Chiral C2-symmetric η6-p-cymene-Ru(II)-phosphinite complexes: Synthesis and catalytic activity in asymmetric reduction of aromatic, methyl alkyl and alkyl/aryl ketones

Article abstract of DOI:10.1016/j.ica.2017.11.044

Chiral C₂-symmetric bis(phosphinite) ligands and their binuclear ruthenium(II) complexes have been synthesized and used as catalysts in the ruthenium-catalyzed asymmetric transfer hydrogenation of aromatic, methyl alkyl and alkyl/aryl ketones using 2-propanol as both the hydrogen source and solvent in the presence of KOH. Under optimized conditions, all complexes showed high catalytic activity as catalysts in the reduction of various ketones to corresponding chiral secondary alcohols. Products were obtained with high conversions (99%) and moderate to good enantioselectivities (82% ee). Furthermore, C₂-symmetric bis(phosphinite) ligands and their binuclear ruthenium(II) complexes were characterized by multinuclear NMR spectroscopy, FT-IR spectroscopy, LC/MS-MS and elemental analysis.

Full text of DOI:10.1016/j.ica.2017.11.044

Accepted Manuscript
Research paper
Chiral C2 -Symmetric η 6-p-cymene-Ru(II)-phosphinite Complexes: Synthesis,
and Catalytic Activity in Asymmetric Reduction of Aromatic, Methyl Alkyl and
Alkyl/Aryl Ketones
Duygu Elma Karakaş, Murat Aydemir, Feyyaz Durap, Akın Baysal
PII:
S0020-1693(17)31308-7
https://doi.org/10.1016/j.ica.2017.11.044
ICA 18014
DOI:
Reference:
Inorganica Chimica Acta
To appear in:
Received Date:
Revised Date:
Accepted Date:
18 August 2017
16 October 2017
22 November 2017
Please cite this article as: D.E. Karakaş, M. Aydemir, F. Durap, A. Baysal, Chiral C2 -Symmetric η 6-p-cymene-
Ru(II)-phosphinite Complexes: Synthesis, and Catalytic Activity in Asymmetric Reduction of Aromatic, Methyl
Alkyl and Alkyl/Aryl Ketones, Inorganica Chimica Acta (2017), doi: https://doi.org/10.1016/j.ica.2017.11.044
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Chiral C2-Symmetric η6-p-cymene-Ru(II)-phosphinite Complexes: Synthesis,
and Catalytic Activity in Asymmetric Reduction of Aromatic, Methyl Alkyl
and Alkyl/Aryl Ketones
Duygu ELMA KARAKAŞa,b, Murat AYDEMİRa, Feyyaz DURAPa*, Akın BAYSALa
aDepartment of Chemistry, Faculty of Science, Dicle University, 21280 Diyarbakır, Turkey
bScience and Technology Application and Research Center (SIUBTAM), Siirt University, 56000 Siirt, Turkey
Abstract
Chiral C2-symmetric bis(phosphinite) ligands and their binuclear ruthenium(II) complexes have
been synthesized and used as catalysts in the ruthenium-catalyzed asymmetric transfer
hydrogenation of aromatic, methyl alkyl and alkyl/aryl ketones using 2-propanol as both the
hydrogen source and solvent in the presence of KOH. Under optimized conditions, all complexes
showed high catalytic activity as catalysts in the reduction of various ketones to corresponding
chiral secondary alcohols. Products were obtained with high conversions (99%) and moderate to
good enantioselectivities (82% ee). Furthermore, C2-symmetric bis(phosphinite) ligands and
their binuclear ruthenium(II) complexes were characterized by multinuclear NMR spectroscopy,
FT-IR spectroscopy, LC/MS-MS and elemental analysis.
Keywords: Ruthenium(II), C2-symmetry, phosphinite, asymmetric transfer hydrogenation,
ketones.
*To whom correspondence should be addressed: Department of Chemistry, Science Faculty, Dicle University, 21280, Diyarbakır, Turkey. Tel:
+90 412 2488550/3065; e-mail: fdurap@dicle.edu.tr ; http://orcid.org/0000-0003-0899-1948
1

1. Introduction
After many decades of intensive investigations, the preparation and study of the coordination
chemistry of the optically pure phosphorus based ligands such as phosphine[1], phosphinite[2-4]
and phosphite[5] have received renewed attention due to their unique catalytic performances.
Phosphorus based ligands are highly versatile ligands with applications ranging from cluster
chemistry[6], bioinorganic chemistry[7], and homogeneous asymmetric catalysis[8, 9] to
materials sciences[10]. Among chiral ligands, C2-symmetric ligands have been dominated in
asymmetric catalysis for a long time[11]. Many improved C2-symmetric phosphinite ligands
have important applications in organometallic chemistry and asymmetric catalysis[11, 12],
giving selective catalysts for asymmetric transfer hydrogenation reactions [4, 13-17].
Phosphinites can be used to fine tune the metal reactivity and selectivity, so use of phosphinites
are widespread in organometallic chemistry and in homogeneous catalysis.
Metal-catalyzed asymmetric transfer hydrogenations without doubt represent a powerful and
practical method for the reduction of pro-chiral ketones to produce the corresponding optically
pure secondary alcohols, which are important class of intermediates for the fine chemicals
especially pharmaceutical[18], agrochemical[19], cosmetic, food and flavour industries[20, 21].
A number of transition metal complexes are known to be used in asymmetric transfer
hydrogenation (ATH) reactions as catalysts [22]. Over the last two decades, a considerable
amount of effort has been devoted to the design and synthesis of new chiral ligands bearing
Ni(II)[22], Fe[23], Ru(II)[17], Rh(I)[13, 24] and Ir(III)[14, 25] complexes. Among the well-
known transition metals used in homogeneous catalysis ruthenium is the most prominent one.
The choice of ruthenium among other metals in hydrogenation catalysis is due to its superior
performances in terms of selectivity and activity. In particular chiral C2-symmetric structures
represent an important class of ligands used in homogeneous asymmetric catalysis with transition
metals[11].
2

Recently, our research group has been attracted by the obvious advantages and aesthetics of
C2- symmetry. Previously, we have reported that the novel half-sandwich complexes based on
the ligands with C2-symmetric P-O backbone are active catalysts in the reduction of pro-chiral
aromatic, methyl alkyl and alkyl/aryl ketones [25, 26]. In this context, herein we present the
synthesis and characterization of new chiral C2-symmetric bis(phosphinite) ligands and their half
sandwich η6-p-cymene-Ru(II)-phosphinite complexes as well as their activities explored as
catalysts for the asymmetric transfer hydrogenation of aromatic, alkyl methyl or alkyl/aryl
ketones.
2. Experimental
2.1.
Materials and Methods
Unless otherwise mentioned, all reactions were carried out under an atmosphere of argon
using conventional Schlenk glassware, Solvents were dried using established procedures and
distilled under argon just prior to use. The starting materials D-phenyl alaninol, D-phenyl
glycinol, (R)-(−)-1-Amino-2-propanol, (R)-(-)-2-amino-1-butanol, PPh2Cl, Et3N and [Ru(ղ 6-p-
cymene)(µ-Cl)Cl]2 were purchased from Fluka and used as received. 2,6-bis-
(bromomethyl)pyridine or 1,3-bis(bromomethyl)benzene, chiral C2-symmetric amino alcohols
(1-6) [27] and bis(phosphinite) ligands (9-12) [12] were synthesized according to the literature
1
13
31
procedures. H (at 400.1 MHz), C (at 100.6 MHz) and P-{1H} NMR (at 162.0 MHz) spectra
were recorded on a Bruker AV 400 spectrometer, with TMS (tetramethylsilane) as an internal
31
reference for 1H NMR and 13C NMR or 85% H3PO4 as an external reference for P-{1H} NMR,
respectively. FTIR-ATR spectra were recorded with a Perkin Elmer Spectrum 100 spectrometer.
Mass analyses were recorded with Shimadzu LC/MS 8040 spectrometer. Specific rotations were
taken on a Perkin-Elmer 341 model polarimeter. Elemental analysis was carried out on a Costech
ECS 4010 instrument. Melting points were recorded by a Gallenkamp Model apparatus with
3

