Ruthenium(II) complexes derived from C2-symmetric ferrocene-based chiral bis(phosphinite) ligands: Synthesis and catalytic activity towards the asymmetric reduction of acetophenones

Article abstract of DOI:10.1002/aoc.3364

Chiral secondary alcohols are very important building blocks and valuable synthetic intermediates both in organic synthesis and in the pharmaceutical industry for producing biologically active complex molecules. A series of new chiral Ru-phosphinite complexes (1, 2, 3, 4, 5, 6, 7, 8) were prepared from chiral C₂-symmetric ferrocenyl phosphinites and corresponding chloro complex, [Ru(η⁶-p-cymene)(μ-Cl)Cl]₂. The complexes were characterized using conventional spectroscopic methods. The binuclear complexes were tested as pre-catalysts and were found to be good pre-catalysts for the asymmetric transfer hydrogenation of substituted acetophenones in basic 2-propanol at 82° C, providing the corresponding optically active alcohols with almost quantitative conversion and modest to high enantioselectivities (46-97%). Amongst the all complexes, complex 6 gave the highest ee of 97% in the reduction of 2-methoxyacetophenone to (S)-1-(2-methoxyphenyl)ethanol at 82° C.

Full text of DOI:10.1002/aoc.3364

Full paper
Received: 11 June 2015
Revised: 13 July 2015
Accepted: 20 July 2015
Published online in Wiley Online Library: 27 August 2015
(wileyonlinelibrary.com) DOI 10.1002/aoc.3364
Ruthenium(II) complexes derived from C2-
symmetric ferrocene-based chiral bis
(phosphinite) ligands: synthesis and catalytic
activity towards the asymmetric reduction
of acetophenones
B. Aka, F. Durapa,b, M. Aydemira,b and A. Baysala*
Chiral secondary alcohols are very important building blocks and valuable synthetic intermediates both in organic synthesis and
in the pharmaceutical industry for producing biologically active complex molecules. A series of new chiral Ru–phosphinite
complexes (1–8) were prepared from chiral C2-symmetric ferrocenyl phosphinites and corresponding chloro complex, [Ru(η6-p-
cymene)(μ-Cl)Cl]2. The complexes were characterized using conventional spectroscopic methods. The binuclear complexes were
tested as pre-catalysts and were found to be good pre-catalysts for the asymmetric transfer hydrogenation of substituted
acetophenones in basic 2-propanol at 82°C, providing the corresponding optically active alcohols with almost quantitative
conversion and modest to high enantioselectivities (46–97%). Amongst the all complexes, complex 6 gave the highest ee of 97%
in the reduction of 2-methoxyacetophenone to (S)-1-(2-methoxyphenyl)ethanol at 82°C. Copyright © 2015 John Wiley & Sons, Ltd.
Keywords: ferrocenyl bis(phosphinite); C2 symmetry; asymmetric transfer hydrogenation; acetophenone; ruthenium
While many studies have been reported concerning phosphine
Introduction
catalysts,[16–20] a notable underdeveloped area is the asymmetric
Over the last few decades, much attention has been devoted
to transition metal complexes with various types of ligands in the
area of homogeneous catalysis.[1,2] There has been a growing inter-
est in the development of new transition metal complexes of
phosphorus- and nitrogen-based ligands for the catalytic asymmet-
ric hydrogenation of prochiral ketones. Following the fascinating
works of Noyori and co-workers, a broad range of transition metal
complexes of phosphorus ligands have been developed, some of
which have been shown to hydrogenate ketones with prominent
catalytic activities.[3–5] Among phosphorus donor ligands, chiral
bis(phosphine) ligands have played a dominant role in the develop-
ment of efficient transition metal-catalysed asymmetric reactions.[6]
In recent years, much effort has been devoted to the use of
rhodium, ruthenium and iridium catalysts containing phosphorus
donor ligands in asymmetric hydrogenation.[7–10] The reduction of
unsaturated molecules can be conducted either by direct hydroge-
nation with gaseous hydrogen, which is more widely applied, or by
hydrogen obtained in situ from a suitable donor such as propan-2-
ol or formic acid.[11,12] The latter has drawn great attention in the
last decade due to its operational simplicity, use of inexpensive
and benign reagents and there being no need for high-pressure
hydrogen that can be potentially dangerous.[13] Asymmetric trans-
fer hydrogenations of functionalized prochiral ketones and imines,
as an efficient method for producing enantiopure alcohols and
amines, have drawn great attention due to their potential for appli-
cations in the fine chemicals, pharmaceuticals and agrochemical
industries and in new materials.[14,15]
transfer hydrogenation of unsaturated molecules catalysed by
phosphinite ligands.
