Imine containing C2-Symmetric chiral half sandwich η6-p-cymene-Ru(II)- phosphinite complexes: Investigation of their catalytic activity in the asymmetric transfer hydrogenation of ketones

Article abstract of DOI:10.1016/j.molstruc.2019.127146

New chiral C₂-symmetric bis(phosphinite) ligands containing imine group were synthesized from 1-({[(1R,2R)-2-{[(2-hydroxynaphthalen-1-yl)methylidene] amino}cyclohexyl]- imino}methyl)- naphthalen-2-ol and two equivalents of Ph₂PCl, (i-Pr)₂PCl or (Cy)₂PCl, in high yields. Binuclear C₂-symmetric half sandwich η⁶-p-cymene-Ru(II) complexes of the chiral phosphinite ligands were synthesized by treating of [Ru(η⁶-p-cymene)(μ-Cl)Cl]₂ with the phosphinites in 1:1 M ratio in CH₂Cl₂. Their catalytic activities in asymmetric transfer hydrogenation (ATH) were investigated for the reaction of acetophenone derivatives with isopropyl alcohol. The corresponding optically active secondary alcohols were obtained in excellent levels of conversion (96–99%) and moderate enantioselectivity (up to 60% ee). Among three complexes investigated, complex 4 was the most efficient one.

Full text of DOI:10.1016/j.molstruc.2019.127146

Journal of Molecular Structure 1200 (2020) 127146
Contents lists available at ScienceDirect
Journal of Molecular Structure
journal homepage: http://www.elsevier.com/locate/molstruc
Imine containing C -Symmetric chiral half sandwich h6-p-cymene-
2
Ru(II)- phosphinite complexes: Investigation of their catalytic activity
in the asymmetric transfer hydrogenation of ketones
a
b
a
a
c
Najmuldain Abdullah Saleh , Salih Pa s¸ a , Cezmi Kayan , Nermin Meriç , Murat Sünkür ,
c
a
a
a, *
Tarık Aral , Murat Aydemir , Akın Baysal , Feyyaz Durap
a
Department of Chemistry, Science Faculty, Dicle University, 21280, Diyarbakir, Turkey
Department of Science, Faculty of Education, Afyon Kocatepe University, Afyonkarahisar, Turkey
Department of Chemistry, Faculty of Science and Art, Batman University, 72100, Batman, Turkey
b
c
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 17 April 2019
Received in revised form
2
New chiral C -symmetric bis(phosphinite) ligands containing imine group were synthesized from 1-
(
{[(1R,2R)-2-{[(2-hydroxynaphthalen-1-yl)methylidene] amino}cyclohexyl]- imino}methyl)- naph-
thalen-2-ol and two equivalents of Ph PCl, (i-Pr) PCl or (Cy) PCl, in high yields. Binuclear C -symmetric
-p-cymene-Ru(II) complexes of the chiral phosphinite ligands were synthesized by
treating of [Ru(h6-p-cymene)(
-Cl)Cl] with the phosphinites in 1:1 M ratio in CH Cl . Their catalytic
2
2
2
2
26 September 2019
6
half sandwich
h
Accepted 27 September 2019
Available online 27 September 2019
m
2
2
2
activities in asymmetric transfer hydrogenation (ATH) were investigated for the reaction of acetophe-
none derivatives with isopropyl alcohol. The corresponding optically active secondary alcohols were
obtained in excellent levels of conversion (96e99%) and moderate enantioselectivity (up to 60% ee).
Among three complexes investigated, complex 4 was the most efficient one.
Keywords:
Phosphinite
Chiral
Catalysis
© 2019 Elsevier B.V. All rights reserved.
