Highly productive CNN pincer ruthenium catalysts for the asymmetric reduction of alkyl aryl ketones

Article abstract of DOI:10.1002/chem.200802112

Chiral pincer ruthenium complexes of formula [RuCl(CNN)-(Josiphos)] (2-7; Josiphos = 1-[1-(dicyclohexylphosphano)ethyl]-2-(diarylphosphano)ferrocene) have been prepared by treating [RuCl₂(PPh₃)₃] with (S,R)-Josiphos diphosphanes and 1-substituted-1-(6-arylpyridin-2-yl)methanamines (HCNN; substituent = H (1a), Me (1b), and tBu (1c)) with NEt₃. By using 1b and 1c as a racemic mixture, complexes 4-7 were obtained through a diastereoselective synthesis promoted by acetic acid. These pincer complexes, which display correctly matched chiral PP and CNN ligands, are remarkably active catalysts for the asymmetric reduction of alkyl aryl ketones in basic alcohol media by both transfer hydrogenation (TH) and hydrogenation (HY), achieving enantioselectivities of up to 99%. In 2-propanol, the enantioselective TH of ketones was accomplished by using a catalyst loading as low as 0.002 mol % and afforded a turnover frequency (TOF) of 10⁵-10⁶ h ^-1 (60 and 82°C). In methanol/ethanol mixtures, the CNN pincer complexes catalyzed the asymmetric HY of ketones with H₂ (5 atm) at 0.01 mol % relative to the complex with a TOF of ≈ 10⁴ h ^-1 at 40°C.

Full text of DOI:10.1002/chem.200802112

DOI: 10.1002/chem.200802112
Highly Productive CNN Pincer Ruthenium Catalysts for the Asymmetric
Reduction of Alkyl Aryl Ketones
Walter Baratta,*[a] Giorgio Chelucci,[b] Santo Magnolia,[a] Katia Siega,[a] and
Pierluigi Rigo[a]
Abstract: Chiral pincer ruthenium
complexes of formula [RuCl(CNN)-
(Josiphos)] (2–7; Josiphos=1-[1-(dicy-
clohexylphosphano)ethyl]-2-(diarylphos-
phano)ferrocene) have been prepared
by treating [RuCl2A(PPh3)3] with (S,R)-
Josiphos diphosphanes and 1-substitut-
ed-1-(6-arylpyridin-2-yl)methanamines
(HCNN; substituent=H (1a), Me
(1b), and tBu (1c)) with NEt3. By
using 1b and 1c as a racemic mixture,
complexes 4–7 were obtained through
a diastereoselective synthesis promoted
by acetic acid. These pincer complexes,
which display correctly matched chiral
PP and CNN ligands, are remarkably
active catalysts for the asymmetric re-
duction of alkyl aryl ketones in basic
alcohol media by both transfer hydro-
genation (TH) and hydrogenation
(HY), achieving enantioselectivities of
up to 99%. In 2-propanol, the enantio-
selective TH of ketones was accom-
plished by using a catalyst loading as
low as 0.002 mol% and afforded a
turnover frequency (TOF) of 105–
106 hÀ1 (60 and 828C). In methanol/eth-
anol mixtures, the CNN pincer com-
plexes catalyzed the asymmetric HY of
ketones with H2 (5 atm) at 0.01 mol%
relative to the complex with a TOF of
ꢀ104 hÀ1 at 408C.
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG
G
U
N
E
T
N
T
H
A
ACHTUNGTRENNUNG
CHTUNGTRENNUNG
AHCTUNGTRENNUNG
Keywords: asymmetric catalysis
·
chiral resolution · hydrogen trans-
fer · hydrogenation · ruthenium
Introduction
tems inspired the development of a large number of cata-
lysts.[2a,6] In the last decade, asymmetric HY systems have
achieved an extremely high level of efficiency in terms of
rate and productivity.[2] By contrast, TH usually requires a
The design of selective and productive transition-metal cata-
lysts is a crucial issue in the asymmetric synthesis of organic
compounds. High catalyst efficiency is of paramount impor-
tance for industrial applications, allowing the use of precious
chiral complexes in small amounts and leading to products
with low metal content.[1] Enantioselective hydrogenation
(HY)[2] and transfer hydrogenation (TH)[3] of carbonyl com-
pounds are core processes in chemistry, which are usually
performed with complexes derived from elements of
Groups 8 and 9, with ruthenium being the metal of choice.
A crucial contribution to catalytic HY and TH was made by
Noyori and Ikariya and co-workers, which led to the synthe-
sis of trans-[RuCl2(diphosphane)(1,2-diamine)][4] and [(h6-
arene)RuCl(H2NCHPhCHPhNTs)].[5] These catalytic sys-
relatively large amount of
1 mol%)[5–7] on account of easy catalyst deactivation.
The robust CNN pincer complexes [RuCl
(CNN)(PP)][8]
(PP=Ph2P(CH2)4PPh2), prepared from 1-[6-(4’-methylphe-
a chiral complex (0.01–
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
nyl)pyridin-2-yl]methanamine (HCNN, 1a), have proven to
be the most active and productive catalysts[9] for the achiral
TH of carbonyl compounds (turnover frequencies (TOFs)
up to 2.5ꢀ106 hÀ1) at a loading of 0.005–0.001 mol%. The
development of the chiral version of this pincer system
would result in catalysts that display both high productivity
and enantioselectivity and thereby make TH a valid comple-
ment to HY. Recently, we found a practical route to the re-
lated chiral complexes cis-[RuCl2(diphosphane)(amino-
AHCTUNGTRENNUNG
[a] Prof. W. Baratta, Dr. S. Magnolia, Dr. K. Siega, Prof. P. Rigo
Dipartimento di Scienze e Tecnologie Chimiche
Universitꢁ di Udine, Via Cotonificio 108
33100 Udine (Italy)
AHCTUNGTRENNUNG
proven to efficiently catalyze the asymmetric TH and HY of
carbonyl compounds.[11]
We report herein that the preparation of the novel chiral
pincer catalysts [RuClACTHNUTRGENN(UG CNN)AHCTUNGTRENN(UGN Josiphos)] (Josiphos=1-[1-(di-
cyclohexylphosphano)ethyl]-2-(diarylphosphano)ferrocene)
Fax : (+39)0432-558803
E-mail: inorg@uniud.it
[b] Dr. G. Chelucci
Dipartimento di Chimica, Universitꢁ di Sassari
Via Vienna 2, 07100 Sassari (Italy)
726
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Chem. Eur. J. 2009, 15, 726 – 732

FULL PAPER
is greatly simplified through a one-pot synthesis that entails
the use of [RuCl2A(PPh3)3], a Josiphos diphosphane, and a
The ligands 1a–1c were used to prepare the CNN pincer
ruthenium complexes for the asymmetric reduction of ke-
N
racemic mixture of a 1-substituted HCNN ligand in the pres-
ence of acetic acid, which avoids the isolation of the pincer
ligands in enantiopure form. These complexes, which con-
tain correctly matched PP/CNN chiral ligands, are highly ef-
ficient catalysts for the asymmetric TH and HY of alkyl aryl
ketones with TOFs of up to 106 hÀ1 at a catalyst loading as
low as 0.002 mol%.
tones. The in situ generated derivative [RuCl
ACHTUNGTRENNUNG(CNN)-
A
CHTUNGTRENNUNG
and 1a,[12] promotes the quantitative TH of acetophenone to
(S)-1-phenylethanol (30 min, 65% enantiomeric excess (ee))
in 2-propanol with NaOiPr (2 mol%) at a ruthenium load-
ing of as low as 0.005 mol% (TOF=1.1ꢀ105 hÀ1 at 608C).
