A new class of well-defined ruthenium catalysts for enantioselective transfer hydrogenation of various ketones

Article abstract of DOI:10.1016/j.jorganchem.2018.06.002

A pair of novel optically pure phosphinite ligands were synthesized by ring opening reaction of chiral amines with (R)-styrene oxide or (S)-glycidyl phenyl ether oxide using a straightforward method in high yields and their ruthenium complexes were described in detail. The ruthenium complexes proved to be highly efficient catalysts for the enantioselective hydrogenation of ketones, affording products up to 99% ee. The results showed that the corresponding chiral alcohols could be obtained with high activity and excellent enantioselectivities at the desired temperature. (2S)-1-{benzyl[(1S)-1-(naphthalen-1-yl)ethyl]amino}-3-phenoxypropan-2-yl diphenylphosphinito[dichloro(η⁶-benzene)ruthenium (II)] acts an excellent catalyst in the reduction of ketones, giving the corresponding alcohol up to 99% ee.

Full text of DOI:10.1016/j.jorganchem.2018.06.002

Accepted Manuscript
A new class of well-defined ruthenium catalysts for enantioselective transfer
hydrogenation of various ketones
Cezmi Kayan, Nermin Meriç, Khadichakhan Rafikova, Alexey Zazybin, Nevin Gürbüz,
Mehmet Karakaplan, Murat Aydemir
PII:
S0022-328X(18)30443-1
10.1016/j.jorganchem.2018.06.002
JOM 20461
DOI:
Reference:
To appear in: Journal of Organometallic Chemistry
Received Date: 12 April 2018
Revised Date: 30 May 2018
Accepted Date: 1 June 2018
Please cite this article as: C. Kayan, N. Meriç, K. Rafikova, A. Zazybin, N. Gürbüz, M. Karakaplan, M.
Aydemir, A new class of well-defined ruthenium catalysts for enantioselective transfer hydrogenation of
various ketones, Journal of Organometallic Chemistry (2018), doi: 10.1016/j.jorganchem.2018.06.002.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT
1
2
3
A New Class of Well-Defined Ruthenium Catalysts for Enantioselective Transfer
Hydrogenation of Various Ketones
∗
,a
a
b ,c
b,c
d
4
5
Cezmi Kayan , Nermin Meriç , Khadichakhan Rafikova , Alexey Zazybin , Nevin Gürbüz ,
a
,a
Mehmet Karakaplan , Murat Aydemir*
6
7
a
Department of Chemistry, Faculty of Science, University of Dicle, 21280 Diyarbakir, Turkey
Satbayev University, Institute of chemical and biological technologies, Almaty, Kazakhstan
Kazakh-British Technical University, School of Chemical Engineering, Almaty, Kazakhstan
Department of Chemistry, Faculty of Science, University of İnönü, 44280 Malatya, Turkey
b
8
9
0
1
2
c
d
1
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
3
4
5
6
7
8
9
0
1
2
3
4
5
ABSTRACT
A pair of novel optically pure phosphinite ligands were synthesized by ring opening reaction of
chiral amines with (R)-styrene oxide or (S)-glycidyl phenyl ether oxide using a straightforward
method in high yields and their ruthenium complexes were described in detail. The ruthenium
complexes proved to be highly efficient catalysts for the enenatioselective hydrogenation of
ketones, affording products up to 99% ee. The results showed that the corresponding chiral
alcohols could be obtained with high activity and excellent enantioselectivities at the desired
temperature.
(2S)-1-{benzyl[(1S)-1-(naphthalen-1-yl)ethyl]amino}-3-phenoxypropan-2-yl
6
diphenylphosphinito[dichloro(η -benzene)ruthenium (II)] acts an excellent catalyst in the
reduction of ketones, giving the corresponding alcohol up to 99% ee
.
Keywords: Asymmetric Transfer Hydrogenation; Chiral Ruthenium Complexes; Phosphinites;
Epoxide Ring opening; Homogeneous Catalysis.
∗
To whom correspondence should be addressed: Department of Chemistry, Dicle University, TR-21280 Diyarbakır, Turkey.
Tel: +90 412 248 8550, Fax: +90 412 248 8300, e-mail: cezmik@dicle.edu.tr, e-mail: aydemir@dicle.edu.tr.
1

ACCEPTED MANUSCRIPT
2
2
2
2
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
4
4
4
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
1. INTRODUCTION
An increasing number of chiral compounds and enantiomerically pure drugs are prepared
through transition metal-catalyzed asymmetric reactions [1]. Since the reactivity and
stereoselectivity of an asymmetric transformation are highly dependent on the structure of the
chiral ligand coordinated to the transition metal, the design and synthesis of efficient chiral
ligands are important in this area and have attracted a great deal of attention both from academia
and industry [2]. For many years, a large number of chiral monodendate and bidendate
phosphorus containing ligands (P,Pꞌ) were widely studied [3,4]. Among the recently developed
transition-metal-based chiral reduction catalysts, the C -symmetric ferrocenyl phosphines were
2
notably reported [5,6,7,8]. Because of its great success in catalytic asymmetric reactions [9],
chiral ferrocenyl-phosphine ligands have attracted considerable attention in recent years [10,11].
These ligands are very efficient for a wide range of reactions, such as hydrogenation [12],
hydrosilylation [13], allylic alkylation [14], palladium catalyzed cross-coupling reactions
[15,16,17] and cyclopropanation [18]. Although ferrocenyl phosphine ligands have found
widespread applications in transition metal catalyzed asymmetric transfer hydrogenation
[19,20,21], the analogous phosphinites have scarcely been reported, which have different
chemical, electronic and structural advantages in comparison with phosphines. For instance, the
metal-phosphorus bond is often stronger in phosphinites compared to the related phosphine due
to the presence of electron-withdrawing P-OR group. In addition, the empty σ*-orbital of the
phosphinite P(OR)R is stabilized, making the phosphinite a better acceptor [22]. The most
2
important advantage of chiral phosphinite ligands over the corresponding P-based ligands is their
facile preparation, which leads to a substantial interest to design highly effective chiral
phosphinite ligands for asymmetric catalysis [23,24,25].
2

ACCEPTED MANUSCRIPT
4
5
5
5
5
5
5
5
5
5
5
6
6
6
6
6
6
6
6
6
6
7
7
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
Catalytic asymmetric transfer hydrogenation (ATH) of ketones has recently emerged as a viable
means of synthesizing chiral alcohols [26]. Due to operational simplicity, the easy availability of
reductants, and the high enantioselectivity, the catalytic enantioselective reduction of ketones has
been extensively studied during the last decades [27]. Particularly, asymmetric transfer
hydrogenation of ketones has recently developed as an alternative method to asymmetric
hydrogenation for the production of chiral alcohols [28,29,30]. Because hydrogen transfer
reactions are mild techniques for reduction of ketones in which a substrate-selective catalyst
transfers hydrogen between the substrate and a hydrogen donor or acceptor, respectively.
Additionally, the donor (e.g. 2-propanol) and the acceptor (e.g. a ketone) are environmentally
friendly and also easy to handle [31,32].
Chiral β-amino alcohols are useful building blocks for biologically active compounds [33] as
well as important auxiliaries and ligands in asymmetric synthesis [34]. Also, amino alcohols
continue to be of importance in modern synthetic chemistry, not only because of their biological
properties, but also due to their wide range of synthetic applications [35]. Hence, the asymmetric
synthesis of enantiomerically enriched amino alcohols has been extensively studied. Especially,
amino alcohol derivative catalysts have received much attention and used in many asymmetric
catalysis reactions, and they have shown powerful utilities in the asymmetric reduction of
prochiral ketones [36,37]. In recent years, we have reported the synthesis and applications of a
number of modified Ru(II) catalysts for ATH which contain well designed groups formed by the
6
reaction of between the chiral ligand component and the η -arene ring [38,39,40,41]. We report
here the synthesis of two novel phosphinite ligands and their application in the Ru(II)-catalyzed
Asymmetric Transfer Hydrogenation of various ketones [42,43,44]. A comparison of the results
obtained with the newly synthesized ligands and those of the corresponding Ru(II) complexes is
3

ACCEPTED MANUSCRIPT
7
7
7
7
7
7
7
7
8
8
8
8
8
8
8
8
8
8
9
9
9
9
9
9
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
5
also discussed. The comparison concerns the structural features of ligands, four of their
ruthenium complexes, and the hydrogenation results.
2. RESULTS AND DISCUSSION
2.1. Synthesis and characterization of the amino alcohols and phosphinite ligands
First of all, the precursor chiral secondary amine, N-benzyl-N-[(S)-1-[α-naphthylethyl]amine (2)
was readily synthesized by the reaction of (S)-(-)-1-[naphthalen-1-yl-ethy]amine with
benzaldehyde with procedures previously described, as shown in Scheme 1 [45,46]. It is well-
known that the regioselective ring opening of epoxides by amines is an important way for the
preparation of β-aminoalcohols [47]. Thus, two novel chiral amino alcohols, 3 and 4, were
synthesized by the ring opening reaction of N-benzyl-N-(S)-1-[α-naphthylethyl]amine 2 with (R)-
styrene oxide or (S)-glycidyl phenyl ether, respectively (Scheme 1) [48]. The products were fully
1
13
characterized by several spectroscopic methods: LC-ESI-IT-TOF MS, H NMR, C NMR and
1
IR as well as elemental analysis. The assignment of the H chemical shifts was derived from 2D
1
3
HH-COSY spectra and the appropriate assignment of the C chemical shifts from APT and 2D
1
HMQC spectra. The results were given in experimental section with full details. Furthermore, H
1
3
NMR, C NMR, IR and LC-ESI-IT-TOF MS spectra of amino alcohols also given in Supporting
Information (SI).
Insert Scheme 1 Here
The synthetic procedure for the preparation of the phosphinite ligands [49] is shown in Scheme
1. Chiral monodendate C -symmetric ligands 5 and 6 were synthesized by hydrogen abstraction
1
from the described chiral amino alcohols by Et N and the subsequent reaction with one
3
equivalent of Ph PCl in anhydrous CH Cl under inert argon atmosphere with the hydrolysis
2
2
2
4

