New benzo[h]quinoline-based ligands and their pincer Ru and Os complexes for efficient catalytic transfer hydrogenation of carbonyl compounds

Article abstract of DOI:10.1002/chem.200800888

New benzo[h]quinoline ligands (HCN'N) containing a CHRNH₂ (R = H (a), Me (b), tBu (c)) function in the 2-position were prepared starting from benzo[h]quinoline N-oxide (in the case of ligand a) and 2-chlorobenzo[h]- quinoline (for ligands b and c). These compounds were used to prepare ruthenium and osmium complexes, which are excellent catalysts for the transfer hydrogenation (TH) of ketones. The reaction of a with [RuCl₂- (PPh₃)₃] in 2-propanol at reflux afforded the terdentate CN′N complex [RuCl(CN′N)(PPh₃)₂] (1), whereas the complexes [RuCl(CN′N)(dppb)] (2-4; dppb = Ph₂P(CH ₂)₄PPh₂) were obtained from [RuCl ₂(PPh₃)(dppb)] with a-c, respectively. Employment of (R,5)-Josiphos, (S,R)-Josiphos*, (S,S)-Skewphos, and (S)-MeO-Biphep in combination with [RuCl₂(PPh₃)₃] and liganda gave the chiral derivatives [RuCl-(CN′N)(PP)] (5-8). The osmium com-_plex [OsCl(CN'N)(dppb)] (12) was prepared by treatment of [OsCl₂(PPh ₃)₃] with dppb and ligand a. Reaction of the chloride 2 and 12 with NaO/Pr in 2-propanol/toluene afforded the hydride complexes [MH(CN'N)(dppb)] (M = Ru 10, Os 14), through elimination of acetone from [M(O/Pr)(CN'N)(dppb)] (M = Ru 9, Os 13). The species 9 and 13 easily reacted with 4,4′-difluorobenzophenone, via 10 and 14, respectively, affording the corresponding isolable alkoxides [M(OR)(CN'N)(dppb)] (M = Ru 11, Os 15). The complexes [MX(CN′N)(P₂)] (1-15) (M = Ru, Os; X = Cl, H, OR; P = PPh₃ and P₂ = diphosphane) are efficient catalysts for the TH of carbonyl compounds with 2-propanol in the presence of NaOiPr (2 mol%). Turnover frequency (TOF) values up to 1.8 × 10⁶ h^-1 have been achieved using 0.02-0.001 mol % of catalyst. Much the same activity has been observed for the Ru-~Cl, -H, -OR, and the Os-Cl derivatives, whereas the Os-H and Os-OR derivatives display significantly lower activity on account of their high oxygen sensitivity. The chiral Ru complexes 5-8 catalyze the asymmetric TH of methyl-aryl ketones with TOF ≈ 10⁵h^-1 at 60°C, up to 97% enatiomeric excess (ee) and remarkably high productivity (0.005 mol % catalyst loading). High catalytic activity (TOP up to 2.2×10⁵h^-1) and enantioselectivity (up to 98% ee) have also been achieved with the in-situ-generated catalysts prepared from [MCl₂(PPh₃)₃], (S,R)-Josiphos or (S,R)-Josiphos*, and the benzo[h]quinoline ligands a-c.

Full text of DOI:10.1002/chem.200800888

DOI: 10.1002/chem.200800888
New Benzo[h]quinoline-Based Ligands and their Pincer Ru and Os
Complexes for Efficient Catalytic Transfer Hydrogenation of Carbonyl
Compounds
Walter Baratta,*[a] Maurizio Ballico,[a] Salvatore Baldino,[b] Giorgio Chelucci,[b]
Eberhardt Herdtweck,[c] Katia Siega,[a] Santo Magnolia,[a] and Pierluigi Rigo[a]
9148
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Chem. Eur. J. 2008, 14, 9148 – 9160

FULL PAPER
Abstract: New benzo[h]quinoline li-
gands (HCN’N) containing a CHRNH2
(R=H (a), Me (b), tBu (c)) function in
the 2-position were prepared starting
from benzo[h]quinoline N-oxide (in the
case of ligand a) and 2-chlorobenzo[h]-
quinoline (for ligands b and c). These
compounds were used to prepare
ruthenium and osmium complexes,
which are excellent catalysts for the
transfer hydrogenation (TH) of ke-
tones. The reaction of a with [RuCl2-
plex [OsCl
pared by treatment of [OsCl2
with dppb and ligand a. Reaction of
the chloride 2 and 12 with NaOiPr in
2-propanol/toluene afforded the hy-
A
G
of NaOiPr (2 mol%). Turnover fre-
quency (TOF) values up to 1.8”106 hÀ1
have been achieved using 0.02–
0.001 mol% of catalyst. Much the same
AHCTREUNG
À
activity has been observed for the Ru
À
À
À
dride complexes [MH
(M=Ru 10, Os 14), through elimina-
tion of acetone from [M(OiPr)(CN’N)-
(dppb)] (M=Ru 9, Os 13). The species
(CN’N)
G
Cl, H, OR, and the Os Cl deriva-
À
À
tives, whereas the Os H and Os OR
derivatives display significantly lower
activity on account of their high
oxygen sensitivity. The chiral Ru com-
plexes 5–8 catalyze the asymmetric TH
of methyl–aryl ketones with TOF
ꢀ105 hÀ1 at 608C, up to 97% enatio-
meric excess (ee) and remarkably high
productivity (0.005 mol% catalyst load-
ing). High catalytic activity (TOF up to
2.2”105 hÀ1) and enantioselectivity (up
to 98% ee) have also been achieved
with the in-situ-generated catalysts pre-
E
ACHTREUNG
AHCTREUNG
9 and 13 easily reacted with 4,4’-di-
fluorobenzophenone, via 10 and 14, re-
spectively, affording the corresponding
A
isolable alkoxides [M(OR)
(dppb)] (M=Ru 11, Os 15). The com-
plexes [MX(CN’N)(P2)] (1–15) (M=
(CN’N)-
AHCTREUNG
A
N
A
N
Ru, Os; X=Cl, H, OR; P=PPh3 and
P2 =diphosphane) are efficient cata-
lysts for the TH of carbonyl com-
pounds with 2-propanol in the presence
ACHTREUNG
A
ACHTREUNG
spectively. Employment of (R,S)-Josi-
phos, (S,R)-Josiphos*, (S,S)-Skewphos,
and (S)-MeO-Biphep in combination
pared from [MCl2(PPh3)3], (S,R)-Josi-
T
phos or (S,R)-Josiphos*, and the ben-
zo[h]quinoline ligands a–c.
Keywords: asymmetric catalysis
hydrogen transfer · osmium · phos-
phane ligands · ruthenium
with [RuCl
the chiral
(CN’N)(PP)] (5–8). The osmium com-
ACHTREUNG
ACHTREUNG
Introduction
both in terms of activity and enantioselectivity (bifunctional
catalysis).[4] In this context our research group found that re-
placement of the diamine in [RuCl2(PP)(1,2-diamine)] with
the mixed bidentate nitrogen ligand 1-(pyridin-2-yl)methan-
amine (Pyme), or the 1-substituted analogous ligands
Asymmetric reduction of prochiral ketones for the synthesis
of optical active alcohols is one of the most researched
areas in homogeneous catalysis. Among the catalytic meth-
ods available for the accomplishment of this transformation,
enantioselective hydrogenation with molecular H2 (HY)[1]
and transfer hydrogenation (TH)[2] are continuously being
developed and represent a current subject of industrial and
academic research. Noyori and co-workers pioneered the re-
search in both areas, leading to the development of the effi-
(RPyme), affords the complexes cis-[RuCl2(PP)(RPyme)]
A
that are highly efficient catalysts for the asymmetric TH of
ketones (Figure 1).[5]
cient catalytic systems [RuCl
A
ACHTREUNG
phane) for the asymmetric TH and HY of ketones, respec-
tively.[3] The use of ancillary ligands featuring an NH func-
tionality is crucial for the achievement of excellent results
[a] Prof. W. Baratta, Dr. M. Ballico, 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)0432-558803
E-mail: inorg@uniud.it
Figure 1. Pyme-type ligands and their Ru and Os complexes
[b] Dr. S. Baldino, Dr. G. Chelucci
Dipartimento di Chimica, Università di Sassari
Via Vienna 2, 07100 Sassari (Italy)
Importantly, the same system has also been proven to effi-
ciently catalyze the HY of several ketones, including bulky
and poor reactive substrates, such as tert-alkyl ketones.[6]
The remarkable acceleration effect of Pyme in TH has also
[c] Dr. E. Herdtweck
Department Chemie, Lehrstuhl für Anorganische Chemie
Technische Universität München
Lichtenbergstrasse 4, 85747 Garching (Germany)
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9149

