P-Stereogenic diphosphines in the ruthenium-catalysed asymmetric hydrogenation of C=C and C=O double bonds

Article abstract of DOI:10.1016/S0957-4166(02)00439-1

Bis(acetato) and dichloro complexes of ruthenium(II) containing P-stereogenic ligands have been prepared and tested in the asymmetric catalytic hydrogenation of functionalised olefins and keto esters. The best performance (52.6% ee) has been obtained in the hydrogenation of ethyl acetoacetate with [RuCl(PPh₃)((S,S)-1,1′-bis(1-naphthylphenylphosphino) ferrocene)] 4.

Full text of DOI:10.1016/S0957-4166(02)00439-1

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 13 (2002) 1817–1824
P-Stereogenic diphosphines in the ruthenium-catalysed
asymmetric hydrogenation of CꢀC and CꢀO double bonds
Francesca Maienza,a Francesco Santoro,a Felix Spindler,b Christophe Malanb and
Antonio Mezzettia,*
aDepartment of Chemistry, Swiss Federal Institute of Technology, ETH Ho¨nggerberg, CH-8093 Zu¨rich, Switzerland
bSolvias AG, Klybeckstrasse 191, CH-4002 Basel, Switzerland
Received 15 July 2002; accepted 30 July 2002
Abstract—Bis(acetato) and dichloro complexes of ruthenium(II) containing P-stereogenic ligands have been prepared and tested
in the asymmetric catalytic hydrogenation of functionalised olefins and keto esters. The best performance (52.6% ee) has been
obtained in the hydrogenation of ethyl acetoacetate with [RuCl(PPh3)((S,S)-1,1%-bis(1-naphthylphenylphosphino)ferrocene)] 4.
© 2002 Elsevier Science Ltd. All rights reserved.
1. Introduction
electronic properties of the diphosphine ligands can
dramatically affect the outcome of standard synthetic
procedures. One of us has previously shown that
After Knowles’ seminal work with dipamp,1 synthetic
problems have long hampered the development of P-
stereogenic ligands.2 In recent years, however, the
development of new synthetic strategies has made a
vast number of P-stereogenic diphosphines (P–P*)
available for catalytic asymmetric reactions.3–8 Most
efforts have been directed to the rhodium-catalysed
hydrogenation of olefins, where Imamoto’s systems
have shown very high efficiency.3 A lesser effort has
been directed to the application of P–P* to other
catalytic reactions, such as rhodium-catalysed
hydrosilylation9 and palladium-catalysed allylic alkyla-
tion.10 As P-stereogenic diphosphines have been rarely
used in connection with ruthenium,11–13 we decided to
extend the scope of such ligands in the ruthenium-
catalysed hydrogenation of CꢀC and CꢀO double
bonds.
dichloro
ruthenium
complexes
of
the
type
[RuCl2(PPh3)(P–P)] (A; P–P=chiral diphosphine; Chart
1) are easily prepared from [RuCl2(PPh3)3] and are
suitable catalyst precursors for the hydrogenation of
1,3-diketones.15 The acetato complexes [Ru(h2-
O2CCX3)2(P–P)] (B) have been developed in Nagoya16
and at Roche17 and Ciba.18 The bis(2-methylallyl) com-
plexes C, prepared with the methodology developed by
Geneˆt,19 are also versatile precatalysts, as they give
ready access to both classes of compounds mentioned
above.
Our investigation was directed to complementing sparse
data concerning the ruthenium-catalysed hydrogenation
with P-stereogenic ligands, such as dipamp 2b and its
analogue Me2Si(CH2P(o-An)Ph)2 3b (o-An=o-anisyl)
(Chart 2).11 In the 1-naphthyl series, we have previously
prepared (S,S)-Ph(1-Np)PCH2CH2P(1-Np)Ph13 2a (1-
It is a well established fact that dichloro complexes of
the general formula ‘[RuCl2(P–P)]n’ are ideally suited
for the hydrogenation of carbonyl functionalities
(ketones and keto esters), whereas acetato complexes of
the type [Ru(RCOO)2(P–P)] are most effective for the
hydrogenation of olefins.14 However, the access to suit-
able catalyst precursors of ruthenium is not always
straightforward, as even subtle changes in the steric and
* Corresponding author. Fax: +41 1 632 13 10; e-mail: mezzetti@
inorg.chem.ethz.ch
Chart 1.