ACCEPTED MANUSCRIPT
9
9
9
9
6
7
8
9
reaction [50]. Typical spectra of these ligands are illustrated in supporting information (SI) and
for details see experimental Section.
Insert Scheme 2 Here
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
00
01 It is well-known that the phosphinite ligands are mostly unstable and decompose gradually to
02 give oxide and the hydrolysis product diphenylphosphinous acid, Ph P(O)H [51]. Furthermore,
2
3
1
1
03 the P-{ H} NMR spectrum displays formation of PPh PPh and P(O)Ph PPh , as indicated by
2
2
2
2
1
04 signals at about δ -15.4 ppm as singlet and δ 35.0 ppm and at δ -21.6 ppm as doublets with J
(PP)
05 226 Hz, respectively [52]. These two compounds are very stable in ambient atmosphere up to 24
06 h because of the well-designed structures. The progress of preparation reactions of the ligands
3
1
1
07 was conveniently monitored by P-{ H} NMR spectroscopy. The signals of the starting material
08 PPh Cl at δ=81.0 ppm disappeared and new singlets appeared downfield due to the phosphinite
2
3
1
1
09 ligands. The P-{ H} NMR spectra of the free ligands are in line with the values previously
10 observed for similar compounds [53,54]. Typical spectra of these ligands are illustrated in Figure
1
13
11 1. The H and C NMR spectra of these ligands are also conclusive. The resonance assignments
1
1
1
13
12 were made on the basis of H- H COSY, NOESY, and H- C COSY experiments. Typical
13 spectra of these ligands are illustrated in supporting information (SI) and for details see
14 experimental Section.
15
16
17
Insert Figure 1 Here
18 Following a similar procedure described by Sawamura, Regadec et al. [55], ruthenium(II)
19 complexes of the phosphinite ligands, (1R)-2-{benzyl[(1S)-1-(naphthalen-1-yl)ethyl]amino}-1-
5

ACCEPTED MANUSCRIPT
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
20 phenylethyl diphenylphosphite, 5 and (2S)-1-{benzyl[(1S)-1-(naphthalen-1-yl)ethyl]amino}-3-
21 phenoxypropan-2-yldiphenyl phosphinite, 6 were readily prepared in quantitative yields by
6
6
22 reacting the appropriate ligands with either [Ru(η -p-cymene)(µ-Cl)Cl] or [Ru(η -benzene)(µ-
2
23 Cl)Cl] precursor as outlined in Scheme 1. The ability of dimers {[Ru(arene)(µ-Cl)Cl] } to form
2
2
6
24 mono- or binuclear complexes of general formula [Ru(η -arene)Cl L] is well-known [56]. For
2
6
25 synthesis of ruthenium(II) complexes 7 and 9, [Ru(η -p-cymene)(µ-Cl)Cl] was initially chosen
2
26 as a starting material, which was prepared from the reaction of the commercially available α-
27 phellandrene(5-isoprophyl-2-methylcyclohexa-1,3-diene) with RuCl [57]. The p-cymene ligand
3
28 is particularly informative with respect to the symmetry of the three legged fragment [58]. One
29 of the most available arene ligands in ruthenium chemistry is p-cymene, whose NMR signals are
6
30 very sensitive to the symmetry of organometallic compound [59]. Thus, when it is η -
1
13
31 coordinated to a ML Lꞌ metal fragment (Cs symmetry), the H and C NMR spectra are very
2
6
32 different from that of η -coordinated to a ML L L fragment (C symmetry) [60]. In this case, the
1
2
3
1
33 steric hindrance of amino alcohol phosphinite ligands seems to prevent free rotation of p-cymene
34 ligand around the arene-Ru axis [61]. In addition, the detailed analysis of NOE interaction
35 between p-cymene and other ligands can give valuable information about the relative orientation
36 of different groups in the molecule and thus establish the stereochemistry of the complex (for
6
37 details see experimental section). After the preparation of the second precursor [Ru(η -
38 benzene)(µ-Cl)Cl] by the reaction cyclo-1.3-hexadiene with RuCl in aqueous solution, we
2
3
6
39 synthesized (2S)-1-{[(1R)-1-phenylethyl]amino}propan-2-yldiphenylphosphinito [dichloro(η -
40 benzene) ruthenium (II)], 8 and (2S)-1-{[(2S)-2-[(diphenylphosphanyl)oxy]propyl][(1R)-1-
6
41 phenylethyl]amino} propan-2-yldiphenylphosphinitobis[dichloro(η -benzene) ruthenium (II)],
42 10 complexes with high yields Scheme 1. The poor solubility of the starting benzene derivative
43 causes a decrease in the yields of the complexes (8 and 10), which are more conveniently
6

ACCEPTED MANUSCRIPT
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
44 prepared by the reaction of the phosphinites with the monomeric adduct [RuCl (C H )(NCCH )]
2
6
6
3
1
45 [62]. Analysis of complexes 8 and 10 by H NMR exhibits multiplet signals corresponding to
46 the aromatic rings for at 8.06-7.58 and 7.94-7.09 ppm and the C H protons as singlets at 4.95
6
6
47 and 5.47 ppm, respectively. The Ru-arene complexes were isolated as indicated by singlets in
3
1
1
48 their P-{ H} NMR spectra at approximately δ 104-111 ppm, in line with the values previously
1
49 observed for similar compounds (Figure 1) [63,64]. H NMR spectra of these compounds clearly
50 exhibit signals corresponding to the aromatic rings. The arene resonances are well resolved, as in
1
3
1
51 the previously reported for mononuclear arene complexes [59]. In the C-{ H} NMR spectra of
3
1
13
52 complexes, J( P- C) coupling constants of the carbons of the phenyl rings were observed,
53 which are in agreement with the literature (for details see experimental Section) [65]. The
54 structure of Ru(II)-complexes were further confirmed by IR spectroscopy as well as
55 microanalysis, and found to be consistent to expected structures.
56 2.2. Catalytic transfer hydrogenation of ketones
57
The admirable catalytic performance and the advanced structural permutability of phosphinite
58 based transition metal complexes prompted us to improve new Ru(II) complexes with well-
59 shaped ligands [66,67]. We paid particular attention to arene ligands [68], because (i) the
60 spectator ligands automatically occupy three adjacent coordination sites of ruthenium in an
61 octahedral coordination environment, leaving three facial sites for other functions, (ii) arene
62 ligands that are relatively weak electron donors may provide a unique reactivity on the metallic
63 center, and (iii) the substitution pattern on the ring is flexible. To take account of these
64 advantages, complexes 7-10 were tested as catalysts in transfer hydrogenation of aromatic
i
i
65 ketones in a PrOH solution. First of all, compounds 7-10 were used as precatalysts, PrOH/KOH
66 as a reducing system, and acetophenone as a model substrate.
7

ACCEPTED MANUSCRIPT
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
1
67
To evaluate the efficiency of our Ru(II) complexes, we deeply investigated the optimal
68 conditions starting with acetophenone as a standard test reaction. Results for the asymmetric
69 transfer hydrogenation of ketones with catalysts, 7-10 are collected in Table 1. Catalytic
i
70 experiments were carried out under argon using standard Schlenk-line techniques. To an PrOH
i
71 solution of each complex, appropriate amounts of acetophenone and KOH/ PrOH solution were
72 added at room temperature. The solution was stirred, and the reaction was monitored by GC. The
73 reactions proceeded to give (R) or (S)-1-phenyl ethanol in 12-28% conversion with 72-91% ee’s
74 after stirring at room temperature for 96 h. An increase in the reaction time to 144 h resulted in
75 22-53% conversion with 65-87% ee’s. Due to the reversibility at room temperature, prolonging
76 the reaction time led to a slight decrease in enantioselectivity. However, when the reactions were
77 carried out at 82 °C, all complexes showed satisfactory catalytic activity (up to 196 TOF values)
78 and enantioselectivity (up to 96% ee) since almost quantitative conversions were observed
79 (Table 1, entries 9-12). These results clearly indicate that the reaction temperature plays an
80 important role on the catalytic activity and enantioselectivity.
81
The ruthenium(II) complexes were very active catalysts, leading to quantitative conversions of
82 (R) or (S)-1-phenyl ethanol with a catalyst/base ratio of 1:5 (Table 1, entries 13-16). A control
83 experiment in the absence of base did not lead to significant conversion (Entries 5-8).
84 Furthermore, replacing KOH with NaOH slightly decreased both the reaction rate and
[
e]
85 enantioselectivity (Table 1, entries 9-12 ). Increase or decrease of the base:Cat ratio from 5:1 to
86 9:1 or 3:1 slightly decrease the reaction with a slight loss of enantiomeric purity of the product
87 (Table 1, entries 13-16).
88
89
90
Insert Table 1 Here
8

ACCEPTED MANUSCRIPT
1
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
91 From the results, it can be obviously seen that generally complex 9 and 10, which include -
92 CH OPh instead of –Ph moiety on the phosphinite skeleton showed higher catalytic activity than
2
93 complexes, 7 and 8. Furthermore, the complexes (1R)-2-{benzyl[(1S)-1-(naphthalen-1-
6
94 yl)ethyl]amino}-1-phenylethyl diphenylphosphinito[dichloro(η -benzene)ruthenium (II)], 8 and
95 (2S)-1-{benzyl[(1S)-1-(naphthalen-1-yl)ethyl]amino}-3-phenoxypropan-2-yl diphenylphosphini-
6
96 to [dichloro(η -benzene) ruthenium (II)], 10 which have benzene fragment are more active than
97 the complexes, 7 and 9 which include more commonly used p-cymene fragment. The good
98 enantioselectivity obtained for initial reduction of acetophenone led us to keep employing Ru-
99 benzene complexes. These results clearly indicate that the skeleton of the phosphinite ligands
00 and the fragment attached to the ruthenium center are responsible for the high conversion (up to
01 99 %) and enantioselectivity (up to 96 ee %), whatever the exact reaction mechanism. The best
02 results were obtained in the (2S)-1-{benzyl[(1S)-1-(naphthalen-1-yl)ethyl]amino}-3-
6
03 phenoxypropan-2-yldiphenylphosphinito [dichloro(η -benzene)ruthenium (II)], 10 catalytic
04 system with up to 96% ee and 98% conversion.
05
Under optimized conditions, aromatic ketones were hydrogenated with high
06 enantioselectivity and the same mode face selection. Table 2 illustrates conversions of the
07 reduction performed in a 0.1 M of isoPrOH solution containing 7-10 and KOH
08 (Ketone:Cat:KOH = 100:1:5). One can easily see from the results that a range of acetophenone
09 derivatives can be hydrogenated with high enantioselectivities. Electronic properties (the nature
10 as well as position) of the substituents on the phenyl ring of the ketone caused the changes in the
11 reduction rate and enantioselectivity. It is well-known that the introduction of electron
12 withdrawing substituents to the aryl ring of the ketone decreases the electron density of the C=O
13 bond so that the activity was improved resulting in easier hydrogenation [69,70,71]. Therefore,
14 the introduction of electron-withdrawing substituents, such as CF or NO , to the aryl ring of the
3
2
9