W. Baratta et al.
been documented by the high activity of cyclometalated
phosphane and N-heterocyclic carbene ruthenium systems.[7]
Subsequently, we reported on the pincer CNN ruthenium
containing either pincer NCN[16] and CNN[8] or bidentate
CN[17] ligands for TH catalysts have been described.
We report herein the synthesis of new 2-aminomethylben-
zo[h]quinoline type ligands (HCN’N) and the isolation of
complexes [RuCl
alation of the 1-[6-(4-methylphenyl)pyridin-2-yl]methan-
amine (HCNN) ligand, displaying sp2 and sp3 N donor
A
the related complexes [MX(CN’N)(P2)] (M=Ru, Os, X=
G
G
Cl, H, OR; P=PPh3 or P2 =diphosphane). The ruthenium
and osmium compounds are highly efficient catalysts for the
TH of ketones (TOF up to 1.8 ”106 hÀ1) at 0.02–
0.001 mol% loading, in basic 2-propanol. Highly enantiose-
lective TH has been achieved by employment of Josiphos li-
gands. Evidence has been provided that the species [MX-
atoms (Figure 1).[8] To the best of our knowledge, these com-
plexes are the most active catalysts for the TH of ketones
and aldehydes reported to date (turnover frequencies
(TOF) up to 2.5”106 hÀ1), requiring a very low ruthenium
loading (0.005–0.001 mol%). The pincer terdentate CNN
ligand was designed to combine the Pyme motif with 2-phe-
nylpyridine which is known to give easily CN ortho-metalat-
ed ruthenium species.[9] More recently, we have shown that
Pyme and the terdentate CNN ligand give with osmium the
A
TH. The results presented here expand the number hetero-
cyclic pincer ligands for highly active and productive metal
based homogeneous catalysts.
related compounds [OsCl2(PP)
A
ACHTREUNG
catalyze both the TH and HY of different ketones with ac-
tivities that appear to rival those of the analogous rutheni-
um systems. These results expand the relatively low number
of osmium catalytic systems capable to reduce carbonyl
compounds with dihydrogen or hydrogen donors with both
high activity and enantioselectivity.[12] The pincer complexes
Results and Discussion
Synthesis of HCN’N benzo[h]quinoline ligands: The inter-
mediate benzo[h]quinoline-2-carbonitrile was prepared by
reaction of benzo[h]quinoline N-oxide[18] with trimethylsilyl-
cyanide and dimethylcarbamyl chloride, according to the
Fifeꢁs procedure for the regioselective cyanation of pyridine
1-oxides (Scheme 1).[19]
[MCl(CNN)(PP)] (M=Ru, Os) appear very attractive for
A
practical applications, because the presence of a metal–
carbon bond gives these compounds with a high degree of
thermal stability, thus preventing their easy deactivation and
leading to highly productive catalysts. With the advances ac-
complished in the decade, TH has emerged as powerful and
versatile tool for the small and medium production of chiral
alcohols[2a] complementary to the pressure HY process.
On account of the excellent catalytic performances of the
Ru– and Os–diphosphane derivatives containing the terden-
tate CNN ligand, we decided to examine the coordination
chemistry and the catalytic po-
Scheme 1. Synthesis of the ligand a.
Catalytic hydrogenation (10% Pd/C; 2 atm of H2) at
room temperature of a solution of benzo[h]quinoline-2-car-
bonitrile in acetic acid afforded the 2-aminomethylbenzo[h]-
quinoline ligand a isolated in 90% yield. The substituted li-
gands b and c, containing a methyl and a tert-butyl group,
respectively, bonded to the carbon atom connected to the
NH2 moiety, were synthesized following the route shown in
Scheme 2.
tential of a new class of CN’N
complexes based on the 2-ami-
nomethylbenzo[h]quinoline
framework (shown here).
Simple ortho-metalated CN’ benzo[h]quinoline complexes
of Ru and Os have extensively been described,[13] and some
of them have been found to be relevant for photochemical
and photophysical applications.[14] However, only one exam-
ple of a terdentate CN’N benzo[h]quinoline complex with
Ru has been reported, starting from the 2-(pyridin-2-yl)ben-
zo[h]quinoline ligand.[15] For the CN’N ligands a higher con-
formational rigidity is expected, compared to those based on
2-phenylpyridine, due to the presence of the planar ben-
zo[h]quinoline system. The great interest in the extension of
the family of the pincer CNN ligands arises from the re-
markable stability of their metal complexes, which allows
the formation of long-living catalytically active species that
can have great potential in organic synthesis. A chiral var-
iant of these CN’N ligands can be obtained by incorporating
a stereochemical center on the benzylic carbon atom of the
Scheme 2. Synthesis of the ligands b and c.
Treatment of 2-chlorobenzo[h]quinoline[18b] with bromotri-
methylsilane gave 2-bromobenzo[h]quinoline (96% yield),
according to the Schlosser method.[20] Addition of n-butyl-
À
CHR NH2 arm. In the recent years a number of studies on
the successful use of cyclometalated ruthenium complexes
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Chem. Eur. J. 2008, 14, 9148 – 9160

Asymmetric Catalysis
FULL PAPER
lithium at À788C and N,N-dimethylacetamide (R=Me) or
pivalonitrile (R=tBu) resulted in the formation of 1-(ben-
zo[h]quinolin-2-yl)ethanone and 1-(benzo[h]quinolin-2-yl)-
2,2-dimethylpropanone, respectively (77 and 80% yield). By
reaction with NH2OH·HCl in ethanol, these ketones were
converted into the corresponding oximes, which were re-
duced with Zn/ammonium acetate/NH4OH to the amine li-
gands b and c in 77 and 48% overall yield, based on the ke-
tones.
metalated carbon appears as a doublet of doublets at d=
2
177.0 ppm, with J
A
and 4 show related NMR spectra with the 13C{1H} NMR sig-
nals for the NCH group at d=58.5 and 72.9 ppm, whereas
those of the ortho-metalated carbon atoms are at d=179.1
and 180.3 ppm, respectively. The molecular structure of 3
was confirmed by X-ray analysis carried out on a single crys-
tal and the selected bond lengths and angles are reported in
Table 1. The ruthenium center of 3 is in a pseudo-octahedral
environment with the ortho-metalated ligand b bound to the
metal in a terdentate fashion, forming two five-membered
chelate rings (Figure 2).
Synthesis and characterization of [RuX
ACHTREUNG
H, and OR) complexes: Reaction of [RuCl2
AHCTREUNG
ligand a and the base NEt3 in 2-propanol at reflux tempera-
ture (2 h) affords, by substitution of PPh3 and HCl elimina-
tion, the thermally stable CN’N pincer complex 1 (74%
yield) [Eq. (1)].
Table 1. Selected bond lengths [Š] and angles [8] for 3·2CH2Cl2.
À
À
Ru Cl1
2.5035(6)
2.2945(5)
2.2512(6)
91.47(2)
172.39(2)
81.55(6)
83.70(5)
86.97(6)
93.62(2)
96.89(5)
170.46(5)
Ru N1
2.244(2)
2.055(2)
2.072(2)
107.34(6)
103.41(6)
92.04(5)
86.12(6)
74.30(6)
153.42(7)
80.69(7)
À
À
Ru P1
À
Ru P2
Ru N2
À
Ru C1
Cl1-Ru-P1
Cl1-Ru-P2
Cl1-Ru-N1
Cl1-Ru-N2
Cl1-Ru-C1
P1-Ru-P2
P1-Ru-N1
P1-Ru-N2
P1-Ru-C1
P2-Ru-N1
P2-Ru-N2
P2-Ru-C1
N1-Ru-N2
N1-Ru-C1
N2-Ru-C1
The 31P{1H} NMR spectrum of 1 in CD2Cl2 shows two
doublets at d=56.5 and 50.5 ppm (2J
ACHTREUNG
1
ACHTREUNG
the CH proton close to the ortho-metalated carbon atom
and no signals at lower field were observed, consistent with
À
the absence of the C H proton in the 10-position of the
benzo[h]quinoline (d=9.37 ppm for a in CD2Cl2). The com-
plexes 2–4 containing the diphosphane Ph2P
(dppb) have been prepared in 52–85% yield by treatment of
[RuCl2(PPh3)(dppb)] with the ligands a–c, respectively, in
A
A
ACHTREUNG
the presence of NEt3 [Eq. (2)].
Figure 2. ORTEP style plot of compound 3 in the solid state. Thermal el-
lipsoids are drawn at the 50% probability level. Hydrogen atoms are
omitted for clarity.
The structure of 3 shows the Me group bound to the
carbon atom that points to the side of the chloride, away
from the phosphane phenyl groups, similarly to the related
The 31P{1H} NMR spectrum of 2 exhibits two doublets at
chiral pyridyl complex of the type [RuCl
A
C
1
d=57.3 and 43.7 ppm (2J
(P,P)=38.2 Hz), while the H NMR
bearing a tert-butyl group bonded to the CHNH2 moiety.[8b]
À
signals of the two nonequivalent NCH2 protons are at d=
4.37 and 3.96ppm and one NH 2 proton is at d=3.60 ppm. In
the 13C{1H} NMR spectrum the NCH2 signal is downfield
shifted at d=52.2 ppm (Dd=5.9 ppm) and coupled with one
The Ru N2 bond length of the benzo[h]quinoline trans to
the phosphorus atom is significantly shorter (2.055(2) Š)
À
than the Ru N1 amino bond length (2.244(2) Š), in agree-
ment with the geometrical constrains of the terdentate
ligand showing narrow N2-Ru-C1 and N1-Ru-N2 bond
phosphorus atom (3J
(C,P)=2.8 Hz), whereas the ortho-
A
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9151

W. Baratta et al.
angles (80.69(7), 74.30(6)8) and the higher trans influence
exerted by the aryl ligand (Table 1).
The amino nitrogen N1 and the CHNH2 carbon are dis-
placed by À0.556(3) and +0.108(3) Š, respectively, from the
best-fit plane through the terdentate ligand. This arrange-
2-propanol (alkoxide route). Treatment of 2 with NaOiPr
(1.1 equiv) in 2-propanol/toluene mixture (1:1 in volume) at
408C (1 h) affords a dark red solution with formation of the
intermediate alkoxide 9 (Scheme 3).
The 31P{1H} NMR spectrum of this solution shows two
ment leads one N H bond to be almost parallel to the Ru
Cl1 bond (H-N1-Ru-Cl1 dihedral angle of about 1.28, with a
H···Cl1 distance of 2.57 Š), suggesting a possible intramolec-
ular hydrogen-bond interaction.[21] In addition, there is a rel-
atively short contact between the benzo[h]quinoline nitro-
gen atom and the ipso-carbon atom C38 of the phosphane
phenyl (3.058(3) Š), indicating a stacking between the ben-
zo[h]quinoline and one phenyl ring.
doublets at d=54.0 and 47.6ppm ( 2J
ACHTREUNG
À
À
A
N
ACHTREUNG
the solvent leads to the hydride complex 10, through a re-
versible elimination of acetone in agreement with the previ-
ous studies on CNN ruthenium complexes. A better conver-
sion into the orange hydride 10, which was isolated in 83%
yield, has been achieved by stirring the alkoxide solution
under dihydrogen for 1 h and by further elimination of the
solvent. The 1H NMR signal for the hydride appears as a
The chiral terdentate CN’N derivatives 5–8 were prepared
by reaction of [RuCl2(PPh3)3] with the appropriate chiral di-
E
phosphane in toluene at 1108C or dichloromethane at RT,
followed by addition of the ligand a and NEt3 in 2-propanol
heated under reflux [Eq. (3)].
doublet of doublets at d=À5.40 ppm with 2J
ACHTREUNG
and 26.2 Hz, similarly to those of [RuH
A
ACHTREUNG
in agreement with the values reported for ruthenium hy-
dride complexes with phosphorus atoms trans and cis to the
hydride.[24] In the 31P{1H} NMR spectrum the two doublets
are at d=66.6 and 35.0 ppm with a small phosphorus–phos-
phorus coupling constant (2J
(P,P)=16.7 Hz). The low value
U
of the Ru H stretching absorption band (1742 cmÀ1) is con-
À
sistent with the presence of a trans-phosphorus atom,[25] in
addition to a possible RuH···HN hydrogen-bonding interac-
tion. The intermediate CN’N isopropoxide 9, which equili-
brates with the hydride 10, promptly reacts with ketones af-
fording the corresponding alkoxides, by elimination of ace-
tone, as previously observed for the CNN analogue.[23] Thus,
the fluoro-substituted alkoxide 11 can easily be prepared by
reaction of the in-situ-prepared 9 with 4,4’-difluorobenzo-
phenone in a 2-propanol/toluene mixture at RT (75%
yield), through the hydride 10 (Scheme 3). The 31P{1H}
With (R,S)-Josiphos the compound 5 was obtained as
single stereoisomer and was isolated in 61% yield. Employ-
ment of the bulkier diphosphane (S,R)-Josiphos*, which
contains 4-OMe-3,5-Me2C6H2 groups instead of Ph ones, led
to 6 (55% yield) as a mixture of two diastereoisomers in a
5:1 ratio, as inferred from 31P{1H} NMR spectroscopy.[22]
Prolonged heating of this mixture inhibited the isolation of
a single stereoisomer. Similarly to 6, the derivative 7 was
prepared using (S,S)-Skewphos and was isolated as mixture
of two isomers (4:1 ratio), whereas 8 containing (S)-MeO-
Biphep was obtained as a mixture of two stereoisomers in a
3:1 ratio.
NMR of 11 in C6D6 exhibits two doublets at d=57.0 and
2
40.3 ppm with a J
A
oxide moiety OCH leads to a 1H NMR doublet at d=
4.46ppm with a 4J(H,P)=3.3 Hz, whereas the 13C{1H} NMR
signal is at d=79.9 ppm, shifted downfield compared to the
free alcohol (d=74.5 ppm). The 19F{1H} NMR spectrum of
11 shows two singlets at d=À119.6and À120.3 ppm for two
nonequivalent C6H4F groups and these signals disappear by
addition of 4,4’-difluorobenzhydrol, affording a broad peak
close to that of free alcohol at d=À116.2 ppm, indicating
that a rapid alkoxide alcohol exchange occurs on the NMR
chemical-shift time scale.[23] It is worth noting that 11 is ob-
tained without the isolation of the hydride and by exploiting
To isolate hydride ruthenium complexes, which are key
species involved in the catalytic TH reactions, we have stud-
ied the reactivity of complex 2 with sodium isopropoxide in
Scheme 3. Formation of Ru and Os hydride and alkoxide complexes.
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Chem. Eur. J. 2008, 14, 9148 – 9160

