Osmium pyme complexes for fast hydrogenation and asymmetric transfer hydrogenation of ketones

Article abstract of DOI:10.1002/chem.200701719

The osmium compound trans,cis-[OsCl₂(PPh₃) ₂(Pyme)] (1) (Pyme = 1 -(pyridin-2-yl)methanamine), obtained from [OsCl₂(PPh₃)₃] and Pyme, thermally isomerizes to cis,cis-[OsCl₂(PPh₃)₂(Pyme)] (2) in mesitylene at 150°C. Reaction of [OsCl₂(PPh₃) ₃] with Ph₂P(CH₂)₄PPh₂ (dppb) and Pyme in mesitylene (150°C, 4h) leads to a mixture of trans-[OsCl₂(dppb)(Pyme)] (3) and cis-[OsCl₂(dppb)(Pyme)] (4) in about an 1:3 molar ratio. The complex trans-[OsCl₂(dppb)(Pyet) ] (5) (Pyet = 2-(pyridin-2-yl)ethanamine) is formed by reaction of [OsCl ₂(PPh₃)₃] with dppb and Pyet in toluene at reflux. Compounds 1, 2, 5 and the mixture of isomers 3/4 efficiently catalyze the transfer hydrogenation (TH) of different ketones in refluxing 2-propanol and in the presence of NaOiPr (2.0 mol%). Interestingly, 3/4 has been proven to reduce different ketones (even bulky) by means of TH with a remarkably high turnover frequency (TOF up to 5.7 × 10⁵h^-1) and at very low loading (0.05-0.001 mol%). The system 3/4 also efficiently catalyzes the hydrogenation of many ketones (H₂, 5.0 atm) in ethanol with KOtBu (2.0 mol %) at 70°C (TOF up to 1.5 × 10⁴h^-1). The in-situ-generated catalysts prepared by the reaction of [OsCl₂- (PPh₃)₃] with Josiphos diphosphanes and (±)-1-alkyl-substituted Pyme ligands, promote the enantioselective TH of different ketones with 91-96% ee (ee = enantiomeric excess) and with a TOF of up to 1.9×10⁴h^-1 at 60°C.

Full text of DOI:10.1002/chem.200701719

FULL PAPER
DOI: 10.1002/chem.200701719
Osmium Pyme Complexes for Fast Hydrogenation and Asymmetric Transfer
Hydrogenation of Ketones
Walter Baratta,* Maurizio Ballico, Alessandro Del Zotto, Katia Siega,
[a]
Santo Magnolia, andPierluigi Rigo
Dedicated to Professor Wolfgang A. Herrmann on the occasion of his 60th birthday
Abstract: The osmium compound
trans,cis-[OsCl2(PPh3)2(Pyme)] (1)
(Pyme=1-(pyridin-2-yl)methanamine),
obtained from [OsCl2(PPh3)3] and
Pyme, thermally isomerizes to cis,cis-
[OsCl2(PPh3)2(Pyme)] (2)in mesitylene
at 1508C. Reaction of [OsCl2(PPh3)3]
with Ph2P(CH2)4PPh2 (dppb)and Pyme
in mesitylene (1508C, 4 h)leads to a
mixture of trans-[OsCl2(dppb)(Pyme)]
(3)and cis-[OsCl2(dppb)(Pyme)] (4)in
about an 1:3 molar ratio. The complex
trans-[OsCl2(dppb)(Pyet)] (5)(Pyet
2-(pyridin-2-yl)ethanamine) is formed
by reaction of [OsCl2(PPh3)3] with
dppb and Pyet in toluene at reflux.
Compounds 1, 2, 5 and the mixture of
isomers 3/4 efficiently catalyze the
transfer hydrogenation (TH)of differ-
ent ketones in refluxing 2-propanol
and in the presence of NaOiPr
(2.0 mol%). Interestingly, 3/4 has been
proven to reduce different ketones
(even bulky)by means of TH with a
remarkably high turnover frequency
(TOF up to 5.7”105 hÀ1)and at very
low loading (0.05–0.001 mol%). The
system 3/4 also efficiently catalyzes the
hydrogenation of many ketones (H2,
5.0 atm)in ethanol with KO tBu
(2.0 mol%)at 70 8C (TOF up to 1.5”
104 hÀ1). The in-situ-generated catalysts
prepared by the reaction of [OsCl2-
G
ACHTREUNG
AHCTREUNG
U
ACHTREUNG
AHCTREUNG
ACHTREUNG
A
U
G
and (Æ)-1-alkyl-substituted Pyme li-
gands, promote the enantioselective
TH of different ketones with 91–
96% ee (ee=enantiomeric excess)and
with a TOF of up to 1.9”104 hÀ1 at
608C.