Asymmetric transfer hydrogenation
Ruthenium
1. Introduction
of catalyst [19]. Morris et al. reported both steric and electronic
effect of R substituents on P atom on the catalytic activity in terms
The development of well-designed catalytic systems is an
important field of modern synthetic chemistry for attaining suit-
able building blocks of all kind of chemicals [1,2]. A great deal of
chiral compounds such as aminoalcohols [3], diamines [4], S-donor
ligands [5], P-donor ligands [6e12], heterocyclic ligands [13] and
ferrocene based ligands [14] have been designed, synthesized and
applied successfully in a numerous of catalytic reactions. Over the
years, among the above named ligands, P-donor ligands are used as
homogeneous catalysts in various catalytic reactions. Complexes
including these types of ligands are of considerable interest
because of their potential use in many organic processes such as
CeH activation [15], allylic substitution [16], CeC cross coupling
arylation [17] and alkylation and transfer hydrogenation [18] pro-
cesses to name a few. It has been shown that the steric and elec-
tronic properties of the ligands play a crucial role in the efficiencies
of TOF and ee values in the reduction of acetophenone catalyzed by
iron phosphine complexes (PeNHeNeP’) in details [20].
Among the synthetic intermediates, chiral alcohols have an
important place in many fields such as pharmaceutical industry and
organic synthesis [21]. ATH (asymmetric transfer hydrogenation) is
an important method to obtain chiral alcohols because its fractional
yields of side products are lower and product yields and enantio-
meric excess are higher [22]. Furthermore, its reaction conditions
are milder and lower cost owing to its operational simplicity
[23,24]. Therefore, development of new chiral catalysts tailored to
the transfer hydrogenation of prochiral ketones has been widely
studied [25]. Among the different transition metals, transfer hy-
drogenation is usually promoted by Rh, Ru, or Ir metal catalysts
[26,27].
In our laboratory we have been engaged in developing chiral
phosphinite ruthenium (II) complex catalysts for the asymmetric
reduction of a variety of aromatic ketones [28e30]. However, to the
best of our knowledge, there are only few reports on the use of
*
Corresponding author. Department of Chemistry, Science Faculty, Dicle Uni-
versity, 21280, Diyarbakır, Turkey.
imine
containing
bis(phosphinite)
ligands
in
transfer
E-mail address: fdurap@dicle.edu.tr (F. Durap).
https://doi.org/10.1016/j.molstruc.2019.127146
0
022-2860/© 2019 Elsevier B.V. All rights reserved.

2
N.A. Saleh et al. / Journal of Molecular Structure 1200 (2020) 127146
hydrogenation reaction [6]. Inspired by these studies, herein, syn-
thesis and characterization of three new imine based binuclear C
2.1.2. Synthesis
2
-
6
2.1.2.1. General procedure for the synthesis of bis(phosphinite) li-
gands (1e3). The new chiral C -symmetric bis(phosphinite) ligands
2
were prepared according to the our recent publications [33]. To a
solution of 1-({[(1R,2R)-2-{[(2-hydroxynaphthalen-1-yl)methyl-
symmetric chiral phosphinite-Ru(II)-
h -p-cymene half sandwich
complexes are reported. For this aim, phosphinite ligands, 1e3,
were synthesized by hydrogen abstraction from synthesized pre-
cursor of 1-({[(1R,2R)-2-{[(2-hydroxynaphthalen-1-yl)methyl-
idene]
amino}cyclohexyl]imino}methyl)-
1.5 mmol) in dry CH Cl (20 mL) was added triethylamine
3.0 mmol) and the mixture was stirred for 10 min under argon
PCl
PCl (3.0 mmol). The
naphthalen-2-ol
idene] amino}cyclohexyl]imino}methyl)naphthalene-2-ol, by
reaction of two equivalents of Ph PCl, (i-Pr) PCl or Cy PCl, respec-
tively. The binuclear ruthenium complexes 4e6 were synthesized
a
(
(
2
2
2
2
2
6
atmosphere. To this solution was added dropwise Ph
3.0 mmol), (i-Pr) PCl (3.0 mmol) or (Cy)
2
by treatment of [Ru(
2
h -p-cymene)(m-Cl)Cl] with phosphinites 1e3
(
2
2
in 1:1 M ratio. Herein, we also present that binuclear phosphinite-
6
mixture was then stirred at room temperature until the reactions
were completed. A white precipitate of triethylamine hydrochlo-
ride was removed by filtration under argon and the remaining
organic phase was evaporated under reduced pressure to produce a
yellow oily product. The progress of these reactions was followed
Ru(II)-
h -p-cymene half sandwich complexes 4e6 are efficient
catalysts for the ATH of acetophenone derivatives with 2-propanol
under optimized conditions.
