Ruthenium(II) complexes bearing (NNN) ligand: Catalytic evaluation of different solvent-mediated coordination modes

Article abstract of DOI:10.1139/cjc-2017-0487

A new (NNN) tridentate ligand was prepared, and its ability to coordinate ruthenium(II) was evaluated. The presence of different functional groups on the ligand allows bi-or tri-coordinated complexes to be obtained depending on complexation conditions. Th

Full text of DOI:10.1139/cjc-2017-0487

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Ruthenium(II) complexes bearing (NNN) ligand: catalytic
evaluation of different solvent-mediated coordination modes
Sara Pellegrino,a Giorgio Facchetti,a Raffella Gandolfi,a Marco Fusè,b Emanuela Erba,a
Isabella Rimoldia*
a Dipartimento di Scienze Farmaceutiche, Università degli Studi di Milano, Via Venezian 21, 20133 Milano,
Italy
bScuola Normale Superiore, Piazza dei Cavalieri 7, 56126 Pisa, Italy
*Corresponding author: isabella.rimoldi@unimi.it
Tel. +39.02.503.14609. Fax.+39.02.503.14615
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ABSTRACT
A new (NNN) tridentate ligand was prepared and its ability to coordinate ruthenium(II) was
evaluated. The presence of different functional groups on the ligand allowed to obtain biꢀ
or triꢀ coordinated complexes depending on complexation conditions. The catalytic activity
of both bidentate and tridentate complexes was studied in asymmetric transfer
hydrogenation of different aryl ketones showing a comparable behavior of the two
complexes in terms of efficiency and stereoselectivity.
Keywords: tridentate ligand, asymmetric hydrogen transfer, asymmetric ketones
reduction.
1. INTRODUCTION
The importance of chirality is widely recognized in fine chemistry, especially in the
pharmaceutical, pesticides and food additives industries. The isolation of a chiral
compound from a racemic mixture is challenging because it requires the separation of
enantiomers. This process is not trivial and in addition half of the product could be lost if
not reꢀconvertible or usable as buildingꢀblock for another synthetic pathway. In this
context, the asymmetric catalysis is one of the best methods to introduce one or more
stereocenters in bioactive molecules.1ꢀ2 The investigation of new stereocontrolled
syntheses by transition metal catalysts modified by incorporating chiral ligands is thus of
wideꢀspreading importance.3ꢀ4
In the last decades, the monosulfonated diamines have been suggested among other
ligands as a very versatile and promising category in homogeneous catalysis.5ꢀ6 Many
ruthenium complexes have been reported and found useful in the stereoselective
reduction of carbonyls in homogeneous phase.7 In many examples, ligand structures are
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based on a twoꢀcarbonꢀatom chain with two nitrogen substituents in the antiꢀposition (1,2
diamine).8ꢀ10 On the other hand, there is a great interest in transition metal complexes with
tridentate amine ligands, especially those containing a pyridine due to its unique electronic
and steric properties.8, 11ꢀ17 Some of them have good efficiency in the catalytic epoxidation
reaction18ꢀ19 and in transfer hydrogenation of aryl ketones.20
Starting from this consideration here is reported the synthesis of a new tridentate ligand 1
(Figure 1) and the study of its different coordination modes to a ruthenium metal center.
Recently we studied the introduction of an unnatural βꢀaminoacidic skeleton in a
octapeptide used as ligand in a Cu(II) complex containing the same pyrrolidineꢀpiperidine
structure as in the compound reported in Figure 1.21 In principle the presence of different
functional groups on compound 1 could allow to obtain biꢀ or triꢀcoordinated complexes
depending on solvent and on additive choice thus leading to the possibility to investigate
the catalytic performance of the different complexes in asymmetric transfer hydrogenation
of aryl ketones.
Figure 1. (NNN) ligand
2. EXPERIMENTAL
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1
2.1. General: H and 13C NMR spectra were recorded in CDCl3 or CD3OD on Bruker
DRX Avance (300 and 75 MHz) equipped with a nonꢀreverse probe. Chemical shifts (in
ppm) were referenced to residual solvent proton/carbon peak. Polarimetry analyses were
carried out on Perkin Elmer 343 Plus equipped with Na/Hal lamp. MS analyses were
performed by using a Thermo Finnigan (MA, USA) LCQ Advantage system MS
spectrometer with an electronspray ionization source and an ‘Ion Trap’ mass analyzer. The
MS spectra were obtained by direct infusion of a sample solution in MeOH under
ionization, ESI positive. Catalytic reactions were monitored by gas chromatography
analysis using a chiral stationary phase column (MEGA DMT β, 25 m, internal diameter
0.25 mm) or by HPLC analysis with MerckꢀHitachi Lꢀ7100 equipped with Detector
UV6000LP and chiral column (ODꢀH or OJꢀH Chiralcel). Commercially reagent grade
solvents were dried according to standard procedures and freshly distilled under nitrogen
before use.
