New Chiral Ruthenium(II) Catalysts Containing 2,6-Bis(4′ -(R)-phenyloxazolin-2′-yl)pyridine (Ph-pybox) Ligands for Highly Enantioselective Transfer Hydrogenation of Ketones

Article abstract of DOI:10.1002/chem.200305170

Treatment of complex trans-[RuCl₂(η²-C ₂H₄){K³-N,N,N-NNN-(R,R)-Ph-pybox}] [(R,R)-Ph-pybox = 2,6-bis{4′-(R)-phenyloxazolin-2′-yl}pyridine] with phosphines or phosphites in dichloromethane at 50°C leads to the formation of novel ruthenium(II)-pybox complexes trans-[RuCl ₂(L){K³-N,N,N-(R,R)-Ph-pybox}] [L = PPh₃ (1a), PPh₂Me (2a), PPh₂(C₃H₅) (3a), PPh₂(C₄H₇) (4a), PMe₃ (5a), PiPr₃ (6a), P(OMe)₃ (7a) and P(OPh)₃ (8a)]. Likewise, reaction of trans-[RuCl₂(η²-C ₂H4₎ {K³-N,N,N-(R,R)-Ph-pybox}] with PPh ₃ or PiPr₃ in refluxing methanol leads to the complexes cis-[RuCl₂(L)(K³-N,N,N-(R,R)-Ph-pybox] [L = PPh ₃ (1b), PiPr₃ (6b)]. No trans-cis isomerisation of complexes 1a-8a has been observed. Complexes 1a-8a, 1b, 6b together with the analogous trans-[RuCl₂{P(O-Me)₃}{K ³-N,N,N-(S,S)-iPr-pybox}] (10a) and the previously reported trans- and cis-[RuCl₂(PPh₃){K³-N,N,N-(S,S)-iPr-pybox}] (9a and 9b, respectively) are active catalysts for the transfer hydrogenation of acetophenone in 2-propanol in the presence of NaOH (ketone/cat/NaOH 500:1:6). cis-Ph-pybox derivatives are the most active catalysts. In particular, cis complexes 1b and 6b led to almost quantitative conversions in less than 5 min with a high enantioselectivity (up to 95%). A variety of aromatic ketones have also been reduced to the corresponding secondary alcohols with very high TOF and ee up to 94%. The overall catalytic performance seems to be a subtle combination of the steric and/or electronic properties both the phosphines and the ketones. A high TOF (27300 h^-1) and excellent ee (94%) have been found for the reduction of 3-bromoacetophenone with catalyst 6b. Reductions of alkyl ketones also proceed with high and rapid conversions but low enantioselectivities are achieved.

Full text of DOI:10.1002/chem.200305170

FULL PAPER
New Chiral Ruthenium(ii) Catalysts Containing 2,6-Bis(4’-(R)-
phenyloxazolin-2’-yl)pyridine (Ph-pybox) Ligands for Highly
Enantioselective Transfer Hydrogenation of Ketones
DarÌo Cuervo, M. Pilar Gamasa, and Josÿ Gimeno*[a]
Dedicated to Professor Josÿ Vicente on the occasion of his 60th birthday
Abstract: Treatment of complex trans-
[RuCl2(h2-C2H4){k3-N,N,N-(R,R)-Ph-
pybox}][( R,R)-Ph-pybox = 2,6-bis{4’-
(R)-phenyloxazolin-2’-yl}pyridine]with
phosphines or phosphites in dichloro-
methane at 508C leads to the forma-
tion of novel ruthenium(ii)-pybox com-
plexes trans-[RuCl2(L){k3-N,N,N-(R,R)-
Ph-pybox}][L = PPh3 (1a), PPh2Me
(2a), PPh2(C3H5) (3a), PPh2(C4H7)
(4a), PMe3 (5a), PiPr3 (6a), P(OMe)3
(7a) and P(OPh)3 (8a)]. Likewise, re-
action of trans-[RuCl2(h2-C2H4){k3-
complexes 1a 8a has been observed.
Complexes 1a 8a, 1b, 6b together
with the analogous trans-[RuCl2{P(O-
Me)3}{k3-N,N,N-(S,S)-iPr-pybox}]( 10a)
and the previously reported trans- and
cis-[RuCl2(PPh3){k3-N,N,N-(S,S)-iPr-
pybox}]( 9a and 9b, respectively) are
active catalysts for the transfer hydro-
genation of acetophenone in 2-propa-
nol in the presence of NaOH (ketone/
cat/NaOH 500:1:6). cis-Ph-pybox deriv-
atives are the most active catalysts. In
particular, cis complexes 1b and 6b led
to almost quantitative conversions in
less than 5 min with a high enantiose-
lectivity (up to 95%). A variety of aro-
matic ketones have also been reduced
to the corresponding secondary alco-
hols with very high TOF and ee up to
94%. The overall catalytic perform-
ance seems to be a subtle combination
of the steric and/or electronic proper-
ties both the phosphines and the ke-
tones. A high TOF (27300 hÀ1) and ex-
cellent ee (94%) have been found for
the reduction of 3-bromoacetophenone
with catalyst 6b. Reductions of alkyl
ketones also proceed with high and
rapid conversions but low enantioselec-
tivities are achieved.
N,N,N-(R,R)-Ph-pybox}]with PPh
or
3
PiPr3 in refluxing methanol leads to the
Keywords: asymmetric catalysis
¥
¥
complexes
cis-[RuCl2(L)(k3-N,N,N-
hydrogen transfer
¥
ketones
(R,R)-Ph-pybox][L = PPh3 (1b), PiPr3
(6b)]. No trans cis isomerisation of
N ligands ¥ ruthenium
Introduction
performance in the catalytic hydride transfer reduction of
ketones.[3] Among other catalytic asymmetric processes,[4]
asymmetric transfer hydrogenation[5] has emerged as a relia-
ble synthetic tool for chiral alcohols, which proves the high
efficiency and stereoselectivity of transition metal complexes
containing chiral nitrogen ligands. Monotosylated 1,2-dia-
mine ligands A and B have promoted outstanding conver-
sions and enantioselectivities, mostly using either rutheni-
um[6] or rhodium and iridium[7] complexes.
The role of nitrogen-containing ligands in the catalytic activ-
ity of transition-metal complexes has become an important
feature in both homogeneous and heterogeneous catalysis.
