"In situ" activation of racemic RuII complexes: Separation of trans and cis species and their application in asymmetric reduction

Article abstract of DOI:10.1002/ejic.201200643

Ruthenium(II) dichlorides with racemic atropos-biaryl-based diphosphanes and optically active 1,2-diphenylethane-1,2-diamine (DPEN) as ligands have been synthesised. trans and cis isomers were formed due to the low basicity of the diphosphane ligands, in particular, with BITIANP and BIMIP. The trans and cis species were easily separated by filtration. In particular, when rac-BITIANP was used in combination with chiral DPEN, the asymmetric separation of optically pure complexes in cis and trans arrangements was realised and they were used as precatalysts in the asymmetric hydrogenation of ketones. Matching and mismatching combinations exhibited different performances.

Full text of DOI:10.1002/ejic.201200643

Job/Unit: I20643
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Date: 13-08-12 16:19:24
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FULL PAPER
DOI: 10.1002/ejic.201200643
“In situ” Activation of Racemic RuII Complexes: Separation of trans and cis
Species and Their Application in Asymmetric Reduction
Giorgio Facchetti,[a] Edoardo Cesarotti,[a] Michela Pellizzoni,[a] Daniele Zerla,[a] and
Isabella Rimoldi*[a]
Keywords: Homogeneous catalysis / Asymmetric catalysis / Ruthenium / Phosphane ligands / Reduction / Hydrogenation /
Atropoisomerism
Ruthenium(II) dichlorides with racemic atropos-biaryl-based
diphosphanes and optically active 1,2-diphenylethane-1,2-
particular, when rac-BITIANP was used in combination with
chiral DPEN, the asymmetric separation of optically pure
diamine (DPEN) as ligands have been synthesised. trans and complexes in cis and trans arrangements was realised and
cis isomers were formed due to the low basicity of the diphos-
phane ligands, in particular, with BITIANP and BIMIP. The
trans and cis species were easily separated by filtration. In
they were used as precatalysts in the asymmetric hydrogen-
ation of ketones. Matching and mismatching combinations
exhibited different performances.
One possibility that has been explored is the resolution
of RuII pre-catalysts by using a chiral diphosphane as re-
solving agent starting from an achiral diamine precursor in
combination with [RuCl2(PPh3)3].[15]
A more economic methodology for the asymmetric acti-
vation of racemic RuII complexes has successfully been real-
ised by employing a chiral diamine in the presence of race-
mic diphosphanes.[14,16] This strategy has been applied to
the resolution of atropoisomeric diphosphanes belonging to
the BINAP family.
Atropoisomeric diphosphanes represent a class of phos-
phorus ligands that have been established as being ex-
tremely efficient in the asymmetric hydrogenation of a wide
range of substrates, particularly aryl and heteroaryl
ketones.[17–22] The classic method reported for isolating
these ligands in enantiopure form involves oxidation fol-
lowed by selective precipitation of the diphosphane oxides
in the presence of dibenzoyltartaric acid. However, this ap-
proach is usable only in the resolution of diphosphanes of
relatively low acidity and has been successfully applied to
BINAP and to the more basic members of a class of di-
phosphanes derived from the condensation of heteroaryl
rings such as Tetra-Me-BITIOP and Tetra-Me-BITIANP
(Figure 1).[23–26] The technique involving the use of di-
benzoyltartaric acid as resolving agent failed when applied
to the oxides of less basic atropoisomeric ligands such as
BITIANP, BICUMP, BISCAP and BIMIP. We therefore fo-
cused our attention on BITIANP and BIMIP and in par-
ticular on the asymmetric activation of the corresponding
RuII complexes formed by these last racemic atropoisomeric
diphosphane ligands, employing the resolving ability of the
chiral diamine 1,2-diphenylethane-1,2-diamine (DPEN).
Furthermore, we highlighted the possibility of forming the
Introduction
In the past, asymmetric homogeneous catalysis was
based on the use of transition-metal complexes as catalysts
in which the source of chirality was often only a phos-
phorus ligand.[1,2] Over the last two decades, Noyori and
co-workers[3–8] have introduced new catalytically active RuII
complexes characterised by the combination of a chiral di-
phosphane and a chiral chelating diamine. These two li-
gands cooperatively accelerate the reaction rate and also
control the enantiofacial selectivity. These types of com-
plexes are very suitable as catalysts for the asymmetric hy-
drogenation of acetophenone-like ketones,[9–12] the corre-
sponding alcohols of which are important building blocks
for industrial and pharmaceutical applications.