0957-4166/02/$ - see front matter © 2002 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(02)00439-1

1818
F. Maienza et al. / Tetrahedron: Asymmetry 13 (2002) 1817–1824
Np=1-naphthyl) and (S,S)-Me2Si(CH2P(1-Np)Ph)2
3a.15c Its ruthenium complex [RuCl2(PPh3)(3a)] has
been tested in the catalytic hydrogenation of 1,3-dike-
tones.15c Ligand 2a has been used in the rhodium-
catalysed hydrogenation of acrylic acid20 and in the
ruthenium-catalysed cyclopropanation of olefins.13
Thus, we have addressed the synthesis of ruthenium(II)
complexes of the general type [RuX2(L)n(P–P)] (X=
anionic ligand) containing one of the diphosphine lig-
ands (S,S)-1a, (S,S)-1b, (S,S)-2a, and (R,R)-3b
depicted in Chart 2 and either two chloro ligands and a
neutral ligand L (such as A), or two acetato ligands
(such as B). The P-stereogenic ligands chosen span a
wide range of steric requirements in view of the differ-
ent diphosphine bridge (ethane-1,2-diyl, 2,2-dimethyl-2-
sila-propane-1,3-diyl, or ferrocene-1,1%-diyl). The
dppf-analogues 1a and 1b have been recently prepared
and tested in connection with rhodium21 and palla-
dium.10 The synthesis and application of these new
complexes in the hydrogenation of prostereogenic keto
esters and olefins are described below.
Scheme 1.
related to the 1-naphthyl groups.15c,21a One PPh3 ligand
partially dissociates from 4 in CD2Cl2 solution at room
temperature, as indicated by the broadened singlet at l
−6 (w1/2=30 Hz) in the 31P NMR spectrum, which is
attributed to free PPh3 in chemical exchange with 4
(Scheme 1). Broad signals at l 41 and 29 are assigned
to the dinuclear species [(1a)ClRu(m-Cl)2RuCl(1a)] 5.
Approximately 25% of 4 dissociates to give the dinu-
clear complex 5. Analogous dissociation equilibria have
been described for [RuCl2(PPh3)3]24 and [RuCl2(PPh3)-
(P–P)].15,22,23
Instead of a five-coordinate complex, the reaction of
[RuCl2(PPh3)3] with 1b afforded the six-coordinate,
orange complex [RuCl2((S,S)-1b)] 6. In agreement with
this formula, 6 is a non-electrolyte in CH2Cl2 and
displays an MS (FAB+) molecular peak at 786. Vapour-
pressure osmometric measurements gave a molecular
weight of 783 g/mol. The diphosphine 1b acts as a
tetradentate ligand by means of coordination of the two
methoxy groups to ruthenium. Several examples of
o-anisyl-substituted phosphines that coordinate ruthe-
nium as a bidentate PꢁO ligand have been reported.25,26
The coordination of both methoxy groups is indicated
2. Results and discussion
2.1. Dichloro complexes
The reaction of [RuCl2(PPh3)3] with the ligand (S,S)-1a
(1 equiv.) in CH2Cl2 at room temperature gave the
dark-red 16-electron complex [RuCl2(PPh3)((S,S)-1a)]
4, whose formula was confirmed by elemental analysis
and mass spectrometry (FAB+)). The room-temperature
31P NMR spectrum of 4 in CD2Cl2 shows a broadened
ABX system analogous to that observed for related
[RuCl2(PPh3)(P–P)] complexes,15,22,23 which possess a
square-pyramidal structure (Scheme 1).23 The low-tem-
perature 31P NMR spectra recorded down to −80°C did
not display a well-resolved ABX system, probably due
to the slowing down of conformational equilibria
1
by the shifts of the H NMR signals of the methoxy
protons (l 3.28 and 4.86) as compared to the free
ligand (l 3.67), with a pattern analogous to that
observed for [RuCl2(CO)(P–O-k1P)(P–O-k2P,O)] (P–
O=P(o-An)Ph2).26 The low-field shift (l 4.86) is typical
of coordinated methoxy groups, whereas the high-field
shift (l 3.28) of one CH3O-signal can be explained by
the close proximity of the corresponding methoxy
group to the face of one aryl group (see below, Fig.
1).26
Chart 2.
Figure 1.