open capillaries. GC analyses were performed on a Shimadzu GC 2010 Plus Gas Chromatograph
equipped with a cyclodex-B (Agilent) capillary column (30 m x 0.32 mm I.D. x 0.25μm film
thickness). Racemic samples of alcohols were obtained by reduction of the corresponding
ketones with NaBH4 and used as the authentic samples for %ee determination. The GC
parameters for asymmetric transfer hydrogenation of ketones were as follows; initial
temperature, 50 ºC; initial time 1.1 min; solvent delay, 4.48 min; temperature ramp 1.3 ºC/min;
final temperature, 150 ºC; initial time 2.2 min; temperature ramp 2.15 ºC/min; final temperature,
250 ºC; initial time 3.3 min; final time, 44.33 min; injector port temperature, 200 ºC; detector
temperature, 200 ºC, injection volume, 1.0 μL.
2.2.
Synthesis
2.2.1. General procedure for the preparation of the chiral C2-symmetric amino
alcohols (7,8)
Corresponding chiral amino alcohol (30 mmol), 1,3-bis(bromomethyl)benzene (15 mmol,
3.96 g), sodium carbonate (46 mmol, 4.86 g) and KI (0.050 g) in EtOH (50 mL) were stirred at
100 oC for 12 h under argon. The mixture was allowed to cool room temperature and CHCl3 (100
mL) was then added to the mixture and refluxed for another 2 h. The solution was filtered,
solvent was removed in vacuo and CHCl3 (50 mL) was added to the residue. The solution was
washed with water and brine (50 mL) twice. The aqueous solution was extracted with CHCl3
(2x50 mL). The combined CHCl3 phases were dried over anhydrous Na2SO4.
2.2.1.1.
(2R)-2-[benzyl({[3-({benzyl[(2R)-1-hydroxybutane-2-yl]amino}
methyl)
phenyl] methyl}) amino]- butane-1-ol (7)
Prepared from (2R)-2-(benzylamino)-butan-1-ol (30 mmol, 5.38 g) to the general procedure
o
2.2.1. The crude product 7 was obtained as yellow oil (6.0 g, 87%) C; [α]D20: -56.5 (c:1,
CH2Cl2); Anal.Calcd. for C30H40O2N2: C: 78.22; H: 8.75; N: 6.08. Found: C: 78.01; H: 8.54; N:
5.92; 1H-NMR (δ ppm, CDCl3 ): 7.33-7.17 (m, 14H, C6H5); 3.84 (m, 4H, -CH2N-); 3.53-3.87 (m,
4

2H, -CH2OH (b)); 3.40-3.47 (m, 2H, -CH2OH (a)+4H, -CH2Ph ); 3.22 (br, 2H, OH ); 2.75-2.72
(m, 2H, N-CH ); 1.77-1.87 (m, 2H, -CH2CH3 (a)); 1.23-1.31 (m, 2H, -CH2CH3 (b)) 0.93 (t, 6H,
J=7.50 Hz -CH2CH3). 13C-NMR (δ ppm, CDCl3): 139.70, 139.37, (i-C6H5); 127.20, 127.89,
128.48, 128.64, 129.03, 129.65 (C6H5 ); 60.95 (-NCH-); 60.56 (-CH2OH); 53.20, 53.42(-CH2Ph,
-CH2N-); 17.99 (-CH2CH3); 11.99 (-CH2CH3); IR (KBr pellet, cm-1) υ(OH): 3426; υ(CH): 3060,
3027, 2960, 2930; υ(C=C): 1494, 1452, 1421.
2.2.1.2.
(2R)-2-[benzyl({[3-({benzyl[(1R)-2-hydroxy-1-
phenylethyl]amino}methyl)phenyl]methyl}) amino]-2-phenyl ethane-1-ol (8)
Prepared from (2R)-2-(benzylamino)-2-phenylethane-1-ol (30 mmol, 6.81 g) according to the
general procedure 2.2.1. The crude product 8 was obtained as yellow oil (8.0 g, 96 %); [α]D20: -
153.5 (c 1, CH2Cl2); Anal.Calcd. for C38H40O2N2 : C: 81.98; H: 7.24; N: 5.03. Found: C: 81.67;
1
H: 7.03; N: 4.91; H-NMR (δ ppm, CDCl3 ): 7.25-7.48 (m, 24H, C6H5); 4.15-4.20 (m, 2H,
CH2OH (b)); 3.93-4.00 (m, 4H, -CH2Ph+2H, CHPh); 3.65 (m, 2H, -CH2OH (a)); 3.22-3.17 (m,
4H, -NCH2); 3.08 (br, 2H, -CH2OH).13C-NMR (δ ppm, CDCl3): 135.23, 139.15, 139.60 (i-C6H5);
127.26, 127.89, 128.03, 128.28, 128.41, 128.59, 128.74, 128.95, 129.37 (C6H5 ); 63.31 (-CHPh);
60.62 (-CH2OH); 53.56, 53.77 (-CH2N+(-CH2Ph); IR (KBr pellet, cm-1) υ(OH): 3419; υ(CH):
3060, 3027, 2834; υ(C=C): 1493, 1451, 1420.
2.2.2. General procedure for the synthesis of the chiral C2-symmetric
bis(diphenylphosphinite) ligands (13-16).
To a solution of aminoalcohol 5-8 (1.5 mmol) in dry toluene (20 mL) was added triethylamine
(3.0 mmol, 0.31 g) and the mixture was stirred for 10 min under argon atmosphere. To this
solution was added dropwise monochlorodiphenylphosphine, Ph2PCl (3.0 mmol, 0.68 g). The
mixture was then stirred at room temperature until the reactions were completed. A white
precipitate of triethylamine hydrochloride was removed by filtration under argon and the
5

remaining organic phase was evaporated under reduced pressure to produce a white viscous oily
product. The phosphinite ligands were observed to be stable in the ambient air.
2.2.2.1.
(2R)-2-[benzyl({[6-{[benzyl[(1R)-2-[(diphenylphosphanyl)oxy]-1-
phenylethyl]amino}
methyl)pyridin-2-yl]methyl})amino]-2-
phenylethyldiphenylphosphinite] (13)
Prepared from chiral amino alcohol 5 (1.5 mmol, 0.84 g) according to the general procedure
2.2.2. White viscous oily product 13 (1.3 g, 94%). Anal. Calcd. for C61H57N3O2P2; C 79.11; H
1
6,21; N 4.54, Found; C 79.01; H 6.08; N 4.42; H-NMR (δ ppm, CDCl3): 7.20-7.39 (m, 43H,
aromatic protons); 4.42 (m, 2H, -CH2OP (b)); 4.18-4.25 (m, 2H, CH2OP (a),+2H, -NCH); 3.91
(m, 4H, -NCH2Py); 3.52 (m, 4H, -NCH2Ph). 13C-NMR (δ ppm, CDCl3): 137.29, 139.72, 141.80,
159.53, (i-carbons); 126.92, 127.41, 128.22, 128.30, 128.81, 128.11, 129.29, 130.20, 130.41,
130.51, 130.54, 130.73 (aromatic carbons); 69.53 (d, J=18,1 Hz, -CH2OP); 63.48 (d, J=8.1 Hz, -
NCH); 56.22 (-NCH2Py); 55.04 (-NCH2Ph); 31P-{1H}-NMR (δ ppm, CDCl3): 114.51 (s, O-
P(Ph)2) (Fig S1); IR (KBr pellet in, cm-1): υ(CH): 3058, 3025, 2934; υ(C=N): 1589; υ(C=C):
1493, 1454, 1434; υ(O-P): 1022.
2.2.2.2.
(2R)-2-[benzyl({[6-({benzyl[(2R)-1-[(diphenylphosphanyl)oxy]butane-2-
yl]amino} methyl)pyridin-2-yl]methyl})amino]butyldiphenylphosphinite (14)
Prepared from chiral amino alcohol 6 (1.5 mmol, 0.69 g) according to the general procedure
2.2.2. White viscous oily product 14 (1.18 g, 95 %). Anal.Calcd. for C53H57N3O2P2; C 76.70; H
1
6.93; N 5.06; Found; C 76.52; H 6.75; N 4.93; H-NMR (δ ppm, CDCl3): 7.21-7.54 (m, 33H,
aromatic protons); 4.04 (m, 2H, -CH2OP (a)); 3.81-3.97 (m, 4H, -NCH2Py+2H, -CH2OP (b));
3.66 (m, 4H, -NCH2Ph); 2.86 (m, 2H, -CHCH2CH3); 1.72 (m, 2H, -CH2CH3 (a)); 1.58 (m, 2H, -
13
CH2CH3 (b)); 0.97 (t, 6H, J=7.2 Hz -CH2CH3). C-NMR (δ ppm, CDCl3): 160.05 (i-pyridine);
142.02 (d, J=18,1 Hz, i-OPC6H5); 136.69 (i-C6H5); 120.30, 126.72, 128.12, 128.30, 128.36,
128.49, 128.82, 129.17, 129.65, 130.29, 130.44, 130.50, 130.65 (aromatic carbons); 69.57 (d,
6