Many new catalysts have incorporated N ligands as a choice
to compete with those containing phosphines.[1,2] It is well
established that the use of polydentate imino and amino li-
gands has provided a considerable improvement in catalyst
Although C2 chiral ligands have been widely used in a
series of catalytic processes because of their ability to gener-
ate high chiral inductions,[8] only a few ruthenium complexes
containing C2 polydentate N ligands have been reported in
transfer hydrogenations. As far as we know, only examples
bearing diaminoferrocenyl derivatives[6e,9] (C), bis(oxazo-
lines)[10] (D, E), aromatic substituted diimines[11] (F) and dia-
mines[12] (G) have been described.[13] In particular, only one
ruthenium complex, containing the tridentate N,N,N ligand
bis(oxazolinylmethyl)amine (D), has been reported (pre-
pared in situ from [RuCl2(PPh3)]and D).[10a] This fact
[a]D. Cuervo, Dr. M. P. Gamasa, Prof. Dr. J. Gimeno
Departamento de QuÌmica Orgµnica e Inorgµnica
Instituto de QuÌmica Organometµlica ™Enrique Moles∫
(Unidad Asociada al C.S.I.C.)
Facultad de QuÌmica, Universidad de Oviedo
c/Juliµn ClaverÌa s/n
33071 Oviedo (Spain)
Fax : (+34)985103446
E-mail: jgh@sauron.quimica.uniovi.es
Supporting information for this article is available on the WWW
under http://www.chemeurj.org/ or from the author.
425
Chem. Eur. J. 2004, 10, 425 432
DOI: 10.1002/chem.200305170
¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

FULL PAPER
In this work we describe the
stereoselective synthesis of
ruthenium(ii) phosphine or
phosphite complexes containing
the Ph-pybox ligand, namely
trans-[RuCl2(L)(k3-N,N,N-
(R,R)-Ph-pybox)]{L
= PPh3
(1a), PPh2Me (2a), PPh2(C3H5)
(3a) (C3H5 = -CH2-CH=CH2),
PPh2(C4H7) (4a) (C4H7
=
-CH2-C(CH3)=CH2), PMe3 (5a),
PiPr3 (6a), P(OMe)3 (7a),
P(OPh)3
(8a)}
and
cis-
[RuCl2(L)(k3-N,N,N-(R,R)-Ph-
pybox)]{L = PPh3 (1b), PiPr3
(6b)}. These complexes are
found to be active catalysts in
prompted us to study the catalytic activity of ruthenium(ii)
complexes with the ligands 2,6-bis(4’-R-oxazolin-2’-yl)pyri-
dine (R-pybox) (R = iPr, Ph) (H) which have shown re-
markable efficiency in catalytic organic transformations in-
volving asymmetric carbon carbon bond formation, with
high enantioselectivity.[14]
asymmetric transfer hydrogenation of ketones, leading to
the formation of sec-alcohols with high conversions and
enantioselectivities, some of which are among those with the
highest ee values reported to date.
Results
Synthesis: Following the synthetic procedure we reported
previously for the preparation of iPr-pybox complexes cis-
and trans-[RuCl2(PPh3){k3-N,N,N-(S,S)-iPr-pybox}]( 9a and
9b), [(S,S)-iPr-pybox = 2,6-bis[4’-(S)-isopropyloxazolin-2’-
yl]pyridine],[15] the related Ph-pybox derivatives trans-
Abstract in Spanish: El tratamiento del complejo trans-
[RuCl2(h2-C2H4){k3-N,N,N-(R,R)-Ph-pybox}][(
R,R)-Ph-
pybox = 2,6-bis{4’-(R)-feniloxazolin-2’-il}piridina]con fosfi-
nas o fosfitos en diclorometano a 508C conduce a la forma-
ciÛn de los nuevos complejos RuII-pybox: trans-
[RuCl2(L){k3-N,N,N-(R,R)-Ph-pybox}](L
=
PPh3 (1a),
[RuCl2(L){k3-N,N,N-(R,R)-Ph-pybox}][L
=
PPh3 (1a),
PPh2Me (2a), PPh2(C3H5) (3a), PPh2(C4H7) (4a), PMe3
(5a), PiPr3 (6a), P(OMe)3 (7a) and P(OPh)3 (8a)) have
been obtained (Scheme 1).
PPh2Me (2a), PPh2(C3H5) (3a), PPh2(C4H7) (4a), PMe3
(5a), PiPr3 (6a), P(OMe)3 (7a) y P(OPh)3 (8a)]. Asimismo,
la reacciÛn de trans-[RuCl2(h2-C2H4){k3-N,N,N-(R,R)-Ph-
Thus, stereoselective substitution of the ethylene ligand in
trans-[RuCl2(h2-C2H4){k3-N,N,N-(R,R)-Ph-pybox}][16]
by
pybox}]con PPh o PiPr3 en metanol a 658C genera los
3
complejos cis-[RuCl2(L)(k3-N,N,N-(R,R)-Ph-pybox][L
=
phosphines or phosphites affords, after 3 4 h of heating at
508C in dichloromethane in a sealed tube, complexes 1a 8a
which are isolated as air-stable purple (phosphines) or dark
pink (phosphites) solids (35 88% yield). Complexes 1a 8a,
which are soluble in chlorinated solvents and 2-propanol,
have been fully characterised by spectroscopic and analyti-
cal methods (see the Experimental Section for details). In
particular, the 31P{1H} NMR spectra show a singlet reso-
nance at d = 0.1 40.6 (1a 6a) and d = 123.4 146.0 (7a
and 8a). The stereochemistry is determined readily on the
basis of the 13C{1H} NMR spectra, which exhibit the expect-
ed resonances in accordance with a C2 symmetry showing
one singlet resonance both for the two methylene groups
and for the two CHPh groups in the oxazoline rings. These
data compare well with those from the known analogous
complex trans-[RuCl2(PPh3){k3-N,N,N-(S,S)-iPr-pybox}].[15]
Similarly, cis isomers 1b and 6b are obtained stereoselec-
PPh3 (1b), PiPr3 (6b)]. No se ha observado isomerizaciÛn
trans cis de los derivados 1a 8a. Los complejos 1a 8a, 1b,
6b junto con los anµlogos trans-[RuCl2{P(OMe)3}{k3-N,N,N-
(S,S)-iPr-pybox}]( 10a) y los previamente descritos trans- y
cis-[RuCl2(PPh3){k3-N,N,N-(S,S)-iPr-pybox}]( 9a y 9b, res-
pectivamente) son catalizadores activos para la reacciÛn de
transferencia de hidrÛgeno de acetofenona en 2-propanol en
presencia de NaOH (cetona/cat/NaOH = 500:1:6). Los de-
rivados cis-Ph-pybox son los catalizadores mµs activos. En
concreto, los complejos cis 1b y 6b conducen a conversiones
casi cuantitativas en menos de 5 min con alta enantioselecti-
vidad (hasta 95%). Otras cetonas aromµticas experimentan
tambiÿn reducciÛn a los correspondientes alcoholes secun-
darios obteniÿndose TOF muy altos y ee hasta 94%. Una
sutil combinaciÛn de las propiedades estÿricas y/o electrÛni-
cas tanto de las fosfinas utilizadas como de las cetonas de-
terminan los mejores resultados. La reducciÛn de 3-bromoa-
cetofenona por el catalizador 6b transcurre con un alto
TOF (27300 hÀ1) y excelente ee (94%). Se han reducido
tambiÿn alquil cetonas encontrµndose altas y rµpidas conver-
siones aunque con baja enantioselectividad.
