New chiral phosphinite ligands with C2-symmetric axis and their possible applications in Ru-catalyzed asymmetric transfer hydrogenation

Article abstract of DOI:10.1002/aoc.1594

The new chiral ligands N,N′-bis-[(1R)-1-ethyl-2-O- (diphenylphosphinite)ethyl]ethanediamide, 1, and N,N′-bis-[(1S)-1- isobutyl- 2-O-(diphenylphosphinite)ethyl]ethanediamide, 2, and the corresponding ruthenium complexes 3 and 4 were prepared and their stru

Full text of DOI:10.1002/aoc.1594

Full Paper
Received: 25 June 2009
Revised: 19 October 2009
Accepted: 26 October 2009
Published online in Wiley Interscience: 17 December 2009
(www.interscience.com) DOI 10.1002/aoc.1594
New chiral phosphinite ligands with
C2-symmetric axis and their possible
applications in Ru-catalyzed asymmetric
transfer hydrogenation
∗
ˇ
Murat Aydemir , Nermin Meric, Akın Baysal, Cezmi Kayan, Mahmut Togrul
and Bahattin Gu¨mgu¨m
The new chiral ligands N,Nꢀ-bis-[(1R)-1-ethyl-2-O-(diphenylphosphinite)ethyl]ethanediamide, 1, and N,Nꢀ-bis-[(1S)-1-isobutyl-
2-O-(diphenylphosphinite)ethyl]ethanediamide, 2, and the corresponding ruthenium complexes 3 and 4 were prepared and
their structures were elucidated by a combination of multinuclear NMR spectroscopy, IR spectroscopy and elemental analysis.
Following activation by NaOH, these chiral ruthenium complexes serve as catalyst precursors for the asymmetric transfer
hydrogenation of acetophenone derivatives in iPrOH. The complexes 3 and 4 showed high catalytic activity but low selectivity
c
in asymmetric transfer hydrogenation reactions. Copyright ꢀ 2009 John Wiley & Sons, Ltd.
Keywords: homogeneous catalysis; chirality; transfer hydrogenation; phosphinite ligands; p-cymene ruthenium(II) complexes
Introduction
ketones hydrogenation and they are well known.[19–21] Hydro-
gen gas presents considerable safety hazards, especially for
large-scale reactions.[22,23] The use of a solvent that can do-
nate hydrogen overcomes these difficulties. 2-Propanol is a
popular reactive solvent for transfer hydrogenation reactions
since it is easy to handle (b.p. 82 ◦C) and is relatively non-
toxic, environmentally benign and inexpensive. The volatile
acetone by-product can also be easily removed to shift un-
favourable equilibria. Noyori and co-workers provided an el-
egant solution for the asymmetric catalytic H2-hydrogenation
of simple aryl ketones.[24,25] Complexes of the type trans-
RuCl2(diamine)(diphosphine) with matching configurations of
chiral diphosphine and diamine, e.g. (S)-BINAP/(S,S)-DPEN, show
high reactivity and enantioselectivity.[26] The use of organometal-
lic complexes as catalysts for asymmetric transfer hydrogenation
from a suitable donor (usually iso-propanol or formic acid) has
been the subject of ongoing research for some decades. Efficient
catalysts for the asymmetric transfer hydrogenation of ketones
include Evans’ samarium complexes with chiral amino alcohols
ligand[27] and Noyori’s ruthenium complexes containing arene
and N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine (TsDPEN)
ligands.[28,29] Chiral diphosphinite ligands derived from the re-
action of 1,1ꢁ-bi-2-naphthol (BINOL) with chlorodiarylphosphine
were easily synthesized and modified and they were widely used
as chiral auxiliaries in rhodium, iridium and palladium asymmetric
catalytic reactions.[30,31]
The chemistry of transition-metal complexes containing hemi-
labile ligands has been the subject of many studies in recent
years.[1–3] ThetermwasfirstintroducedbyJeffreyandRauchfuss;[4]
hemilabile ligands contain both a strong donor group, fixing the
ligand to the metal, and a weaker donor group, which can be
easily replaced by another ligand. Ligands possessing both ‘soft’
and ‘hard’ donors atoms coordinated to the same metal centre
have been found suitable for catalytic purposes since the stability
of intermediate species is favored.[5,6] Recently, many efforts have
been made to improve the catalytic activity of some complexes by
using hemilabile ligands.[7,8] Among ‘soft’ donor atoms, phospho-
rus is the most common in homogeneous catalysis and, for this
reason, itisfoundinmanyligandscombinedwithavarietyof‘hard’
labiledonorgroups(i.e.N-orO-donors).AlthoughhemilabileP–O-
donor ligands have been widely studied,[9–11] increased attention
has recently been given to hemilabile P–N donor ligands.[12,13]
Phosphine and phosphite ligands have found widespread
applications in transition metal-catalyzed asymmetric trans-
formations.[14,15] Phosphinites provide different chemical, elec-
tronic and structural properties compared with phosphines. Thus,
they open many opportunities to design new improved ligands
for asymmetric catalysis. The metal–phosphorus bond is often
stronger for phosphinites compared with the related phosphine
due to the presence of electron-withdrawing P–OR group. In addi-
tion, the empty σ∗-orbital of the phosphinite P(OR)R2 is stabilized
and it makes the phosphinite a better acceptor.[16]
The most important advantage of chiral phosphinite ligands
over the corresponding phosphine ligands is the ease of
Chiral alcohols are very important building blocks and syn-
thetic intermediates in organic synthesis and the pharmaceuti-
cal industry.[17,18] Reduction of prochiral ketones to give chiral
alcohols is among the most fundamental subjects in mod-
ern synthetic chemistry. Catalytic reduction is preferred to
stochiometric reduction for large-scale industrial processes of
∗
Correspondence to: Murat Aydemir, Department of Chemistry, University of
Dicle, 21280 Diyarbakır, Turkey. E-mail: aydemir@dicle.edu.tr
Department of Chemistry, University of Dicle, 21280 Diyarbakır, Turkey
c
Appl. Organometal. Chem. 2010, 24, 215–221
Copyright ꢀ 2009 John Wiley & Sons, Ltd.