31
1
by Pe{ H} NMR spectroscopy.
.1.2.1.1. 1-({[(1R,2R)-2-[({2-[(diphenylphosphanyl)oxy]naph-
thalen-1-yl}methylidene)amino] cyclohexyl]imino}methyl)naph-
thalen-2-yl diphenylphosphinite (1). Yield: 100 mg, (84%). H NMR
CDCl , ppm): 9.07 (s, 2H, eN]CH) 6.88e7.84 (m, 32H, protons of
naphthyl þ OPPh ), 3.78 (br, 2H, CH of Cy), 1.87 (br, 4H, -CH of Cy),
.31e1.37 (m, 4H, -CH 158.08 (d,
J ¼ 44.3 Hz, ipso carbon of OPPh ), 157.86 (-N]CH), 135.32 (d,
J ¼ 20.2 Hz, ortho carbon of OPPh ), 130.95 (para carbon of OPPh ),
30.57 (d, J ¼ 10.1 Hz meta carbon of OPPh ), 176.02, 136.91, 133.97,
28.58, 127.83, 127.49, 124.51, 122.46, 118.77, 106.46 (carbons of
naphthyl), 68.00 (-CH of Cy), 32.26 (-CH of Cy), 24.64 (-CH of Cy).
114.09 (s, OPPh ). IR (KBr pellet in
cm ): ʋ 3068, 3028 (Aromatic CeH), 2922, 2862 (Aliphatic CeH),
436 (P-Ph), 1020 (OeP). Anal. calcd. for C52 (790.884 g/
2
2
. Experimental
1
2.1. Materials and methods
(
3
d
All reactions were performed under an inert atmosphere using
2
2
13
1
2 3
of Cy). C NMR (CDCl , ppm): d
conventional Schlenk glassware. All chemicals were purchased
commercially (Sigma-Aldrich, Merck, Fluka and Alfa Aesar) and
used as received. All solvents were dried and distilled under inert
atmosphere immediately prior to use according to the established
procedures. 1-({[(1R,2R)-2-{[(2-hydroxynaphthalen-1-yl)methyl-
idene] amino}cyclohexyl]imino}methyl)naphthalene-2-ol was
prepared according to the literature [31]. NMR spectra were
2
2
2
1
1
2
2
2
3
1
1
P-{ H} NMR (CDCl
3
, ppm):
d
2
ꢁ1
1
recorded on a Bruker AV400 spectrometer ( H NMR at 400.1 MHz,
13
31
1
1
44 2 2 2
H N O P
C NMR at 100.6 MHz, P-{ H} NMR at 162.0 MHz). A PerkinElmer
mol): C, 78.97; H, 5.61; N, 3.54, found: C, 78.71; H, 5.52; N, 3.38%.
Spectrum 100 spectrometer was used for FTIR-ATR spectra. A Per-
kinElmer 341 model polarimeter was used for specific rotations.
Elemental analysis was carried out on a Costech ECS 4010 instru-
ment. Melting points were recorded by a Gallenkamp Model
apparatus with open capillaries.
2
0
ꢂ
[a
]
D
¼ þ7.0 (c ¼ 1.0, CHCl
3
).
2
.1.2.1.2. 1-({[(1R,2R)-2-{[(2-{[bis(propan-2-yl)phosphanyl]oxy}
naphthalen-1-yl)methylidene]
amino}cyclohexyl]imino}methyl)
(2). Yield: 85 mg,
3
87%). H NMR (CDCl , ppm): d 9.02 (s, 2H, eN]CH), 6.95e7.82 (m,
naphthalen-2-ylbis(propan-2-yl)phosphinite
(
1
1
2H, protons of naphthyl), 3.76 (s, 2H, CH of Cy), 1.85e1.87 (m, 2H,
i
i
-
CH(CH
3
)
2
of OP Pr), 0.90e1.42 (m, 32H, CH(CH
3
)
2
of OP Pr þ -CH
2
1
3
2.1.1. GC analyses
3
of Cys). C NMR (CDCl , ppm): d 172.31, 136.79, 133.18, 129.00,
Shimadzu GC 2010 Plus Gas Chromatograph equipped with a
127.78, 126.60, 122.80, 122.74, 118.39, 107.17 (carbons of naphthyl),
159.22 (-N]CH), 67.98 (-CH of Cy), 32.71 (-CH of Cy), 29.71
of Cy), 17.53, 17.35, (-CH(CH ) of
, ppm): 150.62 (s, OPCH(CH ). IR
(KBr pellet in cm ): ʋ 2963, 2870 (Aliphatic CeH), 1454 (P- Pr),
1039 (OeP). Anal. calcd. for C40 (654.816 g/mol): C,
cyclodex-B (Agilent) capillary column (30 m ꢀ 0.32 mm I.D. x
.25 m film thickness) was used for performed of GC analyses.
