trimethyl borate induced excellent yields of stilbene
products (Scheme 1).
A series of aryl aldehyde tosylhydrazones were sub-
jected to the reaction sequence. Essentially, all gave
N NH Ts
B(OMe)3, t-BuOLi
THF, Reflux
X
X
X
Scheme 1.
* Corresponding author.
0040-4039/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0040-4039(01)00859-0

4760
G. W. Kabalka et al. / Tetrahedron Letters 42 (2001) 4759–4760
Table 1. Synthesis of stilbenes via aryl aldehyde tosylhy-
to gentle reflux for 6 h. The mixture is then cooled,
hydrolyzed, the organic phase separated and dried
(anhydrous MgSO4). Removal of solvent under reduced
pressure followed by silica gel column chromatography
with hexanes as eluent produces an 82% yield of
stilbene.
drazones
Entry
X (Scheme 1) Reaction time Ratio
Yielda,b
(h)
(trans/cis)
1
2
3
4
5
6
7
8
H
4-F
4-Cl
4-Br
3-Br
2-Br
4-Me
4-MeO
3-MeO
2-MeO
4-NO2
4-CN
6
10
8
7
7
7
5
5
5
48/52
49/51
58/42
52/48
46/54
40/60
57/43
48/52
40/60
50/50
91/9
82
87
87
83
80
85
81
83
88
79
84
88
In conclusion, the homocoupling of aryl aldehyde tosyl-
hydrazones in the presence of trimethyl borate and
lithium tert-butoxide provides a simple, inexpensive,
and efficient route to stilbenes, including stilbenes con-
taining electron-withdrawing functional groups.
9
10
11
12
5
12
10
Acknowledgements
99/1
a Isolated yield of both trans and cis isomers.
The authors would like to thank the US Department of
Energy and the Robert H. Cole Foundation for support
of this research.
b The physical properties and spectral characteristics of all products
were consistent with literature values.
.. ..
....
-
Li +
t-BuOLi
[ArCH N N Ts]
ArCH NNHTs
..
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..
∆
+ N2
.
[Ar CH]
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The synthesis of stilbene is representative: benzaldehyde
tosylhydrazone (3 mmol) is dissolved in 20 mL of dry
THF in a dry, argon-flushed, round-bottomed flask
equipped with a reflux condenser and stirring bar.
Trimethyl borate (3.0 mmol) is then added via syringe
followed by lithium tert-butoxide (3.0 mmol, 1.0 M
solution in hexanes) and the reaction mixture is heated
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