Reversal of the ee in enantioselective hydrogenation of activated ketones in continuous-flow fixed-bed reactor system

Article abstract of DOI:10.1016/j.catcom.2010.08.008

A study on the hydrogenation of ethyl pyruvate, methyl benzoylformate and 2,2,2-trifluoroacetophenone over Pt-cinchona alkaloid chiral catalysts and over the "unmodified" catalysts resulted after a cleaning step at 323 K of the chirally modified surfaces in continuous-flow fixed-bed reactor system is presented. According to these investigations the sense of the residual ee observed in the reactions carried out in the absence of modifiers over the catalysts rinsed after the chiral hydrogenations was influenced by the solvent and the structure of the activated ketone, pointing on the effect of these parameters on the structure of the adsorbed intermediate complexes and implicitly on the chiral induction.

Full text of DOI:10.1016/j.catcom.2010.08.008

Catalysis Communications 12 (2010) 14–19
Contents lists available at ScienceDirect
Catalysis Communications
journal homepage: www.elsevier.com/locate/catcom
Reversal of the ee in enantioselective hydrogenation of activated ketones in
continuous-flow fixed-bed reactor system
Szabolcs Cserényi , György Szőllősi , Kornél Szőri , Ferenc Fülöp b,c, Mihály Bartók a,b,
a
b
b
⁎
a
Department of Organic Chemistry, University of Szeged, Dóm tér 8, H-6720 Szeged, Hungary
Stereochemistry Research Group of the Hungarian Academy of Sciences, Dóm tér 8, H-6720 Szeged, Hungary
Institute of Pharmaceutical Chemistry, University of Szeged, Eötvös u 6, H-6720 Szeged, Hungary
b
c
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 22 June 2010
Received in revised form 5 August 2010
Accepted 9 August 2010
Available online 14 August 2010
A study on the hydrogenation of ethyl pyruvate, methyl benzoylformate and 2,2,2-trifluoroacetophenone
over Pt–cinchona alkaloid chiral catalysts and over the “unmodified” catalysts resulted after a cleaning step
at 323 K of the chirally modified surfaces in continuous-flow fixed-bed reactor system is presented.
According to these investigations the sense of the residual ee observed in the reactions carried out in the
absence of modifiers over the catalysts rinsed after the chiral hydrogenations was influenced by the solvent
and the structure of the activated ketone, pointing on the effect of these parameters on the structure of the
adsorbed intermediate complexes and implicitly on the chiral induction.
Keywords:
Asymmetric hydrogenation
Platinum
© 2010 Elsevier B.V. All rights reserved.
Cinchona alkaloids
Activated ketones
Flow reactor
Reversal of ee
1
. Introduction
Enantioselective hydrogenation of activated ketones accompanied
origin for stereo-differentiation in the Orito reaction: Residual chiral
induction and enantiomeric excess reversal during piecewise contin-
uous experiments using a chiral fixed-bed reactor” [19]. This title
aroused the interest of our research group: the ee values reported
were relatively low but, unexpectedly, reversed. In the enantioselec-
tive hydrogenation of ethyl benzoylformate (EBF) over Pt/alumina
modified by cinchonidine (CD) using continuous-flow fixed-bed
reactor system (CFBR), Garland et al. observed that (i) after enantio-
selective hydrogenation of EBF at 273 K, and after cleaning at 273 K, a
racemic “unmodified” hydrogenation could be performed, which
implies effective desorption of chiral species from the surface in the
course of cleaning; (ii) after the same enantioselective hydrogenation
at 273 K, and after a cleaning treatment at 323 K, an “unmodified”
enantioselective hydrogenation was carried out with unexpected
reversal of ee; (iii) in similar experiments with ethyl pyruvate
(EP) and cinchonine (CN) the ee was again reversed; (iv) in EP
hydrogenation over Pt/C and powdered Pt catalysts modified by CD,
residual chiral induction was also detected, but retention of the ee
direction was observed.