F. Maienza et al. / Tetrahedron: Asymmetry 13 (2002) 1817–1824
1819
lower symmetry than C2 in solution. This can be
explained either by a distortion due to steric crowding
or by the existence of an aqua complex in solution. In
agreement with the latter interpretation, a signal at l
1
1.82 in the H NMR spectrum of 9 can be attributed to
a coordinated water molecule, which is accommodated
by the change of hapticity of one acetato ligand from
h2 to h1. In fact, bis(acetato) complexes of ruthenium
containing bulky phosphine ligands have been reported
to react with water even if present in traces.30 In the
analogous [Ru(h2-O2CCF3)2(P–P)], the trifluoroacetato
ligands are monodentate, and 2 mol of the alcohol
solvent are coordinated to ruthenium.18
Complex 6 is formed in the reaction as a single
diastereoisomer, as indicated by its 31P NMR spectrum,
which consists of an AB system (lA=75.8, lB=66.7,
J
AB=39.4 Hz). The non-equivalence of the two P atoms
The reaction of [Ru(h2-O2CCF3)2(COD)] 7b with 1b in
MeOH gave a stable complex that was isolated as an
orange powder and was formulated as [Ru(h2-
O2CCF3)(1b)]O2CCF3 10. In the mass spectrum of 10,
the signal of the [Ru(h2-O2CCF3)(1b)]+ fragment is very
weak, which confirms that CF3COO− is a more labile
ligand than CH3COO−. In agreement with the easy
dissociation of one CF3COO− ligand, 10 is a 1:1 elec-
trolyte in CH2Cl2 solution (LM=16.2 V−1 cm2 mol−1,
10−3 M solution). The 31P NMR spectrum consists of
an AB system with the signals of PA and PB centred at
l 73.3 and 71.8, respectively (JPP%=42.6 Hz), which
indicates the presence of two non-equivalent P atoms in
cis position. The 19F NMR spectrum revealed the pres-
ence of two non-equivalent CF3 groups at l −75.5 and
is indicative of C1-symmetry, and the presence of two
bands at 232.1 and 241.3 cm−1 in the IR spectrum
supports a cis arrangement of the chloro ligands. As we
were unable to grow crystals for X-ray and the determi-
nation of the absolute configuration at ruthenium, we
performed molecular modelling calculations (Cerius2)27
to assess the energy of the possible diastereomeric
structures. The only structure compatible with the fea-
tures discussed above that refined to a reasonable
energy value is shown in Fig. 1. Interestingly, the
methoxy group trans to chloride is close to the face of
one phenyl group, which accounts for the high-field
shift of one MeO-signal discussed above.
2.2. Bis(2-methallyl) complexes
1
−76.1. One of the methoxy signals in H NMR spec-
The reaction of the bis(2-methylallyl) complex [Ru(h3-
(CH)2CHCH3)2(COD)] 7a28 with ligand (R,R)-3b in
pentane at room temperature gave [Ru(h3-
(CH)2CHCH3)2(3b)] 8b in moderate yield. As ligand 2a
did not react with 7a at room temperature, [Ru(h3-
(CH)2CHCH3)2(2a)] 8a was prepared by heating a hex-
ane solution of (S,S)-2a and 7a (1 equiv.) at 70°C for 5
h. The 31P NMR spectrum of 8a consists of a singlet at
l 83.0. Ligands 1a and 1b did not react with [Ru(h3-
(CH)2CHCH3)2(COD)] even when heated at 70°C for
72 h. As higher temperatures are likely to cause
epimerisation at the stereogenic phosphorus atoms, an
alternative approach was devised that started from the
bis(acetato) complexes.
trum is shifted to lower field (l 4.3 and 3.7) as com-
pared to free ligand 1b (l 3.67), in a similar pattern as
observed for the dichloro species 6. The spectroscopic
and conductivity data suggest that 10 features an h2-
bound trifluoroacetato ligand as shown below. The
configuration at ruthenium is arbitrarily drawn, but
corresponds to the energy-minimised structure of 6.
2.3. Bis(acetato) complexes
2.4. Ru-catalysed hydrogenation of keto esters
The bis(trifluoroacetato) dinuclear complex [Ru2(h2-
O2CCF3)4(OH2)(COD)2] 7b29 reacted with ligand 1a
giving a complex that decomposed upon attempted
isolation, probably owing to the lability of the tri-
fluoroacetato ligand. As acetato is a less labile ligand
The complexes [RuCl2(PPh3)(1a)] 4, [RuCl2(1b)] 6,
[Ru(h3-(CH)2CHCH3)2(2a)]
8a,
and
[Ru(h3-
(CH)2CHCH3)2(3b)] 8b were tested in the asymmetric
hydrogenation of keto esters. Complex 6 catalysed the
hydrogenation of methyl benzoylformate 11 to methyl
(R)-mandelate (R)-12 with moderate enantioselectivity
(43.9% ee) (Table 1, entry 2). Complex 4, containing the
naphthyl analogue 1a, is less efficient (9.6% ee, entry 1).