N
ACHTREUNG
Keywords: asymmetric catalysis
·
A
G
=
hydrogen transfer · hydrogenation ·
osmium · phosphane ligands
AHCTREUNG
Introduction
for these two reactions has been given by Noyori and co-
workers, who observed that the activity of ruthenium com-
plexes can be enhanced by using primary amine ligands (bi-
functional catalysis).[3,4] Interestingly, we have observed that
a dramatic increase of activity in TH with ruthenium-based
catalysts is achieved by using the ligand 1-(pyridin-2-yl)me-
thanamine (Pyme).[5] By employment of 1-substituted Pyme
ligands (RPyme; R=Me, tBu, Ph), we have recently isolated
The development of new more-efficient catalysts for the ste-
reoselective reduction of carbonyl compounds represents a
current subject of industrial and academic research. Several
transition-metal complexes have been found to catalyze the
enantioselective hydrogenation (HY)of ketones with dihy-
drogen under pressure.[1] In addition to this atom-efficient
methodology, the catalytic transfer hydrogenation (TH), by
using 2-propanol or formic acid as hydrogen donors, repre-
sents a powerful strategy because of the ease of perfor-
mance and the broad applicability.[2] Homogeneous Rh, Ru,
and to a lesser degree Ir catalysts have successfully been
employed for the both asymmetric HY and TH.[1a,2] A fun-
damental contribution to the development of new catalysts
the complexes cis-[RuCl2
N
N
among the most active catalysts for the asymmetric TH of a
variety of aryl ketones.[6]
It is worth noting that few compounds, namely
[RuCl2(PP)(NN)]
(PP=diphosphane;
NN=Pyme,[5d,7]
diamine[3,8]),
[RuCl(NN)
A
[RuCl2-
(PPh3)(oxazoline)],[10] Ru–Binap,[11] and (cyclopentadieno-
ne)Ru carbonyl complexes,[12] catalyze both the asymmetric
TH and HY of carbonyl compounds. Despite the extensive
work on ruthenium-based catalysts, much less attention has
been directed towards iron[13]and osmium[13e,14] congeners,
the activity of which appears lower than that of the well-es-
tablished ruthenium catalysts. As regards osmium, catalytic
[a] Prof. W. Baratta, Dr. M. Ballico, Prof. A. Del Zotto, Dr. K. Siega,
Dr. S. Magnolia, Prof. P. Rigo
Dipartimento di Scienze e Tecnologie Chimiche
Università di Udine, Via Cotonificio 108
33100 Udine (Italy)
Fax : (+39)0432-558-803
E-mail: inorg@uniud.it
TH of ketones has been reported for [Os(CO)HX(PR3)n]
A
[14a,b]
(X=Cl, H; n=2, 3)and related complexes,
as well as
Chem. Eur. J. 2008, 14, 2557 – 2563
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
2557

a
cis arrangement of the P
atoms. In the 1H NMR spec-
trum, the CH2 protons appear
as a triplet at d=4.54 ppm (3J-
(H,H)=5.7 Hz), whereas the
NH2 ones give a broad signal at
d=3.70 ppm, in agreement with
a geometry with two trans chlo-
[OsCl(ON)
amino acidates).[14c] The com-
pounds [Os(CO)H(NCMe)2-
(PPh3)2]
[BF4],[14d]
[OsH(NHCMe2CMe2NH2)-
A
(ON=
AHCTREUNG
A
ACHTREUNG
A
Scheme 1. Preparation of 1 and 2.
based osmium complexes[14f]
have been found active for HY
of ketones and aldehydes,
whereas the derivatives of formula [Os(CO)HCl
A
ride atoms. Heating of 1 in mesitylene at 1508C for 4 h af-
(P=phosphane or P2 =diphosphane)have been proven to
catalyze both TH and HY of carbonyl compounds.[14a,g,h]
Highly enantioselective reduction of ketones (up to 92% ee)
has been obtained with the system generated in situ from
fords the poorly soluble compound cis,cis-[OsCl2(PPh3)2-
C
G
two doublets at d=À8.0 and À8.5 ppm (2J
C
1
[Os
(cymene)Cl2]2 and b-amino alcohols.[14i] However, the
G
low activity (Os>0.1 mol%)and the relative slow rate of
these osmium systems may limit their employment in organ-
ic synthesis. On the other hand, because of the high thermal
and oxidative stability observed for osmium complexes,
more robust catalysts are expected than those derived from
other metals. This advantage should lead to systems display-
ing high TON values which may counter the higher cost in-
volved in the case of osmium.[14a,15] Furthermore, this en-
hanced stability of osmium complexes can allow kinetic and
mechanistic studies through de-
[RuCl
under milder conditions.[5d] Reaction of [OsCl2
one equivalent of Ph2P(CH2)4PPh2 (dppb)in CH 2Cl2 and
subsequent reaction with Pyme in mesitylene at 1508C leads
to a mixture of trans-[OsCl2(dppb)(Pyme)] (3)and cis-
[OsCl2(dppb)(Pyme)] (4)in about an 1:3 molar ratio
[Eq. (1)].
A
ACHTREUNG
AHCTREUNG
AHCTREUNG
A
ACHTREUNG
A
ACHTREUNG
tecting intermediates which
may lead to a better under-
standing of the catalytic cycle.
We describe here that the
osmium complexes [OsCl2P2-
ACHTREUNG
ACHTREUNG
the rapid reduction of different
ketones by means of both TH and HY in basic alcohol
media. High enantioselectivity (up to 96%)has been
reached in the TH by using catalysts prepared in situ from
The 31P{1H} NMR spectra (CD2Cl2)recorded during the
reaction reveal the formation of the two isomers, with 3 (d=
2
À14.3 and À16.3 ppm, J
A
2
[OsCl
A
verts into 4 (d=À3.9 and À13.1 ppm, J
(P,P)=13.2 Hz).[16]
tures of RPyme ligands.
As a matter of fact, prolonged heating of this mixture inhib-
ited the isolation of 4 as a single product. Compound 3 gives
1
a signal at d=2.63 ppm for the NH2 group in its H NMR
Results andDiscussion
spectrum (CD2Cl2), whereas the resonance at d=4.30 ppm
is for the CH2N moiety, the 13C NMR signal of which is at
d=50.4 ppm, according to the values of the analogue trans-
Synthesis of osmium complexes: Treatment of [OsCl2-
(PPh3)3] with one equivalent of Pyme in mesitylene at 408C
promptly leads to the compound trans,cis-[OsCl2(PPh3)2-
G
[RuCl
N
N
G
1H NMR signals at d=4.54 and 2.77 ppm, whereas the
CH2N 13C NMR resonance is at d=56.2 ppm, close to the
corresponding cis ruthenium compound.[5d] Employment of
2-(pyridin-2-yl)ethanamine (Pyet), which displays a longer
(Pyme)] (1)in 93% yield (Scheme 1).
The 31P{1H} NMR spectrum (CD2Cl2)shows two doublets
2
at d=À11.5 and À16.3 ppm with J
A
2558
www.chemeurj.org
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 2557 – 2563

Hydrogenation of Ketones
FULL PAPER
Table 1. Catalytic TH of acetophenone (0.1m)with 1–5 (Os 0.05 mol%)
and NaOiPr (2 mol%)in 2-propanol at 82 8C.