However, one drawback of this ground-breaking discov-
ery is the expense of isolating the two chiral enantiopure
ligands. One of the best methodologies for reducing costs
without changing the high quality results is to use metal
complexes bearing a racemic ligand in combination with
non-racemic auxiliaries, which are essential for the enantio-
mer/diastereoisomer selective activation of the racemic RuII
pre-catalysts. This strategy is based on the assumption that
the interaction between the two ligands is irreversible and
on the relative turnover frequencies of the diastereoiso-
mers.[13,14]
[a] Università degli Studi di Milano, Dipartimento di Scienze
Farmaceutiche, Sez. Chimica Generale e Organica “A.
Marchesini”,
Via Venezian 21, 20133 Milano, Italy
Fax: +39-02-503-14615
E-mail: isabella.rimoldi@unimi.it
Homepage: http://www.unimi.it/chiedove/cv/
isabella_rimoldi.pdf
Eur. J. Inorg. Chem. 0000, 0–0
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G. Facchetti, E. Cesarotti, M. Pellizzoni, D. Zerla, I. Rimoldi
FULL PAPER
Figure 1. Atropoisomeric diphosphanes and the chiral diamine DPEN.
thermodynamically favoured cis isomers by exploiting the
different electronic properties of these diphosphanes in
combination with DPEN in analogy and/or in comparison
with the studies of James[27,28] and Noyori and their co-
workers.[14]
Results and Discussion
On consideration of the electronic properties of the atro-
poisomeric diphosphanes and on the basis of the method
of Henderson and Streuli,[29,30] the basicities of the diphos-
phanes were evaluated by titration in nitromethane.[31] The
pKa values were determined to have an error of Ϯ0.2 units.
According to this method, the pKa for PPh3 is 2.7 and that
of BINAP is 2.9. Table 1 reports the pKa values of the bihet-
eroaromatic atropoisomeric ligands, which show a linear re-
lationship with the electrochemical oxidative potentials,
previously determined in acetonitrile by voltammetry with
the Ag/Ag+ electrode as reference (Figure 2).[25]
Figure 2. Linear relationship between the pKa values and the oxi-
dative potentials of the heteroaromatic atropisomeric diphosphanes
and BINAP.
The data show that the electron-rich Tetra-Me-BITIOP
has a high basic strength whereas the electron-poor BIMIP
is relatively acidic (Figure 2). The same relationship was ev-
inced by comparing the chemical shifts in the 31P NMR
spectra of the free ligands and the corresponding pKa val-
ues: the chemical shift of the phosphorus atoms in the elec-
tron-rich and more basic Tetra-Me-BITIOP is at δ =
–20.02 ppm, whereas the chemical shift of the phosphorus
atoms in the electron-poor and less basic BIMIP is at δ =
–28.08 ppm. The signal of the intermediate BITIANP is at
δ = –24.06 ppm. All the 31P NMR spectra were recorded in
C6D6.
Table 1. pKa values of some atropoisomeric diphosphanes.[a]
Diphosphane
pKa
E° [V]
Tetra-Me-BITIOP
BINAP
Tetra-Me-BITIANP
BITIANP
BISCAP
BICUMP
3.8
2.9
1.2
1.1
0.7
–0.1
Ͻ–1.6
0.57
0.63
0.76
0.83
0.90
1.03
1.15
James and co-workers[27,28] observed that BINAP is able
to form cis RuII complexes when combined with different
BIMIP
[a] Measurements realised in nitromethane at 50 °C.
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Activation of Racemic RuII Complexes
diamines, whereas only trans species were evinced with mation of two isomers corresponding to trans complexes.
DPEN, as reported by Noyori and co-workers.[14] Thus, the After heating at reflux for 2 h the two trans isomers had
possibility of forming cis and/or trans complexes from com- partially converted into the thermodynamically favoured
binations of these biheteroaromatic diphosphanes and isomers with a cis arrangement of the chloride ligands.
DPEN was evaluated.