The bis(2-methylallyl) complexes 8a and 8b show the
same trend of the enantioselectivity, which increases on
changing from 1-naphthyl (8a, 16.6% ee) to o-anisyl
(8b, 26.7% ee) as P-substituents. However, this trend
does not apply for other substrates.
than
trifluoroacetato
is,
we
tested
[Ru(h2-
O2CCH3)2(COD)] 7c as precursor.17 Indeed, the reac-
tion of 7c with ligand 1a yielded the stable complex
[Ru(h2-O2CCH3)2(1a)] 9 that was isolated and charac-
terised by elemental analysis and mass spectrometry
(FAB+). The 31P NMR spectrum consisted of an AX
system with two doublets centred at l 64.40 and 78.39,
respectively, and with JPP%=42 Hz. The presence of two
inequivalent P atoms indicates that the complex has a

1820
F. Maienza et al. / Tetrahedron: Asymmetry 13 (2002) 1817–1824
Indeed, ethyl acetoacetate 13 is hydrogenated to ethyl
(R)-3-hydroxybutyrate (R)-14 with higher enantioselec-
tivity in the case of the naphthyl-substituted ligand 1a
in complex 4 (52.6% ee, Table 2, entry 1) than with the
o-anisyl derivative 1b, whose derivative 6 gave racemic
product (entry 3). The enantioselectivity found for the
hydrogenation of ethyl acetoacetate with 1a is com-
parable to that obtained in the hydrogenation of acetyl-
acetone with the related complex [RuCl2(PPh3)((S,S)-
3a)], which gave (S,S)-pentane-2,4-diol with 56% ee.15c
Precatalyst 4 also hydrogenated methyl 3-oxopen-
tanoate 15 to methyl (R)-3-hydroxypentanoate (16) in
CH2Cl2 with 28% yield and 23% ee (Table 2, entry 2).
As observed with substrate 11, complex 8a shows the
least activity, as it failed to hydrogenate 13 even at high
pressure of H2 and high temperature (P(H2)= 80 bar in
the presence of HCl (entry 4). In the hydrogenation of
methyl 3-oxopentanoate 15, complex 8b is more active
and enantioselective (51% ee, entry 5) than 4 (28% ee,
entry 2). For comparison, some results concerning the
related ligands R(Me)PCH2CH2P(Me)R (BisP*; R=
bulky alkyl group)12 and some atropisomeric ligands.31
are given in Table 1 (entries 5, 6) and Table 2 (entries
6, 7).
2.5. Ru-catalysed hydrogenation of olefins
Functionalised olefins such as (E)-2-methylcinnamic
acid 17, methyl Z-a-N-methyl-acetamidocinnamate 19,
and dimethyl itaconate 21 were chosen as standard
substrates. Complexes 4, 6, 8a, 8b, and 10 were scarcely
effective in the hydrogenation of 17 to 2-methylhy-
drocinnamic acid 18 (Table 3). Only 4 gave a quantita-
tive yield of 18, but at high H2 pressure and with low
enantioselectivity (21.6% ee, entry 1). The enantioselec-
tivity was slightly higher with ligand 1b, either in
complex 6, (32.0% ee, entry 2), or in 10 (35.7% ee, entry
3), but the chemical yield was low at 20 bar H2 pres-
sure. The bis(2-methylallyl) derivatives 8a and 8b were
inactive towards 17 (<2% yield under comparable con-
ditions) (entries
(CH)2CHCH3)2(P–P*)]
4
and 5). In contrast, [Ru(h3-
(P–P=2b or 3b (8b))
hydrogenate tiglic acid quantitatively with 15 and 25%
ee, respectively.11b For comparison, (E)-2-methylcin-
namic acid is hydrogenated with up to 89% ee by
[Ru(h2-O2CCH3)2(H8-binap)]
(H8-binap=2,2%-bis-
(diphenylphosphino) - 5,5%,6,6%,7,7%,8,8% - octahydro - 1,1%-
binaphthyl) (entry 6).32
Table 1. Hydrogenation of methyl benzoylformate 11 to methyl (R)-mandelate 12
Entry
Ligand
Cat.
S/C
Yield (%)
Ee (%)
Conf.
1
2
3
4
5
6
1a
1b
2a
3b
4
6
8a
200
200
100
200
200
100
99
99
B50
95
90
\99
9.6
43.9
16.6
26.7
70
S
R
R
R
R
S
8b
a
(S)-BisP*
(R)-Bichep
b
\99
a From Ref. 12, ‘RuBr2(BisP*)’ as catalyst (BisP*=Me(But)PCH2CH2P(But)Me).
b From Ref. 31a, [RuI(h6-p-cymene)(bichep)] as catalyst under transfer-hydrogenation conditions (bichep=2,2%-bis(dicyclohexylphosphino)-6,6%-
dimethyl-1,1%-biphenyl).
Table 2. Hydrogenation of b-keto esters 13 and 15 to b-hydroxyesters 14 and 16a
Entry
Subst.
R1
R2
Ligand
Cat.
S/C
Solvent
t (h)
Yield (%)
Ee (%)
Conf.