Interestingly, an increase in enantioselectivity was achieved
by using a racemic mixture of the 1-methyl-substituted
pincer ligand 1b in place of 1a (75% ee, TOF=1.0ꢀ105 hÀ1)
(Scheme 2).
Results and Discussion
Employment of 1a with the bulkier diphosphane (S,R)-Jo-
siphos*, with 4-OMe-3,5-Me2C6H2 instead of Ph, led to the
S alcohol with 90% ee (TOF=1.2ꢀ105 hÀ1). On account of
the high productivity of these in situ generated catalysts, we
decided to isolate the corresponding complexes. The ther-
mally stable ortho-metalated chiral derivative 2 was easily
Preparation of the chiral pincer complexes [RuCl
ACHTUNGTRENNUNG
ACHTUNGTRNE(NUNG CNN)-
and a tert-butyl group bonded to the carbon atom connected
to the NH2 moiety, were easily synthesized by treating the
corresponding ketones with NH2OH·HCl and reduction of
the oxime intermediate with Zn/ammonium acetate/NH4OH
(91 and 67% yields, respectively), as shown in Scheme 1.
prepared (67% yield) by treatment of [RuCl2ACTHNUTRGEN(UGN PPh3)3] with
1.2 equiv of (S,R)-Josiphos in toluene (1058C, 2 h), followed
by reaction with 1a (1.3 equiv) and NEt3 in 2-propanol at
reflux temperature (2 h; see Scheme 2). The 31P{1H} NMR
spectrum of 2 shows two doublets at d=67.2 and 40.8 ppm
(2J
ACTHNUTRGNEUNG(P,P)=41.3 Hz), which indicates the formation of a single
stereoisomer. The 13C{1H} NMR signal for the NCH2 group
is at d=46.1 ppm, whereas the ortho-metalated signal is at
d=185.9 ppm (dd, J
ACHTUNGTRENNUNG
complex 3 was prepared by reaction of [RuCl CHTUNGTRENNUNG
the bulkier (S,R)-Josiphos* and 1a (74% yield). Treatment
of (S,R)-Josiphos with a racemic mixture of 1b resulted in
Scheme 1. Synthesis of the ligands 1b and 1c.
Scheme 2. Synthesis of the chiral pincer CNN complexes 2–7.
Chem. Eur. J. 2009, 15, 726 – 732
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727

W. Baratta et al.
the formation of two ruthenium diastereoisomers in a ratio
of about 1:1, as inferred from the 31P{1H} NMR spectrum.[13]
Interestingly, by performing the reaction with an excess of
(Æ)-1b (4 equiv) in the presence of NEt3 and 0.5 equiv of
acetic acid, complex 4 was formed predominantly as one ste-
reoisomer (>92% major isomer) and was isolated in 70%
yield (Scheme 2). Under these conditions, the combination
of (S,R)-Josiphos* and (Æ)-1b led to the species 5 (>93%
major isomer), isolated in 63% yield. The weak acid proved
to facilitate the formation of the thermodynamically most
stable diastereoisomer, possibly through protonation and de-
coordination of the ortho-metalated CNN ligand of the ki-
netic product. Control experiments showed that reaction of
the [RuCl2ACHTUNGTRENNUNG(PPh3)3]/ACHTUNGTRENNUNG(S,R)-Josiphos or (S,R)-Josiphos* system
with the chiral ligand (R)-1b led to 4 and 5 as single stereo-
isomers, namely, the major isomers obtained in the synthesis
of 4 and 5 from (Æ)-1b. In addition, the use of (Æ)-1b or
(R)-1b leads to complexes that display the same catalytic ac-
tivity. Finally, derivatives 6 and 7 were isolated as single iso-
Scheme 3. Asymmetric TH and HY of ketones catalyzed by the chiral
pincer complexes 2–7.
mers (65 and 67% yields) from [RuCl2ACHTNUTRGNEG(UN PPh3)3], (S,R)-Josi-
phos or (S,R)-Josiphos*, and (Æ)-1c in the presence of
CH3CO2H. In these cases, the higher steric hindrance exert-
ed by the tBu group of 1c relative to the Me group of 1b re-
sulted in an increase in the diastereoselectivity. Attempts to
obtain suitable crystals for X-ray analysis failed. The stereo-
Table 1. Catalytic TH of alkyl aryl ketones with 2–7 and NaOiPr in 2-
propanol at 608C.[a]
Complex
Ketone
Conv.[b] [%]
t [min]
TOF[c] [hÀ1
]
ee[b] [%]
2
3
4
5
8a
8a
8a
8a
8a
8e
8g
8h
8h
8i
8j
8j
8k
8l
8o
8a
8a
8b
8d
8h
97
94
98
98
94
97
97
97
98
99
98
96
97
98
98
95
96
96
92
95
30
30
30
10
30
10
30
10
2
30
30
30
5
60
60
30
30
30
60
10
1.3ꢀ105
1.0ꢀ105
1.6ꢀ105
1.8ꢀ105
2.1ꢀ105
1.5ꢀ105
1.4ꢀ105
1.8ꢀ105
1.3ꢀ106
1.2ꢀ105
1.6ꢀ105
2.1ꢀ105
2.0ꢀ105
5.5ꢀ104
1.1ꢀ104
1.1ꢀ105
9.0ꢀ104
1.3ꢀ105
7.0ꢀ104
1.6ꢀ105
70 S
92 S
81 S
95 S
95 S
96 S
97 S
98 S
95 S
93 S
95 S
95 S
97 S
98 S
99 S
85 S
95 S
92 S
91 S
97 S
chemistry of the pincer complexes [RuCl
was proposed on the basis of the NMR control experiments
and the structures of the analogous [RuCl
(CNN)(PP)][8a,b]
(Josiphos)(aminopyridine)][10] de-
ACHUTGTNRENN(GU CNN)ACHUTNGTREN(NUNG Josiphos)]
AHCTUNGTRENNUNG
5[d]
5
and the related cis-[RuCl2ACHTUNGTRENNUNG
rivatives.
