Asymmetric hydrogenation of prochiral olefins catalysed by furanoside thioether-phosphinite Rh(I) and Ir(I) complexes

Article abstract of DOI:10.1039/b502843d

Thioether-phosphinite ligands (P-SR, R = Ph, Prⁱ and Me) bearing substituents with different steric demands on the sulfur centre were tested in the rhodium- and iridium-catalysed asymmetric hydrogenation of prochiral olefins. High enantiomeric excesses (up to 96%) and good activities (TOF up to 860 mol product × (mol catalyst precursor × h)^-1) were obtained for α-acylaminoacrylates derivatives. Our results show that enantiomeric excesses depended strongly on the steric properties of the substituent in the thioether moiety, the metal source and the substrate structure. A bulky group in the thioether moiety along with the metal Rh had a positive effect on enantioselectivity. Reaction of these chiral ligands with [M(cod)₂]BF₄ (M = Ir, Rh; cod = 1,5-cyclooctadiene) yielded complexes [M(cod)(P-SR)]BF₄, which were present in only one diastereomeric form having the sulfur substituent in a pseudoaxial disposition. The addition of H₂ to iridium complexes gave the cis- dihydridoiridium(III) complexes [IrH₂(cod)(P-SR)]BF₄. For complexes [IrH₂(cod)(P-SPh)]BF₄ and [IrH ₂(cod)(P-SMe)] only one isomer was present in solution. However, for the complex [IrH₂(cod)(P-Si-Pr)]BF₄, which contained the more hindered substituent on sulfur, two isomers were detected. In all cases there was a pseudoaxial disposition of the sulfur substituents. The Royal Society of Chemistry 2005.

Full text of DOI:10.1039/b502843d

View Article Online / Journal Homepage / Table of Contents for this issue
F U L L P A P E R
Asymmetric hydrogenation of prochiral olefins catalysed by
furanoside thioether–phosphinite Rh(I) and Ir(I) complexes
Eugeni Guimet, Montserrat Di e´ guez,* Aurora Ruiz* and Carmen Claver
Departament de Qu ´ı mica F ´ı sica i Inorg a` nica, Universitat Rovira i Virgili, C/ Marcel·l ´ı
Domingo s/n, 43007 Tarragona, Spain.
E-mail: montserrat.dieguez@urv.net, aruiz@quimica.urv.es; Fax: +34-977559563
Received 25th February 2005, Accepted 31st May 2005
First published as an Advance Article on the web 29th June 2005
i
Thioether–phosphinite ligands (P–SR, R = Ph, Pr and Me) bearing substituents with different steric demands on the
sulfur centre were tested in the rhodium- and iridium-catalysed asymmetric hydrogenation of prochiral olefins. High
−
1
enantiomeric excesses (up to 96%) and good activities (TOF up to 860 mol product × (mol catalyst precursor × h) )
were obtained for a-acylaminoacrylates derivatives. Our results show that enantiomeric excesses depended strongly
on the steric properties of the substituent in the thioether moiety, the metal source and the substrate structure. A
bulky group in the thioether moiety along with the metal Rh had a positive effect on enantioselectivity. Reaction of
these chiral ligands with [M(cod)
M(cod)(P–SR)]BF , which were present in only one diastereomeric form having the sulfur substituent in a
pseudoaxial disposition. The addition of H
IrH (cod)(P–SR)]BF . For complexes [IrH
in solution. However, for the complex [IrH
sulfur, two isomers were detected. In all cases there was a pseudoaxial disposition of the sulfur substituents.
2
]BF
4
(M = Ir, Rh; cod = 1,5-cyclooctadiene) yielded complexes
[
4
2
2
to iridium complexes gave the cis-dihydridoiridium(III) complexes
(cod)(P–SPh)]BF and [IrH (cod)(P–SMe)] only one isomer was present
, which contained the more hindered substituent on
[
2
4
4
2
2
(cod)(P–Si–Pr)]BF
4
1
Introduction
Asymmetric hydrogenation of prochiral compounds catalysed
by chiral transition-metal complexes has been widely used
in stereoselective organic synthesis and some processes have
1
found industrial applications. Over the years the scope of this
reaction, in terms of reactant structure and catalyst efficiency,
has gradually extended. Many chiral ligands, mainly P- and N-
1
Fig. 1 Thioether–phosphinite ligands 1–3.
containing ligands with either C2 or C1 symmetry, have been
successfully applied. Diphosphines and diphosphinites have
1
proprieties whose effects on catalytic performance can be
studied. We also discuss the synthesis and characterisation of
their Rh(I) and Ir(I) complexes and the solution structures of the
important dihydridoiridium(III) complexes. Ligands 1–3 have
been recently applied in the Pd-catalyzed allylic substitution
played a dominant role among the P-ligands. Mixed donor
1d,2
ꢀ
3
4
ligands (such as P,N-,
P,P -, and P,S- ) have only recently
demonstrated their potential utility in this process. Of the
few mixed phosphorus–thioether ligands used in this process,
6
4b
reactions.
thioether–phosphinite ligands have had the best results in
asymmetric hydrogenation. The first thioether–phosphinite lig-
ands, developed by Hauptman and co-workers in 1998, showed
2 Results and discussion
4e
moderate enantioselectivity. However, a new class of thioether–
phosphinite ligands developed by Evans and co-workers has
recently proven to be very effective for the Rh-catalysed asym-
2
.1. Synthesis of rhodium and iridium complexes
The reaction of the corresponding chiral thioether–phosphinite
4b
metric hydrogenation of a variety of a-acylaminoacrylates.
ligands 1–3 with [M(cod) ]BF (M = Rh, Ir) in dichloromethane
2
4
Despite this success, other thioether–phosphinite ligands and
their use in the metal-catalysed hydrogenation of other sub-
strate types, have not yet been reported. More research is
therefore needed to study the possibilities offered by thioether–
phosphinites as a new class of ligands for this process. For this
purpose, carbohydrates are particularly advantageous due to
their availability at low price and easy modular constructions.
Although carbohydrate ligands have been successfully used in
solution proceeded with the displacement of one molecule of the
1,5-cyclooctadiene ligand (cod) to afford the cationic mononu-
clear complexes [M(cod)(P–SR)]BF 4–9 (P–SR = Ligands 1–3)
4
(Scheme 1). All complexes were isolated as air stable solids by
adding diethyl ether.
