Conversion of alcohols to bromides using a fluorous phosphine

Article abstract of DOI:10.1016/j.tetlet.2003.08.064

Reaction of alcohols with the fluorous phosphine-carbon tetrabromide complex in toluene or in a two-phase toluene-FC-72 system afforded the corresponding bromides in good yields. The fluorous-phosphine oxide is readily separated by liquid-liquid extraction, providing an alternative to the homogeneous triphenylphosphine-carbon tetrachloride conversion, as well as to the polymer-supported phosphine method. The fluorous phosphine oxide could be reduced and the product reused.

Full text of DOI:10.1016/j.tetlet.2003.08.064

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 7589–7591
Conversion of alcohols to bromides using a fluorous phosphine
Laurence Desmaris, Nathalie Percina, Louis Cottier and Denis Sinou*
Laboratoire de Synth e` se Asym e´ trique, associ e´ au CNRS, Universit e´ Claude Bernard Lyon 1, CPE Lyon, 43,
boulevard du 11 novembre 1918, 69622 Villeurbanne c e´ dex, France
Received 3 July 2003; revised 9 August 2003; accepted 18 August 2003
Abstract—Reaction of alcohols with the fluorous phosphineꢀcarbon tetrabromide complex in toluene or in a two-phase
toluene-FC-72 system afforded the corresponding bromides in good yields. The fluorous-phosphine oxide is readily separated by
liquid–liquid extraction, providing an alternative to the homogeneous triphenylphosphine–carbon tetrachloride conversion, as well
as to the polymer-supported phosphine method. The fluorous phosphine oxide could be reduced and the product reused.
©
2003 Elsevier Ltd. All rights reserved.
The conversion of alcohols to halides is a well-docu-
mented transformation. One of the most widely used
Among the most recent reagents used in organic syn-
1
6
thesis are fluorous tin hydrides, fluorous allyltin
7
8
reagents is the triphenylphosphine–carbon tetrabromide
reagents, fluorous organoselenium reagents, fluorous
2
9
10
complex. However, one of the main drawbacks of this
phosphines, fluorous DEAD reagents, as well as
fluorous-protecting groups.
11
reagent is the formation of a stoichiometric amount of
triphenylphosphine oxide; the work-up of the reaction
is sometimes problematic due to the difficulty in com-
pletely removing this oxide from the reaction products.
Different approaches have been developed in order to
circumvent this problem and to find new technologies
Following our interest in the use of fluorous phosphines
9c
as reagents for cleaner synthesis, we present in this
communication their application in the conversion of
alcohols to bromides using the fluorous triphenylphos-
phine–carbon tetrabromide system in stoichiometric
amounts (Scheme 1). In order to show the usefulness of
this methodology, the reaction of various alcohols with
for cleaner synthesis of bromides. One solution is the
3
use
of
polymer-supported
triphenylphosphine.4
Recently Pollastri et al. used diphos as the phosphine;
performing the reaction in THF allowed the complete
conversion of the alcohol to the corresponding bro-
mide, with the subsequent precipitation of the diphos
oxide which was readily removed by simple filtration.
CBr in the presence of tris[4-(1H,1H-perfluorooctyl-
4
12
oxyphenyl)]phosphine was performed in a monopha-
sic system using toluene as the solvent, and in the
biphasic system toluene-FC-72 (FC-72 being a mixture
of fluorous hexanes). As a reference, the reaction was
Since the pioneering work of Horvath and Rabai in
5
also performed in toluene using CBr /PPh using
1
994, fluorous biphasic chemistry has found many
4
3
applications in the field of catalysis, as well as in
organic chemistry. This is due mainly to the easy purifi-
cation or removal of fluorous compounds by a simple
liquid–liquid extraction or a liquid–solid separation.
exactly the same conditions. Some results using typical
alcohols are shown in Table 1. We chose toluene as the
non-fluorous solvent since the highest conversion of
octanol to octyl bromide with PPh /CBr was obtained
3 4
Scheme 1.
Keywords: fluorous triphenylphosphine; tetrabromomethane; fluorous solvent; recycling.
*
Corresponding author. Tel.: 33 (0)4 72 44 81 83; fax: 33 (0)4 78 89 89 14; e-mail: sinou@univ-lyon1.fr
0
040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2003.08.064

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L. Desmaris et al. / Tetrahedron Letters 44 (2003) 7589–7591
a
Table 1. Conversion of alcohols to bromides using CBr –fluorous triphenylphosphine
4
using this solvent: 60, 32 and 53% conversions were
observed using toluene, acetonitrile, and diethyl ether
Asexpected, theadvantageofthismethodologyisthevery
easy separation of the fluorous phosphine oxide from the
reaction products. At the end of the reaction, the mixture
was cooled and extracted twice with FC-72. Evaporation
of the fluorous solvent gave more than 85% of the starting
phosphine oxide which was readily reduced quantitatively
(
reflux, 4 h), respectively.
The results contained in Table 1 indicated that bromi-
nation occurred efficiently at 50°C using toluene or the
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to the fluorous phosphine, and so could be reused. It
is to be noted that no traces of phosphine oxide could
be detected in the bromide, by NMR.
two-phase toluene-FC-72 as the solvent. The conver-
sion of a primary alcohol such as octanol (entry 1), or
a tertiary alcohol such as triethylcarbinol (entry 3), to
the corresponding bromide was the same, whatever the
conditions used. The conversion obtained using the
fluorous phosphine in toluene or in the two-phase
system toluene-FC-72 competed well with the usual
reagent PPh –CBr in toluene. Surprisingly, the conver-
In conclusion, bromination of alcohols using fluorous
phosphine-CBr as the reagent can be easily performed
4
in toluene or in a two-phase toluene-FC-72 system. This
method offers a very attractive procedure for the separa-
tion of the resulting bromide from the phosphine oxide
by a simple liquid–liquid extraction, and is an alternative
to the standard triphenylphosphine–carbon tetrabromide
conversion, aswellastothepolymer supported phosphine
reagents. This fluorous phosphine oxide could also be
recycled, after reduction.
3
4
sion of octan-2-ol (entry 2) was almost quantitative
using the biphasic system, but only 54 and 60% in
toluene using the fluorous and the non-fluorous phos-
phine, respectively.
Bromination of (R)-menthol (entry 4) afforded the
corresponding bromide quantitatively, whatever the
conditions used. This bromide exhibited a specific rota-
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