M. Aydemir et al.
preparation. The synthesis of phosphinites by reacting the
corresponding alcohols with chlorophosphines in the presence
of an organic base is very convenient, and the yields are usually
quantitative. From a practical standpoint, it is of substantial
interest to develop highly effective chiral phosphinite ligands
for asymmetric catalysis. The excellent catalytic performance of
phosphinite-based transition metal complexes[32,33] prompted
us to develop new Ru(II) complexes with well-shaped ligands.
Thus, following our continuous interest in the chemistry of phos-
phinite ligands and the applications of ruthenium complexes[34]
herein, we report the convenient, modular synthesis and
characterization of new chiral phosphinite ligands N,Nꢁ-bis-
[(1R)-1-ethyl-2-O-(diphenylphosphinite)ethyl]ethanediamide,
Procedure for the Preparation of the Chiral Ligands and
Ruthenium Complexes
Synthesis of N,Nꢁ-bis-[(1R)-1-ethyl-2-O-(diphenylphosphinite)
ethyl]ethane-diamide, 1
PPh2Cl (0.20 g, 0.86 mmol) was slowly added to a solution
of N,Nꢁ-bis[(1R)-1-ethyl-2-hydroxyethyl]ethanediamide (0.10 g,
0.43 mmol) and triethylamine (0.09 g, 0.86 mmol) in 25 ml of
toluene at room temperature. The mixture was stirred for
4 h and triethylammonium chloride was filtered off. Evapo-
ration of the solvent in vacuo gave N,Nꢁ-bis-[(1S)-1-ethyl-2-O-
(diphenylphosphinite)ethyl]ethanediamide, 1 as a white solid
(yield: 0.24 g, 92.0%); m.p.: 86–88 ◦C. [α]D = +32.6 (c 1.0,
25
DMSO). C34H38N2O4P2: calcd C, 67.99; H 6.38; N 4.66; anal.
found: C, 67.85; H 6.34; N 4.62%. Selected IR, υ (cm−1): 3405
(N–H), 3028, 3075 (Ar–H), 1658 (C O, first amide band), 1516
(C O, second amide band), 1035 (C–O), 962 (P–O). 1H NMR
(CDCl3) δ (ppm): 0.94 (t, 6H, J = 7.4 Hz, -CH2CH3), 1.59 (m,
2H, -CH2CH3) (a), 1.70 (m, 2H, -CH2CH3) (b), 3.86 (m, 4H, -
CH2O-P), 4.00 (m, 2H, -CH-N), 7.20–7.56 (m, 20H, o-, m- and
1,
and
N,Nꢁ-bis-[(1S)-1-isobutyl-2-O-(diphenylphosphinite)
ethyl]ethanediamide, 2, and corresponding ruthenium com-
plexes 3 and 4 and their application in the asymmetric
transfer hydrogenation reactions of acetophenone derivatives
with iso-propanol as the hydrogen source. This approach
allows the opportunity for rapid tuning of the catalyst
structure due to the modular nature of the ligands and
precatalysts. These compounds were also fully character-
ized using elemental analysis, FT-IR and multi-nuclear NMR
spectroscopies.
1
p-protons of phenyls), 7.71 (d, 2H, J = 8.4 Hz, NH). 13C–{ H}
NMR (CDCl3) δ (ppm): 10.38 (-CH2CH3), 24.36 (-CH2CH3), 52.35
(-CH-N), 70.15 (-CH2O-P), 129.53 (d, 3J31P−13C = 7.0 Hz, m-carbons
of phenyls), 129.53 (d, 4J31P−13C = 2.0 Hz, p-carbons of phenyls),
2
130.50 (d, J31P−13C = 20.1 Hz, o-carbons of phenyls), 141.30 (d,
1J31P−13C = 18.1 Hz, i-carbons of phenyls), 159.41 (s, C O), as-
Experimental
signment was based on the 1H–13C HETCOR and 1H–1H COSY
1
spectra. 31P–{ H} NMR (CDCl3) δ (ppm): 117.20 (s, O-P-(C6H5)2).
Materials and Methods
Unless otherwise stated, all reactions were carried out under
an atmosphere of argon using conventional Schlenk glassware.
Solvents were dried using established procedures and distilled
under argon immediately prior to use. Analytical grade and
deuterated solvents were purchased from Merck. The start-
ing materials [Ru(η6-p-cymene)(µ-Cl)Cl]2 and PPh2Cl were pur-
chased from Fluka and were used as received. N,Nꢁ-bis[(1R)-1-
ethyl-2-hydroxyethyl]ethanediamide and N,Nꢁ-bis[(1S)-1-isobutyl-
2-hydroxyethyl]ethanediamide were prepared according to the
literature procedure.[35]
Synthesis of N,Nꢁ-bis-[(1S)-1-isobutyl-2-O-(diphenylphosphinite)
ethyl]ethane-diamide, 2
PPh2Cl (0.16 g, 0.70 mmol) was slowly added to a solution
of N,Nꢁ-bis[(1S)-1-isobutyl-2-hydroxyethyl]ethanediamide (0.10 g,
0.35 mmol) and triethylamine (0.07 g, 0.70 mmol) in 25 ml of
toluene at room temperature. The mixture was stirred for
4 h and triethylammonium chloride was filtered off. Evapora-
tion of the solvent in vacuo gave N,Nꢁ-bis-[(1S)-1-isobutyl-2-
O-(diphenylphosphinite)ethyl]ethanediamide,2 as a colorless oil
25
(yield:0.22 g, 95.0%);[α]D = −35.2(c1.0, DMSO). C38H46N2O4P2:
calcd C, 69.50; H 7.06; N 4.27; anal. found: C, 69.43; H 7.01; N
4.24%. Selected IR, υ (cm−1): 3295 (N–H), 3056, 3112 (Ar–H),
1655 (C O, first amide band), 1512 (C O, second amide band),
1035 (C–O), 951 (P–O). 1H NMR (CDCl3) δ (ppm): 0.89 [d, 6H,
J = 6.4 Hz, -CH(CH3)2 (a)], 0.93 [d, 6H, J = 6.0 Hz, -CH(CH3)2
(b)], 1.50 [m, 4H, -CH2-CH(CH3)2], 1.60 [m, 2H, -CH(CH3)2], 3.70
(m, 4H, -CH2O-P), 4.05 (m, 2H, -CH-N), 7.28–7.53 (m, 20H, o-
, m- and p-protons of phenyls), 7.73 (d, 2H, J = 8.8 Hz, NH).