J=17,1 Hz, -CH2OP); 60.88 (d, J=9.1 Hz-CHCH2CH3); 56.09 (-NCH2Py); 55.09 (-NCH2Ph);
21.11 (-CH2CH3); 11.88 (-CH2CH3); 31P-{1H}-NMR (δ ppm, CDCl3): 115.02 (s, O-P(Ph)2) (Fig
S2); IR (KBr pellet in, cm-1): υ(CH): 3034, 3022, 2944; υ(C=N): 1575; υ(C=C): 1483, 1444,
1424; υ(O-P): 1026.
2.2.2.3.
(2R)-2-[benzyl({[3-({benzyl[(2R)-1-[(diphenylphosphanyl)oxy]butane-2-
yl]amino} methyl) phenyl]methyl})amino]butyldiphenylphosphinite (15)
Prepared from chiral amino alcohol 7 (1.5 mmol, 0.69 g) according to the general procedure
2.2.2. White viscous oily product 15 (1.15 g, 93 %). Anal.Calcd. for C54H58N2O2P2; C 78.24; H
1
7.06; N 3.38; Found; C 78.08; H 6.94; N 3.18; H-NMR (δ ppm, CDCl3): 7.24-7.59 (m, 34H,
aromatic protons); 4.01 (m, 4H, -CH2OP); 3.87 (m, 4H, -NCH2Py); 3.70 (m, 4H, -NCH2Ph); 2.87
(m, 2H, -CHCH2CH3); 1.66 (m, 2H, -CH2CH3 (b)); 1.57 (m, 2H, -CH2CH3 (a)); 0.98 (t, 6H, J=
7.2 Hz -CH2CH3). 13C-NMR (δ ppm, CDCl3): 140.41, 140.71, 142.05, 142.23 (i-carbons);
126.67, 127.34, 128.13, 128.34, 128.41, 128.81, 129.32, 129.42, 130.33, 130.48, 130.54, 130.70
(aromatic carbons); 69.51(d, J=17,1 Hz, -CH2OP); 59.74 (d, J= 8.1 Hz-CHCH2CH3); 54.37 (-
NCH2Py); 54.27 (-NCH2Ph); 21.83 (-CH2CH3); 11.76 (-CH2CH3); 31P-{1H}-NMR (δ ppm,
CDCl3): 114.17 (s, O-P(Ph)2) (Fig S3); IR (KBr pellet in, cm-1): υ(CH): 3377, 3057, 2961;
υ(C=C): 1493, 1452, 1438; υ(O-P): 1027.
2.2.2.4.
phenylethyl]amino}
phenylethyldiphenylphosphinite (16)
(2R)-2-[benzyl({[3-({benzyl[(1R)-2-[(diphenylphosphanyl)oxy]-1-
methyl)phenyl]methyl})
amino]-2-
Prepared from chiral amino alcohol 8 (1.5 mmol, 0.69 g) according to the general procedure
2.2.2. White viscous oily product 16 (1.28g, 92 %); Anal.Calcd. for C62H58N2O2P2; C 80.50; H
6.33; N 3.03; found; C 80.40; H 6.21; N 2.94; 1H-NMR (δ ppm, CDCl3): 7.23-7.47 (m, 44H,
aromatic protons); 4.43 (m, 2H, -CH2OP (b)); 4.31 (m, 2H, -CH2OP (a)); 4.19 (m, 2H, -NCH);
13
3.83 (m, 4H, -NCH2Py); 3.45 (m, 4H, -NCH2Ph); C-NMR (δ ppm, CDCl3): 137.88, 139.89,
7

140.01, 141.79, 141.97, (i-carbons); 126.83, 127.23, 127.41, 128.09, 128.18, 128.25, 128.32,
128.75, 129.34, 130.23, 130.48, 130.70, 130.83 (aromatic carbons); 69.36 (d, J=18.1 Hz, -
CH2OP); 62.48 (d, J=8.0 Hz, -NCH); 54.44 (-NCH2Py); 54.39 (-NCH2Ph). 31P-{1H}-NMR (δ
ppm, CDCl3): 114.87 (s, O-P(Ph)2); (Fig S4); IR (KBr pellet in, cm-1): υ(CH): 3055, 3026, 2924;
υ(C=C): 1480, 1453, 1452; υ(O-P): 1021.
2.2.3. General procedure for the synthesis of bis(phoshinite) ruthenium(II) complexes,
(17-24).
[Ru(ղ 6-p-cymene)(µ-Cl)Cl]2 (1.5 mmol, 0.92 g) and bis(phosphinite) ligands 9-16 (1.5
mmol) were dissolved in 30 mL of CH2Cl2 under argon atmosphere and stirred for 1 h at room
temperature. The resulting solution was concentrated to 2 mL under reduced pressure, and
addition of petroleum ether (15 mL) caused the precipitation of a tile-red solid. The supernatant
solution was decanted, the solid was washed with hexane:diethylether (1:1) and dried in vacuum,
yielding ruthenium(II) complex 17-24.
Complex 17
Prepared from bis(phosphinite) ligand 9 (1.5 mmol, 1.43 g ) according to the general procedure
o
20
2.2.3. Yield (17); 0.21 2.10 g, 89%, m.p: 145-147 C. [α]D = -41.3o (c: 0.5, CH2Cl2);
Anal.Calcd for C83H89N3O2P2Ru2Cl4; C 63.64; H 5.73; N 2.68; Found; C 63.40; H 5.48; N 2.55;
1H NMR (δ, ppm, CDCl3): 7.08-7.93 (m, 43H, aromatic protons); 5.07 (d, 2H, J= 5.8 Hz p-
cymene C6H4); 5.01 (d, 2H, J= 5.8 Hz p-cymene C6H4); 4.79 (d, 2H, J= 5.8 Hz p-cymene C6H4);
4.73 (d, 2H, J= 5.7 Hz p-cymene C6H4); 3.62-3.89 (m, 4H, -CH2Py+4H, - CH2OP + 4H,
NCH2Ph); 3.17 (m, 2H, -CHN); 3.01 (m, 4H, -CH2Ph); 2.55 (m, 2H CH(CH3)2 p-cymene); 1.46
13
(s, 6H, -CH3 p-cymene); 1.06 (d, 12H, J= 8.0 Hz, CH(CH3)2 p-cymene); C NMR (δ ppm,
CDCl3): 138,09, 139.51, 139.75, 159.51 (aromatic ipso carbons); 127.62, 127.86, 128.20, 128.45,
128.69, 129.52, 130.70, 130.86, 131.59, 131.69, 133.38, (aromatic carbons); 98.51, 113,20 (ipso
p-cymene); 88.30, 87.86, 88.43, 88.92 (p-cymene C6H4); 66.10 (-CH2OP); 61.41 (d, J= 8.1 Hz, -
8