CH2 chain than Pyme, results in the formation of the trans
isomer. Treatment of [OsCl
followed by addition of Pyet in refluxing toluene (3 h)gives
trans-[OsCl2(dppb)(Pyet)] (5)[Eq. (2)].
A
[b]
Compound
Conv. [%][a]
t [min]
TOF [hÀ1
]
A
N
1
2
3/4
5
98
98
98
94
5
5
30 s
10
7.5”104
8.6”104
5.7”105
1.4”104
[a] The conversion was determined by GC analysis. [b] Turnover frequen-
cy (moles of ketone converted to alcohol per mole of catalyst per hour)
at 50% conversion.
of 3/4 appears higher than that of the analogue cis-[RuCl2-
The 31P{1H} NMR spectrum of 5 exhibits two doublets at
A
(Pyme)]
(TOF=3.0”105 hÀ1),[5d]
showing
that
2
d=À10.1 and À15.9 ppm with J
C
osmium systems may be used as fast catalysts for the reduc-
tion of carbonyl compounds, a result which has not been
previously reported. Compound 5, containing a longer pyri-
dine chain, is also catalytically active, with a low rate
(TOF=1.4”104 hÀ1)relative to 3/4, indicating that the use
of Pyme is crucial to achieve high activity with osmium, as
observed for ruthenium.[18] It should be noted that with 3/4,
the complete reduction of MeCOPh has been obtained at
extremely low catalyst loading. At variance with the rutheni-
um analogues (TON=104), 3/4 is catalytically active even at
0.001 mol% (TON ꢀ1.8”105)with a gradual decrease of
the rate by reducing the osmium concentration (TOF=5.5”
105 to 3.4”105 hÀ1 at 0.02 to 0.001 mol%, respectively;
Table 2).
1
tent with a trans geometry. At variance with 3, no isomeriza-
tion has been observed by subsequent heating of 5, indicat-
ing that the length of the pyridine CH2 chain affects the ge-
ometry of the complex. With Pyme, the trans-[OsCl2P2-
ACHTREUNG
behavior resembles that observed for ruthenium Pyme com-
plexes, even though the isomerization occurs with osmium
under harsher conditions and no complete cis isomerization
has been obtained with 3.
Catalytic results: The osmium compounds 1, 2, and 5 have
been proven to be catalytically active for the reduction of
acetophenone by means of TH in refluxing 2-propanol. Im-
portantly, with the system 3/4 (1/3 molar ratio)many ke-
tones have been quickly converted into alcohols by means
of fast TH and also HY with dihydrogen (Scheme 2).
Table 2. Catalytic TH of acetophenone (0.1m)at different loadings of 3/4
and NaOiPr (2 mol%)in 2-propanol at 82 8C.
[b]
Mol% of 3/4
Conv. [%][a]
t [min]
TOF [hÀ1
]
0.02
0.01
0.005
0.002
0.001
98
98
97
99
98
2
5
5
30
120
5.5”105
4.8”105
4.5”105
3.7”105
3.4”105
[a] The conversion was determined by GC analysis. [b] Turnover frequen-
cy (moles of ketone converted to alcohol per mole of catalyst per hour)
at 50% conversion.
These data indicate that 3/4 is more robust compared to
the ruthenium analogues, that is, the deactivation process is
retarded, and, therefore, this osmium system can be em-
ployed in the synthesis of alcohols on a preparative scale.
Interestingly, the mixture 3/4 enables the fast chemoselec-
tive reduction of unsaturated dialkyl ketones, such as 5-
hexen-2-one (TOF=3.2”105 hÀ1), without reduction or iso-
merization of the terminal olefinic bond (Table 3).
Most importantly, tert-butyl ketones, which are feebly re-
active in the TH leading to low conversion or requiring
severe reaction conditions,[13e,19] are here efficiently reduced
to alcohols with 3/4. As a matter of fact, 3,3-dimethyl-2-bu-
tanone and 2,2-dimethylpropiophenone are quantitatively
converted to alcohols in minutes by using 0.05 mol% of 3/4,
with TOF=8.0”103 and 1.7”104 hÀ1, respectively (Table 3).
The lower rate observed for these substrates relative to that
of acetophenone is in agreement with the less-favorable
Scheme 2. Reduction of ketones catalyzed by osmium complexes by
means of TH or HY.
When compound 1 (Os 0.05 mol%)is added to acetophe-
none (0.1m)in refluxing 2-propanol that contains NaO iPr
(2 mol%), quantitative formation of 1-phenylethanol is ach-
ieved in 5 min, leading to a turnover frequency (TOF)of
7.5”104 hÀ1. Employment of the isomer 2 gives a slightly
higher rate (TOF=8.6”104 hÀ1; Table 1).
With the mixture 3/4, the TH of MeCOPh occurs in 30 s,
leading to a TOF of 5.7”105 hÀ1. This rate is surprisingly
high and can be compared with that of the most active cata-
lysts for TH-based on ruthenium.[5,17] Actually, the activity
Chem. Eur. J. 2008, 14, 2557 – 2563
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
2559

W. Baratta et al.
Table 3. Catalytic TH of unsaturated and bulky ketones (0.1m)with 3/4
(Os 0.05 mol%)and NaO iPr (2 mol%)in 2-propanol at 82 8C.
5 atm of H2 in a 100 mL glass autoclave at 708C, complete
reduction of the ketone was achieved in 10 min (TOF=1.5”
104 hÀ1; Table 4).