Since the relevant CFBR technique was available in our laboratory
[19–21], it seemed expedient to perform similar experiments. In order
to reproduce these unexpected results and to supplement them
with new data, or, if possible, even to obtain information on the
general character of the phenomenon, we studied the enantioselec-
tive hydrogenation of EP, methyl benzoylformate (MBF) and 2,2,2-
trifluoroacetophenone (TFAP) on Pt catalyst modified by the four
parent cinchona alkaloids.
by the formation of chiral alcohols is the most intensively studied
asymmetric heterogeneous catalytic reaction [1,2] (Scheme 1). The
diversity of these studies is most probably explained by the fact
that enantioselectivities (ee) exceeding 90% could be attained with
substrates with a wide structural variety. High enantioselectivities
have not only economic but also theoretical significance: research-
ers in this field are eager to find the explanation for the high ee
attainable under mild, undemanding conditions, using relatively
simple starting materials. Better understanding of the details of
the reaction has been hoped to contribute to the interpretation
of other asymmetric transformations and to studies on the origin
of chiral induction, with special regard to heterogeneous catalytic
reactions. Reviews on the results obtained in studies on the Orito
reaction have been published continuously (e.g. in the last four
years [3–7]).
The subject of many recently published reports has been the origin
of chiral induction [8–18]. However, these reports have not reflected
on the unusual results published in 2006 in an article entitled “A new
⁎
Corresponding author. Department of Organic Chemistry, University of Szeged,
Dóm tér 8, H-6720 Szeged, Hungary. Tel.: +36 62 544279; fax: +36 62 544200.
E-mail address: bartok@chem.u-szeged.hu (M. Bartók).
1566-7367/$ – see front matter © 2010 Elsevier B.V. All rights reserved.
doi:10.1016/j.catcom.2010.08.008

S. Cserényi et al. / Catalysis Communications 12 (2010) 14–19
15
OH
O
OH
H , Pt-alumina
H , Pt-alumina
2
2
O
O
O
R
S
R''
R
R''
R
R
R''
rt, solvent
rt, solvent
3
3
O
O
O
N
S
8
N
OH
H
HO
H
8
R' = H:
cinchonine (CN)
R' = OMe:
R' = H:
cinchonidine (CD)
R' = OMe:
9
R
H
R
R = Me, R" = Et: EP
H
5'
S
9
5'
R' 6'
7'
R
'
4
'
3
'
R = Ph, R" = Me: MBF
3'
2'
4'
6'
7'
quinidine (QD)
quinine (Q)
2'
N
1
N
8'
`
8'
1'
Scheme 1. The Orito reaction.
2
. Experimental
respectively) [27]. The hydrogenation conditions were selected on
the basis of the preliminary experiments and using the earlier
published results [19].
2
.1. Materials
Cinchona alkaloids — CD, CN, quinine (QN) and quinidine (QD),
3.1. Enantioselective hydrogenation of EP
trifluoroacetic acid (TFA), reagents and solvents were purchased from
Aldrich or Fluka, and used as received. EP, MBF and TFAP were
The majority of the experimental data are summarized in Table 1.
The experimental data clearly show that the catalyst is deactivated
by the end of each measurement sequence, with the exception of the
series in 2P. During “unmodified” hydrogenation following desorption
of the chiral modifier, reversal in ee was observed in toluene/AcOH
solvent with one exception (hydrogenation in the presence of
TFA) (entries 1–4) as well as in 2P (entries 6 and 7), similarly to
hydrogenation in EtOH [19]. The conversions obtained in the
enantioselective hydrogenations were higher than in hydrogenations
over “unmodified” catalysts.
distilled using a Vigreaux-column. The catalyst, Engelhard 5% Pt/Al
E4759) was pre-treated in a fixed-bed reactor in H flow at 673 K as
previously described [22].
2 3
O
(
2
2
.2. Hydrogenations in flow system
Continuous hydrogenations were carried in H-Cube high-pressure
continuous-flow system. The experimental set-up has been described
in detail in our previous publication [17]. A typical series of mea-
surements began with pre-hydrogenation of the catalyst and
continued with chiral hydrogenation, followed by desorption of
the chiral modifier using a flow of the same solvent at 323 K and
by hydrogenation on “unmodified” catalyst (racemic hydrogenation).
The measurement series was ended by a second chiral hydrogenation
under conditions identical with those of the first one.