Racemic samples of alcohols were obtained by reduction of the
corresponding ketones with NaBH and used as the authentic
2
i
0
m
(-CH(CH
3
)
2
of OP Pr), 24.70 (-CH
2
3 2
)
i
31
1
OP Pr). P-{ H} NMR (CDCl
3
d
3 2
)
ꢁ1
i
4
samples for % ee determination. The GC parameters used for the
product analysis in our one of previous studies were applied to
product analysis done for the current study [32].
52 2 2 2
H N O P
73.37; H, 8.01; N, 4.28, found: C, 73.17; H, 7.90; N, 4.08%,
2
0
ꢂ
[a
]
D
¼ ꢁ4.2 (c ¼ 2, CHCl
3
).
2
Scheme 1. Synthesis of C -symmetric bis(phosphinite) ligands (1e3).

N.A. Saleh et al. / Journal of Molecular Structure 1200 (2020) 127146
3
2.1.2.1.3. 1-({[(1R,2R)-2-[({2-[(dicyclohexylphosphanyl)oxy]naph-
(-N]CH), 67.98 (-CH of Cy), 32.71 (-CH
2
of Cy), 24.95 (CH
2
of Cy),
thalen-1-yl}methylidene)amino]
cyclohexyl]imino}methyl)naph-
37.02, 26.23, 26.40, 26.52, 26.75, 26.97, 29.71 (carbons of OPCy
2
).
). IR (KBr pellet in
cm ): ʋ 2963, 2870 (Aliphatic CeH), 1454 (P-Cy), 1039 (OeP). Anal.
1
31
1
thalen-2-yl dicyclohexylphosphinite (3). Yield: 110 mg, (90%).
NMR (CDCl , ppm): 9.19 (s, 2H, eN]CH), 7.05e7.82 (m, 12H,
protons of naphthyl), 3.75e3.78 (m, 2H, -CH of Cy), 1.87e1.97 (m,
H, CH of Cy), 1.22e1.78 (m, 48H, protons of OPCy of Cy).
þ -CH
C NMR (CDCl , ppm): 172.22, 136.42, 133.39, 128.84, 127.78,
26.53, 123.36, 122.82, 118.62, 107.16 (carbons of naphthyl), 157.89
H
3 2
P-{ H} NMR (CDCl , ppm): d 146.75 (s, OP(Cy)
ꢁ1
3
d
calcd. for C52
found: C, 76.47; H, 8.29; N, 3.32%, [
H
68
N
2
O
2
P
2
(815.076 g/mol): C, 76.63; H, 8.41; N, 3.44,
2
0
ꢂ
4
2
2
2
a
]
D
¼ þ2.0 (c ¼ 0.65, CHCl
3
).
1
3
3
d
1
Fig. 1. 31P-{ H} NMR spectra of C
1
2
-symmetric bis(phosphinite) ligands (1e3).

4
N.A. Saleh et al. / Journal of Molecular Structure 1200 (2020) 127146
2
.1.2.2. General procedure for synthesis of the C
2
-symmetric
h
6-p-
(OeP). Anal. Calc. for [C60
56.87, H 6.36, N 2.21; found: C 56.72, H 6.22, N 2.09%, [
(c ¼ 1, CHCl ).