Numerous chiral ligands with ferrocenyl backbones have
been prepared and used successfully in a variety of catalytic
applications.[21–23] Enantiopure ferrocenyl phosphorus or nitrogen
donor ligands have been reported as active catalysts in a variety
of asymmetric catalytic reactions such as hydrogenation,[24]
hydrosilylation,[25] allylic alkylation,[26] Grignard cross-coupling
reactions,[27] cyclopropanation[28] and aldol-type condensation,[29]
and further development of new ligands is still in progress.[30]
Although some phosphines and aminoalcohols containing ferro-
cene skeletons have been employed successfully as ligands in
ruthenium(II)-promoted transfer hydrogenation of ketones, a
screening of catalytic activity of ferrocenyl phosphinites in this
reaction is quite limited.[31–34]
Encouraged by these observations and the fact that C2-symmet-
rical phosphines have wide potential in asymmetric synthesis, we
*
Correspondence to: A. Baysal, Department of Chemistry, Science Faculty, Dicle
University, Diyarbakir 21280, Turkey. E-mail: akinb@dicle.edu.tr
a Department of Chemistry, Science Faculty, Dicle University, Diyarbakir 21280,
Turkey
b Science and Technology Application and Research Center (DUBTAM), Dicle
University, Diyarbakir 21280, Turkey
Appl. Organometal. Chem. 2015, 29, 764–770
Copyright © 2015 John Wiley & Sons, Ltd.

C2-symmetric bis(phosphinite) Ru(II) complexes for reduction of ketones
have synthesized new ruthenium(II) complexes of C2-symmetric
ferrocenyl bis(phosphinite) ligands and used them as catalysts in
ruthenium-catalysed asymmetric transfer hydrogenation of various
ketones.
68.90, 69.11, 69.89 (br, C5H4 + CH2OP), 58.25 (CHN), 46.11 (CH2NH),
36.07 (CH2Ph), 30.09 (CH(CH3)2 of p-cymene), 21.79, 22.02 (CH(CH3)2
of p-cymene), 17.50 (CH3 of p-cymene). 31P-{1H} NMR (162.0 MHz,
CDCl3, δ, ppm): 113.8 (s, O-PPh2). IR (KBr pellet, cmꢀ1): ν(NH): 3332;
ν(CH): 2860, 2925, 3028, 3060; ν(C¼C–Cp): 1447; ν(O–P): 1021. Anal.
Calcd for [C74H82N2O2P2FeRu2Cl4] (1493.3 g molꢀ1) (%): C, 59.52; N,
1.88; H, 5.55. Found (%): C, 59.48, N, 1.80, H, 5.51%. [α]2D0 +66.44 (C
1.2, MeOH).
Experimental
Materials and methods
(S)-Bis[[N-(2-diphenylphosphinite-1-phenyl)ethyl]-1,1′-ferrocenylmethyldiamine
(dichloro η6-p-cymene ruthenium(II))] (2)
Unless otherwise stated, all reactions were performed under argon
in flame-dried glassware using standard Schlenk techniques. All
solvents were purified by distillation over drying agents using
certain procedures prior to use and were transferred under argon.
All reagents were purchased from Fluka and used as received.
Analytical-grade and deuterated solvents were purchased from
Merck.
Yield 195 mg, 92%; m.p. 168–170°C. 1H NMR (400.1 MHz, CDCl3, δ,
ppm): 7.76–7.85 (m, 8H, o-C6H5OP), 7.28, 7.37 (m, 10H, C6H5
+
12H, C6H5OP), 5.15 (br, 8H, C6H4 of p-cymene), 3.86–4.03 (br, 8H,
C5H4 + 2H, CHNH+ 4H, CH2OP), 3.26 (br, 4H, CH2NH), 2.60 (br, 2H,
CH(CH3)2 of p-cymene), 1.83 (br, 6H, CH3 of p-cymene), 1.06 (m,
12H, CH(CH3)2 of p-cymene). 13C NMR (100.6 MHz, CDCl3, δ, ppm):
127.97, 128.06, 128.74, 129.45, 130.96, 131.22 (C6H5 + C6H5OP),
97.10, 111.36 (quaternary carbons of p-cymene), 87.55, 87.70,
90.49, 91.15 (C6H4 of p-cymene), 67.18, 67.83, 68.14, 68.74, 71.03
(C5H4 + CH2OP), 62.33 (CHN), 46.05 (CH2NH), 30.10 (CH(CH3)2 of
p-cymene), 21.74–21.92 (CH(CH3)2 of p-cymene), 17.55 (CH3 of
p-cymene). 31P-{1H} NMR (162.0 MHz, CDCl3, δ, ppm): 109.5 (s,
O-PPh2). IR (KBr pellet, cmꢀ1): ν(NH): 3323; ν(CH): 2865, 2917,
3025, 3064; ν(C¼C–Cp): 1436; ν(O–P): 1018. Anal. Calcd
for [C72H78N2O2P2FeRu2Cl4] (1465.2 g molꢀ1) (%): C, 59.02; N, 1.91;
H, 5.38. Found (%): C, 58.92; N, 1.80; H, 5.22. [α]2D0 +77.8 (C 1.2,
MeOH).