In the 31P NMR spectra of [RuCl2(BIMIP)(DPEN)], the
We focused our attention on Tetra-Me-BITIOP and BI- trans isomers are represented by two singlets (δ = 36.19 and
MIP, placed at either end of the scale above, and BITIANP, 34.79 ppm) and the cis species by two pairs of doublets (δ
which is in the middle. This methodology was particularly = 49.29 and 38.51 ppm, and 48.33 and 38.38 ppm). Thus,
interesting if applied to racemic mixtures of BIMIP and the spectra in Figure 3 show that both trans isomers evolve
BITIANP with the aim of bypassing the problems con- into cis species in the presence of this more electron-poor
nected with their resolution in enantiomerically pure form. ligand. After standing in solution for a week, the ratio be-
Note that the more acidic members of this family have tween the two cis isomers reached at least 30% (Figure 3).
never been resolved by the classic method, their corre- The cis and trans species were completely separated by the
sponding oxides selectively forming precipitates in the pres- slow diffusion of hexane into an ethanol-saturated solution,
ence of dibenzoyltartaric acid.
which led to a red precipitate. The solvent was removed by
As a starting material for the synthesis of RuII complexes filtration to leave the cis isomers as a red solid and the trans
bearing atropoisomeric ligands and diamines, [RuCl2(p- complex was obtained as a yellow solid after concentration
cymene)]2 was the best choice for two main reasons. The in vacuo.
first being that the arene ligands are easily removed from
the complex leading to the formation of coordinatively un-
saturated species and secondly for its capacity to form the
corresponding RuII–diphosphane complexes in high yields
and purity.[32] The [RuII(diphosphane)(diamine)] complexes
were synthesised as shown in Scheme 1.
Figure 3. 31P NMR spectra of [RuCl2(rac-BIMIP)(R,R)-DPEN]
from 2 h to a week.
With regard to BITIANP, this diphosphane showed in-
termediate behaviour compared with the other ligands in
the same class, both in terms of electron properties and ba-
sicity.
Also in this case, the combination of [RuCl2(rac-BITI-
ANP)(p-cymene)] and (R,R)- or (S,S)-DPEN gave rise to
the formation of trans isomers with signals of equal inten-
Scheme 1. Synthesis of RuII complexes.
The formation of the trans complexes and their potential sities in the 31P NMR spectra (δ = 45.15 and 44.75 ppm).
isomerisation to the thermodynamically favoured cis spe- After standing in solution for 3 d at 60 °C, the trans isomers
cies[16] were evaluated by 31P NMR spectroscopy. As ex- at δ = 44.75 ppm quantitatively converted into the cis spe-
pected for the more basic diphosphane, rac-Tetra-Me- cies, as evinced by the presence of only one singlet at δ =
BITIOP, only trans complexes were formed (two singlets at 45.15 ppm and the appearance of a pair of doublets corre-
δ = 46.9 and 47.1 ppm by 31P NMR) with no evidence for sponding to a single cis isomer (δ = 59.82 and 37.76 ppm;
the formation of cis complexes even after heating the solu- Figure 4). The cis species appeared as a yellow solid precipi-
tion at reflux at 60 °C for several weeks.
When the least basic rac-BIMIP was used as the ligand, two pure isomers was easily achieved by filtration.
the addition of enantiopure DPEN to [RuCl2(diphos- The assignment of the absolute configuration of the dia-
phane)(p-cymene)] led rapidly and quantitatively to the for- stereopure isomer obtained with this last ligand was based
tated in solution and thus the complete separation of the
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G. Facchetti, E. Cesarotti, M. Pellizzoni, D. Zerla, I. Rimoldi
FULL PAPER
Figure 5. Substrates used in the asymmetric hydrogenation reac-
tions.
The asymmetric reduction of 1 with BITIANP as a li-
gand showed that matching and mismatching combinations
of the cis and trans isomers occurred (entries 2–5). The per-
formance of the matched and mismatched pairs markedly
depends on the nature of the carbonyl substrate: in the case
of the reduction of 2, the trend was opposite to that found
for 1 (entries 6–8 vs. 2 and 3).