5
5
The synthesis of complexes 4–7 represents a straightfor-
ward approach to the preparation of catalysts containing
both chiral phosphane and pincer ligands, which enable a
high level of asymmetric induction in catalysis to be ach-
ieved without the need to synthesize the optically active 1-
substituted-1-(6-arylpyridin-2-yl)methanamines.[8b]
5[e]
5
5
5[d]
5[f]
5[f]
5
6
7
7
7
Catalytic results: Complexes 2–7 were found to be highly ef-
ficient catalysts for the TH and HY of ketones in basic alco-
hol media (Scheme 3).
In 2-propanol and with NaOiPr (2 mol%), TH occurred
at a high rate (TOFꢀ105–106 hÀ1) at a remarkably low cata-
lyst loading (0.005–0.002 mol%). Derivative 2 catalyzed the
quantitative reduction of acetophenone 8a (0.1m) to (S)-1-
phenylethanol (70% ee) at 608C in 30 min with TOF=1.3ꢀ
105 hÀ1 (Table 1).
7
[a] Unless stated otherwise the following reagents were used: 0.1m alkyl
aryl ketones, 0.005 mol% 2–7, and 2 mol% NaOiPr. [b] The conversion
and ee were determined by GC analysis. [c] Turnover frequency (moles
of ketone converted to alcohol per mole of catalyst per hour) at 50%
conversion. [d] [Ru]=0.002 mol%. [e] T=828C. [f] [Ru]=0.01 mol%.
With 3, with a bulkier diphosphane, the S alcohol was ob-
tained with 92% ee. Employment of 4 and 5, which contain
the methyl–substituted CNN ligand, led to a slightly higher
rate (TOFs up to 1.8ꢀ105 hÀ1) and a significant increase in
the ee of the S alcohol (81 and 95% ee, respectively) com-
pared with 2 and 3. By using a lower amount of 5
(0.002 mol%), neither erosion of the enantioselectivity or a
decrease in the rate was observed (TOF=2.1ꢀ105 hÀ1,
95% ee). To the best of our knowledge, no complexes capa-
ble of catalyzing asymmetric TH at such a low loading have
been reported, which indicates that these pincer systems can
find practical applications in the preparation of chiral alco-
hols. The derivatives 6 and 7, with a tBu group, catalyzed
the TH of 8a with TOFs of up to 1.1ꢀ105 hÀ1 and 85 and
95% ee of the S alcohol, respectively. These results show
that the bulkiness of the diphosphane aryl groups plays a
crucial role in the attainment of high asymmetric induction
and further improvement is achieved by using the 1-substi-
tuted HCNN ligands. With complexes 3, 5, and 7, a number
of ketones were quickly converted into the S alcohols. Che-
moselective TH of the aliphatic ketone 5-hexen-2-one (8m)
728
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Chem. Eur. J. 2009, 15, 726 – 732

Asymmetric Reduction of Alkyl Aryl Ketones
FULL PAPER
Table 2. Catalytic HY of alkyl aryl ketones with 2, 3, and 5, and KOtBu
under H2 at 408C.[a]
was observed with 3 (0.01 mol%), but with only low enan-
tioselectivity (30% ee), whereas heptan-2-one (8n) was re-
duced to the linear S alcohol with 50% ee. The substrates 4’-
chloroacetophenone (8e), 3’-methoxyacetophenone (8g),
and 3’,5’-dimethoxyacetophenone (8h) in the presence of 5
(0.005 mol%) gave the corresponding alcohols with TOFs
of up to 1.8ꢀ105 hÀ1 and 96, 97, and 98% ee, respectively.
When the TH of 8h was carried out in 2-propanol at reflux,
the alcohol was formed within 2 min (98% conversion) with
a remarkably high rate (TOF=1.3ꢀ106 hÀ1) and a slightly
lower enantioselectivity (95% ee) (Table 1). Notably, the
heterocyclic ketone 2-acetylpyridine (8i) was rapidly con-
verted into the intermediate (S)-1-(2-pyridyl)ethanol
(93% ee), whereas (S)-1-(3-trifluoromethylphenyl)ethanol,
which is a building block in the synthesis of the wide-spec-
trum agricultural fungicide (S)-MA20565, was obtained in
95% ee from 8j in 30 min (TOF=1.6ꢀ105 hÀ1).[14] The latter
ketone 8j was also reduced with 5 at a loading as low as
0.002 mol% (30 min; TOF=2.1ꢀ105 hÀ1), without deactiva-
tion of the catalyst or erosion of the enantioselectivity. To
show the practical potential of this system, (S)-1-(3-trifluo-
Complex Ketone Solvent[b]
Conv.[c]
[%]
t
TOF[d]
[104 hÀ1
ee[c]
[%]
[min]
G
]
2
3
3
3
8a
8a
8a
8a
8a
8a
8a
8b
8c
8 f
8k
8o
EtOH
EtOH
>99
99
30
30
30
90
60
30
30
20
30
30
30
30
4.3
3.6
2.9
2.5
1.7
2.8
3.3
3.8
3.0
2.9
3.6
2.5
70 S
71 S
88 S
88 S
77 S
87 S
90 S
93 S
90 S
91 S
93 S
99 S
MeOH/EtOH=3:7 >99
MeOH/EtOH=1
EtOH
94
>99
5[e]
5[e]
5[e]
5
MeOH/EtOH=3:7 >99
MeOH/EtOH=1
MeOH/EtOH=1
MeOH/EtOH=1
MeOH/EtOH=1
MeOH/EtOH=1
MeOH/EtOH=1
>99
99
99
>99
>99
>99
5
5
5
5
[a] Unless stated otherwise the following reagents were used: 0.5m alkyl
aryl ketones, 0.02 mol% 2, 3, and 5, 6 mol% KOtBu, and 5 atm of H2.