Spectroscopic Analyses
The IR spectra were recorded on a Mattson 1000 ATI Unicam
FT-IR spectrometer as KBr pellets. 1H (400.1 MHz), 13C NMR
1
(100.6 MHz)and31P–{ H}NMR(162.0 MHz)spectrawererecorded
on a Bruker Avance 400 spectrometer, with δ referenced to
external TMS and 85% H3PO4, respectively. Elemental analysis
was carried out on a Fisons EA 1108 CHNS-O instrument. Melting
points were recorded by Gallenkamp Model apparatus with open
capillaries.
1
13C–{ H} NMR (CDCl3) δ (ppm): 22.14 [-CH(CH3)2 (a)], 22.97 [-
CH(CH3)2 (b)], 24.72 [-CH(CH3)2], 40.43 [-CH2-CH(CH3)2], 50.63
(-CH-N), 65.29 (-CH2O-P), 128.41 (d, 3J31P−13C = 8.0 Hz, m-carbons
of phenyls), 129.56 (d, 4J31P−13C = 3.0 Hz, p-carbons of phenyls),
2
130.75 (d, J31P−13C = 12.0 Hz, o-carbons of phenyls), 141.30 (d,
GC Analyses
1J31P−13C = 18.0 Hz, i-carbons of phenyls), assignment was based
GC analyses were performed on a HP 6890N Gas Chromato-
graph equipped with cyclodex B (Agilent) capillary column (30 m
× 0.32 mm i.d. × 0.25 µm film thickness). The GC parame-
ters were for asymmetric transfer hydrogenation of ketones
as follows: initial temperature, 110 ◦C; initial time, 1 min; sol-
vent delay, 4.48 min; temperature ramp 80 ◦C/min; final tem-
perature, 200 ◦C; final time, 21.13 min; injector port temper-
ature, 200 ◦C; detector temperature, 200 ◦C, injection volume,
2.0 µL.
1
on the 1H–13C HETCOR and 1H–1H COSY spectra. 31P–{ H} NMR
(CDCl3) δ (ppm): 117.50 [s, O-P-(C6H5)2].
Synthesis
of
[Ru{chloro(p-cymene)(N,Nꢁ-bis[(1R)-1-ethyl-2-O-
(diphenylphosp-hinite)ethyl]ethanediamide)}]chloride, 3
[Ru(η6-p-cymene)(µ-Cl)Cl]2 (0.05 g, 0.085 mmol) and N,Nꢁ-bis-
[(1R)-1-ethyl-2-O-(diphenylphosphinite)ethyl]ethanediamide,
(0.10 g, 0.170 mmol) were dissolved in 20 ml of toluene and
1
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Copyright ꢀ 2009 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2010, 24, 215–221

New chiral phosphinite ligands with C2-symmetric axis
stirred for 3 h at room temperature. The volume was con-
centrated to ca 1–2 ml under reduced pressure and addi-
tion of diethyl ether (20 ml) gave 3 a clear red solid. The
product was collected by filtration and dried in vacuo (yield:
General procedure for the transfer hydrogenation of ketones
Typical procedure for the catalytic hydrogen-transfer re-
action: a solution of the ruthenium complexes [Ru{chloro
(p-cymene)(N,Nꢁ-bis[(1S)-1-ethyl-2-O-(diphenylphosphinite)
ethyl]-ethanediamide)}]chloride, 3, or [Ru{chloro(p-cymene)
(N,Nꢁ-bis[(1S)-1-isobutyl-2-O-(diphenyl-phosphinite)ethyl]
ethanediamide)}]chloride, 4 (0.005 mmol), NaOH (0.025 mmol)
and the corresponding ketone (0.5 mmol) in degassed iso-
propanol (5 ml) was refluxed for 1 h. After this time a sample of the
reaction mixture is taken off, diluted with acetone and analyzed
immediately by GC, yields obtained are related to the residual
unreacted ketone.
0.13 g, 86.1%); m.p.: 204–206 ◦C. [α]D = +36.0 (c 1.0, DMSO).
25
[(C34H38N2O4P2)RuCl2(CH3C6H4CH(CH3)2]: calcd C, 58.28; H 5.78;
N 3.09; anal. found: C, 58.13; H 5.73; N 3.06%. Selected IR, υ
(cm−1): 3396 (N–H), 3032, 3055 (Ar–H), 1674 (C O, first amide
band), 1507 (C O, second amide band), 1038 (C–O), 997 (P–O).
1H NMR (CDCl3) δ (ppm): 0.85 (t, 6H, J = 7.2 Hz, -CH2CH3), 1.05
[d, 6H, J = 7.2 Hz, (CH3)2CHPh of p-cymene], 1.60 (m, 4H, -
CH2CH3), 1.86 (s, 3H, CH3-Ph of p-cymene), 2.66 (m, 1H, -CH- of
p-cymene), 3.82 (d, 4H, J = 3.6 Hz, -CH2O-P), 3.91 (m, 2H, -CH-
N), 5.21 (d, 2H, J = 6.0 Hz, aromatic protons of p-cymene), 5.30
(d, 2H, J = 6.0 Hz, aromatic protons of p-cymene), 7.32–7.48
(m, 12H, m- and p-protons of phenyls), 7.54 (d, 2H, J = 8.8 Hz,
NH), 7.86 (dd, 8H, J = 7.2 and 10.6 Hz, o-protons of phenyls).
