Enantioselective hydroformylation of 2- and 4-substituted styrenes with PtCl2[(R)-BINAP] + SnCl2‘in situ’ catalyst

Article abstract of DOI:10.1016/j.jorganchem.2016.10.013

Two sets of styrenes possessing various substituents either in ortho or para position were hydroformylated in the presence of ‘in situ’ catalyst formed from PtCl₂[(R)-BINAP] and tin(II) chloride. The reversal of the absolute configuration of the preferred enantiomers was observed using both sets of substrates by the variation of the reaction temperature in the range of 40–100 °C. In case of the 4-substituted styrenes, the reversal temperature of the enantioselectivity shows correlation with the Hammett substituent constants, i.e., with the electron donor or electron acceptor properties of the para-substituents. This phenomenon was explained by the reversible formation of the Pt-branched alkyl intermediates, leading to the corresponding (R)- and (S)-enantiomers of 2-arylpropanals. Strong substituent effect on the regioselectivity was observed in the hydroformylation of 2-substituted styrenes: the presence of substituents characterised by larger steric parameter resulted in the highly favoured formation of the linear aldehyde. For instance, regioselectivities of 45%, 22% and 7% towards branched aldehyde were obtained with styrene, 2-fluoro- and 2-bromostyrene, respectively, at 80 °C reaction temperature. In addition to the characteristic change of regioselectivity, the reversal of absolute configuration as a function of reaction temperature was also observed.

Full text of DOI:10.1016/j.jorganchem.2016.10.013

Accepted Manuscript
Enantioselective hydroformylation of 2- and 4-substituted styrenes with PtCl [(R)-
2
BINAP] + SnCl ‘in situ’ catalyst
2
Péter Pongrácz, László Kollár
PII:
S0022-328X(16)30460-0
DOI:
10.1016/j.jorganchem.2016.10.013
JOM 19657
Reference:
To appear in: Journal of Organometallic Chemistry
Received Date: 3 August 2016
Revised Date: 28 September 2016
Accepted Date: 5 October 2016
Please cite this article as: P. Pongrácz, L. Kollár, Enantioselective hydroformylation of 2- and 4-
substituted styrenes with PtCl [(R)-BINAP] + SnCl ‘in situ’ catalyst, Journal of Organometallic
2
2
Chemistry (2016), doi: 10.1016/j.jorganchem.2016.10.013.
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ACCEPTED MANUSCRIPT
Enantioselective Hydroformylation of 2- and 4-Substituted Styrenes with PtCl2[(R)-
BINAP] + SnCl2 ‘in situ’ Catalyst: a Substituent Effect on the Reversal of
Enantioselectivity.
Péter Pongrácz and László Kollár*
Graphical abstract (pictogram)
H
H
CHO OHC
CHO
X
X
X
+
X
CO/H2
+
PtCl2[(R)-BINAP]
(R)
(S)
2 SnCl2
T<Trev
T>Trev
X = H (a), F (b), OMe (c), Cl (d), Br (e), CH3 (f), CF3 (g)
1