2.2. (S)-1-[(3R,4R)-1-benzyl-4-(4-tosylamido)-piperidin-3-yl]pyrrolidine-2-
carboxamide 3: Pyridine (0.14 mL, 1.75 mmol), diꢀtertꢀbutyl dicarbonate (0.687 g, 3.15
mmol) and (NH4)2CO3 (0.37 g, 3.85 mmol) were added to a solution of ((3R,4R)ꢀ1ꢀbenzylꢀ
4ꢀ((4ꢀmethylphenyl)sulfonamido)piperidinꢀ3ꢀyl)ꢀLꢀproline 222 (0.8 g, 1.7 mmol) in DMF (10
mL) . The reaction mixture was stirred for 24 h at room temperature then the solvent was
removed under vacuum. The residue, taken up in CH2Cl2 (15 mL), was washed twice with
a NaCl saturated solution. The organic layer was dried on Na2SO4 and the solvent was
removed under vacuum affording compound 3. Yield 85%, yellow powder. mp 109ꢀ112°C
1
(from Et2O); [α]D =+ 19,6 (c=0.23, CHCl3), MS (ESI) m/z = 457,4[M+H]+; H NMR (300
MHz, CDCl3) δ 1.25ꢀ1.70 (m, 3H), 1.75ꢀ1.84 (m, 2H), 1.95ꢀ2.12 (m, 1H), 2.25ꢀ2.76 (m,
5H), 2.42 (s, 3H), 2.81ꢀ3.05 (m, 1H), 3.12ꢀ3.20 (m, 2H), 3.30ꢀ3.41(m, 1H), 3.74ꢀ3.88
13
(m,2H), 2.22ꢀ7.80 (m, 9H) ppm; C NMR (75MHz, CDCl3) δ 20.4 (CH3), 24.5 (CH2), 30.9
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(CH2), 31.2 (CH2), 45.7 (CH2), 51.1 (CH2), 51.3 (CH2), 52.8 (CH), 59.4 (CH), 62.0 (CH2),
63.6 (CH), 127.1 (CH), 128.5 (CH), 128.7 (CH), 129.8 (CH), 130.2 (CH), 138.5 (C), 143.8
(C), 134.5 (C), 179.8 (C) ppm. Elemental analysis: calcd. for C24H32N4O3S C, 63.13; H,
7.06; N, 12.27; found C, 63.00; H, 7.18; N, 12.08.
2.3. N-(3R,4R)-3-[(S)-2-(aminomethyl)pyrrolidin-1-yl]-1-benzylpiperidin-4-yl-4-
tosylamide 1: RedꢀAl 60% solution in toluene (2.21 mL, 6.57 mmol) was added to a
solution of carboxamide 3 (0.5 g, 1.1 mmol) in toluene (10 mL). The solution was refluxed
under N2 atmosphere for 1,5 h (TLC analysis: CH2Cl2/CH3OH 10:1). The reaction mixture
was poured into the ice, the obtained precipitate was filtered off. The precipitate,
solubilized in 20 mL of ethyl acetate, was washed with water. The organic phases were
acidified with 0.1N HCl until pH 3 and the phase separated. The acid aqueous solution
was then pH was raised to 8 with a saturated NaHCO3 solution and extracted with ethyl
acetate, dried with Na2SO4 and evaporated. The crude was purified by RPꢀHPLC using a
gradient elution of 95–30% solvent A (solvent A: water/acetonitrile/trifluoracetic acid 95 : 5
: 0.1; solvent B: water/acetonitrile/trifluoracetic acid 5 : 95 : 0.1) over 20 min at a flow rate
of 20 mL/minꢀ1. The purified compound 1 was freezeꢀdried and stored at 0 °C. Yield 40%,
1
white solid, mp 35ꢀ40°C; [α]D = ꢀ49,6 (c=0.26 , CHCl3); MS (ESI) m/z = 443,3[M+H]+; H
NMR (300 MHz, CDCl3) δ 1.25ꢀ2.56 (m, 10H), 2.42 (s, CH3), 2.61ꢀ2.98 (m, 7H), 3.42ꢀ3.58
(m, 2H), 7.21ꢀ7ꢀ82 (m, 9H) ppm; 13C NMR (75MHz, CDCl3) δ 21.9 (CH3), 23.9 (CH2), 29.0
(CH2), 33.2 (CH2), 45.1 (CH2), 45.4 (CH2), 52.2 (CH2), 52.3 (CH2), 54.5 (CH), 58.4 (CH),
60.5 (CH), 63.5 (CH2), 127.5 (CH), 128.3 (CH), 129.3 (CH), 129.7 (CH), 129.9 (CH), 138.3
(C), 138.4 (C), 143.1 (C) ppm. Elemental Analysis: calcd. for C24H34N4O2S C, 65.13; H,
7.74; N, 12.66; found C, 65.02; H, 7.92; N, 12.48.