Results and Discussion
Synthesis of chiral ligands, 1 and 2
1
13C–{ H} NMR (CDCl3) δ (ppm): 10.30 (-CH2CH3), 17.58 (CH3Ph
Compounds 1 and 2 were prepared from the reaction of N,Nꢁ-
bis[(1R)-1-ethyl-2-hydroxyethyl]ethanediamide or N,Nꢁ-bis[(1S)-1-
isobutyl-2-hydroxyethyl]ethanediamide and two equivalents of
chlorodiphenylphosphine in the presence of Et3N at room
temperature under argon atmosphere in high yield, respectively
(Scheme 1).
of p-cymene), 21.69 [(CH3)2CHPh of p-cymene], 24.37 (-CH2CH3),
30.09 (-CH- of p-cymene), 51.93 (-CH-N), 68.06 (-CH2O-P), 87.44,
88.13 (aromatic carbons of p-cymene), 97.41, 111.98 (quaternary
carbons of p-cymene), 128.16 (d, 3J31P−13C = 11.1 Hz, m-carbons
of phenyls), 131.25 (d, 4J31P−13C = 2.0 Hz, p-carbons of phenyls),
2
132.81 (d, J31P−13C = 11.1 Hz, o-carbons of phenyls), 136.45 (d,
1
The 31P–{ H} NMR spectra of compounds 1 and 2 show single
1J31P−13C = 42.4 Hz, i-carbons of phenyls), 159.37 (s, C O), as-
signment was based on the 1H–13C HETCOR and 1H–1H COSY
resonances due to phosphinite at 117.20 and 117.50 ppm, respec-
tively, indicating that two phosphorus atoms in the molecules are
1
spectra. 31P–{ H} NMR (CDCl3) δ (ppm): 115.12 [s, O-P-(C6H5)2].
1
equivalent.[36–38] The 31P–{ H} NMR spectra also display forma-
tionofPPh2PPh2 andP(O)Ph2PPh2, asindicatedbysignalsatabout
Synthesis of [Ru{chloro(p-cymene)(N,Nꢁ-bis[(1S)-1-isobutyl-2-O-
(diphenyl-phosphinite)ethyl]ethanediamide)}]chloride, 4
δ −15.0 ppm as singlet and δ 37.2 ppm and δ −21.6 ppm as dou-
1
blets with J(PP) 224 Hz, respectively.[39] These by-products were
easily eliminated by washing the residue with copious amounts of
dry diethyl ether. Solutions of 1 and 2 in CDCl3, prepared under
anaerobic conditions, are unstable and decompose gradually to
give oxide and bis(diphenylphosphino)monoxide [P(O)Ph2PPh2]
derivatives. Compounds 1 and 2 are also not stable in air and
decompose rapidly on exposure to air or moisture. Characteristic
J(31P−13C) coupling constants of the carbons of the phenyl rings
were observed in the 13C NMR spectra (including i-, o-, m-, p-
carbons of phenyl rings, for details see Experimental section),
which are consistent with the literature values.[40–44] Furthermore,
1H NMR spectral data 1 and 2 are consistent with the structures
proposed. The FT-IR spectra of 1 and 2 give characteristic bands
at 3405, 1655, 1516, 1035 cm−1 and 3295, 1655, 1512, 1035 cm−1
due to υ(N–H), υ(C O, first amide band), υ(C O, second amide
band) and υ(P–O) stretching, respectively, and υ(O–H) stretching
bandswerenotobserved. Thecompounds1and2wereisolatedas
analytically pure materials and fully characterized by microanalysis
as well, and found to be in good agreement with the theoretical
values.
[Ru(η6-p-cymene)(µ-Cl)Cl]2 (0.05 g, 0.076 mmol) and N,Nꢁ-bis-
[(1S)-1-isobutyl-2-O-(diphenylphosphinite)ethyl]ethanediamide,
2 (0.10 g, 0.152 mmol) were dissolved in 20 ml of toluene
and stirred for 3 h at room temperature. The volume was
concentrated to ca 1–2 ml under reduced pressure and ad-
dition of diethyl ether (20 ml) gave 4 a clear red solid. The
product was collected by filtration and dried in vacuo (yield:
0.12 g, 81.8%); m.p.: 119–121 ◦C. [α]D = −38.2 (c 1.0, DMSO)
25
[(C38H46N2O4P2)RuCl2(CH3C6H4CH(CH3)2]: calcd C, 59.87; H 6.28;
N 2.91; anal. found: C, 59.74; H 6.23; N 2.86%. Selected IR, υ
(cm−1): 3210 (N–H), 3050, 3063 (Ar–H), 1671 (C O, first amide
band), 1508 (C O, second amide band), 1032 (C–O), 896 (P–O).
1H NMR (CDCl3) δ (ppm):[1]H NMR (CDCl3) δ (ppm): 0.86 [d, 6H,
J = 6.0 Hz, -CH(CH3)2 (a)], 0.88 [d, 6H, J = 6.0 Hz, -CH(CH3)2 (b)],
1.08 [d, 6H, J = 6.8 Hz, (CH3)2CHPh of p-cymene], 1.36 [m, 4H,
-CH2-CH(CH3)2], 1.48 [m, 2H, -CH(CH3)2], 1.85 (s, 3H, CH3-Ph of
p-cymene), 2.65 (m, 1H, -CH- of p-cymene), 3.76 [m, 2H, -CH2O-P
(a)], 3.82 [m, 2H, -CH2O-P (b)], 4.08 (m, 2H, -CH-N), 7.28–7.84 (m,
20H, o-, m- and p-protons of phenyls), 8.56 (d, 2H, J = 8.4 Hz,
1
NH). 13C–{ H} NMR (CDCl3) δ (ppm): 17.55 (CH3Ph of p-cymene),
Synthesis of the Ruthenium Complexes 3 and 4
21.70 [(CH3)2CHPh of p-cymene], 21.91 [-CH(CH3)2 (a)], 22.80
[-CH(CH3)2 (b)], 24.56 [-CH(CH3)2], 30.10 (-CH- of p-cymene),
40.37 [-CH2-CH(CH3)2], 48.67 (-CH-N), 68.89 (-CH2O-P), 87.44,
88.02 (aromatics carbons of p-cymene), 97.34, 112.03 (quaternary
carbons of p-cymene), 128.17 (d, 3J31P−13C = 10.1 Hz, m-carbons
of phenyls), 131.23 (d, 4J31P−13C = 2.5 Hz, p-carbons of phenyls),
The whole reactions with [Ru(η6-p-cymene)(µ-Cl)Cl]2 with ligands
1 and 2 are depicted in Scheme 2. The reactions of [Ru(η6-p-
cymene)(µ-Cl)Cl]2 with 2 equivalents of 1 and 2 in toluene at
room temperature gave the red compounds 3 and 4 in high yields
(86.1% 3 and 81.8% 4).