CHCH2Ph): 55.58 (-NCH2Py); 54.33 (-NCH2Ph); 33.49 (-CHCH2Ph); 30.04 (-CH(CH3)2 p-
31
cymene); 21.81, 21.89 (-CH(CH3)2 p-cymene); 17.24 (-CH3 p-cymene); P-{1H}-NMR (δ ppm,
CDCl3): 112.13 (s); (Fig S5); IR (KBr pellet in, cm-1): υ(CH): 3056, 3025, 2958; υ(C=C): 1488,
1447, 1436; υ(O-P): 1025; m/z: 1567.45 [M-H+] C83H89N3O2P2Ru2Cl4 ( MA: 1566.503) (Fig
S6).
Complex 18
Prepared from bis(phosphinite) ligand 13 (1.5 mmol, 1.39 g ) according to the general procedure
o
2.2.3. Yield (18); 2.15 g, 93%, m.p: 136-138 C. [α]D20 = -47.5o (c: 0.5, CH2Cl2); Anal. Calcd.
1
for C81H85N3O2P2Ru2Cl42; C 63.20; H 5.57; N 2.73, Found; C 62.98; H 5.32; N 2.55; H NMR
(δ, ppm, CDCl3): 7.14-7.65 (m, 43H, aromatic protons); 4.98-5.13 (m, 8H, p-cymene C6H4);
3.93-4.31 (m, 6H, -CH2OP+ -CHN); 3.77 (m, 4H, -NCH2Py); 3.42 (m, 4H, -NCH2Ph); 2.59 (m,
2H, -CH(CH3)2 p-cymene); 1.64 (s, 6H, -CH3 p-cymene); 1.02 (d, 12H, J= 6.3 Hz, -CH(CH3)2 p-
13
cymene); C NMR (δ ppm, CDCl3): 135.94, 136,89, 139.42, 159.52 (aromatic ipso carbons);
120.87, 126.94, 127.69, 127.79, 128.28, 128.77, 128.85, 129.21, 130.79, 132.59, 132.70
(aromatic carbons); 97.49, 111,93 (ipso p-cymene); 87.37, 87.69, 90.12, 90.31 (p-cymene C6H4);
67.07 (-CH2OP); 61.88 (-NCH); 55.94 (-NCH2Py); 54.57 (-NCH2Ph); 30.08 (-CH(CH3)2 p-
cymene); 21.72, 21.90 (-CH(CH3)2 p-cymene); 17.35 (-CH3 p-cymene); 31P-{1H}-NMR (δ ppm,
CDCl3): 112.27 (s); (Fig S7); IR (KBr pellet in, cm-1): υ(CH): 3055, 2957, 2923; υ(C=C): 1452,
1448, 1375; υ(O-P): 1024; m/z: 1540.35 [M-H+] C81H85N3O2P2Ru2Cl4 ( MA: 1538.16) (Fig S8).
Complex 19
Prepared from bis(phosphinite) ligand 14 (1.5 mmol, 1.24 g ) according to the general procedure
o
2.2.3. Yield (19); 2.0 g, 92%, m.p: 125-127 C. [α]D20 = -41.4o (c: 1, CH2Cl2); Anal.Calcd. for
1
C73H85N3O2P2Ru2Cl4; C 60.79; H 5.94; N 2.91; Found; C 60.40; H 5.68; N 2.55; H NMR (δ,
ppm, CDCl3): 7.18-7.93 (m, 33H, aromatic protons); 5.15 (m, 8H, p-cymene C6H4); 3.86 (d, 4H,
J= 4.0 Hz, -CH2OP); 3.80 (m, 4H, -NCH2); 3.66 (s, 4H, -NCH2Ph); 2.72 (m, 2H, -CHCH2CH3);
9

2.61 (m, 2H, -CH(CH3)2 p-cymene); 1.77 (s, 6H, -CH3 p-cymene); 1.60 (m, 2H, -CHCH2CH3
(a)); 1.39 (m, 2H, -CHCH2CH3 (b)); 1.06 (m, 12H, -CH(CH3)2 p-cymene); 0.84 (t, 6H, J= 7.2 Hz
-CHCH2CH3); 13C NMR (δ ppm, CDCl3): 135.48, 140.04, 159.96 (aromatic ipso carbons);
120.44, 126.81, 127.80, 128.15, 128.75, 130.80, 132.20, 133.07, (aromatic carbons); 97.47,
111,73 (i-C6H4); 87.59, 90.17, 90,42 (p-cymene C6H4); 67.02 (-CH2OP); 60.51 (-CHCH2CH3):
55.81-54.56 (-NCH2 + -NCH2Ph); 30.08 (CH(CH3)2 p-cymene); 21.77, 21.95 (-CH(CH3)2 p-
cymene); 20.71 (-CHCH2CH3); 17.53 (-CH3 p-cymene); 11.90(-CHCH2CH3); 31P-{1H}- NMR (δ
ppm, CDCl3): 111.88 (s); (Fig S9); IR (KBr pellet in, cm-1): υ(CH): 3056, 2960, 2926; υ(C=C):
1448, 1435, 1375; υ(O-P): 1026; m/z: 1443.30 [M-H+] C73H85N3O2P2Ru2Cl4 ( MA: 1442.38)
(Fig S10).
Complex 20
Prepared from bis(phosphinite) ligand 11 (1.5 mmol, 1.20 g ) according to the general procedure
o
2.2.3. Yield (20); 1.9 g, 90%, m.p: 126-128 C. [α]D20 = -30.8o (c: 1, CH2Cl2); Anal.Calcd. for
1
C71H81N3O2P2Ru2Cl4; C 60.30; H 5.77; N 2.97; Found; C 60.09; H 5.58; N 2.75; H NMR (δ,
ppm, CDCl3): 7.23-7.90 (m, 33H, aromatic protons ); 5.29 (br, 2H, p-cymene C6H4); 5.10 (br,
6H, p-cymene C6H4); 4.63 (br, 2H, -CHCH3); 3.65 (d, 2H, J= 14.5 Hz, -CHCH2 (a)); 3.56 (d,
2H, J:13.72 Hz, -NCH2 (a)); 3.40 (d, 2H, J= 14.5 Hz, -CHCH2 (b)); 3.27 (d, 2H, J= 13.7 Hz, -
NCH2 (b)); 2.54-2.69 (m, 4H, -NCH2Ph(a)+-CH(CH3)2 p-cymene); 2.39 (m, 2H, -NCH2Ph(b));
1.81 (s, 6H, -CH3 p-cymene); 1.02-1.10 (m, 18H, -CH(CH3)2 p-cymene + -CHCH3); 13C NMR (δ
ppm, CDCl3): 137.63, 133.10, 139.43, 158.95 (ipso aromatic carbons); 121.01, 126.79, 127.74,
128.08, 128.95, 130.85, 132,86, 132.97, (aromatic carbons) ; 97.48, 111,25 (i-C6H4); 87.40,
88.17, 89.54, 90.63, 87.42 (d, J= 4.0 Hz, ipso p-cymene), 88.14 (d, J= 6.0 Hz, ipso p-cymene),
89.56 (d, J= 4.0 Hz, ipso p-cymene), 90.61 (d, J= 4.0 Hz, ipso p-cymene); 74.31 (-CHCH2);
60.77 (-CHCH2); 59.27-59.66 (-NCH2+NCH2Ph); 29.99 (-CH(CH3)2 p-cymene); 21.79, 21.93 (-
CH(CH3)2 p-cymene); 20.45 (-CHCH3); 17.45 (-CH3 p-cymene); 31P-{1H}-NMR (δ ppm,
10