The complexes were characterised by elemental analysis, FAB
1
13
31
mass spectrometry and H, C, and P NMR spectroscopy. The
spectral assignments (see Experimental section) were based on
5
1
1
13
1
asymmetric hydrogenation, to our knowledge, carbohydrate-
information from H– H and C– H correlation measurements
1 1
based thioether–phosphinite ligands have not been tested in this
process.
in combination with H– H NOESY experiments.
The elemental analysis of C, H, and S matched the stoichiom-
etry [Rh(cod)(PSR)] (BF ) . The FAB mass spectra confirmed
Following our interest in carbohydrates as an inexpensive
n
4 n
5
and highly modular chiral source for preparing ligands, and
the formation of the mononuclear species in all cases.
encouraged by the results of Evans’ thioether–phosphinite
Upon coordination to the metal, the sulfur atom of the
thioether moiety of the ligands becomes stereogenic centre. The
reaction could therefore lead to a mixture of two stereoisomers
with different configurations of the sulfur stereocentre and
different spatial arrangements of the substituent. The outcome
may become even more complicated than anticipated if differ-
ent conformations of comparable energy are available to the
4b
ligands in asymmetric hydrogenation, we have applied fu-
ranoside thioether–phosphinite ligands 1–3 (Fig. 1) in the
Rh- and Ir-catalysed enantioselective hydrogenation of a-
acylaminoacrylates and itaconic acid derivatives. These ligands,
4a
6
easily prepared in a few steps from inexpensive D-(+)-xylose,
contain thioether moieties with different electronic and steric
T h i s j o u r n a l i s © T h e R o y a l S o c i e t y o f C h e m i s t r y 2 0 0 5
D a l t o n T r a n s . , 2 0 0 5 , 2 5 5 7 – 2 5 6 2
2 5 5 7

View Article Online
Scheme 1 Synthesis of rhodium and iridium complexes 4–9.
seven-membered chelate ring of the metal-complexes. However,
1
13
for all the complexes prepared, variable temperature H, C and
3
1
◦
P NMR (from 40 to −80 C) measurements indicated that only
one stereoisomer was present in solution.
The 2D-NOESY experiments provided spatial orientation of
the thioether substituents and the conformation adopted for
the seven-membered chelate ring. For complexes 5, 6, 8 and
9
4
, the 2D-NOESY spectra showed that protons H-3 and H-
have cross peaks with the methyl signals of the thioether
2
Scheme 2 Reactivity of complexes 7–9 with H .
groups. In addition, H-3 and the methyl signals of the thioether
groups showed cross peaks with one of the phenyl groups of the
phosphinite moiety. From these data we can conclude that the
All attempts to isolate the cis-dihydride iridium complexes 10–
1
2 led to the isolation of the corresponding olefinic iridium(I)
7
◦
substituents at the sulfur atom occupy a pseudoaxial position
complexes even at −70 C under a hydrogen atmosphere. The
1
in a distorted chair conformation of the seven-membered
chelate ring (Fig. 2). This pseudoaxial orientation is important
because it fixes the orientation of the P-phenyl substituents.
The importance of P-phenyl edge-on/face-on relationships for
high enantioselectivities in the Rh-catalysed hydrogenation of
complexes were therefore characterised in solution using the H
3
1
and P NMR measurements (Table 1). The spectral assignments
1
1
were based on information from H– H correlation measure-
1
1
ments, in combination with H– H NOESY experiments.
In these species, as well as the sugar backbone and the
sulfur atom, even the metal is stereogenic, so the number of
possible diastereomers in solution increases. The four potential
cis-dihydride addition products are illustrated in Fig. 3.
1c,8
acetamidocinnamates has already been documented.
This
encouraged us to explore the potential of these complexes as
chiral catalysts in asymmetric hydrogenation (see section 2.3).
Fig. 3 Possible products of cis-dihydrogen addition to compounds 7–9.
Fig. 2 Scheme of complexes 5, 6, 8 and 9 with pseudoaxial location of
the sulfur substituents and chair conformation of the seven-membered
chelate ring. The arrows show the cross peaks.
1
31
For complexes 10 and 12 the variable temperature H and
P
◦
NMR (from 40 to −80 C) measurements indicated the presence
of one isomer with an overall C
for complex 11 two isomers (denoted as a and b), in a ratio of
.7 : 1, were detected.
In the low-field region of the H NMR spectra, the signals
1
-symmetry in solution. However,
For the related complexes with the -SPh groups (rhodium
complex 4 and iridium complex 7), NOESY experiments do not
allow us to propose their stereochemistry.
1
1
from the thioether–phosphinite ligands produced the expected
NMR pattern for the xylo-furanoside nucleus (positions 1–5 in
Table 1).
2
.2. Preparation of cis-dihydridoiridium complexes
Transition-metal hydride complexes have been the focus of
considerable research because of their prominent role in many
catalytic hydrogenation processes. The oxidative addition of
hydrogen is usually the rate-determining step in the asym-
metric hydrogenation of acrylic acid derivatives catalysed by
rhodium complexes with chiral diphosphines, diphosphinites,
1
The high-field region of the H NMR spectra of complexes 10
1,9
31
and 12 showed two doublets due to P coupling corresponding
10
to the two hydride protons (Table 1, H-6 and H-7). As expected
for complex 11, two sets of two doublets in a ratio of 1.7 : 1
for isomers a and b were observed (Table 1). For all complexes,
11
12
13
3f –g
diphosphites and phosphite–phosphines.
For this reason
the hydride resonances (H-6 and H-7) have T
1
min values of
◦
we studied the reactivity of the cationic complexes 4–9 with
hydrogen before testing the catalytic performance of these
complexes in the catalytic hydrogenation of some benchmark
around 300 ms in CD
2
Cl
2
at −70 C and 400 MHz, which
are consistent with classical hydrides. For all complexes, the
phosphorus–hydride coupling constants were in agreement with
a structure in which the phosphorus atom is located cis to two
olefins (see section 2.3).
◦
15
Iridium complexes 7–9 reacted with H
2
at −70 C to afford the
hydrides. Only structures II and IV satisfied these conditions.
corresponding cis-dihydridoiridium complexes [Ir(H)
SR)]BF
10–12 (P–SR = 1–3) (Scheme 2). However, the rhodium
complexes did not react with H under these conditions.