The reactions between Ru(II) precursor and bis(phosphinite)
ligands, 1 and 2 are not affected by the molar ratio of
[Ru(η6-p-cymene)(µ-Cl)Cl]2 as well as the steric and electronic
properties of the donor phosphorus atoms. The initial color
2
132.88 (d, J31P−13C = 11.1 Hz, o-carbons of phenyls), 136.48 (d,
1J31P−13C = 50.3 Hz, i-carbons of phenyls), assignment was based
1
on the 1H–13C HETCOR and 1H–1H COSY spectra. 31P–{ H} NMR
(CDCl3) δ (ppm): 114.96 [s, O-P-(C6H5)2].
c
Appl. Organometal. Chem. 2010, 24, 215–221
Copyright ꢀ 2009 John Wiley & Sons, Ltd.
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M. Aydemir et al.
Scheme 1. Synthesis of the N,Nꢁ-bis-[(1R)-1-ethyl-2-O-(diphenylphosphinite)ethyl]ethanediamide,
phosphinite)ethyl]ethanediamide, 2.
1
and N,Nꢁ-bis-[(1S)-1-isobutyl-2-O-(diphenyl-
Scheme 2. Synthesis of the Ru{chloro(p-cymene)(N,Nꢁ-bis[(1R)-1-ethyl-2-O-(diphenylphosphinite)ethyl]ethanediamide)}]chloride, 3 and [Ru{chloro(p-
cymene)(N,Nꢁ-bis[(1S)-1-isobutyl-2-O-(diphenylphosphinite)ethyl]ethanediamide)}]chloride, 4.
1
change, i.e. from clear orange to deep red, was attributed
to the dimer cleavage most probably by the bis(phosphinite)
In the 13C–{ H} NMR spectra of compounds 3 and 4, J(31P-13C)
coupling constants of the carbons of the phenyl rings were
observed, which are consistent with the literature values.[49,50]
In the compounds 3 and 4, the coupling between i-carbons and
the phosphorus is relatively large, 1J(PC) 42.4 and 50.3 Hz, while
the coupling between o-carbon and the phosphorus relatively
small 2J(PC) 11.1 and 11.0 Hz, respectively. The most relevant
ligand.[45]
Ru{chloro(p-cymene)(N,Nꢁ-bis[(1R)-1-ethyl-2-O-
(diphenylphosphinite)ethyl]ethanediamide)}]chloride, 3, and
[Ru{chloro(p-cymene)(N,Nꢁ-bis[(1S)-1-isobutyl-2-O-(diphenyl-
phosphinite)ethyl]ethanediamide)}]chloride, 4, were isolated as
1
indicated by singlets in the 31P–{ H} NMR spectra at (δ) 115.12
1
and 114.96 ppm, respectively in line with the values previously
observed for similar compounds.[46,47] It is significant to remark
signals of 13C–{ H} NMR spectra of complexes 3 and 4 are those
corresponding to arene ligands (p-cymene). Carbon atoms of the
arene rings in p-cymene ligands are observed as two singlets 87.44
and 88.13 ppm in complex 3 and 87.44 and 88.02 ppm in complex
4. Furthermore, 1H NMR spectral data of complexes are consistent
with the structures proposed. In the 1H NMR spectra, 3 and 4 are
characterized by isopropyl methyl doublets of p-cymene groups,
at δ 1.05 and 1.08 ppm, respectively (for details see Experimental
section).
1
that 31P–{ H} NMR signals of ligands and complexes do not
differ significantly.[48] Elemental analyses of products 3 and 4 are
consistent with the suggested molecular formulas. The absorption
bands corresponding to compounds in the infrared spectra do not
show significant differences with respect to those of free ligands
1
except disappearance of OH bands. H and 13C NMR spectra of
compounds 3 and 4 display all the signals of coordinated ligands.
c
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Appl. Organometal. Chem. 2010, 24, 215–221

New chiral phosphinite ligands with C2-symmetric axis
1-phenylethanol occurred with conversion ranging from 87 to
88% after 30 min for 3 and 4. The catalytic activities of 3
and 4 are comparable, with the TOF values referred to 30 min
of 174 and 176 h−1, respectively (Table 1, entries 5 and 6). In
addition, the ees do not vary with the time, as indicated by
the catalytic results collected with 3 and 4 after 10 min of
the reaction. In these cases conversions higher than 20% have
always been obtained (TOFs up to 120 h−1), indicating that the
reactions start immediately after the addition of NaOH without
any induction time. Furthermore, as can be inferred from the
Table 1 (entries 7 and 8), the precatalysts and the presence of
NaOH are necessary to observe appreciable conversions and the
absence of base leads to the deactivation of the catalysts.[53]
The base facilitates the formation of ruthenium alkoxide by
abstracting proton of the alcohol and subsequently alkoxide
undergoes β-elimination to give ruthenium hydride, which is
an active species in this reaction. This is the mechanism proposed
by several workers on the studies of ruthenium-catalyzed transfer
hydrogenation reaction by metal hydride intermediates.[54–57]
The results show that conversions are significantly affected by
the substrate concentration. A lower concentration of substrate
gives a higher conversion of the alcohol. Furthermore, the ratio of
the substrate to catalyst has less effect on the enantioselectivity.