ACCEPTED MANUSCRIPT
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
15 ketone, led to improved activity with good enantioselectivity (Table 2, entries 1-16). On the
16 contrary, the introduction of an electron-donating group such as methyl or methoxy group
17 decelerates the reaction with similar enantioselectivity, whatever the position of substitution
18 (Table 2, entries 17-36). It can be seen from Table 2, ortho-substituted acetophenones can
19 dramatically increase the enantioselectivity, while meta- and para- substitution to ring of the
20 ketone caused the changes in the reduction rate and enantioselectivity. As expected, the lowest
21 enantioselectivity was observed in transfer hydrogenation of p-methoxyacetophenone, whereas
22 the highest one was found in that of m-methoxyacetophenone (96% ee). Overall, the chiral
23 efficiency attains a very high level in the asymmetric reduction of aromatic ketones and
24 compares well with the recently discovered catalyst systems [72,73].
25
26
27
Insert Table 2 Here
28 Complexes 7-10 were further investigated in transfer hydrogenation of a variety of ketones to be
29 converted to the corresponding chiral alcohols under the optimum conditions. The reaction of
30 methyl/alkyl or methyl/aryl ketones gave the corresponding chiral alcoholic products in an
31 acceptable chemical yield and enantiomeric purity. Firstly, we carried out further experiments to
32 study the influence of bulkiness of the alkyl groups on the catalytic activity and selectivity
33 (Table 3, entries 1-16). For this aim, a variety of simple aryl/alkyl ketones were transformed to
34 the corresponding secondary alcohols, and it was found that the activity and selectivity are
35 extremely dependent on the steric hindrance of the alkyl group. Reaction of methyl/alkyl ketones
36 possessing a bulky alkyl substituent proceeded rather sluggish and led a decrease in
37 enantioselectivity. As the bulkiness of the alkyl group increases from ethyl to sec-butyl, the level
38 of enantioselectivity lowers. Indeed, lower activity and enantioselectivity were obtained in case
1
0

ACCEPTED MANUSCRIPT
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
39 of methyl sec-butyl ketone (Entries 13-16, 61-80% ee) [74,75,76,77]. Furthermore, as seen in
40 Table 3, the best result in terms of enantioselectivity was observed with 1-naphtyl methyl ketone
41 (up to 97% ee, entries 17-20). In that case, the highest enantioselectivity, up to 98% ee, were
42 obtained for catalyst (2S)-1-{benzyl[(1S)-1-(naphthalen-1-yl)ethyl]amino}-3-phenoxypropan-2-
6
43 yldiphenylphosphinito[dichloro(η -benzene) ruthenium(II)] (10). Furthermore, the hydrogenation
44 of ketones including cyclohexyl group was very slow and the enantioselectivities were
45 remarkable lower (Table 3, entries 25-32).
46
47
Insert Table 3 Here
48
49 3. Conclusion and Perspectives
50 This work presents new chiral phosphinite ligands which form highly efficient and practical
51 catalysts with ruthenium precursor for asymmetric transfer hydrogenation of aryl/alkyl ketones.
52 High conversion and enantioselectivity were obtained in the catalytic reaction. The high catalytic
53 activity and enantioselectivity for this kind of ligands show great potential for further exploring
54 similar system and achieving outstanding stereoselectivity for a wider scope of ketone substrates.
55 Furthermore, the simplicity and efficiency clearly make it an excellent choice of catalyst for the
56 practical preparation of highly valued alcohols via catalytic asymmetric transfer hydrogenation
57 of ketones.
58 4. Materials and Methods
59 All manipulations were carried out under an atmosphere of argon using conventional Schlenk
60 glassware. Solvents were dried using established procedures and distilled under argon
61 immediately prior to use. Analytical grade and deuterated solvents were purchased from Merck.
62 The starting materials D-glycine, D-alanine, PPh Cl and Et N are purchased from Fluka and
2
3
1
1

ACCEPTED MANUSCRIPT
6
6
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
63 were used as received. [Ru(η -p-cymene)(µ-Cl)Cl] [78], and [Ru(η -benzene)(µ-Cl)Cl] [79]
2
2
64 were prepared according to the literature procedures. The IR spectra were recorded on a Mattson
1
13
65 1000 ATI UNICAM FT-IR spectrometer as KBr pellets. H (400.1 MHz), C NMR (100.6
3
1
1
66 MHz) and P-{ H} NMR (162.0 MHz) spectra were recorded on a Bruker AV400 spectrometer,
67 with δ referenced to external TMS and 85% H PO respectively. Elemental analysis was carried
3
4
68 out on a Fisons EA 1108 CHNS-O instrument. Melting points were recorded by a Gallenkamp
69 Model apparatus with open capillaries.
70 GC analyses were performed on a Shimadzu GC 2010 Plus Gas Chromatograph equipped with
71 cyclodex B (Agilent) capillary column (30 m x 0.32 mm I.D. x 0.25 µm film thickness). The GC
72 parameters for asymmetric transfer hydrogenation of ketones were as follows; initial
73 temperature, 50 ºC; initial time 1.1 min; solvent delay, 4.48 min; temperature ramp 1.3 ºC/min;
74 final temperature, 150 ºC; initial time 2.2 min; temperature ramp 2.15 ºC/min; final temperature,
75 250 ºC; initial time 3.3 min; final time, 44.33 min; injector port temperature, 200 ºC; detector
76 temperature, 200 ºC, injection volume, 2.0 µL.
77 4.1 General procedure for the transfer hydrogenation of ketones
78 Typical procedure for the catalytic hydrogen-transfer reaction: a solution of the ruthenium
79 complexes (5-8) (0.005 mmol), KOH (0.025 mmol) and the corresponding ketone (0.5 mmol) in
80 degassed isoPrOH (5 mL) was refluxed until the reaction completed. A sample of the reaction
81 mixture was taken off, diluted with acetone and analyzed immediately by GC, the conversions
1
82 obtained are related to the residual unreacted ketone. Furthermore, H NMR spectral data for the
83 resultant products were consistent with previously reported results.
84 4.2. Synthesis and Characterization of Amino Alcohols
85 4.2.1. N-benzyl-N-[(S)-1-[α-naphthylethyl]amine (2)
1
2

ACCEPTED MANUSCRIPT
2
2
2
2
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
3
3
3
3
3
86 (S)-(-)-1-[Naphthalen-1-yl-ethy]amine 1 (1.00 g, 5.84 mmol) was dissolved in anhydrous MeOH
87 (5 mL) and heated to reflux. Benzaldehyde (0.62 g, 5.84 mmol) was added dropwise over a
88 period of 2 min and the mixture was stirred at reflux temperature for 3 h. The solution was
89 allowed to cool to room temperature and sodium borohydride (0.24 g, 6.13 mmol) was added
90 portionwise. The mixture was stirred for further 2 h at room temperature and then heated to
91 reflux temperature for 30 min. The reaction was then quenched by the addition of water (5 mL)
92 and the aqueous phase extracted with DCM (3×10 mL). The separated organics were dried over
93 MgSO and filtered. The solution was concentrated under reduced pressure. The residue was
4
94 purified by silica-gel column chromatography (n-hexane/EtOAc = 2/1), to afford product (1.01 g,
2
0
o
1
95 66 %) as an oil. [α]D = +21.3 (c 1, CH Cl ). H NMR (CDCI , ppm): δ 8.22 (d, 1H, J =6.7 Hz,
2
2
3
96 Ar-H), 7.93-7.95 (m, 1H, Ar-H), 7.82-7.84 (m, 2H, Ar-H), 7.54-7.59 (m, 3H, Ar-H), 7.30-7.39
97 (m, 5H, Ar-H), 4.76 (q, 1H, J = 6.6 Hz -CHCH ), 3.75-3.86 (m, 2H, -CH Ph), 1.81 (br, 1H, -
3
2
1
3
98 NH), 1.59 (d, 3H, J = 6.6 Hz, -CH ); C NMR (CDCI , ppm): δ 23.69 (-CH ), 51.92 (-CH Ph),
3
3
3
2
99 53.06 (-CHCH ), 122.94, 123.04, 125.33, 125.74, 125.79, 126.94, 127.27, 128.24, 128.42,
3
1
13
00 128.98, 131.41, 134.04, 140.67, 140.99 (Ar-C), assignment was based on the H- C HETCOR
1
1
-1
01 and H- H COSY spectra; IR (cm ): υ 3051, 3028 (aromatic C-H), 2964, 2925 (aliphatic C-H)
-1
02 cm ; Anal. Calc. for C H N (261.37 g/mol): C 87.31, H 7.33, N 5.36; found C 87.19, H 7.28,
19
19
+
03 N 5.29. IT-TOF MS ([M+H] ): 262.15 g/mol.
04 4.2.2. (1R)-2-{benzyl[(1S)-1-(naphthalen-1-yl)ethyl]amino}-1-phenylethan-1-ol, (3)
05 (R)-Styrene oxide (0.51 g, 4.21 mmol) was added to the solution of N-benzyl-N-(S)-1-[α-
o
06 naphthylethyl]amine 2 (1.00 g, 3.83 mmol) in methanol (5 ml). The solution was heated to 70 C
07 and the reaction was followed by TLC (n-hexane/EtOAc/TEA = 80/10/1). After 24 h, the
08 reaction finished, the solvent was removed. The crude product was purified by silica-gel column
09 chromatography (n-hexane//EtOAc / TEA = 80/10/1) to afford 3 (1.02 g, 70 %) as a white solid.
1
3

ACCEPTED MANUSCRIPT
o
20
o
1
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
10 M.p = 104-106 C. [α]D = +16.4 (c 1, CHCl ). H NMR (CDCl , ppm): δ 8.16 (d, J = 9.3 Hz,
3
3
11 1H, Ar-H), 7.90 (d, J = 9.5 Hz, 1H, Ar-H), 7.83 (d, J = 8.1 Hz, 1H, Ar-H), 7.48-7.60 (m, 4H, Ar-
12 H), 7.15-7.30 (m, 10H, Ar-H), 4.88 (q, J = 6.8 Hz, 1H, -CHCH ), 4.03-4.06 (m, 1H, -CHPh),
3
13 3.76 (s, 2H, -CH Ph), 3.37 (s, 1H, OH), 2.95-3.00 (m, 1H, -CH N, (a)), 2.79-2.85 (m, 1H, -
2
2
1
3
14 CH N, (b)), 1.66 (d, J = 6.8 Hz, 3H, -CH ); C NMR (CDCl , ppm): δ 14.76 (-CHCH ), 56.57,
2
3
3
3
15 56.59 (-CH Ph, -CHCH ), 61.31 (-CH N), 70.99 (-CHPh), 124.03, 124.53, 125.06, 125.70,
2
3
2
16 125.82, 126.11, 127.30, 127.36, 128.25, 128.55, 128.93, 128.97, 132.25, 134.10, 138.70, 139.92,
1
13
1
1
-
17 142.55 (Ar-C), assignment was based on the H- C HETCOR and H- H COSY spectra; IR (cm
1
-1
18
): υ 3394 (O-H), 3058, 3030 (aromatic C-H), 2965, 2940, 2906 (aliphatic C-H) cm ; Anal. Calc.
19 for C H NO (381.52 g/mol): C 85.00, H 7.13, N 3.67; found C 84.90, H 7.05, N 3.60; IT-TOF
2
7
27
+
20 MS ([M+H] ): 382.22 g/mol.
21 4.2.3. (2S)-1-{benzyl [(1S)-1-(naphthalen-1-yl)ethyl]amino}-3-phenoxypropan-2-ol, (4)
22 (S)-Glycidyl phenyl ether (0.63 g, 4.21 mmol) was added to the solution of N-benzyl-N-(S)-1-[α-
o
23 naphthylethyl]amine 2 (1.00 g, 3.83 mmol) in methanol (5 ml). The solution was heated to 70 C
24 and the reaction was followed by TLC (n-hexane/EtOAc/TEA = 40/8/3). After 24 h, the reaction
25 finished, the solvent was removed. The crude product was purified by silica-gel column
26 chromatography (n-hexane/EtOAc / TEA = 40/8/3) to afford 4 (1.44 g, 91 %) as a viscous
20
o
1
27 product. [α]D = +80.4 (c 1, CHCl ). H NMR (CDCl , ppm): δ 7.99 (d, J = 8.6 Hz, 1H, Ar-H),
3
3
28 7.93 (d, J = 8.1 Hz, 1H, Ar-H), 7.83 (d, J = 8.2 Hz, 1H, Ar-H), 7.22-7.62 (m, 11H, Ar-H), 6.97
29 (t, J = 7.3 Hz, 1H, Ar-H), 6.45 (d, J = 8.1 Hz, 2H, Ar-H), 4.83 (q, J = 6.7 Hz, 1H, -CHCH3),
30 3.90 (s, 2H, CH Ph), 3.73-3.75 (m, 1H, CHCH ), 3.55 (m, 1H, CH OPh a)), 3.02 (m, 1H,
2
2
2
31 CH OPh b)), 2.82-2.89 (m, AB system, 2H, CH N), 2.68 (s, 1H, OH), 1.68 (d, J = 6.7 Hz, 3H, -
2
2
1
3
32 CHCH ). C NMR (CDCl ppm): δ 12.03 (-CHCH ), 53.29 (-CH N), 55.23 (-CHCH ), 57.59 (-
3
3,
3
2
3
33 CH Ph), 68.02 (-CHCH ), 70.46 (-CH OPh), 114.35, 120.70, 124.72, 124.83, 125.07, 125.60,
2
2
2
1
4