2
(cod)(P–
Both of these structures were the product of additions parallel
to the Ir–S axis, but they could not be distinguished by analysing
4
14
1
31
2
their monodimensional H NMR and P NMR spectra.
2
5 5 8
D a l t o n T r a n s . , 2 0 0 5 , 2 5 5 7 – 2 5 6 2

View Article Online
1
a
Table 1 The H-NMR spectroscopic data for complexes 10–12
Position
10
11a
6.12 (d)
11b
12
1
2
3
5.90 (d)
6.02 (d)
5.98 (d)
3
3
3
3
J
1–2 = 3.6
J
1–2 = 3.6
J
1–2 = 3.6
J
1–2 = 3.6
4.29 (d)
5.11 (d)
4.45 (d)
4.31 (d)
3
3
3
3
J
2–1 = 3.6
J
2–1 = 3.6
J
2–1 = 3.6
J
2–1 = 3.6
4.55 (dd)
4.14 (dd)
4.30 (dd)
4.44 (dd)
3
3
3
3
3
3
3
3
J
3–4 = 2.8; J3-P = 16.4
J
3–4 = 2.0; J3-P = 12.8
J
3–4 = 1.6; J3-P = 15.2
J
3–4 = 2; J3-P = 16
4
5
5
3.88 (m)
3.98 (m)
3.32 (m)
4.60 (m)
2.88 (b)
2.80 (b)
4.45 (b)
3.98 (m)
3.37 (m)
4.56 (m)
3.76 (m)
3.32 (m)
ꢀ
CH
CMe
3
1.11 (s), 1.12 (s)
1.20(s), 1.54 (s)
1.37 (s), 1.49 (s)
1.18 (s), 1.40 (s)
—
2.83 (s)
—
2
—
—
—
—
—
—
—
CH
CH
3
S
–CH
3
3
3
1.38 (d, J = 6.4)
0.94 (d, J = 6.8)
3
3
1
.53 (d, J = 7.2)
1.56 (d, J = 6.4)
SCH
Ph
—
3.11 (m)
3.21 (m)
—
7.2–8.1 (m)
1.8–3.0 (b)
3.88 (m), 3.98 (m)
7.2–8.0 (m)
2.0–2.6 (b)
7.2–8.0 (m)
2.0–2.6 (b)
7.2–8.0 (m)
1.8–2.8 (b)
CH
2
CH=
3.40 (m), 3.42 (m)
5.51 (m), 5.87 (m)
4.37 (m), 4.43 (m),
4.79 (m), 5.85 (m)
3.48 (m), 4.23 (m)
4.39 (m), 5.90 (m)
4
.45 (m), 5.86 (m)
b
b
b
H6
−14.37 (d)
−14.32 (d)
−14.75 (d)
−14.35 (d)
2
2
2
2
J
H–P = 22.4
J
H–P = 20.0
J
H–P = 24.0
J
H–P = 22.4
b
b
b
H7
−12.63 (d)
−13.33 (d)
−12.25 (d)
−12.70 (d)
2
2
2
2
J
H–P = 17.3
J
H–P = 14.4
J
H–P = 18.8
J
H–P = 18.9
a
◦
1
Chemical shifts in ppm; coupling constants in Hz. T = −70 C. H NMR in CD
2 2
Cl . Abbreviations: s, singlet; d, doublet; dd, doublet doublet; m,
b
multiplet; br, broad. H6 is located trans to cod and H7 is located trans to SR.
The 2D-NOESY experiments provided the isomer adopted
for the cis-dihydrogen complexes. For complexes 11a and 12,
the 2D-NOESY spectra showed that H-6 had cross peaks with
Table 2 Asymmetric hydrogenation of 13 with [M(cod)]BF
4
/1–3, M =
a
Rh, Ir
b
c
Entry
M/L
P
H2/bar
Solvent
% Conv (t/min)
% e.e.
the methyl signals of the thioether groups and the phenyl group
of the phosphinite moiety. H-7 showed cross peak with the other
phenyl group of the phosphinite moiety. In addition, H-3 and
H-4 had cross peaks with the methyl signals of the thioether
groups. These observations correspond to isomer IV (Fig. 3)
with a pseudoaxial disposition of the sulfur substituent in a
distorted chair conformation for the seven-membered chelate
ring. Interestingly, this isomer is the result of adding dihydrogen
1
2
3
4
5
6
7
8
9
0
Rh/1
Rh/1
Rh/1
Rh/1
Rh/1
Rh/1
Rh/1
Rh/1
Ir/1
Rh/2
Ir/2
Rh/3
Ir/3
Rh/2
1
1
1
1
1
CH
THF
MeOH
2
Cl
2
100 (50)
100 (60)
100 (90)
100 (50)
100 (50)
84 (20)
86 (10)
86 (60)
100 (60)
83 (10)
95 (30)
75 (10)
60 (60)
83 (30)
55 (R)
45 (R)
39 (R)
54 (R)
55 (R)
61 (R)
68 (R)
68 (R)
50 (R)
93 (R)
63 (R)
54 (R)
30 (R)
96 (R)
d
e
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
CH
2
2
2
2
2
2
2
2
2
2
2
Cl
2
Cl
2
Cl
2
Cl
2
Cl
2
Cl
2
Cl
2
Cl
2
Cl
2
Cl
2
Cl
2
5
30
30
1
30
1
30
1
30
f
16
to the more sterically encumbered face of the complex. Adding
to the opposite face would lead to strong steric interaction
between the migrating olefin, the pseudoaxial sulfur substituent
and the phenyl groups of the phosphinite moiety.
1
11
12
1
1
3
4
For complex 11b, the NOESY experiment suggests the
formation of isomer II, which resulted from the addition of
dihydrogen to the less sterically encumbered face, probably due
g
a
[
M(cod)
2
]BF
4
= 0.01 mmol. Ligand/M = 1.1. Substrate/M = 100.
◦
b c
i
to the greater hindrance and rigidity of the Pr group.
Solvent = 6 mL. T = 25 C. % Conversion measured by GC.
%
For complex 10 the 2D-NOESY spectra were less clear and
did not allow us to draw any conclusions.
Enantiomeric excess measured by GC using a Permabond L-Chirasil-Val
d
e
column. Ligand/Rh = 2. Using preformed complex [Rh(cod)(1)]BF
4
f
g
◦
(
0.01 mmol). Substrate/Rh = 1000. T = 0 C.