3.2. Enantioselective hydrogenation of MBF
The characteristic experimental data obtained in the hydrogena-
tions of MBF are summarized in Table 2 and examples for the
dependence of conversion and ee versus time on stream are shown in
Fig. 1.
2
.3. Product analysis
In toluene/AcOH solvent mixture, after desorption of the chiral
modifiers CD, CN and QN the hydrogenations over the washed
“unmodified” catalysts yielded racemic products (entries 1–6), unlike
in the case of EP. After desorption of QD reversal of ee was observed
(entry 7). The presence of the strongly acidic TFA also led to the
formation of racemic products (entry 8). Hydrogenation in 2P,
however, produced reversal of ee, similarly to EtOH [19] (entries 9–
14, Fig. 1a,b). Decreasing the concentration of MBF affected our
basic conclusions inasmuch as at [MBF]=11 mM the conversions in
“unmodified” and in first and second modified hydrogenations
were nearly identical (entry 11).
The products were identified by mass spectrometric analysis (HP
890 N GC–HP 5973 MSD, HP-1MS, 60 m capillary column). Conver-
6
sions and enantiomeric excesses, ee%=|[R]−[S]|×100/([R]+[S]),
were determined by gas chromatography (HP 6890 N GC-FID, 30 m
Cyclodex-B chiral capillary column) [23,24]. The reproducibility of the
results was ± 1%.
3
. Results
Measurement series similar to Garland and coworkers' experi-
Pt–QN and Pt–QD do not perform well in the hydrogenation of
MBF in 2P, however these experiments also gave unexpected results
(entries 9, 13, and 14 and Fig. 1c,d). Namely, the first chiral hydro-
genation yielded racemic products, whereas both the “unmodified”
hydrogenation and the following second chiral hydrogenation
produced reversal of ee. In order to reveal the causes underlying
this surprising results, we studied the catalyst pre-treatment in
the presence of QN, hydrogenations in the absence of oxygen or
accompanied by flushing the reaction mixture with air (based on
earlier experiences [28]) and the effect of further reductions in MBF
concentration (entries 13–17). These experiments pointed to the
competition of the modifiers and MBF on the catalyst adsorption sites.
MBF present at concentrations significantly higher than the chiral
modifier inhibits adsorption of the cinchonas with lower adsorption
strength (QN and QD [29,30]), as a consequence the decrease in the
number or lack of chirally active sites on the surface leads to the
formation of racemic products. The data obtained at [MBF]=1.1 mM
ments [19] were carried out to study the enantioselective hydroge-
nation of EP, MBF and TFAP over Pt/Al catalyst modified by
2 3
O
cinchona alkaloids (CD, CN, QN, and QD) in CFBR system. These
experiments were performed under similar conditions as used in the
hydrogenations of other activated ketones, in a toluene/AcOH (9/1)
solvent mixture [17,25] with and without 0.1% (v/v) TFA content and
in 2-propanol (2P). Although AcOH is not a favorable component in
TFAP hydrogenation [25,26], it was used in our CFBR studies due to its
effect to increase the solubility of cinchonas, as in these experiments
higher modifier concentrations are required. We used 2P rather than
EtOH, because of its lower reactivity with the substrates. It was
confirmed already by Orito et al. that there is no significant difference
between the effects of these two solvents on the ee [27]. For example,
in the hydrogenation of EBF over Pt–CD catalyst the ee values attained
were 36.5% in EtOH and 47.3% in 2P (in the hydrogenation of
methyl pyruvate 83.2% and 80.6% ees were obtained in these solvents,

16
S. Cserényi et al. / Catalysis Communications 12 (2010) 14–19
Table 1
Conversions and ees obtained in the enantioselective hydrogenation of EP in CFBR.