tively
from
trans-[RuCl2(h2-C2H4){k3-N,N,N-(R,R)-Ph-
pybox}]by the reaction with PR (R = Ph, iPr) in refluxing
3
methanol (70 80% yield) (Scheme 1). The 31P{1H} NMR
spectra show a singlet resonance at d = 39.0 (1b) and d =
38.8 (6b). The 13C{1H} NMR spectra of 1b and 6b reveal
loss of the C2 symmetry, since two resonances appear for
426
¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2004, 10, 425 432

Chiral Ruthenium(ii) Catalysts
425 432
complexes (9a, 9b and 10a) as
catalysts. The most remarkable
features are:
1) Although the iPr-pybox
complexes are active cata-
lysts, Ph-pybox derivatives
show much better efficiency
and enantioselectivity (en-
tries 1 vs 4, 2 vs 5 and 3 vs
6). All major secondary al-
cohols had the S configura-
tion, except for complex
10a.
Scheme 1. Synthesis of the complexes 1a 8a, 1b and 6b.
Table 1. Catalytic activity for transfer hydrogenation of acetophenone
each of the nonequivalent carbon nuclei of CHPh and CH2
groups of the oxazoline rings (see the Experimental Section
for further details). These data can be compared with those
for cis-[RuCl2(PPh3){k3-N,N,N-(S,S)-iPr-pybox}], for which
the structure has been confirmed by X-ray crystallogra-
phy.[15] All attempts to isolate other cis-Ph-pybox complexes
have failed, leading instead either to the corresponding trans
isomers (L = PMe3, P(OMe)3) or to an uncharacterised
mixture of products (L = PPh2Me, PPh2(C3H5), P(OPh)3).
No trans cis isomerisation of complexes 1a 8a has been
observed. This is in sharp contrast with the behaviour of the
known analogous iPr-pybox complex trans-[RuCl2(PPh3){k3-
N,N,N-(S,S)-iPr-pybox}]( 9a), which isomerises rapidly in
methanol at room temperature to generate the thermody-
namically stable cis isomer 9b.[15] Apparently, the steric in-
teractions between the phosphines and the oxazoline sub-
stituents (phenyl vs isopropyl groups) govern the cis or trans
preference. This is confirmed by the observed stability of
the unsubstituted pybox complex trans-[RuCl2(PPh3)(k3-
N,N,N-pybox)], which remains unchanged when heated in
methanol for several hours.[15]
catalysed by RuII complexes containing either Ph-pybox or iPr-pybox.[a]
[b]
Catalyst
t [min]Conversion [%]
ee [%][b]
Ph-pybox complexes
1
2
3
1a
1b
7a
30 (60)
5
5
78 (90)
96
96
82 (80)
92
61
iPr-pybox complexes
4
5
6
9a
9b
10a
30 (120)
30 (120)
30
36 (56)
29 (50)
97
16 (16)
5 (2)
17
[a]Reactions were carried out at 82 8C using a 0.1m acetophenone solu-
tion in 50 mL of 2-propanol (ketone/catalyst/NaOH 500:1:24). [b]Deter-
mined by GC analysis with a Supelco b-DEX 120 chiral capillary column.
All the major secondary alcohols had the S configuration except for
entry 6. Absolute configuration was determined by comparing optical ro-
tations with literature values.
2) Very rapid conversions (almost quantitative in 5 min)
are achieved at 828C with complexes cis-
Catalytic transfer hydrogenation of ketones: Ruthenium(ii)
complexes have been widely applied as efficient catalysts in
hydrogen transfer reactions between alcohols and ketones,
so we have checked the catalytic activity of the complexes
reported herein. Moreover, it was expected that the asym-
metric induction of pybox ligands, in which the chiral cen-
tres on the oxazoline rings are located close to the metal,
might lead to good enantioselectivities. In a typical experi-
ment the ruthenium catalyst precursor (0.2 mol%) and
NaOH were added to a solution of the ketone in iPrOH at
828C, the reactions being monitored by gas chromatography.
Phenyl or isopropyl substituents in oxazoline rings of pybox
ligands have been shown to be crucial in the catalytic enan-
tioselectivities of ruthenium catalysts.[17] Therefore, we first
explored, for comparative purposes, the catalytic activities
of both trans- and cis-(R,R)-Ph-pybox with those of the cor-
responding (S,S)-iPr-pybox derivatives 9a and 9b and the
[RuCl2(PPh3)(k3-N,N,N-(R,R)-Ph-pybox)](
1b)
and
trans-[RuCl2{P(OMe)3}(k3-N,N,N-(R,R)-Ph-pybox)]( 7a)
(entries 2 and 3). The reactions become notably slower
as the temperature decreases, with no enhancement of
the enantioselectivity.
3) The efficiency and enantioselectivity of the catalyst seem
to depend not only on the phosphine (L = PPh3 (1a) vs
L = P(OMe)3 (7a); entry 1 vs 3) but also on the stereo-
isomer (entry 1 vs 2), cis-1b (L = PPh3) giving rise to
better conversion and ee value than the corresponding
trans-1a (96% in 5 min vs 90% in 60 min; 92% vs 80%
ee).
On the basis of these results, we next examined the optimi-
sation of the reaction conditions using the Ph-pybox com-
plexes as catalysts (Table 2). As a general feature, a strong
dependence is observed on the NaOH/catalyst molar ratio,
which should be not lower than approximately 6:1. Other-
wise, the reaction becomes slower and less enantioselective
(entry 1 vs 2, 3, 4).[19] On the other hand, when a higher
molar ratio is used (up to approximately 24:1) a slightly
analogous
trans-[RuCl2{P(OMe)3}{k3-N,N,N-(S,S)-iPr-
pybox}]( 10a).[18]
Table 1 summarises the conversion of acetophenone in 1-
phenylethanol with Ph-pybox (1a, 1b and 7a) and iPr-pybox
427
Chem. Eur. J. 2004, 10, 425 432
www.chemeurj.org
¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

J. Gimeno et al.
FULL PAPER
Table 2. Optimisation of reaction conditions for transfer hydrogenation
of acetophenone catalysed by RuII complexes containing Ph-pybox.[a]
Table 3. Transfer hydrogenation of acetophenone catalysed by Ph-pybox
complexes under optimised conditions.[a]
À1 [b]
Catalyst
Base [equiv][b]
t [min]Conversion [%]
ee [%]
Catalyst
t [min]TOF [h
]
Conversion [%]
ee [%]
1[c]
2
3a
3a
3a
3a
3a
1b
1b
7a
7a
6b
6b
6b
6:1
5:1
5:1
4:1
24:1
6:1
24:1
6:1
24:1
6:1
6:1
6:1
15
15
30
180
30
5
5
5
5
3
95
96
96
63
97
95
96
97
96
97
64(95)
79(97)
92
87
90
81
84
95
92
63
61
91
54(25)
86(75)
1
2
3
4
1b
6b
1a
2a
3a
4a
5a
6a
7a
8a
5
3
5700
95
97
95
97
94
95
98
96
97
25
95
91
90
94
93
90
6
90
63
5
9700
3480
3840
2760
4320
2580
5760
5820
360
3[c]
4
30
30
30
15
30
5
5
6
7
8
5[c]
6[c]
7
8
9
10
9
5
60
10
11[d]
12[e]
3(15)
3(15)
[a]Reactions were carried out at 82 8C with a 0.1m acetophenone solu-
tion in 50 mL of 2-propanol (ketone/cat/NaOH = 500:1:6). All the major
secondary alcohols had the S configuration. [b]TOF at t = 5 min, except
for entry 2 (TOF at t = 3 min). [c]Base was added 10 min before ketone.