[b]
Ketone
Conv. [%][a]
t [min]
TOF [hÀ1
]
At a lower loading of osmium (0.01 and 0.005 mol%), the
reduction occurs completely with almost the same rate, indi-
cating that 3/4 should be considered a robust catalytic
system for HY (Table 4). The system 3/4 promotes the effi-
cient HY of 5-hexen-2-one to the corresponding unsaturated
alcohol with high rates and no reduction of the C=C bond
has been observed. Importantly, the osmium system (3/4
0.01 mol% and 5 atm of H2)also enables the reduction of
the bulky tert-butyl substrates 3,3-dimethyl-2-butanone and
2,2-dimethylpropiophenone with almost the same rate of
acetophenone (Table 4). This is a remarkable result as the
HY of these types of compounds is described to occur at a
96
2
3.2”105
98
93
30
30
1.7”104
8.0”103
99
30
2.7”104
[a] The conversion was determined by GC analysis. [b] Turnover frequen-
cy (moles of ketone converted to alcohol per mole of catalyst per hour)
at 50% conversion.
lower rate, due to the bulkiness of the tert-butyl group.[20]
point to note is that the related ruthenium complex
[RuCl2(PP)(Pyme)] (PP=(S)-tolbinap) was found to effi-
A
AHCTREUNG
ciently catalyze the asymmetric HY of tert-butyl ketones.[7]
With 3/4, also the cyclic ketones 2-methyl-cyclohexanone
and menthone have been reduced to alcohols under these
catalytic conditions and with high rates of reaction. A com-
parison of the results obtained with 3/4 in TH with those
achieved in HY show that while in the TH, the rate strongly
depends on the bulkiness of the substrates, in HY, the rate
is apparently slightly affected by the steric properties of the
ketone, suggesting that the H2 activation is likely to be the
rate-determining step.
access of the carbonyl group to the metal center as a result
of steric factors. Under these catalytic conditions, complete
conversion of menthone has also been obtained. It is worth
noting that when the system [OsCl
ated in situ by refluxing a 2-propanol solution of [OsCl2-
(PPh3)3] with dppb (1 h)and Pyme (2 h,) it promotes the
TH of acetophenone with the same activity of 3/4.
As ruthenium complexes [RuCl2(PP)
(Pyme)][5d,7] have
A
G
ACHTREUNG
AHCTREUNG
been proven to catalyze both TH and HY, we have investi-
gated the catalytic activity of 3/4 in the HY of ketones at
low dihydrogen pressure. Among the different alcohols
(ROH; R=Me, Et, iPr), ethanol has been found to give the
best performance in the presence of the base KOtBu. Thus,
when an ethanol solution of acetophenone (0.5m)containing
3/4 (Os 0.05 mol%)and KO tBu (2 mol%)was stirred under
As regards the asymmetric reduction of ketones with
osmium, fast enantioselective TH in basic 2-propanol has
been observed with the catalytic system generated in situ by
the reaction of [OsCl2(PPh3)3], (S,R)-Josiphos in refluxing 2-
A
propanol (1 h), and Pyme (1 h) in 1:1.5:2 molar ratios, re-
spectively. This system enables the quantitative TH of
PhCOMe (30 min at 608C)to
(S)-1-phenylethanol (91% ee)
Table 4. Catalytic HY of ketones (0.5m)with 3/4 and KOtBu (2 mol%)in ethanol under 5 atm H at 708C.
2
by using a low-catalyst loading
(Os 0.05 mol%)and NaO iPr
(2 mol%), affording a TOF of
9.7”103 hÀ1 (Table 5).
[b]
Mol% of 3/4
Ketone
Conv. [%][a]
t [h]
TOF [hÀ1
]
0.05
0.01
0.005
>99
>99
>99
10 min
1
4
1.5”104
1.4”104
1.3”104
According to our studies on
the asymmetric TH of ketones
with ruthenium by using race-
mic RPyme ligands, which af-
forded higher ee values com-
pared to Pyme,[6] employment
of (Æ)-MePyme in the reduc-
tion of acetophenone gives the
(S)-alcohol with both a higher
enantiomeric excess (95%)and
0.01
0.01
>99
>99
1
3
1.4”104
1.1”104
0.01
0.01
97
99
2
3
1.1”104
7.0”103
reaction
rate
(TOF=1.5”
104 hÀ1)(Table 5.) Furthermore,
a high ee (94% (S)) and reac-
tion rate (TOF=1.9”104 hÀ1)
have also been obtained with
the racemic mixture of tBu-
Pyme. When the bulkier (S,R)-
0.01
>99
2
1.4”104
[a] The conversion was determined by GC analysis. [b] Turnover frequency (moles of ketone converted to al-
cohol per mole of catalyst per hour)at 50% conversion.
2560
www.chemeurj.org
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 2557 – 2563

Hydrogenation of Ketones
FULL PAPER
Table 5. Enantioselective catalytic TH of acetophenone (0.1m)with the system [OsCl
(Os: 0.05 mol%)and NaO iPr (2 mol%)in 2-propanol at 60 8C.
N
in 2-propanol. Reaction of 1
with NaOiPr (three equiva-
PP
(S,R)ÀJosiphos
(S,R)-Josiphos
(S,R)-Josiphos
(S,R)-Josiphos*
(S,R)-Josiphos*
(S,R)-Josiphos*
Ar of PP
R of Pyme
Conv. [%][a]
t [min]
lents)in
C 6D6/2-propanol at
A
Ph
Ph
Ph
H
96
96
97
97
92
98
30
30
10
40
30
30
room temperature leads to the
formation of two trans OsP2 hy-
dride species which, after evap-
oration of the solvent mixture,
show two 31P{1H} NMR singlets
at d=23.9 and 23.0 ppm, in a
3:1 molar ratio. The 1H NMR
spectrum of the main product
in C6D6 shows a triplet at d=
G
Me
tBu
H
Me
tBu
R
N
4-OMe-3,5-Me2C6H2
4-OMe-3,5-Me2C6H2
4-OMe-3,5-Me2C6H2
N
ACHTREUNG
[a] The conversion and ee were determined by GC analysis. [b] Turnover frequency (moles of ketone convert-
ed to alcohol per mole of catalyst per hour)at 50% conversion.