Performing the reaction in air slowed down the reaction but did
not affect enantioselectivity (Table 1, entries 15 and 16). For the
asymmetric transfer hydrogenation of acetophenone, the catalyst
systemsshowedhighactivityeveninthepresenceofsmallamount
of water. When we increased the amount of water in the reaction
system, the high conversion remained intact (Table 1, entries 13
and 14).
Table 1. Transfer hydrogenation of acetophenone with iso-propanol
catalyzed by Ru{chloro(p-cymene)(N, Nꢁ-bis[1R)-1-ethyl-2-O-(diphenyl-
(p-cymene)(N, Nꢁ-bis[(1S)-1-isobutyl-2-O-(diphenylphosphinite)ethyl]
ethanediamide)}] chloride, 4
phosphinite)ethyl]ethanediamide)}]chloride,
3
and [Ru{chloro
O
OH
Cat (0.005 mmol)/NaOH
+
OH
O
+
Entry Catalyst
s/c
Time
Conversion(%)i TOF(h−1 k
)
1
3a
4a
3b
4b
3c
4c
3d
4d
3e
4e
3f
100 : 1
100 : 1
100 : 1
100 : 1
100 : 1
100 : 1
100 : 1
100 : 1
500 : 1
500 : 1
1000 : 1
1000 : 1
30 min
30 min
24 h
<1
<1
–
–
2
3
35
–
4
24 h
34
–
5
30 min
30 min
60 min
60 min
4 h
87
174
176
–
6
88
7
–
8
–
–
9
94
118
119
145
140
62
64
16
16
10
11
12
13
14
15
16
4 h
95
2 h (7 h)
2 h (7 h)
29 (100)
28 (100)
62 (100)
64 (100)
93.
4f
3g
4g
3h
4h
100 : 1 60 min (4 h)
100 : 1 60 min (4 h)
These complexes were extensively investigated with variety
of substrates. After optimizing the reaction conditions, the
excellent yields were achieved in the reduction of acetophenone
to 1-phenylethanol when [Ru{chloro(p-cymene)(N,Nꢁ-bis[(1R)-1-
ethyl-2-O-(diphenylphosphinite)ethyl]ethanediamide)}]chloride,
100 : 1
100 : 1
6 h
6 h
93
Reaction conditions: a at room temperature; acetophe-
none–Ru–NaOH, 100 : 1 : 5. b At 50 ◦C; acetophenone–Ru–NaOH,
100 : 1 : 5. c Refluxing in iPrOH; acetophenone–Ru–NaOH, 100 : 1:5. d In
the absence of base. e Refluxing in iPrOH; acetophenone–Ru–NaOH,
500 : 1 : 5. f Refluxing in iPrOH; acetophenone–Ru–NaOH, 1000 : 1 : 5.
g Added 0.1 ml H2O. h Carried out (refluxing) the reaction in air.
i Determined by GC (three independent catalytic experiments).
3,
and
[Ru{chloro(p-cymene)(N,Nꢁ-bis[(1S)-1-isobutyl-2-O-
(diphenylphosphinite)ethyl]ethanediamide)}]chloride, 4, were
used as the catalytic precursors in 60 min and it is noteworthy
that 3 and 4 complexes display the same catalytic activities
and selectivities in the transfer hydrogenation of acetophenone
derivatives (Table 2). That is to say, replacing an ethyl moiety
by isobutyl group induced no increase in the conversion and
enantioselectivity. The highest ee (14%) was obtained in the
case of the reduction of acetophenone to (S),(R)-1-phenylethanol
catalyzed by 3 or 4, respectively. The catalytic reduction of
acetophenone derivatives was tested with the conditions
optimized for acetophenone. Complexes 3 and 4 showed very
high activity for most of the ketones. The rate was also affected
by the electronic properties of the substituent on the phenyl
rings. The introduction of electron withdrawing substituents,
such as F, Cl and Br, to the para position of the aryl ring
k Referred at the reaction time indicated in column; TOF
=
(mol product/mol Ru(II) Cat.) × h−1. No significant ee was observed.
Asymmetric Transfer Hydrogenation of Prochiral Ketones
In a preliminary study, complexes 3 and 4 were evaluated as pre-
cursors for the catalytic transfer hydrogenation of acetophenone
by iPrOH. A comparison of complexes 3 and 4 as precatalysts for
the asymmetric transfer hydrogenation of acetophenone by iPrOH
in the presence of NaOH is summarized in Table 1.
Basedonourresults,thesecomplexescatalyzedthereductionof
acetophenone to corresponding alcohol [(R), (S)-1-phenylethanol]
via hydrogen transfer from iPrOH with NaOH as a promoter.
At room temperature, transfer hydrogenation of acetophenone
occurred very slowly with low conversion (1–2% after 1 h, entries
1 and 2) and enantioselectivity (3–5% ee) in all the reactions. At
50 ◦C,theratesremainedlow(5%after24 h,entries3and4)andthe
enantiomeric excess was still low. In addition, the catalytic activity
of [Ru(η6-p-cymene)(µ-Cl)Cl]2 under the applied experimental
conditions is negligible.[51,52] However, when the temperature
was increased to 82 ◦C, smooth reduction of acetophenone into
of the ketone decreased the electron density of the C
bond so that the activity was improved, giving rise to easier
hydrogenation.[58–60]
O
Conclusions
In conclusion, we have synthesized the two new ruthenium com-
plexes from chiral bidendate ligands and investigated their use
in the asymmetric transfer hydrogenation of aromatic ketones.