a
Entry
Modifier
Solvent
[EP]
mM)
Hydrogenations
st modified
(
1
“unmodified”
2nd modified
Cb
eec
C
ee
C
ee
1
2
3
4
5
6
7
CD
CN
QN
QD
CD
CD
CN
T/AcOH
T/AcOH
T/AcOH
T/AcOH
T/AcOHd
2P
45
45
45
45
11
11
11
60
60
85
70
97
98
90
50 R
40 S
70 R
43 S
90 R
28 R
10 S
30
20
30
40
33
96
88
7 Se
40
30
60
45
87
98
90
45 R
48 S
67 R
43 S
87 R
23 R
5 S
e
5 R
e
6 S
e
5 R
13 R
e
2 S
e
2P
11 R
a
2 3 2
Reaction conditions: 40 mg Pt/Al O , 4 MPa H , 293 K, [modifier] = 0.044 mM, in situ desorption of the modifier between the first modified and “unmodified” hydrogenations by
rinsing with the solvent at 293 K 60 min, 323 K 60 min and 293 K 30 min, respectively.
b
Conversion (%).
c
Enantiomeric excess (%) and absolute configuration of the major enantiomer.
In the presence of 0.1% (v/v) TFA.
Reversed sense of the ee over rinsed catalyst without added modifier.
d
e
(
entries 18–21) are quite surprising: the formation of racemic
It was already clear from our batch reactor and CFBR studies that in
the Orito reaction, TFAP does not follow the general rule according
to which C8(S) C9(R) cinchonas (CD and QN) favor the formation of
(R)-alcohols, whereas C8(R) C9(S) cinchonas (CN and QD) promote
the formation of (S)-alcohols in excess [24]. It is also known that in
the presence of TFA, i.e. in highly acidic medium, hydrogenation over
Pt–CN chiral catalyst yields the expected (S)-alcohol in excess [32], as
also confirmed in the present study (entry 6).
products over the “unmodified” catalyst proceeds at a higher rate
than does the subsequent second chiral hydrogenation (entries 14, 17,
1
interpretation needs further studies, since rate acceleration was
occasionally replaced by rate deceleration [31].
8, and 21). There may be several reasons for this phenomenon; its
3
.3. Enantioselective hydrogenation of TFAP
According to these experimental data (Table 3), in the hydro-
genations of TFAP in various solvents over the “unmodified” catalyst
formed in the course of the desorption of the chiral modifier,
The experimental data obtained in the hydrogenations of TFAP can
be seen in Table 3.
Table 2
a
Conversions and ees obtained in the enantioselective hydrogenation of MBF in CFBR.
Entry
Modifier
Solvent
Catalyst
mg)
[MBF]
(mM)
Hydrogenations
(
1
st modified
Cb
99
“unmodified”
2nd modified
eec
C
ee
C
ee
1
2
3
4
5
6
7
8
9
CD
CD
CD
CD
CN
QN
QD
CD
CD
CD
CD
CN
QN
QD
T/AcOH
T/AcOH
T/AcOH
T/AcOH
T/AcOH
T/AcOH
T/AcOH
T/AcOH
2P
2P
2P
2P
2P
50
50
50
50
50
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
20
45
45
45
11
11
11
11
11
45
22
11
11
11
11
11
11
11
1.1
1.1
1.1
1.1
45
45
95 R
95 R
94 R
90 R
69 S
47 R
3 S
82 R
55 R
51 R
55 R
25 S
0
0
10 S
0
0
42 R
11 S
55
74
70
58
75
20
23
40
44
63
76
55
57
60
60
55
60
84
75
84
95
44
74
0
0
0
0
99
87
96
88
85
30
25
32
65
72
78
58
56
50
58
56
53
75
76
88
80
40
25
95 R
93 R
93 R
95 R
55 S
46 R
7 S
82 R
54 R
45 R
39 R
17 S
98
90
100
97
40
35
56
72
81
78
53
55
50
60
55
53
84
69
80
60
d
0
4 R
5 R
0
11 S
16 S
7 S
12 R
10 S
6 R
5 S
6 S
5 S
0
4 R
0
0
i
e
i
i
10
11
12
13
14
15
16
17
18
19
20
21
22
23
i
i
i
i
15 S
7 Ri
20 S
15 S
13 S
42 R
9 S
i
2P
f
i
QN
2P
g
QN
QN
CD
CN
QN
QD
QN
QD
2P
h
2P
2P
2P
2P
2P
2P
2P
i
i
i
13 S
7 R
12 R
4 R
27 S
7 Ri
3 R
i
i
5 S
9 R
i
i
7 Ri
27
a
2
Reaction conditions: 4 MPa H , 293 K, [modifier] = 0.44 mM, in situ desorption of the modifier between the first modified and “unmodified” hydrogenations by rinsing with the
solvent at 293 K 60 min.
b
Conversion (%).
c
Enantiomeric excess (%) and absolute configuration of the major enantiomer.