1H NMR (at 400.1 MHz), 13C NMR (at 100.6 MHz) and 31P-{1H} NMR
(at 162.0 MHz) spectra were recorded using a Bruker AV400 spec-
trometer, with tetramethylsilane as an internal standard for 1H
NMR and 13C NMR or 85% H3PO4 as the external reference for
31P-{1H} NMR. Infrared (IR) spectra were recorded with a Mattson
1000 ATI UNICAM FT-IR spectrometer as KBr pellets. Elemental
analysis was carried out using a Fision EA 1108 CHNS-O instrument.
Melting points were recorded with Gallenkamp apparatus with
open capillaries. GC analyses were performed using a Shimadzu
GC 2010 Plus gas chromatograph equipped with a Cyclodex
B (Agilent) capillary column (30 m × 0.32 mm inner diameter ×
0.25 μm film thickness). Racemic samples of alcohols were obtained
by reduction of the corresponding ketones with NaBH4 and used
as authentic samples for ee determination. The GC parameters
for asymmetric transfer hydrogenation of ketones were as follows:
initial temperature, 50°C; initial time, 1.1 min; solvent delay,
4.48 min; temperature ramp, 1.3°C minꢀ1; final temperature,
150°C; initial time, 2.2 min; temperature ramp, 2.15°C minꢀ1; final
temperature, 250°C; initial time, 3.3 min; final time, 44.33 min; injec-
tor port temperature, 200°C; detector temperature, 200°C; injection
volume, 2.0 μl.
(S)-Bis[[N-(2-diphenylphosphinite-1-isobutyl)ethyl]-1,1′-
ferrocenylmethyldiamine (dichloro η6-p-cymene ruthenium(II))] (3)
Yield 198 mg, 88%; m.p. 126–128°C. 1H NMR (400.1 MHz, CDCl3, δ,
ppm): 7.80–7.49 (m, 8H, o-C6H5OP), 7.40–7.42 (b, 12H, m- and p-
C6H5OP), 5.20–5.29 (m, 8H, C6H4 of p-cymene), 4.25 (s, 4H, C5H4),
4.08 (s, H C5H4), 3.61–3.70 (b, 4H, CH2NH + 2H, CH2OP (a)), 3.91 (b,
2H, CH2OP (b)), 2.79 (b, 2H, NHCH), 2.59–2.63 (m, 2H, CH(CH3)2 of
p-cymene), 1.88 (s, 6H, CH3 of p-cymene), 1.33–1.35 (b, 4H, CHCH2
+ 2H, CH(CH3)2), 1.03–1.09 (m, 12H, CH(CH3)2 of p-cymene), 0.72–
0.77 (m, 12H, CH(CH3)2). 13C NMR (100.6 MHz, CDCl3, δ, ppm):
127.95, 128.04, 132.11, (C6H5OP), 97.24, 111.30 (quaternary carbons
of p-cymene), 87.42, 87.87, 90.32, 91.22 (p-cymene C6H4), 67.68,
68.13, 68.85, 69.03, 69.79 (C5H4 + CH2OP), 55.01 (CHN), 45.81
(CH2NH), 40.46 (CHCH2), 30.11 (CH of p-cymene), 24.63 (CHCH3),
21.69, 21.98, 22.36, 23.03 (CH(CH3)2 + CH(CH3)2 of p-cymene),
17.58 (CH3 of p-cymene). 31P-{1H} NMR (162.0 MHz, CDCl3, δ,
ppm): 109.5 (s, O-PPh2). IR (KBr pellet, cmꢀ1): ν(NH): 3330; ν(CH):
2867, 2955, 2961, 3070; ν(C¼C–Cp): 1436; ν(O–P): 1021. Anal. Calcd
for [C68H86N2O2P2FeRu2Cl4] (1425.2 g molꢀ1) (%): C, 57.30; N, 1.97;
H, 6.08. Found (%): C, 57.23; N, 1.94; H, 6.01. [α]2D0 +47.3 (C 1.2,
MeOH).
General procedure for synthesis of ferrocene-based bis
(phosphinite) ruthenium(II) complexes (1–8)
To a solution of ferrocene-based phosphinite ligand[35] (1 equiv.) in
dry toluene (20 ml), the metal precursor [Ru(η6-p-cymene)(μ-Cl)Cl]2
(1 equiv.) was added at room temperature. The mixture was stirred
until the resonance of free ligand disappeared in the 31P NMR spec-
trum (1 to 14 h). The solvent was evaporated to ca 1–2 ml and
petroleum ether (20 ml) was added to yield a tile-red powder which
was washed with diethylether–n-hexane (1:1) and then dried in
vacuum.