2
.3. Asymmetric hydrogenation
In the first set of experiments, we used the rhodium-catalysed
hydrogenation of methyl N-acetamidoacrylate 13 to evaluate the
potential of ligands 1–3.
We studied the effect of several reaction parameters (i.e.
solvent, ligand-to-rhodium ratio, catalyst preparation, hydrogen
pressure and metal source) using the catalyst precursor contain-
ing ligand 1. The results are given in Table 2.
Thioether–phosphinite ligands 1–3 were tested in the Rh- and
Ir-catalysed asymmetric hydrogenation of a-acylaminoacrylates
and itaconic acid derivatives 13–16 (Scheme 3). The catalysts
were prepared in situ by adding the corresponding thioether–
phosphinite ligands to the catalyst precursor [M(cod)
Rh, Ir).
2
]BF
4
(M =
These results show that the efficiency of the process depended
on the nature of the solvent (entries 1–3). Therefore, the catalytic
performance (activity and enantioselectivity) was best when
dichloromethane was used (entry 1).
Adding one-fold excess of ligand did not affect the outcome
of the reaction (entry 4). Also, using preformed catalyst
precursor [Rh(cod)(1)]BF did not affect the efficiency of the
4
process (entry 5).
Interestingly, both enantioselectivity and activity were en-
hanced when the hydrogen pressure was raised from 1 to 30 bars
(entry 1 vs. entry 6 and 7). This contrasts with the usual decrease
Scheme 3 Asymmetric hydrogenation of prochiral olefins with
M(cod)]BF
/1–3 (M = Rh, Ir).
[
4
D a l t o n T r a n s . , 2 0 0 5 , 2 5 5 7 – 2 5 6 2
2 5 5 9

View Article Online
a
Table 3 Asymmetric hydrogenation of 14–16 with [M(cod)]BF
4
/1–3, M = Rh, Ir
b
c
Entry
M/L
Substrate
P
H2/bar
Solvent
% Conv (t/min)
% e.e.
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
Rh/1
Rh/1
Rh/1
Rh/1
Ir/1
Rh/2
Rh/3
Rh/1
Rh/1
Rh/1
Rh/1
Ir/1
14
14
14
14
14
14
14
15
15
15
15
15
15
15
15
15
16
16
16
16
16
16
1
1
1
30
1
30
30
1
1
1
30
1
30
1
30
1
1
1
1
30
1
30
CH
THF
MeOH
2
Cl
2
100 (90)
100 (120)
100 (300)
100 (50)
100 (120)
100 (50)
75 (90)
100 (120)
100 (120)
96 (120)
100 (80)
100 (120)
90 (100)
100 (150)
90 (110)
100 (160)
83 (180)
52 (180)
12 (120)
83 (120)
85 (180)
83 (120)
56 (R)
47 (R)
39 (R)
68 (R)
50 (R)
93 (R)
45 (R)
48 (S)
31 (S)
27 (S)
57 (S)
46 (S)
64 (S)
51 (S)
35 (S)
13 (S)
37 (S)
14 (S)
14 (S)
47 (S)
32 (S)
55 (S)
CH
CH
CH
CH
CH
2
2
2
2
2
Cl
2
Cl
2
Cl
2
Cl
2
Cl
2
THF
MeOH
1
1
1
1
1
1
1
1
1
1
2
2
2
CH
CH
CH
CH
CH
CH
CH
2
2
2
2
2
2
2
Cl
2
Cl
2
Cl
2
Cl
2
Cl
2
Cl
2
Cl
2
Rh/2
Ir/2
Rh/3
Ir/3
Rh/1
Rh/1
Rh/1
Rh/1
Ir/1
THF
MeOH
CH
CH
CH
2
2
2
Cl
2
Cl
2
Cl
2
Rh/2
a
◦
b
c
[
M(cod)
2
]BF
4
= 0.01 mmol. Ligand/M = 1.1. Substrate/M = 100. Solvent = 6 mL. T = 25 C. % Conversion measured by GC. % Enantiomeric
excess measured by GC using a Permabond L-Chirasil-Val column for substrate 14 and a Chiraldex-G-TA for substrates 15 and 16.
in enantioselectivity with bidentate ligands when hydrogen
structure. A bulky group in the thioether moiety along with
the metal Rh had a positive effect on enantioselectivity. Results
for a-acylaminoacrylates derivatives were satisfactory, while
enantiomeric excesses for itaconic acid derivatives were low.
Note that these thioether–phosphinite ligands showed much
higher reaction rates and higher enantioselectivities than their
thioether–phosphite analogues in the asymmetric hydrogenation
11
pressure is raised. This enabled us to perform the reaction at
a lower catalyst concentration without losing enantioselectivity
and obtain a good activity (TOF = 860 mol product × (mol
−
1
catalyst precursor × h) ) (entry 8).
When [Ir(cod)
2
]BF /1 was used as the catalyst precursor, the
4
activity and enantioselectivity were lower than with the catalytic
system Rh/1 (entry 1 vs. 9).
Under the optimised conditions, we then studied how the
thioether substituents affected the catalytic performance with
ligands 2 and 3 (Table 2).
17
17,4c
of a-acylaminoacrylates and itaconic derivatives.
Characterisation of complexes [M(cod)(P–SR)]BF
4
(M =
Rh, Ir; cod = 1,5-cyclooctadiene) by variable temperature
NMR indicated that only one diastereomer, with pseudoaxial
location of the sulfur substituents, was present in solution.
This pseudoaxial orientation is important because it fixes the
orientation of the P-phenyl substituents in an edge-on/face-
on relationship, which is reported to be important for high
enantioselectivity.
The use of ligand 2 with a isopropyl substituent in the
thioether moiety showed much higher enantioselectivity (93%
(
3
R) e.e., entry 10 and 63% (R) e.e., entry 11). The use of ligand
with a methyl substituent in the thioether moiety showed the
lowest asymmetric induction (entries 12 and 13).
◦
Lowering the temperature to 0 C increased enantioselectivity
Adding
dihydridoiridium(III) complexes [IrH
complexes [IrH (cod)(P–SPh)]BF and [IrH
H
2
to the iridium complexes gave the cis-
(cod)(P–SR)]BF . For
(cod)(P–SMe)]BF
(
up to 96%) (entries 10 vs. 14).