2.1.2.2.3. 1-({[(1R,2R)-2-[({2-[(dicyclohexylphosphanyl)oxy]
naphthalen-1-yl}methylidene)amino] cyclohexyl]imino}methyl)
naphthalen-2-yldicyclohexylphosphinite(bis(dichloro-ɳ -p-cymener-
80 2 2 2 2 4
H N O P Ru Cl ] (1267.206 g/mol): C
20
ꢂ
cymene-Ru(II)-phosphinite complexes, 4-6. The binuclear half
sandwich Ru(II) complexes 4e6 were synthesized by reacting
equimolar amounts of the phosphinite ligands, 1e3 and {[Ru(ղ -p-
cymene)(m-CI)Cl] in 30 mL of CH Cl under argon atmosphere.
2 2 2
General procedure for the synthesis of Ru(II) complexes 4e6 can be
a
]
D
¼ ꢁ10.3
3
6
6
ꢂ
1
found in our recent publications [1,32,34].
uthenium(II)) (6). Yield: 190 mg (89%), m.p: 120e122 C. H NMR
(CDCl , ppm): 9.16 (s, 2H, eN]CH), 7.10e7.81 (m, 12H, protons of
naphthyl), 5.29e5.55 (m, 8H, aromatic protons of p-cymene),
3.80e3.85 (m, 2H, CH of Cy), 2.10e2.30 (m, 2H, -CH(CH of p-
cymene), 1.96e2.06 (m, 4H, -CH of Cy), 1.82 (s, 6H, -CH3, of p-
cymene), 1.24e1.80 (m, 48H, protons of OPCy of Cy)
þ -CH
of p-cymene). C NMR (CDCl
172.10, 136.62, 133.40, 128.28, 127.80, 126.55, 123.30,
2
.1.2.2.1. 1-({[(1R,2R)-2-[({2-[(diphenylphosphanyl)oxy]naph-
thalen-1-yl}methylidene)amino] cyclohexyl]imino}methyl)naph-
thalen-2-yldiphenylphosphinite(bis(dichloro-ɳ -p-cymener-
3
d
6
3 2
)
ꢂ
1
uthenium(II))(4). Yield: 180 mg (86%), m.p: 120e122 C. H NMR
CDCl , ppm): 9.16 (br, 2H, eN]CH), 7.27e8.03 (m, 32H, protons
of naphthyl þ OPPh ), 5.06e5.41 (m, 8H, aromatic protons of p-
cymene), 3.10 (br, 2H, -CH of Cy), 2.47 (m, 2H, -CH(CH of p-
cymene), 1.81 (br, 4H, -CH of Cy), 1.66 (s, 6H, -CH of p-cymene),
.32 (br, 4H, -CH of Cy), 0.85e0.87 (m, 12H, eCH(CH
CDCl , ppm): 171.11, 136.94, 133.78, 128.65, 128.27, 128.17, 124.36,
22.72, 121.37, 110.41 (carbons of naphthyl), 158.87 (-N]CH), (not
observed ipso carbon of OPPh ), 135.17, 132.07, 129.81 (ortho, para,
meta carbons of OPPh ), 111.62, 96.72 (ipso carbons of p-cymene),
7.47, 87.54, 92.02, 92.07 (aromatic carbons of p-cymene), 66.95
CH of Cy), 30.16 (-CH(CH of p-cymene), 29.82 (-CH of Cy), 24.24
-CH of Cy), 21.31 (-CH(CH of p-cymene), 17.36 (-CH of p-
, ppm): 118.18 (s, OPPh ). IR (KBr
pellet in cm ): ʋ 3054, 3015 (Aromatic CeH), 2907, 2855 (Aliphatic
CeH),1426 (P-Ph),1008 (OeP). Anal. Calc. for [C72 Ru Cl
2
(
3
d
2
2
1
3
2
0.80e0.92 (m, 12H, eCH(CH
ppm):
3
)
2
3
,
3
)
2
d
2
3
122.80, 118.50, 107.20 (carbons of naphthyl), 158.03 (-N]CH),
110.98, 97.51 (ipso carbons of p-cymene), 88.70, 87.98, 87.74, 86.48
(aromatic carbons of p-cymene), 68.00 (CH of Cy)), 30.35
1
3
1
(
1
2
3 2
) ). C NMR
3
d
(-CH(CH
26.21 (-CH
ene), 17.44 (-CH
155.42 (s, OP(Cy)
matic CeH), 2960, 2823 (Aliphatic CeH): 1436 (P-Cy), 1024 (OeP).