Disappointingly, in no case was a significant ee observed, even
c
Appl. Organometal. Chem. 2010, 24, 215–221
Copyright ꢀ 2009 John Wiley & Sons, Ltd.
www.interscience.wiley.com/journal/aoc

M. Aydemir et al.
Table 2. Asymmetric transfer hydrogenation results for substituted acetophenones with the catalyst systems prepared from
[Ru(η6-p-cymene)(µ-Cl)Cl]2 and N, Nꢁ-bis-[(1R)-1-ethyl-2-O-(diphenylphosphinite)ethyl]ethanediamide, 3, and N, Nꢁ-bis-[(1S)-1-isobutyl-2-O-
(diphenylphosphinite)ethyl]ethanediamide, 4a
O
OH
OH
O
Cat / NaOH
R
R
+
+
TOF (h−1
98
)
c
Entry
Catalyst
Substrate
Product
Conversion(%)b
98
1
3
O
OH
2
3
4
3
99
99
100
100
OH
O
F
F
Cl
Br
4
5
4
3
100
100
100
100
O
OH
OH
Cl
Br
6
7
4
3
100
99
100
99
O
8
9
4
3
99
98
99
98
O
OMe
OH
OMe
10
11
4
3
98
97
98
97
OH
O
H3CO
H3CO
12
4
96
96
a Catalyst (0.005 mmol), substrate (0.5 mmol), iPrOH (5 ml), NaOH (0.025 mmol%), 82 ◦C, 1.0 h for 3 and 4; concentration of acetophenone, 0.1 M.
b Purity of compounds checked by NMR and GC (three independent catalytic experiments), yields are based on methyl aryl ketone.
c TOF = (mol product/mol cat.) × h−1
.
No significant ee was observed.
though the activities of the two catalysts were good. In a cer-
tain case, optically active alcohols with up 14% ee in high yield
were obtained. This can be attributed to: (i) the oxygen atoms
in complexes 3 and 4 increase the distance between the chi-
ral bis(amino alcohol)oxalamide moiety and the PPh2 groups
and therefore decrease the influence of the bis(amino alco-
hol)oxalamidyl functionality on the stereopositions of the phenyl
rings of the PPh2 group – consequently there is no less con-
trol of stereoselectivity in the catalyst–substrate interactions; (ii)
the presence of the C–O–P bond in ligand moiety substantially
increases the flexibility of the backbone and consequently de-
creases the enantioselectivity of the catalyst.[61–63] Therefore, the
modular construction of these catalysts and their flexibility to-
ward transfer hydrogenation make these promising systems to
pursue.
Acknowledgment
We are deeply indebted to highly talented group of co-workers
whose names are listed in the relevant references. Partial support
from Dicle University (project numbers DUAPK 05-FF-27 and
¨
¨
DUBAP-07-01-22) is gratefully acknowledged.
References
[1] P. Braunstein, J. Organomet. Chem. 2004, 689, 3953.
[2] U. Shubert, J. Pfeiffer, F. Stohr, D. Sturmayr, S. Thompson, J.
Organomet. Chem. 2002, 646, 53.
[3] L. Pascale, N. Le Bris, H. des Abbayes, Trends Organomet. Chem.
2002, 4, 131.
[4] J. C. Jeffrey, T. B. Rauchfuss, Inorg. Chem. 1979, 18, 2658.
[5] S. Priya, M. S. Balakrishna, J. T. Mague, S. M. Mobin, Inorg. Chem.
2003, 42, 1272.
c
www.interscience.wiley.com/journal/aoc
Copyright ꢀ 2009 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2010, 24, 215–221

New chiral phosphinite ligands with C2-symmetric axis
¨
[6] A. M. Z. Slawin, J. Wheatly, J. D. Woollins, Polyhedron 2004, 23, 2569.
[7] V. Cadierno, P. Crochet, J. Diez, J. Garcia-Alvarez, S. E. Garcia-
Cadierno, J. Gimeno, Inorg. Chem. 2003, 42, 3293.
[36] A. Baysal, M. Aydemir, F. Durap, B. Gu¨mgu¨m, S. Ozkar, L. T. Yildırım,
Polyhedron 2007, 26, 3373.
[37] R. Ceron-Camacho, V. Gomez-Benitez, R. Le Lagadec, D. Morales-
Morales, R. A. Toscano, J. Mol. Catal. A 2006, 247, 124.
[38] E. A. Broger, W. Burkart, M. Hennig, M. Scalone, R. Schmid,
Tetrahedron: Asymmetry 1998, 9, 4043.
[39] Z. Fei, R. Scopelliti, P. J. Dyson, Eur. J. Inorg. Chem. 2004, 530.
[40] E. Lindler, M. Mohr, C. Nachtigal, R. Favzi, G. Henkel, J. Organomet.
Chem. 2000, 595, 166.
[41] F. Majoumo, P. Lo¨nnecke, O. Ku¨hl, E. Hey-Hawkins, Z. Anorg. Allg.
Chem. 2004, 630, 305.
[42] M. Aydemir, A. Baysal, G. Oztu¨rk, B. Gu¨mgu¨m, Appl. Organomet.
[8] M. Dieguez, O. Pamies, A. Ruiz, Y. Diaz, S. Castillon, C. Claver, Coor.
Chem. Rev. 2004, 248, 2165.
[9] M. R. Zuburi, A. M. Z. Slawin, M. Wainwright, J. D. Woollins,
Polyhedron 2002, 21, 1729.
[10] T. Appleby, J. D. Woollins, Coord. Chem. Rev. 2002, 235, 121.
[11] Z. Fei, R. Scopelliti, P. J. Dyson, Inorg. Chem. 2003, 42, 2125.
[12] P. Braunstein, F. Naud, Angew. Chem., Int. Ed. Engl. 2001, 40, 680.
[13] A. Caballero, F. A. Jalon, B. R. Manzano, G. Espino, M. Perez-
Manrique, A. Mucientes, F. J. Poblete, M. Maestro, Organometallics
2004, 23, 5694.
¨
Chem. 2009, 23, 108.
[14] R. H. Crabtree, TheOrganometallicChemistryoftheTransitionMetals,
Wiley- Interscience: New York, 2001.
[43] M. Aydemir, A. Baysal, B. Gu¨mgu¨m, J. Organomet. Chem. 2008, 693,
3810.
[15] H. B. Kagan, M. Sasaki, Transition Metals for Organic Synthesis, Wiley-
VCH: Weinheim, 1998.
[44] D. Morales-Morales, R. Redon, C. Yung, C. M. Jensen, Chem.
Commun. 2000, 1619.
[16] P. W. Galka, H.-B. Kraatz, J. Organomet. Chem. 2003, 674, 24.