The results obtained for the combination of rac-BIMIP
with DPEN in the different pure forms furnished 1-phenyl-
ethanol in almost 80% ee in both cases (entries 9 and 10),
which confirms that the interaction between the RuCl2(di-
phosphane) complex and DPEN was almost irreversible, as
in the case of TolBINAP.[9,12,14,35–37]
Figure 4. 31P NMR spectra of [RuCl2(rac-BITIANP)(R,R)-DPEN]
from 2 h to 3 d.
When 3-quinuclidinone (2) was reduced, the S configura-
tion of 3-quinuclidinol was obtained in a modest 21% ee
with trans-[RuCl2(rac-BIMIP)(R,R)-DPEN] (entry 11)
whereas the same configuration was achieved with an ee of
7% by using cis-[RuCl2(rac-BIMIP)(R,R)-DPEN] (en-
try 12).
on a comparison with the chiral BITIANP in the R config-
uration.
All the species obtained were utilised in the hydrogena-
tion of a standard substrate like acetophenone (1) under
both hydrogen transfer and asymmetric hydrogen transfer
conditions. The results were comparable by both ap-
proaches in terms of enantioselectivity, although the TOFs
were lower in the hydrogen transfer (3–4 h–1) than in the
asymmetric hydrogen transfer (40–50 h–1)
The results obtained for the asymmetric hydrogenation
of 1 are summarised in Table 2 and are compared with the
results of the hydrogenation of a pharmaceutical precursor
like 3-quinuclidinone (2; Figure 5).[33,34]
Conclusions
In accordance with the work of James and co-workers,[27]
we have demonstrated that the trans/cis rearrangement of
the [Ru(diphosphane)(DPEN)] is related to the electron
properties and/or basicity of one of the chelating ligands.
In particular, when complexes with rac-BITIANP and
optically pure DPEN were used, two different efficient pre-
catalysts were formed, one in the cis and one in the trans
arrangement of chlorides, resulting in different matching
and mismatching combinations. The performances of these
catalysts were studied in the hydrogenation of acetophen-
one (1) and 3-quinuclidinone (2) under hydrogen-transfer
conditions. The effect of different substrates has been high-
lighted: in the reduction of 2; matching and mismatching
combinations were opposite to those observed in the re-
duction of 1.
When the ligand rac-BIMIP was used, we achieved asym-
metric activation, otherwise unrealisable by the classic
method. In fact, it has been demonstrated that the less basic
or more acidic ligands of this family can be resolved by
using a chiral palladium complex, di(μ-chloro)bis[(R)-di-
methyl(α-methylbenzyl)aminato-C2N]dipalladium(II),[24]
but in unacceptably low yields.
Table 2. Asymmetric hydrogenation of 1 and 2 under hydrogen
transfer conditions.[a]
Complex
Substrate ee [%][b]
1
trans-[RuCl2(rac-Tetra-Me-BITIOP){(R,R)-
DPEN}]
1
48 (S)
2
3
4
cis-[RuCl2{(R)-BITIANP}{(R,R)-DPEN}][c]
trans-[RuCl2{(S)-BITIANP}{(R,R)-DPEN}][c]
cis/trans-[RuCl2(rac-BITIANP){(R,R)-
DPEN}][d]
1
1
1
85 (S)
12 (S)
53 (S)
5
6
7
8
9
cis-[RuCl2{(R)-BITIANP}{(R,R)-DPEN}][e]
cis-[RuCl2{(R)-BITIANP}{(R,R)-DPEN}][c]
trans-[RuCl2{(S)-BITIANP}{(R,R)-DPEN}][c]
cis-[RuCl2{(R)-BITIANP}{(R,R)-DPEN}][e]
trans-[RuCl2(rac-BIMIP){(R,R)-DPEN}]
1
2
2
2
1
1
2
2
87 (S)
10 (S)
73 (S)
12 (S)
81 (S)
80 (S)
21 (S)
7 (S)
10 cis-[RuCl2(rac-BIMIP){(R,R)-DPEN}]
11 trans-[RuCl2(rac-BIMIP){(R,R)-DPEN}]
12 cis-[RuCl2(rac-BIMIP){(R,R)-DPEN}]
The “in situ” activation of the cis-RuII complexes has
been achieved in the presence of two racemic heteroarom-
atic atropoisomeric diphosphanes with chiral DPEN. This
behaviour depended on the electron properties of these li-
gands and differed to that of BINAP with which only trans
isomers were formed.