Asymmetric Catalysis
FULL PAPER
the higher redox potential of the diaryl ketone, relative to
acetone.[26]
Catalytic results: The ruthenium and osmium chloride, hy-
dride, and alkoxide complexes [MX(CN’N)(P2)] (1–15) are
A
efficient catalysts for the TH of carbonyl compounds with 2-
propanol in the presence of NaOiPr (2 mol%; Scheme 4).
Complex 1 (0.02 mol%) containing PPh3 catalyzes the re-
duction of acetophenone (d) in 15 min with turnover frquen-
cy (TOF) of 7.0”104 hÀ1 (Table 2).
Synthesis and characterization of [OsX
Cl, H, and OR) complexes: The thermally stable pincer
CN’N osmium complex 12 has easily been prepared in quan-
A
G
titative yield by treatment of [OsCl2(PPh3)3] with dppb in di-
G
chloromethane at RT and by further reaction with the
ligand a in the presence of NEt3 in 2-propanol at reflux tem-
perature (3 h) [Eq. (4)].
Scheme 4. TH of carbonyl compounds catalyzed by [MX(CN’N)P2] (M=
Ru, Os; X=Cl, H, OR) complexes (0.02–0.001 mol%).
The 31P{1H} NMR spectrum of 12 in CD2Cl2 shows a pat-
tern for an AB system with the two signals at d=0.9 and
0.8 ppm (2J(P,P)=13.7 Hz). The 13C{1H} NMR signal of
A
Table 2. Catalytic TH of carbonyl compounds (0.1m) to the correspond-
ing alcohols with [MX(CN’N)P2] (M=Ru, Os; X=Cl, H, OR) and
NaOiPr (2 mol%) in 2-propanol at 828C.
CH2N is at d=54.6ppm, shifted downfield compared to 2,
whereas the ortho-metalated carbon atom appears as a
pseudo triplet at d=157.2 ppm (2J
(C,P)=6.5 Hz), signifi-
A
Complex Loading
[mol%]
Substrate Conv.
[%][a]
t
TOF
[b]
[min] [hÀ1
]
cantly upfield shifted with respect to 2.
1
2
0.02
d
d
d
f
h
i
94
97
97
99
97
99
97
>99
98
98
97
98
965
94
99
97
98
97
99
15
2
10
2
2
5
2
5
5
5
2
2
1.3”10
30
2
10
5
5
7.0”104
1.2”106
2.7”105
1.8”106
1.8”106
1.1”106
1.2”106
2.0”105
8.3”105
1.1”106
1.3”106
The osmium complex 12 reacts with sodium isopropoxide
(1.2 equiv) in 2-propanol/toluene (1:1 in volume) at 358C
(3 h) affording a dark red solution containing the alkoxide
13 and the hydride 14 in 5:1 molar ratio, respectively
0.005
0.005
0.005
0.005
0.005
0.005
0.01
0.005
0.005
0.005
0.005
0.005
0.001
0.005
0.005
0.005
0.005
0.005
2[c]
2
2
2
2
(Scheme 3). The 31P{1H} NMR data of 13 (d=6.0 and
2
j
À0.5 ppm with J
ACHTREUNG
2[d]
3
k
d
d
d
d
d
d
g
i
gous complex [Os
N
G
ACHTREUNG
osmium, the equilibrium between the isopropoxide 13 and
the hydride 14 is shifted more to the hydride, with respect
to the corresponding ruthenium complexes 9 versus 10, and
4
10
11
12
12
12
12
12
14
15
1.4”106
6
À
À
this is consistent with a stronger M H versus M OR bond-
ing for Os compared to Ru. The oxygen-sensitive hydride–
osmium complex 14 was easily obtained in 74% yield by
4.3”105
1.8”106
3.0”105
7.0”105
6.1”105
8.1”105
j
d
d
evaporation of the alcohol media and elimination of ace-
1
tone.[27] The Os H H NMR signal of 14 is at d=À5.14 ppm
À
5
2
(dd, J
(H,P)=73.9, 23.9 Hz) close to that of the ruthenium
10, whereas the 31P{1H} NMR spectrum exhibits two dou-
[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. [c] Reaction at 608C. [d] K2CO3 5 mol%.
2
blets at d=19.9 and 5.4 ppm with a small J
A
The mixture 13/14, obtained from 12 and NaOiPr, rapidly
and quantitatively reacts with 4,4’-difluorobenzophenone, af-
fording the osmium alkoxide 15, which was isolated in 72%
Interestingly, the complex 2 bearing the diphosphane
dppb promotes the quantitative conversion of d into 1-phe-
nylethanol in 2 min, with a lower amount of catalyst
(0.005 mol%) and affording a TOF value of 1.2”106 hÀ1.
This rate is slightly higher than that observed for the reduc-
tion of d with the analogous CNN pyridine derivative [Ru-
yield (Scheme 3). This complex gives two 31P NMR doublets
2
at d=1.8 and À0.8 ppm with a J
A
1H and 13C{1H} NMR signals for the OsOCH moiety are at
d=4.61 and 79.7 ppm, respectively, close to those of 11. The
19F{1H} NMR spectrum of 15 shows two singlets at d=
À119.4 and À120.1 ppm and similarly to the behavior ob-
served for 11, addition of 4,4’-difluorobenzhydrol results in
a fast exchange between the coordinated alkoxide and alco-
hol on the NMR timescale.
G
G
acetophenone (f) and 3’-methoxyacetophenone (h) are quick-
ly reduced to alcohols in 2 min with remarkably high rate
(TOF=1.8”106 hÀ1). Chemoselective carbonyl TH of the
Chem. Eur. J. 2008, 14, 9148 – 9160
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
9153