ACCEPTED MANUSCRIPT
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
34 125.88, 127.55, 128.23, 128.50, 128.77, 129.30, 129.58, 132.30, 134.14, 138.72, 139.51, 158.55
1
13
1
1
-1
35 (Ar-C), assignment was based on the H- C HETCOR and H- H COSY spectra; IR (cm ): υ
-1
36 3445 (O-H), 3050, 3029 (aromatic C-H), 2968, 2923, 2834 (aliphatic C-H) cm ; Anal. Calc. for
37 C H NO (411.54 g/mol): C 81.72, H 7.10, N 3.40; found C 81.66, H 7.01, N 3.32; IT-TOF
28
29
2
+
38 MS ([M+H] ): 412.23 g/mol.
39 4.3. Synthesis of chiral ruthenium(II) phosphinite ligands and their complexes
40 4.3.1.(1R)-2-{benzyl[(1S)-1-(naphthalen-1-yl)ethyl]amino}-1-phenylethyldiphenylphosphite,
41 (5)
42 (1R)-2-{benzyl[(1S)-1-(naphthalen-1-yl)ethyl]amino}-1-phenylethan-1-ol, (3) (0.100 gr, 0.26
43 mmol) and Et N (0.027 gr, 0.26 mmol) were dissolved in dry CH Cl (30 mL) under an argon
3
2
2
44 atmosphere. Next, Ph PCl (0.059 gr, 0.26 mmol) was added dropwise with a syringe to this
2
o
45 solution. The mixture was stirred at 0 C for 30 min, and the solvent was removed under reduced
46 pressure. After addition of dry thf, the white precipitate (triethylammonium chloride) was filtered
47 off under argon and dried in vacuo to produce a white viscous oily compound 5 (Yield: 0.14 g,
2
0
1
48 94.7 %). [α]D = +34.3 (c 1, CH Cl ). H NMR (CDCl , ppm): δ 8.16 (d, J = 9.1 Hz, 1H, Ar-H),
2
2
3
49 7.17-7.92 (m, 24 H, Ar-H), 7.01 (m, 1H, Ar-H), 6.90 (d, J = 7.6 Hz, 1H, Ar-H), 4.88 (q, J = 6.9
50 Hz, 1H, -CHCH ), 4.04-4.06 (m, 1H, CHPh), 3.77 (s, 2H, -CH Ph), 2.98 (m, 1H, -CH N (a)),
3
2
2
13
51 2.83 (m, 1H, -CH N (b)), 1.66 (d, J = 6.9 Hz, 3H, -CHCH ); C NMR (CDCl , ppm): δ 14.72
2
3
3
52 (CHCH ), 56.53, 56.62 (CH Ph, CHCH ), 61.28 (CH N), 70.91 (CHPh), 123.96, 124.47,
3
2
3
2
53 125.00, 125.75, 126.05, 127.03, 127.69, 128.04, 128.18, 128.48, 128.86, 129.48, 132.02, 134.03,
54 138.65, 139.87, 142.50 (aromatic carbons), 125.16 (d, J = 4.0 Hz, m-carbons of OPPh ), 125.63
2
55 (s, p-carbons of PPh ), 127.26 (d, J = 6.0 Hz, o-carbons of OPPh ), 135.38 (d, J = 19.1 Hz, i-
2
2
31
1
56 carbons of OPPh ); P-{ H} NMR (CDCl , ppm): δ 108.80 (s, O-PPh ) assignment was based
2
3
2
1
13
1
1
-1
57 on the H- C HETCOR and H- H COSY spectra; IR (cm ): υ 3054 (aromatic C-H), 2967
1
5

ACCEPTED MANUSCRIPT
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
58 (aliphatic C-H), 1437 (P-Ph), 971 (O-P); Anal. Calc. for C H NOP (565.69 g/mol): C 82.81, H
3
9
36
59 6.41, N 2.48; found C 82.69, H 6.35, N 2.43.
60 4.3.2. (2S)-1-{benzyl[(1S)-1-(naphthalen-1-yl)ethyl]amino}-3-phenoxypropan-2-yl diphen-
61 ylphosphinite, (6)
62 (2S)-1-{benzyl[(1S)-1-(naphthalen-1-yl)ethyl]amino}-3-phenoxy propan-2-ol, (4) (0.100 gr,
63 0.24 mmol) and Et N (0.025 gr, 0.24 mmol) were dissolved in dry CH Cl (30 mL) under an
3
2
2
64 argon atmosphere. Next, Ph PCl (0.055 gr, 0.24 mmol) was added dropwise with a syringe to
2
65 this solution. The mixture was stirred at room temperature for 30 min, and the solvent was
66 removed under reduced pressure. After addition of dry thf, the white precipitate
67 (triethylammonium chloride) was filtered off under argon and dried in vacuo to produce a white
2
0
1
68 viscous oily compound 6 (Yield: 0.14 g, 96.8 %). [α]D = +83.0 (c 1, CH Cl ). H NMR (CDCI ,
2
2
3
69 ppm): δ 7.23-7.86 (m, 22H, Ar-H), 7.05 (t, J = 7.8 Hz, 2H, Ar-H), 6.82 (t, J = 7.3 Hz, 1H, Ar-
70 H), 5.90 (d, J = 8.2 Hz, 2H, Ar-H), 4.68 (q, J = 6.6 Hz, 1H, CHCH ), 4.10-4.12 (m, 1H,
3
71 CHCH ), 3.89 (s, 2H, CH Ph), 3.35 (m, 1H, CH OPh a)), 2.70-2.74 (m, AB system, 1H, CH N
2
2
2
2
72 a)), 2.79-2.85 (m, AB system, 1H, CH N b)), 2.64 (m, 1H, CH OPh b)), 1.55 (d, J = 6.6 Hz, 3H,
2
2
13
73 -CHCH ); C NMR (CDCl ): δ 10.34 (-CHCH ), 50.89 (d, J = 5.0 Hz, -CH N), 53.36 (CHCH ),
3
3
3
2
3
74 57.84 (CH Ph), 69.66 (-CH OPh), 78.32 (d, J = 19.1Hz, -CHCH ), 114.11, 119.99, 124.87,
2
2
2
75 125.42, 127.55, 128.20, 128.30, 128.78, 128.84, 129.23, 130.07, 130.49, 130.71, 132.13, 133.95,
76 138.47, 138.76, 158.33 (aromatic carbons), 128.04 (d, J = 7.0 Hz, m-carbons of OPPh ), 128.41
2
77 (s, p-carbons of OPPh ), 130.08 (d, J = 21.2 Hz, o-carbons of OPPh ), 142.51 (d, J = 25.2 Hz, i-
2
2
1
13
1
1
31
78 carbons of OPPh ) assignment was based on the H- C HETCOR and H- H COSY spectra; P-
2
1
-1
79 { H} NMR (CDCl , ppm): δ 113.60 (s, O-PPh ); IR (cm ): υ 3055 (aromatic C-H), 2965
3
2
80 (aliphatic C-H), 1438 (P-Ph), 971 (O-P); Anal. Calc. for C H NO P (595.72 g/mol): C 80.65, H
40
38
2
81 6.43, N 2.35; found C 80.55, H 6.37, N 2.29.
1
6