[a]Reactions were carried out at 82 8C using a 0.1m acetophenone solu-
tion with 0.2 mol% catalyst in 50 mL of 2-propanol, except for entry 11.
All the major secondary alcohols had the S configuration. [b]Equivalents
of NaOH to catalyst. [c]Base was added 10 min before ketone. [d]A 1 m
acetophenone solution in 5 mL of 2-propanol with 0.2 mol% catalyst was
used. [e]Reaction in the presence of 2 equiv of P iPr3.
and enantioselectivity; complex 6a containing the bulkier
phosphine PiPr3 had the best performance (TOF
=
5760 hÀ1; ee 90%) (entry 8). This is in contrast to the trend
found in phosphite complexes, for which the bulkier ligand
P(OPh)3 is almost inactive (8a (L = P(OPh)3, TOF =
360 hÀ1, ee 5%) vs 7a (L = P(OMe)3, TOF = 5820 hÀ1, ee
63%) (entry 10 vs 9).
lower enantioselectivity (entry 6 vs 7; 8 vs 9) and/or a slower
reactivity (entry 2 vs 5) are found. Intermediate molar ratios
(for example, 10:1) were tested; a value of 6:1 gave the best
performance, apparently indicating that
a
compromise
Various aryl-substituted ketones have also been reduced
to the corresponding sec alcohols. Table 4 (entries 1 10)
shows the best results in terms of TOF and ee values for
each substrate (additional tables collecting complete data,
including catalysts 1a, 1b, 3a, 6a, 6b and 7a, are available
as Supporting Information).[21] Confirming the catalytic ac-
tivity observed for the reduction of acetophenone, complex
6b also shows the best activities and enantioselectivities for
most of the substrates (TOF and ee values in the range
2820 27300 hÀ1 and 86 94%, respectively) (entries 3, 5, 7, 8
should be reached in the amount of the stoichiometric
excess of base. In a more concentrated solution (1m vs 0.1m
ketone; entry 11), high losses of both the activity (64% vs
97% in 3 min) and enantioselectivity (54% vs 91%) occur-
red, along with a rapid erosion of the ee value over time.[20]
Preliminary experiments proved the influence of the coor-
dinated phosphine in the activity of the catalyst (Table 1).
To evaluate the influence of the electronic and/or steric
properties of the phosphines we examined the catalytic ac-
tivity of all cis and trans (R,R)-
Table 4. Transfer hydrogenation of ketones catalysed by Ph-pybox complexes under optimised conditions.[a]
Ph-pybox complexes (1b, 6b
and 1a 8a, respectively) for the
reduction
of
acetophenone
under the optimised reaction
conditions (Table 3). Except for
À1 [b]
Ketone
Catalyst t [min]Conversion [%T] OF [h
]
ee [%]Configuration
1
2
3
R = Me[c]
R = Me[c]
R = Et
1b
6b
6b
5
3
5
95
97
97
5700
95
91
92
S
S
S
complex 8a (L
=
P(OPh)3,
9700[d]
5820
entry 10), the reactions were
almost complete in a short time
(3 30 min), demonstrating that
the performances of the cis iso-
mers 1b and 6b, with excellent
enantioselectivities, were better
than those of the corresponding
trans isomers (entries 1 and 2).
When cis isomers are used the
conversion seems to be favoured
for 6b (L = PiPr3) over 1b (L
= PPh3), (97% in 3 min vs 95%
in 5 min) whilst there is a slight
decrease in the enantioselectivi-
ty (91% vs 95% ee) (entry 1 vs
2). For the trans isomers 1a 8a,
the steric properties of the phos-
phines seem to have the domi-
4
5
X = MeO
X = Br
7a 15
99
32(65)
3490
2820
76
86(80)
S
S
6b
1(60)
6[e]
7
X = MeO
X = Br
3a 15
97
91(>99)
4320
91
94(93)
S
S
6b
1(3)
27300[f]
8
X = MeO
X = Br
6b
3a 120
5
83
97
4980
600
89
70
S
S
9[e]
10
6b
5
97
5820
92
S
11
12
13
R = Et
R = Et
R = iPr
6b 10
7a 10
7a 10
>99
>99
99
5700
5820
4440
11
11
31
R
S
S
[a]Reactions were carried out at 82 8C using a 0.1m ketone solution in 50 mL of 2-propanol (ketone/catalyst/
NaOH 500:1:24). [b]TOF at t = 5 min. [c]Ketone/catalyst/NaOH 500:1:6. [d]TOF at t = 3 min. [e]Base was
nant influence on the efficiency added 10 min before ketone. [f]TOF at t = 1 min.
428
¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2004, 10, 425 432

Chiral Ruthenium(ii) Catalysts
425 432
and 10). However, trans isomers are the most active for the
reduction of 2-methoxyacetophenone (7a; entry 4), 3-me-
thoxyacetophenone (3a; entry 6) and 4-bromoacetophenone
(3a; entry 9) (TOF and ee values in the range 600 4320 hÀ1
and 70 91%, respectively).
Alkyl ketones are also reduced rapidly and quantitatively
in approximately 10 min (entries 11, 12 and 13), but low
enantioselectivities are achieved.
Discussion
Figure 1. Transition structures of asymmetric transfer hydrogenation of
aromatic ketones.
We report here a series of six-coordinate cis- and trans-di-
chlororuthenium(ii) complexes containing the chiral terden-
tate ligands 2,6-bis(4’-R-oxazolin-2’-yl)pyridine (R = Ph,
iPr). Starting from the readily accessible precursor trans-
2) the higher activity of the cis than the trans precursors
from which the active species (A) are directly accessible;
3) the absolute configurations of the sec-alcohols (S) result-
ing from the selective enantiofacial binding ability of the
metal fragment which enables the approach of the aryl
ketones to the coordination site through the less hin-
dered enantioface. This leads to an optimisation of the
chiral pocket by reducing the steric interactions between
the aryl groups of the oxazoline ring and the ketones.