2.4. Synthesis of complex A: In a 10 mL Schlenk tube, the ligand (1.1 eq) was added
to a solution of [RuCl2(pꢀcymene)]2 (0.5 eq) in 5 mL of 2ꢀpropanol under argon atmosphere
and stirred for 5 hours at 85°C. After cooling to room temperature, a yellow precipitate has
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been formed. The solid was filtered and washed with diethyl ether; finally, the precipitate
was dried under vacuum. Quantitative yield, reddish solid; MS (ESI) of C34H47Cl2N4O2RuS
[MꢀCl] (m/z): calcd. 713.22, found 713.3 [M], 677.4 [MꢀCl]; 1H NMR (CD3Cl, 300 MHz): δ =
1.18ꢀ1.28 (m, 10H), 2.04ꢀ2.09 (m, 4H), 2.15 (s, 3H), 2.27 (s, 3H), 2.35ꢀ2.37 (m, 3H), 2.38ꢀ
2.40 (m, 4H), 2.89ꢀ2.91(m, 2H), 2.94ꢀ3.04(m, 2H), 3.46ꢀ3.48 (m, 2H), 4.10ꢀ4.12 (m, 1H),
5.32ꢀ5.34 (m, 2H), 5.46ꢀ5.48 (m, 2H), 7.16ꢀ7.37 (m, 7H), 7.70 (d, J = 8.1 Hz, 2H) ppm;
Elemental Analysis: calcd. for C34H47Cl2N4O2RuS C, 54.54; H, 6.46; N, 7.48; found C,
54.98; H, 6.58; N, 7.51.
2.5. Synthesis of complex B: In a 10 mL Schlenk tube, the ligand (1.1 eq) and TEA (2
eq) were dissolved in 5 mL of toluene. The dimer [RuCl2(pꢀcymene)]2 (0.5 eq) was added
and the suspension was stirred for 3 h at room temperature. Then the orange solution was
refluxed for 1 h and during this period the solution became yellowꢀorange. After cooling to
room temperature, a yellow precipitate has been formed. The solid was filtered and
washed, first with water and then with diethyl ether; finally, the precipitate was dried under
vacuum. Quantitative yield, brown solid; MS (ESI) of C48H66Cl4N8O4Ru2S2 (m/z): calcd.
1230.15, found 543.4 [(MꢀC):2]l;1H NMR (CD3OD, 300 MHz): δ = 0.83ꢀ1.2 (m, 1H), 1.21ꢀ
1.25 (m, 2H), 1.40ꢀ1.48 (m, 2H), 1.49ꢀ1.53 (m, 2H), 1.68ꢀ2.10 (m, 2H), 2.53 (s, 2H), 2.58ꢀ
2.90 (m, 4H), 3.16ꢀ3.23 (m, 4H), 3.53ꢀ3.70 (m, 5H), 3.82ꢀ4.01 (m, 1H), 7.13ꢀ7.37 (m, 5H),
7.76ꢀ7.81 (m, 2H), 8.47ꢀ8.61 (m, 1H) ppm; Elemental Analysis: calcd. for
C48H66Cl4N8O4Ru2S2 C, 46.98; H, 5.42; N, 9.13; found C, 45.94; H, 5.13; N, 9.04.
2.6. General procedure for asymmetric transfer hydrogenation (ATH): In a Schlenk
tube sealed under argon, ketone (1 mmol) was added to the Ruꢀcomplex (A or B) (5 x 10ꢀ3
mmol) followed by 1.5 mL of solvent and hydrogen donor (10 mmol). The solution was
stirred for 24 h at 40°C. The conversion and enantioselectivity were evaluated by chiral GC
or HPLC analysis.23ꢀ25
GC analysis condition for 4a: iso 120°C, rtR=11 min., rtS=12 min.