(S)-Bis[[N-(2-diphenylphosphinite-1-benzyl)ethyl]-1,1′-ferrocenylmethyldiamine
(dichloro η6-p-cymene ruthenium(II))] (1)
(S)-Bis[[N-(2-diphenylphosphinite-1-sec-butyl)ethyl]-1,1′-
Yield 180 mg, 88%; m.p. 136–138°C. 1H NMR (400.1 MHz, CDCl3, δ,
ppm): 7.82–7.88 (m, 8H, o-C6H5P), 7.05–7.44 (m, 10H, C6H5 +12H,
m- and p-C6H5P), 5.13–5.22 (m, 8H, C6H4 of p-cymene), 3.68–4.17
(m, 8H, C5H4 + 4H, (CH2OP) + 4H, CH2NH), 3.06 (br, 2H, CHNH),
2.84–2.93 (m, 4H, CH2Ph), 2.60–2.53 (m, 2H, CH(CH3)2 of p-cymene),
1.80 (s, 6H, CH3 of p-cymene), 1.06 (d, 6H, J = 6.9 Hz, CH(CH3)2 of p-
ferrocenylmethyldiamine (dichloro η6-p-cymene ruthenium(II))] (4)
Yield 180 mg, 80%; m.p. 129–131°C. 1H NMR (400.1 MHz, CDCl3, δ,
ppm): 7.84–7.95 (m, 8H, o-C6H5P), 7.42 (b, 12H, m- and p-C6H5P),
5.21–5.33 (m, 8H, C6H4 of p-cymene), 4.07–4.16 (br, 8H, C5H4), 3.91
(br, 2H, CH2OP (a)), 3.69 (br, 2H, CH2OP (b)), 3.48 (br, 4H, CH2NH),
2.61–2.65 (b, 2H, CHNH + 2H, CH of p-cymene), 1.60 (b, 2H, CH3CH),
1.28–1.33 (m, 4H, CH2CH3), 1.88 (s, 6H, CH3 of p-cymene), 1.10 (d, 6H,
J = 7.0 Hz, CH(CH3)2 of p-cymene), 1.06 (d, 6H, J = 6.7 Hz, CH(CH3)2 of
p-cymene), 0.80–0.92 (m, 6H, CHCH3 + 6H, CH2CH3). 13C NMR (100.6
cymene (a)), 1.01 (d, 6H, J = 6.6 Hz, CH(CH3)2 of p-cymene (b)). 13
C
NMR (100.6 MHz, CDCl3, δ, ppm): 127.97, 128.07, 129.03, 131.00,
131.43, 132.39 (C6H5 + C6H5OP), 97.34, 111.41 (quaternary carbons
of p-cymene), 87.33, 87.89, 89.97, 91.14 (C6H4 of p-cymene), 68.71,
Appl. Organometal. Chem. 2015, 29, 764–770
Copyright © 2015 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc

B. Ak et al.
MHz, CDCl3, δ, ppm): 127.84, 130.90, 132.64 (C6H5P), 97.34, 11.28
(quaternary carbons of p-cymene), 87.55, 87.65, 87.71, 90.36 (C6H4
of p-cymene), 67.10, 67.90, 68.12, 68.64, 69.33 (C5H4 + CH2OP),
61.10 (CHNH), 46.79 (CH2NH), 36.01 (CHCH3), 30.01 (CH of p-
cymene), 25.72 (CH2CH3), 21.73, 22.01 (CH(CH3)2 of p-cymene),
17.55 (–CH3 of p-cymene), 11.98, 14.71 (CHCH3 + CH2CH3). 31P-{1H}
NMR (162.0 MHz, CDCl3, δ, ppm): 110.80 (s, O-PPh2). IR (KBr pellet,
cmꢀ1): ν(NH): 3325; ν(CH): 2872, 2921, 2959, 3063; ν(C¼C–Cp):
1460; ν(O–P): 1015. Anal. Calcd for [C68H86N2O2P2FeRu2Cl4]
(1425.2 g molꢀ1) (%): C, 57.30; N, 1.97; H, 6.08. Found (%): C, 57.20;
N, 1.82; H, 5.91. [α]2D0 +64.2 (C 1.2, MeOH).