ACCEPTED MANUSCRIPT
Enantioselective Hydroformylation of 2- and 4-Substituted Styrenes with PtCl2[(R)-
BINAP] + SnCl2 ‘in situ’ Catalyst.
Péter Pongrácz a) and László Kollára,b)*
a) MTA-PTE Research Group for Selective Chemical Syntheses, H-7624 Pécs, Ifjúság u. 6., Hungary
b) Department of Inorganic Chemistry, University of Pécs and Szentágothai Research Centre, H-7624
Pécs, P.O. Box 266, Hungary; e-mail: kollar@gamma.ttk.pte.hu
Abstract: Two sets of styrenes possessing various substituents either in ortho or para
position were hydroformylated in the presence of ‘in situ’ catalyst formed from
PtCl2[(R)-BINAP] and tin(II) chloride. The reversal of the absolute configuration of
the preferred enantiomers was observed using both sets of substrates by the variation
o
of the reaction temperature in the range of 40-100 C. In case of the 4-substituted
styrenes, the reversal temperature of the enantioselectivity shows correlation with the
Hammett substituent constants, i.e., with the electron donor or electron acceptor
properties of the para-substituents. This phenomenon was explained by the reversible
formation of the Pt-branched alkyl intermediates, leading to the corresponding (R)- and
(S)-enantiomers of 2-arylpropanals.
Strong substituent effect on the regioselectivity was observed in the hydroformylation
of 2-substituted styrenes: the presence of substituents characterised by larger steric
parameter resulted in the highly favoured formation of the linear aldehyde. For
instance, regioselectivities of 45%, 22% and 7% towards branched aldehyde were
o
obtained with styrene, 2-fluoro- and 2-bromostyrene, respectively, at 80 C reaction
temperature. In addition to the characteristic change of regioselectivity, the reversal of
absolute configuration as a function of reaction temperature was also observed.
Corresponding author: L. Kollár
Department of Inorganic Chemistry, University of Pécs and Szentágothai Research Centre, H-7624 Pécs,
P.O. Box 266, Hungary; Phone: +36-72-503600; e-mail: kollar@gamma.ttk.pte.hu
Key-words: hydroformylation, platinum, enantioselectivity, substituent effect, temperature effect
1

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1. Introduction
The highly selective hydroformylation of alkenes is one of the oldest success-story of homogeneous
catalysis. Its application is widely known for the chemo- and regioselective synthesis of n-butyraldehyde in
cobalt- and rhodium-catalysed reaction,1,2 as well as for the synthesis of 2-arylpropanals in rhodium-catalysed
enantioselective hydroformylation of vinyl aromatics.3 In the latter case, both rhodium- and platinum-catalysts
can be used for the synthesis of the precursors of non-steroidal anti-inflammatory drugs (NSAIDs), such as
ibuprofen, naproxen or suprofen.4. The rhodium-BINAPHOS catalysts, discovered by Takaya,5 enabled
enantioselective hydroformylationst using several types of substrates, therefore, their application has been
predominating over the platinum catalysts in enantioselective hydroformylation.
Since the early discovery of the hydroformylation activity of platinum-monophosphine-tin(II)halide
type ‘in situ’ systems,6 several platinum-chiral diphosphine-tin(II) chloride catalysts were developed and
successfully applied not only for the enantioselective hydroformylation of vinylaromatics but also for the
highly enantio- and regioselective hydroformylation of 1,1-disubstituted olefins resulting in chiral building
blocks (CBBs).7 Furtherrmore, the relative kinetic inertness and facile NMR investigations still made platinum
catalysts a perfect tool for mechanistic studies (vide infra).
In addition to the application of dozens of mono- and bidentate phosphorus ligands in platinum-tin(II)
halide-catalysed hydroformylation,8 some examples on the tin(II) halide-free hydroformylation using
diphenylphosphinous acid platinum complexes9 or platinum-alkyl/aryl–BF3/B(ArF)3 boron additive systems10
were also published.
Regarding the clearing-up of the reaction mechanism, both rhodium-11,12 and platinum containing
systems were investigated. The latter ones were studied by both analytical13 and computational14 methods. The
importance of the good leaving properties of the trichlorostannato ligand was also proved by high pressure
NMR studies.15
An unprecedented phenomenon, a strong dependence of the enantioselectivity on the reaction
temperature in asymmetric hydroformylation was first observed using styrene as substrate in the presence of
PtCl(SnCl3)[(2S,4S)-BDPP)]8d,e and PtCl2[(S)-BINAP]8l catalyst precursors. The temperature dependence of
the reversal of enantioselectivity in Pt-BDPP-catalysed hydroformylation of styrene was rationalized in a
seminal deuterioformylation work published by Casey et al.16 It was discovered that the step determining the
stereochemical outcome of the reaction, i.e., the styrene insertion into the Pt-H bond forming a Pt-alkyl
o
intermediate, can be considered as largely irreversible at low temperature (40 C) but reversible at higher
o
temperature (100 C). In our group, the same Pt-(2S,4S)-BDPP-tin(II) chloride system was used in the
hydroformylation of 4-substituted styrenes. The electronic effect of the 4-substituents on the reversal
temperature was rationalised by the reversibility of of the platinum-alkyl formation step.17
2