Josiphos*, which contains the 4-OMe-3,5-Me2C6H2 groups
instead of Ph ones, is used in combination with Pyme or (Æ
)-RPyme (R=Me, tBu), reduction of acetophenone is quick-
ly achieved (TOF values 8.0”103–1.3”104 hÀ1)with forma-
tion of (S)-1-phenylethanol in 92–95% ee (Table 5). With
3.10 ppm (3J
(H,H)=6.0 Hz)for CH 2N, a broad signal for
NH2 (d=2.37 ppm), and two signals at d=À7.80 (pseudo q,
J=8.8 Hz)and À10.8 ppm (broad signal)for two hydrides,
which are consistent with a cis,trans-[OsH
A
N
dihydride compound, similar to the analogous ruthenium
complex.[5d] Employment of 2 in place of 1 leads to identical
results, indicating that in basic 2-propanol, the trans and cis
osmium precursors give the same hydride species. These
data suggest that in the catalytic TH mediated by trans or
the catalyst generated in situ from [OsCl2(PPh3)3], (S,R)-Jo-
A
siphos, and (Æ)-tBu-Pyme, asymmetric TH of the aryl-sub-
stituted ketones 2’-methyl- 2’-chloro- and 2’-methoxyaceto-
phenone has been observed, affording (S)-alcohols with 94–
96% ee, indicating that this osmium system can be efficient-
ly used for the preparation of chiral alcohols (Table 6).
The 31P NMR analysis of the reaction mixtures of the
cis osmium Pyme complexes, the species [OsHXP2(Pyme)]
C
(X=H, OR’)are the intermediates involved in b-hydrogen
elimination versus ketone-insertion reaction, according to
the studies on ruthenium-hydride/alkoxide complexes.[21]
[OsCl
A
of numerous stereoisomers. Attempts to obtain a single cat-
alytic precursor by using different solvents at high tempera-
ture failed. These results can be compared with those ob-
tained with ruthenium which showed that [RuCl
(S,R)-Josiphos, and (Æ)-RPyme led in refluxing toluene to
the single stereoisomer cis-[RuCl2(PP)(RPyme)] through a
G
We have found that the novel osmium complexes of general
formula [OsCl2P2(Pyme)] (P=P phosphane or P2 =diphos-
G
highly diastereoselective reaction.[6] Interestingly, with (S,R)-
Josiphos and (Æ)-RPyme-based systems, similar values of ee
have been obtained in the catalytic TH of ketones by using
the structurally well-defined ruthenium complexes as well as
the in-situ-prepared osmium system as catalytic precursors.
As regards the species which form during catalysis, it is
likely that osmium hydrides are generated when [OsCl2P2-
phane)are active catalysts for the reduction of ketones in
basic alcohol media with remarkably high reaction rates
(TOF up to 5.7”105 hÀ1). The osmium system 3/4 has been
proven to rapidly catalyze both the TH and HY of different
ketones at very low loading of catalyst (0.001 and
0.005 mol%). With the catalysts generated in situ from
[OsCl
A
A
cient asymmetric TH of methyl–aryl ketones (up to 96% ee)
and good rates of reaction have been observed. Work is in
progress to establish the structure of the in-situ-generated
chiral osmium compounds and the species involved in the
catalytic TH and HY reactions. These results clearly show
that when a suitable set of ligands is employed, osmium
complexes may display extremely high catalytic activity in
reduction processes, comparable to other elements, includ-
ing ruthenium, with the advantage that deactivation is re-
tarded. This study may help in the design of new efficient
homogeneous osmium catalysts and to stimulate research in
this relatively less-studied area of chemistry.
Table 6. Enantioselective catalytic TH of ketones (0.1m)with the system
[OsCl2(PPh3)3]/
(S,R)-Josiphos/(Æ)-tBuPyme (Os 0.05 mol%)and NaO iPr
(2 mol%)in 2-propanol at 60 8C.
A
ACHTREUNG
[b]
Ketone
Conv. [%][a]
t [min]
ee [%][a]
TOF [hÀ1
]
99
30
94 S
1.2”104
98
99
60
60
95 S
96 S
9.1”103
8.6”103
Experimental Section
[a] The conversion and ee were determined by GC analysis. [b] Turnover
frequency (moles of ketone converted to alcohol per mole of catalyst per
hour)at 50% conversion.
General: All reactions were carried out under an argon atmosphere by
using standard Schlenk techniques. The solvents and the ketones were
carefully dried by standard methods and distilled under argon before use.
Chem. Eur. J. 2008, 14, 2557 – 2563
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
2561

W. Baratta et al.
The diphosphane, Pyme, and Pyet ligands and all other chemicals were
purchased from Aldrich and were used without further purification. The
pressure. Yield: 62 mg (81%); 1H NMR (200.1 MHz, CD2Cl2, 208C): d=
3
9.87 (d, J
A
3
7.88–6.70 (m, 20H; aromatic protons), 6.28 (d, J(H,H)=7.4 Hz, 1H; aro-
H
complex [OsCl2(PPh3)3] was prepared according to the literature proce-
A
dure.[22] NMR measurements were recorded on a Bruker AC 200 spec-
trometer and chemical shifts, in ppm, are relative to TMS for 1H and
13C{1H} NMR, whereas 85% H3PO4 was used for 31P{1H} NMR spectros-
copy. Elemental analyses (C, H, N)were carried out with a Carlo Erba
1106 elemental analyzer, whereas the GC analyses were performed with
a Varian GP-3380 gas chromatograph equipped with a MEGADEX-
ETTBDMS-b chiral column.
matic proton), 4.09 (brs, 2H; NH2), 3.93 (m, 1H; CH2), 3.18 (m, 4H;
CH2), 2.50–1.12 ppm (m, 7H; CH2); 13C{1H} NMR (50.3 MHz, CD2Cl2,
208C): d=160.6 (s; NCCH2), 154.9 (s; NCH), 141.1–122.5 (m; aromatic
carbon atoms), 40.3 (d, J
ACHTREUNG
36.0 (dd, J(C,P)=33.9, 3.7 Hz; PCH2), 29.8 (d, J
A
ACHTREUNG
27.6 (s; PCH2CH2), 18.8 ppm (t, J(CP)=1.8 Hz; PCH2CH2);
31P{1H} NMR (81.0 MHz, CD2Cl2, 208C): d=À10.1 (d, 2J
C
À15.9 ppm (d, 2J
A
Synthesis of 1: [OsCl2(PPh3)3] (135 mg, 0.129 mmol)and Pyme (17 mL,
A
C35H38Cl2N2OsP2: C 51.92, H 4.73, N 3.46; found: C 51.93, H 4.67, N 3.48.