1
2
3
13
15
13
13
15
15
15
H
Me
H
Et
Me
Et
1a
1a
1b
2a
4
4
6
8a
8b
1000
1000
200
200
100
EtOH
CH2Cl2
EtOH
16
18
16
24
16
10
36
\99
28
66
B1
66
96
52.6
23
rac.
–
51
98
R
R
–
4
H
Et
EtOH
–
5b
6
Me
Me
Me
Me
Me
Me
3b
MeOH
MeOH/H2O
MeOH
R
R
R
c
BisP*
(R)-binap
800
2000
d
7
99
\99
a Other reaction conditions: A 1N HCl solution (50–120 mL) was added to the reaction solution.
b T=80°C, p(H2)=100 bar.
c From Ref. 12, see Table 1, footnote a.
d From Ref. 31b, the catalyst was ‘RuCl2((R)-binap)’, P(H2)=100 atm, T=23°C.

F. Maienza et al. / Tetrahedron: Asymmetry 13 (2002) 1817–1824
1821
Table 3. Hydrogenation of (E)-2-methylcinnamic acid 17 to 2-methylhydrocinnamic acid 18
Entry
Ligand
Cat.
S/C
Additive (equiv./Ru)
p(H2) (bar)
t (h)
Yield (%)
Ee (%)
Conf.
1a
2
3
4
5
1a
1b
1b
2a
4
6
10
8a
200
200
200
100
200
200
iPr2NEt2 (4)
NEt3 (6)
NEt3 (6)
CF3COOH (2)
CF3COOH (4)
–
80
20
20
5
20
1.5
19
16
18
16
17
48
\99
12
16
B1
B2
87
21.6
32.0
35.7
n.d.
n.d.
89
R
R
R
n.d.
n.d.
S
3b
8b
b
6
(S)-H8-Binap
a 2-Propyl alcohol was used in place of MeOH.
b From Ref. 32, the catalyst was [Ru(h2-O2CCH3)2(H8-binap)] (H8-binap=2,2%-bis(diphenylphosphino)-5,5%,6,6%,7,7%,8,8%-octahydro-1,1%-binaph-
thyl).
The hydrogenation of 19 to N-acetylphenylalanine
methyl ester 20 is quantitative with 4, but the enantiose-
lectivity is low (18.2% ee, Table 4, entry 1). Changing
the solvent from methanol to dichloromethane
improves the enantioselectivity (42.2% ee, entry 2) at
the expense of the chemical yield. The catalyst precur-
sors containing ligand 1b give racemic product (entries
3 and 4). The bis(2-methylallyl) complexes 8a and 8b
are nearly inactive (entries 5 and 6). For comparison,
[RuH(MeCN)3(binap)] catalyses the hydrogenation of
19 giving 20 with up to 94% ee (entry 7).33 Dimethyl
itaconate 21 was the last olefin tested. Complex 4
quantitatively hydrogenated 21 to dimethyl methylsuc-
cinate 22 with 17.1% ee (Table 5, entry 1), whereas 6
and 8a gave racemic 22 (entries 2 and 3). Indeed, the
analogue substrate itaconic acid was hydrogenated with
up to 98% ee by binap or biphemp complexes of
ruthenium (entry 4).11b
Table 4. Hydrogenation of methyl (Z)-a-acetamidocinnamate 19 to N-acetylphenylalanine methyl ester 20
Entry
Ligand
Catalyst
t (h)
Yield (%)
Ee (%)
Conf.
1
1a
1a
1b
1b
2a
3b
4
4
6
10
8a
8b
19
16
17
24
16
\99
11
25
98
18
18.2
42.2
Racemic
4.5
9.4
S
S
–
R
S
–
2a
3
4
5b
6b
7
16
17
\99
Racemic
94
c
c
(R)-Binap
R
a The solvent was CH2Cl2.
b The precatalyst was activated with CF3COOH (2 and 4 equiv. versus Ru for 8a and 8b, respectively).
c From Ref. 33, the catalyst was [RuH(solv)3((R)-binap)] (solv=MeCN or acetone).
Table 5. Hydrogenation of dimethyl itaconate 21 to dimethyl methylsuccinate 22
Entry
R
Ligand
Cat.
S/C
P(H2) (bar)
T (°C)
t (h)
Yield (%)
Ee (%)
Conf.
1
2
3
4
Me
Me
Me
H
1a
1b
2a
4
6
8a
200
200
100
100
5
5
40
3
25
25
40
50
16
16
\99
89
\99
\99
17
Racemic
3
98
R
–
R
S
16
a
a
(R)-Binap
a From Ref. 11b, ‘RuBr2((R)-binap)’ as catalyst in THF solvent.

1822
F. Maienza et al. / Tetrahedron: Asymmetry 13 (2002) 1817–1824
3. Final remarks
1.7–1.45 (dd, 2H, SiCH2), −0.175 (s, 6H, SiCH3). MS
(FAB+): m/z 543 (M+, 46), 529 (M+−BH3, 100), 517
(M+−2BH3, 23).