[b] Ratio by volume. [c] The conversion and ee were determined by GC
analysis. [d] Turnover frequency (moles of ketone converted to alcohol
per mole of catalyst per hour) at 50% conversion. [e] [Ru]=0.01 mol%.
methanol to ethanol resulted in a decrease in the rate
(TOF=3.6ꢀ104, 2.9ꢀ104, and 2.5ꢀ104 hÀ1) and an increase
of enantioselectivity (71, 88, and 88% ee; MeOH/EtOH=0,
3:7, and 1 by volume). Conversely, with 5 (0.01 mol%), ad-
dition of MeOH led to an increase in both activity (TOF=
1.7ꢀ104, 2.8ꢀ104, and 3.3ꢀ104 hÀ1) and enantioselectivity
(77, 87, and 90% ee; MeOH/EtOH=0, 3:7, and 1). In meth-
anol the reduction of 8a (0.5m) with 5 under dihydrogen has
to be regarded as pure HY, affording 89% ee (78% conver-
sion in 3 h), whereas in 2-propanol the S alcohol was formed
by TH with a negligible contribution from HY (91% ee and
75% conversion). These results suggest that the alcohol sol-
vent plays an important role in the HY of ketones mediated
by these pincer complexes. By using the mixture MeOH/
EtOH=1, complex 5 has been shown to catalyze rapidly the
HY of different substrates. Thus, compounds 8b, 8c, 8 f, and
8k have been reduced to the corresponding S alcohols
within 30 min (TOFs of up to 3.8ꢀ104 hÀ1) and 90–93% ee.
Finally, ketone 8o was efficiently hydrogenated under these
conditions to the corresponding S alcohol with 99% ee, an
identical result to that observed in the TH using the same
complex.
ACHTUNGTRENNUNGromethylphenyl)ethanol (4.10 g, 95% ee, 90% yield) were
obtained from 8j (4.53 g) in 1 h at 608C, using complex 5
(0.50 mg, 0.002 mol%). In addition the TH of the bulky
naphthyl ketones 8k and 8l led to the S alcohols with 97
and
98% ee,
respectively.
Interestingly,
with
5
(0.005 mol%), propiophenone (8o) was efficiently convert-
ed (1 h) into (S)-1-phenyl-1-propanol with 99% ee. By using
catalyst 7, with a tBu group, the substrates 3’-methylaceto-
phenone (8b), 2’-chloroacetophenone (8d), and 8h were re-
duced to S alcohols with TOFs of up to 1.6ꢀ105 hÀ1 and 92,
91, and 97% ee, respectively (Table 1). The high perfor-
mance of these pincer complexes has led to a new standard
in the asymmetric TH of ketones in terms of productivity
and rate, such that TH is an alternative to HY. To investi-
gate the matched/mismatched ligand effect, the in situ pre-
pared catalytic system [RuCl2ACTHNUTRGENN(UG PPh3)3]/ACHTUNTGREN(NUGN R,S)-Josiphos*/(R)-
1b afforded a slow reduction of 8a to (R)-1-phenylethanol
(TOF=3.6ꢀ104 hÀ1, 74% ee), whereas the use of (S,R)-Josi-
phos* led to the S alcohol with a higher rate and enantiose-
lectivity (TOF=1.6ꢀ105 hÀ1, 94% ee), with values similar to
those observed with the isolated complex 5. These results
and the NMR control experiments indicate that (S,R)-Josi-
phos*/(R)-1b is the correctly matched combination for the
catalysis and complex 5, obtained from (Æ)-1b, displays the
same ligand combination.
A few ruthenium systems have been found to efficiently
catalyze both asymmetric TH and HY of carbonyl com-
pounds.[5,7b,d,15] Interestingly, the chiral pincer complexes 2,
3, and 5 also display high catalytic activity in the asymmetric
HY of ketones in ethanol or methanol/ethanol under 5 atm
of dihydrogen (Scheme 3). With 2 (0.02 mol%) and KOtBu
(6 mol%) in EtOH, the substrate 8a was rapidly and quanti-
tatively reduced to (S)-1-phenylethanol at 408C (30 min,
TOF=4.3ꢀ104 hÀ1, 70% ee; Table 2).
With regards to the mechanism for the reduction of ke-
tones in basic alcohol media, the formation of alkoxide and
hydride ruthenium complexes is expected.[16] The reaction of
5 with NaOiPr (2 equiv) in 2-propanol/C6D6 (1:1 by volume)
at RT leads to the quantitative formation of a new species,
which was ascribed to the corresponding isopropoxide com-
plex [Ru
64.5 and 42.5 ppm with J
study of analogous alkoxides [Ru
{(S,R)-Josiphos*}] (31P{1H} NMR: d=
ACHTUNGTREN(GNUN OiPr)ACHTUNTRGEG(NNUN CNN)CAHTNUGTRENNGUN
2
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUNG
1,4-bis(diphenylphosphino)butane (dppb), (2S,4S)-bis(diphe-
nylphosphano)pentane).[17a] Evaporation of this solution
leads to the formation of a mixture of complexes that con-
tains the hydride [RuHACTHNUTRGENN(GU CNN)HCATUNGTRENN{UGN (S,R)-Josiphos*}] as the main
The catalytic activity and selectivity of 3 in the HY of 8a
was strongly affected by the alcohol medium. Addition of
product, which is formed by a b-hydrogen elimination reac-
tion from the ruthenium alkoxide, as observed for [RuH-
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729

W. Baratta et al.
further purification (4.81 g, 95%). M.p. 85–878C; 1H NMR (200.1 MHz,
1
G
ACHTUNGTRENNUNG
(dppb)].[8a,17a] In the H NMR spectrum recorded in
CDCl3, 208C): d=9.76 (s, 1H), 8.08 (dd, 3J
ACTHNUGRTNENUG(H,H)=7.8, JCAHTUNGTREN(NNGU H,H)=1.8 Hz,
2H), 7.81–7.65 (m, 3H), 7.54–7.35 (m, 3H), 2.52 ppm (s, 3H); elemental
analysis calcd (%) for C13H12N2O: C 73.56, H 5.70, N 13.20; found: C
73.67, H 5.73, N 13.15.