[RuCl2(h2-C2H4){k3-N,N,N-(R,R)-Ph-pybox}],
complexes
trans-1a 8a, cis-1b and 6b, along with the previously re-
ported trans- and cis-[RuCl2(PPh3){k3-N,N,N-(S,S)-iPr-
pybox}][15] (9a and 9b, respectively) and the analogous
(S,S)-iPr-pybox complex trans-[RuCl2{P(OMe)3}{k3-N,N,N-
(S,S)-iPr-pybox}],[18] (10a) are prepared stereoselectively in
good yield. These derivatives belong to the series of chloride
ruthenium(ii) complexes which fulfil the requirement to be
precursors of active species in the catalytic hydrogenation of
ketones by hydrogen transfer from iPrOH/base. It is well es-
tablished that the hydrogen transfer occurs through the for-
mation of ruthenium hydride intermediates and that the
role of the base is the generation of the hydride species
from the chloride derivatives.[22] An active 16-electron spe-
cies is also required mechanistically, to provide the vacant
site that enables attachment of the ketone (hydridic
route).[22] We have not performed a mechanistic study, but
the basic solution used in the catalytic processes most prob-
ably leads to the formation of the hydride intermediate re-
quired: that is, extraction of one chloride ligand and genera-
tion of the metal hydride bond (by b-elimination of isoprop-
oxide), in addition to ketone coordination through dissocia-
tion of the other chloride ligand. Figure 1 shows the putative
four-membered cyclic transition state which should govern
the coordination of the ketone (A or B) and the kinetically
controlled formation of the major diastereoisomer responsi-
ble for the enantioselectivity.
It is apparent that the cis complexes 1b (L = PPh3) and
6b (L = PiPr3) also containing the bulkier phosphines show
the best performances in the reductions of acetophenone
(Table 3), for which the highest activity and enantioselectivi-
ty are achieved. However, as shown in Table 4 for substitut-
ed aryl ketones, the overall catalytic performance seems to
be the result of a subtle combination of the steric and/or
electronic properties of both the phosphines and the ke-
tones. Although conversion and ee values are affected in
each catalyst by the substituent and its position with respect
to the ketone group, a general trend in terms of steric and/
or electronic effects cannot be deduced.
Table 5 shows the influence of the substituent and its posi-
tion in the aryl group on the catalytic activity of complex
6b. Whereas 2- and 4-bromoacetophenone are reduced with
moderate conversions and/or ee values (entries 2 and 6), ex-
cellent values are achieved for 3-bromoacetophenone
(entry 4). No equivalent influence on conversion and ee is
This proposal is consistent
with:
Table 5. Transfer hydrogenation of aryl-substituted ketones catalysed by complex 6b under optimised condi-
tions.[a]
À1 [b]
Ketone
t [min]Conversion [%]TOF [h
]
ee [%]
1) the observed loss in the cat-
alytic activity (from 97 to
79%) and the fast erosion
of the ee value (from 91 to
86 and 75% after 15 min) in
the presence of free phos-
phine (Table 2; entry 10 vs
12), which indicates un-
equivocally the interference
of the phosphine with the
ketone by occupying the
vacant site;[23]
1
2
X = MeO
X = Br
120
60
94
65
2100
2820
47
80
3
4
X = MeO
X = Br
5
97
5820
82
94 (93)
1(3)
91 (>99)
27300[b]
5
6
X = MeO
X = Br
5
60
83
69
4980
1260
89
54
[a]Reactions were carried out at 82 8C using a 0.1m ketone solution in 50 mL of 2-propanol (ketone/catalyst/
NaOH = 500:1:24). All the major secondary alcohol products had the S-configuration. [b]TOF at t = 5 min.
[c]TOF at t = 1 min.
429
Chem. Eur. J. 2004, 10, 425 432
www.chemeurj.org
¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

J. Gimeno et al.
FULL PAPER
Complex 1a: Yield 53% (0.075 g); elemental analysis (%): calcd for
C41H34Cl2N3O2PRu¥0.5CH2Cl2: C 58.91, H 4.17, N 4.97; found: C 59.27, H
4.34, N 5.35; 31P{1H} NMR (CDCl3): d = 40.56 (s); 1H NMR (CDCl3):
d = 4.43 and 4.74 (m, 2H each, CH2), 4.89 (t, 2H, J(H,H) = 8.4 Hz,
CHPh), 6.72 7.42 (m, 25H, Ph), 7.92 (s, 3H, C5H3N); 13C{1H} NMR
(CDCl3): d = 69.85 (s, CHPh), 80.39 (s, CH2), 124.12, 127.54, 128.32
128.91, 134.54, 134.67, 139.50 (s, Ph, and CH of C5H3N), 137.14 (d, J(C,P)
= 37.6 Hz, iPPh3), 149.56 (s, C2,6 of C5H3N), 168.24 (s, C=N).
found for derivatives containing the electron-releasing me-
thoxy group. Thus, the highest conversion is again found for
the 3-substituted ketone (entry 3), but a better ee is ach-
ieved for the 4-substituted one (entry 5). The 2-methoxy
ketone (entry 1) produces a moderate performance. There-
fore, the optimisation of the chiral pocket apparently re-
quires an appropriate phosphine with specific steric and
electronic properties for each substrate.
Nevertheless, as far as we know, cis complexes 1b and 6b
are among the best catalysts reported to date for asymmet-
ric transfer hydrogenation of ketones, with efficiencies and
selectivities comparable to those of the Noyori catalysts.[6]
The highest TOF (27300 hÀ1) and excellent ee (94%) found
for the reduction of 3-bromoacetophenone by catalyst 6b
are noteworthy. Although reductions with highly efficient
asymmetric ruthenium(ii) catalysts containing the chiral
ligand [(4S)-2-(Sp)-2-diphenylphosphinoferrocenyl]-4-isopro-
pyloxazoline have also been described, they proceed with a
slower rate and in addition a larger quantity of catalyst is re-
quired (0.5 mol%).[24]
Complex 4a: Yield 73% (0.100 g); elemental analysis (%): calcd for
C39H36Cl2N3O2PRu: C 59.93, H 4.64, N 5.38; found: C 59.11, H 4.14, N
5.19; 31P{1H} NMR (CDCl3): d = 38.16 (s); 1H NMR (CDCl3): d = 0.82
(s, 3H, Me), 2.06 and 2.82 (m, 1H each, PCH2), 3.88 and 4.11 (s, 1H
each, C(Me)=CH2), 4.36 (m, 2H, CHPh), 4.81 4.93 (m, 4H, OCH2),
6.56 7.30 (m, 20H, Ph), 7.75 (m, 3H, C5H3N); 13C{1H} NMR (CDCl3): d
= 24.60 (s, Me), 35.55 (d, J(C,P) = 17.3 Hz, PCH2), 69.38 (s, CHPh),
78.91 (s, OCH2), 114.09 (d, 3J(C,P)
= 6.2 Hz, C(Me)=CH2), 123.55,
126.51 140.54 (s, Ph, C(Me)=CH2, and CH of C5H3N), 148.70 (s, C2,6 of
C5H3N), 167.20 (s, C=N).