The present work is, to the best of our knowledge, the
first systematic investigation directed to prepare ruthe-
nium complexes containing P-stereogenic ligands with
different frameworks and aryl substituents at the phos-
phorus atoms. Overall, the P–P* ligands screened,
which feature two aryl substituents at the stereogenic
phosphorus atom, are less efficient than the related
ligands R(Me)PCH2CH2P(Me)R (BisP*; R=bulky
alkyl group) and cannot compete with the atropiso-
meric ligands of the binap family, at least in the asym-
metric hydrogenation of CꢀC and CꢀO functionalities.
The ferrocene-based ligands 1a and 1b give the highest
activity and enantioselectivity, confirming that bulky
ligands are best suited for ruthenium-based hydrogena-
tion catalysts. A remarkable feature of the above sys-
tems is the ability of 1b to act as a tetradentate
O,P,P,O-ligand with ruthenium. This feature is benefi-
cial in the hydrogenation of methyl methyl benzoylfor-
4.3. (R,R)-Si(Me)2(CH2P(o-An)Ph)2, 3b
The
diborane
adduct
(R,R)-Si(Me)2[(CH2P(o-
An)(Ph)(BH3)]2 (1.09 g, 2.01 mmol) was dissolved in
morpholine (100 mL) at room temperature. After 3
days, morpholine was evaporated under vacuum, and
the yellowish product was purified by flash chromatog-
raphy (silica gel, toluene, Rf 0.23) to remove the amine
borane complex. Evaporation of the solvent under vac-
uum gave a colourless oil. Yield: 0.217 g (21%). [h]2D0=
156 (c 1, CHCl3). 31P NMR (CDCl3): l −31.7 (s, 2P),
1H NMR (CDCl3): l 7.95–6.8 (m, 18H, ArH), 3.8 (s,
6H, OCH3), 1.6 (d, 6H, SiCH3). MS (FAB+): m/z 517
(M+, 62). Anal. calcd for C30H34O2P2Si 0.77C7H8: C,
72.14; H, 6.87. Found: C, 72.22; H, 6.89%.
mate. Together with Imamoto’s results with
a
ruthenium/BisP* system, this study suggests that a fur-
ther exploration of ruthenium complexes containing
P-stereogenic ligands with bulky alkyl groups may
prove fruitful.
4.4. [RuCl2(PPh3)((S,S)-1a)], 4
[RuCl2(PPh3)3] (213 mg, 0.222 mmol) and (S,S)-1a (144
mg, 0.222 mmol) were dissolved in CH2Cl2 (5 mL).
After stirring for 2 h at room temperature, 2-PrOH (5
mL) was slowly added. After evaporation of the sol-
vent, the dark-brown precipitate was filtered off,
washed with 2-PrOH, and dried under vacuum (198
mg, 82%). 31P NMR (CD2Cl2): 31P NMR (CD2Cl2): 4:
broad ABX system, l 58.3 (PX, 1P), 35.8 (PB, 1P), 31.7
(PA, 1P). 5: l 40.8 (br, 2P), 29.3 (br, 2P). Free PPh3: l
4. Experimental
4.1. General
Reactions with air- or moisture-sensitive materials were
carried out under an argon atmosphere using Schlenk
techniques or in a glove box under purified nitrogen.
1
−6 (br s, PPh3, w1/2=30 Hz). H NMR (CD2Cl2): l
7.87–6.89 (m, 39H, ArH), 4.85, 4.53, 4.37, 4.13 (4 s,
1
Solvents were purified by standard procedures. The H,
8H, 2CpH). MS (FAB+): m/z 1017 (M+−2Cl, 27%), 755
31P, and 11B NMR and mass spectra, HPLC, GC,
melting points, specific rotations, and elemental analy-
ses were measured as described before.21a The com-
pounds (S,S)-1a,21a (S,S)-1b,21a (S,S)-2a,13 [Ru(h3-
(CH)2CHCH3)2(COD)] 7a,28 [Ru2(h2-O2CCF3)4(OH2)-
(COD)] 7b,29 and [Ru(h2-O2CCH3)(COD)] 7c17 were
prepared according to literature procedures. The use of
ligand 3b has been reported,11 but its synthesis has not
been described, thus we report the preparation of
(R,R)-3b.
(M+−2Cl−PPh3,
72%).
Anal.
calcd
for
C60H47Cl2FeP3Ru: C, 66.19; H, 4.35. Found: C, 66.18;
H, 4.55%.
4.5. [RuCl2((S,S)-1b)], 6
[RuCl2(PPh3)3] (244 mg, 0.254 mmol) and (S,S)-1b (156
mg, 0.254 mmol) were dissolved in CH2Cl2 (5 mL).
