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Applied Catalysis A: General
Origin of the rate enhancement and enantiodifferentiation in the heterogeneous
enantioselective hydrogenation of 2,2,2-trifluoroacetophenone over Pt/alumina
studied in continuous-flow fixed-bed reactor system
György Szo˝ llo˝ sia, Szabolcs Cserényib, Imre Bucsib, Tibor Bartókc, Ferenc Fülöpd, Mihály Bartóka,b,∗
a Stereochemistry Research Group of the Hungarian Academy of Sciences, Dóm tér 8, H-6720 Szeged, Hungary
b Department of Organic Chemistry, University of Szeged, Dóm tér 8, H-6720 Szeged, Hungary
c Faculty of Engineering, University of Szeged, P.O. Box 433, H-6701 Szeged, Hungary
d Institute of Pharmaceutical Chemistry, University of Szeged, Eötvös u 6, H-6720 Szeged, Hungary
a r t i c l e i n f o
a b s t r a c t
Article history:
A study on the origin of rate enhancement and enantiodifferentiation in the enantioselective hydrogena-
tion of 2,2,2-trifluoroacetophenone (TFAP) over a Pt/alumina catalyst modified by cinchona alkaloids in
toluene/acetic acid (AcOH) solvent mixture with and without trifluoroacetic acid (TFA) using continuous-
flow fixed-bed reactor system is presented. The experimental data of the racemic – cinchona 1–cinchona
2–cinchona 1 hydrogenation series confirm the intrinsic nature of rate enhancement, namely the so-
called “ligand acceleration” phenomenon. Hydrogenation in the presence of 0.1% (v/v) TFA follows the
general rule of the Orito reaction, according to which the products formed in excess are (R)-alcohols
on Pt-cinchonidine and Pt-quinine and (S)-alcohols on Pt-cinchonine and Pt-quinidine chiral catalysts.
In toluene/AcOH mixture without TFA, unexpected inversion took place on the Pt-cinchonine and Pt-
quinidine catalysts since the (R)-product formed in excess instead of the (S)-product. The observed
unexpected inversion can be interpreted on the basis of the nucleophilic intermediate complex. Based on
these observations we propose that in the hydrogenation of TFAP the reaction route involves the equi-
librium of electrophilic and nucleophilic intermediate complexes, which was found to be dependent on
the acid strength and concentration.
Received 10 March 2010
Received in revised form 29 April 2010
Accepted 5 May 2010
Available online 13 May 2010
Keywords:
Asymmetric hydrogenation
Platinum
Cinchona alkaloids
Trifluoroactophenone
Continuous-flow fixed-bed reactor
Origin of rate enhancement
Origin of enantiodifferentiation
© 2010 Elsevier B.V. All rights reserved.
1. Introduction
in the enantioselective heterogeneous catalytic hydrogenation
of activated ketones under the Orito reaction conditions using
Among the most studied heterogeneous catalytic enantioselec-
tive hydrogenations are the hydrogenations of ketones and -keto
esters over tartaric acid modified Ni and the hydrogenations of acti-
vated ketones over cinchona alkaloid modified Pt (the so-called
Orito reaction). The most significant results obtained in these
reactions have been reviewed several times [1–8]. As a result of
extensive studies, nowadays, in both enantioselective hydrogena-
tions over 90% enantiomeric excess (ee) may be attained [3]. The
main objective of recent studies on the Orito reaction (Scheme 1)
has been to expand its field of utilization, to elucidate the reaction
mechanism and to interpret the origin of enantiodifferentiation and
rate enhancement in this context.
continuous-flow fixed-bed reactor over Pt catalyst modified with
parent cinchona alkaloids was presented. To avoid repetition, we
simply refer to Section 1 of our latest report [9], where the sig-
nificance of this research, its status and future research objectives
were discussed in detail. Here we only outline recent results on the
Orito reaction to demonstrate the present state of the art of this
area.
The recent research has mainly been focused on a better
understanding of the reaction mechanism. New information has
been presented on the relationship between modifier structure
(their adsorption modes), the substrates and enantiodifferentia-
tion [10–15] and between the rates of enantioselective and racemic
hydrogenation [16–19]. Addressing the structure of the interme-
diate responsible for chiral induction has greatly contributed to
the clarification of the mechanism of enantioselective hydrogena-
tion and the origin of chiral induction [12,14,20–23]. Recognition
and further investigation of the unexpected inversions of enan-
tioselectivity (reversal of the sense of the ee as compared with
the generally accepted one) in certain conditions also gave new
The results described here represent the continuation of our pre-
vious work [9] in which a study on the origin of rate enhancement
∗
Corresponding author at: Department of Organic Chemistry, University of
Szeged, Dóm tér 8, H-6720 Szeged, Hungary.
0926-860X/$ – see front matter © 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.apcata.2010.05.003