Complex 6a: Yield 80% (0.148 g); elemental analysis (%): calcd for
C32H40Cl2N3O2PRu: C 54.78, H 5.75, N 5.99; found: C 53.97, H 5.46, N
5.83; 31P{1H} NMR (CDCl3): d = 34.14 (s); 1H NMR (CDCl3): d = 0.74
(br, 7H) and 1.20 (br, 11H) (Me), 2.19 (br, 3H, CHMe2), 4.51 (m, 2H,
CHPh), 5.00 5.18 (m, 4H, CH2), 7.14 7.33 (m, 10H, Ph), 7.87 (s, 3H,
C5H3N); 13C{1H} NMR (CDCl3): d = 16.55 and 18.58 (br, Me), 27.65 (br,
CHMe2), 69.83 (s, CHPh), 78.65 (s, CH2), 124.26, 126.90, 127.65, 128.01,
128.61, 128.76 and 132.54 (s, Ph, and CH of C5H3N), 139.31 (s, Cipso of
Ph), 149.03 (s, C2,6 of C5H3N), 168.32 (s, C=N).
Conclusion
Complex 8a: Yield 35% (0.078 g); elemental analysis (%): calcd for
C41H34Cl2N3O5PRu: C 57.82, H 4.02, N 4.93; found: C 57.39, H 4.43, N
This work reports a new type of highly efficient catalysts for
transfer hydrogenation of aryl ketones. The presence of the
phenyl substituent in the oxazoline ring of the tridentate
chiral ligand pybox is important for attainment of high cata-
lytic activity and enantioselectivity, which indeed are among
the best reported to date for the asymmetric reduction of
ketones. Providing that the pybox chiral ligands are com-
mercially available[25] and the ruthenium(ii) complexes are
air-stable and exhibit good thermal stability, wide practical
utility in transfer hydrogenation of ketones may be predict-
ed.
1
4.99; 31P{1H} NMR (CDCl3): d = 123.41 (s); H NMR (CDCl3): d = 4.47
(t, J(H,H) = 7.4 Hz, 2H, CHPh), 5.07 and 5.18 (m, 2H each, CH2), 6.58
7.11 (m, 25H, Ph), 7.92 (d, 2H, J(H,H) = 6.5 Hz, H3,5 of C5H3N), 8.02 (t,
1H, J(H,H) = 7.1 Hz, H4 of C5H3N); 13C{1H} NMR (CDCl3): d = 70.10
(s, CHPh), 79.33 (s, CH2), 121.40, 121.45, 123.05, 123.60, 127.10, 127.44,
128.30, 128.36, 136.83 and 138.98 (s, Ph, and CH of C5H3N), 147.92 (s,
C2,6 of C5H3N), 152.39 (d, 2J(C,P) = 14.6 Hz, Cipso of Ph of P(OPh)3),
166.26 (s, C=N).
Synthesis of trans complexes 2a, 3a, 5a and 7a: A solution of trans-
[RuCl2(h2-C2H4){k3-N,N,N-(R,R)-Ph-pybox}](0.150 g, 0.263 mmol) and a
small excess of phosphine or phosphite (0.316 mmol) in dichloromethane
(15 mL) was heated at 508C in a sealed tube for 4 h. The residue was
then concentrated to ca. 3 mL and a mixture (50 mL) of pentane/diethyl
ether (2:1) was added, yielding a purple (for 2a, 3a and 5a) or a dark
pink solid (for 7a) which was washed with pentane (3î30 mL) and
vacuum-dried.
Complex 2a: Yield 73% (0.142 g); elemental analysis (%): calcd for
C36H32Cl2N3O2PRu: C 58.30, H 4.35, N 5.67; found: C 58.09, H 4.22, N
5.62; 31P{1H} NMR (CDCl3): d = 17.46 (s); 1H NMR (CDCl3): d = 1.36
Experimental Section
General: The manipulations were performed under an atmosphere of dry
nitrogen using vacuum-line and standard Schlenk techniques. All re-
agents were obtained from commercial suppliers and used without fur-
ther purification. Solvents were dried by standard methods and distilled
under nitrogen before use. [RuCl2(h2-C2H4){k3-N,N,N-(R,R)-Ph-pybox}]
and PPh2(C3H5) were prepared by the methods reported in the literature.
Infrared spectra were recorded on a Perkin-Elmer 1720-XFT spectrome-
ter. The conductivities were measured at room temperature, in acetone
(ca. 10À4 m) solutions, with a Jenway PCM3 conductimeter. The C, H and
N analyses were carried out with a Perkin-Elmer 240-B microanalyser.
2
(d, 3H, J(H,P) = 5.6 Hz, Me), 4.45 (m, 2H), 4.72 (m, 2H) and 4.98 (m,
2H) (CH2 and CHPh), 6.74 7.43 (m, 20H, Ph), 7.90 (s, 3H, C5H3N);
13C{1H} NMR (CDCl3): d = 14.45 (d, J(C,P) = 28.0 Hz, Me), 69.14 (s,
CHPh), 79.39 (s, CH2), 123.41, 126.80 133.37 and 138.68 (s, Ph, and CH
of C5H3N), 135.99 (d, J(C,P) = 36.7 Hz, Cipso of Ph of PPh2Me), 141.39
(d, J(C,P) = 33.2 Hz, Cipso of Ph of PPh2Me), 148.87 (s, C2,6 of C5H3N),
167.33 (s, C=N).
Complex 3a: Yield 88% (0.179 g); elemental analysis (%): calcd for
C38H34Cl2N3O2PRu: C 59.46, H 4.46, N 5.47; found: C 58.54, H 4.94, N
5.55; 31P{1H} NMR (CDCl3): d = 33.93 (s); 1H NMR (CDCl3): d = 1.93
and 2.97 (m, 1H each, PCH2), 4.27 4.43 (m, 4H) and 4.81 4.95 (m, 4H)
(OCH2, CHPh and CH=CH2), 6.63 (m, 1H, CH=CH2), 6.84 (m, 3H),
6.98 7.25 (m, 17H), 7.72 (m, 1H) and 7.87 (m, 2H) (Ph and C5H3N);
13C{1H} NMR (CDCl3): d = 33.06 (d, J(C,P) = 21.0 Hz, PCH2), 69.30 (s,
CHPh), 78.91 (s, OCH2), 116.74 (d, 3J(C,P) = 7.6 Hz, CH=CH2), 123.53,
126.74 129.00, 132.56, 133.39, 133.50, 133.60, 136.84 and 138.80 (s, Ph,
CH=CH2, and CH of C5H3N), 148.69 (s, C2,6 of C5H3N), 167.21 (s, C=N).