3
)
2
of p-cymene), 37.10, 29.73, 26.96, 26.70, 26.55, 26.35,
of Cys þ -CH of OPCy ), 22.15 (-CH(CH of p-cym-
of p-cymene). P-{ H} NMR (CDCl , ppm):
). IR (KBr pellet in cm ): ʋ 3073, 3053 (Aro-
2
2
2
2
3 2
)
3
1
1
2
3
3
ꢁ1
8
(
(
d
2
3
)
2
2
2
3
)
2
3
Anal. Calc. for [C72
6.78, N 1.96; found: C 60.35, H 6.49, N 1.53%, [
CHCl ).
H
96
N
2
O
2
P
2
Ru
2
Cl
4
] (1427.466 g/mol): C 60.58, H
3
1
1
20
ꢂ
cymene). P-{ H} NMR (CDCl
3
d
2
a]
D
¼ þ9.0 (c ¼ 0.65,
ꢁ
1
3
72
H N
2
O
2
P
2
2
4
]
(
1
1403.274 g/mol): C 61.63, H 5.17, N 2.00; found: C 61.49, H 4.98, N
2
.1.3. General procedure for the asymmetric transfer hydrogenation
of ketones
The details of the procedure used for the catalytic asymmetric
20
ꢂ
.92%, [
a
]
D
¼ þ8.3 (c ¼ 1, CHCl
3
).
2
.1.2.2.2. 1-({[(1R,2R)-2-{[(2-{[bis(propan-2-yl)phosphanyl]oxy}
naphthalen-1-yl)methylidene]
naphthalen-2-ylbis(propan-2-yl)phosphinite (bis(dichloro-ɳ -p-cym-
amino}cyclohexyl]imino}methyl)
transfer hydrogenation of ketones and the methods for product
analysis can be found in our recent publications [34,35].
6
ꢂ
1
eneruthenium(II)) (5). Yield: 170 mg (90%), m.p: 120e122 C.
NMR (CDCl , ppm): 9.28 (s, 2H, eN]CH), 7.28e7.78 (m, 12H,
protons of naphthyl), 5.31e5.54 (m, 8H, aromatic protons of p-
cymene), 3.82 (s, 2H, -CH of Cy), 2.06e2.30 (m, 2H, -CH(CH of p-
of OP Pr), 1.72 (s, 6H, -CH3, of
H
3
d
3
. Results and discussion
3 2
)
i
3.1. Synthesis and characterization of the bis(phosphinite) ligands
(1e3) and their binuclear half sandwich h -p-cymene-Ru(II)
complexes
cymene), 1.84e1.98 (m, 2H, -CH(CH
p-cymene), 1.11e1.45 (m, 32H, eCH(CH
.85e0.89 (m, 12H, eCH(CH of p-cymene). C NMR (CDCl
ppm): 173.30,137.20, 133.61,129.50,127.81, 126.73,124.54,122.60,
18.66, 111.63 (carbons of naphthyl), 160.13 (-N]CH), 111.31, 99.51
ipso carbons of p-cymene), 88.79, 88.74, 86.50, 85.64 (aromatic
carbons of p-cymene), 68.05 (-CH of Cy), 32.07 (-CH of Cy), 30.44
3 2
)
6
i
3
)
2
of OP Pr þ -CH
2
of Cy),
1
3
0
3
)
2
3
,
d
In
the
present
work,
firstly,
1-({[(1R,2R)-2-{[(2-
1
(
hydroxynaphthalen-1-yl)methylidene] amino}cyclohexyl]imino}
methyl)naphthalen-2-ol was synthesized as precursors for phos-
phinites. Then, new chiral C
were prepared from the reaction of above mentioned correspond-
ing alcohol with two equivalents of Ph PCl, (i-Pr) PCl or (Cy) PCl
(Scheme 1). P-{ H} NMR spectroscopy was used to follow the
progress of these reactions. Resonances of the starting materials
disappeared and new singlets obtained in downfield corresponding
2
i
2
-symmetric bis(phosphinite) ligands
(
-CH(CH
3
)
2
of p-cymene), 29.79 (-CH(CH
3
)
2
of OP Pr), 24.74 (-CH
2
of
of
Cy), 22.11 (-CH(CH
OP Pr), 17.42 (-CH3, of p-cymene). P-{ H} NMR (CDCl
d
3
)
2
of p-cymene), 18.20, 18.51 (-CH(CH )
3 2
i
31
1
2
2
2
3
, ppm):
31
1
ꢁ
1
160.84 (s, OPCH(CH
Aromatic CeH), 2907, 2855 (Aliphatic CeH), 1426 (P- Pr), 1008
3 2
) ). IR (KBr pellet in cm ): ʋ 3054, 3015
i
(
Scheme 2. Synthesis of C
2
-symmetric half sandwich h6-p-cymene-Ru(II) complexes (4e6) from the bis(phosphinite) ligands (1e3).