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HPLC condition for 4b: column: ODꢀH Chiralcel, hexane: ethanol = 95:5, flow = 0.8
mL/min, λ = 216 nm: rtR = 12.6 min, rtS = 15.8 min; for 4c: ODꢀH Chiralcel, hexane: ethanol
= 98:2, flow = 0.8 mL/min, λ = 220 nm: rtS = 16.1 min, rtR = 17.2 min; for 4d: ODꢀH
Chiralcel, hexane: ethanol = 95:5, flow = 1.0 mL/min, λ = 220 nm: rtR 11.9, rtS =12.7 min;
for 4e: ODꢀH Chiralcel, hexane: 2ꢀpropanol = 95:5, flow = 1.0 mL/min, λ = 230 nm: rtR
=6.5, rtS =7.5 min; for 4f: ODꢀH Chiralcel, hexane: ethanol = 95:5, flow = 0.8 mL/min, λ =
216 nm: rtR = 13.9 min, rtS = 14.6 min; for 4g: OJꢀH Chiralcel, eluent: hexane: 2ꢀpropanol =
90:10, flow = 1.0 mL/min, λ = 216 nm: rtS = 23.4 min, rtR = 29.7 min.
3. RESULTS and DISCUSSION
Scheme 1. Synthesis of (NNN) ligand 1
Compound 1 was synthesized starting from known acid 2 that was obtained in good yields
through a multicomponent reaction as recently described elsewhere.22 Compound 2 was at
first transformed in carboxamide 3 (85%) by reaction with diꢀtertꢀbutylꢀdicarbonate (1.8 eq),
ammonium carbonate (2.2 eq) and pyridine (1 eq) in DMF. The intermediate 3 was turned
into the final tridentate ligand 1 (40%) by reduction with bis(2ꢀmethoxyethoxy) aluminum
hydride (6.5:1 molar ratio) in toluene solution at reflux temperature (Scheme 1).
The Ru(II) complexes bearing the tridentate ligand were synthesized using two different
methodologies: in the first case the use of 2ꢀpropanol, a protic and polar solvent in
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absence of a base, at reflux for 5 h allowed to obtain a bidentate coordination involving the
two over three more nucleophilic amino functions leaving the one bearing the sulfonic
moiety aside. In the second method, the synthesis of the complex was realized in toluene
for 3 h in presence of 2 equivalents of TEA employing in this case an aprotic apolar
solvent in presence of a base with the aim of involving in coordination all the three amino
functions (Scheme 2). Either the use of 2ꢀpropanol in presence of TEA or only toluene led
the formation of complex which involved heterogeneously the three N atoms.
Scheme 2. Synthetic pathways of Ru(II) complexes.
1
As confirmed by HꢀNMR and ESI spectroscopy investigations two different complexes A
1
and B were formed bearing a bidentate or tridentate ligand.26ꢀ28 In the HꢀNMR spectra of
complex A the presence of the pꢀcymene ring as evinced by the two multiplet signals at
5.32ꢀ5.34 and 5.46ꢀ5.48 ppm for the aromatic protons, confirmed a bidentate coordination
mode. When the reaction takes place in the absence of a base, we can exclude the
involvement of the tosylamine Na in the coordination of the metal center. It is likely, thus,
that the possible coordination mode preferentially involves the Nb and Nc of methylaminoꢀ
proline moiety. In this way, a more stable fiveꢀmembered ring at the metal center is
obtained.
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On the contrary, in the presence of TEA and toluene, the tridentate complex B is obtained
1
as evinced by the absence of the peaks belonging to pꢀcymene group in the HꢀNMR
spectrum. Satisfactory elemental analyses and ESIꢀMS data corresponding to the
proposed structures were obtained for both complexes.
Considering the distinctive features of the complexes here proposed, we then evaluated
their capability to be used as precatalysts in asymmetric transfer hydrogenation of different
aryl ketones (Table 1).29
Table 1: ATH of different substituted aryl ketones.
Entry[a] Substrate
H donor
HCOOH
Reaction solvent Catalyst Conversion[b] e.e.
1
2
3
H2O
H2O
63%
ꢀ
17%
ꢀ
HCOOH/TEA
HCOONa
HCOOH
A
B
H2O
85%
ꢀ
81%
ꢀ
4
5
4a
H2O
HCOONa
HCOONa
HCOONa
HCOOH
H2O
63%
65%
54%
30%
45%
22%
30%
ꢀ
44%
70%
82%
33%
58%
5%
15%
ꢀ
6
H2O/MeOH 1:1
2ꢀpropanol
H2O
7
8
9
HCOONa
HCOONa
HCOONa
HCOOH
H2O
A
B
10
11
12
4b
H2O/MeOH 1:1
2ꢀpropanol
H2O
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13
14
15
16
17
18
19
20
21
22
23
HCOONa
HCOOH
H2O
H2O
35%
65%
55%
48%
20%
35%
23%
20%
32%
67%
90%
54%
ꢀ
HCOONa
HCOONa
HCOONa
HCOONa
HCOONa
HCOONa
HCOONa
HCOONa
HCOOH
H2O
A
B
9%
33%
2%
ꢀ
2ꢀpropanol
H2O
4c
H2O/MeOH 1:1
2ꢀpropanol
H2O
22%
ꢀ
4d
4e
4f
A
A
A
H2O
31%
96%
12%
H2O
H2O
4g
24
HCOONa
H2O
>99%
28%
A
[a]Reactions were carried out at 40°C using 1 mmol of substrate with 0.5 mol % of ruthenium complex in 2 mL of solvent with 10
equivalents of HCOOH, HCOONa or HCOOH/TEA azeotropic mixture as hydrogen donors. [b] Conversion and e.e. were determined by
GC and by HPLC after 24 h.