ACCEPTED MANUSCRIPT
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
3
4
4
4
4
4
4
82 4.3.3.(1R)-2-{benzyl[(1S)-1-(naphthalen-1-yl)ethyl]amino}-1-phenylethyldiphenyl
6
83 phosphinito[dichloro(η -p-cymene) ruthenium(II)] (7)
6
84 [Ru(η -p-cymene)(µ-Cl)Cl] (0.05 g, 0.09 mmol) and (1R)-2-{benzyl[(1S)-1-(naphthalen-1-
2
85 yl)ethyl]amino}-1-phenylethyl diphenylphosphinite, (5) (0.10 g, 0.18 mmol) were dissolved in
86 30 mL of dry CH Cl under an argon atmosphere and stirred for 30 min at room temperature.
2
2
87 The volume was concentrated to ca. 1-2 mL under reduced pressure and addition of petroleum
88 ether (25 mL) gave 7 as a red solid. The product was collected by filtration and dried in vacuo
0
25
D
o
1
89 (yield: 0.13 g, 85.8 %; mp: 123-124 C); [α] = + 27 (c 1, CH Cl ). H NMR (CDCl , ppm): δ
2
2
3
90 7.88 (t, J = 7.8 Hz, 4H, Ar-H), 7.57 (t, J = 8.3 Hz, 3H, Ar-H), 7.29-7.37 (m, 12 H, Ar-H), 6.65-
91 7.07 (m, 8H, Ar-H), 5.41 (m, 1H, CHPh), 5.17 (d, J = 5.8 Hz, 1H, aromatic proton of p-cymene),
92 4.96 (d, J = 6.0 Hz, 1H, aromatic proton of p-cymene), 4.84 (d, J = 6.0 Hz, 1H, aromatic proton
93 of p-cymene), 4.47 (d, J = 5.8 Hz, 1H, aromatic proton of p-cymene), 4.25 (q, J = 6.5 Hz, 1H, -
94 CHCH ), 3.38 (d, J = 13.2 Hz, 1H, -CH Ph, (a)), 3.20 (d, J = 13.3 Hz, 1H, -CH Ph, (b)), 2.87
3
2
2
95 (dd (pseudo t), J = 11.6 Hz, J = 11.5 Hz 1H, -CH N (a)), 2.59 (m, 1H, -CH N (b)), 2.37 (m, 1H,
2
2
96 –CH- of p-cymene), 1.49 (s, 3H, CH Ph of p-cymene), 1.20 (d, J = 7.9 Hz, 3H, -CHCH ), 1.05
3
3
1
3
97 (m, 6H, CH ) CHPh of p-cymene); C NMR (CDCl , ppm): δ 10.51 (CHCH ), 17.01 (CH Ph of
3
2
3
3
3
98 p-cymene), 21.99 ((CH ) CHPh of p-cymene), 29.80 (–CH- of p-cymene), 52.22 (CHCH ),
3
2
3
99 54.54, 55.39 (CH Ph, CH N), 77.24 (CHPh), 87.16, 88.23, 88.56, 89.00 (aromatic carbons of p-
2
2
00 cymene), 99.54, 111.76 (quaternary carbons of p-cymene), 124.63, 124.78, 126.91, 126.97,
01 127.09, 127.72, 127.82, 130.00, 130.73, 130.83, 132.13, 132.38, 132.49, 133.67, 138.47, 138.97,
02 140.13 (aromatic carbons), 124.18 (d, J = 4.0 Hz, m-carbons of OPPh ), 125.19 (s, p-carbons of
2
03 PPh ), 127.36 (d, J = 6.0 Hz, o-carbons of OPPh ), 134.25 (d, J = 11.1 Hz, i-carbons of OPPh );
2
2
2
1
13
1
1
31
1
04 assignment was based on the H- C HETCOR and H- H COSY spectra; P-{ H} NMR
-1
05 (CDCl , ppm): δ 109.70 (s, O-PPh ); IR (cm ): υ 3057 (aromatic C-H), 2963 (aliphatic C-H),
3
2
1
7

ACCEPTED MANUSCRIPT
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
06 1435 (P-Ph), 970 (O-P), 531 (Ru-P); Anal. Calc. for C H NOPRuCl (871.89 g/mol): C 67.50,
4
9
50
2
07 H 5.78, N 1.61; found C 67.41, H 5.70, N 1.52.
08 4.3.4.
(1R)-2-{benzyl[(1S)-1-(naphthalen-1-yl)ethyl]amino}-1-phenylethyldiphenyl
6
09 phosphinito [dichloro(η -benzene)ruthenium (II)] (8)
6
10 [Ru(η -benzene)(µ-Cl)Cl] (0.04 g, 0.09 mmol) and (1R)-2-{benzyl[(1S)-1-(naphthalen-1-
2
11 yl)ethyl]amino}-1-phenylethyl diphenylphosphinite, (5) (0.10 g, 0.18 mmol) were dissolved in
12 30 mL of dry CH Cl under an argon atmosphere and stirred for 30 min at room temperature. The
2
2
13 volume was concentrated to ca. 1–2 mL under reduced pressure and addition of petroleum ether
14 (25 mL) gave 8 as a red solid. The product was collected by filtration and dried in vacuo (yield:
0
25
o
1
15 0.12 g, 83.9 %; mp: 191-193 C); [α]D = + 113 (c 1, CH Cl ). H NMR (CDCl , ppm): δ 8.06
2
2
3
16 (t, J = 8.9 Hz, 2H, Ar-H), 7.96 (t, J = 8.5 Hz, 2H, Ar-H), 6.73-7.58 (m, 23H, Ar-H), 5.63-5.70
17 (m, 1H, CHPh), 4.95 (s, 6H, aromatic protons of benzene), 4.27 (q, J = 6.6 Hz, 1H, -CHCH3),
18 3.39 (d, J = 13.2 Hz, 1H, -CH Ph, (a)), 3.14 (d, J = 13.2 Hz, 1H, -CH Ph, (b)), 2.88 (dd (pseudo
2
2
19 t), J = 11.5 Hz, J = 11.3 Hz, 1H, -CH N (a)), 2.32 (d, J = 10.0 Hz, 1H, -CH N (b)), 1.17 (d, J =
2
2
13
20 6.6 Hz, 3H, -CHCH ); C NMR (CDCl , ppm): δ 10.61 (CHCH ), 51.99 (CHCH ), 54.98, 55.44
3
3
3
3
21 (CH Ph, CH N), 77.23 (CHPh), 90.13 (d, J = 4.0 Hz, aromatic carbons of benzene), 124.71,
2
2
22 124.82, 126.85, 126.99, 127.16, 127.59, 127.79, 127.92, 128.12, 130.06, 130.42, 130.70, 131.48,
23 133.68, 138.37, 138.72, 140.44 (aromatic carbons), 124.07 (d, J = 7.0 Hz, m-carbons of OPPh2),
24 125.13 (s, p-carbons of PPh ), 127.46 (d, J = 6.0 Hz, o-carbons of OPPh ), 135.42 (d, J = 13.1
2
2
1
13
1
1
25 Hz, i-carbons of OPPh ); assignment was based on the H- C HETCOR and H- H COSY
2
3
1
1
-1
26 spectra; P-{ H} NMR (CDCl , ppm): δ 104.76 (s, O-PPh ); IR (cm ): υ 3049 (aromatic C-H),
3
2
27 2966, 2935, 2888, 2841, 2806 (aliphatic C-H), 1436 (P-Ph), 992 (O-P), 524 (Ru-P); Anal. Calc.
28 for C H NOPRuCl (815.78 g/mol): C 66.26, H 5.19, N 1.72; found C 66.18, H 5.10, N 1.67.
4
5
42
2
1
8

ACCEPTED MANUSCRIPT
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
29 4.3.5. (2S)-1-{benzyl[(1S)-1-(naphthalen-1-yl)ethyl]amino}-3-phenoxypropan-2-yldiphenyl
6
30 phosphinito[dichloro(η -p-cymene) ruthenium (II)] (9)
6
31 [Ru(η -p-cymene)(µ-Cl)Cl] (0.05 g, 0.08 mmol) and (2S)-1-{benzyl[(1S)-1-(naphthalen-1-
2
32 yl)ethyl]amino}-3-phenoxypropan-2-yl diphenylphosphinite, (6) (0.10 g, 0.17 mmol) were
33 dissolved in 30 mL of dry CH Cl under an argon atmosphere and stirred for 30 min at room
2
2
34 temperature. The volume was concentrated to ca. 1-2 mL under reduced pressure and addition of
35 petroleum ether (25 mL) gave 9 as a red solid. The product was collected by filtration and dried
0
25
D
o
1
36 in vacuo (yield: 0.13 g, 85.9 %; mp: 168-170 C); [α] = + 56 (c 1, CH Cl ). H NMR (CDCI ,
2
2
3
37 ppm): δ 7.99 (t, J = 8.7 Hz, 2H, Ar-H), 7.11-7.82 (m, 22H, Ar-H), 6.91 (t, J = 7.3 Hz, 1H, Ar-H),
38 5.98 (d, J = 8.0 Hz, 2H, Ar-H), 5.48 (q, J = 5.8 Hz, 2H, aromatic protons of p-cymene), 5.35 (d,
39 J = 5.8 Hz, 1H, aromatic proton of p-cymene), 5.22 (d, J = 5.8 Hz, 1H, aromatic proton of p-
40 cymene), 4.75 (br, 1H, CHCH ), 4.47 (q, J = 6.6 Hz, 1H, CHCH ), 3.71 (d, J = 13.4 Hz, 1H,
2
3
41 CH Ph, (a)), 3.60 (d, J = 10.4 Hz, 1H, CH OPh (a)), 3.41 (d, J = 13.4 Hz, 1H, CH Ph, (b)), 2.61
2
2
2
42 (t, J = 9.3 Hz, 1H, CH OPh (b)), 2.50 (m, 1H, –CH- of p-cymene), 2.30 (m, 2H, CH N), 1.70 (s,
2
2
43 3H, CH Ph of p-cymene), 1.26 (d, J = 6.7 Hz, 3H, -CHCH ), 1.09 (d, J = 6.9 Hz, 3H,
3
3
1
3
44 CH ) CHPh of p-cymene), 0.93 (d, J = 6.9 Hz, 3H, CH ) CHPh of p-cymene); C NMR
3
2
3 2
45 (CDCl ): δ 8.79 (-CHCH ), 17.00 (CH Ph of p-cymene), 21.60, 22.14 ((CH ) CHPh of p-
3
3
3
3 2
46 cymene), 29.98 (–CH- of p-cymene), 49.20 (CH N), 51.90 (CHCH ), 56.14 (CH Ph), 69.29 (-
2
3
2
47 CH OPh), 75.91 (d, J = 6.0 Hz, -CHCH ), 86.19 (d, J = 6.0 Hz, aromatic carbon of p-cymene),
2
2
48 87.94 (d, J = 5.0 Hz, aromatic carbon of p-cymene), 89.64 (s, aromatic carbon of p-cymene),
49 92.29 (d, J = 5.0 Hz, aromatic carbon of p-cymene), 97.51, 111.20 (quaternary carbons of p-
50 cymene), 113.75, 120.38, 124.73, 125.01, 125.20, 125.41, 127.22, 127.33, 127.90, 129.20,
51 130.27, 131.96, 132.12, 133.88, 134.17, 138.51, 139.13, 158.26 (aromatic carbons), 127.82 (d, J
52 = 10.1 Hz, m-karbons of OPPh ), 128.07 (s, p-carbons of OPPh ), 130.65 (d, J = 15.1 Hz, o-
2
2
1
9