N.A. Saleh et al. / Journal of Molecular Structure 1200 (2020) 127146
5
Fig. 2. 31P-{ H} NMR spectra of C -symmetric half sandwich h6-p-cymene-Ru(II) complexes (4e6).
1
2

6
N.A. Saleh et al. / Journal of Molecular Structure 1200 (2020) 127146
to the phosphinites at
d
114.09, 150.62, 146.24 ppm for compounds
systems or media several times but we failed.
1
, 2 and 3 (Fig. 1), respectively, in accord with the values previously
1
observed for similar compounds [36e38]. Additionally, H NMR,
3.2. Transfer hydrogenation studies
13
1
C-{ H} NMR, IR spectra and C, H, N elemental analyses were in
agreement with the proposed structures for the new phosphinite
ligands.
Ruthenium complexes 4e6 were applied to asymmetric transfer
hydrogenation of aromatic ketones using 2-propanol as a source of
hydrogen in the presence of base. The asymmetric transfer hydro-
genation reaction conditions were optimized using acetophenone
as a model substrate (Table 1). As expected, complexes catalyzed
the reduction of acetophenone to 1-phenylethanol in high con-
versions, preferring the (R) enantiomer. In a typical experiment,
The binuclear half sandwich Ru(II) complexes were synthesized
by reacting equimolar amounts of the phosphinite ligands, 1e3 and
6
{
[Ru(ղ -p-cymene)(
m
-CI)Cl]
2
under argon atmosphere (Scheme 2).
They were obtained as orange-red crystalline solids in good yields.
31
Singlet resonances were observed in the P-{H} NMR spectra at
118.18, 160.84 and 155.42 ppm for 4e6 (Fig. 2.), respectively. The
observed downfield shifts compared to free ligands were attributed
d
0
.005 mmol of the Ru(II) complex and 0.5 mmol of acetophenone
were added to a solution of KOH in 2-propanol (0.025 mmol of KOH
1
13
1
to formation of the complexes [36e38]. The H, C-{ H} NMR, IR
spectroscopic data and the elemental analysis data of the com-
plexes were in agreement with the expected compounds. We tried
to obtain single crystal suitable for X-ray in different solvent
ꢂ
in 5 mL 2-propanol), refluxed at 82 C and the progress of the re-
action was monitored by gas chromatography at regular intervals.
The catalytic activity of the catalyst was investigated in four tem-
ꢂ
perature protocols (25, 40, 60 and 82 C). At room temperature,
Table 1
Transfer hydrogenation of acetophenone with 2-propanol catalyzed by C
2
-symmetric half sandwich h6-p-cymene-Ru(II) complexes (4, 5 and 6).
Conv.(%)f
ee (%)b
Config.
TOF (h )g
ꢁ1
Entry
Cat.