The catalysts performance was evaluated using different reaction conditions (solvent,
temperature) and different hydrogen donors (HCOOH, HCOONa, azeotropic mixture
5:2=TEA:HCOOH).
Water was found as the best solvent for carrying out the reaction. Indeed, when 2ꢀ
propanol or the mixture H2O/MeOH were employed the reaction conversion significantly
decreased (Table 1, entries 6, 7, 10, 11, 16, 18 and 19). Only in the case of complex B, it
is worth noting that the enantiomeric excess in the reduction of acetophenone resulted
increased under these conditions (entries 6 and 7 vs 5). The temperature variation (20°C,
40°C or 60°C) did not show any significant effect on enantioselectivity (data not shown).
Regarding the hydrogen donors, HCOONa resulted the more effective in terms of
enantioselectivity, in a ratio 10:1 with the substrate. On the contrary, using HCOOH, the
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reaction didn’t proceed with complex B (entries 4 and 12) while in the case of complex A,
a racemic mixture or endowed with a low e.e. of the product was obtained (entries 1 vs 3,
8 vs 9, 14 vs 15 and 23 vs 24).
The comparison of different catalytic systems revealed that TOF (turnover frequency) for
the pꢀcymeneꢀcontaining complex A is 7 hꢀ1 similarly to 5 hꢀ1 for dimer complex B
(calculated for ATH of acetophenone in water and in the presence of HCOONa as
hydrogen donor, Table 1 entry 3 vs entry 5). The corresponding alcohol was achieved in
good yield by both catalytic systems but with modest enantioselectivity in the case of dimer
B.12, 30
The cooperation of the metal hydride and the amine nitrogen hydrogen functions in the
ATH of ketones and imines with 2ꢀpropanol or triethylammonium formate as the hydrogen
source, was a key discovery by Noyori group and this represented an outstanding example
of outerꢀsphere mechanism.31ꢀ34 This last one remains the generally accepted mechanism
for hydrogenꢀtransfer step in the case of complex A, in which only two nitrogen atoms
resulted coordinated to metal center.23, 35ꢀ36
In the case of complex B, in which there are three functional groups coordinated, the
formation of dimer afforded two 16ꢀelectron ruthenium precatalysts that might rearrange in
the formation of the active hydride species.
In spite of the loss of pꢀcymene moiety, the mechanism of ATH probably involved, also in
this case, a classical catalytic cycle.37ꢀ40
Taking into consideration the differences in both structural coordination mode, our
complexes resulted less active and straightly less stereoselective in comparison with other
similar catalytic systems reported in literature.16, 35, 41ꢀ42 In those systems better results
might depend on the presence of an additive in formation of bimetallic 6ꢀmembered
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transition state or in alternative on the presence of an additional phosphine ligand known
for reducing the acidity of metal center that favors the hydride transfer. Furthermore, the
results obtained with our complexes, indicated that the steric hindrance around the Ru
center in the transition state, deriving both from the ligand and the substrate, could affect
the reactivity and the enantioselectivity of the reactions.27, 37
In summary, the best result in terms of reaction rate and enantioselectivity was obtained
with complex A in the reduction of the activated ketone substrate 4f, ethyl 3ꢀoxoꢀ3ꢀ
phenylpropanoate (entry 22).
4. CONCLUSION
In conclusion, we developed a new (NNN) compound able to be used as ligand in
ruthenium(II) complexes. Depending on complexation conditions, it was possible to obtain
a biꢀ or a triꢀdentate coordinated complex. The catalytic activity in asymmetric transfer
hydrogenation shown by the tridentate complex B could be compared to areneꢀRu(II)
complexes (bidentate complex A) only in terms of reactivity whereas stereoselection is
influenced by the reaction conditions and the substituents on aromatic ketones.
REFERENCES
1.
industrial applications. Curr Opin Drug Discov Devel 2010, 13 (6), 698ꢀ716.
2. Lühr, S.; Holz, J.; Börner, A., The Synthesis of Chiral Phosphorus Ligands for use in
Homogeneous Metal Catalysis. ChemCatChem 2011, 3 (11), 1708ꢀ1730.