After stirring for 3 h at room temperature, 2-PrOH (5
mL) was added as a layer over the CH2Cl2 solution.
Crystals of 6 were formed overnight by diffusion of
2-PrOH into the CH2Cl2 solution, and the orange solid
was filtered off and dried under vacuum (136 mg, 68%).
[h]D20=+81.2 (c 0.25, CHCl3). Mp 206°C (dec.). LM
(0.001 M in CH2Cl2): 0.0 V−1 cm2 mol−1. 31P NMR
(CDCl3): l 75.8 (d, 1P, JPP%=39.4 Hz), 66.7 (d, 1P,
4.2. (R,R)-Si(Me)2(CH2P(o-An)(Ph)(BH3))2, 3
sec-BuLi (1.24 M hexane solution, 4.4 mL, 1 equiv.)
was added dropwise over 10 min to a solution of
(R)-P(BH3)(Ph)(o-An)(Me) (1.43 g, 5.85 mmol) in THF
(20 mL) at a constant temperature of −78°C. After
stirring for 2 h, Cl2SiMe2 (0.35 mL, 3.0 mmol) was
rapidly added by syringe. The solution was left to reach
rt overnight. The reaction was quenched with 1 M HCl
(18 mL). The THF was evaporated, and the aqueous
phase was extracted with CH2Cl2 and dried over
MgSO4. The solvent was evaporated, and the crude
product was recrystallised from hot hexane. Yield:
1.204 g (75.5%). 31P NMR (CDCl3): l 12.4 (br q, 2P).
1H NMR (CDCl3): l 8.1–7.9 (m, 2H, ArH), 7.7-7.19
(m, 12H, ArH), 7.2-7.0 (m, 2H, ArH), 6.9–6.75 (m, 2H,
ArH), 3.62 (s, 6H, OCH3), 2.3–2.1 (dd, 2H, SiCH2),
1
JPP%=39.4 Hz). H NMR (CDCl3): l 8.14-8.07 (m, 3H,
ArH), 7.57–6.91 (m, 14H, ArH), 6.42–6.37 (m, 1H,
ArH), 5.72, 5.07, 4.79, 4.44, 4.36, 4.32, 4.28, 4.11 (8 s,
8H, 2CpH), 4.86, 3.28 (2 s, 6H, 2 OCH3). IR (CsI): 232,
241 cm−1 (w(RuCl2)). MS (FAB+): m/z 786 (M+, 100%),
751 (M+−Cl, 93%), 660 (M+−Cl−PhO+H, 11%), 583
(M+−Cl−PhO+H−Ph, 8%). Molecular mass (vapour-
pressure osmometry): 783 g/mol. Anal. calcd for
C36H32Cl2FeO2P2Ru: C, 54.98; H, 4.10. Found: C,
54.69; H, 4.25%.

F. Maienza et al. / Tetrahedron: Asymmetry 13 (2002) 1817–1824
Table 6. Analytical details of ee determination
1823
Product
Method
Column
T (°C)
Carrier
P (kPa)
Rt (R) (s)
Rt (S) (s)
12
14
16
18
20
22
GC
GC
GC
HPLC
GC
Lipodex A
Lipodex E
Lipodex E
Chiralcel OB
125
85
85
rt
170
85
H2
He
150
150
150
9.05
5.4
6.75
58.9b
17.52
11.5
9.25
6.9
He
7.9
a
64.4b
17.70
11.0
L
-Chirasil-Val
He
He
120
150
GC
Lipodex E
a Eluent:hexane/iPrOH (97:3), flow 0.1 mL min−1
.
b The attribution is arbitrary. Absolute configuration not determined.
4.6. [Ru(h2-O2CCH3)2((S,S)-1a)], 9
4.9. [Ru(h2-O2CCF3)((S,S)-1b)]O2CCF3, 10
A CH2Cl2 solution (2 mL) of 7c (11 mg, 0.034 mmol)
was added to a CH2Cl2 solution (3 mL) of (S,S)-1a (22
mg, 0.034 mmol). The reaction solution was stirred in a
glove box at room temperature for 24 h, after which the
solvent was removed under vacuum, and the product
was isolated as an orange powder (18 mg, 61%). LM
(0.001 M in CH2Cl2): 0.0 V−1 cm2 mol−1. 31P NMR
(CD2Cl2): (AX system) l 64.40 (d, 1P, PA, J(PA, PB)=
A solution of 8b (72.3 mg, 0.0814 mmol) in methanol (2
mL) was added to a CD2Cl2 solution (0.3 mL) of
(S,S)-1b (100 mg, 0.1627 mmol). The reaction mixture
was stirred in a glove box for 2 days under purified N2
at room temperature. The solvent was removed under
vacuum, and the solid was dissolved in Et2O. Partial
evaporation of Et2O gave the pure product as an
orange powder (62 mg, 81%). LM (0.001 M in CH2Cl2):
16.2 V−1 cm2 mol−1. 31P NMR (CD2Cl2): l 73.3 (d, 1P,
JPP%=42.6), 71.8 (d, 1P, JPP%=42.6). 1H NMR (CD2Cl2):
l 7.7–6.8 (m, 28H, ArH), 4.7–4.1 (m, 8H, CpH), 4.3 (br
s, 3H, OCH3), 3.7 (br s, 3H, OCH3). 19F NMR l −75.5,
−76.1 (2 s, 6F, 2CF3). MS (FAB+): m/z 829 (M+−
OCOCF3, 100). Anal. calcd for C40H32Cl2F6FeO6P2Ru:
C, 51.03; H, 3.42. Found: C, 50.75; H, 4.03%.