General procedure for asymmetric transfer hydrogenation of
ketones
The ruthenium catalyst (0.005 mmol) and anhydrous 2-propanol
(5 ml) were placed in a flame-dried Schlenk tube under inert
atmosphere. Then, the corresponding ketone (0.5 mmol) and
NaOH (0.025 mmol) were added and the mixture was heated at
the required temperature with stirring until the reaction was
complete. Subsequently, a sample of reaction mixture was taken
off and diluted with acetone. The product distribution was deter-
mined immediately using GC. Conversions obtained are related
to unreacted ketone.
(R)-Bis[[N-(2-diphenylphosphinite-1-ethyl)ethyl]-1,1′-ferrocenylmethyldiamine
(dichloro η6-p-cymene ruthenium(II))] (5)
Results and discussion
Yield 175 mg, 91%; m.p. 130–132°C. 1H NMR (400.1 MHz, CDCl3, δ,
ppm): 7.26–7.80 (m, 20H, C6H5P ), 5.20–5.28 (m, 8H, C6H4 of p-
cymene), 4.10–4.24 (m, 8H, C5H4), 3.85–3.93 (m, 4H, CH2OP), 3.62–
3.67 (m, 4H, CH2NH), 2.78–2.85 (m, 2H, CHN), 1.31–1.52 (m, 4H,
CH2CH3), 2.64 (m, 2H CH(CH3)2 of p-cymene), 1.80 (s, 6H, CH3 of
p-cymene), 1.04–1.10 (m, 12H, CH(CH3)2 of p-cymene), 0.91–0.95
(m, 6H, CH2CH3). 13C-NMR (100.6 MHz, CDCl3, δ, ppm): 141.76 (d, J
= 9.0 Hz, i-C6H5P), 128.03, 130.95, 132.14 (o-, m-, p-C6H5), 97.32,
111,27 (quaternary carbons of p-cymene), 87.47, 87.88, 90.32,
91.09 (C6H4 of p-cymene), 86.59 (i-C5H4), 71.24 (d, J = 18.1 Hz,
CH2OP), 68.46, 68.88, 69.51, 69.65 (C5H4), 58.37 (CHN), 46.05
(CH2NH), 23.41 (CH2CH3), 21.96, 21.71 (CH(CH3)2 of p-cymene),
30.10 (CH(CH3)2 of p-cymene), 17.57 (CH3 of p-cymene), 10.22
(CH2CH3). 31P-{1H} NMR (162.0 MHz, CDCl3, δ, ppm): 110.9 (s,
O-PPh2). IR (KBr pellet, cmꢀ1): ν(NH): 3342; ν(CH): 2868,
2920, 3038, 3101; ν(C¼C–Cp): 1457; ν(O–P): 1011. Anal. Calcd
for [C64H78N2O2P2FeRu2Cl4] (1369.1 g molꢀ1) (%): C, 56.14; N, 2.05;
H, 5.75. Found (%): C, 56.02; N, 1.99; H, 5.71. [α]2D0 ꢀ63.2 (C 1.2,
MeOH).
The complexes [Ru2Cl4L], where L is L1–L8, were prepared by the
addition of an equivalent of [Ru(η6-p-cymene)(μ-Cl)Cl]2 to a dry
solution of ferrocene-based bis(phosphinite) ligands (Fig. 1). After
1–14 h stirring at room temperature, the 31P NMR spectrum of the
reaction mixture displays the complete disappearance of the signal
corresponding to the free bisphosphinites and the appearance of a
new signal for the expected complexes. All complexes are obtained
as tile-red powders in high yields. A single resonance ranging from
109.5 to 113.8 ppm is obtained for all complexes in the 31P-{1H} NMR
spectra. The 1H NMR and 13C NMR data for complexes 1–5 are con-
sistent with the formulation of [Ru2Cl4L] and in line with the values
1
previously observed for similar complexes. However, H NMR and
13C NMR spectra were not recorded for complexes 6–8 due to the
low solubility of these complexes in common NMR solvents.
We have recently reported the synthesis of several chiral
ferrocenyl phosphinite ligands and their applications in Ru(II)(ar-
ene)-catalysed transfer hydrogenation of ketones.[27–29] As part of
our continuing interest in ferrocene-based chiral ligands and their
applications in asymmetric catalysis, we herein report the results
obtained for the asymmetric transfer hydrogenation of various
ketones using ruthenium(II) complexes of C2-symmetric chiral
phosphinite ligands containing ferrocenyl moiety.
(R)-Bis[[N-(2-diphenylphosphinite-2-phenyl)ethyl]-1,1′-ferrocenylmethyldiamine
(dichloro η6-p-cymene ruthenium(II))] (6)
Yield 218 mg, 93%; m.p. 156–158°C. 31P-{1H} NMR (162.0 MHz,
CDCl3, δ, ppm): 111.2 (s, O-PPh2). IR (KBr pellet, cmꢀ1): ν(NH): 3310;
ν(CH): 2861, 2926, 3029, 3056; ν(C¼C–Cp): 1437; ν(O–P): 1026. Anal.