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This paper describes the asymmetric hydroformylation of two sets of styrenes possessing various
substituents either in 2- or in 4-position in the presence of an ‘in situ’ catalyst formed from PtCl2[(R)-BINAP]
and tin(II) chloride. It is worth noting that the Pt-BINAP complexes showing a rigid chelate ring is completely
diffrent from the abovementioned BDPP-containg ones, forming a chelate ring with several possible
conformers. Here we report a systematic study on the influence of the electron donor or electron acceptor
properties of the para-substituents of styrene, as well as the steric parameters of the ortho-substituents on
chemo-, regio- and enantioselectivities in Pt-BINAP-catalysed hydroformylation.
2. Materials and Methods
2.1. General procedures
18
The PtCl2(PhCN)2 and the PtCl2[(R)-BINAP]8l precursors were synthesized as described earlier.
Toluene was distilled and purified by standard methods and stored under argon. The substrates, 2- and 4-
substituted styrenes and tin(II) chloride (anhydrous) were used as obtained from Sigma-Aldrich without any
further purification. All reactions were carried out under argon atmosphere using standard Schlenk technique.
Mass-spectrometry data have been obtained using a GC-MS system consisting of a Perkin Elmer
AutoSystem XL gas-chromatograph. The GC and chiral GC measurements were run on a Chrom-Card Trace
GC-Focus GC gas-chromatograph. The enantiomeric excesses were determined on a capillary Cyclodex-
column, (S)-2-arylpropanals were eluted before the (R) enantiomers, except 6c and 6f derivatives. (In these two
cases the (R)-enantiomer were eluted first.)
2.2. Hydroformylation experiments
In a typical experiment, a solution of PtCl2[(R)-BINAP] (4.5 mg; 0.005 mmol) and tin(II) chloride (1.9
mg; 0.01 mmol) in toluene (5 mL) containing styrene derivatives (1a-g, 5a-g) (1.0 mmol) was transferred
under argon into a 100 mL stainless steel autoclave. The reaction vessel was pressurized to 80 bar total
pressure (CO/H2 = 1:1) and placed in an oil bath of constant temperature. The mixture was stirred with a
magnetic stirrer for the given reaction time. The pressure was monitored throughout the reaction. After cooling
and venting of the autoclave, the pale yellow solution was removed and immediately analyzed by GC-MS and
chiral GC.
3. Results
3.1. Enantioselective hydroformylation of 4-substituted styrenes with PtCl2[(R)-BINAP] + SnCl2 ‘in situ’
catalyst
An ‘in situ’ catalyst, formed from PtCl2[(R)-BINAP] and tin(II) chloride, was used at various temperatures
with 80 bar of CO/H2 (1:1) mixture (Scheme 1) for the hydroformylation of 4-substituted styrenes (1a-g). As
3

