A convenient method for the synthesis of electron-rich phosphonates

Article abstract of DOI:10.1016/j.tetlet.2003.08.110

Very electron-rich benzylic-type phosphonates can be prepared by treating the corresponding alcohols in triethyl phosphite with one equivalent of iodine at an appropriate temperature in a general one-pot process.

Full text of DOI:10.1016/j.tetlet.2003.08.110

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 7989–7992
A convenient method for the synthesis of electron-rich
phosphonatesꢀ
Shijun Zheng, Stephen Barlow, Timothy C. Parker and Seth R. Marder*
Department of Chemistry, University of Arizona, Tucson, AZ 85721-0041, USA†
Received 21 August 2003; accepted 27 August 2003
Abstract—Very electron-rich benzylic-type phosphonates can be prepared by treating the corresponding alcohols in triethyl
phosphite with one equivalent of iodine at an appropriate temperature in a general one-pot process.
© 2003 Elsevier Ltd. All rights reserved.
The growing interest in organic materials for nonlinear-
optical, electronic and opto-electronic applications has
led to the development of many new p-conjugated
molecules.1 One of the most important reactions uti-
lized to synthesize these types of molecules is the
Horner–Emmons condensation of an aldehyde with a
phosphonate to form an alkene with exclusively trans
stereochemistry.2 The general method to synthesize a
phosphonate from the corresponding alcohol typically
involves two steps: (i) conversion of the alcohol to a
halide; (ii) the Michaelis–Arbuzov reaction of the halide
with a trialkyl phosphite for several hours at high
temperature (Scheme 1).3 This two-step procedure has
drawbacks for very electron-rich benzylic-type alcohols
such as 4-(diarylamino)benzyl alcohols and metallo-
cenyl alcohols, which are potentially useful building
blocks for electron-rich conjugated molecules. In partic-
ular, preparation of the halides can be complicated by
oxidative or electrophilic side-reactions, and isolation
of halides can be complicated by covalent/ionic
equilibria.
sion of 4-(dialkylamino)-benzylic alcohols to the corre-
sponding 4-(dialkylamino)-benzyl chloride hydro-
chloride salts by refluxing the alcohol in concentrated
aqueous HCl; reflux of this product in triethyl phos-
phite gives the corresponding phosphonate (Scheme 2).4
However, this method is unsuccessful with 4-(diaryl-
amino)benzylic alcohols, which are extremely weak
Brønsted bases at the nitrogen center. The method is
also not applicable to ferrocenylmethanol and
octamethylferrocenylmethanol; under acidic conditions
these are converted to the corresponding carbocations
which then readily undergo dimerization reactions.5
We have found a very simple general one-pot method
to convert electron-rich benzylic-type alcohols to phos-
Scheme 1.
These complications can be avoided in some cases by
rendering the aromatic ring electron deficient through
protonation. A method has been described for conver-
ꢀ Supplementary data associated with this article can be found at
doi:10.1016/j.tetlet.2003.08.110
* Corresponding author. Tel.: 404-385-6048; fax: 404-894-7452;
e-mail: seth.marder@chemistry.gatech.edu
† Current address: School of Chemistry and Biochemistry, Georgia
Institute of Technology, Atlanta, GA 30332-0400, USA.
Scheme 2.
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.08.110

7990
S. Zheng et al. / Tetrahedron Letters 44 (2003) 7989–7992
and their solubility in triethyl phosphite. For the less
electron-rich benzylic alcohols (entries 8 and 9) the
present method does not show significant advantages
over the traditional method of Scheme 1; the substi-
tution of the presumed iodide intermediate with tri-
ethyl phosphite does not appear to proceed as rapidly
at room temperature as for the more electron-rich
examples.
An example of the application of the electron-rich
phosphonates, synthesized by the method described
here, to the synthesis of conjugated materials is illus-
trated in Scheme 4. Compound 12 has a structural
motif that is anticipated to show interesting two-pho-
ton absorbing properties.8
Scheme 3.
phonates by treating the alcohols in triethyl phosphite
with one equivalent of iodine at an appropriate tem-
perature (Scheme 3). Presumably [(EtO)3PI]+[I]− and/
or (EtO)2P(O)I are intermediates, since triethyl
phosphite is known to form these species rapidly on
reaction with iodine, even at low temperatures.6
In summary, we have discovered a convenient high-
yielding method for making very electron-rich ben-
zylic-type phosphonates, which are otherwise difficult
to make.
Supporting information available. Experimental proce-
dures, and characterizing data for entries 1–11 and
for the preparation of compounds 12 and 13.
The scope of the method was tested by examination
of a broad range of substrates (Table 1). This method
not only renders the preparation of entries 1 and 5
possible (the preparation of these types of phospho-
nates has not been reported in literature) and pro-
vides a more convenient route to 4b,7 but also has
the advantage that this one-pot reaction often pro-
ceeds at room temperature, which is useful for the
synthesis of more complex electron-rich benzylic
phosphonates that might not be stable at the elevated
temperatures required for typical Michaelis–Arbuzov
reactions. The rates of these reactions are highly
dependent on the electron-richness of the substrates
Acknowledgements
This work was supported by the United States Gov-
ernment through the National Renewable Energy
Laboratory, Department of Energy (NREL grant
ACQ-13061901), and the STC Program of the
National Science Foundation (grant No. DMR
0120967).
Scheme 4.

S. Zheng et al. / Tetrahedron Letters 44 (2003) 7989–7992
Table 1. Summary of the applicability of the method
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S. Zheng et al. / Tetrahedron Letters 44 (2003) 7989–7992
J. Am. Chem. Soc. 1990, 112, 7578.
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