ACCEPTED MANUSCRIPT
1
13
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
4
53 carbons of OPPh ), (i-carbons of OPPh were not observed); assignment was based on the H- C
2
2
1
1
31
1
54 HETCOR and H- H COSY spectra; P-{ H} NMR (CDCl , ppm): δ 111.15 (s, O-PPh ); IR
3
2
-1
55 (cm ): υ 3051 (aromatic C-H), 2963, 2925, 2871 (aliphatic C-H), 1435 (P-Ph), 1019 (O-P), 537
56 (Ru-P); Anal. Calc. for C H NO PRuCl (901.92 g/mol): C 66.59, H 5.81, N 1.55; found C
50
52
2
2
57 66.42, H 5.75, N 1.49.
58 4.3.6. (2S)-1-{benzyl[(1S)-1-(naphthalen-1-yl)ethyl]amino}-3-phenoxypropan-2-yldiphenyl
6
59 phosphinito[dichloro(η -benzene) ruthenium (II)] (10)
6
60 [Ru(η -benzene)(µ-Cl)Cl] (0.04 g, 0.08 mmol) and (2S)-1-{benzyl[(1S)-1-(naphthalen-1-
2
61 yl)ethyl]amino}-3-phenoxypropan-2-yl diphenylphosphinite, (6) (0.10 g, 0.17 mmol) were
62 dissolved in 30 mL of dry CH Cl under an argon atmosphere and stirred for 30 min at room
2
2
63 temperature. The volume was concentrated to ca. 1-2 mL under reduced pressure and addition of
64 petroleum ether (25 mL) gave 10 as a red solid. The product was collected by filtration and dried
0
25
D
o
1
65 in vacuo (yield: 0.12 g, 85.6 %; mp: 147-149 C); [α] = + 90 (c 1, CH Cl ). H NMR (CDCI ,
2
2
3
66 ppm): δ 7.09-7.94 (m, 24H, Ar-H), 6.90 (t, J = 7.2 Hz, 1H, Ar-H), 5.98 (d, J = 8.0 Hz, 2H, Ar-
67 H), 5.47 (s, 6H, aromatic protons of benzene), 4.94 (m, 1H, CHCH ), 4.56 (q, J = 6.3 Hz, 1H,
2
68 CHCH ), 3.92 (d, J = 13.4 Hz, 1H, CH Ph, (a)), 3.65 (d, J = 9.6 Hz, 1H, CH OPh (a)), 3.49 (d, J
3
2
2
69 = 13.4 Hz, 1H, CH Ph, (b)), 2.68 (t, J = 9.1 Hz, 1H, CH OPh (b)), 2.39 (dd (pseudo t), J = 11.8
2
2
70 Hz, J = 11.7 Hz 1H, CH N (a)), 2.26 (d, J = 9.5 Hz, 1H, CH N (b)), 1.27 (d, J = 6.6 Hz, 3H, -
2
2
1
3
71 CHCH ); C NMR (CDCl ): δ 9.09 (-CHCH ), 49.19 (CH N), 52.47 (CHCH ), 56.40 (CH Ph),
3
3
3
2
3
2
72 69.04 (-CH OPh), 76.74 (d, J = 3.0 Hz, -CHCH ), 90.32 (d, J = 4.0 Hz, aromatic carbons of
2
2
73 benzene), 113.82, 120.52, 124.71, 125.00, 125.24, 125.44, 127.22, 127.98, 129.21, 130.30,
74 130.64, 131.18, 132.15, 133.92, 134.62, 138.45, 139.25, 158.18 (aromatic carbons), 127.46 (d, J
75 = 10.1 Hz, m-carbons of OPPh ), 128.10 (s, p-carbons of OPPh ), 128.28 (d, J = 22.1 Hz, o-
2
2
76 carbons of OPPh ), 140.19 (d, J = 58.4 Hz, i-carbons of OPPh ); assignment was based on the
2
2
2
0

ACCEPTED MANUSCRIPT
1
13
1
1
31
1
4
4
4
4
4
4
4
4
4
77
H- C HETCOR and H- H COSY spectra; P-{ H} NMR (CDCl , ppm): δ 109.59 (s, O-PPh );
3 2
-1
78 IR (cm ): υ 3058 (aromatic C-H), 2966, 2935 (aliphatic C-H), 1435 (P-Ph), 967 (O-P), 537 (Ru-
79 P); Anal. Calc. for C H NO PRuCl (845.81 g/mol): C 65.32, H 5.24, N 1.66; found C 65.18,
4
6
44
2
2
80 H 5.17, N 1.60.
81 Acknowledgements
82 Partial supports of this work by TUBİTAK (Project number: 113Z297), Dicle University
83 (Project numbers: FEN.17.018 and FEN.17.023), FEN.17.019 and IRN: AP05132833,
84 BR05236800 is gratefully acknowledged.
85 References
[
1] T. Ohkuma, M. Kitamura, R Noyori, Catalytic Asymmetric Synthesis. 2nd ed. Ojima I, editor. New York, John
Wiley & Sons; (2000) 796 p.
[
[
(
[
2] R. Noyori Asymmetric Catalysis in Organic Synthesis. New York: John Wiley & Sons; (1994) 400 p.
3] W. Tang, X. Zhang, New Chiral Phosphorus Ligands for Enantioselective Hydrogenation, Chem Rev. 103
2003) 3029-3070.
4] H. B. Blaser, C. Malan, B. Pugin, F. Spindler, H. Steiner, H. Studer, Selective Hydrogenation for Fine
Chemicals: Recent Trends and New Developments, Adv Synth Catal. 345 (2003) 103-151.
5] T. Hayashi, Asymmetric Catalysis with Chiral Ferrocenylphosphine Ligands. In Togni A, Hayashi T. Editors.
Ferrocenes: Homogeneous Catalysis, Organic Synthesis, Materials Science. Weinheim: John Wiley & Sons;
[
(
1995) 105-142.
[
6] R.G. Arrayas, J. Adrio, J. C. Carretero, Recent Applications of Chiral Ferrocene Ligands in Asymmetric
Catalysis, Angew. Chem, Int Ed. 45 (2006) 7674-7715.
7] A. Togni, New Chiral Ferrocenyl Ligands for Asymmetric Catalysis. In Togni A, Halterman RL, editors.
Metallocenes: Synthesis Reactivity Applications. Weinheim: Wiley-VCH; (1998) 685-721.
8] O. B. Sutcliffe, M. R. Bryce, Planar chiral 2-ferrocenyloxazolines and 1,1′-bis(oxazolinyl)ferrocenes—syntheses
and applications in asymmetric catalysis, Tetrahedron: Asymmetry 14 (2003) 2297-2325.
9] H. A. Blaser, F. Spindler, Enantioselective Catalysis for Agrochemicals: The Case History of the DUAL
MAGNUM® Herbicide, Chimia 51 (1997) 297-299.
10] A. Togni, T. Hayashi Editors. Ferrocene: Homogeneous Catalysis, Organic Synthesis, Materials
Science. Weinheim: Wiley-VCH; (1995) 531.
[
[
[
[
[
11] M. J. Burk, M. F. Gross, New chiral 1,1′-bis(phospholano)ferrocene ligands for asymmetric catalysis,
Tetrahedron Lett. 35 (1994) 9363-9366.
2
1

ACCEPTED MANUSCRIPT
[
12] J. Kang, J. H. Lee, S. H. Ahn, J. S. Choi, Asymmetric synthesis of a new cylindrically chiral and air-stable
ferrocenyldiphosphine and its application to rhodium-catalyzed asymmetric hydrogenation, Tetrahedron Lett. 39
(
1998) 5523-5526.
[
13] M. Sawamura, R. Kuwano, Y. Ito. trans‐ Chelating Chiral Diphosphane Ligands Bearing Flexible P‐ Alkyl
Substituents (AlkylTRAPs) and their Application to the Rhodium‐ Catalyzed Asymmetric Hydrosilylation of
Simple Ketones, Angew. Chem. Int. Ed. Engl. 33 (1994) 111-113.
[
14] M. Sawamura, Y. Ito, Catalytic asymmetric synthesis by means of secondary interaction between chiral ligands
and substrates, Chem. Rev. 92 (1992) 857-871.
15] F.Y. Zhang, A. S. C Chan. Enantioselective conjugate addition of diethylzinc to cyclic enones catalyzed by
[
chiral copper complexes containing a new phosphorus ligand with an H8-binaphthoxy moiety Tetrahedron:
Asymmetry 9 (1998) 1179-1185.
[
16] W. Zhang, T. Shimanuki, T. Kida, Y. Nakatsuji, I. Ikeda, C -Symmetric Diphosphine Ligands with Only the
2
Planar Chirality of Ferrocene for the Palladium-Catalyzed Asymmetric Allylic Alkylation J. Org. Chem. 64 (1999)
247-6251.
17] Q. Dai, W. Gao, D. Liu, L. M. Kapes, X. Zhang, Triazole-Based Monophosphine Ligands for Palladium-
Catalyzed Cross-Coupling Reactions of Aryl Chlorides J. Org. Chem. 71 (2006) 3928-3934.
18] J. H. Song, D. J. Cho, S. J. Jeon, Y. H. Kim, T. J. Kim, Synthesis of Chiral C(2)-Symmetric
Bisferrocenyldiamines. X-ray Crystal Structure of Ru(2)Cl(2).2CHCl(3) (2 N1,N2-Bis{(R)-1-[(S)-2-
diphenylphosphino)]ferrocenylethyl}- N1,N2-dimethyl-1,2-ethanediamine). Inorg. Chem. 38 (1999) 893-896.
19] A. Patti, S. Pedotti, Screening of chiral ferrocenyl amino alcohols as ligands for ruthenium-catalysed transfer
6
[
[
=
(
[
hydrogenation of ketones, Tetrahedron: Asymmetry 14 (2003) 597-602.
[
(
[
20] T. Sammakia, E. L. Stangeland. Transfer Hydrogenation with Ruthenium Complexes of Chiral
Phosphinoferrocenyl)oxazolines J. Org. Chem. 62 (1997) 6104-6105.
21] L. Schwink, T.Ireland, K. Püntener, P. Knochel, New C -symmetrical ferrocenyl diamines as ligands for
2
ruthenium catalyzed transfer hydrogenation Tetrahedron: Asymmetry 9 (1998) 1143-1163.
22] P. W. Galka, H. B. Kraatz, Synthesis and study of amino acid based phosphinite ligands, J. Organomet. Chem.
74 (2003) 24-31.
23] R. Guo, X. Chen, C. Elphelt, D. Song, R. H. Morris, Applications of Ruthenium Hydride Borohydride
Complexes Containing Phosphinite and Diamine Ligands to Asymmetric Catalytic Reactions Organic Lett. 7 (2005)
757-1759.
24] T. Ohta, H. Takaya, R. Noyori, Bis(diarylphosphino)-1,1 binaphthyl (BINAP)-ruthenium(II) dicarboxylate
complexes: new, highly efficient catalysts for asymmetric hydrogenations Inorg. Chem. 27 (1998) 566-569.
25] R. H. Grubbs, R. A. DeVries, Asymmetric hydrogenation by an atropisomeric diphosphinite rhodium complex
Tetrahedron Lett. 18 (1977) 1879-1880.
26] M. J. Palmer, M. Wills, Asymmetric Transfer Hydrogenation of C=O and C=N Bonds Tetrahedron: Asymmetry
0 (1999) 2045-2061.
[
6
[
1
[
[
[
1
2
2