2
4
We subsequently applied these new thioether–phosphinite
2
4
2
4
,
ligands 1–3 in the Rh- and Ir-catalysed hydrogenation of
other benchmark dehydroaminoacid derivatives (methyl N-
acetamidocinnamate 14, dimethyl itaconate 15 and itaconic acid
variable temperature NMR measurements indicated that only
one isomer, was present in solution. However, for complex
i
[IrH
2
(cod)(P–SPr )]BF
4
, which contains the more hindered
1
6, Scheme 3).
substituent on sulfur, two isomers were detected. In all the
cases a pseudoaxial disposition of the sulfur substituents was
The results are summarised in Table 3. The effect of the
reaction parameters (i.e. solvent, hydrogen pressure, metal
source, etc.) and ligand parameters followed the same trends as
for substrate 13. However, while substrate 14 showed the same
level of enantioselectivities with somewhat lower activities than
present. Interestingly, despite this lack of selectivity in the
i
oxidative addition step, [IrH
best enantioselectivities.
2
(cod)(P–SPr )]BF
4
provided the
1
3, substrates 15 and 16 showed lower activities and much lower
4
Experimental
enantioselectivities than 13.
4.1. General comments
All syntheses were performed using standard Schlenk techniques
under argon atmosphere. Solvents were purified by standard
3
Conclusions
i
Thioether–phosphinite ligands (P–SR; R = Ph, Pr and Me),
which contain a furanoside as a simple but effective backbone,
were tested in the rhodium- and iridium-catalysed asymmetric
hydrogenation of a-acylaminoacrylates and itaconic acid deriva-
tives. High enantiomeric excesses (up to 96%) and good activities
procedures. Complexes [M(cod)
prepared using methods described in the literature. Ligands
1–3 were prepared as previously described. All other reagents
2
]BF
4
(M = Rh and Ir) were
18
6
were used as commercially available. Elemental analyses were
1
13
1
performed on a Carlo Erba EA-1108 instrument. H, C{ H}
and P{ H} NMR spectra were recorded on a Varian Gemini
400 MHz spectrometer. Chemical shifts are relative to SiMe
−
1
31
1
(
TOF up to 860 mol product × (mol catalyst precursor × h) )
were obtained. Our results show that enantiomeric excesses
depend strongly on the steric properties of the substituent
in the thioether moiety, the metal source and the substrate
4
1
13
31
( H and C) as internal standard or H
3
PO ( P) as external
4
standard. All assignments in NMR spectra were determined by
2
5 6 0
D a l t o n T r a n s . , 2 0 0 5 , 2 5 5 7 – 2 5 6 2

View Article Online
1
1
13
1
ꢀ
H– H and C– H spectra. Proton T
1
studies were performed
1.55 (s, 3H, CH
3
), 2.1–2.5 (b, 8H, CH
2
), 3.08 (m, 1H, H-5 ), 3.40
◦
◦
using the standard inversion recovery 180 –s–90 pulse sequence
method. A VG-Autospect was used for FAB mass spectral
analyses. The matrix was m-nitrobenzyl alcohol. The reaction
(m, 1H, CH=), 3.52 (m, 1H, CH=), 3.68 (m, 1H, H-5), 4.60 (m,
19
1H, H-4), 4.83 (m, 1H, CH=), 4.92 (m, 1H, CH=), 5.03 (d, 1H,
3
3
3
J
2–1 = 3.6 Hz, H-2), 5.61 (dd, 1H, J3–4 = 2.4 Hz, J3-P = 12 Hz,
3
under 1 atm of H
hydrogen vacuum line. The reactions under 5 and 30 atm
of H were carried out in a home-made 100 mL stainless
steel autoclave. Gas chromatography analyses were performed
in a Hewlett-Packard Model 5890A instrument. Enantiomeric
excesses (e.e.) were measured using a fused silica capillary
column 25 m × 0.25 mm Permabond L-Chirasil-Val for the
determination of e.e. for substrates 13 and 14, and a capillary col-
umn 30 m × 0.25 mm Chiraldex-G-TA for substrates 15 and 16.
2
was performed in a previously described
H-3), 6.02 (d, 1H, J2–1 = 3.6 Hz, H-1), 7.2–8.1 (m, 5H, CH=).
20
13
C NMR (CD
2
Cl
2
, ppm), d: 26.6 (CH
3
), 26.9 (CH
3
), 28.6 (CH ),
2
2
30.2 (CH
2
), 32.0 (CH
2
), 33.9 (CH
2
), 39.6 (C-5), 71.1 (CH=), 74.9
(CH=), 76.9 (C-4), 84.2 (C-3), 84.4 (C-2), 101.8 (d, JC-P = 13 Hz,
CH=), 102.5 (d, JC-P = 10 Hz, CH=), 105.7 (C-1), 113.5 (CMe
),
2
128–134 (C, Ar).
+
[Ir(cod)(2)]BF
(M-BF ). Anal. Calc. for C31
S, 3.91. Found: C, 45.01; H, 4.89; S, 3.60. P NMR (CD
4
8. colour: orange; Yield 55%; FAB : 733 m/z
4
H
41BF
4
IrO PS: C, 45.42; H, 5.04;
4
31
2
3
2
Cl ,
1
ppm), d: 112.3. H NMR (CD
2
Cl
2
, ppm), d: 1.18 (d, 3H, J =
3
6
CH
.4 Hz, CH
3
iPr), 1.39 (s, 3H, CH
3
), 1.48 (d, 3H, J = 6.4 Hz,
4
.2. Synthesis of rhodium and iridium complexes
i
3
ꢀ
Pr ), 1.58 (s, 3H, CH
3
), 2.1–2.5 (b, 8H, CH ), 2.79 (m, 1H,
2
i
General procedure.Thioether–phosphinite ligand (0.11 mmol)
H-5 ), 3.34 (m, 1H, CH Pr ), 3.43 (b, 2H, CH=), 3.59 (m, 1H,
3
was added to a solution of [M(cod)
2
]BF
4
(0.1 mmol M = Rh, Ir)
H-5), 4.53 (m, 1H, H-4), 4.98 (d, 1H, J2–1 = 4.0 Hz, H-2), 5.36
3
in 2 mL of dichloromethane. After stirring for 30 min, diethyl
ether was added to precipitate the corresponding complex, which
was filtered off, washed with cold diethyl ether and vacuum
(b, 3H, CH=, H-3), 6.02 (d, 1H, J2–1 = 4 Hz, H-1), 7.2–8.1 (m,
1
3
i
5H, CH=). C NMR (CD
Cl
2
, ppm), d: 22.9 (CH Pr ), 23.6
2
3
i
(CH
3
Pr ), 26.5 (CH
3
), 27.1 (CH
3
), 29.0 (d, CH
2
, JC-P = 3 Hz),
2
dried.