NMR spectra were recorded on
a Bruker DPX-300 instrument at
300 MHz (1H), 121.5 MHz (31P) or 75.4 MHz (13C) using SiMe4 or 85%
H3PO4 as standards. DEPT experiments have been carried out for all the
complexes.
Synthesis of trans complexes 1a, 4a, 6a and 8a: A solution of trans-
[RuCl2(h2-C2H4){k3-N,N,N-(R,R)-Ph-pybox}](0.150 g, 0.263 mmol) and an
excess of the phosphine or phosphite (1.315 mmol) in dichloromethane
(15 mL) was heated at 508C in a sealed tube for 4 h. The solvent was
then concentrated to about 3 mL and the residue transferred to a silica
gel chromatography column. Elution with a mixture of dichloromethane/
methanol (50:1) gave a purple band (for 1a, 4a and 6a) or a dark pink
band (for 8a) from which the corresponding complex was isolated by sol-
vent removal.
Complex 5a: Yield 65% (0.105 g); elemental analysis (%): calcd for
C26H28Cl2N3O2PRu: C 50.57, H 4.57, N 6.81; found: C 49.61, H 4.88, N
6.65; 31P{1H} NMR (CDCl3): d = 0.08 (s); 1H NMR (CDCl3): d = 1.02
(d, 2J(H,P) = 8.6 Hz, Me), 4.52 (m, 2H) and 5.16 (m, 4H) (CH2 and
CHPh), 7.24 7.34 (m, 10H, Ph), 7.92 (m, 3H, C5H3N); 13C{1H} NMR
430
¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
Chem. Eur. J. 2004, 10, 425 432

Chiral Ruthenium(ii) Catalysts
425 432
(CDCl3): d = 16.89 (d, J(C,P) = 25.7 Hz, Me), 69.90 (s, CHPh), 78.69 (s,
CH2), 123.46 (s, C3,5 of C5H3N), 127.33, 128.04, 128.65 (s, Ph), 132.01 (s,
C4 of C5H3N), 139.26 (s, Cipso of Ph), 148.21 (s, C2,6 of C5H3N), 167.47 (s,
C=N).
ganic Synthesis, Vol. 2 (Eds.: M. Beller, C. Bolm), Wiley-VCH,
Weinheim, 1998, p. 97.
[4]a) A. Pfaltz, Acta Chem. Scand. Ser. B 1996, 50, 189 194; b) B.
Trost, D. L. Van Vranken, Chem. Rev. 1996, 96, 395 422; c) D. J.
Ager, I. Prakash, D. R. Schaad, Chem. Rev. 1996, 96, 835 875;
d) A. K. Ghosh, P. Mathivanan, J. Cappiello, Tetrahedron 1998, 54,
Complex 7a: Yield 72% (0.085 g); elemental analysis (%): calcd for
C26H28Cl2N3O5PRu: C 46.93, H 4.24, N 6.31; found: C 46.91, H 4.40, N
1
6.12; 31P{1H} NMR (CDCl3): d = 146.05 (s); H NMR (CDCl3): d = 3.12
1
45.
(d, 9H, 3J(H,P) = 10.2 Hz, Me), 4.55 (m, 2H, CHPh), 5.17 (m, 4H,
[5]For recent reviews see: a) R. Noyori, S. Hashiguchi, Acc. Chem. Res.
1997, 30, 97 102; b) M. J. Palmer, M. Wills, Tetrahedron: Asymme-
try 1999, 10, 2045 2061; c) R. Noyori, M. Yamakawa, S. Hashiguchi,
J. Org. Chem. 2001, 66, 7931 7944; d) K. Everaere, A. Mortreux, J.-
F. Carpentier, Adv. Synth. Catal. 2003, 345, 67 77; e) D. Carmona,
M. P. Lamata, L. A. Oro, Eur. J. Inorg. Chem. 2002, 2239 2251.
[6]a) S. Hashiguchi, A. Fujii, J. Takehara, T. Ikariya, R. Noyori, J. Am.
Chem. Soc. 1995, 117, 7562 7563; b) A. Fujii, S. Hashiguchi, N. Ue-
matsu, T. Ikariya, R. Noyori, J. Am. Chem. Soc. 1996, 118, 2521
2522; c) K. Matsumura, S. Hashiguchi, T. Ikariya, R. Noyori, J. Am.
Chem. Soc. 1997, 119, 8738 8739; d) K.-J. Haack, S. Hashiguchi, A.
Fujii, T. Ikariya, R. Noyori, Angew. Chem. 1997, 109, 297 300;
Angew. Chem. Int. Ed. Engl. 1997, 36, 285 288; e) K. P¸ntener, L.
Schwink, P. Knochel, Tetrahedron Lett. 1996, 37, 8165 8168;
f) water-soluble ruthenium(ii) catalysts containing (S)-proline amide
ligands have also given excellent performances: H. Y. Rhyoo, H.-J.
Park, Y. K. Chung, Chem. Commun. 2001, 2064 2065.
[7]a) K. Murata, T. Ikariya, R. Noyori, J. Org. Chem. 1999, 64, 2186
2187; b) K. Mashima, T. Abe, K. Tani, Chem. Lett. 1998, 1199 1200;
c) K. Mashima, T. Abe, K. Tani, Chem. Lett. 1998, 1201 1202.
[8]a) I. Ojima in Comprehensive Asymmetric Catalysis (Eds.: E. N. Ja-
cobsen, A. Pfaltz, H. Yamamoto), Springer, Heidelberg, 1999; b) I.
Ojima, Catalytic Asymmetric Synthesis, 2nd ed., VCH, Weinheim,
2000; c) S. E. Denmark, E. N. Jacobsen (Eds.), Acc. Chem. Res.
2000, 33(6), special issue on Catalytic Asymmetric Synthesis.
CH2), 7.25 7.31 (m, 10H, Ph), 7.90 (m, 3H, C5H3N); 13C{1H} NMR
2
(CDCl3): d = 51.39 (d, J(C,P) = 5.6 Hz, Me), 70.39 (s, CHPh), 79.24 (s,
CH2), 123.08 (s, C3,5 of C5H3N), 127.42, 127.74, 128.39 (s, CH of Ph),
135.83 (s, C4 of C5H3N), 139.45 (s, Cipso of Ph), 148.17 (s, C2,6 of C5H3N),
166.32 (s, C=N).
Synthesis of cis complexes 1band 6b : A solution of trans-[RuCl2(h2-
C2H4){k3-N,N,N-(R,R)-Ph-pybox}](0.150 g, 0.263 mmol) and an excess of
phosphine (0.789 mmol) in methanol (15 mL) was heated at 658C for 5 h.
The solvent was then concentrated to ca. 3 mL and the residue transfer-
red to a silica gel chromatography column. Elution with a mixture of di-
chloromethane/methanol (50:1) gave a red band from which the corre-
sponding complex was isolated by solvent removal.