ACCEPTED MANUSCRIPT
[
27] H. Y. Rhyoo, H. J. Park, Y. K. Chung, The first Ru(II)-catalysed asymmetric hydrogen transfer reduction of
aromatic ketones in aqueous media Chem. Commun. (2001) 2064-2065.
28] X. Li, X. Wu, W. Chen, F. E. Hancock, F. King, J. Xiao, Asymmetric Transfer Hydrogenation in Water with a
Supported Noyori−Ikariya Catalyst Org. Lett. 19 (2004) 3321-3324
29] K. Everaere, A. Mortreux, J. F. Carpentier, Ruthenium(II)‐ Catalyzed Asymmetric Transfer Hydrogenation of
Carbonyl Compounds with 2‐ Propanol and Ephedrine‐ Type Ligands Adv. Synth. Catal. 345 (2003) 67-77.
[
[
[
(
[
30] Q. H. Fan, Y. M. Li, A. S. C. Chan, Recoverable Catalysts for Asymmetric Organic Synthesis Chem. Rev. 102
2002) 3385-3446.
31] J. S. M. Samec, J. E. Backwall, P. G. Andersson, P. Brandt, Mechanistic aspects of transition metal-catalyzed
hydrogen transfer reactions Chem. Soc. Rev. 35 (2006) 237-248.
32] S. E. Clapham, A. Hadzovic, R. H. Morris, Mechanisms of the H -Hydrogenation and Transfer Hydrogenation
[
2
of Polar Bonds Catalyzed by Ruthenium Hydride Complexes Coord. Chem. Rev. 248 (2004) 2201-2237.
[
[
33] S. C. Bergmeier, The Synthesis of Vicinal Amino Alcohols Tetrahedron 56 (2000) 2561-2576.
34] D. J. Ager, I. Prakash, D. R. Schaad, 1,2-Amino Alcohols and Their Heterocyclic Derivatives as Chiral
Auxiliaries in Asymmetric Synthesis Chem. Rev. 96 (1996) 835-876.
35] E. H. Corey, C. J. Helal, Reduction of Carbonyl Compounds with Chiral Oxazaborolidine Catalysts: A New
Paradigm for Enantioselective Catalysis and a Powerful New Synthetic Method Angew. Chem. Int. Ed. Eng. 37
[
(
1998) 1986-2012.
[
36] E. J. Korey, S. Shibata, R. K. Bakshi, A stable and easily prepared catalyst for the enantioselective reduction of
ketones. Applications to multistep syntheses J. Am. Chem. Soc. 109 (1987) 7925-7926.
[
[
37] H. B. Kagan, O. Riant, Catalytic asymmetric Diels Alder reactions Chem. Rev. 92 (1992) 1007-1019.
38] B. Ak, D. Elma, N. Meriç, C. Kayan, U. Işık, M. Aydemir, F. Durap, A. Baysal, New chiral ruthenium(II)–
phosphinite complexes containing a ferrocenyl group in enantioselective transfer hydrogenations of aromatic
ketones Tetrahedron: Asymmetry 24 (2013) 1257-1264.
[
39] M. Aydemir, N. Meric, A. Baysal, C. Kayan, M. Toğrul, B. Gümgüm, New chiral phosphinite ligands with
C -symmetric axis and their possible applications in Ru-catalyzed asymmetric transfer hydrogenation Appl.
2
Organomet. Chem. 24 (2010) 215-221.
[
40] B. Ak, F. Durap, M. Aydemir, A. Baysal. Ruthenium(II) complexes derived from C ‐ symmetric
2
ferrocene‐ based chiral bis(phosphinite) ligands: synthesis and catalytic activity towards the asymmetric reduction
of acetophenones Appl. Organomet. Chem. 29 (2015) 764-770.
[
41] F. Durap, D. E. Karakaş, B. Ak, A. Baysal, M. Aydemir. Asymmetric transfer hydrogenation of alkyl/aryl or
alkyl/methyl ketones catalyzed by known C -symmetric ferrocenyl-based chiral bis(phosphinite)-Ru(II), Rh(I) and
2
Ir(III) complexes J. Organomet. Chem. 818 (2016) 92-97.
[
42] M. Aydemir, F. Durap, A. Baysal, N. Meriç, A Buldağ, B. Gümgüm, S. Özkar, L. T. Yıldırım, Novel neutral
phosphinite bridged dinuclear ruthenium(II) arene complexes and their catalytic use in transfer hydrogenation of
aromatic ketones: X-ray structure of a new Schiff base, N3,N3′-di-2-hydroxybenzylidene-[2,2′]bipyridinyl-3,3′-
diamine J. Mol Catal A: Chemical 326 (2010) 75-81.
2
3

ACCEPTED MANUSCRIPT
[
43] M. Aydemir, A. Baysal, E. Şahin, B. Gümgüm, S. Özkar, Aminophosphine–palladium(II) complexes:
Synthsesis, structure and applications in Suzuki and Heck cross-coupling reactions Inorg. Chim. Acta. 378 (2011)
0-18.
44] B. Ak, M. Aydemir, Y. S. Ocak, F. Durap, C. Kayan, A. Baysal, H. Temel, Readily available ferrocenyl-
1
[
phosphinite ligands for Ru(II)-catalyzed enantioselective transfer hydrogenation of ketones and fabrication of hybrid
heterojunctions Inorg Chim Acta 409 (2014) 244-253.
[
45] H. Tye, C. Eldred, M. Wills, An efficient method for the synthesis of N,N′-dimethyl-1,2-diaminesTetrahedron
Lett. 43 (2002) 155-158.
46] T. Aral, M. Karakaplan, H. Hoşgören. Asymmetric Organocatalytic Efficiency of Synthesized Chiral b-Amino
Alcohols in Ring-Opening of Glycidol with Phenols Catal. Lett. 142 (2012) 794-802.
47] S. P. Panchgalle, R. G, Gore, S. P. Chavan, U. R. Kalkote, Organocatalytic enantioselective synthesis of β-
blockers: (S)-propranolol and (S)-naftopidil Tetrahedron: Asymmetry 20 (2009) 1767-1770.
[
[
[
[
48] K. Kitaori, Y, Furukawa, H, Yoshimoto, J. Ctera. Tetrahedron Lett. 36 (1995) 2379-2382.
49] A. Tribo, S. Munoz, J. Pons, R. Yanez, A. Alvarez-Larena, J. F. Piniella, J. Ros, Synthesis and characterisation
of new pyrazole–phosphinite ligands and their ruthenium(II) arene complexes J. Organomet. Chem. 690 (2005)
072-4079.
50] A. Baysal, M. Aydemir, F. Durap, B Gümgüm, S. Özkar, LT. Yıldırım Synthesis and characterizations of 3,3′-
4
[
bis(diphenylphosphinoamine)-2,2′-bipyridine and 3,3′-bis(diphenylphosphinite)-2,2′-bipyridine and their
chalcogenides Polyhedron 25 (2007) 3373-3378.
[
51] Z. Fei, R. Scopelliti, P. J. Dyson. Understanding Structure Does Not Always Explain Reactivity:ꢀ A
Phosphinoamide Anion Reacts as an Iminophosphide Anion Inorg. Chem. 42 (2003) 2125-2130.
52] Z. Fei, R. Scopelliti, P. J. Dyson, On the Reactivity of the Iminodiphosphane C6H4(o‐ CN)N=PPh2−PPh2:
Fragmentation Versus Isomerisation Eur. J. Inorg. Chem. (2004) 530-537.
53] K. Ruhlan, P. Gigler, E. Herdweck, Some phosphinite complexes of Rh and Ir, their intramolecular reactivity
and DFT calculations about their application in biphenyl metathesis J. Organomet Chem. 693 (2008) 874-893.
54] E.A. Broger, W. Burkart, M. Hennig, M. Scalone, R. Schmid, New amidophosphine-phosphinites (tLANOPs)
as chiral ligands for asymmetric hydrogenation reactions Tetrahedron: Asymmetry 9 (1998) 4043-4054.
55] T. Iwai, Y. Akiyama, K. Tsunoda, M. Sawamura, Synthesis and structures of a chiral phosphine–phosphoric
acid ligand and its rhodium(I) complexes Tetrahedron: Asymmetry 26 (2015) 1245-1250.
56] H. Le Bozec, D. Touchard, P.H. Dixneuf, Organometallic Chemistry of Arene Ruthenium and Osmium
Complexes Adv. Organomet Chem. 29 (1989) 163-247.
57] M.A. Bennet, G.B. Robertson, A.K. Smith, Divalent ruthenium complexes containing non-planar hexahapto-
benzene J. Organomet. Chem. 43 (1972) C41-C43.
58] E. de la Encarnacion, J. Pons, R. Yanez, J. Ros, Stereochemical structure determination of p-cymene Ru(II)
complexes containing the PPh Py ligand with 2-D NOESY and HMQC NMR experiments Inorg Chim Acta 358
[
[
[
[
[
[
[
2
(
2005) 3272-3276.
2
4

ACCEPTED MANUSCRIPT
[
59] I. Moldes, E. de la Encarnacion, J. Ros, A. Alvarez-Larena, J.F. Piniell, Ruthenium(II) complexes containing
both arene and functionalized phosphines. Synthesis and catalytic activity for the hydrogenation of styrene and
phenylacetylene J. Organomet. Chem. 566 (1998) 165-174.
[
60] A. Caballero, F.J. Jalon, B. Manzano, G. Espino, M. Perez-Manrique, A. Mucientes, F.J. Poblete, M. Maestro,
Ruthenium Arene Derivatives with P-N Hemilabile Ligands. P−C Cleavage and Phosphine to Phosphinite
Transformation, Organometallics 23 (2004) 5694-5706.
[
61] A.J. Davenport, D.L. Davies, J. Fawcett, D.R. Russell, Arene–ruthenium complexes with salicyloxazolines:
diastereoselective synthesis, configurational stability and applications as asymmetric catalysts for Diels–Alder
reactions, Dalton Trans. (2004) 1481-1492.
[
62] H. Takahashi, K. Kobayashi, M. Osawa, Crystal structure of monomerix arene chloro ruthenium (II) complex,
[
RuCl C H (MeCN)], Anal. Sci. 16 (2000) 777-779.
2
6
6
[63] M.S. Balakrishna, P.P. George, S.M. Mobin, A new diphosphinite derived from cyclohexane-1,4-
diol:oxidation reactions, metal complexes, P–O bond cleavage and X-ray crystal structures of
Ph P(E)O(C H )OP(E)Ph (E = S, Se), Polyhedron 24 (2005) 475-480.
2
6
10
2
[
64] I.D. Kostas, B.R. Steele, A. Trezis, S.V. Amosova, A palladium complex with a new hemilabile amino- and
sulfur-containing phosphinite ligand as an efficient catalyst for the Heck reaction of aryl bromides with styrene. The
effect of the amino group, Tetrahedron 59 (2003) 3467-3473.
[
65] Q. Zhang, G. Hua, P. Bhattacharrya, A.M.Z. Slawin, J.D. Woollins, Synthesis and coordination chemistry of
aminophosphine derivatives of adenine, J. Chem. Soc, Dalton. Trans. (2003) 3250-3257.
66] M. Alvarez, N. Lugan, R Mathieu, Synthesis and evaluation of the bonding properties of a potentially tridentate
ligand: 1-(diphenylphosphino)-2-ethoxy-1-(2-pyridyl)ethane, J. Chem. Soc. Dalton Trans. (1994) 2755-2760.
67] H. Yang, M. Alvarez, N. Lugan, R. Mathieu, Ruthenium(II) complexes with new tridentate ligands containing
[
[
P, N, O donor atoms: highly efficient catalysts for transfer hydrogenation of ketones by propan-2-ol, J. Chem Soc,
Chem. Commun. (1995) 1721-1722.
[
68] E.L. Muetterties, J.R. Bleeke, E.J. Wucherer, T.A. Albright, Structural, stereochemical, and electronic features
of arene-metal complexes, Chem. Rev. 82 (1982) 499-525.
[
69] J.W. Faller, A.R. Lavoie, Catalysts for the Asymmetric Transfer Hydrogenation of Ketones Derived from l-
Prolinamide and (p-CymeneRuCl ) or (Cp*RhCl ) , Organometallics 20 (2001) 5245-5247.
2
2
2 2
[
70] A. Kiliç, M. Aydemir, M. Durgun, N. Meriç, Y.S. Ocak, A. Keleş, H. Temel, Fluorine/phenyl chelated boron
complexes: Synthesis, fluorescence properties and catalyst for transfer hydrogenation of aromatic ketones, J. Fluor.
Chem. 162 (2014) 9-16.
[
71] M. Aydemir, N. Meriç, C. Kayan, F. Ok, A. Baysal, Rhodium-catalyzed transfer hydrogenation with
functionalized bis(phosphino)amine ligands, Inorg. Chim. Acta, 398 (2013) 1-10.
72] S. Hashiguchi, A. Fujii, J. Takehara, T. Ikariya, R. Noyori, Asymmetric Transfer Hydrogenation of Aromatic
Ketones Catalyzed by Chiral Ruthenium(II) Complexes, J. Am. Chem. Soc. 115 (1995) 7562-7563.
73] K. Rafikova, N. Kystaubayeva, M. Aydemir, C. Kayan, Y. S. Ocak, H. Temel, A. Zazybin, N. Gürbüz, I.
Özdemir, Transfer hydrogenation of ketones catalyzed by new rhodium and iridium complexes of aminophosphine
[
[
2
5