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generally observed in platinum-catalysed hydroformylation, some catalytic activities were observed at room
o
temperature, however, rather low conversions were obtained even at 40 C. At higher temperatures, some
degradation of the catalyst was observed (typically above ca. 120 oC). Therefore, the evaluation of the catalysts
was carried out in the temperature range of 60 oC to 100 oC. As expected, two aldehyde regioisomers (2 and 3)
and a hydrogenation product (4) were obtained in all cases (Scheme 1).
CHO
CHO
CO/H2
+
+
PtCl2[(R)-BINAP]
2 SnCl2
X
X
X
X
1
2
3
4
X = H (a), F (b), OMe (c), Cl (d), CH3 (f), CF3 (g)
Scheme 1. Hydroformylation of 4-substituted styrenes in the presence of PtCl2[(R)-BINAP] + SnCl2 ‘in situ’
catalyst
In general, chemoselectivities towards aldehydes higher than 85%, at lower temperatures typically higher
than 90% were observed (Table 1). The tendency of increasing selectivity towards aldehydes with decreasing
reaction temperature was observed with all substrates 1a-g. For example, 85%, 91% and 94%
o
o
o
chemoselectivities were obtained using 1g as substrate at 100 C, 80 C and 60 C, respectively (entries 16-
18). The aldehyde selectivities obtained with various substrates at the same temperature show small
o
differences especially at low reaction temperatures (3% difference at 60 C), while slightly wider range of
chemoselectivity (a difference of 5%) was obtained at 100 oC. For example, the chemoselectivities obtained at
o
60 C and 100 oC were varied in the range of 93% (1a) to 96% (1c) (entries 3, 6, 9, 12, 15), and 85% (1g) to
90% (1c) (entries 1, 4, 7, 10, 13), respectively (Table 1).
Unlike the general trends observed with platinum catalysts, the application of a BINAP-containing catalyst
results in a characteristic increase of regioselectivity towards branched aldehyde by increasing temperature. For
o
o
o
instance, 48%, 52% and 54% regioselectivity was obtained at 60 C, 80 C and 100 C for 4-methoxystyrene
(1c) (entries 7-9). Much lower regioselectivities towards branched aldehyde regioisomers were shown with 1b,
1d and 1g, containing electron acceptor groups such as 4-fluoro, 4-chloro and 4-trifluoromethyl substituents,
respectively. In these cases the preference of the linear aldehyde was observed resulting in a branched to linear
aldehyde ratio of ca. 1:2.
A strong dependence of e.e. on the reaction temperature was obtained in the enantioselective
hydroformylation of all substrates (1a-g) (Figure 1), reflecting to a same phenomenon as observed previously
with the parent styrene (1a) in the presence of Pt-BINAP-tin(II) halide catalysts.8l That is, the formation of the
4

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(S)-enantiomer is favoured at low temperatures, while the (R)-enantiomer of 2-arylpropanals (2a-g) is
predominating at higher temperatures. The difference in substrate behaviour is characterised by the
temperature of the reversal of the enantioselectivity, i.e., by the temperature of the change of the absolute
configuration of the dominating enantiomer. When this ‘reversal temperature’ is plotted against Hammett-
constants (σpara) of the corresponding substituents19 (Figure 2), although the correlation is not strong, an
increase of the reversal temperature by increasing electron acceptor properties of the 4-substituents such as F
o
o
o
(b), Cl (d) and CF3 (g) was shown. The reversal of the enantioselectivity occurred at 76 C, 80 C and 84 C
with fluoro (σpara = +0.062), chloro (σpara = +0.227) and trifluoromethyl (σ = +0.540) substituents,
para
respectively. Accordingly, much lower reversal temperatures were observed with electron donor substituents.
o
o
That is, the reversal of the enantioselectivity occurred at 71 C and 70 C with methyl (σpara = -0.170) and
methoxy (σpara = -0.268) substituents, respectively. (It has to be added that the reversal temperatures might
o
have ca. ± 1 C error due to the difficulties in their determination, i.e., to provide perfect racemic mixtures
experimentally under the conditions of the enantioselective hydroformylation above.)
5

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Figure 1. Effect of temperature on the enantioselectivity in the hydroformylation of 1a-g in the presence of Pt-
(R)-BINAP catalyst.
Figure 2. The reversal temperatures of the enantioselectivity (Trev) plotted against the Hammett constants (σp
in the hydroformylation of 1a-g in the presence of Pt-(R)-BINAP catalyst.
)
6