3. Cesarotti, E.; Rimoldi, I.; Spalluto, P.; Demartin, F., Chiral 1,4ꢀbisꢀdiphosphine ligands from
optically active (Z)ꢀolefins. Tetrahedron: Asymmetry 2007, 18, 1278ꢀ1283.
4. Cesarotti, E.; Abbiati, G.; Rossi, E.; Spalluto, P.; Rimoldi, I., DIOPHEP, a chiral
Palmer, A.; ZanottiꢀGerosa, A., Homogeneous asymmetric hydrogenation: recent trends and
diastereoisomeric bisphosphine ligand: synthesis and applications in asymmetric hydrogenations.
Tetrahedron: Asymmetry 2008, 19 (14), 1654ꢀ1659.
12

Page 13 of 15
5.
Itsuno, S.; Takahashi, S., Synthesis of Chiral Polyamides Containing an (R,R)ꢀ1,2ꢀ
Diphenylethylenediamine Monosulfonamide Structure and Their Application to Asymmetric
Transfer Hydrogenation Catalysis. ChemCatChem 2017, 9 (3), 385ꢀ388.
6.
Doucet, H.; Ohkuma, T.; Murata, K.; Yokozawa, T.; Kozawa, M.; Katayama, E.; England,
A. F.; Ikariya, T.; Noyori, R., transꢀ[RuCl2(phosphane)2(1,2ꢀdiamine)] and Chiral transꢀ
[RuCl2(diphosphane)(1,2ꢀdiamine)]: ShelfꢀStable Precatalysts for the Rapid, Productive, and
Stereoselective Hydrogenation of Ketones. Angew. Chem. Int. Ed. 1998, 37 (12), 1703ꢀ1707.
7.
Clapham, S. E.; Hadzovic, A.; Morris, R. H., Mechanisms of the H2ꢀhydrogenation and
transfer hydrogenation of polar bonds catalyzed by ruthenium hydride complexes. Coord. Chem.
Rev. 2004, 248 (21), 2201ꢀ2237.
8.
Darwish, M. O.; Wallace, A.; Clarkson, G. J.; Wills, M., Use of tridentate TsDPEN/pyridine
ligands in rutheniumꢀcatalysed asymmetric reduction of ketones. Tetrahedron Lett. 2013, 54 (32),
4250ꢀ4253.
9.
hydrogenation of aromatic ketones in water. Org. Biomol. Chem. 2004, 2 (13), 1818ꢀ1821.
10. Liu, X.; Zhang, T.; Hu, Y.; Shen, L., Asymmetric Transfer Hydrogenation of Aromatic
Wu, X.; Li, X.; Hems, W.; King, F.; Xiao, J., Accelerated asymmetric transfer
Ketones Catalyzed by New Chiral C2ꢀSymmetric Bis(sulfonyl) tetraaza Ligands Complexed with
[Ru(η 6ꢀpꢀcymene)Cl2]2 in Water. Catal Lett 2014, 144 (7), 1ꢀ7.
11.
Dayan, O.; Çetinkaya, B., Monoꢀ and binuclear ruthenium(II) complexes containing
pyridineꢀ2,6ꢀdiimine (Pydim) ligands: Synthesis, characterization and catalytic activity in the
transfer hydrogenation of acetophenone. J. Mol. Catal. A: Chem. 2007, 271 (1ꢀ2), 134ꢀ141.
12.
Yamamura, T.; Nakane, S.; Nomura, Y.; Tanaka, S.; Kitamura, M., Development of an
axially chiral sp3P/sp3NH/sp2Nꢀcombined linear tridentate ligand—facꢀselective formation of
Ru(II) complexes and application to ketone hydrogenation. Tetrahedron 2016, 72 (26), 3781ꢀ3789.
13.
Matesanz, A. I.; Hernández, C.; Perles, J.; Souza, P., Synthesis and crystal structure of a
novel ruthenium(II) complex with in situ generated dithiobiurea ligand. J. Organomet. Chem. 2016,
804, 13ꢀ17.
14.
Zhang, Y.; Liu, L.; Cao, X.; Zhao, J., Synthesis, single crystal structure and efficient
catalysis for alcohol oxidation of a novel Ru(II) complex with both a N,N,Nꢀtridentate ligand and a
pyridinedicarboxylate. Polyhedron 2016, 105, 170ꢀ177.
15.
Johnson, T. C.; Totty, W. G.; Wills, M., Application of Ruthenium Complexes of Triazoleꢀ
Containing Tridentate Ligands to Asymmetric Transfer Hydrogenation of Ketones. Org. Lett. 2012,
14 (20), 5230ꢀ5233.
16.