0.165 mmol)were suspended in mesitylene (2 mL)and the mixture was
heated at 408C for 30 min, affording a yellow precipitate, which was fil-
tered, washed with diethyl ether (2”5 mL)and dried under reduced
Typical procedure for the catalytic transfer hydrogenation of ketones:
Osmium complex (2.0 mmol)was added to 2-propanol (2 mL.) The
ketone (2.00 mmol)was dissolved in 2-propanol and the solution
(18.6 mL)was refluxed under argon. Addition of NaO iPr (400 mL, 0.1m
in 2-propanol)and the solution containing the osmium complex (1.0 mL,
1.0 mmol)afforded the reduction of the ketone (osmium 0.05 mol%,
NaOiPr 2.0 mol%, ketone 0.1m).
pressure. Yield: 107 mg (93%); 1H NMR (200.1 MHz, CD2Cl2, 208C):
3
d=8.41 (d, J
ACHTREUNG
protons), 6.54 (pseudot, 3J
(pseudot, 3J
ACHTREUNG
ACHTREUNG
AHCTREUNG
ACHTREUNG
Typical procedure for the catalytic hydrogenation of ketones: The mix-
ture 3/4 (1.4 mg, 1.76 mmol)was added to 2 mL of ethanol. The ketone
(4.30 mmol)and KO tBu (9.7 mg, 0.086 mmol)were dissolved in ethanol
(total volume 8.1 mL)and the solution containing the osmium complex
(0.49 mL, 0.43 mmol)was added. The resulting solution was transferred
into a thermostated reactor at 708C and dihydrogen was introduced at a
pressure of 5 atm, affording the reduction of the ketone (osmium
0.01 mol%, KOtBu 2 mol%, ketone 0.5m).
matic carbon atoms), 51.3 ppm (pseudot,
J(C,P)=2.3 Hz; NCH2);
G
31P{1H} NMR (81.0 MHz, CD2Cl2, 208C): d À11.5 (d, 2J
(P,P)=11.7 Hz),
À16.3 ppm (d, 2J
(P,P)=11.7 Hz); elemental analysis calcd (%) for
C42H38Cl2N2OsP2: C 56.44, H 4.29, N 3.13; found: C 56.48, H 4.41, N 3.00.
Synthesis of 2: Compound 1 (80 mg, 0.090 mmol)was suspended in mesi-
tylene (3 mL)and the mixture was heated at 150 8C for 4 h. The dark-
yellow product was filtered, washed with diethyl ether (10 mL), dichloro-
methane (1 mL), and dried under reduced pressure. Yield: 70 mg (88%);
Typical procedure for enantioselective catalytic transfer hydrogenation of
1H NMR (200.1 MHz, CD2Cl2, 208C): d=8.82 (d, 3J
ACHTREUNG
ketones:
A
2-propanol (2 mL)solution of [OsCl 2(PPh3)3] (2.1 mg,
A
2.0 mmol)and the ( S,R)-Josiphos diphosphane (3.0 mmol)was refluxed
for 1 h and, after addition of the (Æ)-RPyme ligand (4.0 mmol), for an ad-
ditional 1 h. The ketone (2.00 mmol)was dissolved in 2-propanol and the
solution (18.6 mL)was heated at 60 8C. Addition of NaOiPr (400 mL,
0.1m in 2-propanol)and the solution that contained the osmium complex
(1.0 mL)afforded the reduction of the ketone (osmium 0.05 mol%,
NaOiPr 2 mol%, ketone 0.1m).
3.74 (dd, J(H,H)=16.1, 4.7 Hz, 1H; CH2), 3.04 (m, 1H; CH2), 2.68 ppm
N
(d, 2J
N
G
calcd (%)for C 42H38Cl2N2OsP2: C 56.44, H 4.29, N 3.13; found: C 56.29,
H 4.35, N 3.02.
Synthesis of 3/4: [OsCl2(PPh3)3] (120 mg, 0.115 mmol)and dppb (49 mg,
U
0.115 mmol)were dissolved in dichloromethane (4 mL), and the solution
was stirred at room temperature for 2 h. After evaporation of the solvent,
mesitylene (4 mL)and Pyme (14 mL, 0.136 mmol)were added, and the
resulting suspension was heated at 1508C for 4 h and stirred at room tem-
perature overnight. The yellow–green precipitate was filtered, washed
with diethyl ether (3”4 mL)and dried under reduced pressure. Yield:
76 mg (83%); 1H NMR (200.1 MHz, CDCl3, 208C): d=9.41 (d, 3J-
Acknowledgements
A
N
This work was supported by the Ministero dell’Università e della Ricerca
(MiUR)and the Regione Friuli Venezia Giulia. The authors also thank
P. Polese for carrying out the elemental analyses.
A
ACHTREUNG
minor complex), 4.10–3.95 (m; NCH2 major complex), 3.30–3.10 (m;
CH2), 2.70–1.10 ppm (m; CH2 and NH2); 13C{1H} NMR (50.3 MHz,
CDCl3, 208C): d=163.8 (s; NCCH2, minor complex), 158.6 (s; NCCH2,
major complex), 155.1 (s; o-NCH, minor complex), 149.4 (s; o-NCH,
major complex), 140.9–119.2 (m; aromatic carbon atoms), 56.0 (s; NCH2,
[1] a) The Handbook of Homogeneous Hydrogenation, Vols. 1–3 (Eds.:
J. G. de Vries, C. J. Elsevier), Wiley-VCH, Weinheim, 2007;
b) Asymmetric Catalysis on Industrial Scale (Eds.: H. U. Blaser, E.