W. Baratta et al.
aliphatic substrate 5-hexen-2-one (i) has been achieved in
5 min (TOF=1.1”106 hÀ1), whereas cyclohexanone (j) was
reduced with TOF=1.2”106 hÀ1. Complex 2 (0.01 mol%)
also rapidly catalyzes the complete reduction of the alde-
hyde k with K2CO3 (5 mol%) as a weak base (TOF=2.0”
105 hÀ1) and no aldol condensation or catalyst deactivation
(i.e. through decarbonylation) reactions have been observ-
ed.[8c] High catalytic activity is also observed for the deriva-
tiomeric excess (ee). The derivatives 5–8 (0.005 mol%) af-
forded complete reduction of d in 30–40 min with TOF up
to 1.9”105 hÀ1 at 608C (Table 3).
By employment of 5 containing (R,S)-Josiphos, (R)-1-phe-
nylethanol was obtained with 86% ee, whereas use of 6,
with the bulkier (S,R)-Josiphos*, led to an increase of the
enantioselectivity (96% ee of (S)-alcohol). The complexes 7
and 8 with (S,S)-Skewphos and (S)-MeO-Biphep, repsective-
ly afforded (S)- and (R)-1-phenylethanol, respectively, with
moderate and poor enantioselectivity (73 and 26% ee, re-
spectively). With 5, the ketone f was reduced to the (R)-al-
cohol with 89% ee, whereas with 6 the substrates 2’-methyl-
acetophenone e and f were converted into the correspond-
ing (S)-alcohols with TOF up to 1.2”105 hÀ1 and high enan-
tioselectivity (94 and 97% ee). Recently, we have reported
that efficient ruthenium catalysts for asymmetric TH can be
prepared by a combination of a chiral Josiphos with a race-
mic mixture of RPyme through a diastereoselective reaction,
thus avoiding the necessity of using both ligands in enantio-
pure form.[5b] According to this strategy, the in-situ-generat-
ed catalyst, obtained by refluxing a 2-propanol solution of
À
tives 3 and 4 containing the CHR NH2 (R=Me and tBu)
À
arm instead of CH2 NH2. Recently, Milstein and co-workers
reported a pincer PNN ruthenium complex which catalyzes
alcohol dehydrogenation.[28] Interestingly, the CH2 bonded
to the 2-position of the pyridine ligand undergoes easy C-H
cleavage with reversible dearomatization–aromatization of
the pyridine core. It is worth pointing out that also the hy-
dride 10 and the alkoxide 11 in the presence of base effi-
ciently catalyze the fast TH of d with TOF=1.3”106 and
1.4”106 hÀ1, which are slightly higher values compared to
the chloride precursor 2. This suggests that under catalytic
À
À
À
conditions the isolable Ru Cl, H, and OR complexes (2,
10, and 11) quickly lead to the catalytically active 9/10
system, through fast ligand substitution and ketone insertion
[RuCl2(PPh3)3] with (S,R)-Josiphos* (1 h) and a racemic
N
[23]
À
into Ru H bond reactions. As regards osmium, it is inter-
mixture of the Me-substituted ligand b (1 h), promotes the
reduction of d to (S)-1-phenylethanol with high rate (TOF=
1.7”105 hÀ1) and 90% ee at 0.005 mol% of catalyst loading
(Table 3). By using the tBu ligand c the (S)-alcohol is
formed with 93% ee, whereas the substrates f and g were
converted to (S)-alcohols with 98 and 97% ee, respectively
(TOF up to 1.1”105 hÀ1). We want to point out that the in-
situ-generated species display much the same rate as the iso-
estingly to note that the complex 12 catalyzes the TH of d
with a rate (TOF=1.3”106 hÀ1) slightly higher than that of
the analogous ruthenium complex 2, in agreement with our
recent studies on pincer CNN pyridine complexes.[11] In ad-
dition, 12 displays also high productivity in the TH, afford-
ing the conversion of d into 1-phenylethanol in 30 min at
0.001 mol% of catalyst (Table 2). A serious drawback of the
commonly used TH catalysts is their easy deactivation that
requires a catalyst loading higher than 0.01 mol%, thus lim-
iting the TH protocol for industrial applications. As for the
ruthenium systems, 12 catalyzes the rapid and chemoselec-
tive TH of aryl and alkyl ketones, namely g, i, and j with
TOF up to 1.8”106 hÀ1. It is worth noting that the hydride
14 and the alkoxide 15 afforded the reduction of d with a
rate (TOF=6.1”105 and 8.1”105 hÀ1) lower than that of the
chloride 12. By contrast to
lated complexes [RuCl(CN’N)(P2)] and high enantioselectiv-
G
ity can be achieved through the combination of alkyl-substi-
tuted benzo[h]quinolines with bulky Josiphos ligands. As re-
gards osmium, the species prepared in-situ from [OsCl2-
(PPh3)3], (S,R)-Josiphos, and ligand a, afforded the reduc-
tion of d to (S)-alcohol with 80% ee and higher rate (TOF=
2.1”105 hÀ1 at 608C), compared to ruthenium. Furthermore,
the use of the bulky (S,R)-Josiphos* resulted in an increase
ruthenium, high catalytic per-
formance with osmium is ach-
Table 3. Enantioselective catalytic TH of ketones (0.1m) with 5–8 and the system [MCl2(PPh3)3]/PP/HCN’N
(M=Ru, Os), in the presence of NaOiPr (2 mol%) at 608C using 0.005 mol% of catalyst.
ieved by in-situ-formation of
Complex
PP
HCN’N
Ketone
Conv.
[%][a]
t
TOF
ee
À
À
[min]
[hÀ1
]
[%][a]
the Os H and Os OR species,
on account of their higher
oxygen sensitivity respect to the
Ru analogues.
[b]
5
5
6
6
6
7
8
d
f
d
e
f
d
d
d
d
f
g
d
d
97
97
98
96
98
95
97
98
98
99
95
9610
9610
30
60
40
60
40
30
30
30
30
30
30
1.3”105
6.4”104
1.0”105
6.0”104
1.2”105
1.1”105
1.9”105
1.7”105
1.2”105
1.1”105
86 R
89 R
96 S
94 S
97 S
73 S
26 R
90 S
93 S
98 S
97 S
80 S
90 S
Asymmetric TH of methyl
aryl ketones has been achieved
using CN’N ruthenium com-
plexes containing chiral diphos-
[RuCl2(PPh3)3][c]
[RuCl2(PPh3)3][d]
[RuCl2(PPh3)3][d]
[RuCl2(PPh3)3][d]
[OsCl2(PPh3)3][e]
[OsCl2(PPh3)3][e]
(S,R)-Josiphos*
(S,R)-Josiphos*
(S,R)-Josiphos*
(S,R)-Josiphos*
(S,R)-Josiphos
(S,R)-Josiphos*
b
c
c
c
a
a
phanes. Since
2
has been
proven to be highly active for
1.0”105
the reduction of d also at 608C
5
2.1”10
2.2”10
(TOF=2.7”105 hÀ1,
Table 2),
5
the chiral Ru complexes were
tested at this temperature in
[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. [c] [Ru]/PP/b=1:1.5:3. [d] [Ru]/PP/c=1:1.5:3.
order to achieve higher enan- [e] [Os]/PP/a=1:1.5:2.
9154
www.chemeurj.org
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 9148 – 9160

Asymmetric Catalysis
FULL PAPER
of the enantioselectivity (90% ee of (S)-alcohol). On ac-
count of the robustness of the CN’N/diphosphane frame-
work, these chiral ruthenium and osmium systems display
remarkable high rate (TOF ꢀ105 hÀ1 at 608C) at low loading
(0.005 mol%), thus representing a significant progress in the
designing of more efficient catalysts for the asymmetric TH
of ketones. Moreover, the benzo[h]quinoline complexes 2
and 12 have been proven to be catalytically active also in
the hydrogenation of ketones at low H2 pressure in alcohol
media and these results will be published in the due course.
The TH of ketones catalyzed by transition-metal com-
plexes is generally conceived to occur via metal-hydride spe-
cies that deliver the hydride ligand to the substrate, afford-
ing a metal–alkoxide complex (inner sphere mechanism) or
a metal–amide species when a NH2 functionality is present
(outer-sphere mechanism). Recently, we have suggested that
with terdentate CNN ruthenium complexes, the Ru–alkox-
ides are key species of the catalytic TH and the role of the
NH2 linkage is to favor a hydrogen-bonding network involv-
ing the alkoxide and the alcohol.[23,29] According to the pres-
ent studies, which show that in basic alcohol the Ru and Os
pressure. Experiments carried out with the chloride com-
plexes in basic alcohol showed the formation of the hydride
derivatives [MH
ketones leading to the alkoxide species [M(OR)
(dppb)]. These studies suggest that the catalytic TH mediat-
ed by Ru and Os complexes with CN’N benzo[h]quinoline
A
ACHTREUNG
ACHTREUNG
AHCTREUNG
À
À
involves the formation of M H and M OR species contain-
ing the NH2 functionality. Work is in progress to extend the
application of these complexes in other catalytic reactions,
including asymmetric hydrogenation of prochiral ketones,
and to develop new homogeneous catalysts based on ben-
zo[h]quinoline ligands.
Experimental Section
General: All reactions were carried out under an argon atmosphere
using standard Schlenk techniques. The solvents and the ketones were
carefully 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. Benzo[h]quino-
line N-oxide,[18a] 2-chlorobenzo[h]quinoline,[18b] the complexes [MCl2-
À
chloride precursors 2 and 12 give M OR (M=Ru, Os) in
A
(PPh3)
(dppb)][33] were prepared
N
À
equilibrium with the M H complexes, we believe that these
according to literature procedure. NMR measurements were recorded on
a Bruker AC 200 spectrometer and the chemical shifts, in ppm, are rela-
tive to TMS for 1H and 13C{1H}, whereas CFCl3 was used for 19F{1H} and
85% H3PO4 for 31P{1H}. Elemental analyses (C, H, N) were carried out
with a Carlo Erba 1106elemental analyzer, whereas the GC analyses
were performed with a Varian GP-3380 gas chromatograph equipped
with a MEGADEX-ETTBDMS-b chiral column.
species containing the NH2 functionality are involved in
TH.[30] Thus, [MH
ACHTREUNG
AHCTREUNG
A
ACHTREUNG
ACHTREUNG
Benzo[h]quinoline-2-carbonitrile: Dimethylcarbamyl chloride (1.44 g,
13.5 mmol) was added dropwise to a solution of benzo[h]quinoline N-
oxide (2.63 g, 13.5 mmol) and trimethylsilylcyanide (1.59 g, 14.8 mmol) in
CH2Cl2 (100 mL). The solution was stirred at room temperature for 3 d
and then heated under reflux for 18 h. A 10% Na2CO3 aqueous solution
was added and stirring continued for 15 min. The organic phase was sepa-
rated and the aqueous layer was extracted with CH2Cl2. The combined
organic phase was dried over anhydrous Na2SO4 and the solvent was
evaporated. The residue was taken up with diethyl ether and the formed
solid was filtered to give benzo[h]quinoline-2-carbonitrile. Yield: 2.07 g
(75%); m.p. 161–1628C; 1H NMR (200.1 MHz, CDCl3, 208C): d=9.27
activity of these pincer complexes can be ascribed to the
À
M NH2 linkage, which is involved in hydrogen-bonding in-
teractions with the ketone and alcohol, and to the flat ben-
zo[h]quinoline system that appears crucial for the easy
access of the substrate to the metal center. In addition, high
productivity is achieved by the combination of the diphos-
phane with the robust pincer CN’N frame.
(m, 1H), 8.27 (d, J
A
Conclusion
7.70 ppm (d, J
AHCTREUNG
208C): d=147.0, 136.5, 133.7, 131.6, 131.0, 130.5, 129.4, 128.0, 127.9,
127.7, 124.7, 124.6, 124.3, 118.0 ppm (CN); elemental analysis calcd (%)
for C14H8N2: C 82.33, H 3.95, N 13.72; found: C 82.14, H 3.98, N 13.75.
In summary, we have reported on the preparation of novel
2-aminomethylbenzo[h]quinoline type ligands (HCN’N) that
easily react with ruthenium and osmium precursors, afford-
2-Aminomethylbenzo[h]quinoline (a): A solution of benzo[h]quinoline-
2-carbonitrile (2.04 g, 10.0 mmol) in acetic acid (120 mL) was hydrogen-
ated in a Parr apparatus at 2 atm of dihydrogen at room temperature in
the presence of 10% palladium on carbon (0.40 g). The dihydrogen ab-
sorption ceased after the uptake of two equivalents of H2 (about 4 h).
The reaction mixture was then filtered and the organic solution was
evaporated under reduced pressure. The oil residue was taken up in di-
ethyl ether and the resulting solution was washed up to alkaline pH with
a 10% aqueous solution of NaOH. The organic phase was dried over
Na2SO4, the solvent was evaporated, and the residue was purified by
flash chromatography (MeOH) to give a as a reddish low melting point
solid. Yield: 1.87 g (90%); 1H NMR (200.1 MHz, CDCl3, 208C): d=9.58
ing the terdentate complexes [MCl(CN’N)(P2)] (M=Ru,
A
Os). These species are found to promote the transfer hydro-
genation (TH) of carbonyl compounds in basic 2-propanol
with high rate (TOF up to 1.8”106 hÀ1) and low loading (as
little as 0.001 mol%), which are among the best performan-
ces for a TH catalyst reported to date. Interestingly, with
this novel class of ligands the ruthenium and osmium com-
plexes display similar high activity and productivity. The de-
rivatives containing chiral diphosphanes (e.g., Josiphos)
have proven to catalyze the TH of ketones with both high
enantioselectivity (up to 98% ee) and productivity
(0.005 mol% loading). This last point is particularly relevant
for promoting asymmetric TH as a valuable method for the
synthesis of alcohols, in alternative to dihydrogen under
(d, J(H,H)=7.4 Hz, 1H; aromatic proton), 8.11–7.71 (m, 7H; aromatic
A
protons), 4.37 (s, 2H; CH2), 2.90 ppm (s, 2H; NH2); 13C{1H} NMR
(50.3 MHz, CDCl3, 208C): d=158.5 (s; NCCH2), 143.9 (s; NCC), 134.4–
118.2 (m; aromatic carbon atoms), 46.3 ppm (s; CH2); elemental analysis
calcd (%) for C14H12N2: C 80.74, H 5.81, N 13.45; found: C 80.55, H 5.91,
N 13.66.
Chem. Eur. J. 2008, 14, 9148 – 9160
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
9155