ACCEPTED MANUSCRIPT
containing cyclohexyl moiety and photosensing behaviors of rhodium and iridium based devices, J. Organomet.
Chem. 758 (2014) 1-8.
[
74] J.X. Gao, X.D. Yi, P.P. Xu, C.L. Tang, H.L. Wan, T. Ikariya, New chiral cationic rhodium–aminophosphine
complexes for asymmetric transfer hydrogenation of aromatic ketones, J. Organomet. Chem. 592 (1999) 290-295.
75] J.X. Gao, H. Zhang, X.D. Yi, P.P. Xu, C.L. Tang, H.L. Wan, K.R. Tsai, T. Ikariya, New chiral catalysts for
reduction of ketones, Chirality 12 (2000) 383-388.
76] J.S. Chen, Y.Y. Li, Z.R. Dong, B.Z. Li, J.X. Gao, Asymmetric transfer hydrogenation of aromatic ketones
catalyzed by the iridium hydride complex under ambient conditions, Tetrahedron Lett. 45 (2004) 8415-8418.
[
[
[
77] Z.R. Dong, Y.Y. Li, J.S. Chen, B.Z. Li, Y. Xing, J.X. Gao, Highly Efficient Iridium Catalyst for Asymmetric
Transfer Hydrogenation of Aromatic Ketones under Base-Free Conditions, Org. Lett. 7 (2005) 1043-1045.
[
[
78] M. A. Bennet, A. K. Smith, J. Chem. Soc. Dalton Trans. (1974) 233-241.
79] R. A. Zelonka, M. C. Baird. Arene ruthenium(II) complexes formed by dehydrogenation of cyclohexadienes
with ruthenium(III) trichloride J. Organomet. Chem. 35 (1972) C43.
2
6

ACCEPTED MANUSCRIPT
Captions
Scheme 1 Synthesis of aminoalcohols and phosphinites. (i) a) PhCHO, MeOH, (reflux); b)
NaBH , (reflux); MeOH equiv. (ii) (R)-Styrene oxide, MeOH; (iii) (S)-Glycidyl phenyl ether,
4
MeOH; (iv and v) 1/2 equiv. Ph PCl, 1/2 equiv. Et N, thf.
2
3
Scheme 2
Synthesis of aminoalcohols, phosphinites and their corresponding Ru(II)-arene
6
6
complexes. (i and iii) 1/2 equiv. [Ru(η -p-cymene)(µ-Cl)Cl] , thf; (ii and iv) 1/2 equiv. [Ru(η -
2
benzene)(µ-Cl)Cl] , thf.
2
3
1
1
Figure 1 The P-{ H} NMR spectra of phosphinites (3, 4) and their Ru(II)-complexes (5-8).
2
7

ACCEPTED MANUSCRIPT
Table 1 Transfer hydrogenation of acetophenone with 2-propanol catalyzed by (1R)-2-{benzyl[(1S)-1-(naphthalen-
6
1
{
-yl)ethyl]amino}-1-phenylethyl
diphenylphosphinito[dichloro(η -p-cymene)ruthenium(II)]
(7),
(1R)-2-
6
benzyl[(1S)-1-(naphthalen-1-yl)ethyl]amino}-1-phenylethyl diphenylphosphinito[dichloro(η -benzene) ruthenium
(8), (2S)-1-{benzyl[(1S)-1-(naphthalen-1-yl)ethyl]amino}-3-phenoxypropan-2-yl diphenyl-
phosphinito[dichloro(η -p-cymene)ruthenium (II)] (9) and (2S)-1-{benzyl[(1S)-1-(naphthalen-1-yl)ethyl]amino}-3-
(
II)]
6
6
phenoxypropan-2-yl diphenylphosphinito [dichloro(η -benzene) ruthenium (II)] (10).
O
OH
OH
O
Cat.
*
+
+
[f]
[g]
[h]
-1 [i]
Entry
Complex
S/C/KOH
Time
Conversion(%)
% ee
Conf.
S
S
R
R
TOF(h )
[
a]
d
d
1
7
8
9
100:1:5
96h
12 (22) d
72 (65) d
<5
[a]
a]
2
3
4
100:1:5
100:1:5
100:1:5
96h
96h
96h
16 (28) d
21 (34)
81 (77) d
86 (81)
<5
<5
<5
[
[
a]
d
d
10
28 (53)
91 (87)
[
[
[
b]
b]
b]
5
6
7
8
7
8
9
100:1
100:1
100:1
100:1
1h
1h
1h
1h
trace
trace
trace
trace
….
….
….
….
….
….
….
….
….
….
….
….
[b]
10
[
[
[
c]
c]
c]
e
e
9
7
8
9
100:1:5
100:1:5
100:1:5
100:1:5
2 h
1 h
1 h
1/2 h
97 (91) e
78 (70) e
S
S
R
R
48
98
99
196
10
11
12
98 (93) e
99 (93) e
98 (92)
87 (79) e
91 (86) e
96 (91)
[c]
10
[k]
[k]
[k]
[k]
13
14
15
16
10
10
10
10
100:1:3
100:1:5
100:1:7
100:1:9
1/2 h
1/2 h
1/2 h
1/2 h
94
98
90
87
89
96
90
91
S
S
R
R
188
196
180
174
[
a]
[b]
Reaction conditions:
At room temperature; acetophenone/Cat./KOH, 100:1:5;
Refluxing in 2-propanol;
[c]
[d]
acetophenone/Cat., 100:1, in the absence of base; Refluxing in 2-propanol; acetophenone/Cat./KOH, 100:1:5; At room
temperature; acetophenone/Cat./KOH, 100:1:5, (120 h); Refluxing in 2-propanol; acetophenone/Cat./NaOH, 100:1:5;
Determined by GC (three independent catalytic experiments); Determined by capillary GC analysis using a chiral cyclodex
B (Agilent) capillary column (30 m x 0.32 mm I.D. x 0.25 µm film thickness); Determined by comparison of the retention
[e]
[f]
[g]
[h]
times of the enantiomers on the GC traces with the literature values, (S) or (R) configuration was obtained in all experiments;
[i]
-1 [k]
TOF = (mol product/mol Cat.) x h ; Refluxing in 2-propanol; acetophenone/Cat.,100:1.

ACCEPTED MANUSCRIPT
Table 2 Transfer hydrogenation results for substituted acetophenones with the catalyst systems prepared from (1R)-
6
2
-{benzyl[(1S)-1-(naphthalen-1-yl)ethyl]amino}-1-phenylethyl
diphenylphosphinito[dichloro(η -p-
cymene)ruthenium(II)]
diphenylphosphinito[dichloro(η -benzene)
yl)ethyl]amino}-3-phenoxypropan-2-yl diphenyl- phosphinito[dichloro(η -p-cymene)ruthenium (II)] (9) and (2S)-
(7),
(1R)-2-{benzyl[(1S)-1-(naphthalen-1-yl)ethyl]amino}-1-phenylethyl
6
ruthenium
(II)]
(8),
(2S)-1-{benzyl[(1S)-1-(naphthalen-1-
6
6
1
-{benzyl[(1S)-1-(naphthalen-1-yl)ethyl]amino}-3-phenoxypropan-2-yl diphenylphosphinito [dichloro(η -benzene)
[a]
ruthenium (II)] (10).
[b]
[c]
[d]
Entry
Cat.
Substrate
Product
Time
Conv.(%)
% ee
Config.
O
OH
1
2
3
4
7
8
9
10
45 min
20 min
20 min
10 min
98
97
99
99
77
85
90
94
S
S
R
R
O
2
N
O N
2
CF3
CF
3
5
6
7
8
7
8
9
10
O
OH
1 h
97
98
98
97
79
87
92
96
S
S
R
R
30 min
30 min
20 min
O
OH
9
7
8
9
10
45 min
20 min
20 min
10 min
99
98
98
99
76
85
90
94
R
R
R
R
F
3
C
F3C
10
11
12
O
OH
OH
OH
1
1
1
1
3
4
5
6
7
8
9
10
30 min
15 min
15 min
5 min
99
99
97
98
74
84
86
90
S
S
R
R
F
3
C
F3C
O
17
18
19
20
7
8
9
10
13 h
8 h
8 h
5 h
97
99
98
98
81
89
92
98
S
S
R
R
H CO
H CO
3
3
O
21
22
23
24
7
8
9
10
8 h
5 h
5 h
3 h
99
99
97
99
66
73
81
87
S
S
R
R
H CO
3
H CO
3
CH3
CH3
25
26
27
28
7
8
9
10
O
OH
12 h
7 h
7 h
4 h
97
99
98
99
70
74
85
93
S
S
R
R
O
OH
29
30
31
32
7
8
9
10
9 h
5 h
5 h
3 h
97
98
98
99
67
71
81
90
S
S
R
R
H C
3
H C
3
O
OH
33
34
35
36
7
8
9
10
6 h
3 h
3 h
2 h
98
99
97
99
64
68
79
84
S
S
R
R
H C
3
H C
3