Schmidt), Wiley-VCH, Weinheim, 2004; c) Comprehensive Asym-
metric Catalysis, Supplements 1–2 (Eds.: E. N. Jacobsen, A. Pfaltz,
H. Yamamoto), Springer, Berlin, Germany, 2004; d) Catalytic Asym-
metric Synthesis (Ed.: I. Ojima), 2nd ed., Wiley-VCH, New York,
2000.
[2] a)J. S. M. Samec, J. E. Bäckvall, P. G. Andersson, P. Brandt, Chem.
Soc. Rev. 2006, 35, 237; b)S. Gladiali, E. Alberico, Chem. Soc. Rev.
2006, 35, 226; c)T. Ikariya, K. Murata, R. Noyori, Org. Biomol.
Chem. 2006, 4, 393; d)S. E. Clapham, A. Hadzovic, R. H. Morris,
Coord. Chem. Rev. 2004, 248, 2201.
major complex), 50.1 (s; NCH2, minor complex), 36.4 (d,
33.8 Hz; PCH2 major complex), 35.3 (d, J(C,P)=35.9 Hz; PCH2, minor
complex), 28.6 (d, J(C,P)=35.5 Hz; PCH2, major complex), 27.2 (s;
PCH2CH2, major complex), 25.6 (s; PCH2CH2, minor complex), 24.4 (d,
(C,P)=32.6 Hz; PCH2, minor complex), 19.1 (s; PCH2CH2, minor com-
J
A
AHCTREUNG
ACHTREUNG
J
ACHTREUNG
plex), 18.4 ppm (s; PCH2CH2, major complex); 31P{1H} NMR (81.0 MHz,
CDCl3, 208C): d=À3.6 (d, 2J
ACHTREUNG
(d, 2J
(P,P)=13.3 Hz), À14.7 (d, 2J
ACHTREUNG
À16.1 ppm (d, 2J
(P,P)=10.5 Hz); elemental analysis calcd (%) for
C34H36Cl2N2OsP2: C 51.32, H 4.56, N 3.52, found: C 51.12, H 4.61, N 3.46.
Synthesis of 5: [OsCl2(PPh3)3] (100 mg, 0.095 mmol)and dppb (45 mg,
A
[3] H. Doucet, T. Ohkuma, K. Murata, T. Yokozawa, M. Kozawa, E.
Katayama, A. F. England, T. Ikariya, R. Noyori, Angew. Chem.
1998, 110, 1792; Angew. Chem. Int. Ed. 1998, 37, 1703.
[4] a)J. Takehara, S. Hashiguchi, A. Fujii, S. Inoue, T. Ikariya, R.
Noyori, Chem. Commun. 1996, 233; b)K. J. Haack, S. Hashiguchi,
A. Fujii, T. Ikariya, R. Noyori, Angew. Chem. 1997, 109, 297;
Angew. Chem. Int. Ed. Engl. 1997, 36, 285.
0.106 mmol)were dissolved in dichloromethane (2 mL)and the solution
was stirred at room temperature for 2 h. After elimination of the solvent,
toluene (2 mL)and Pyet (14.8 mL, 0.124 mmol)were added and the mix-
ture was refluxed for 3 h. The resulting solution was concentrated (1 mL)
and addition of diethyl ether (5 mL)afforded a green–yellow precipitate,
which was washed with diethyl ether (2”5 mL)and dried under reduced
2562
www.chemeurj.org
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 2557 – 2563

Hydrogenation of Ketones
FULL PAPER
[5] a)W. Baratta, P. Da Ros, A. Del Zotto, A. Sechi, E. Zangrando, P.
Rigo, Angew. Chem. 2004, 116, 3668; Angew. Chem. Int. Ed. 2004,
43, 3584; b)W. Baratta, A. Del Zotto, G. Esposito, A. Sechi, M. To-
niutti, E. Zangrando, P. Rigo, Organometallics 2004, 23, 6264; c)W.
Baratta, J. Schütz, E. Herdtweck, W. A. Herrmann, P. Rigo, J. Orga-
nomet. Chem. 2005, 690, 5570; d)W. Baratta, E. Herdtweck, K.
Siega, M. Toniutti, P. Rigo, Organometallics 2005, 24, 1660.
[6] W. Baratta, G. Chelucci, E. Herdtweck, S. Magnolia, K. Siega, P.
Rigo, Angew. Chem. Int. Ed. 2007, 46, 7651.
[7] T. Ohkuma, C. A. Sandoval, R. Srinivasan, Q. Lin, Y. Wei, K.
MuÇiz, R. Noyori, J. Am. Chem. Soc. 2005, 127, 8288.
Catal. A 1997, 116, 167; g)M. K. Jung, S. Huh, W. Y. Lee, M. J. Jun,
Bull. Korean Chem. Soc. 1997, 18, 806; h)R. A. Sµnchez-Delgado,
N, Valencia, R. L. Mµrquez-Silva, A. Andrillo, M. Medina, Inorg.
Chem. 1986, 25, 1106; i)J. W. Faller, A. R. Lavoie, Org. Lett. 2001, 3,
3703.
[15] R. H. Morris, The Handbook of Homogeneous Hydrogenation
(Eds.: J. G. de Vries, C. J. Elsevier), Vol. 1, Wiley-VCH, Weinheim,
2007, p. 45.
