Dimerization of resveratrol trimethyl ether by phosphotungstic acid, structure confirmation of resformicol A and B

Article abstract of DOI:10.1016/j.tetlet.2012.04.132

Dimerization of the trimethyl ether of resveratrol catalyzed by phosphotungstic acid gave two tetralins and a naphthalene derivative. The structure of the tetralins was obtained by X-ray crystallography and confirms the reported stereochemical configuration of resformicol A and B.

Full text of DOI:10.1016/j.tetlet.2012.04.132

Tetrahedron Letters 53 (2012) 3521–3523
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Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Dimerization of resveratrol trimethyl ether by phosphotungstic acid,
structure confirmation of resformicol A and B
⇑
Matthew C. Davis , Thomas J. Groshens
Chemistry & Materials Division Naval Air Warfare Center, China Lake, CA 93555, USA
a r t i c l e i n f o
a b s t r a c t
Article history:
Dimerization of the trimethyl ether of resveratrol catalyzed by phosphotungstic acid gave two tetralins
and a naphthalene derivative. The structure of the tetralins was obtained by X-ray crystallography and
confirms the reported stereochemical configuration of resformicol A and B.
Published by Elsevier Ltd.
Received 13 April 2012
Revised 25 April 2012
Accepted 29 April 2012
Available online 3 May 2012
Keywords:
Resveratrol trimethyl ether
Phosphotungstic acid
Tetralins
Dimerization
Phenols are useful since they can be made into a wide variety of
polymers encompassing a broad range of properties.1 In thermo-
setting materials such as phenol/formaldehyde (Bakelite ),
found that 1 would undergo reaction with phosphotungstic acid in
chlorocarbon solvent without the need for any support or drying of
the commercial hydrate, Scheme 2. However, the reaction was
much slower than reported (two hours) requiring twelve hours
in refluxing 1,2-dichloroethane (bp 83 °C) for complete consump-
tion of the starting material. It was a surprise to discover the major
product obtained from the reaction mixture in modest yield (43%)
was the naphthalene derivative 7, confirmed by X-ray analysis. It
Ò
2
increasing the number of phenolic sites also increases the crosslink
3
density resulting, ultimately, in a material with greater strength.
As part of a project to develop new polyphenolic compounds from
which to make polymers, dendrimers, and aerogels, we briefly de-
4
scribe here some studies into the acid-catalyzed dimerization of
0
the natural product resveratrol trimethyl ether (trans 3,4 ,5-tri-
was initially unclear how such a product could have formed before
5
13
methoxystilbene, 1). Resveratrol and its family of oligomers are
finding the recent report of Song et al.
who inadvertently
currently of interest owing to their potential therapeutic applica-
tions. The present work only addresses a minute structural subset
synthesized 7 by a curious iodine-catalyzed dimerization of
6
0
0
14
2,3 ,4,5 -tetramethoxystilbene. Evidently, under the present reac-
tion conditions, dimerization of 1 must have led to a tetralin ring
system which underwent subsequent elimination of two
of the wider field of resveratrol oligomers and the reader is direc-
ted to these more elegant synthetic studies for further
7
15
information.
equivalents of anisole to give the naphthalene derivative 7.
The synthesis of 1 is shown in Scheme 1. Exhaustive methyla-
Further experiments were conducted in order to provide support
tion of
a
-resorcylic acid (2) with dimethyl sulfate gave ester 3 in
for this hypothesis. When the dimerization of 1 was performed in
8
excellent yield. Carboxylic ester reduction by lithium aluminum
hydride provided the benzyl alcohol 4. Chlorination of the alcohol
9
with thionyl chloride gave 5 which by Michaelis–Arbuzov reac-
tion with triethyl phosphite gave the key phosphonate intermedi-
1
0
11
ate 6. Finally, Horner–Wadsworth–Emmons reaction of 6 and
p-anisaldehyde using potassium tert-butoxide as base gave 1 in
6
1 % overall yield over the five steps.
It was shown by Alesso et al.12 that stilbene derivatives will
dimerize to indanes and/or tetralins by silica-supported heteropoly
acids of group VI metals such as molybdenum and tungsten. It was
Scheme 1. Reagents and conditions: (a) K
2
CO
3
, SO
2
(OMe)
2
, acetone, reflux; (b) LAH,
⇑
Corresponding author. Tel.: +1 760 939 0196; fax: +1 760 939 1617.
E-mail address: matthew.davis@navy.mil (M.C. Davis).
THF, 0 °C; (c) SOCl
KOtBu, THF, reflux.
2
, pyridine, Et
2
O, 0 °C; (d) P(OEt)
3
, reflux; (e) p-anisaldehyde,
0
040-4039/$ - see front matter Published by Elsevier Ltd.
http://dx.doi.org/10.1016/j.tetlet.2012.04.132

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M. C. Davis, T. J. Groshens / Tetrahedron Letters 53 (2012) 3521–3523
Scheme 2. Dimerization of 1 by phosphotungstic acid.
Figure 1. Crystal structures of tetralins 8 and 9.
components formed in the dimerization reaction of 1 which will
require more intense chromatographic scrutiny. It should also be
mentioned that similar reaction of resveratrol itself could not be
run owing to its poor solubility in non-polar solvents. Further re-
search on this topic, in addition to results from polymerization
studies of the resformicols, will be the subject of a future
communication.
Chart 1. Relative configuration and nomenclature of the hexamethyl ethers of
resformicol A and B. (corresponding isomers not shown).
Acknowledgment
Financial support through an In-house Laboratory Independent
Research award from the Office of Naval Research is gratefully
acknowledged.
refluxing chloroform (bp 61 °C), the reaction was further slowed
down (24 h reflux) and one major new spot was observed by
thin-layer chromatography (TLC) with only a small amount of 7
present. Careful chromatography of the product mixture gave what
appeared to be a single component by TLC but was found to contain
two substances in virtually a 1:1 ratio by 1H NMR. A portion was
subjected to fractional crystallization from hexanes which sepa-
rated the two products and X-ray structural analysis showed them
to be the new tetralin derivatives 8 and 9, Figure 1.16 Tetralins 8 and
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2012.04.132.
References and notes
9
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