29.5 (C-5), 30.3 (d, CH
3 Hz), 33.2 (d, CH
2
, JC-P = 3 Hz), 32.2 (d, CH
, JC-P
=
+
i
[
Rh(cod)(1)]BF
M-BF ). Anal. Calc. for C34
S, 4.19. Found: C, 53.00; H, 5.00; S, 4.20. P NMR (CD
4
4. colour: yellow; Yield 82%; FAB : 677 m/z
2
, JC-P = 3 Hz), 45.5 (CH Pr ), 71.1 (CH=),
(
4
H
39BF
4
O
4
PRhS: C, 53.42; H, 5.14;
73.6 (CH=), 77.7 (C-4), 84.0 (C-3), 84.4 (d, C-2, JC-P = 10 Hz),
100.3 (d, CH=, JC-P = 10.7 Hz), 101.2 ((d, CH=, JC-P = 12.2 Hz),
3
1
2
Cl
, ppm),
), 2.2–2.6 (b, 8H, CH ), 2.83
2
,
1
1
ppm), d: 135.7 (d, JP-Rh = 163.0 Hz). H NMR (CD
2
Cl
2
105.4(C-1), 113.4 (CMe ), 129–134 (C, Ar).
2
+
d: 1.42 (s, 3H, CH
3
), 1.56 (s, 3H, CH
3
2
[Ir(cod)(3)]BF
(M-BF ). Anal. Calc. for C29
S, 4.05. Found: C, 43.90; H, 4.61; S, 3.90. P NMR (CD
4
9. colour: yellow; Yield 56%; FAB : 705 m/z
ꢀ
(
m, 1H, H-5 ), 3.18 (m, 1H, H-5), 3.89 (m, 1H, CH=), 4.03 (m,
4
H
37BF
4
IrO PS: C, 44.00; H, 4.71;
4
3
31
1
5
2
7
2
(
(
(
H, CH=), 4.55 (m, 1H, H-4), 5. 03 (d, 1H, J2–1 = 3.6 Hz, H-2),
2
Cl
, ppm), d: 1.42 (s, 3H, CH
2
,
3
1
.13 (m, 1H, CH=), 5.16 (m, 1H, CH=), 5.64 (dd, 1H, J3–4
=
ppm), d: 111.2. H NMR (CD
1.59 (s, 3H, CH ), 2.0–2.5 (b, 8H, CH
Cl
2
),
), 2.63 (m, 1H, H-5 ), 2.68
2
3
3
3
ꢀ
Hz, J3-P = 14 Hz, H-3), 6.01 (d, 1H, J2–1 = 3.6 Hz, H-1),
.2–8.1 (m, 5H, CH=). C NMR (CD
Cl , ppm), d: 26.6 (CH ),
6.9 (CH ), 28.2 (CH ), 29.5 (CH ), 32.0 (CH ), 33.5 (CH ), 38.1
3
2
1
3
2
2
3
(s, 3H, CH
3
–S), 3.27 (m, 1H, CH=), 3.52 (m, 1H, H-5), 3.55 (m,
3
1H, CH=), 4.58 (m, 1H, H-4), 5.03 (d, 1H, J2–1 = 3.6 Hz, H-2),
3
2
2
2
2
3
C-5), 76.9 (C-4), 84.7 (C-2), 84.9 (C-3), 88.3 (m, CH=), 105.7
5.20 (m, 1H, CH=), 5.38 (m, 1H, CH=), 5.60 (dd, 1H, J3–4
=
3
3
C-1), 112.2 (m, CH=), 112.5 (m, CH=), 113.5 (CMe
), 128–136
2.4 Hz, J3-P = 11.6 Hz, H-3), 6.03 (d, 1H, J2–1 = 3.6 Hz, H-1),
7.1–7.9 (m, 5H, CH=). C NMR (CD
Cl , ppm), d: 26.2 (CH ),
26.7 (CH ), 29.7 (CH ), 30.0 (CH ), 32.4 (CH ), 32.6 (CH ), 36.4
(CH
–S), 36.5 (C-5), 71.7 (CH=), 73.9 (CH=), 76.5 (C-4), 84.3
2
1
3
C, Ar).
2
2
3
+
[
Rh(cod)(2)]BF
M-BF ). Anal. Calc. for C31
4
5. colour: orange; Yield 52%; FAB : 643 m/z
3
2
2
2
2
(
4
H
41BF
4
O
4
PRhS: C, 50.98; H, 5.66;
3
3
1
S, 4.39. Found: C, 49.90; H, 5.20; S, 4.38. P NMR (CD
2
Cl
, ppm),
), 1.47
), 2.1–2.7 (b,
2
,
(C-3), 84.7 (C-2), 98.2 (d, CH=, JC–P = 10 Hz), 102.3 (d, CH=,
1
1
ppm), d: 133.4 (d, JP–Rh = 170.5 Hz). H NMR (CD
2
Cl
2
J
C–P = 12 Hz), 105.6 (C-1), 113.2 (CMe
2
), 128–135 (C, Ar).
3
d: 1.13 (d, 3H, J = 6.4 Hz, CH
3
iPr), 1.41 (s, 3H, CH
Pr ), 1.58 (s, 3H, CH
3
3
i
(
8
d, 3H, J = 6.4 Hz, CH
3
3
4
.3. In situ preparation of cis-dihydridoiridium complexes
ꢀ
i
H, CH
2
), 2.52 (b, 1H, H-5 ), 2.84 (m, 1H, CH, Pr ), 3.11 (m,
General procedure. In a typical experiment, hydrogen was
1
H, H-5), 3.94 (m, 2H, CH=), 4.48 (m, 1H, H-4), 5.02 (d, 1H,
3
bubbled through a solution of [Ir(cod)
2
]BF
4
(0.1 mmol) and
Cl (2 mL) at
J
2–1 = 4.0 Hz, H-2), 5.46 (m, 1H, CH=), 5.50 (m, 1H, H-3), 5.60
3
thioether–phosphinite ligand (0.11 mmol) in CD
2
2
(
m, 1H, CH=), 6.02 (d, 1H, J2–1 = 4 Hz, H-1), 7.1–8.0 (m, 5H,
◦
1
3
i
−70 C. After 30 min, the solution was transferred to an NMR
CH=). C NMR (CD
Cl
2
, ppm), d: 22.1 (CH
Pr ), 23.8 (CH
), 29.6 (C-5),
2
3
3
1
31
i
spectrometer tube ( H NMR and P NMR were recorded to the
Pr ), 26.1 (CH
3
), 26.8 (CH
3
), 28.3 (CH ), 28.5 (CH
), 43.9 (CH Pr ), 77.5 (C-4), 84.3 (C-2),
2
2
1
i
desired temperature). H NMR details are reported in Table 2.