2
À7.87 ppm with J
ACHTUNGTRENNUNG(H,P)=88.6 and 30.2 Hz due to the pres-
ence of trans and cis phosphorus atoms, whereas the
31P{1H} NMR signals are at d=55.8 and 41.7 ppm, with a sig-
1-(6-Phenylpyridin-2-yl)ethanamine (1b): 1-(6-Phenylpyridin-2-yl)eth-
AHCTUNGTREGaNNNU none oxime (4.81 g, 22.7 mmol) and ammonium acetate (2.16 g,
nificantly small 2J
(CNN)
and HY reactions in alcohol media, the alkoxide and hy-
ACHTUNGTRENNUNG
28.0 mmol) in a solution of 30% NH3/H2O/96% EtOH (81.3, 54.2, and
54.2 mL) were stirred for 30 min at room temperature. Powdered zinc
(8.13 g) was added portionwise over a period of 2 h at room temperature
and then the reaction mixture was heated under reflux for 3 h. The grey
precipitate was filtered under reduced pressure and the solvent was
evaporated to give a residue, which was made alkaline with 10% NaOH
and extracted with diethyl ether (3ꢀ30 mL). The combined organic
phase was dried over Na2SO4 and the solvent was evaporated to give 1b
as a pale-orange oil (4.34 g, 96%). 1H NMR (200.1 MHz, CDCl3, 208C):
A
ACHTUNGTRENNUNG
dride intermediates [RuXACHTNUGRTNEUNG
(CNN)(PP)] (X=OR, H)[17] are
the species involved in the catalysis.[18] Recently, evidence
for the formation of the ruthenium alkoxide [RuH-
C
ACHTUNGTRENNUNG(binap)ACHUTNGTRENN(NGU dpen)] (dpen=1,2-diphenylethylenedi-
C
ACHTUNGTRENNUNG
d=8.06–7.98 (m, 2H), 7.64 (t, 3J
7.5 Hz, 1H), 7.50–7.33 (m, 3H), 7.16 (d, 3J
3J(H,H)=6.6 Hz, 1H), 2.05 (s, 2H), 1.45 ppm (d, 3J
ACHTUNGTRENNUNG
C
ACHTUNGTRENNUNG(H,H)=
step in the catalytic hydrogenation of ketones, was provided
by Hamilton and Bergens.[19]
AHCTUNGTRENNUNG
N
Conclusion
2,2-Dimethyl-1-(6-phenylpyridin-2-yl)propan-1-one oxime: A mixture of
2,2-dimethyl-1-(6-phenylpyridin-2-yl)propanone (0.95 g, 3.97 mmol) and
hydroxylamine hydrochloride (0.50 g, 7.19 mmol) in 96% ethanol
(35.5 mL) was stirred at room temperature for 24 h. The solvent was re-
moved under reduced pressure and the residue was taken up with
CH2Cl2 and with a saturated solution of NaHCO3. The resulting mixture
was vigorously stirred for 30 min, the organic phase was separated, and
the aqueous phase was extracted with CH2Cl2 (2ꢀ20 mL). The combined
organic phase was dried over anhydrous Na2SO4 and the solvent was
evaporated to give 2,2-dimethyl-1-(6-phenylpyridin-2-yl)propan-1-one
oxime as a white solid, which was used in the next step without further
purification (0.95 g, 94%). M.p. 190–1918C; 1H NMR (200.1 MHz,
The chiral pincer complexes [RuClACHTUNTRGENN(UG CNN)ACHUTNGTRENN(UGN Josiphos)], ob-
tained from (Æ)-HCNN ligands by diastereoselective syn-
thesis, are efficient catalysts for the asymmetric transfer hy-
drogenation (TH) and hydrogenation (HY) of alkyl aryl ke-
tones. High enantioselectivity (up to 99%) has been ach-
ieved in TH with a remarkably high rate (TOF=105–
106 hÀ1) and low catalyst loading (0.005–0.002 mol%). By
changing the reaction parameters, these pincer complexes
also catalyze the HY of ketones (0.02–0.01 mol% of Ru)
with H2 (5 atm) to give up to 99% ee. On account of the re-
markably high activity and productivity of these complexes,
this class of ruthenium derivatives has potential for applica-
tion in homogeneous asymmetric catalysis.
CDCl3, 208C): d=8.30 (s, 1H), 8.05 (dd, J
ACHTUNGTRENNUNG
7.68 (m, 2H), 7.52–7.37 (m, 3H), 7.17 (dd, JACHTUNGTRENNNUG
1.26 ppm (s, 9H); elemental analysis calcd (%) for C16H18N2O: C 75.56,
H 7.13, N 11.01; found: C 75.44, H 7.16, N 11.04.
2,2-Dimethyl-1-(6-phenylpyridin-2-yl)propan-1-amine (1c): 1-(6-Phenyl-
pyridin-2-yl) tert-butyl ketoxime (0.92 g, 3.62 mmol) and ammonium ace-
tate (0.344 g, 4.46 mmol) in a solution of 30% NH3/H2O/96% EtOH
(12.9, 8.6, and 8.6 mL) were stirred for 30 min at room temperature. Pow-
dered zinc (1.29 g) was added portionwise over a period of 2 h at room
temperature and then the reaction mixture was heated under reflux for
3 h. The grey precipitate was filtered under reduced pressure and the sol-
vent was evaporated to give a residue, which was made alkaline with
10% NaOH and extracted with diethyl ether (3ꢀ20 mL). The combined
organic phase was dried over Na2SO4 and the solvent was evaporated to
give 1c as a colorless oil (0.62 g, 71%). 1H NMR (200.1 MHz, CDCl3,
Experimental Section
General: All reactions were carried out under an argon atmosphere by
using standard Schlenk techniques. The solvents and ketones were care-
fully dried by standard methods and distilled under argon before use.
The diphosphane ligands and all other chemicals were purchased from
Aldrich and Strem and used without further purification. Compounds
1a,[8b] 1-(6-phenylpyridin-2-yl)ethanone,[20] 2,2-dimethyl-1-(6-phenylpyri-
208C): d=8.03 (d, 3J
(m, 3H), 7.09 (dd, J
ACHTUNGTRENNUNG
2ACTHNUTRGNEUNG
din-2-yl)propan-1-one,[20] and [RuCl (PPh3)3][21] were prepared according
AHCTUNGTRENNUNG
to literature procedures. NMR spectra were recorded on a Bruker AC
200 spectrometer and the chemical shifts were measured in ppm relative
0.97 ppm (s, 9H); 13C{1H} NMR (50.3 MHz, CDCl3, 208C): d=162.1,
155.7, 139.5, 136.1, 128.7, 128.6, 126.8, 121.9, 118.2, 65.7, 35.4, 26.7 ppm;
elemental analysis calcd (%) for C16H20N2: C 79.96, H 8.39, N 11.66;
found: C 79.84, H 8.41, N 11.68.
to TMS for H and 13C{1H} NMR and 85% H3PO4 for 31P{1H} NMR. Ele-
1
mental analyses (C, H, and N) were carried out with a Carlo Erba 1106
elemental analyzer. GC analyses were performed with a Varian GP-3380
gas chromatograph equipped with a MEGADEX-ETTBDMS-b chiral
column.
Synthesis of 2: [RuCl
2ACHTUNGERTN(NUNG PPh3)3] (100 mg, 0.104 mmol) and (S,R)-Josi-
AHCTUNGRTEGNpNNU hos·C2H5OH (80 mg, 0.125 mmol) were treated with toluene (2 mL);
the suspension was stirred at 1058C for 2 h, and the solvent was evapo-
rated. The ligand 1a (27 mg, 0.136 mmol) and triethylamine (176 mL,
1.26 mmol) were added to the complex suspended in 2-propanol (2 mL)
and the mixture was heated at reflux for 2 h. The solution was concen-
trated to 0.5 mL and addition of pentane afforded an orange precipitate,
which was filtered and dried under reduced pressure. The solid was dis-
solved in dichloromethane (2 mL) and the filtrate was concentrated. Ad-
dition of pentane gave a yellow precipitate, which was filtered and dried
under reduced pressure (65 mg, 67%). 1H NMR (200.1 MHz, CD2Cl2,
1-(6-Phenylpyridin-2-yl)ethanone oxime: A solution of 1-(6-phenylpyri-
din-2-yl)ethanone (4.70 g, 23.8 mmol) and hydroxylamine hydrochloride
(3.06 g, 44.0 mmol) in 96% ethanol (150 mL) was stirred for 24 h at room
temperature. The solvent was removed under reduced pressure and the
residue was taken up with CH2Cl2 and a saturated solution of NaHCO3.