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Table 1. Hydroformylation of 4-substituted styrenes in the presence of PtCl2[(R)-BINAP] +
SnCl2 ‘in situ’ catalyst a)
c)
d)
Entry Substrate
T
time conv.b) Rc
Rbr
[%] [%] [%] [%]
e.e. e)
[oC] [h]
1
1a
1a
1a
1b
1b
1b
1c
1c
1c
1d
1d
1d
1f
100 23
>99 88
44
40
36
42
40
36
54
52
48
41
37
34
49
46
46
35
35
34
24 (S)
3 (S)
2
80
60
24
120 56
80
12
86
93
85
3
16 (R)
23 (S)
5 (S)
4
100 28
5
80
60
24
240 >99 95
>99 90
>99 89
6
15 (R)
30 (S)
12 (S)
12 (R)
17 (S)
1 (S)
7
100 25
8
80
60
96
91
94
96
86
93
9
166 88
10
11
12
13
14
15
16
17
18
100 24
88
98
80
60
72
140 >99 95
20 (R)
25 (S)
14 (S)
13 (R)
13 (S)
6 (R)
100 24
99
97
90
92
94
85
1f
80
60
48
1f
164 19
73
1g
1g
1g
100 24
80
60
48
96
>99 91
88 94
17 (R)
a) Reaction conditions (unless otherwise stated): 0.005 mmol of PtCl2[(R)-BINAP], 0.01
mmol of SnCl2, 1 mmol of substrate (1), p(CO)=p(H2)=40 bar, 5mL of toluene
b) Determined by GC
c) Chemoselectivity towards aldehydes: (2+3)/(2+3+4)x100
d) Regioselectivity towards branched aldehyde: 2/(2+3)x100
e) Determined by chiral GC (dominating enantiomer in brackets)
7

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3.2. Enantioselective hydroformylation of 2-substituted styrenes with PtCl2[(R)-BINAP] + SnCl2 ‘in situ’
catalyst
Although some sporadic results can be found in the literature on the diastereoselective hydroformylation of
chromium-tricarbonyl complexes of 2-substituted styrenes bearing planar element of chirality20 and the control
of stereochemistry by 2-amino groups in anionic polymerization of 2-substituted styrenes is also known21,
there is no precedence for the ‘direct’ hydroformylation of similar compounds.
Based on earlier findings in the hydroformylation of styrene,8l the ‘in situ’ catalyst, formed from PtCl2[(R)-
BINAP] and tin(II) chloride seemed to be a good choice of catalyst to study the factors controlling regio- and
enantioselectivity in the hydroformylation of 2-substituted styrenes (5a-g). The series of 2-substituted styrenes
were hydroformylated at various temperatures with 80 bar of CO/H2 (1:1) mixture in the presence of Pt-
BINAP-tin(II) chloride catalyst. Branched and linear aldehyde regioisomers (6 and 7, respectively) and a
hydrogenation product (8) were formed (Scheme 2).
CHO
CHO
X
X
X
X
CO/H2
+
+
PtCl2[(R)-BINAP]
2 SnCl2
5
6
7
8
X = H (a), F (b), OMe (c), Cl (d), Br (e), CH3 (f), CF3 (g)
Scheme 2. Hydroformylation of 2-substituted styrenes in the presence of PtCl2[(R)-BINAP] + SnCl2 ‘in situ’
catalyst
The chemoselectivities towards aldehydes (6 and 7) are rather similar to those obtained with 4-substituted
styrenes bearing the same series of substituents. Chemoselectivities of 90% or higher were observed at low
temperatures except to 5g. For example, the corresponding aldehyde regioisomers were formed with 84%,
o
o
o
89%, 93% and 94% chemodelectivities using 5f as substrate at 100 C, 80 C, 60 oC and 40 C, respectively
(Table 2, entries 21-24).
As for the regioselectivity towards branched aldehyde (6), both increase and decrease of regioselectivity by
increasing temperature was shown depending on the 2-substituent. For instance, a slight increase from 25%
(40 oC) to 29% (100 oC) in case of 5c (entries 9-12), and a decrease from 28% (40 oC) to 22% (100 oC) in case
of 5b (entries 5-8) were observed. It has to be noted that in general much lower regioselectivities were
observed with 2-substituted styrenes than with the corresponding 4-substituted ones and with the parent
styrene (1a=5a). (It seems to be obvious that the formation of the platinum-branched alkyl catalytic
intermediate, leading to 6, is less favoured due to steric factors.) In three cases (5e, 5f, 5g) the regioselectivities
8