CDCl3): 110.30 (s); (Fig S11); IR (KBr pellet in, cm-1): υ(CH): 3056, 2960, 2923; υ(C=C): 1574,
1456, 1435; υ(O-P): 970; m/z: 1415.25 [M-H+] C71H81N3O2P2Ru2Cl4 (MA: 1414.23) (Fig S12).
Complex 21
Prepared from bis(phosphinite) ligand 10 (1.5 mmol, 1.43 g ) according to the general procedure
2.2.3. Yield (21); 2.15 g, 92 %, m.p: 144-146 oC. [α]D20 = -40.9o (c: 0.5, CH2Cl2); Anal.Calcd. for
C84H90N2O2P2Ru2; C 64.46; H 5.80; N 1.79; found; C 64.12; H 5.53; N 1.58; 1H NMR (δ, ppm,
CDCl3): 7.02-7.95 (m, 44H aromatic protons); 5.08 (d, 2H, J= 5.8 Hz p-cymene C6H4); 4.99 (d,
2H, J= 5.9 Hz, p-cymene C6H4); 4.81 (d, 2H, J= 5.8 Hz p-cymene C6H4); 4.77 (d, 2H, J= 5.7 Hz
p-cymene C6H4); 3.90 (m, 4H, (-CH2OP); 3.57-3.71 (m,4H, -NCH2+4H, NCH2Ph); 3.14 (m, 2H,
-CHN); 3.00 (m, 2H, CHCH2Ph (a)); 2.54-2.60 (m, 2H, CHCH2Ph (b) + 2H CH(CH3)2 p-
cymene); 1.50 (s, 6H, CH3 p-cymene); 1.06 (t, 12H, J= 6.1 Hz, CH(CH3)2 p-cymene); 13C NMR
(δ ppm, CDCl3): 138,24, 139.74, 139.77, 139.89 (aromatic ipso carbons); 126.07, 126.81,
127.88, 128.16, 128.43, 128.55, 128.67, 129.45, 130.73, 130.94, 131.64, 133.48, 133.59,
(aromatic carbons) ; 98.40 (s, ipso p-cymene), 112,91 (d, J= 4.0 Hz, ipso p-cymene), 87.83,
88.15, 88.57, 87.86 (d, J= 5.0 Hz, ipso p-cymene), 88.12 (d, J= 6.0 Hz, ipso p-cymene), 88.57
(br, ipso p-cymene), 89.11 (d, J= 4.0 Hz, ipso p-cymene); (p-cymene C6H4); 65.97 (CH2OP);
60.42 (-CHCH2Ph): 53.48, 53.79 (-NCH2+NCH2Ph); 33.94 (-CHCH2Ph); 30.04 (CH(CH3)2 p-
31
cymene); 21.82, 21.90 (CH(CH3)2 p-cymene); 17.27 (CH3 p-cymene); P-{1H}-NMR (δ ppm,
CDCl3): 112.40 (s); (Fig S13); IR (KBr pellet in, cm-1): υ(CH): 3056, 3025, 2958; υ(C=C): 1478,
1452, 1377; υ(O-P): 1024; m/z: 1566.35 [M-H+] C84H90N2O2P2Ru2Cl4 (MA: 1565.23) (Fig S14).
Complex 22
Prepared from bis(phosphinite) ligand 16 (1.5 mmol, 1.39 g ) according to the general procedure
o
2.2.3. Yield (22); 2.05 g, 89 %, m.p: 139-141 C. [α]D20 = -30.8o (c:1, CH2Cl2); Anal.Calcd. for
1
C82H86N2O2P2Ru2Cl4; C 64.06; H 5.64; N 1.82; found; C 63.90; H 5.48; N 1.75; H NMR (δ,
ppm, CDCl3): 7.16-7.79 (m, 44H, aromatic protons ); 5.13 (d, 2H, J= 5.8 Hz p-cymene C6H4);
11

5.08 (d, 2H, J= 5.8 Hz p-cymene C6H4); 5.04 (d, 2H, J= 5.8 Hz p-cymene C6H4); 4.97 (d, 2H,
J= 5.8 Hz p-cymene C6H4); 4.32 (m, 2H, -CH2OP (a)); 4.15 (m, 2H, -CH2OP (b)); 3.98 (m, 2H, -
NCH); 3.69 (d, 4H, J=13.8 Hz -NCH2 (a)+NCH2Ph (a)); 3.29 (d, 4H, J= 13.8 Hz -NCH2
(b)+NCH2Ph (b)); 2.59 (m, 2H, -CH(CH3)2 p-cymene); 1.66 (s, 6H, -CH3 p-cymene); 1.02 (m,
12H, -CH(CH3)2 p-cymene); 13C NMR (δ ppm, CDCl3): 136.02, 136.40, 136.05, 136.52, 137.29,
139.65, (i-C6H4); 126.87, 127.48, 127.73, 127.79, 127.83, 128.15, 128.24, 128.78, 129.15,
130.81, 132.58, 132.69, 132.73, (aromatic carbons) ; 97.40, 111,80 (ipso p-cymene); 90.44 (d,
J= 4.0 Hz, p-cymene C6H4); 90.12 (d, J= 3.1 Hz, p-cymene C6H4); 87.70 (d, J= 6.0 Hz, p-
cymene C6H4); 87.31 (d, J= 6.0 Hz, p-cymene C6H4); 66.83 (-CH2OP); 62.45 (d, J= 8.1 Hz -
CHPh): 53.99 (-NCH2+NCH2Ph); 30.06 (-CH(CH3)2 p-cymene); 21.73, 21.86 (-CH(CH3)2 p-
31
cymene); 17.34 (-CH3 p-cymene); P-{1H}- NMR (δ ppm, CDCl3): 112.54 (s); (Fig S15); IR
(KBr pellet in, cm-1):υ(CH): 3055, 2958, 2923; υ(C=C): 1436, 1417, 1373; υ(O-P): 1023. m/z:
1539.30 [M-H+] C82H86N2O2P2Ru2Cl4 (MA: 1537.48) (Fig S16).
Complex 23
Prepared from bis(phosphinite) ligand 15 (1.5 mmol, 1.24 g ) according to the general procedure
o
2.2.3. Yield (23); 1.9 g, 88%, m.p: 140-142 C. [α]D20 = -20.7o (c:1, CH2Cl2); Anal.Calcd. for
1
C74H86N2O2P2Ru2Cl4; C 61.67; H 6.01; N 1.94; Found; C 61.22; H 5.88; N 1.65; H NMR (δ,
ppm, CDCl3): 7.21-7.92 (m, 34H, aromatic protons); 5.15 (br, 8H, p-cymene C6H4); 3.84 (br, 4H,
-CH2OP), 3.48-3.65 (m, 8H, -NCH2 + -NCH2Ph); 2.62-2.64 (m, 4H, -CHCH2CH3 + -CH(CH3)2
p-cymene); 1.79 (s, 6H, -CH3 p-cymene); 1.63 (m, 2H, -CHCH2CH3 (a)); 1.29 (m, 2H, -
CHCH2CH3 (b)); 1.07 (m, 12H, -CH(CH3)2 p-cymene); 0.84 (br, 6H, -CHCH2CH3); 13C NMR (δ
ppm, CDCl3): 137.76, 140.24, 140.38 (aromatic ipso carbons); 126.69, 127.74, 127.84, 128.09,
128.74, 130.81 130.99, 132.14, 133.26 (aromatic carbons); 97.29, 111,67 (i-C6H4); 87.41 (d, J=
6.0 Hz, ipso p-cymene), 87.52 (d, J= 6.0 Hz, ipso p-cymene), 90.31 (d, J= 4.0 Hz, ipso p-
12