Du, W.; Wang, Q.; Yu, Z., Ru(II) pyridylꢀbased NNN complex catalysts for (asymmetric)
transfer hydrogenation of ketones at room temperature. Chinese Journal of Catalysis 2013, 34 (7),
1373ꢀ1377.
17.
Boukachabia, M.; Vriamont, N.; Lambin, D.; Riant, O.; AribiꢀZouioueche, L., Screening of
a library of hemisalen ligands in asymmetric Hꢀtransfer: Reduction of aromatic ketones in water. .
Comptes Rendus Chimie 2014, 17 (5), 403ꢀ412.
18.
Serrano, I.; López, M. I.; Ferrer, Í.; Poater, A.; Parella, T.; Fontrodona, X.; Solà, M.; Llobet,
A.; Rodríguez, M.; Romero, I., New Ru(II) Complexes Containing Oxazoline Ligands As
Epoxidation Catalysts. Influence of the Substituents on the Catalytic Performance. Inorg. Chem.
2011, 50 (13), 6044ꢀ6054.
19.
Britovsek, G. J. P.; England, J.; Spitzmesser, S. K.; White, A. J. P.; Williams, D. J.,
Synthesis of iron(ii), manganese(ii) cobalt(ii) and ruthenium(ii) complexes containing tridentate
nitrogen ligands and their application in the catalytic oxidation of alkanes. Dalton Trans. 2005, (5),
945ꢀ955.
20.
Wang, D.; Astruc, D., The Golden Age of Transfer Hydrogenation. Chem. Rev. 2015, 115
(13), 6621ꢀ6686.
13

Page 14 of 15
21.
Pellegrino, S.; Facchetti, G.; Contini, A.; Gelmi, M. L.; Erba, E.; Gandolfi, R.; Rimoldi, I.,
Ctrꢀ1 Mets7 motif inspiring new peptide ligands for Cu(i)ꢀcatalyzed asymmetric Henry reactions
under green conditions. RSC Advances 2016, 6 (75), 71529ꢀ71533.
22.
Pellegrino, S.; Contini, A.; Gelmi, M. L.; Lo Presti, L.; Soave, R.; Erba, E., Asymmetric
Modular Synthesis of a Semirigid Dipeptide Mimetic by Cascade Cycloaddition/Ring
Rearrangement and Borohydride Reduction. J. Org. Chem. 2014, 79 (7), 3094ꢀ3102.
23.
Zerla, D.; Facchetti, G.; Fuse, M.; Pellizzoni, M.; Castellano, C.; Cesarotti, E.; Gandolfi, R.;
Rimoldi, I., 8ꢀAminoꢀ5,6,7,8ꢀtetrahydroquinolines as ligands in iridium(III) catalysts for the
reduction of aryl ketones by asymmetric transfer hydrogenation (ATH). Tetrahedron: Asymmetry
2014, 25, 1031ꢀ1037.
24.
Facchetti, G.; Gandolfi, R.; Fuse, M.; Zerla, D.; Cesarotti, E.; Pellizzoni, M.; Rimoldi, I.,
Simple 1,3ꢀdiamines and their application as ligands in ruthenium(ii) catalysts for asymmetric
transfer hydrogenation of aryl ketones. New J. Chem. 2015, 39 (5), 3792ꢀ3800.
25.
Rimoldi, I.; Facchetti, G.; Nava, D.; Contente, M. L.; Gandolfi, R., Efficient methodology to
produce a duloxetine precursor using whole cells of Rhodotorula rubra. Tetrahedron: Asymmetry
2016, 27 (9–10), 389ꢀ396.
26.
Dayan, O.; Dayan, S.; Kani, Đ.; Çetinkaya, B., Ruthenium(II) complexes bearing pyridineꢀ
based tridentate and bidentate ligands: catalytic activity for transfer hydrogenation of aryl ketones.
Appl. Organomet. Chem. 2012, 26 (12), 663ꢀ670.
27.
and Their Application in Asymmetric Synthesis. Synthesis 2015, 47 (04), 569ꢀ574.
28. Jarenmark, M.; Carlström, G.; Fredin, L. A.; Hedberg Wallenstein, J.; Doverbratt, I.;
Roszkowski, P.; Małecki, P.; Maurin, J. K.; Czarnocki, Z., Novel (+)ꢀ3ꢀCarene Derivatives
Abrahamsson, M.; Persson, P., Diastereomerization Dynamics of a Bistridentate RuII Complex.
Inorg. Chem. 2016, 55 (6), 3015ꢀ3022.
29.
Watanabe, M.; Murata, K.; Ikariya, T., Practical Synthesis of Optically Active Amino
Alcohols via Asymmetric Transfer Hydrogenation of Functionalized Aromatic Ketones. J. Org.
Chem. 2002, 67 (5), 1712ꢀ1715.
30.