[17] H. U. Blaser, C. Malan, B. Pugin, F. Spindler, H. Steiner, M. Studer,
Adv. Synth. Catal. 2003, 345, 103.
[45] A. M. Maj, K. M. Michal, I. Suisse, F. Agbossou, A. Mortreux,
Tetrahedron: Asymmetry 1999, 10, 831.
[46] R. Tribo, S. Munoz, J. Pons, R. Yanez, A. Alvarez-Larena, J. F. Piniella,
J. Ros, J. Organomet. Chem. 2005, 690, 4072.
[47] M. S. Balakrishna, P. P. George, S. M. Mobin, Polyhedron 2005, 24,
475.
[18] R. Noyori, T. Ohkuma, Angew. Chem. Int. Ed. Engl. 2001, 40, 40.
[19] J. P. Genet, Acc. Chem. Res. 2003, 36, 908.
¨
[20] M. Yidit, B. Yidit, Y. Ozdemir, E. C¸etinkaya, B. C¸etinkaya,
Appl.Organomet. Chem. 2006, 20, 322.
[21] H.-U. Blaser, C. Malan, B. Pugin, F. Spindler, H. Steiner, M. Studer,
Adv. Synth. Catal. 2003, 345, 103.
[22] G. Zassinovich, G. Mestroni, S. Gladiali, Chem. Rev. 1992, 92, 1051.
[23] R. Noyori, S. Hashiguchi, Acc. Chem. Res. 1997, 30, 97.
[24] T. Ohkuma, M. Koizumi, H. Doucet, T. Pham, M. Kozawa, K. Murata,
E. Katayama, T. Yokozawa, T. Ikariya, R. Noyori, J. Am. Chem. Soc.
1998, 120, 13529.
[48] D. Kostas, B. R. Steele, A. Trezis, S. V. Amosova, Tetrahedron 2003,
59, 3467.
[49] P. Le Gendre, M. Offenbecher, C. Bruneau, P. H. Dixneuf,
Tetrahedron: Asymmetry 1998, 9, 2279.
[50] Q. Zhang, G. Hua, P. Bhattacharrya, A. M. Z. Slawin, J. D. Woollins, J.
Chem. Soc., Dalton Transaction 2003, 3250.
[51] J. Takehara, S. Hashiguchi, A. Fujii, S. Inoue, T. Ikariya, R. Noyori, J.
Chem. Soc., Chem. Commun. 1996, 233.
[25] H. Doucet, T. Ohkuma, K. Murata, T. Yokozawa, M. Kozawa,
E. Katayama, A. F. England, T. Ikariya, R. Noyori, Angew. Chem. Int.
Ed. Engl. 1998, 37, 1703.
[26] R. Guo, C. Elpelt, X. Chen, D. Song, R. H. Morris, Chem. Commun.,
2005, 3050.
[27] D. A. Avans, S. G. Nelson, M. R. Gagne, A. R. Muci, J. Am. Chem. Soc.
1993, 115, 9800.
[28] X. Li, X. Wu, W. Chen, F. E. Hancock, F. King, J. Xiao, Org. Lett. 2004,
6, 3321.
[52] P. Palegatti, M. Carcelli, F. Calbiani, C. Cassi, L. Elviri, C. Pelizzi,
U. Rizzotti, D. Rogolino, Organometallics 2005, 24, 5836.
[53] O. Pamies, J.-E. Backvall, Chem. Eur. J. 2001, 7(23), 5052.
[54] G. Venkatachalam, R. Ramesh, Inorg. Chem. Commun. 2005, 8, 1013.
[55] H. Zhang, B. C. Yang, Y. Y. Li, Z. R. Donga, J. X. Gao, H. Nakamura,
K. Murata, T. Ikariya, J. Chem. Soc., Chem. Commun. 2003, 142.
[56] J. Hannedouche, G. J. Clarkson, M. Wills, J.Am.Chem.Soc. 2004, 126,
986.
[57] A. Bacchi, M. Balordi, R. Cammi, L. Elviri, C. Pelizzi, F. Picchioni,
V. Verdolino, K. Goubitz, R. Peschar, P. Pelagatti, Eur. J. Inorg. Chem.
2008, 4462.
[29] T. Hamada, T. Torii, T. Onishi, K. Izawa, T. Ikariya, J. Org. Chem. 2004,
69, 7391.
[30] M. Mori, N. Nakanishi, D. Kajishima, Y. Sato, J. Am. Chem. Soc. 2003,
125, 9801.
[58] J.-S. Chen, Yan.-Y. Li, Z.-R. Dong, B.-Z. Li, J.-X. Gao, Tetrahedron Lett.
2004, 45, 8415.
[31] Y.-G. Zhou, W. Tang, W.-B. Wang, W. Li, Z. Zhang, J. Am. Chem. Soc.
[59] J. W. Faller, A. R. Lavoie, Organometallics 2001, 20, 5245.
¨
2002, 124, 4952.
[60] I. Ozdemir, S. Yas¸ar, Trans. Met. Chem. 2005, 30, 831.
[32] H. Yang, M. Alvarez, N. Lugan, R. Mathieu, J. Chem. Soc., Chem.
Commun. 1995, 1721.
[61] R. Guo, X. Chen, C. Elpeit, D. Song, R. H. Morris, Organic Lett. 2005,
7(9), 1757.
[33] G. Venkatachalam, R. Ramesh, Inorg. Chem. Commun. 2005, 8, 1009.
[34] M. Aydemir, A. Baysal, N. Meric, B. Gu¨mgu¨m, J. Organomet. Chem.
2009, 694, 2488.
[62] A. S. C. Chan, W. Hu, C.-C. Pai, C.-P. Lau, J. Am. Chem. Soc. 1997, 119,
9570.
[63] Y. Jiang, Q. Jiang, G. Zhu, X. Zhang, Tetrahedron Lett. 1997, 38(2),
[35] M. Sunkur, D. Baris, H. Hosgoren, M. Togrul, J. Org. Chem. 2008, 73,
2570.
215.
c
Appl. Organometal. Chem. 2010, 24, 215–221
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