1294
LETTER
Hexafluoroisopropanol: A Powerful Solvent for the Hydrogenation of
Functionalized Aromatic Compounds
H
ydrogenation
a
of
F
unctio
b
nalized Aro
i
atic
C
e
ompounds nne Fache,* Olivier Piva
Laboratoire de Chimie Organique, Photochimie et Synthèse, Université Claude Bernard Lyon I, UMR CNRS 5181, Bât. Raulin,
43 bd du 11 Novembre 1918, 69622 Villeurbanne Cedex, France
Fax +33(4)72448136; E-mail: fache@univ-lyon1.fr
Received 24 February 2004
case of phenylethanol type compounds (entries 4–6). In
Abstract: Various substituted aromatic compounds have been
methanol, reduction of 5a takes 100 hours to go to com-
pletion whereas only 7 hours is necessary in HFIP. More-
reduced under H2 using RuCl3. The fluorous solvent hexafluoro-
isopropanol turned out to be particularly efficient in the case of
over, in HFIP the reduction becomes possible under less
than 2 bars of hydrogen but requires longer reaction times.
This could be interesting for sensitive molecules. We first
explained this low reactivity by the electron withdrawing
effect of the CF3 group. We therefore tested compound 4a
and found that in methanol, 44% conversion to hydroge-
nated product is obtained whereas 100% conversion is
achieved in HFIP. We thus assume that the low reactivity
of phenylethanol derivatives is due to the formation of an
OH-p hydrogen bond.12 Methanol is not strong enough to
break this intramolecular bond and the adsorption-desorp-
tion rate on the ruthenium particles was low due to steric
and/or electronic effects. In the case of HFIP, which can
form stronger H bonds than other alcohols,13 intermolec-
ular hydrogen bonds between the substrate and the solvent
are preferred. The substrate can thus approach the metal
particles easily and therefore the reduction rate increases.
To support this hypothesis, we performed several NMR
experiments (Figure 1). In CDCl3, we observe a shift of
0.0757 ppm for the protons in the a-position of the OH
group when we add 2 equivalents of HFIP to the phenyle-
thanol 5a. Addition of the same amount of methanol led
to almost no shift (0.0141 ppm). At the same time, the sig-
nal of the aromatic protons was modified by solvent effect
and the peaks were sharper with HFIP than with methanol
or in the case of phenylethanol alone. These data are in
agreement with the formation of hydrogen bond between
HFIP and OH of the phenylethanol and a breakage of the
OH-p bond. Moreover, the methylether of 5a (compound
7a) was easily hydrogenated whatever the solvent (meth-
anol or HFIP).
compounds difficult to reduce in organic solvents.
Key words: hydrogenation, aromatic compounds, ruthenium,
fluorous media, hexafluoroisopropanol
The reduction of aromatic compounds is an important
chemical process which gives access to valuable fine
chemicals.1 Numerous methods have been published so
far, among them the Birch method,2 the use of sodium
borohydride–rhodium chloride,3 homogeneous or hetero-
geneous hydrogenation4 and recently, the use of ionic liq-
uids.5 Colloidal systems have also been developed by
different groups using either biphasic water-liquid
systems6 or aqueous-supercritical fluid media.7 These par-
ticles are well characterized thanks to numerous tech-
niques now available.8 In 1995, one of us published the
hydrogenation of aromatic compounds with colloidal ru-
thenium metal stabilized with trioctylamine (TOA) in
methanol–water.9 This method was stereoselective (main-
ly cis-products) and above all chemoselective. Neverthe-
less, it was inefficient in some cases. Taking into account
the high solubility of hydrogen in hexafluoroisopropanol
(HFIP),10,11 we performed the hydrogenation of substitut-
ed aromatic compounds in this solvent. The use of TOA
and water was still necessary to ensure the formation and
stability of colloidal particles.
In a typical procedure, substrate (2 mmol), TOA (0.168
mmol, 59.4 mg) and RuCl3 (2.4%/substrate, 10 mg, 0.048
mmol), were dissolved in the media (HFIP–H2O: 2.1
mL:0.9 mL) and stirred under 50 bar H2 at room tempera-
ture for the requisite time. The reaction mixture was
passed through silica and analyzed by NMR. Results are
summarized in Table 1.
As for the stereoselectivity, cis-isomers are always the
1
major products (structure assignments by H NMR, 19F
NMR and GC-MS analyses).14
In all cases, isolated yields are good (>70%). As for the
chemoselectivity, the ester function remains untouched
(entries 1, 2) as do the ether function (entries 3 and 7) and
the CF3 group (entries 5 and 6). Phenol derivatives (en-
tries 2 and 3) are reduced more rapidly in HFIP than in
methanol but this effect is much more important in the
In summary, we have shown that HFIP is a good solvent
for the reduction of aromatic compounds. It is compatible
with ether and ester functionalities, the CF3 group, and is
particularly suitable for compounds which can form OH-
p intramolecular hydrogen bonds, and to a lesser extent to
phenol derivatives.
SYNLETT 2004, No. 7, pp 1294–1296
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Advanced online publication: 10.05.2004
DOI: 10.1055/s-2004-825603; Art ID: D05304ST
© Georg Thieme Verlag Stuttgart · New York
Fache, Fabienne