The resulting mixture was vigorously stirred for 30 min, the organic
phase was separated, and the aqueous phase was extracted with CH2Cl2
(2ꢀ20 mL). The combined organic phase was dried over anhydrous
Na2SO4 and the solvent was evaporated to give 1-(6-phenylpyridin-2-yl)-
ethanone oxime as a white solid, which was used in the next step without
208C): d=8.13 (t, 3J
ACTHUNGTERNNU(G H,H)=7.8 Hz, 2H; aromatic protons), 7.87 (s, 1H;
730
www.chemeurj.org
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2009, 15, 726 – 732

Asymmetric Reduction of Alkyl Aryl Ketones
FULL PAPER
aromatic proton), 7.80–7.17 (m, 11H; aromatic protons), 6.93 (d, 3J-
(d, J
(d, J(C,P)=18.5 Hz; CH of Cy), 31.6–26.5 (m; CH2 of Cy, PCMe), 23.2
(s; NCMe), 15.5 ppm (d,
(C,P)=6.7 Hz; PCMe); 31P{1H} NMR
(81.0 MHz, CD2Cl2, 208C): d=66.1 (d, J
(P,P)=42.3 Hz); elemental analysis calcd (%) for C49H57ClFeN2P2Ru: C
ACHUTNGTNERNUG(C,P)=2.5 Hz; CHNH2) 40.3 (d, JACHTUNGTNER(NUGN C,P)=14.5 Hz; CH of Cy), 37.8
A
N
ACHTUNGTRENNUNG
3
omatic proton), 4.67 (s, 1H; PCH), 4.50–4.28 (m, 3H; C5H3), 4.12 (dd, J-
(H,H)=15.6, 4.6 Hz, 1H; CH2N), 3.91 (m, 1H; CH2N), 3.73 (s, 5H;
JACHTUNGTRENNUNG
2
2
R
ACHTUNGTNER(NUNG P,P)=42.3 Hz), 41.3 ppm (d, J-
C5H5), 3.16 (brs, 1H; NH2), 2.26 (s, 3H; CH3), 1.95–0.60 ppm (m, 26H;
ACHTUNGTRENNUNG
CH3, Cy, NH2); 13C{1H} NMR (50.3 MHz, CD2Cl2, 208C): d=185.9 (dd, J-
63.40, H 6.19, N 3.02; found: C 63.64, H 6.33, N 3.09.
ACHTUNGTRENNUNG
Synthesis of 5
JACHTUNGTRENNUNG
Method a: [RuCl2ACTHNUTRGEN(UNG PPh3)3] (50 mg, 0.052 mmol) and (S,R)-Josiphos*
AHCTUNGTRENNUNG
(44 mg, 0.062 mmol) were treated with dichloromethane (2 mL), the solu-
tion was stirred at room temperature for 2 h, and the solvent was evapo-
rated. Addition of (Æ)-1b (41 mg, 0.207 mmol), acetic acid (1.5 mL,
0.026 mmol), and triethylamine (85 mL, 0.61 mmol) to the complex sus-
pended in 2-propanol (2 mL) led to a solution that was heated at reflux
for 4 h and concentrated to give an oily product. Pentane (2 mL) was
added to afford an orange precipitate, which was filtered and dried under
reduced pressure. The solid was treated with dichloromethane (1 mL)
and after filtration pentane (2 mL) was added to the solution to give an
orange precipitate, which was filtered and dried under reduced pressure
(34 mg, 63%; >93% major isomer).
G
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG
C49H57ClFeN2P2Ru: C 63.40, H 6.19, N 3.02; found: C 63.70, H 6.28, N
3.14.
Synthesis of 3: [RuCl2ACHTUNGTRENNUNG(PPh3)3] (50 mg, 0.052 mmol) and (S,R)-Josiphos*
(44 mg, 0.062 mmol) were treated with dichloromethane (2 mL); the so-
lution was stirred at room temperature for 2 h, and the solvent was
evaporated. The ligand 1a (12 mg, 0.061 mmol) and triethylamine (85 mL,
0.61 mmol) were added to the complex suspended in 2-propanol (2 mL)
and the mixture was heated at reflux for 3 h. The solution was concen-
trated to 0.5 mL and addition of pentane (2 mL) afforded an orange pre-
cipitate, which was filtered and dried under reduced pressure. The solid
was dissolved in dichloromethane (2 mL) and the filtrate was concentrat-
ed. Addition of pentane gave a yellow-orange precipitate, which was fil-
tered and dried under reduced pressure (40 mg, 74%). 1H NMR
(200.1 MHz, CD2Cl2, 208C): d=7.81 (brs, 3H; aromatic protons), 7.76 (s,
Method b: Complex 5 was synthesized as described in Method a by using
(R)-1b (26 mg, 0.131 mmol, enantiomeric ratio 80:20) in place of (Æ)-1b.