cymene), 90.55 (d, J= 4.0 Hz, ipso p-cymene); 66.73 (-CH2OP); 59.51 (-CHCH2CH3): 53.66-
53.82 (-NCH2+ -NCH2Ph); 30.10 (CH(CH3)2 p-cymene); 21.77, 21.92 (-CH(CH3)2 p-cymene);
21.13 (-CHCH2CH3); 17.52 (-CH3 p-cymene); 11.78 (-CHCH2CH3); 31P-{1H}-NMR (δ ppm,
CDCl3): 111.80 (s); (Fig S17); IR (KBr pellet in, cm-1): υ(CH): 3055, 2959, 2927; υ(C=C): 1459,
1435, 1375; υ(O-P): 1026; m/z: 1442.30 [M-H+] C74H86N2O2P2Ru2Cl4 ( MA: 1441.39) (Fig
S18).
Complex 24
Prepared from bis(phosphinite) ligand 12 (1.5 mmol, 1.20 g ) according to the general procedure
o
2.2.3. Yield (24); 1.8 g, 85%, m.p: 132-134 C. [α]D20 = -20.8o (c:1, CH2Cl2); Anal.Calcd. for
1
C72H82N2O2P2Ru2Cl4; C 61.19; H 5.85; N 1.98; Found; C 60.97; H 5.58; N 1.86; H NMR (δ,
ppm, CDCl3): 7.09-7.87 (m, 34H, aromatic protons ); 5.06-5.29 (m, 8H, p-cymene C6H4); 4.57
(br, 2H, -CHCH3); 3.50 (d, 4H, J= 13.5 Hz, -NCH2); 3.14 (d, 4H, J= 13.4 Hz, -NCH2Ph); 2.58
(br, 2H, -CH(CH3)2 p-cymene); 2.44 (d, 2H, J= 8.7 Hz, -CHCH2 (a)); 2.32 (d, 2H, J= 8.8 Hz, -
CHCH2 (b)); 1.79 (s, 6H, -CH3 p-cymene); 0.99-1.08 (m, 18H, -CH(CH3)2 p-cymene + -
13
CHCH3); C NMR (δ ppm, CDCl3): 137.86, 139.40, 139.60 (ipso aromatic carbons); 126.70,
127.37, 127.78, 128.06, 128.87, 129.29, 130.79, 130.88, 132.96, (aromatic carbons); 97.32,
110.91 (i-C6H4); 87.23 (d, J= 5.0 Hz, ipso p-cymene), 88.15 (d, J= 6.0 Hz, ipso p-cymene),
89.58 (br, ipso p-cymene), 90.55 (br, ipso p-cymene); 74.41 (-CHCH3); 59.27-59.02 (-
NCH2+NCH2Ph+ -CHCH2); 30.00 (-CH(CH3)2 p-cymene); 21.96, 21.73 (-CH(CH3)2 p-cymene);
20.48 (-CHCH3); 17.44 (-CH3 p-cymene); 31P-{1H}-NMR (δ ppm, CDCl3): 110.21 (s); (Fig
S19); IR (KBr pellet in, cm-1): υ(CH): 3054, 2960, 2925; υ(C=C): 1436, 1408, 1376; υ(O-P):
969; m/z: 1413.20 [M-H+] C72H82N2O2P2Ru2Cl4 (MA: 1413.36) (Fig S20).
2.3.
General procedure for the asymmetric transfer hydrogenation of ketones.
13

Typical procedure for the catalytic hydrogen-transfer reaction: a solution of the Ru(II)-
complexes 17-24 (0.005mmol), KOH (0.025 mmol) and the corresponding ketone (0.5 mmol) in
degassed 2-propanol (5 mL) was refluxed until the reaction was completed. Periodically samples
taken from the reaction medium were passed through acetone silicagel column and conversion
rates were observed in gas chromatography, which were calculated on unreacted ketone.
3. Results and discussion
3.1.
Synthesis and characterization of the C2-symmetric bis(phosphinites) and
their binuclear η6-p-cymene-Ru(II)-phosphinite complexes
Corresponding chiral amino alcohol (D-phenyl alaninol, D-phenyl glycinol, (R)-(−)-1-amino-
2-propanol or (R)-(-)-2-amino-1-butanol) was reacted with commercially available 2,6-bis-
o
(bromomethyl)pyridine) or 1,3-bis(bromomethyl)benzene at 100 C for 12 h under argon
atmosphere in EtOH according to the literature procedure, respectively[27]. C2-symmetric chiral
amino alcohols 1-8, were characterized by elemental analysis, FT-IR, and multinuclear NMR
spectroscopies. All spectroscopic data for 1-8 are consistent with the proposed structures.
Insert Scheme 1 Here
C2-symmetric bis(phosphinite) ligands were synthesized by deprotonation of the corresponding
chiral amino alcohols 1-8 with two equivalents of Ph2PCl in the presence of triethylamine in
anhydrous toluene under argon atmosphere (Scheme 2). 31P-{1H} NMR spectroscopy was used
to follow the progress of these reactions. The signal of the starting material Ph2PCl at δ= 81.0
ppm disappeared and new singlets appeared at δ = 114.51, 115.02, 114.17, 114.87 ppm (Fig S1-
4). The chemical shifts in the 31P–{1H} NMR spectra of the free ligands are in line with the
values previously observed for similar compounds[2-4, 16, 28]. The observed singlets indicate
that two phosphorus atoms in the each molecule are equivalent [29-31]. Generally, phosphinites
14

are unstable in the solid state and decompose rapidly when it exposes to air or moisture.
However, phosphinite ligands synthesized in this study 9-16 are stable for up to 2 weeks in the
ambient air and then decompose gradually to give the corresponding oxide and hydrolysis
product diphenylphosphinous acid, Ph2P(O)H[32].
Insert Scheme 2 Here
The ability of dimer {[Ru(p-cymene)(µ-Cl)Cl]2} to form mononuclear complexes of
general formula [Ru(η6- p-cymene) Cl2L] have been well known for a long time [33, 34]. The p-
cymene moiety which is strongly coordinated to the ruthenium atom can be modified by simply
attaching different substituents. The three remaining coordination sites opposite to the p-cymene
ligand can be complexed with a wide number of mono-, bi-, or tri-dentate ligands such as
phosphorus containing ones (phosphine [1, 29, 30], phosphinite [2-4], phosphite[5] etc.),
aminoalcohols [35], diamines[36], sulphur containing ligands[37], heterocyclic ligands[38], with
N-, O-, S-, or P-donor atom. The reactions of [Ru(p-cymene)(µ-Cl)Cl]2 with ligands 9-16 are
depicted in Scheme 3. The reactions of [Ru(p-cymene)(µ-Cl)Cl]2 with one equivalent of 9-16 in
CH2Cl2 at room temperature gave air stable red compounds 17-24, in high yields. They are all
high melting solids and very soluble in most organic solvents. Generally, the P-based ligands
were expected to cleave the [Ru(p-cymene)(µ-Cl)Cl]2 dimer to give the corresponding
monohapto P-coordinated ruthenium complexes[39]. The initial colour change of reaction
medium from orange to deep red is attributed to the dimer cleavage by the phosphinite ligand.
The chemical purity of the ruthenium complexes was confirmed by 31P-{1H} NMR spectroscopy.
31P-{1H} NMR spectrum exhibits a unique single signal values ranging from 110.21 to 112.54
indicative of both phosphorus being equivalent as a result of the high symmetry of the complexes
(please see SI) due to the diphenylphosphinite moiety. A small coordination shift was attributed
15