Complex 1b: Yield 70% (0.295 g); elemental analysis (%): calcd for
C41H34Cl2N3O5PRu¥0.5CH2Cl2: C 58.91, H 4.17, N 4.97; found: C 59.27, H
1
4.34, N 5.35; 31P{1H} NMR (CDCl3): d = 39.03 (s); H NMR (CDCl3): d
= 4.30 4.63 (m, 4H, CH2), 5.03 and 5.50 (m, 1H each, CHPh), 6.91 7.64
(m, 28H, Ph and C5H3N); 13C{1H} NMR (CDCl3): d
= 67.90, 68.30,
78.18, 81.13 (s, CH2 and CHPh), 124.44, 124.54, 127.62 128.91, 130.88,
131.92, 132.06, 132.35, 132.48, 133.03, 136.62, 139.04 (s, Ph, and CH of
C5H3N), 151.79, 152.15 (s, C2,6 of C5H3N), 167.70, 169.44 (s, C=N).
Complex 6b: Yield 81% (0.148 g); elemental analysis (%): calcd for
C41H34Cl2N3O5PRu¥0.5CH2Cl2: C 52.46, H 5.55, N 5.65; found: C 53.12,
1
H 5.89, N 5.74; 31P{1H} NMR (CDCl3): d = 38.83 (s); H NMR (CDCl3):
d = 0.69 0.76 (br, 6H) and 1.06 1.40 (br, 12H) (Me), 1.90 (m, 1H) and
2.12 (m, 2H) (CHMe2), 4.48 (m, 1H), 4.97 (m, 1H), 5.19 (m, 3H) and
5.42 (m, 1H) (CH2 and CHPh), 7.22 7.29 (m, 7H) and 7.56 7.70 (m, 6H)
(Ph and C5H3N); 13C{1H} NMR (CDCl3): d = 19.04 and 20.17 (s, Me),
28.30 (d, J(C,P) = 19.7 Hz, PCH), 67.49 and 69.75 (s, CHPh), 78.46 and
79.63 (s, CH2), 124.90 and 125.11 (s, C3,5 of C5H3N), 128.03 129.63 (s, Ph,
and C4 of C5H3N), 137.18 and 139.11 (s, Cipso of Ph), 154.51 and 155.28 (s,
C2,6 of C5H3N), 168.65 and 169.37 (s, C=N).
[9]L. Schwink, T. Ireland, K. P¸ntener, P. Knochel, Tetrahedron: Asym-
metry 1998, 9, 1143 1163.
[10]a) Y. Jiang, Q. Jiang, X. Zhang, J. Am. Chem. Soc. 1998, 120, 3817
3818; b) M. GÛmez, S. Jansat, G. Muller, M. C. Bonnet, J. A. J. Breu-
zard, M. Lemaire, J. Organomet. Chem. 2002, 659, 186 195.
[11]P. Krasik, H. Alper, Tetrahedron 1994, 50, 4347 4354.
[12]a) F. Touchard, P. Gamez, F. Fache, M. Lemaire, Tetrahedron Lett.
1997, 38, 2275 2278; b) F. Touchard, F. Fache, M. Lemaire, Tetrahe-
dron: Asymmetry 1997, 8, 3319 3326.
[13]A series of ruthenium complexes containing tridentate N,P,N ligands
have also been found to be active in asymmetric transfer hydrogena-
tion: a) Q. Jiang, D. Van Plew, S. Murtuza, X. Zhang, Tetrahedron
Lett. 1996, 37, 797 800; b) Y. Jiang, Q. Jiang, G. Zhu, X. Zhang,
Tetrahedron Lett. 1997, 38, 215 218; c) Y. Jiang, Q. Jiang, G. Zhu,
X. Zhang, Tetrahedron Lett. 1997, 38, 6565 6568.
General procedure for hydrogen transfer reactions: The ketone (5 mmol)
and the catalyst (0.01 mmol) were placed in a three-bottomed Schlenck
flask under a dry nitrogen atmosphere and 2-propanol (50 mL) was
added. The solution was heated at 828C and the corresponding amount
of base from a 0.080m solution in 2-propanol was added after 15 min
(unless otherwise specified). The reaction was monitored by gas chroma-
tography. The corresponding alcohol and acetone were the only products
detected in all cases.
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Acknowledgement
This work was supported by the FICYT (project PR-01-GE-4) and
DGICYT (project FEDER 1FD97-0565).
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431
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¹ 2004 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim

J. Gimeno et al.
FULL PAPER
[15]V. Cadierno, M. P. Gamasa, J. Gimeno, L. Iglesias, S. GarcÌa-
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[16]H. Nishiyama, Y. Itoh, H. Matsumoto, S.-B. Park, K. Itoh, J. Am.
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[17]See, for instance: a) H. Nishiyama, Y. Itoh, Y. Sugawara, H. Matsu-
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in the asymmetric cyclopropanation of olefins with diazoacetates
base, which may occur before the chloride abstraction from the
metal. Therefore, the active species probably contain diphenyl(2-
methylvinyl)phosphine.
[20]Pathways that favour the reverse reaction leading to loss of ee
cannot be discarded either.
[21]We have found that a base/catalyst of ca. 24:1 leads to better con-
versions for these substrates, in contrast to the ratio (ca. 6:1) found
for acetophenone.
catalysed by the [RuCl2(C2H4)(R-pybox)]complexes,
iPr-pybox
complex has been found to be much more active and selective than
the Ph-pybox analogues; according to ref. [14k]: copper(i)-Ph-pybox
complexes are more active and enantioselective catalysts in the ad-
dition of terminal alkynes to imines than the corresponding iPr-
pybox analogues.
[22]For a short review and mechanistic studies see: a) J.-E. B‰ckvall, J.
Organomet. Chem. 2002, 652, 105 111; b) O. P‡mies, J.-E. B‰ckvall,
Chem. Eur. J. 2001, 7, 5052 5058.
[23]The dissociation of the coordinated phosphine or phosphite has to
be discarded; otherwise, no influence on ee values would be ob-
served.
[24]Y. Nishibayashi, I. Takei, S. Uemura, M. Hidai, Organometallics
1999, 18, 2291 2293.
[25]From Aldrich 2003 2004: ( R,R)-Ph-pybox (49606-5); (S,S)-Ph-
pybox (49607-3). From TCI 2003: (R,R)-Ph-pybox (B2219); (S,S)-
Ph-pybox (B2220).
[18]Complex 10a has been prepared by heating a mixture of [RuCl2(h2-
C2H4){k3-N,N,N-(S,S)-iPr-pybox}]and an excess of P(OMe) at 408C
3
in dichloromethane for 1 h (35% yield) (unpublished results from
this laboratory).
[19]For complexes containing the allyl-substituted phosphines an im-
provement in performance has been obtained by adding the base
10 min before the ketone (entry 3 vs 2). This fact may be explained
by assuming an isomerisation of the allyl group in the presence of
Received: May 23, 2003
Revised: July 2, 2003 [F5170]
432
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