Yield: 37 mg (68%). 1H NMR (200.1 MHz, CDCl3, 208C): d=8.15–6.89
(m, 11H; aromatic protons), 4.70 (m, 1H; PCH), 4.44–4.26 (m, 3H;
C5H3), 3.97 (m, 1H; NCHMe), 3.71 (s, 6H; OMe), 3.68 (s, 5H; C5H5),
3.18 (m, 1H; NH2), 2.19 (s, 12H; Me), 1.80–0.50 ppm (m, 29H; CH3, Cy,
NH); 13C{1H} NMR (50.3 MHz, CDCl3, 208C): d=185.8 (m; CRu),
165.5–116.2 (m; aromatic carbons), 97.0 (dd, J
FeC5H3), 74.0 (s; FeC5H3), 69.8 (s; FeC5H5), 67.8–67.3 (m; FeC5H3), 59.6
(s; OMe), 59.5 (s; OMe), 57.5 (s; CHNH2), 40.1 (d, J(C,P)=15.2 Hz; CH
of Cy), 37.6 (d, J(C,P)=17.8 Hz; CH of Cy), 31.9–25.3 (m; CH2 of Cy,
PCMe), 22.9 (s; NCHMe), 16.4 (s; Me), 16.1 (s; Me), 15.4 ppm (d, J-
(C,P)=7.0 Hz; PCMe); 31P{1H} NMR (81.0 MHz, C6D6, 208C): d=66.4
(d, 2J(P,P)=41.0 Hz), 38.2 ppm (d, 2J
(P,P)=41.0 Hz); elemental analysis
ACHTUNGERTN(NUNG C,P)=17.7, 3.3 Hz; ipso-
AHCTUNGTRENNUNG
1H; aromatic proton), 7.62 (m, 2H; aromatic protons), 7.28 (d, 3J-
(H,H)=8.6 Hz, 2H; aromatic protons), 6.93 (d, J
omatic proton), 6.76 (d, JACTHNUTRGNE(NUG H,H)=8.6 Hz, 1H; aromatic proton), 4.71 (m,
1H; PCH), 4.48–4.42 (m, 2H; C5H3), 4.29–3.92 (m, 3H; C5H3, CH2N),
3.71 (s, 6H; OMe), 3.70 (s, 5H; C5H5), 3.05 (m, 1H; NH2), 2.25 (s, 3H;
Me), 2.19 (s, 6H; Me), 2.17 (s, 6H; Me), 1.94–0.58 ppm (m, 26H; CH3,
Cy, NH2); 13C{1H} NMR (50.3 MHz, CD2Cl2, 208C): d=186.4 (dd, J-
AHCTUNGTRENNUNG
3
(H,H)=7.6 Hz, 1H; ar-
3
AHCTUNGTRENNUNG
A
ACHTUNGTRENNUNG
calcd (%) for C55H69ClFeN2O2P2Ru: C 63.25, H 6.66, N 2.68; found: C
63.69, H 6.87, N 2.82.
Synthesis of 6: Complex 6 was synthesized as described for 4 (Method a)
by using (Æ)-1c (50 mg, 0.208 mmol) in place of (Æ)-1b. Yield: 33 mg
ACHTUNGTRENNUNG
J
N
ACHTUNGTRENNUNG
1
(65%). H NMR (200.1 MHz, CD2Cl2, 208C): d=8.21–6.98 (m, 17H; aro-
matic protons), 4.69 (m, 1H; PCH), 4.52–4.36 (m, 3H; C5H3), 3.92 (brs,
1H; CHtBu), 3.76 (s, 5H; C5H5), 3.10 (t, JACTHNUTRGNEUNG(H,H)=11.6 Hz, 1H; NH2),
AHCTUNGTRENNUNG
JACHTUNGTRENNUNG
2.00–0.99 (m, 24H; Me, Cy, NH), 0.97 (s, 9H; tBu), 0.54 ppm (m, 2H;
ACHTUNGTRENNUNG
Cy); 13C{1H} NMR (50.3 MHz, CD2Cl2, 208C): d=187.6 (m; CRu), 166.7–
AHCTUNGTRENNUNG
116.9 (m; aromatic carbons), 97.3 (dd,
FeC5H3), 73.7 (s; FeC5H3), 72.5 (m; ipso-FeC5H3), 71.9 (d, J
2.4 Hz; CHNH2), 70.3 (s; FeC5H5), 68.6 (d, J(C,P)=4.3 Hz; FeC5H3), 68.3
(d, J(C,P)=8.0 Hz; FeC5H3), 40.2 (d, J(C,P)=14.6 Hz; CH of Cy), 38.0
(d, J(C,P)=18.5 Hz; CH of Cy), 35.2–30.9 (m; CH2 of Cy and CMe3),
28.8 (dd, J(C,P)=21.9, 4.2 Hz; PCMe), 28.2–27.5 (m; CH2 of Cy), 27.3 (s;
CMe3), 26.9 (s; CH2 of Cy), 26.4 (s; CH2 of Cy), 15.5 ppm (d, J(C,P)=
6.8 Hz; PCMe); 31P{1H} NMR (81.0 MHz, CD2Cl2, 208C): d=65.7 (d, 2J-
(P,P)=42.6 Hz), 42.0 ppm (d, 2J
(P,P)=42.6 Hz); elemental analysis calcd
JACHTUNGTRENNUNG
AHCTUNGTRENNUNG
ACHTUNGTRENNUNG
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
C55H69ClFeN2O2P2Ru: C 63.25, H 6.66, N 2.68; found: C 63.68, H 6.89, N
2.76.
A
ACHTUNGTRENNUNG
AHCTUNGTRENNUNG
Synthesis of 4
AHCTUNGTRENNUNG
Method a: [RuCl
ACHTUNGTRENNUNG
2ACHTUNGTRENNUNG(PPh3)3] (50 mg, 0.052 mmol) and (S,R)-Josi-
ACHTUNGTRENNUNG
the suspension was stirred at 1058C for 2 h, and the solvent was evapo-
rated. Addition of (Æ)-1b (41 mg, 0.207 mmol), acetic acid (1.5 mL,
0.026 mmol), and triethylamine (85 mL, 0.61 mmol) to the complex sus-
pended in 2-propanol (2 mL) led to a solution that was heated at reflux
for 4 h and concentrated to give an oily product. Pentane (2 mL) was
added to afford an orange precipitate, which was filtered and dried under
reduced pressure. The solid was treated with dichloromethane (1 mL)
and after filtration pentane (2 mL) was added to the solution to give an
orange precipitate, which was filtered and dried under reduced pressure
(34 mg, 70%; >92% major isomer).
A
ACHTUNGTRENNUNG
(%) for C52H63ClFeN2P2Ru: C 64.36, H 6.54, N 2.89; found: C 64.88, H
6.72, N 2.65.
Synthesis of 7: Complex 7 was synthesized as described for 5 (Method a)
by using (Æ)-1c (50 mg, 0.208 mmol) in place of (Æ)-1b. Yield: 38 mg
(67%). 1H NMR (200.1 MHz, CD2Cl2, 208C): d=8.18 (m, 2H; aromatic
protons), 7.87 (d, 3J
ACHTNUTRGNEUNG(H,H)=8.0 Hz, 1H; aromatic proton), 7.76–7.31 (m,
6H; aromatic protons), 6.97 (m, 2H; aromatic protons), 4.70 (m, 1H;
PCH), 4.49–4.31 (m, 4H; C5H3, CHNH2), 3.73 (s, 5H; C5H5), 3.70 (s, 3H;
OMe), 3.66 (s, 3H; OMe), 3.13 (t, JACHTNUGRTENUNG(H,H)=11.5 Hz, 1H; NH2), 2.19 (s,
Method b: Complex 4 was synthesized as described in Method a by using
(R)-1b (26 mg, 0.131 mmol, enantiomeric ratio 80:20) in place of (Æ)-1b.