In situ desorption of the modifier 2 hours at 50°C.
In the presence of 0.1% (v/v) TFA.
Catalyst pre-treated with QN.
Using deoxygenated solutions.
d
e
f
g
h
i
Oxygen was bubbled through the solutions before use.
Reversed sense of the ee as compared to expected one based on the configuration of the modifier used in the chiral hydrogenation.

S. Cserényi et al. / Catalysis Communications 12 (2010) 14–19
17
(
a)
(b)
8
7
6
5
4
3
2
1
0
0
0
0
0
0
0
0
0
60
(
%)
(%)
50
40
CN
CD
without
CN
without
30
modifier
R
modifier
R
2
1
0
0
0
CD
0
20
40
100
120
140
160
180
-
-
10
20
S
0
20
40
100
120
140
160
180
S
-10
Time on stream (min)
-30
Time on stream (min)
(
c)
(d)
6
5
4
3
2
1
0
0
0
0
0
0
0
70
60
50
40
30
20
(
%)
(%)
R
QN
without
QN
modifier
R
without
QD
QD
modifier
1
0
0
0
20
40
100
120
140
160
180
-
-
10
20
0
20
40
1
00
120
140
160
180
S
Time on stream (min)
Time on stream (min)
Fig. 1. The conversions (○) and ees (●) as a function of time on stream in the enantioselective hydrogenation of MBF over Pt–CD (a), Pt–CN (b), Pt–QN (c) and Pt–QD (d) catalysts in
-propanol (see Table 2 for conditions).
2
formation of the products having reversed sense of the ee as
compared with the first chiral hydrogenation was not observed.
This means that the conversions of the three activated ketones (EP,
MBF, and TFAP) during their enantioselective hydrogenations
under nearly identical conditions take significantly different routes.
presence of TFA in similar hydrogenations; (ii) similarly to (i), reversal
in ee was also observed in 2P over the “unmodified” versions of Pt–CD
and Pt–CN catalysts in EP hydrogenation; (iii) “unmodified” hydroge-
nation of MBF yielded racemic products in toluene/AcOH both in the
absence and in the presence of TFA; in 2P, however, reversal in ee was
observed; and (iv) in the hydrogenation of TFAP over “unmodified”
catalysts the sense of enantioselection was not changed relative to the
modified catalysts (Table 4).
4
. Discussions
4
.1. Summary of the new results
Based on the new experimental observations summarized in
Table 4 it can be established that the phenomenon recognized by
Garland et al. [19] may not be generalized to the enantioselective
hydrogenation of activated ketones. Namely, in the case of MBF a
significant solvent effect can be observed (there is no effect in
toluene/AcOH), and the phenomenon does not manifest at all in the
TFAP hydrogenation.
Based on the unexpected results reported by Garland et al., we
carried out further studies using systematically varied experimental
conditions. Experiments were performed using Pt/Al catalyst
2 3
O
modified by each of the four parent cinchonas, using EP, MBF and
TFAP as substrates in 2P and toluene/AcOH as solvents (occasionally
in the presence of TFA). The most important, so far unpublished
findings of these experiments were the following: (i) reversal in ee
was observed over the so-called “unmodified” catalysts (obtained by
previous modification and subsequent desorption of the cinchonas) in
the enantioselective hydrogenation of EP in toluene/AcOH solvent
mixture, while no change was observed in the sense of ee in the
4.2. Interpretation of the residual chiral induction
As regards the interpretation of the phenomenon recognized in the
present study, the explanation proposed by Garland et al. based on
their pertinent experimental data can be agreed: ee reversal in the

18
S. Cserényi et al. / Catalysis Communications 12 (2010) 14–19
Table 3
Conversions and ees obtained in the enantioselective hydrogenation of TFAP in CFBR.