W. Baratta et al.
2-Bromobenzo[h]quinoline:
A
mixture of 2-chlorobenzo[h]quinoline
analysis calcd (%) for C15H14N2: C 81.05, H 6.35, N 12.60; found: C
81.24, H 6.38, N 12.58.
(2.43 g, 11.4 mmol), bromotrimethylsilane (3.00 mL, 22.8 mmol) and pro-
pionitrile (12 mL) was heated under reflux for 110 h. The reaction mix-
ture was then poured into a 10% NaOH aqueous solution containing ice.
The organic phase was separated and the aqueous layer was extracted
with diethyl ether (3”15 mL). The combined organic phase was dried
over anhydrous Na2SO4 and the solvent was evaporated. The residue was
purified by chromatography (petroleum ether/ethyl acetate=9:1) to give
2-bromobenzo[h]quinoline as a yellow solid. Yield: 2.82 g (96%); m.p.
113–1148C; 1H NMR (200.1 MHz, CDCl3, 208C): d=9.35–9.15 (m, 1H),
1-(Benzo[h]quinolin-2-yl)-2,2-dimethylpropanone: A solution of 2-bro-
mobenzo[h]quinoline (1.52 g, 5.89 mmol) in THF (36mL) was cooled at
À788C. After 10 min a 2.5m solution of n-butyllithium in n-hexane
(2.47 mL, 6.19 mmol) was added dropwise. The resulting deep red solu-
tion was stirred at this temperature for 1 h and then pivalonitrile
(0.78 mL, 7.07 mmol) in THF (5 mL) was added dropwise. The obtained
purple solution was further stirred for 1 h at À788C and then was allowed
to warm slowly at room temperature. A 1m solution of H2SO4 was added
(25 mL) and the mixture was heated under reflux for 3 h. After cooling
to room temperature the organic phase was separated and the aqueous
phase extracted with diethyl ether (3”15 mL). The combined organic
phase was washed with a diluted NaOH solution and dried over Na2SO4.
The solvent was evaporated and the residue was purified by flash chro-
matography (petroleum ether/ethyl acetate=9:1) to give 1-(benzo[h]qui-
7.96(d,
8.4 Hz, 1H), 7.74–7.67 (m, 2H), 7.61 ppm (dd, 3J
(H,H)=1.5 Hz, 2H); 13C{1H} NMR (50.3 MHz, CDCl3, 208C): d=147.1,
J
A
A
AHCTREUNG
ACHTREUNG
140.7, 138.0, 133.7, 130.4, 128.7, 128.2, 127.7, 127.3, 126.1, 125.1, 124.7,
124.5 ppm; elemental analysis calcd (%) for C13H8BrN: C 60.49, H 3.12,
N 5.43; found: C 60.33, H 3.25, N 5.38.
nolin-2-yl)-2,2-dimethylpropanone as a yellow solid. Yield: 1.24 g (80%);
1-(Benzo[h]quinolin-2-yl)ethanone: A solution of 2-bromobenzo[h]qui-
noline (1.52 g, 5.89 mmol) in THF (36mL) was cooled at À788C. After
1
m.p. 88–908C; H NMR (200.1 MHz, CDCl3, 208C): d=9.20 (d, J
ACHTREUNG
7.8 Hz, 1H), 8.13 (s, 2H), 7.84 (d, J
2H), 7.73–7.62 (m, 1H), 7.56 (d, J
ACHTREUNG
10 min
a 2.5m solution of n-butyllithium in n-hexane (6.19 mmol,
AHCTREUNG
2.47 mL) was added dropwise. The resulting deep red solution was stirred
at this temperature for 1 h and then N,N-dimethylacetamide (6.48 mmol,
0.60 mL) was added dropwise. The solution was further stirred for 1 h at
À788C and then allowed to warm slowly at room temperature. A 1m so-
lution of HCl was added (7.4 mL), the organic phase was separated and
the aqueous phase was extracted with diethyl ether (2”15 mL). The com-
bined organic phase was dried over Na2SO4, the solvent was evaporated,
and the residue was purified by flash chromatography (petroleum ether/
CH3); 13C{1H} NMR (50.3 MHz, CDCl3, 208C): d=206.7 (CO), 152.1,
144.5, 136.3, 133.7, 131.8, 129.5, 128.4, 127.9, 127.5, 124.9, 124.5, 121.2,
44.3 (CMe3), 28.0 ppm (CH3); elemental analysis calcd (%) for
C18H17NO: C 82.10, H 6.51, N 5.32; found: C 82.26, H 6.67, N 5.17.
AHCTREUNG
AHCTREUNG
ethyl acetate=95:5) to give 1-(benzo[h]quinolin-2-yl)ethanone as
a
stirred at room temperature for 36h (a white precipitate was formed
after 30 min). The reaction was monitored by TLC (petroleum ether/
ethyl acetate=9:1). The solvent was removed 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 extracted with
CH2Cl2 (2”20 mL). The combined organic phase was dried over Na2SO4
and the solvent was evaporated to give (benzo[h]quinolin-2-yl)-tert-butyl
ketoxime as a slightly brown powder (quite insoluble in almost common
solvents) that was used in the next step without further purification.
Yield: 0.69 g (50%); m.p. 234–2368C; elemental analysis calcd (%) for
C18H18N2O: C 77.67, H 6.52, N 10.06, found: C 77.55, H 6.55, N 10.02.
1
yellow solid. Yield: 1.00 g (77%); m.p. 113–1158C; H NMR (200.1 MHz,
3
4
ACHTREUNG
CDCl3, 208C): d=9.08 (dd, J
(d, J(H,H)=8.1 Hz, 1H), 7.92 (d, J
1H), 7.69–7.55 (m, 3H), 7.39 (d, J(H,H)=9.0 Hz, 1H), 2.83 ppm (s, 3H;
N
(H,H)=1.5 Hz, 1H), 8.02
A
ACHTREUNG
AHCTREUNG
CH3); 13C{1H} NMR (50.3 MHz, CDCl3, 208C): d=200.2 (CO), 151.0,
144.8, 135.9, 133.3, 131.1, 129.5, 128.2, 127.8, 127.6, 127.1, 124.5, 124.1,
118.3, 25.4 ppm (CH3); elemental analysis calcd (%) for C15H11NO: C
81.43, H 5.01, N 6.33; found: C 81.16, H 4.92, N 6.40.
A
nolin-2-yl)ethanone (2.62 g, 11.85 mmol) and hydroxylamine hydrochlo-
ride (1.52 g, 21.88 mmol) in 96% ethanol (100 mL) was stirred for 30 h at
room temperature. The reaction was monitored by TLC (petroleum
ether/ethyl acetate=9:1). The solvent was removed under reduced pres-
sure 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 extracted with
CH2Cl2 (2”20 mL). The combined organic phase was dried over Na2SO4
and the solvent was evaporated to give (benzo[h]quinolin-2-yl)methyl ke-
toxime as a yellow solid that was used in the next step without further
purification. Yield: 2.7 g (96%); m.p. 200–202 8C; elemental analysis
calcd (%) for C15H12N2O: C 76.25, H 5.12, N 11.86; found: C 76.44, H
5.15, N 11.89.
1-(Benzo[h]quinolin-2-yl)-2,2-dimethylpropanamine (c):
A solution of
(benzo[h]quinolin-2-yl)-tert-butyl ketoxime (1.3 g, 4.68 mmol) and ammo-
nium acetate (0.447 g, 5.80 mmol) in 30% NH3/H2O/96% EtOH
(16.8:11.2:11.2 mL) was stirred for 30 min at room temperature. Zinc
powder (1.68 g, 25.7 mmol) was added portionwise over a period of 2 h at
room temperature and then the reaction mixture was heated under reflux
for 4 h. After cooling, the mixture was acidified up to pH 1 by adding of
36% HCl. The resulting clean solution was concentrated under reduced
pressure. The amine was liberated with a 50% aqueous solution of KOH
and extracted with diethyl ether (4”25 mL). The combined organic
phase was dried over Na2SO4, the solvent was evaporated, and the resi-
due was purified by flash chromatography with MeOH as the eluant to
give c as an orange liquid. Yield: 0.59 g (48%); 1H NMR (200.1 MHz,
1-(Benzo[h]quinolin-2-yl)ethanamine (b): A solution of (benzo[h]quino-
lin-2-yl)methyl ketoxime (2.6g, 11.0 mmol) and ammonium acetate
(1.05 g, 13.6mmol) in 30% NH 3/H2O/96% EtOH (39.5:26.3:26.3 mL)
was stirred for 30 min at room temperature. Zinc powder (3.95 g,
60.4 mmol) was added portionwise over a period of 2 h at room tempera-
ture 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 that was alkalized with 10% NaOH, and ex-
tracted with diethyl ether (3”30 mL). The combined organic phase was
dried over Na2SO4, the solvent was evaporated, and the residue was puri-
fied by flash chromatography by using MeOH as the eluant to give b as
an orange liquid. Yield: 1.88 g (77%); 1H NMR (200.1 MHz, CDCl3,
CDCl3, 208C): d=9.31 (d,
J
G
J
G
8.1 Hz, 1H), 7.84 (d, J(H,H)=7.5 Hz, 1H), 7.76–7.55 (m, 4H), 7.34 (d, J-
AHCTREUNG
(H,H)=8.1 Hz, 1H), 3.88 (s, 1H; CHN), 2.65 (s, 2H; NH2), 0.99 ppm (s,
9H; CH3); 13C{1H} NMR (50.3 MHz, CDCl3, 208C): d=161.1, 145.1,
134.8, 133.4, 131.4, 127.8, 127.5, 126.8, 126.6, 125.0, 124.8, 124.3, 122.2,
65.8 (CHN), 35.5 (CMe3), 26.5 ppm (CH3); elemental analysis calcd (%)
for C18H20N2: C 81.78, H 7.63, N 10.60, found: C 81.66, H 7.67, N 10.63.
Synthesis of 1: The ligand a (36mg, 0.173 mmol) and NEt 3 (0.22 mL,
0.158 mmol) were added to [RuCl2(PPh3)3] (0.150 g, 0.156mmol) in 2-
G
propanol (2 mL) and the mixture was heated under reflux for 2 h. The re-
sulting solution was concentrated (1 mL) and addition of pentane (2 mL)
afforded an orange precipitate. The product was filtered, washed with
pentane (3”5 mL), and dried under reduced pressure. Yield: 100 mg
208C): d=9.36(d,
7.88 (d, J(H,H)=8.1 Hz, 1H), 7.80–7.59 (m, 4H), 7.47 (d, J
8.1 Hz, 1H), 4.37 (q, 3J
(H,H)=6.6 Hz, 1H; CHCH3), 2.26(s, 2H; NH 2),
1.56ppm (d, 3J(H,H)=6.6 Hz, 3H; CH3); 13C{1H} NMR (50.3 MHz,
J
A
ACHTREUNG
A
ACHTREUNG
ACHTREUNG
A
(74%); 1H NMR (200.1 MHz, CD2Cl2, 208C): d=8.32 (dd, 3J
4J
4.30 (dd, J(H,H)=16.1, J(H,H)=3.8 Hz, 1H; CH2N), 3.83–3.55 (m, 2H;
ACHTREUNG
CDCl3, 208C): d=164.2, 145.5, 136.3, 133.6, 131.3, 127.9, 127.7 127.0,
126.7, 125.1, 124.9, 124.3, 119.0, 52.8 (CCH3), 24.8 ppm (CH3); elemental
ACHTREUNG
2
3
ACHTREUNG
A
9156
www.chemeurj.org
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 9148 – 9160