Yield: 30 mg (62%). 1H NMR (200.1 MHz, CD2Cl2, 208C): d=8.22–6.90
(m, 17H; aromatic protons), 4.68 (m, 1H; PCH), 4.53–4.36 (m, 3H;
12H; Me), 2.00–1.10 (m, 20H; CH3, Cy, NH2), 1.02 (s, 9H; CMe3), 0.98–
0.52 ppm (m, 6H; Cy); 13C{1H} NMR (50.3 MHz, CD2Cl2, 208C): d=
188.0 (m; CRu), 166.7–117.1 (m; aromatic carbons), 97.5 (d, J
24.7 Hz; ipso-FeC5H3), 73.9 (s; FeC5H3), 72.0 (s; CHNH2), 70.2 (s;
FeC5H5), 68.4 (d, (C,P)=7.9 Hz; FeC5H3), 68.1 (d, (C,P)=4.1 Hz;
FeC5H3), 59.8 (s; OMe), 40.3 (d, J(C,P)=14.2 Hz; CH of Cy), 38.0 (d, J-
AHCTUNGRTENGUN(N C,P)=18.5 Hz; CH of Cy), 35.3–27.5 (m; CH2 of Cy, PCMe, and CMe3),
ACHTUNGTRENNUNG(C,P)=
C5H3), 4.01 (m, 1H; CHMe), 3.74 (s, 5H; C5H5), 3.12 (t, J
G
J
N
JACHTUNGTRENNUNG
11.6 Hz, 1H; NH2), 2.00–0.52 ppm (m, 29H; Me, Cy, NH); 13C{1H} NMR
(50.3 MHz, CD2Cl2, 208C): d=187.2 (m; CRu), 165.7–116.9 (m; aromatic
carbons), 74.1 (s; FeC5H3), 70.3 (s; FeC5H5), 68.6–68.4 (m; FeC5H3), 57.9
ACHTUNGTRENNUNG
27.3 (s; CMe3), 16.5 (s; Me), 16.2 (s; Me), 15.5 ppm (d, JACTHNUTRGENUG(N C,P)=6.9 Hz;
Chem. Eur. J. 2009, 15, 726 – 732
ꢂ 2009 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
731

W. Baratta et al.
PCMe); 31P{1H} NMR (81.0 MHz, CD2Cl2, 208C): d=65.8 (d, 2J
42.8 Hz), 38.4 ppm (d, 2J
(P,P)=42.8 Hz); elemental analysis calcd (%)
for C58H75ClFeN2O2P2Ru: C 64.11, H 6.96, N 2.58: found: C 64.28, H
7.12, N 2.65.
(P,P)=
Rautenstrauch, X. Hoang-Cong, R. Churlaud, K. Abdur-Rashid,
R. H. Morris, Chem. Eur. J. 2003, 9, 4954; e) D. Cuervo, M. P.
Gamasa, J. Gimeno, Chem. Eur. J. 2004, 10, 425.
AHCTUNGTRENNUNG
[8] a) W. Baratta, G. Chelucci, S. Gladiali, K. Siega, M. Toniutti, M. Za-
nette, E. Zangrando, P. Rigo, Angew. Chem. 2005, 117, 6370; Angew.
Chem. Int. Ed. 2005, 44, 6214; b) W. Baratta, M. Bosco, G. Chelucci,
A. Del Zotto, K. Siega, M. Toniutti, E. Zangrando, P. Rigo, Organo-
metallics 2006, 25, 4611; c) W. Baratta, K. Siega, P. Rigo, Adv. Synth.
Catal. 2007, 349, 1633.
[9] a) E. Mothes, S. Sentets, M. A. Luquin, R. Mathieu, N. Lugan, G.
Lavigne, Organometallics 2008, 27, 1193; b) R. J. Lundgren, M. A.
Rankin, R. McDonald, G. Schatte, M. Stradiotto, Angew. Chem.
2007, 119, 4816; Angew. Chem. Int. Ed. 2007, 46, 4732; c) M. Ga-
gliardo, P. A. Chase, S. Brouwer, G. P. M. van Klink, G. van Koten,
Organometallics 2007, 26, 2219; d) Z. E. Clarke, P. T. Maragh, T. P.
Dasgupta, D. G. Gusev, A. J. Lough, K. Abdur-Rashid, Organome-
tallics 2006, 25, 4113; e) P. Braunstein, M. D. Fryzuk, F. Naud, S. J.
Rettig, J. Chem. Soc. Dalton Trans. 1999, 589.
Typical procedure for the catalytic TH of ketones: The ruthenium com-
plex (2.50 mmol) was dissolved in 2-propanol (5 mL). The ketone
(2.00 mmol) was dissolved in 2-propanol (final volume 19.6 mL) and the
solution was heated at 608C under argon. The ketone was reduced by the
addition of NaOiPr (0.1m, 400 mL, 40 mmol) in 2-propanol and the cata-
lyst solution (200 mL, 0.1 mmol) to the ketone solution. The yield of the
product was determined by GC (Ru 0.005 mol%, NaOiPr 2 mol%,
ketone 0.1m).
Typical procedure for the catalytic HY of ketones: The ruthenium com-
plex (1.72 mmol) was dissolved in alcohol (1 mL of EtOH or MeOH/
EtOH mixture). The ketone (4.30 mmol), KOtBu (0.26 mmol), and the
catalyst solution (500 mL, 0.86 mmol) were added to alcohol (final volume
8.6 mL). The resulting solution was transferred into a thermostated reac-
tor at 408C and the reduction was performed by introducing dihydrogen
at a pressure of 5 atm (Ru 0.02 mol%, KOtBu 6 mol%, ketone 0.5m).
[10] W. Baratta, G. Chelucci, E. Herdtweck, S. Magnolia, K. Siega, P.
Rigo, Angew. Chem. 2007, 119, 7795; Angew. Chem. Int. Ed. 2007,
46, 7651.
[11] W. Baratta, M. Ballico, G. Chelucci, K. Siega, P. Rigo, Angew.
Chem. 2008, 120, 4434; Angew. Chem. Int. Ed. 2008, 47, 4362.
[12] The in situ generated catalyst was prepared by heating at reflux
Acknowledgements
temperature a 2-propanol solution of [RuCl2ACTHNUTRGEN(UNG PPh3)3] with (S,R)-Josi-
This work was supported by the Ministero dellꢃUniversitꢁ e della Ricerca
(MIUR) and the Regione Friuli Venezia Giulia. We thank Johnson-Mat-
they/Alfa Aesar for a generous loan of ruthenium and Mr. P. Polese for
carrying out the elemental analyses.
phos (1.5 equiv, 1 h) and 1a (2 equiv, 1 h).
[13] 31P{1H} NMR (81.0 MHz, CD2Cl2): d=66.1, 41.3 (d, 2J
N
2
42.3 Hz), 64.7, 40.9 ppm (d, J
N
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Received: October 13, 2008
Published online: December 3, 2008
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