Aliende, C.; PérezꢀManrique, M.; Jalón, F. A.; Manzano, B. R.; Rodrıguez, A. M.; Espino,
́
G., Arene Ruthenium Complexes as Versatile Catalysts in Water in both Transfer Hydrogenation of
Ketones and Oxidation of Alcohols. Selective Deuterium Labeling of racꢀ1ꢀPhenylethanol.
Organometallics 2012, 31 (17), 6106ꢀ6123.
31.
Zhou, Z.; Ma, Q.; Sun, Y.; Zhang, A.; Li, L., Ruthenium(II)ꢀcatalyzed asymmetric transfer
hydrogenation of aromatic ketones in water using novel waterꢀsoluble chiral monosulfonamide
ligands. Heteroatom Chemistry 2010, 21 (7), 505ꢀ514.
32.
Matsuoka, A.; Sandoval, C. A.; Uchiyama, M.; Noyori, R.; Naka, H., Why pꢀCymene?
Conformational Effect in Asymmetric Hydrogenation of Aromatic Ketones with a η6ꢀ
Arene/Ruthenium(II) Catalyst. Chemistry – An Asian Journal 2015, 10 (1), 112ꢀ115.
33.
Wu, X.; Liu, J.; Di Tommaso, D.; Iggo, J. A.; Catlow, C. R. A.; Bacsa, J.; Xiao, J., A
Multilateral Mechanistic Study into Asymmetric Transfer Hydrogenation in Water. Chem. Eur. J.
2008, 14 (25), 7699ꢀ7715.
34.
Sandoval, C. A.; Ohkuma, T.; Utsumi, N.; Tsutsumi, K.; Murata, K.; Noyori, R., Mechanism
of Asymmetric Hydrogenation of Acetophenone Catalyzed by Chiral η6ꢀArene–Nꢀ
Tosylethylenediamine–Ruthenium(II) Complexes. Chemistry – An Asian Journal 2006, 1 (1ꢀ2),
102ꢀ110.
35.
Li, X.ꢀN.; Zhou, H.ꢀY.; Feng, L.; Duan, K.; Wang, J.ꢀX., Temperatureꢀtuned
enantioselectivity in transfer hydrogenation: preparation and catalytic property of amino acidꢀ
modified benzimidazole. Appl. Organomet. Chem. 2012, 26 (4), 168ꢀ174.
36.
VázquezꢀVilla, H.; Reber, S.; Ariger, M. A.; Carreira, E. M., Iridium Diamine Catalyst for
the Asymmetric Transfer Hydrogenation of Ketones. Angew. Chem. Int. Ed. 2011, 50 (38), 8979ꢀ
8981.
14

Page 15 of 15
37.
Ito, J.ꢀi.; Sugino, K.; Matsushima, S.; Sakaguchi, H.; Iwata, H.; Ishihara, T.; Nishiyama, H.,
Synthesis of NHCꢀOxazoline Pincer Complexes of Rh and Ru and Their Catalytic Activity for
Hydrogenation and Conjugate Reduction. Organometallics 2016, 35 (11), 1885ꢀ1894.
38.
Wettergren, J.; Buitrago, E.; Ryberg, P.; Adolfsson, H., Mechanistic Investigations into the
Asymmetric Transfer Hydrogenation of Ketones Catalyzed by PseudoꢀDipeptide Ruthenium
Complexes. Chem. Eur. J. 2009, 15 (23), 5709ꢀ5718.
39.
Bøgevig, A.; Pastor, I. M.; Adolfsson, H., Highly Enantioselective RutheniumꢀCatalyzed
Reduction of Ketones Employing Readily Available Peptide Ligands. Chem. Eur. J. 2004, 10 (1),
294ꢀ302.
40.
Margalef, J.; Slagbrand, T.; Tinnis, F.; Adolfsson, H.; Diéguez, M.; Pàmies, O., Thirdꢀ
Generation Amino Acid FuranosideꢀBased Ligands from dꢀMannose for the Asymmetric Transfer
Hydrogenation of Ketones: Catalysts with an Exceptionally Wide Substrate Scope. Adv. Synth.
Catal. 2016, 358 (24), 4006ꢀ4018.
41.
ketones in ethanol. Tetrahedron Lett. 2011, 52 (21), 2754ꢀ2758.
42. Slagbrand, T.; Lundberg, H.; Adolfsson, H., RutheniumꢀCatalyzed Tandemꢀ
Lundberg, H.; Adolfsson, H., Rutheniumꢀcatalyzed asymmetric transfer hydrogenation of
Isomerization/Asymmetric Transfer Hydrogenation of Allylic Alcohols. Chem. Eur. J. 2014, 20
(49), 16102ꢀ16106.
15