Asymmetric Catalysis
FULL PAPER
CH2N, NH2), 1.96ppm (s, 1H; NH 2); 31P{1H} NMR (81.0 MHz, CD2Cl2,
0.91 ppm (s, 9H; tBu); 13C{1H} NMR (50.3 MHz, CD2Cl2, 208C): d=
208C): d=56.5 (d, 2J
A
N
180.3 (dd, 2J
atoms), 72.9 (d, 3J
1J(C,P)=24.7 Hz, 4J
PCH2), 27.5 (s; C
(CH3)3), 27.0 (d, 2J
(d, 2J(C,P)=3.1 Hz; PCH2CH2); 31P{1H} NMR (81.0 MHz, CD2Cl2,
208C): d=57.1 (d, 2J(P,P)=38.6Hz), 44.5 ppm (d, 2J
(P,P)=38.6Hz); ele-
ACHTREUNG
mental analysis calcd (%) for C50H41ClN2P2Ru: C 69.16, H 4.76, N 3.23;
found: C 69.35, H 4.85, N 3.34.
A
ACHTREUNG
A
N
ACHTREUNG
A
ACHTREUNG
Synthesis of 2: The ligand a (232 mg, 1.11 mmol) and NEt3 (1.55 mL,
AHCTREUNG
11.1 mmol) were added to [RuCl2
N
N
A
ACHTREUNG
2-propanol (15 mL). The mixture was heated under reflux for 2 h, obtain-
ing an orange precipitate which was filtered, washed with methanol (3”
10 mL), and dried under reduced pressure. Yield: 608 mg (85%);
mental analysis calcd (%) for C46H47ClN2P2Ru: C 66.86, H 5.73, N 3.39;
found: C 67.10, H 5.70, N 3.19.
1H NMR (200.1 MHz, CD2Cl2, 208C): d=8.19 (pseudot, J
A
Synthesis of 5: Toluene (2 mL) was added to [RuCl2(PPh3)3] (0.150 g,
H
2H; aromatic protons), 7.99 (d, J
7.82 (pseudot, J
A
0.156mmol) and ( R,S)-Josiphos·C2H5OH (120 mg, 0.187 mmol) and the
suspension was heated under reflux for 1 h. The solvent was removed
under reduced pressure and the residue was treated with 2-propanol
A
ACHTREUNG
A
N
(2 mL), the ligand a (36mg, 0.172 mmol), and NEt 3 (0.22 mL,
A
1.58 mmol). The mixture was heated under reflux for 2 h and then cooled
to room temperature. Addition of pentane (5 mL) afforded a precipitate
which was filtered, washed with pentane (4”3 mL), and dried under re-
duced pressure. The solid was dissolved in CH2Cl2 (0.5 mL), kept at
À208C for 18 h, to afford the precipitation of triethylammonium chloride
which was eliminated by filtration. The solution was concentrated (1 mL)
and addition of pentane (2 mL) afforded an orange precipitate which was
filtered, washed with pentane (2”2 mL), and dried under reduced pres-
sure. Yield: 90 mg (61%); 1H NMR (200.1 MHz, CD2Cl2, 208C): d=8.33
ACHTREUNG
G
U
J
ACHTREUNG
11.0, 5.0 Hz, 1H; NCH2), 3.60 (m, 1H; NH2), 3.01 (m, 2H; CH2), 2.35–
1.00 ppm (m, 7H; CH2 and NH2); 13C{1H} NMR (50.3 MHz, CDCl3,
208C): d=177.0 (dd; 2J
(d, 3J
52.2 (d, 3J
1.8 Hz; PCH2), 29.9 (d, 1J
1.3 Hz; PCH2CH2), 21.5 ppm (dd, 2J
PCH2CH2); 31P{1H} NMR (81.0 MHz, CD2Cl2, 208C): d=57.3 (d, 2J-
(P,P)=38.2 Hz), 43.7 ppm (d, 2J
(P,P)=38.2 Hz); elemental analysis calcd
ACHTREUNG
ACHTREUNG
N
U
ACHTREUNG
N
ACHTREUNG
G
G
(d, J(H,H)=7.0 Hz, 1H; aromatic proton), 8.22–7.16(m, 16H; aromatic
A
protons), 4.70–4.35 (m, 4H; C5H3, PCH), 4.24–4.10 (m, 2H; NCH2), 3.79
(s, 5H; C5H5), 3.45 (m, 1H; NH2), 2.95–0.60 ppm (m, 26H; CH, CH2,
CH3, NH2); 13C{1H} NMR (50.3 MHz, CD2Cl2, 208C): d=158.0–117.0 (m;
aromatic carbon atoms), 97.6(m; ipso-C 5H3), 74.4 (s; C5H3), 72.5 (m;
N
ACHTREUNG
(%) for C42H39ClN2P2Ru: C 65.49, H 5.10, N 3.64; found: C 65.18, H
5.23, N 3.47.
ipso-C5H3), 70.8 (s; C5H5), 70.3 (d, J(C,P)=4.3 Hz; C5H3), 68.9 (d, J-
G
Synthesis of 3: The ligand b (39 mg, 0.175 mmol) and NEt3 (0.16mL,
3
1
ACHTREUNG
G
N
1.15 mmol) were added to [RuCl
N
G
AHCTREUNG
2-propanol (2 mL). The mixture was heated under reflux for 3 h, giving
an orange precipitate which was filtered, washed with pentane (4”3 mL),
and dried under reduced pressure. The solid was dissolved in CH2Cl2
(0.5 mL), kept at À208C for 18 h, affording the precipitation of triethyl-
ammonium chloride which was eliminated by filtration. The resulting so-
lution was concentrated (1 mL) and addition of pentane (2 mL) gave an
orange precipitate which was filtered, washed with pentane (2 mL), and
dried under reduced pressure. Yield: 60 mg (66%); 1H NMR
A
ACHTREUNG
G
ACHTREUNG
calcd (%) for C50H55ClFeN2P2Ru: C 64.00, H 5.91, N 2.99; found: C
64.30, H 6.02, N 3.05.
Synthesis of 6: CH2Cl2 (2 mL) was added to [RuCl2(PPh3)3] (0.150 g,
U
0.156mmol) and ( S,R)-Josiphos* (133 mg, 0.187 mmol) and the mixture
was stirred for 1 h at room temperature. The solvent was removed under
reduced pressure and the residue was treated with 2-propanol (1 mL),
heptane (1 mL), the ligand a (36mg, 0.172 mmol), and NEt 3 (0.22 mL,
1.58 mmol). The suspension was heated under reflux overnight and after
filtration the solvent was removed. The residue was treated with heptane
(2 mL) and the solution was heated under reflux for 2 h, concentrated
(1 mL), and addition of pentane (1 mL) led to a precipitate, which was
filtered and dried under reduced pressure. The solid was dissolved in
CH2Cl2 (0.5 mL), kept at À208C for 18 h to afford the precipitation of
the residual NEt3HCl, which was filtered. The resulting solution was con-
centrated (1 mL) and addition of pentane (2 mL) led to an orange pre-
cipitate, which was filtered, washed with pentane (2”2 mL), and dried
under reduced pressure. Yield: 90 mg (55%) as mixture of two diastereo-
isomers in 5:1 ratio; 1H NMR (200.1 MHz, CD2Cl2, 208C): d=8.37–6.60
(m; aromatic protons), 5.02–4.01 (m; PCH, C5H3, CH2NH2), 3.74–3.70
(m; OMe, C5H5), 2.57 (s; CH3), 2.20 (s; CH3), 2.18 (s; CH3), 1.84–
0.78 ppm (m; CH3, Cy, NH2); 13C{1H} NMR (50.3 MHz, CD2Cl2, 208C):
d=182.8 (m; CRu), 161.3–116.4 (m; aromatic carbons), 97.5 (dd, J-
(200.1 MHz, CD2Cl2, 208C): d=8.18 (pseudot, J
matic protons), 8.01 (d, J(H,H)=7.0 Hz, 1H; aromatic proton), 7.82
(pseudot, J(H,H)=8.4 Hz, 2H; aromatic protons), 7.68 (d, J(H,H)=
5.4 Hz, 1H; aromatic proton), 7.65 (d, J(H,H)=6.0 Hz, 1H; aromatic
proton), 7.49–7.22 (m, 14H; aromatic protons), 6.98 (d, J(H,H)=8.4 Hz,
1H; aromatic proton), 6.45 (t, J(H,H)=7.4 Hz, 1H; aromatic proton),
6.16 (pseudot, J(H,H)=8.2 Hz, 2H; aromatic protons), 5.45 (t, J(H,H)=
8.4 Hz, 2H; aromatic protons), 4.37 (m, 1H; NCHMe), 3.55 (t, J(H,H)=
11.4 Hz, 1H; NH2), 3.20–2.85 (m, 3H; CH2), 2.40–1.70 (m, 6H; CH2 and
NH2), 1.58 ppm (d, 3J(H,H)=6.7 Hz, 3H; CHCH3); 13C{1H} NMR
(50.3 MHz, CD2Cl2, 208C): d=179.1 (dd, 2J
(C,P)=16.3, 8.4 Hz; CRu),
157.8–116.5 (m; aromatic carbon atoms), 58.5 (d, 3J
(C,P)=2.6Hz;
NCHMe), 33.3 (dd, 1J(C,P)=24.9 Hz, 4J
(C,P)=2.2 Hz; PCH2), 30.5 (d,
1J(C,P)=32.1 Hz; PCH2), 26.8 (d, 2J
(C,P)=2.0 Hz; PCH2CH2), 23.4 (s;
CHCH3), 22.0 ppm (m; PCH2CH2); 31P{1H} NMR (81.0 MHz, CD2Cl2,
208C): d=57.3 (d, 2J(P,P)=38.3 Hz), 43.6ppm (d, 2J
(P,P)=38.3 Hz); ele-
A
AHCTREUNG
A
ACHTREUNG
AHCTREUNG
AHCTREUNG
AHCTREUNG
A
ACHTREUNG
AHCTREUNG
ACHTREUNG
AHCTREUNG
AHCTREUNG
A
ACHTREUNG
A
ACHTREUNG
A
ACHTREUNG
mental analysis calcd (%) for C43H41ClN2P2Ru: C 65.85, H 5.27, N 3.57;
found: C 66.10, H 5.40, N 3.74.
AHCTREUNG
Synthesis of 4: Compound 4 was prepared in a way similar to that de-
scribed for 3, using the ligand c in place of b and heating the [RuCl2-
A
ACHTREUNG
AHCTREUNG
A
ACHTREUNG
AHCTREUNG
AHCTREUNG
2
AHCTREUNG
AHCTREUNG
PCMe); 31P{1H} NMR (81.0 MHz, CD2Cl2, 208C): d=67.3 (d, 2J
ACHTREUNG
G
ACHTREUNG
41.9 Hz; major complex), 60.1 (d, 2J
G
ACHTREUNG
AHCTREUNG
2
40.0 Hz), 38.5 ppm (d, J
A
AHCTREUNG
ysis calcd (%) for C56H67ClFeN2O2P2Ru: C 63.79, H 6.40, N 2.66; found:
C 64.02, H 6.60, N 2.86.
AHCTREUNG
AHCTREUNG
J
A
Synthesis of 7: Toluene (3 mL) was added to [RuCl
A
0.156mmol) and ( S,S)-Skewphos (89 mg, 0.202 mmol) and the mixture
Chem. Eur. J. 2008, 14, 9148 – 9160
ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.chemeurj.org
9157