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were below 10%. In the latter case, the formation of the linear aldehyde (7g) is especially highly favoured.
As above, a strong dependence of e.e. on the reaction temperature was obtained in the Pt-(R)-BINAP-
catalysed enantioselective hydroformylation of all substrates (5a-g) (Figure 3). As in case of 4-substituted
styrenes (1a-g) (Chapter 2.1.), the formation of the (S)-enantiomer is favoured at low temperatures and that of
the (R)-enantiomer at higher temperatures.23 It has to be added that due to extremely low branched selectivity,
and therefore large errors in the determination of e.e-s, they were not determined in case of 5g. Furthermore,
the temperature dependence of enantioselectivity in case of the 2-fluoro-substituted derivative (5b) is quite
unexpected. (Table 2, entries 5-8).
The reversal temperatures proved to be the lowest when substrates 5f and 5e possessing substituents
characterised by large steric factors (CH3 (Es=-1.24), Br ((Es=-1.16), respectively) were hydroformylated. The
ortho-substituent characterised by small Es (OCH3 (Es=-0.55) shifted the reversal temperature to higher
values.
9

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Figure 3. Effect of temperature on the enantioselectivity in the hydroformylation of 5a-g in the presence of Pt-
(R)-BINAP catalyst.
Figure 4. The reversal temperatures of the enantioselectivity (Trev) plotted against the steric constants (Es) in
the hydroformylation of 5a-g in the presence of Pt-(R)-BINAP catalyst.
10

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Table 2. Hydroformylation of 2-substituted styrenes in the presence of PtCl2[(R)-BINAP] +
SnCl2 ‘in situ’ catalyst a)
c)
d)
Entry Substrate
T
time conv.b) Rc
Rbr
[%] [%] [%] [%]
e.e. e)
[oC] [h]
1
5a=1a
5a=1a
5a=1a
5a=1a
5b
100 23
>99 88
44
40
36
31
22
22
23
28
29
30
25
25
10
10
9
24 (S)
3 (S)
2
80
60
40
24
12
86
93
91
85
3
120 56
120 16
16 (R)
32 (R)
29 (S)
2 (R)
41 (S)
60 (S)
9 (S)
4
5
100 24
83
6
5b
80
60
40
168 >99 89
7
5b
240 13
264 28
87
90
8
5b
9
5c
100 23
>99 91
>99 82
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
5c
80
60
40
72
12 (R)
37 (R)
67 (R)
30 (S)
16 (S)
0
5c
144 97
120 55
96
96
79
5c
5d
100 24
97
5d
80
60
40
72
>99 86
5d
168 60
240 31
91
92
5d
10
8
33 (R)
30 (S)
18 (S)
2 (S)
5e
100 24
>99 79
5e
80
60
40
72
91
84
90
93
84
89
93
94
77
84
7
5e
144 79
6
5e
128
8
7
24 (R)
43 (S)
37 (S)
17 (S)
25 (R)
n.d.
5f
100 24
97
89
8
5f
80
60
40
96
5
5f
144 93
240 36
4
5f
2
5g
100 24
45
168 57
120
2
5g
80
60
3
n.d.
5g
0
n.d. n.d. n.d.
a) Reaction conditions (unless otherwise stated): 0.005 mmol of PtCl2[(R)-BINAP], 0.01
mmol of SnCl2, 1 mmol of substrate, p(CO)=p(H2)=40 bar, 5mL of toluene.
b) Determined by GC.
c) Chemoselectivity towards aldehydes: (6+7)/(6+7+8)x100
d) Regioselectivity towards branched aldehyde: 6/(6+7)x100
e) Determined by chiral GC (favoured enantiomer in brackets)
11