to formation of the corresponding C2-symmetric η6-p-cymene-Ru(II)-phosphinite complexes 17-
24. The structures of complexes were also confirmed by FT-IR spectroscopy, microanalysis, and
LC/MS-MSspectra, and found to be in good agreement with the proposed structures (see
experimental section in details).
Insert Scheme 3 Here
3.2.
Binuclear η6-p-cymene-Ru(II)-phosphinite-catalyzed asymmetric transfer
hydrogenation of aryl, alkyl/aryl and alkyl/methyl ketones
Excellent catalytic performance of phosphinite ligands bearing η6-arene-Ru(II) complexes in
transfer hydrogenation of various ketones with 2-propanol, prompted us to search for new
phosphinite ligands bearing ruthenium(II) complexes for asymmetric transformation. To evaluate
the effectiveness of our new chiral C2-symmetric binuclear η6-p-cymene-Ru(II)-phosphinite 17-
24 as pre-catalysts in asymmetric transfer hydrogenation of aryl, alkyl/aryl and alkyl/methyl
ketones, we first investigated the optimal conditions starting with acetophenone as the model
substrate and the results are listed in Table 1.
Insert Scheme 4 Here
Initially, complexes 17-24 were tested as catalysts for transfer hydrogenation of
acetophenone to (R) or (S)-1-phenylethanol using 2-propanol in the presence of KOH as base.
The results in Table 1 (Entry 17) clearly show that the base is necessary for these reactions.
Herewith, we did not observe any conversion in the absence of any base. A blank experiment
was also showed that transfer hydrogenation does not occur in the absence of catalyst.
Results of the optimization studies showed that the best conversions were obtained using
o
KOH, as the base, in 2-propanol as solvent and hydrogen source at 82 C with 1 mol% of the
catalyst. Increasing the substrate-to-catalyst (S/C; 250:1, 500:1, 1000:1) ratio does not cause any
16

decrease in the conversion of the product (except enantioselectivity and reaction time) in most
cases as seen in Table 1, entries 22-25. For example, transfer hydrogenation of acetophenone
could be achieved with 90% yield even when the S/C ratio reached 1000:1 though with an
increase in the reaction time (7h, TOF 13h-1) and decrease in enantioselectivity (51 %) (Table 1,
entry 25). Due to the reversibility in reaction medium, the prolonged the reaction time led to a
decrease in enantioselectivity. Thus, we concluded that prolonged exposure of the product to the
catalyst tends to gradually deteriorate the enantiometric purity[40]. These results are presented in
Table 1. At room temperature, no significant formation of (R)-1-phenylethanol was observed
(Table 1, entries 1-8). An increase in the reaction time up to 96 h resulted in 35-48 % conversion
with 41-48% ee’s. As mentioned above, because of the reversibility of TH reactions at room
temperature, the prolonged the reaction time led to a slight decrease in enantioselectivity.
Optimization studies obviously indicated that complexes 17, 18, 21 and 22 are quite effective
catalysts for transfer hydrogenation of acetophenone.
Insert Table 1 Here
In the next round of experiments, we extended our investigations to include
hydrogenation of substituted acetophenone derivatives and the results are summarized in Table
2. For this aim, the reaction of several aromatic ketones with different electronic and steric
variations on the substrate backbone was investigated. On comparing the electronic effects of the
fluoro, chloro, bromo and nitro substituents on ortho- and para- position of acetophenone as
electron withdrawing group, it was found that the reaction of p-fluoro acetophenone took shorter
time of (10 min, TOF; 594 h-1) 1/2 h to reach completion as compared to acetophenone for
catalyst 17 (Table 2, entries 5-8). The introduction of electron withdrawing substituents, attached
to the aryl ring of the ketone, decreased the electron density of the C=O group making it
susceptible to attack so that the activity was improved, giving rise to easier hydrogenation [41,
17

42]. It can be also seen from in Table 2, the effect of changing the location of the substituents
from the para- to ortho- position of the acetophenone resulted in a slightly increase in
enantioselectivity, while meta- and para- substitution to acetophenones have detrimental effect
[40]. Hence, the lowest enantioselectivities were observed in transfer hydrogenation of p-
substituted acetophenones, whereas the highest one was found in the case of o-
methoxyacetophenone (80% ee) as seen in Table 2.
Insert Table 2 Here
Inspired by these results, the scope of the catalytic study was further extended to investigate a
wide range of alkyl/aryl and alkyl/methyl ketones (Table 3). From the results in Table 3, one can
easily conclude that the catalytic asymmetric transfer hydrogenation of aliphatic ketones is more
difficult than that of aromatic ketones. Thus, it was found that the reaction times are strongly
dependent on the linear chain length and steric hindrance of the ketones (Table 3, entries 1-16).
The results clearly show that the bulkiness of alkyl group significantly affects the
enantioselectivity, which decreases with increasing bulkiness of the alkyl group as anticipitated.
Using alkyl/aryl or alkyl methyl ketones as substrates, we found that the efficiency of the chiral
ligands have a moderate influence on the final yields, but from moderate to high selectivity was
observed (up to 82% ee, Table 3, entry 18).
Insert Table 3 Here
Table 4 shows the various phosphinite based Ru(II) complexes which have been tested in the
ATH reactions of various ketones to produce the corresponding secondary alcohols at reflux
temperature. Our C2-symmetric Ru(II)-phosphinite complexes 18 and 22 showed quantative
conversion (98-99%) and good enantioselectivity (74,76%) for ATH reactions of various ketones
(Table 4, entries 1, 2). [5, 43-46]
18

Insert Table 4 Here
4. Conclusions
In summary, we synthesized eight new binuclear ruthenium(II) complexes bearing a chiral
C2-symmetric bis(phosphinite) unit and a p-cymene moiety. The binuclear ruthenium(II)
complexes were employed as precursors of catalysts in the hydrogen transfer reaction of
ruthenium-catalyzed asymmetric transfer hydrogenation of aromatic, methyl alkyl and alkyl/aryl
ketones using 2-propanol as both the hydrogen source and solvent in the presence of KOH. The
results indicated that complexes 17, 18, 21 and 22 showed higher conversions (between 96-99%,
up to 594 h-1 TOF) and enantioselectivities (up to 82% ee) among eight binuclear Ru(II)
complexes. These ruthenium complexes are selective and active hydrogenation catalysts and
hold promise for application in transfer hydrogenation of other substrates.
Acknowledgment
Financial support from Dicle University Research Fund DUBAP (Project number: 13-FF-
114, FEN.16.008 and FEN.16.010) is gratefully acknowledged.
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22

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Scheme 1. Synthesis of chiral C2-symmetric amino alcohols (1-8).
Scheme 2. Synthesis of chiral C2-symmetric bis(phosphinite) ligands (9-16).
23

Scheme 3. Synthesis of chiral C2-symmetric bis(phosphinite)-Ru(II) complexes (17-24).
Scheme 4. Transfer hydrogenation of acetophenone.
24

Table 1 Asymmetric transfer hydrogenation of acetophenone with iso-PrOH catalyzed by C2-symmetric
bis(phosphinite) Ru(II) complexes (17-24).
Entry
Cat.
Subs./Cat./Base
Time(h)
Conv.(%)a
ee (%)b
Config.c
TOF (h-1)d
17e
18e
19e
20e
21e
22e
23e
24e
1
2
3
4
5
6
7
8
100:1:5
100:1:5
100:1:5
100:1:5
100:1:5
100:1:5
100:1:5
100:1:5
24(96)
24(96)
24(96)
24(96)
24(96)
24(96)
24(96)
24(96)
13(40)
11(44)
10(38)
10(46)
15(42)
13(45)
11(35)
14(48)
50(43)
52(46)
44(40)
48(42)
52(45)
56(47)
47(41)
50(44)
R
R
R
R
R
R
R
R
<3
<3
<3
<3
<3
<3
<3
<3
17f
18f
19f
20f
21f
22f
23f
24f
9
100:1:5
100:1:5
100:1:5
100:1:5
100:1:5
100:1:5
100:1:5
100:1:5
1/2
1
1/4
1/2
1/2
1
99
98
98
98
99
99
98
99
62
76
50
61
63
74
51
62
R
R
R
R
R
R
R
R
198
98
392
196
198
99
10
11
12
13
14
15
16
1/4
1/2
392
196
17g - 24g
17
100:1
96
-
-
-
-
18h
18h
18h
18h
18
19
20
21
100:1:3
100:1:5
100:1:7
100:1:9
1
1
1
1
98
98
94
92
70
76
72
65
R
R
R
R
98
98
94
92
18k
18k
18k
18k
22
23
24
25
100:1:5
250:1:5
500:1:5
1000:1:5
1
3
5
7
98
98
95
90
76
64
59
R
R
R
R
98
33
19
13
51
b
Reaction conditions: aDetermined by GC (three independent catalytic experiments), Determined by capillary GC analysis using a
c
chiral Cyclodex B (Agilent) capillary column, Determined by comparison of retention times of enantiomers on the GC traces with
literature values; (S) or (R) configuration was obtained in all experiments, dTOF= (mol product/mol catalyst) x h-1, At room
e
f
g
temperature; acetophenone/Ru/KOH, 100:1:5, Refluxing in iso-PrOH; acetophenone/Ru/KOH, 100:1:5, Refluxing in iso-PrOH;
acetophenone/Ru, 100:1, in the absence of base, h Refluxing in iso-PrOH; acetophenone/Ru/KOH, 100:1:3, 5, 7, 9, Refluxing in
k
iso-PrOH; acetophenone/Ru/KOH, 250, 500 or 1000:1:5.
25