Calcd for [C72H78N2O2P2FeRu2Cl4] (1465.2 g molꢀ1) (%): C, 59.02; N,
1.91; H, 5.38. Found (%): C, 58.89; N, 1.96; H, 5.32. [α]2D0 ꢀ73.3 (C 1.2,
MeOH).
To evaluate the effectiveness of our ruthenium(II) complexes
(1–8) as catalysts in asymmetric transfer hydrogenation reaction
of ketones, we prefer starting with the reduction of acetophenone
as a standard test reaction. For screening the activity and
enantioselectivity for the reaction, the optimal conditions were
investigated, such as reaction temperature and molar ratio of
substrate to catalyst. The results presented in Table 1 clearly show
that the catalysts are active and selective for asymmetric transfer
(1S,2R)-Bis[[N-(2-diphenylphosphinite-1,2-diphenyl)ethyl]-1,1′-
ferrocenylmethyldiamine (dichloro η6-p-cymene ruthenium(II))] (7)
Yield 218 mg, 93%; m.p. 160–162°C. 31P-{1H} NMR (162.0 MHz,
CDCl3, δ, ppm): 113.6 (s, O-PPh2). IR (KBr pellet, cmꢀ1): ν(NH): 3342;
ν(CH): 2865, 2935, 3040, 3057; ν(C¼C–Cp): 1460; ν(O–P): 1018. Anal.
Calcd for [C84H86N2O2P2FeRu2Cl4] (1617.4 g molꢀ1) (%): C, 62.37;
N, 1.73; H, 5.37. Found (%): C, 58.86; N, 1.60; H, 5.17. [α]2D0 +55.2 (c
1.2, MeOH).
(S)-Bis[[N-(2-diphenylphosphinitepropyl)]-1,1′-ferrocenylmethyldiamine
(dichloro η6-p-cymene ruthenium(II))] (8)
Yield 181 mg, 90%; m.p. 126–128°C. 31P-{1H} NMR (162.0 MHz,
CDCl3, δ, ppm): 110.0 (s, O-PPh2). IR (KBr pellet, cmꢀ1): ν(NH): 3372;
ν(CH): 2850, 2915, 3018, 3066; ν(C¼C–Cp): 1442; ν(O–P): 1031. Anal.
Calcd for [C62H74N2O2P2FeRu2Cl4] (1341.1 g molꢀ1) (%): C, 55.52; N,
2.09; H, 5.57. Found (%): C, 55.42; N, 2.01; H, 5.49. [α]2D0 +43.2 (C 1.2,
MeOH).
Figure 1. Synthetic route for the preparation of C2-symmetric ferrocene-
based chiral bis(phosphinite) ruthenium(II) complexes 1–8.
wileyonlinelibrary.com/journal/aoc
Copyright © 2015 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2015, 29, 764–770

C2-symmetric bis(phosphinite) Ru(II) complexes for reduction of ketones
Table 1. Asymmetric transfer hydrogenation of acetophenone with iso-PrOH catalysed by C2-symmetric bisphosphinite ruthenium(II) complexes (1–8)
TOF (hꢀ1
)
d
Entry
Complex
Substrate/catalyst/base
Time (h)
Conv. (%)a
ee (%)b
Config.c
1
1e
2e
3e
4e
5e
6e
7e
8e
1f
100:1:5
100:1:5
100:1:5
100:1:5
100:1:5
100:1:5
100:1:5
100:1:5
100:1
1
1
99
98
90
92
64
78
62
98
95
96
—
—
—
—
—
—
—
—
84
87
59
64
55
95 (92)h
84
89
92
95
93
89
89
79
83
82
71
76
77
64
68
R
S
99
98
8
2
3
12
12
12
12
12
12
24
24
24
24
24
24
24
24
0.5
0.5
0.5
0.5
0.5
2 (2)h
0.5
1
97
R
4
98
S
8
5
98
R
8
6
99
R
8
7
98
R
8
8
99
S
8
9
<10
<10
<10
<10
<10
<10
<10
<10
98
—
—
—
—
—
—
—
—
R
—
—
—
—
—
—
—
—
196
198
196
196
196
49 (48)
196
98
48
49
48
47
48
47
47
31
30
30
17
16
16
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
2f
100:1
3f
100:1
4f
100:1
5f
100:1
6f
100:1
7f
100:1
8f
100:1
1g
2g
3g
4g
5g
6g
7g
8g
6g
6g
6g
6g
6g
7g
8g
6g
7g
8g
6g
7g
8g
100:1:5
100:1:5
100:1:5
100:1:5
100:1:5
100:1:5
100:1:5
100:1:5
100:1:3
100:1:5
100:1:7
100:1:9
250:1:5
250:1:5
250:1:5
500:1:5
500:1:5
500:1:5
1000:1:5
1000:1:5
1000:1:5
99
S
98
R
98
S
98
98 (96)h
R
R
98
R
98
S
2
96
R
2
98
R
2
96
R
2
93
R
2
96
R
2
93
R
2
94
S
3
93
R
3
90
R
3
91
S
5
87
R
5
80
R
5
82
S
aDetermined by GC (three independent catalytic experiments).