[a] Reactions were conducted with a 0.16 m solution of the sub-
strate (0.8 mmol) in 2-propanol in the presence of tBuOK (ketone/
base = 1:200) at room temperature and under 10 atm of H2 for
24 h. [b] Determined by chiral GC. [c] Pure isomer obtained by
isomerisation. [d] Ratio cis/trans = 39:61. [e] Pre-catalyst containing
chiral pure ligand.
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Activation of Racemic RuII Complexes
[RuCl2(rac-BIMIP){(R,R)- or S,S)-DPEN}]: rac-BIMIP (30.1 mg,
Experimental Section
0.05 mmol) was added to
a solution of [RuCl2(p-cymene)]2
General: All manipulations involving air-sensitive materials were
carried out in an inert atmosphere in a glovebox or by using stan-
dard Schlenk line techniques under nitrogen or argon in oven-dried
glassware. All the solvents used were anhydrous. Catalytic reactions
were performed in a 200 mL stainless-steel autoclave equipped with
temperature control and magnetic stirrer. DPEN was obtained
from commercial suppliers. Tetra-Me-BITIOP, BITIANP and BI-
MIP were synthesised according to literature procedures.[24,25] The
ruthenium catalysts were prepared by the well-established literature
procedure.[32] 1H and 31P NMR spectra were recorded with a
Bruker DRX Avance 300 MHz spectrometer equipped with a non-
reverse probe or with a Bruker DRX Avance 400 MHz spectrome-
ter. Gas chromatography was performed with a Carlo–Erba HRGC
5160 MEGA SERIES instrument equipped with a DIMEDEB-086
chiral column (length 25 m, internal diameter 0.25 mm). MS analy-
ses were performed with a Thermo Finnigan (MA, USA) LCQ
Advantage mass spectrometer equipped with an electronspray ion-
isation source and an “Ion Trap” mass analyser. The MS spectra
were obtained by direct infusion of a sample in MeOH/H2O/AcOH
(10:89:1) under ionisation (ESI positive).
(15.0 mg, 0.025 mmol) in a mixture of benzene and ethanol (8 mL,
1:3) under argon and stirred for 1 h at 65 °C. (R,R)- or (S,S)-DPEN
(10.6 mg, 0.05 mmol) was then added and the mixture was stirred
for 1 h at 60 °C. trans isomers were initially obtained. After a week
at reflux at 60 °C, four different species were identified in the solu-
tion: two cis isomers and two trans isomers. Recrystallisation of the
crude product by slow diffusion of hexane into an ethanol-satu-
rated solution afforded a red precipitate of the cis species and a
solution containing the trans isomers. The solvent was removed by
filtration to leave the cis isomers as a red solid and the trans com-
plex was obtained as a yellow solid after concentration in vacuo.
cis-[RuCl2(rac-BIMIP){(R,R)-DPEN}]: Yield 18.2 mg, 37%.31P
NMR (300 MHz, CDCl3): δ = 49.29 (d, J = 34.2 Hz, cis isomer),
38.51 (d, J = 33.9 Hz, cis isomer), 48.33 (d, J = 34.3 Hz, cis isomer),
38.38 (d, J = 34.0 Hz, cis isomer) ppm. 1H NMR (300 MHz,
CDCl3): δ = 6.76–8.17 (m, 38 H, aromatic), 4.28 (m, 2 H, NH2CH),
3.7(m, 2 H, NHHCH), 1.56 (m, 2 H, NHHCH) ppm.
trans-[RuCl2(rac-BIMIP){(R,R)-DPEN}]: Yield 22.19 mg, 45%. 31
P
NMR (300 MHz, CDCl3): δ = 36.19 (s, trans isomer), 34.79 (s, trans
1
isomer) ppm. H NMR (300 MHz, CDCl3): δ = 6.72–7.85 (m, 38
[RuCl2(rac-TetraMe-BITIOP){(R,R)- or (S,S)-DPEN}]: rac-Tetra-
Me-BITIOP (11.8 mg, 0.02 mmol) was added to a solution of
[RuCl2(p-cymene)]2 (6.0 mg, 0.01 mmol) in a mixture of benzene
and ethanol (8 mL, 1:3) under argon and stirred for 1 h at 65 °C.