a
Entry
Modifier
Solvent
Catalyst
mg)
[TFAP]
(mM)
pH
(MPa)
2
Hydrogenations
st modified
(
1
“unmodified”
2nd modified
Cb
eec
C
ee
C
ee
1
2
3
4
5
6
7
8
9
CD
CD
CD
CD
CN
CN
QN
QD
CD
CN
QN
QD
T/AcOH
T/AcOH
T/AcOH
T/AcOHd
T/AcOH
T/AcOHd
T/AcOH
T/AcOH
2P
100
50
20
50
100
50
100
100
50
50
50
45
11
11
11
45
11
45
45
11
11
11
11
10
40
10
40
10
40
10
10
20
20
20
20
54
35
16
30
43
25
38
18
71
85
52
62
42 R
25 R
18 R
50 R
14 R
15S
27 R
5 R
12
8
3
9
14
7
11
16
66
80
74
77
0
0
0
0
2 R
0
2 R
0
10 R
2 R
5 R
1 R
20
25
7
35 R
15 R
18 R
48 R
9 R
10S
17 R
4 R
13
24
10
22
17
71
73
70
55
13 R
7 R
0
13 R
3 R
0
10
11
12
2P
2P
2P
50
6 R
3 R
a
2
Reaction conditions: 1 MPa H , 283 K, [modifier]=0.44 mM, in situ desorption of the modifier between the first modified and “unmodified” hydrogenations by rinsing with the
solvent at 323 K 60 min.
b
Conversion (%).
c
Enantiomeric excess (%) and absolute configuration of the major enantiomer.
In the presence of 0.1% (v/v) TFA at 293 K under 4 MPa H .
2
d
Table 4
Reversal of the ee (*) in the enantioselective hydrogenations of EP, MBF and TFAP over
morphology of the metal particles, in other words metal atoms of
the surface participate in chiral induction. Irreversible adsorptions
detected mainly in the case of CD represent experimentally verified
interactions [28,33–36], which may be not only spectators but also
relevant species [37].
Pt/Al
2
O
3
“unmodified” catalysts.
In toluene/AcOH (9/1)
In 2-propanol
Using TFAa
CD
CN
QN
QD
CD
CN
QN
QD
CD
CN
EP
MBF
TFAP
*
–
*
–
*
–
*
*
*
*
*
*
–
–
–
–
There are no experimental data published on the examination of
the quantity and quality of the organic residues adsorbed irreversible
*
–
*
–
–
–
–
–
–
–
–
(
chemisorbed) on the surface of the catalysts used in CFBR experi-
a
In toluene/AcOH (9/1) in the presence of 0.1% (v/v) TFA.
ments. For this reason elemental analysis of the catalyst was carried
out to obtain information on the chemisorbed organic materials. The
Pt–CD catalyst used in the hydrogenation of MBF in 2P after cleaning
1 h at 323 K contained 1.50 wt.% C and 0.06 wt.% N (similarly as
observed previously by examining the catalyst used in batch reactor
[38]). Since the only source of N is the modifier and the commercial
CD contains up to ~8% QD the chemisorbed compounds can be
attributed to CD, QD and their decomposition products. Thus, one
could suppose that the reason of the inversion in the ee is the QD
present in the commercial CD, as due to its “tilted” adsorption QD can
be hydrogenated slower than the flatly adsorbed CD. However, the
results presented in Fig. 1d contradicted this assumption.
“
2 3
unmodified” hydrogenation over Pt/Al O can be explained by a
superposition of two more or less irreversible modifications of the
surface during the 323 K cleaning phase. One is associated with a
more or less irreversible change of the Pt surface and a minor ee
retention effect, and the other modification is associated with the
presence of the alumina support leading to predominant ee reversal
effect [19].