1
42 Hz), 78.39 (d, 1P, PB, J(PAB)=42 Hz). H NMR
(CD2Cl2): l 7.94-6.59 (m, 39H, ArH), 4.71, 4.52, 4.33,
4.18, 4.09, 4.00, 3.97, 3.72 (8 s, 8H, 2CpH), 1.91 (d, 6H,
2CH3, JPH=6.1 Hz), 1.82 (s, 2H, H2O). MS (FAB+):
m/z 873 (M+, 5%), 814 (M+−O2CCH3, 16%), 755 (M+−
2O2CCH3−1a, 35%). Anal. calcd for C46H38FeO4P2Ru:
C, 63.24; H, 4.38. Found: C, 63.32; H, 4.61%.
4.7. [Ru(h3-(CH)2CHCH3)2((S,S)-2a)], 8a
4.10. Catalytic hydrogenation
The standard procedure was as follows: the substrate
and the catalyst (3 mmol) (and, when appropriate, the
additive) were dissolved in the solvent (10 mL) under
argon. The solution was stirred for 15 min, and then
transferred via steel capillary into a 180 mL thermostat-
ically controlled glass reactor or a 50 mL stainless steel
autoclave. The inert gas was then replaced with hydro-
gen (three cycles), and the pressure was set. After
completion of the reaction, the conversion was deter-
mined by gas chromatography, and the product was
recovered after filtration of the reaction solution on a
plug of silica to remove the catalyst. Analytical details
concerning the determination of the enantiomeric
excess of the products are given in Table 6.
Complex 7a (96 mg, 0.3 mmol) and (S,S)-2a (149 mg,
0.3 mmol) were dissolved in hexane (6 mL). After
stirring for 5 h at 70°C, the solution was concentrated
under vacuum (1 mL). The resulting yellow precipitate
was filtered off, washed with hexane, and dried under
vacuum (128 mg, 61%). 31P NMR (CDCl3, 162 MHz):
l 82.6 (s, 2P). 1H NMR (CDCl3): l 8.73 (m, 2H, NpH),
7.97–6.84 (m, 22H, ArH), 4.90, 3.75 (2 s br, 4H, 4
ꢀCH), 3.94–3.32 (m, 4H, 2CH2), 1.81 (s, 6H, 2CH3).
MS (FAB+): m/z 709 (M+, 24), 598 (M+−2 (h3-
(CH)2CHCH3), 64). Anal. calcd for C42H42P2Ru: C,
71.07; H, 5.96. Found: C, 71.10; H, 6.02%.
4.8. [Ru(h3-(CH)2CHCH3)2((R,R)-2b)], 8b
A pentane solution (1 mL) of (R,R)-2b (0.217 g, 0.42
mmol) was added to 7a (0.134 g, 0.42 mmol) in pentane
(3 mL). After stirring for 2 days at room temperature,
evaporation of the solvent yielded a yellow–green pre-
cipitate, which was filtered off under argon and dried
under vacuum (0.160 g, 52%). 31P NMR (CD2Cl2): l 34
Acknowledgements
We thank the Novartis Forschungsstiftung for financial
support to F.M.
1
(s, 2P). H NMR (CD2Cl2): l 7.8–6.3 (m, 18H, ArH),
3.2 (s, 6H, OCH3), 2.2 (s, 6H, Si(CH3)2). MS (FAB+):
m/z 672 (M+−(h3-(CH)2CHCH3), 10), 617 (M+−2 (h3-
(CH)2CHCH3), 6), 442 (M+−2 (h3-(CH)2CHCH3)−Ru−
Ph+3H, 100). Anal. calcd for C38H48O2P2SiRu·
0.5C5H12: C, 63.67; H, 7.12. Found: C, 63.87; H, 6.95%.
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