W. Baratta et al.
was heated under reflux for 2 h, following the procedure described for 5.
Yield: 70 mg (57%) as mixture of two diastereoisomers in 4:1 ratio;
1H NMR (200.1 MHz, CD2Cl2, 208C): d=8.31–5.80 (m; aromatic pro-
matic protons), 5.28 (br s, 1H; NH2), 4.46(d, 4J
OCH), 3.24–2.65 (m, 4H; CH2, NH2), 2.35–0.80 ppm (m, 7H; CH2, NH2);
13C{1H} NMR (50.3 MHz, C6D6, 208C): d=183.4 (dd, 2J
(C,P)=15.0,
8.5 Hz; CRu), 161.1 (d, 1J(C,F)=240.6Hz; C-F), 160.6 (d, 1J
(C,F)=
240.2 Hz; C-F), 156.0–113.4 (m; aromatic carbon atoms), 79.9 (s, OCH),
52.0 (d, 3J(C,P)=2.5 Hz; NCH2), 31.3 (d, 1J
(C,P)=28.3 Hz; PCH2), 30.7
(d, 1J(C,P)=29.5 Hz; PCH2), 26.8 (s; PCH2CH2), 22.3 ppm (d, 2J
(C,P)=
2.3 Hz; PCH2CH2); 31P{1H} NMR (81.0 MHz, C6D6, 208C): d=57.0 (d, J-
(P,P)=34.3 Hz), 40.3 ppm (d, 2J(P,P)=34.3 Hz); 19F{1H} NMR
G
tons), 6.44 (t,
6.4 Hz; aromatic proton), 5.84 (t, J
(s), 4.20 (d, J(H,H)=3.4 Hz), 3.68 (br s), 3.37 (m), 3.03 (m), 2.78 (br s),
2.36(pseudoq, (H,H)=13.5 Hz; CHCH2), 2.00–1.40 (m), 1.35 (t, J-
(H,H)=7.4 Hz), 1.29 (dd, J
m, CHCH2), 0.76(br s), 0.55 ppm (dd, 3J
CH3); 13C{1H} NMR (50.3 MHz, CD2Cl2, 208C): d=178.5 (m; CRu),
159.3–116.2 (m; aromatic carbon atoms), 51.3 (d, 3J
(C,P)=1.5 Hz;
NCH2), 37.9 (m; CHCH2), 33.0 (m; PCH), 32.6(m; PCH), 19.5 (d, 2J-
(C,P)=6.1 Hz; PCHCH3), 17.5 ppm (dd, 2J(C,P)=6.5, 4J
(C,P)=3.0 Hz;
J
A
J
A
G
AHCTREUNG
N
E
ACHTREUNG
J
A
A
3
2
ACHTREUNG
G
A
A
N
E
ACHTREUNG
(188.3 MHz, C6D6, 208C, CFCl3): d=À119.6, À120.3 ppm; elemental
analysis calcd (%) for C55H48F2N2OP2Ru: C 69.24, H 5.07, N 2.94; found:
C 69.16, H 5.29, N 2.93.
AHCTREUNG
A
N
ACHTREUNG
Synthesis of 12: CH2Cl2 (5 mL) was added to [OsCl2(PPh3)3] (200 mg,
A
2
PCHCH3); 31P{1H} NMR (81.0 MHz, CD2Cl2, 208C): d=66.2 (d, J
ACHTREUNG
0.191 mmol) and dppb (98 mg, 0.230 mmol), and the green solution was
stirred at RT for 2 h. The solvent was removed under reduced pressure
and the residue was suspended in 2-propanol (5 mL). Addition of the
ligand a (48 mg, 0.230 mmol) and NEt3 (0.32 mL, 2.30 mmol) afforded a
mixture which was heated under reflux for 3 h, leading to a red precipi-
tate. After filtration the product was washed with 2-propanol (3”10 mL)
and pentane (2”10 mL) and dried under reduced pressure at 458C.
Yield: 144 mg (88%); 1H NMR (200.1 MHz, CD2Cl2, 208C): d=8.13
46.2 Hz; major complex), 64.4 (d, 2J
A
ACHTREUNG
2
48.7 Hz), 47.8 ppm (d, J
A
ysis calcd (%) for C43H41ClN2P2Ru: C 65.85, H 5.27, N 3.57; found: C
66.06, H 5.37, N 3.63.
Synthesis of 8: Toluene (2 mL) was added to [RuCl2(PPh3)3] (0.150 g,
E
0.156mmol) and ( S)-MeO-Biphep (136mg, 0.233 mmol) and the mixture
was heated under reflux for 2 h, following the procedure described for 5.
Yield: 95 mg (66%) as mixture of two diastereoisomers in 3:1 ratio;
(pseudot, J
6.9 Hz, 1H; aromatic proton), 7.76 (t, J
tons), 7.64–7.20 (m, 16H; aromatic protons), 6.98 (d, J
1H; aromatic proton), 6.44 (t, J(H,H)=7.3 Hz, 1H; aromatic proton),
6.17 (pseudot, J(H,H)=7.8 Hz, 2H; aromatic protons), 5.49 (t, J(H,H)=
7.9 Hz, 2H; aromatic protons), 4.50 (d, J(H,H)=20.7 Hz, 1H; NCH2),
A
N
1H NMR (200.1 MHz, CDCl3, 208C): d=8.45 (d, J
G
ACHTREUNG
2
matic protons), 8.07–5.52 (m; aromatic protons), 4.43 (dd, J
ACHTREUNG
3J
A
ACHTREUNG
complex), 3.88 (s; OCH3, major complex), 3.74 (s; OCH3, minor com-
plex), 3.39 (s; OCH3, major complex), 3.28 (s; OCH3, minor complex),
A
ACHTREUNG
AHCTREUNG
2.05 ppm (t, 1H,
J
A
4.00 (m, 2H; NH2 and NCH2), 3.53 (m, 1H; CH2), 3.30–2.65 (m, 2H;
CH2 and NH2), 2.42–1.48 ppm (m, 6H; CH2); 13C{1H} NMR (50.3 MHz,
CDCl3, 208C): d=177.8 (m; CRu), 164.8–110.6 (m; aromatic carbon
atoms), 55.8 (s, OCH3), 55.7 (s, OCH3), 54.9 (s, OCH3), 54.6(s, OCH 3),
CD2Cl2, 208C): d=157.2 (t; 2J
ACHTREUNG
52.2 ppm (d, 3J(C,P)=1.7 Hz; NCH2); 31P{1H} NMR (81.0 MHz, CD2Cl2,
T
208C): d=60.3 (d, 2J
C
G
A
ACHTREUNG
G
A
A
ACHTREUNG
complex); elemental analysis calcd (%) for C52H43ClN2O2P2Ru: C 67.42;
H 4.68; N 3.02; found: C 67.73, H 4.80, N 3.12.
ACHTREUNG
A
ACHTREUNG
AHCTREUNG
Synthesis of 10: A 0.1m solution of NaOiPr (2.9 mL, 0.290 mmol) in 2-
propanol was added to a suspension of complex 2 (150 mg, 0.195 mmol)
in toluene (2.9 mL). The mixture was stirred at 608C for 1 h. The result-
ing dark red solution was concentrated to half volume, stirred at RT for
1 h and after addition of toluene (3 mL), kept at À208C for 18 h to
afford the precipitation of NaCl, which was filtered on celite (fine frit).
The solution was stirred under H2 (1 atm) at RT for 1 h, and the solvent
was eliminated obtaining a bright orange product, which was dried under
reduced pressure. Yield: 119 mg (83%); 1H NMR (200.1 MHz, C6D6,
AHCTREUNG
C42H39ClN2OsP2: C 58.70, H 4.57, N 3.26; found: C 58.42, H 4.74, N 3.27.
Synthesis of 14: A 0.1m solution of NaOiPr (1.3 mL, 0.130 mmol) in 2-
propanol was added to a suspension of complex 12 (100 mg, 0.116mmol)
in toluene (1.3 mL), and the mixture was stirred at 358C for 3 h. The re-
sulting dark red solution was kept at À208C for 4 h to afford the precipi-
tation of NaCl, which was filtered on celite (fine frit). The solvent was
eliminated at low pressure and the solid was extracted with pentane
(1 mL), affording a brown product which was dried under reduced pres-
208C): d=8.58 (t, J
18H; aromatic protons), 6.37 (d, J
6.27 (d, J(H,H)=7.7 Hz, 2H; aromatic protons), 6.14 (m, 2H; aromatic
ACHTREUNG
1
T
sure. Yield: 71 mg (74%); H NMR (200.1 MHz, C6D6, 208C): d=8.53 (t,
H
J
G
ACHTREUNG
protons), 5.50 (t, J
U
ACHTREUNG
H); 31P{1H} NMR (81.0 MHz, C6D6, 208C): d=66.6 (d, J
(t, J
N
J(H,H)=6.9 Hz, 1H;
U
35.0 ppm (d, 2J
A
(H,P)=73.9,
mental analysis calcd (%) for C42H40N2P2Ru: C 68.56, H 5.48, N 3.81;
found: C 68.20, H 5.44, N 3.45.
23.9 Hz, 1H; OsH); 31P{1H} NMR (81.0 MHz, C6D6, 208C): d=19.9 (d,
2J
A
(%) for C42H40N2OsP2: C 61.15, H 4.89, N 3.40; found: C 60.85, H 5.02, N
3.13.
Synthesis of 11: A 0.1m solution of NaOiPr (3.9 mL, 0.390 mmol) in 2-
propanol was added to a suspension of complex 2 (200 mg, 0.260 mmol)
in toluene (3.9 mL). The mixture was stirred at 608C for 2 h, and at RT
for an additional 1 h. The resulting dark red solution was kept at À208C
for 4 h to afford the precipitation of NaCl, which was filtered on celite
(fine frit). 4,4’-Difluorobenzophenone (68.0 mg, 0.312 mmol) was added
and the solution was stirred at RT for 30 min. The solvent was eliminat-
ed, toluene (2 mL) was added, and the mixture was kept at À208C for
2 h, filtered on celite, and the solution was concentrated (1 mL). Addi-
tion of pentane afforded the precipitation of a red-orange product which
was dried under reduced pressure. Yield: 186mg (75%); 1H NMR
(200.1 MHz, C6D6, 208C): d=8.15 (m, 2H; aromatic protons), 8.03 (t, J-
Synthesis of 15: A 0.1m solution of NaOiPr (1.6mL, 0.160 mmol) in 2-
propanol was added to a suspension of complex 12 (123 mg, 0.143 mmol)
in toluene (1.6mL), and the mixture was stirred at 35 8C for 3 h. The re-
sulting dark red solution was kept at À208C for 4 h to afford the precipi-
tation of NaCl, which was filtered on celite (fine frit). 4,4’-Difluorobenzo-
phenone (35 mg, 0.160 mmol) was added and the mixture was stirred at
RT for 1 h. The solvent was eliminated, toluene (2 mL) was added and
the mixture was kept at À208C for 2 h and filtered on celite; the resulting
solution was concentrated. Addition of pentane (5 mL) afforded the pre-
cipitation of a dark-yellow product, which was filtered and dried under
reduced pressure. Yield: 107 mg (72%); 1H NMR (200.1 MHz, C6D6,
ACHTREUNG
A
208C): d=8.18 (t, J
ACHTREUNG
A
G
A
ACHTREUNG
9158
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ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 9148 – 9160