Nevertheless, our data pointing to the role of the solvent effect and
of the structure of the substrate to be hydrogenated also call attention
to the effect of the structure of adsorbed intermediate complexes (ICs)
on chiral induction (Scheme 2). Naturally, this also means that chiral
induction is dependent (among other factors) on the surface
However, the hydrogenated derivatives of CD are desorbed easier
from the surface [31,39–42]. According to our experimental results
X
C
O
X
X
R
X
O
N
+
+
C
O
+
N
H
O
C
N
H
H
C
R
N
R
R
A
HO
B
QH
C
D
+
N
8
8
H
O
O
C
C
OMe
N
X
O
H
H
H
Pt
C
R
H
Me
Ph
9
9
HO
Q
O
E
F
+
N
+
N
H
O
C Ph
8
H
F
CF2
H
HC
O
F3C
CF3
H
H
O
C
9
HO
H
O
C
O
Q
G
H
Scheme 2. Proposed intermediate complexes adsorbed on Pt in the enantioselective hydrogenation of EP, MBF and TFAP (X = activating group, R = Me or Ph, Q = quinolinyl):
A [3,18,39–41], B [3,18,39–41], C [42], D [44], E [43], F [28], G [11,24], H [24,45].

S. Cserényi et al. / Catalysis Communications 12 (2010) 14–19
19
[
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30 (2008) 5386–5387.
during the reductive regeneration of the catalyst at 323 K the chem-
isorbed cinchonas cannot be removed (see section 2.2, Tables 1–3).
When the solvent contained AcOH one may not neglect the formation
(
[
1
from the Pt/Al
MS [22,44–46] and their effect on the hydrogenation. The continuous
reconstruction of the surface of the Pt/Al under the conditions of
2 3
O of acetates and other compounds identified by ESI-
[
[
12] T.A. Martinek, T. Varga, F. Fülöp, M. Bartók, J. Catal. 246 (2007) 266–276.
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2 3
O
the Orito reaction [28,33–35,43,47–49] may affect the sense of the
enantioselection, which besides the unexpected experimental results
presented in Fig. 1c,d makes necessary further investigation of the
phenomenon.
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(
[
15] A. Urakawa, D.M. Meier, H. Rugger, A. Baiker, J. Phys. Chem. A 112 (2008)
7250–7255.
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[
[
17] Gy. Szőllősi, Sz. Cserényi, F. Fülöp, M. Bartók, J. Catal. 260 (2008) 245–253.
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5
. Conclusion
[
[
[
[
19] F. Gao, L. Chen, M. Garland, J. Catal. 238 (2006) 402–411.
20] Y. Zhao, F. Gao, L. Chen, M. Garland, J. Catal. 221 (2004) 274–284.
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A large variety of hypothetic structures of surface ICs potentially
responsible for enantiodifferentiation (ED) are shown in Scheme 2
for EP, MBF and TFAP [3,11,18,24,28,50–57]. In addition to kinetic
studies, various spectroscopic techniques have also been successfully
applied to study the IC structure and the mechanism of the Orito
reaction [11–13,39,40], particularly to find explanations for the
unexpected inversions detected in these systems (see review in [8]).
Direct experimental identification of the ICs presented in Scheme 2
under the conditions of the Orito reaction is at present impossible.
Complexes A and B, and to a lesser extent complex C are generally
accepted for the interpretation of the enantioselective hydrogenation
of activated ketones in protic solvents. In the case of non-protic
solvents, complexes of type D cannot be excluded either (in addition
to A and B). The role of complexes E, G, and H in ED has been proposed
recently. Type F complexes may develop on the most active surface
atoms (kink and adatom) by irreversible adsorption (chemisorption).
Pt–cinchona complexes produced by chemisorption may have an
important role in the phenomenon described in ref. [19]. They are
converted to products on surface sites not identical with the original
ones, formed after desorption at 323 K, via ICs with structures
determined by the structure of the ketone to be hydrogenated.
As a final note: what the authors defined as “a new origin for
stereo-differentiation in the Orito reaction” in [19] is indeed a new
phenomenon; in our opinion, however, it can hardly be considered to
be an Orito reaction, since hydrogenation takes place after desorption
of the chiral modifier at 323 K, i.e. in the absence of the modifier.
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(
[
(
(
[
1
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[
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[
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B 110 (2006)
Financial support by the Hungarian National Science Foundation
OTKA Grant K 72065) is highly appreciated. The project was
2
(
[
supported by the János Bolyai Research Scholarship of the Hungarian
Academy of Sciences (Gy. Sz.).
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