(R,R)- or (S,S)-DPEN (4.26 mg, 0.02 mmol) was then added and
the mixture was stirred for 1 h at 60 °C to give trans isomers. The
solvent was removed by filtration to leave the complex as a yellow
solid (17.3 mg, 89% yield). 31P NMR (300 MHz, CDCl3): δ = 46.99
(s), 47.10 (s) ppm. 1H NMR (300 MHz, CDCl3): δ = 6.82–8.34 (m,
30 H, aromatic), 5.26 (m, 4 H, NHHCH), 4.52 (m, 2 H, NH2CH),
4.49 (m, 2 H, NH2CH), 3.74 (m, 2 H, NHHCH), 3.62 (m, 2 H,
NHHCH), 1.88 (s, 6 H, CH3), 1.74 (s, 6 H, CH3) ppm. MS (ESI,
+ve): calcd. for C50H48N2P2S2RuCl2 974.12; found 938.1 [M –
2Cl]+. C50H48Cl2N2P2RuS2 (974.99): calcd. C 61.59, H 4.96, N
2.87; found C 61.65, H 4.75, N 2.75.
H, aromatic), 4.32(m, 2 H, NH2CH), 3.99(m, 2 H, NHHCH), 1.71
(m, 2 H, NHHCH) ppm. 13C NMR (300 MHz, CDCl3): δ =
133.55–140.18 (C, aromatic), 120.76–131.70 (CH, aromatic), 63.35
(s, NH2CH) ppm. MS (ESI, +ve): calcd. for C52H44N6P2RuCl2
986.15; found 1009.2 [M
+
Na]+, 915.3 [M
–
2Cl]+.
C52H44Cl2N6P2Ru (986.88): calcd. C 63.29, H 4.49, N 8.52; found
C 62.89, H 4.18, N 8.12.
General Procedure for the Determination of pKa Values: The pKa
values were determined in CH3NO2 at 50 °C by using standard
perchloric acid solutions (0.1 n) in acetic acid with a glass-calomel
electrode system under an inert atmosphere. The temperature was
set at 50 °C because some ligands were not completely soluble at
room temperature. The relative basicities were determined through
the use of E1/2 or ΔHNP (half neutralisation potential) values.[29,30]
[RuCl2(rac-BITIANP){(R,R)- or (S,S)-DPEN}]: rac-BITIANP
(12.68 mg, 0.02 mmol) was added to a solution of [RuCl2(p-cy-
mene)]2 (6.0 mg, 0.01 mmol) in a mixture of benzene and ethanol
(8 mL, 1:3) under argon and the mixture was stirred for 1 h at
65 °C. (R,R)- or (S,S)-DPEN (4.24 mg, 0.02 mmol) was then added
and the mixture was stirred for 1 h at 60 °C. trans isomers were
initially obtained. After 3 d at 60 °C, a solid, found to be a cis
thermodynamically favoured species, precipitated from solution.
The yellow solid cis species and the solution containing the trans
isomers were separated by filtration. The trans complex was ob-
tained as an orange solid after concentration in vacuo.
cis-[RuCl2{(R)-BITIANP}{(R,R)-DPEN}]: Yield 7.6 mg, 38%. 31P
NMR (300 MHz, CDCl3): δ = 59.82 (d, J = 38.0 Hz, cis isomer),
37.76 (d, J = 38.7 Hz, cis isomer) ppm. 1H NMR (300 MHz,
CDCl3): δ = 6.74–7.89 (m, 38 H, aromatic), 4.58 (m, 2 H, NH2CH),
3.65 (m, 2 H, NHHCH), 2.06 (m, 2 H, NHHCH) ppm..
General Procedure for the Asymmetric Hydrogenation of Aceto-
phenone Under Hydrogen-Transfer Conditions: Acetophenone
(96 mg, 0.8 mmol) was added to the Ru complex (8ϫ10–4 mmol)
in a Schlenk tube sealed under argon, followed by 2-propanol
(1.5 mL). Solid t-C4H9OK (4.5 mg, 0.04 mmol) and 2-propanol
(3.5 mL) were then added to the Schlenk tube. The solution was
stirred for 30 min and then transferred to a stainless-steel autoclave
(200 mL) through a cannula. The autoclave was purged with H2
five times, the mixture was added, then the vessel was pressurised
at 25 atm, and the temperature was maintained at 25 °C. At the
end of the reaction, the autoclave was opened and the mixture ana-
lysed by GC and NMR spectroscopy. GC analysis conditions: T1
= 90 °C, rate 2 °C/min, T2 = 120 °C for 20 min; Rt(acetophenone)
= 6.47 min, Rt(R) = 9.05 min, Rt(S) = 9.3 min.