bDetermined by capillary GC analysis using a chiral Cyclodex B (Agilent) capillary column.
cDetermined 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) × hꢀ1
.
eAt room temperature, in the presence of NaOH.
fRefluxing in iso-PrOH, in absence of base.
gRefluxing in iso-PrOH, in presence of NaOH.
hRefluxing in iso-PrOH; acetophenone/Ru/KOH, 100:1:5.
hydrogenation of acetophenone. The transfer hydrogenation of
acetophenone using complexes 1–8 as catalysts at a molar
substrate-to-catalyst ratio of 100 in 2-propanol with NaOH at room
temperature gives almost quantitative conversion and moderate to
high enantioselectivities (62–98%, entries 1–8). As evident from
Table 1, the reaction rate is markedly increased on increasing the
Appl. Organometal. Chem. 2015, 29, 764–770
Copyright © 2015 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc

B. Ak et al.
Table 2. Transfer hydrogenation of substituted acetophenones catalysed by 1–8a
TOF (hꢀ1
)
Config.e
d
Entry
Catalyst
R
Time (h)
Conv. (%)b
ee (%)c
1
1
2
3
4
5
6
7
8
1
2
3
4
5
6
7
8
1
2
3
4
5
6
7
8
1
2
3
4
5
6
7
8
1
2
3
4
5
6
7
8
1
2
3
4
5
6
7
8
1
2
H
0.5
0.5
0.5
0.5
0.5
2
98
99
98
98
98
98
98
98
98
99
99
98
99
98
98
98
97
98
98
98
98
99
99
99
98
98
98
97
98
98
98
98
98
98
97
98
98
97
99
98
96
98
96
97
98
98
98
98
96
95
84
87
59
64
55
95
86
89
78
79
49
55
47
88
78
82
80
82
53
60
51
92
83
86
81
83
56
62
50
91
84
87
82
83
55
63
53
94
85
89
85
90
61
65
57
97
90
94
72
79
196
198
196
196
196
49
R
S
R
S
R
R
R
S
R
S
R
S
R
R
R
S
R
S
R
S
R
R
R
S
R
S
R
S
R
R
R
S
R
S
R
S
R
R
R
S
S
R
S
R
S
S
S
R
R
S
2
3
4
5
6
7
0.5
1
196
98
8
9
2-F
0.5
0.5
0.5
0.5
0.5
1
196
198
198
196
196
98
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
0.5
1
196
98
4-F
0.25
0.25
0.25
0.33
0.33
0.75
0.25
0.5
0.75
0.75
0.75
0.75
1
388
392
392
294
294
132
396
198
131
131
131
129
98
2-Br
3
33
0.75
1
131
98
4-Br
0.5
0.5
0.5
0.5
0.75
2
196
196
194
196
131
49
0.5
0.5
2
198
198
48
2-OCH3
2
49
2
48
2
49
2
49
4
25
2
49
3
33
4-OCH3
1
96
1
95
(Continues)
wileyonlinelibrary.com/journal/aoc
Copyright © 2015 John Wiley & Sons, Ltd.
Appl. Organometal. Chem. 2015, 29, 764–770

C2-symmetric bis(phosphinite) Ru(II) complexes for reduction of ketones
Table 2. (Continued)
TOF (hꢀ1
)
Config.e
d
Entry
Catalyst
R
Time (h)
Conv. (%)b
ee (%)c
51
52
53
54
55
56
57
58
59
60
61
62
63
64
65
66
67
68
69
70
71
72
3
4
5
6
7
8
1
2
3
4
5
6
7
8
1
2
3
4
5
6
7
8
1
94
96
96
97
97
96
97
99
98
97
98
98
98
99
98
99
99
97
99
99
99
99
52
56
51
88
79
82
81
84
55
60
51
92
83
88
78
81
49
55
46
89
81
84
94
96
R
S
R
R
R
S
R
S
R
S
R
R
R
S
R
S
R
S
R
R
R
S
1
1
96
3
32
1
97
2
48
4-NO2
1
97
1
99
1
98
1
97
4
25
6
16
1
98
3
33
4-CF3
0.33
0.33
0.33
0.33
0.33
0.5
0.33
0.33
294
297
297
291
297
198
297
297
aCatalyst (0.005 mmol), substrate (0.5 mmol), iso-PrOH (5 ml), NaOH (0.025 mmol%), 82°C, concentration of acetophenone derivatives 0.1 M.