Asymmetric Catalysis
FULL PAPER
matic protons), 7.66–6.21 (m, 26H; aromatic protons), 6.04 (dt, J
A
Tables for Crystallography.[34] CCDC-687367 contains the supplementary
crystallographic data for this paper. These data can be obtained free of
charge from The Cambridge Crystallographic Data Centre via
www.ccdc.cam.ac.uk/data_request/cif.
7.6, 1.8 Hz, 2H; aromatic protons), 5.83 (d, J
ic proton), 5.42 (t, J(H,H)=7.9 Hz, 2H; aromatic protons), 5.28 (brs,
1H; NH2), 4.61 (m, 1H; OCH), 3.48 (m, 1H; NCH2), 3.26(s, 2H; CH
(H,H)=8.2 Hz, 1H; aromat-
ACHTREUNG
and NH2), 2.91 (pseudot, J
CH2), 2.25 (m, 2H; CH2), 1.94–0.77 ppm (m, 4H; CH2); 13C{1H} NMR
(50.3 MHz, C6D6, 208C): d=162.4 (brd, 1J
(C,F)=245 Hz; C-F), 162.0
(dd, 2J
(C,P)=7.9, 3.7 Hz; C-Os), 156.4 (s; CCN), 155.1 (s; NCCH2),
147.9–113.0 (m; aromatic carbon atoms), 79.7 (brs; OCH), 54.0 (d, 3J-
(C,P)=2.2 Hz; NCH2), 33.7 (d, 2J(C,P)=33.2 Hz; PCH2), 30.8 (d, 2J-
(C,P)=34.4 Hz; PCH2), 26.7 (s; CH2), 21.6ppm (s; CH 2); 31P{1H} NMR
(81.0 MHz, C6D6, 208C): d=1.8 (d, 2J
(P,P)=8.2 Hz), À0.8 ppm (d, 2J-
G
ACHTREUNG
E
Acknowledgement
ACHTREUNG
This work was supported by the Ministero dellꢁUniversità e della Ricerca
(MIUR) and the Regione Friuli Venezia Giulia. We thank Johnson-Mat-
they/Alfa Aesar for a generous loan of ruthenium and P. Polese for carry-
ing out the elemental analyses.
G
À120.1 ppm; elemental analysis calcd (%) for C55H48F2N2OOsP2: C 63.33,
H 4.64, N 2.69; found: C 62.84, H 4.72, N 2.62.
Typical procedure for the catalytic TH of ketones: The complex
(2.5 mmol) was dissolved in 2-propanol (5 mL). The ketone (2.0 mmol)
was dissolved in 2-propanol (final volume 19.4 mL) and the solution was
heated under argon. By addition of NaOiPr in 2-propanol (0.1m, 400 mL,
40 mmol) and a solution of the catalyst in 2-propanol (200 mL), the reduc-
tion of the ketone starts immediately and the yield was determined by
GC (complex 0.005 mol%, NaOiPr 2 mol%, ketone 0.1m).
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Typical procedure for the catalytic TH of ketones with the in-situ-pre-
pared catalyst: A solution of [MCl2(PPh3)3] (M=Ru, Os; 2.5 mmol) and
N
the diphosphane (3.8 mmol) in 2-propanol (5 mL) was heated under
reflux for 1 h and, after addition of the HCN’N ligand (5.0 mmol of a or
7.5 mmol of b, c), for an additional 1 h. The ketone (2.00 mmol) was dis-
solved in 2-propanol (final volume: 19.4 mL) and the solution was heated
at 608C. Addition of NaOiPr in 2-propanol (0.1m, 400 mL, 40 mmol) and
the solution of the complex in 2-propanol (200 mL), affords the reduction
of the ketone (complex 0.005 mol%, NaOiPr 2 mol%, ketone 0.1m).
Single-crystal X-ray structure determination of compound 3: Crystal data
and
details
of
the
structure
determination:
formula:
C43H41ClN2P2Ru·2CH2Cl2; Mr =954.09; crystal color and shape: orange
fragment, crystal dimensions=0.28”0.43”0.61 mm; crystal system: tri-
¯
clinic; space group P1 (no. 2); a=10.8227(2), b=12.1648(2), c=
17.3533(3) Š; a=96.0103(13), b=91.1186(12), g=112.3160(14)8; V=
2097.57(7) Š3; Z=2;
m
A
;
1calcd =1.511 gcmÀ3
;
q
range=3.02–25.328; data collected: 38733; independent data [Io >2s(Io)/
all data/Rint]: 6940/7635/0.014; data/restraints/parameters: 7635/0/679; R1
[Io >2s(Io)/all data]: 0.0244/0.0287; wR2 [Io >2s(Io)/all data]: 0.0542/
0.0572; GOF=1.084; D1max/min: 0.88/À0.71 eŠÀ3. Suitable single crystals
for the X-ray diffraction study were grown from dichloromethane. A
clear orange fragment was stored under perfluorinated ether, transferred
in a Lindemann capillary, fixed, and sealed. Preliminary examination and
data collection was carried out on an area detecting system with graph-
ite-monochromated MoKa radiation (l=0.71073 Š, OXFORD DIF-
FRACTION, Xcalibur, k-CCD, sealed tube, Enhance X-ray Source,
SPELLMAN, DF3). The unit cell parameters were obtained by full-
matrix least-squares refinements during the scaling procedure. Data col-
lection was performed at low temperature (T=153 K, OXFORD CRYO-
SYSTEMS cooling device). The crystal was measured with nine data sets
in rotation scan modus (dp/dw=1.008; dx=50). Intensities were integrat-
ed and the raw data were corrected for Lorentz, polarization, and, arising
from the scaling procedure for latent decay and absorption effects. The
structure was solved by a combination of direct methods and difference
Fourier syntheses. All non-hydrogen atoms were refined with anisotropic
displacement parameters. All hydrogen positions could be located in the
final Fourier maps and were allowed to refine freely.
A disorder
[0.52(3):0.48(3)] of one of the two solvent molecules could be resolved
clearly. Those hydrogen atoms were placed in ideal positions and refied
using a riding model. Small extinction effects were corrected with the
SHELXL-97 procedure with e=0.0048(3). Full-matrix least-squares re-
finements were carried out by minimizing Ew(F02ÀF2c)2 with the
SHELXL-97 weighting scheme and stopped at shift/err <0.002. The final
residual electron density maps showed no remarkable features. Neutral
atom scattering factors for all atoms and anomalous dispersion correc-
tions for the non-hydrogen atoms were taken from the International
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34.5 Hz).
Received: May 9, 2007
Published online: September 18, 2008
9160
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ꢀ 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Chem. Eur. J. 2008, 14, 9148 – 9160