[16] A small amount of an uncharacterized osmium complex (<5%)
gives 31P{1H} NMR spectroscopic signals at d=À6.5 and À12.1 ppm
2
with J
A
[8] V. Rautenstrauch, X. Hoang-Cong, R. Churlaud, K. Abdur-Rashid,
R. H. Morris, Chem. Eur. J. 2003, 9, 4954.
[9] T. Ohkuma, N. Utsumi, K. Tsutsumi, K. Murata, C. A. Sandoval, R.
Noyori, J. Am. Chem. Soc. 2006, 128, 8724.
[10] a)Y. Nishibayashi, I. Takei, S. Uemura, M. Hidai, Organometallics
1999, 18, 2291; b)F. Naud, C. Malan, F. Spindler, C. Rüggeberg,
A. T. Schmidt, H. U. Blaser, Adv. Synth. Catal. 2006, 348, 47.
[11] a)T. Ohta, H. Takaya, M. Kitamura, K. Nagai, R. Noyori, J. Org.
Chem. 1987, 52, 3174; b)J. M. Brown, H. Brunner, W. Leitner, M.
Rose, Tetrahedron: Asymmetry 1991, 2, 331.
[12] a)Y. Blum, D. Czarkle, Y. Rahamim, Y. Shvo, Organometallics
1985, 4, 1459; b)C. P. Casey, S. W. Singer, D. R. Powell, R. K. Haya-
shi, M. Kavana, J. Am. Chem. Soc. 2001, 123, 1090.
[13] a)C. P. Casey, H. Guan, J. Am. Chem. Soc. 2007, 129, 5816; b)S. En-
thaler, G. Erre, M. K. Tse, K. Junge, M. Beller, Tetrahedron Lett.
2006, 47, 8095; c)S. Enthaler, B. Hagemann, G. Erre, K. Junge, M.
Beller, Chem. Asian J. 2006, 1, 598; d)J. S. Chen, L. L. Chen, Y.
Xing, G. Chen, W. Y. Shen, Z. R. Dong, Y. Y. Li, J. X. Gao, Huaxue
Xuebao 2004, 62, 1745; e)C. Bianchini, E. Farnetti, M. Graziani, M.
Peruzzini, A. Polo, Organometallics 1993, 12, 3753; f)K. Jothimony,
S. Vancheesan, J. Molec. Catal. 1989, 52, 301.
[17] a)P. Braunstein, M. D. Fryzuk, F. Naud, S. J. Rettig J. Chem. Soc.
Dalton Trans. 1999, 589; b)H. Yang, M. Alvarez-Gressier, N. Lugan,
R. Mathieu Organometallics 1997, 16, 1401; c)P. Dani, T. Karlen,
R. A. Gossage, S. Gladiali, G. van Koten, Angew. Chem. 2000, 112,
759; Angew. Chem. Int. Ed. 2000, 39, 743.
[18] W. Baratta et al., unpublished results.
[19] a)H. Matsunaga, T. Ishizuka, T. Kunieda, Tetrahedron Lett. 2005,
46, 3645; b)V. Cadierno, P. Crochet, J. Díez, S. E. García-Garrido, J.
Gimeno, Organometallics, 2004, 23, 4836; c)P. Brandt, P. Roth, P. G.
Andersson, J. Org. Chem. 2004, 69, 4885; d)H. Zhang, C. B. Yang,
Y. Y. Li, Z. R. Donga, J. X. Gao, H. Nakamura, K. Murata, T. Ikar-
iya, Chem. Commun. 2003, 142; e)S. Lutseko, C. Moberg, Tetrahe-
dron: Asymmetry 2001, 12, 2529; f)D. A. Alonso, S. J. M. Nordin, P.
Roth, T. Tarnai, P. G. Andersson, M. Thommen, U. Pittelkow, J.
Org. Chem. 2000, 65, 3116; g)Y. Arikawa, M. Ueoka, K. Matoba, Y.
Nishibayashi, M. Hidai, S. Uemura, J. Organomet. Chem. 1999, 572,
163.
[20] a)C. Hedberg, K. Källstrçm, P. I. Arvidsson, P. Brandt, P. G. Ander-
sson, J. Am. Chem. Soc. 2005, 127, 15083; b)Q. Jiang, Y. Jang, D.
Xiao, P. Cao, X. Zhang, Angew. Chem. 1998, 110, 1203; Angew.
Chem. Int. Ed. 1998, 37, 1100.
[14] a)R. A. Sµnchez-Delgado, M. Rosales, M. A. Esteruelas, L. O. Oro,
J. Mol. Catal. A 1995, 96, 231, and references therein; b)C. Schlünk-
en, M. A. Esteruelas, F. J. Lahoz, L. A. Oro, H. Werner, Eur. J.
Inorg. Chem. 2004, 2477; c)D. Carmona, M. P. Lamata, F. Viguri, I.
Dobrinovich, F. J. Lahoz, L. A. Oro, Adv. Synth. Catal. 2002, 344,
499; d)M. Rosales, A. Gonzµles, M. Mora, N. Nader, J. Navarro, L.
Sµnchez, H. Soscffln, Transition Met. Chem. 2004, 29, 205; e)S. E.
Clapham, R. H. Morris, Organometallics 2005, 24, 479; f)R. A.
Sµnchez-Delgado, M. Medina, F. López-Linares, A. Fuentes, J. Mol.
[21] a)O. Pàmies, J. E. Bäckvall, Chem. Eur. J. 2001, 7, 5052; b)A. Ara-
nyos, G. Csjernyik, K. J. Szabó, J. E. Bäckvall, Chem. Commun.
1999, 351; c)W. Baratta, G. Chelucci, S. Gladiali, K. Siega, M. To-
niutti, M. Zanette, E. Zangrando, P. Rigo, Angew. Chem. 2005, 117,
6370; Angew. Chem. Int. Ed. 2005, 44, 6214.
[22] G. P. Elliott, N. M. McAuley, W. R. Roper, Inorg. Synth. 1989, 26,
184.
Received: October 31, 2007
Published online: December 28, 2007
Chem. Eur. J. 2008, 14, 2557 – 2563
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
2563