bPurity of compounds checked by 1H NMR and GC (three independent catalytic experiments); yields are based on aryl ketone.
cDetermined by capillary GC analysis uꢀsi1ng a chiral Cyclodex B (Agilent) capillary column (30 m × 0.32 mm inner diameter × 0.25 μm film thickness).
dTOF = (mol product/mol catalyst) × h
.
eDetermined by comparison of the retention times of the enantiomers on the GC traces with literature.
reaction temperature from 25 to 82°C, whereas the reactivity tophenone change the reduction rate but have only little effect
decreases on increasing the substrate concentration 10-fold. The on the enantioselectivity. As observed in many studies, the pres-
enantioselectivity also decreases markedly on increasing both reac- ence of an electron-withdrawing group on the phenyl ring gener-
tion temperature and substrate concentration. Among the catalysts ally facilitates the hydrogenation reaction, which is attributed to
screened, complex 6 proves to be the best catalyst, yielding (R)-1- the hydridic nature of the reducing species involved.[36] Table 2
phenylethanol with 99% conversion and 98% ee after 12 h at room shows that the ortho-substituted acetophenone is reduced more
temperature (Table 1, entry 6). At reflux temperature of 82°C, the slowly than para-substituted ones and shows a slightly lower selec-
reaction takes less time to complete than at room temperature but tivity probably due to an undesirable steric clash.
gives lower enantiomeric excess. As evident from Table 1, changing
4-Methoxyacetophenone is known to be a tough substituent
the base does not affect the product conversion (entry 22). It is probably because of its rather low redox potential, and it gives
worth mentioning that the opposite absolute configuration of
1-phenylethanol is obtained compared to the configuration of
the complexes (1 and 3) used as catalysts, while for all other
complexes the product configurations do not change.
lower conversion and enantioselectivity.[37] However, in the
present work, the reduction of 2- or 4-methoxyacetophenone
occurs with 98 or 97% conversion and 97 or 88% ee, respectively,
at 82°C. Compared to our previous report[29] in which Ru(II)
Following investigation of the optimal conditions, these com- complexes were derived from chiral monophosphinite ligands
plexes were also evaluated for catalytic activity towards transfer containing a ferrocenyl moiety, using 1 or 2 as catalyst under
hydrogenation of substituted acetophenones using 2-propanol identical conditions the hydrogenation of acetophenone or its
both as the hydrogen source and solvent in the presence of NaOH derivatives is accomplished with similar conversion but with
as the base. The results clearly indicate that all the substituted slightly higher enantiolesectivity. It is well known that structural
acetophenones are transformed into the corresponding secondary differences considerably affect catalytic activity. Experimental
alcohols in high yields. The results also show that the electronic results obtained from the catalytic evaluation reveal that com-
properties of the substituent on the phenyl ring of the ace- plexes 6, 7 and 8 are efficient catalysts for the reduction of
Appl. Organometal. Chem. 2015, 29, 764–770
Copyright © 2015 John Wiley & Sons, Ltd.
wileyonlinelibrary.com/journal/aoc

B. Ak et al.
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atom in the ligands of complexes 1–8 results in a significant dif-
ference in both catalyst reactivity and enantioselectivity. The re-
sults clearly indicate that when the chiral centre is present near
the metal atom, high enantioselectivity is observed. Moreover,
the aryl moiety on the carbon atom having a chiral centre is
more responsible for both higher activity and selectivity than
the alkyl moiety. Among the eight new catalysts described herein,
catalyst 6 gives almost quantitative conversions (97–99%) for all
ketones screened. The enantioselectivities obtained using this
catalyst range from 88 to 97% ee at 82°C. Reduction of 2-
methoxyacetophenone to (S)-1-(2-methoxyphenyl)ethanol is
achieved with both high conversion and enantioselectivity of 98
and 97%, respectively, at 82°C.
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A series of C2-symmetric bis(phosphinite) ruthenium(II) complexes
bearing ferrocenyl moiety were developed and evaluated for
catalytic activity towards asymmetric transfer hydrogenation of
acetophenone derivatives using 2-propanol in the presence of
NaOH. Almost complete conversion and moderate to excellent
enantioselectivity were obtained using all complexes as catalysts.
Complex 6 is the most efficient catalyst among the eight com-
plexes. The most efficient conversion and enantioselectivity were
found in the case of 2-methoxyacetphenone with catalyst 6.
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Partial support from the Scientific and Technological Research
Council of Turkey (TUBITAK; project no. 111T419) and Dicle University
Scientific Research Projects Coordination Unit (DUBAP) is gratefully
acknowledged.
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