3
8
(
(
1.7 (CH
4.7 (C-3), 84.8 (m, CH=), 87.1 (m, CH=), 105.2 (C-1), 110.1
), 128–133 (C, Ar).
2
), 32.9 (CH
2
3
1
[
[
Ir H
IrH
2
(cod)(1)]BF
(cod)(2)]BF
4
10. P NMR (CD
2
Cl
Cl
2
, ppm), d: 109.3.
, ppm), d: 100.7.
3
1
2
4
11a. P NMR (CD
Cl
2
2
m, CH=), 112.0 (m, CH=), 113.2 (CMe
Rh(cod)(3)]BF 6. colour: yellow; Yield 42%; FAB : 615 m/z
M-BF ). Anal. Calc. for C29 PRhS: C, 49.59; H, 5.31;
2
3
1
+
11b. P NMR (CD
Ir H (cod)(3)]BF
2
2
, ppm), d: 105.6.
[
4
3
1
[
2
4
12. P NMR (CD
2
Cl
2
, ppm), d: 108.0.
4
H
37BF
4
O
4
3
1
S, 4.57. Found: C, 49.00; H, 5.12; S, 4.67. P NMR (CD
2
Cl
, ppm),
), 2.3–2.6 (b, 8H, CH ), 2.40
2
,
1
1
4
.4. Asymmetric hydrogenation reactions
Hydrogenation of prochiral olefins under 1 atm. In a typical
experiment, a schlenk tube was filled with a solvent solution
6 mL) of substrate (1 mmol), [M(cod) ]BF (0.01 mmol) and
ligand (0.011 mmol). This was then purged three times with
vacuum and H . The reaction mixture was then shaken under
(1 bar) at room temperature. To remove the catalyst, the
solution was placed on a short silica gel column and eluted with
CH Cl . Conversion and enantiomeric excesses were determined
ppm), d: 134.4 (d, JP–Rh = 165.9 Hz). H NMR (CD
2
Cl
2
d: 1.42 (s, 3H, CH
s, 3H, CH
3
), 1.59 (s, 3H, CH
3
2
ꢀ
(
3
–S), 2.50 (b, 1H, H-5 ), 3.02 (m, 1H, H-5), 3.82 (m,
1
H, CH=), 4.02 (m, 1H, CH=), 4.54 (m, 1H, H-4), 5.04 (d, 1H,
(
2
4
3
J
2–1 = 4.0 Hz, H-2), 5.44 (m, 1H, CH=), 5.59 (m, 1H, CH=),
3 3
5
.65 (dd, 1H, J3–4 = 2 Hz, J3-P = 11.6 Hz, H-3), 6.02 (d, 1H,
2
3
13
J
2–1 = 4.0 Hz, H-1), 7.1–8.1 (m, 5H, CH=). C NMR (CD
2
Cl
), 32.4
–S), 76.7 (C-4), 84.5
2
,
H
2
ppm), d: 26.5 (CH
(
(
1
3
), 27.0 (CH
3
), 29.4 (CH
2
), 29.5 (CH
2
CH
2
), 33.6 (CH
2
), 35.3 (C-5), 35.6 (CH
3
2
2
C-2), 85.5 (C-3), 85.6 (m, CH=), 87.6 (m, CH=), 105.8 (C-1),
by gas chromatography.
09.1 (m, CH=), 112.8 (m, CH=), 113.5 (CMe
), 128–135 (C,
2
Ar).
Hydrogenation of prochiral olefins under 5 or 30 atm.
In a typical experiment, the autoclave was filled with a
dichloromethane solution (6 mL) of substrate (1 mmol),
+
[
Ir(cod)(1)]BF
M-BF
4
7 colour: yellow; Yield 93%; FAB : 767 m/z
(
4
). Anal. Calc. for C34
H
39BF
4
IrO PS: C, 47.83; H, 4.60;
4
31
S, 3.76. Found: C, 47.10; H, 4.12; S, 3.20. P NMR (CD
ppm), d: 112.9. H NMR (CD
2
Cl
2
,
[M(cod)
2
]BF
4
(0.01 mmol) and ligand (0.011 mmol). This was
. The reaction
1
2
Cl
2
, ppm), d: 1.41 (s, 3H, CH
3
),
then purged three times with vacuum and H
2
D a l t o n T r a n s . , 2 0 0 5 , 2 5 5 7 – 2 5 6 2
2 5 6 1

View Article Online
mixture was then stirred under H
temperature. To remove the catalyst, the solution was placed on a
short silica gel column and eluted with CH Cl . Conversion and
2
(5 or 30 atm) at room
J. S. Tedrow and K. R. Campos, J. Am. Chem. Soc., 2003, 125,
3534; (c) O. P
a` mies, M. Di e´ guez, G. Net, A. Ruiz and C. Claver,
Organometallics, 2000, 19, 1488; (d) E. Hauptman, P. J. Fagan and
W. Marshall, Organometallics, 1999, 18, 2061; (e) E. Hauptman, R.
Shapiro and W. Marshall, Organometallics, 1998, 17, 4976.
(a) M. Di e´ guez, O. P a` mies and C. Claver, Chem. Rev., 2004, 104,
3189; (b) M. Di e´ guez, O. P a` mies, A. Ruiz, Y. Diaz, S. Castill o´ n and
C. Claver, Coord. Chem. Rev., 2004, 248, 2165; (c) O. P a` mies, M.
Di e´ guez, A. Ruiz and C. Claver, Chem. Today, 2004, 12.
6 E. Guimet, M. Di e´ guez, A. Ruiz and C. Claver, Tetrahedron:
Asymmetry, 2005, 16, 959.
The tendency for sulfur substituents in metal P/S chelate rings to
adopt a pseudoaxial orientation has been previously noted. See: P.