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4. Discussion
Using BINAP as bidentate diphosphine ligand, able to form conformationally rigid chelate ring, (S)-2-
arylpropanals and the corresponding (R)-enantiomers predominate at low and high temperature, respectively,
when the hydroformylation of the corresponding 4-substituted styrene (1a-g) was carried out in the presence of
Pt-(R)-BINAP-tin(II) chloride catalytic systems.
Using 1a-g as substrates, our results have shown that unexpected reversal of the enantioselectivity occurs
in a temperature range of 70 oC to 84 oC depending on the electron donor/electron acceptor properties of the 4-
substituents of the substrate. Since the stereochemical outcome of the reaction is determined in the formation
of the platinum-alkyl leading to the formation of (S)- and (R)-2a-g, the electronic properties of the substituents
play a crucial role. The weakening of the Pt-carbon bond and increase of the reversal temperature is due to
electron acceptor substituents, such as CF3 or Cl. Based on these results, a facile insertion of carbon monoxide
but not a β-hydride elimination resulting in the styrene derivative can be supposed.
The electron donor substituents such as CH3 or OCH3 increase electron density on the Pt-carbon bond and
therefore, increase reversibility of the Pt-alkyl formation. Consequently, the reversal temperature of
enantioselectivity was decreased. In these cases β-hydride elimination is preferred to carbon monoxide
insertion. The corresponding styrene derivatives are ‘re-formed’ and are inserted into the Pt-H bond resulting
in the favoured formation of the corresponding (S)-2-arylpropanals.
It can be stated that using 4-substituted substrates,17 much lower reversal temperatures (lower by 20-35
oC!) were observed in the presence of the Pt-BINAP catalysts than with the corresponding Pt-BDPP systems.
One of the main differences between Pt-BDPP and Pt-BINAP is the conformational rigidity of chelate ring
formed by the latter one. While BDPP forms a 6-membered chelate with transition metals which has several
ring conformations and high flexibility of the chelate ring, the 7-membered BINAP-transition metal chelate
ring is relatively rigid, i.e., the rotation of the binaphthyl ring around C1-C1’ axis is the only possibility to alter
the distance between phosphorus donor atoms. According to NMR8l and crystallographic investigations,22 the
chiral arrangement of the phenyl rings of coordinated BINAP, determining the ‘chiral pocket’ available for
styrene derivatives for coordination from re or si enantiosites, can be considered as more crowded. Focusing
our attention on the stereodefining step of the hydroformylation, it can be stated that this crowded arrangement
leads to the reversibility of the Pt-alkyl formation, and as above, resulted in the decrease the reversal
temperature of enantioselectivity.
5. Conclusion
Platinum–(R)-BINAP–tin(II) chloride 'in situ' systems proved to be active catalyst in the hydroformylation
of 2- and 4-substituted styrenes. The reversal of the absolute configuration of the branched formyl regioisomer
(2-arylpropanal derivatives) can be rationalised explained by the reversible formation of the corresponding Pt-
12

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branched alkyl intermediates. In addition to the unexpected change of absolute configuration, a strong
substituent effect on the regioselectivity was observed in the hydroformylation of 2-substituted styrenes:
substituents with larger steric parameters, due to steric reasons, favour the formation of the linear aldehyde.
Acknowledgement: The authors thank the Hungarian Research Fund (K113177) for the financial
support. The present scientific contribution is dedicated to the 650th anniversary of the foundation of the
University of Pécs, Hungary.
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Captions to Scheme and Figures
Scheme 1. Hydroformylation of 4-substituted styrenes in the presence of PtCl2[(R)-BINAP] + SnCl2 ‘in situ’
catalyst.
Scheme 2. Hydroformylation of 2-substituted styrenes in the presence of PtCl2[(R)-BINAP] + SnCl2 ‘in situ’
catalyst.
Figure 1. Effect of temperature on the enantioselectivity in the hydroformylation of 1a-g in the presence of Pt-
(R)-BINAP catalyst.
Figure 2. The reversal temperatures of the enantioselectivity (Trev) plotted against the Hammett constants (σp)
in the hydroformylation of 1a-g in the presence of Pt-(R)-BINAP catalyst.
Figure 3. Effect of temperature on the enantioselectivity in the hydroformylation of 5a-g in the presence of Pt-
(R)-BINAP catalyst.
Figure 4. The reversal temperatures of the enantioselectivity (Trev) plotted against the steric constants (Es) in
the hydroformylation of 5a-g in the presence of Pt-(R)-BINAP catalyst.
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Highlights
•
•
•
•
Platinum-catalysed enantioselective hydroformylation of 2- and 4-substituted styrenes.
Unusual temperature dependence of the enantioselectivity.
Explanation on the reversal of the favoured enantiomer..
Reversal temperature vs σp, regioselectivity vs σp correlations.