Table 2 Asymmetric transfer hydrogenation results for substituted acetophenones catalyzed by C2-symmetric
bis(phosphinite) Ru(II) complexes [a]
.
Entry
Cat.
R
Time
Conv.(%)[b]
ee(%)[c]
60
TOF (h-1)[d]
Conf.[e]
1
2
3
4
5
6
7
8
15 min
30 min
15 min
30 min
10 min
15 min
10 min
15 min
15 min
30 min
15 min
30 min
30 min
60 min
30 min
60 min
25 min
45 min
25 min
45 min
15 min
20 min
15 min
20 min
2 h
99
98
99
98
99
97
98
98
99
97
98
96
98
96
98
98
99
98
98
97
99
98
98
98
99
99
98
96
99
99
98
96
396
196
396
196
594
388
588
392
396
194
392
192
196
96
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
17
18
21
22
17
18
21
22
17
18
21
22
17
18
21
22
17
18
21
22
17
18
21
22
17
18
21
22
17
18
21
22
74
61
72
57
70
59
68
56
69
57
66
54
66
56
64
50
62
53
60
59
72
62
70
67
82
65
80
60
76
60
75
2-F
4-F
4-Cl
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
2-Br
196
98
238
131
235
129
396
294
392
294
50
33
49
33
25
4-Br
4-NO2
2-MeO
4-MeO
3 h
2 h
3 h
4 h
7 h
4 h
7 h
14
25
14
Reaction conditions: [a] Catalyst (0.005 mmol), substrate (0.5 mmol), 2-propanol (5 mL), KOH (0.025 mmol %), 82
[b]
ºC, the concentration of acetophenone derivatives are 0.1 M;
Purity of compounds is checked by NMR and GC
[c]
(three independent catalytic experiments), yields are based on aryl ketone;
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); [d] TOF = (mol
product/mol Cat.) x h-1; [e] Determined by comparison of the retention times of the enantiomers on the GC traces with
literature values, (S) or (R) configuration was obtained in all experiments.
Table 3 Asymmetric transfer hydrogenation results for various ketones catalyzed by C2–symmetric bis(phosphinite)
Ru(II) complexes[a].
26

Entry
1
Cat.
17
R1
R2
Time Conv.(%)b
ee (%)b
60
TOF(h-1)d
98
Conf.e
R
1 h
98
98
99
98
99
99
98
98
98
98
98
99
96
98
97
98
98
98
99
99
97
98
96
99
98
99
98
98
98
99
99
2
2 h
74
61
72
56
70
57
68
50
64
52
60
52
63
49
58
67
82
69
80
57
72
59
70
48
63
50
64
51
68
53
66
49
99
49
50
33
49
33
33
20
33
20
48
25
49
25
196
98
198
99
49
33
48
33
98
49
98
49
33
25
33
25
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
18
21
22
17
18
21
22
17
18
21
22
17
18
21
22
17
18
21
22
17
18
21
22
17
18
21
22
17
18
21
22
CH3
CH2CH3
3
1 h
4
2 h
5
2 h
6
3 h
CH3
CH3
CH3
CH3
CH3
CH3
C6H5
CH2CHC6H5
CH(CH3)2
CH2CH(CH3)2
1-naphthyl
n-C4H9
7
2 h
8
3 h
9
3 h
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
5 h
3 h
5 h
2 h
4 h
2 h
4 h
1/2 h
1 h
1/2 h
1 h
2 h
3 h
2 h
3 h
1 h
2 h
C6H5
1 h
2 h
3 h
4 h
C6H11
3 h
4 h
99
Reaction conditions: [a] Catalyst (0.005 mmol), substrate (0.5 mmol), 2-propanol (5 mL), KOH (0.025 mmol %), 82
[b]
ºC, the concentration of acetophenone derivatives are 0.1 M;
Purity of compounds is checked by NMR and GC
[c]
(three independent catalytic experiments), yields are based on aryl ketone;
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); [d] TOF = (mol
product/mol Cat.) x h-1; [e] Determined by comparison of the retention times of the enantiomers on the GC traces with
literature values, (S) or (R) configuration was obtained in all experiments.
27

Table 4 Comparing catalytic activity of various phosphinite based Ru(II) complexes have been
tested for asymmetric transfer hydrogenation of various ketones.*
Temp.
(oC)
Con.
(%)
ee
(%)
Entry
R1/R2
Ph/CH3
Ph/CH3
Cat.
18
Time Subs./Cat.
Ref.
This
1
2
3
4
82
82
82
82
1 h
1 h
1 h
1 h
100:1
100:1
100:1
100:1
98
99
98
99
76
74
82
80
study
This
study
This
study
This
study
[43]
22
CH3/1-
Naphthyl
CH3/1-
Naphthyl
Ph/Ph
18
22
5
6
7
82
82
82
48 h
48 h
48 h
30
min
30
min
30
min
200:1
200:1
200:1
89
77
58
-
-
-
1a
3
6
Ph/Ph
Ph/Ph
[43]
[43]
CH3/1-
Naphthyl
CH3/1-
Naphthyl
CH3/1-
Naphthyl
CH3/1-
Naphthyl
Ph/CH3
Ph/CH3
Ph/CH3
Ph/CH3
Ph/CH3
Ph/Ph
8
9
82
82
82
82
100:1
100:1
100:1
100:1
99
98
97
99
62
70
50
77
[44]
[44]
[44]
1
2
5
4
10
11
1 h
[25]
[5]
12
13
14
15
16
17
18
19
20
21
80
80
80
80
82
82
50
82
82
50
10 h
10 h
10 h
10 h
10 h
10 h
52 h
6 h
100:1
100:1
100:1
100:1
100:1
100:1
100:1
100:1
100:1
100:1
69
61
68
87
84
91
98
96
97
32
-
-
-
-
-
1
3
4
6
1
1
3
3
1f
1f
[5]
[5]
[5]
[45]
-
[45]
[46]
[46]
[2]
Ph/CH3
Ph/CH3
Ph/CH3
Ph/CH3
69
67
16
16
1 h
24 h
[2]
*The catalysts used in Table 4 are given according to the numbers in the references cited.
28

RESEARCH HIGHLIGHTS



Chiral C2-symmetric bis(phosphinite) ligands and their binuclear η6-p-cymene-Ru(II) complexes
have been synthesized.
The asymmetric transfer hydrogenation of alkyl methyl or alkyl/aryl ketones by binuclear η6-p-
cymene-Ru(II) complexes have been reported.
Products were obtained with high conversions (99%) and moderate to good enantioselectivities
(up to 82% ee).
29