General Procedure for the Asymmetric Hydrogenation of 3-Quinu-
clidinone Under Hydrogen-Transfer Conditions: 3-Quinuclidinone
(129 mg, 0.8 mmol) was added to the Ru complex (8ϫ10–4 mmol)
in a Schlenk tube sealed under argon, followed by ethanol
(1.5 mL). Solid t-C4H9OK (94 mg, 0.84 mmol) and ethanol
trans-[RuCl2{(S)-BITIANP}{(R,R)-DPEN}]: Yield 9.2 mg, 46%.
31P NMR (300 MHz, CDCl3): δ = 45.15 (s, trans isomer), 44.75 (s,
trans isomer) ppm. 1H NMR (300 MHz, CDCl3): δ = 6.76–7.93 (m,
38 H, aromatic), 4.60 (m, 2 H, NH2CH), 3.99 (m, 2 H, NHHCH), (3.5 mL) were then added to the Schlenk tube. The solution was
2.34 (m, 2 H, NHHCH) ppm. 13C NMR (300 MHz, CDCl3): δ =
138.83–143.33 (C, aromatic), 121.93–134.60 (CH, aromatic), 63.25
(s, NH2CH) ppm. MS (ESI, +ve): calcd. for C54H44N2P2S2RuCl2
stirred for 30 min and then transferred to a stainless-steel autoclave
(200 mL) through a cannula. The autoclave, equipped with tem-
perature control and a magnetic stirrer, was purged five times with
hydrogen, after the transfer of the reaction mixture, the autoclave
was pressurised at 25 atm and heated at 40 °C. At the end of the
reaction, the autoclave was opened and the mixture analysed by
1018.08; found 983.0 [M
–
Cl]+, 947.1 [M
–
2Cl]+.
C54H44Cl2N2P2RuS2 (1019.00): calcd. C 63.65, H 4.35, N 2.75;
found C 61.02, H 4.11, N 2.20.
Eur. J. Inorg. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjic.org
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Job/Unit: I20643
/KAP1
Date: 13-08-12 16:19:24
Pages: 7
G. Facchetti, E. Cesarotti, M. Pellizzoni, D. Zerla, I. Rimoldi
FULL PAPER
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for 30 min; Rt(3-quinuclidinone) = 11.31 min, Rt(R) = 22.78 min,
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(1 equiv.), 4-DMAP (0.5 equiv.) and DCC (1.5 equiv.) were added
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1H NMR (300 MHz, CDCl3): δ = 3.82–3.92 [m, CH, R configura-
tion], 3.93–3.99 [m, CH, S configuration] ppm.
1
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We thank the European Social Found (FSE), Regione Lombardia
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Received: June 13, 2012
Published Online: ᭿
6
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Inorg. Chem. 0000, 0–0

Job/Unit: I20643
/KAP1
Date: 13-08-12 16:19:24
Pages: 7
Activation of Racemic RuII Complexes
Ru Phosphane Complexes
RuII complexes with racemic atropoiso-
meric diphosphanes and 1,2-diphenyl-
ethane-1,2-diamine as ligands have been
synthesised. trans and cis complexes were
obtained with atropoisomeric ligands of
low basicity. The cis and trans isomers were
completely separated and their use in the
asymmetric reduction of ketones was
evaluated.
G. Facchetti, E. Cesarotti, M. Pellizzoni,
D. Zerla, I. Rimoldi* ........................ 1–7
“In situ” Activation of Racemic RuII Com-
plexes: Separation of trans and cis Species
and Their Application in Asymmetric Re-
duction
Keywords: Homogeneous catalysis / Asym-
metric catalysis / Ruthenium / Phosphane
ligands / Reduction / Hydrogenation /
Atropoisomerism
Eur. J. Inorg. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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7