Barbaro, A. Currao, J. Herrmann, R. Nesper, P. Pregosin and R.
Salzmann, Organometallics, 1996, 15, 1879.
2
2
enantiomeric excesses were determined by gas chromatography.
5
Acknowledgements
We would like to thank the Spanish Ministerio de Educaci o´ n,
Cultura y Deporte for their financial support (BQU2001–0656).
7
References
1
See for example: (a) R. Noyori, in Asymmetric Catalysis in Organic
Synthesis, Wiley, New York, 1994; (b) I. Ojima, in Catalytic Asym-
metric Synthesis, vol. 1, Wiley, New York, 2000; (c) E. N. Jacobsen, A.
Pfaltz and H. Yamamoto, in Comprehensive Asymmetric Catalysis,
vol. 1, Springer, Berlin, 1999; (d) W. Tang and X. Zhang, Chem. Rev.,
8 J. Brown and P. Evans, Tetrahedron, 1988, 44, 4905.
9 P. A. Chaloner, M. A. Esteruelas, F. Jo o´ and A. Oro, in Homogeneous
Hydrogenation, Kluwer Academic, Dordrecht, 1994.
2
003, 103, 3029; (e) H. U. Blaser and E. Schmidt, in Asymmetric
10 For an example where the rate-determining step appears to be
migratory insertion, see reference: I. D. Gridnev, N. Higashi, K.
Asakura and T. Imamoto, J. Am. Chem. Soc., 2000, 122, 7183.
11 C. R. Landis and J. Halpern, J. Am. Chem. Soc., 1987, 109, 1746.
12 (a) T. V. RajanBabu, T. A. Ayers and A. L. Casalnuovo, J. Am.
Chem. Soc., 1994, 116, 4101; (b) T. V. RajanBabu, T. A. Ayers, G. A.
Halliday, K. K. You and J. C. Calabrese, J. Org. Chem., 1997, 62,
6012; (c) T. V. RajanBabu, B. Radetich, K. K. You, T. A. Ayers, A. L.
Casalnuovo and J. C. Calabrese, J. Org. Chem., 1999, 64, 3429.
13 O. P a` mies, G. Net, A. Ruiz and C. Claver, Eur. J. Inorg. Chem., 2000,
1287.
Catalysis on Industrial Scale, Wiley-VCH, Weinheim, 2004; (f) H. U.
Blaser, C. Malan, B. Pugin, F. Spindler, H. Steiner and M. Studer,
Adv. Synth. Catal., 2003, 345, 103.
See for example: (a) M. T. Powell, D. R. Hou, M. C. Perry, X. Cui
and K. Burgess, J. Am. Chem. Soc., 2001, 343, 450; (b) A. Zanotti-
Gerosa, C. Malan and D. Herzberg, Org. Lett., 2001, 3, 3687; (c) A.
Lightfoot, P. Schnider and A. Pfaltz, Angew. Chem., Int. Ed. Engl.,
2
1
998, 37, 2897; (d) R. Hilgraf and A. Pfaltz, Synlett., 1999, 1814;
(
e) P. G. Cozzi, N. Zimmermann, R. Hilgraf, S. Schaffner and A.
Pfaltz, Adv. Synth. Catal., 2001, 343, 450; (f) F. Menges and A. Pfaltz,
Adv. Synth. Catal., 2002, 344, 40; (g) D. R. Hou, J. Reibenspies, T. J.
Colacot and K. Burgess, Chem. Eur. J., 2001, 7, 5391; (h) W. Tang,
W. Wang and X. Zhang, Angew. Chem., Int. Ed. Engl., 2003, 42, 943.
See for recent successful application: (a) Y. Yan, Y. Chi and X. Zhang,
Tetrahedron: Asymmetry, 2004, 15, 2173; (b) X. Jia, X. Li, W. S. Lam,
S. H. L. Kok, L. Xu, G. Lu, C. H. Yeung and A. S. C. C Chan,
Tetrahedron: Asymmetry, 2004, 15, 2273; (c) X. P. Hu and Z. Zheng,
Org. Lett., 2004, 6, 3585; (d) H. P. Wu and G. Hoge, Org. Lett.,
14 This phenomen has also been reported for other rhodium complexes.
See reference 4b.
15 Hydride trans to the phosphorus donor generally have coupling
constants of 80–100 Hz. See for example:B. F. M. Kimmich, E.
Somsook and C. R. Landis, J. Am. Chem. Soc., 1998, 120, 10115.
16 Although diastereomeric equilibration is not impossible, previous
studies of iridium dihydrides have shown that isomerisation only
3
◦
occurs above −50 C, see references: (a) M. J. Burk, M. P. McGrath,
2
004, 6, 3645; (e) S. Andr e´ s, M. A. M e´ ndez-Rojas and A. Pizzano,
R. Wheeler and R. H. Crabtree, J. Am. Chem. Soc., 1988, 110, 5034;
(b) P. P. Deutsch and R. Eisenberg, Chem. Rev, 1988, 88, 1147.
17 O. P a` mies, PhD Thesis, Universitat Rovira i, Virgili, 1999.
18 M. Green, T. A. Kuc and S. H. Taylor, J. Chem. Soc. A, 1971, 2334.
19 R. H. Crabtree, in The Organometallic Chemistry of the Transition
Metals, John Wiley & Sons; New York, 1988.
Organometallics, 2002, 21, 4611; (f) S. Deerenberg, O. P a` mies, M.
Di e´ guez, C. Claver, P. C. J. Kamer and P. W. N. M. van Leeuwen,
J. Org. Chem., 2001, 66, 7626; (g) O. P a` mies, M. Di e´ guez, G. Net, A.
Ruiz and C. Claver, J. Org. Chem., 2001, 66, 8364; (h) M. Di e´ guez,
A. Ruiz and C. Claver, Chem. Commun., 2001, 2702.
(a) A. M. Masdeu-Bult o´ , M. Di e´ guez, E. Martin and M. G o´ mez,
Coord. Chem. Rev., 2003, 242, 159; (b) D. A. Evans, F. E. Michael,
4
20 E. Guimet, M. Di e´ guez, A. Ruiz and C. Claver, Tetrahedron:
Asymmetry, 2004, 15, 2247.
2
5 6 2
D a l t o n T r a n s . , 2 0 0 5 , 2 5 5 7 – 2 5 6 2