Subs./Cat/KOH
Time(h)
1
2
3
4
5
6
7
8
9
4a
100:1:5
100:1:5
100:1:5
100:1
100:1
100:1
1
4
3
24
24
24
72
72
72
2
6
5
20
24
24
1
1
1
1
1
98
97
99
trace
trace
trace
<10
<10
<10
96
98
95
97
98
96
95
91
98
44
22
24
e
R
R
R
-
-
-
98
25
34
e
a
5
6
4
5
6
4
5
6
4
5
6
4
5
6
4
4
a
b
b
e
e
b
e
e
c
100:1:5
100:1:5
100:1:5
100:1:5
100:1:5
100:1:5
500:1:5
500:1:5
500:1:5
100:1:5
100:1:5
100:1:5
100:1:5
100:1:5
100:1:5
100:1:5
100:1:5
60
34
37
40
25
28
38
17
19
42
41
37
38
35
34
31
23
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
e
c
e
c
e
d
10
11
12
13
14
15
16
17
18
19
20
21
22
23
48
16
19
<10
<10
<10
95
91
98
96
97
20
31
<10
d
d
e
e
e
h
i
j
4
4
4
4
k
96
97
95
93
l
m
5
3
1
n
4
o
4
6
Reaction conditions.
a
Refluxing in iso-PrOH; acetophenone/Ru/KOH, 100:1:5.
b
c
Refluxing in iso-PrOH; acetophenone/Ru, 100:1, in the absence of base.
At room temperature; acetophenone/Ru/KOH, 100:1:5.
Refluxing the reaction in air.
Refluxing in iso-PrOH; acetophenone/Ru/KOH, 500:1:5.
Determined by GC (three independent catalytic experiments).
d
e
f
g
h
i
ꢁ1
Referred at the reaction time indicated in column; TOF¼ (mol product/mol Ru(II)Cat.)x h
.
Refluxing in iso-PrOH; acetophenone/Ru/NaOH, 100:1:5.
t
Refluxing in iso-PrOH; acetophenone/Ru/ BuOK, 100:1:5.
j
Refluxing in iso-PrOH; acetophenone/Ru/KOiPr, 100:1:5.
k
l
t
Refluxing in iso-PrOH; acetophenone/Ru/ BuONa, 100:1:5.
Refluxing in iso-PrOH; acetophenone/Ru/NaOiPr, 100:1:5.
m
n
o
ꢂ
ꢂ
At 40 C; acetophenone/Ru/KOH.
At 60 C; acetophenone/Ru/KOH.
Refluxing in ethanol; acetophenone/Ru/KOH, 100:1:5.

N.A. Saleh et al. / Journal of Molecular Structure 1200 (2020) 127146
7
transfer hydrogenation of acetophenone occurred considerably
was observed (Table 1, entries 4e6). The optimized molar ratio of
sluggishly and its conversion was too low (<10% after 72 h, Table 1,
the acetophenone/Cat/KOH was found to be 100:1:5. Asymmetric
transfer hydrogenation of acetophenone at 82 C catalyzed by
ꢂ
ꢂ
entries 7e9) with all catalysts. A survey of the reactions at 40 C and
ꢂ
6
0 C (Table 1, entries 21e22) reveals that overall reduction is faster
complex 4 in the presence of ethanol as sole solvent gave (R)-1-
phenylethanol in 23% ee and 6% conversion after 1 h (Table 1, en-
try 23). From Table 1, it can be seen that all complexes catalyze
almost quantitatively (%97 to 99) the transfer hydrogenation of
acetophenone within a period of 4 h. Furthermore, complex 4
showed higher enantioselectivity than those of the ruthenium
complexes 5 and 6. As Morris et al. showed catalytic activity
than that at rt while ee values were lower than those obtained at rt.
ꢂ
However, when the temperature was increased to 82 C, the con-
version of acetophenone to 1-phenylethanol became satisfactory.
During the reaction, the colour of the reaction solution altered from
orange to deep red. When the base was added, the reaction began
instantly without any induction time. A blank experiment was
performed to demonstrate that the presence of a base is necessary
for conversion in transfer hydrogenation (Table 1, entries 4e6). The
optimization of acetophenone/Cat/KOH molar ratio and reaction
temperature were essential to achieve high enantioselectivity or
conversion. So, in a series of experiments, the optimal conditions
were investigated, such as molar ratios of both substrate to catalyst
and base to catalyst (Table 1). The optimization studies exhibited
that good catalytic activity was gained with a base/cat. ratio of 5:1.
Table 1, entries 1 and 16e20 shows the effect of different bases on
the asymmetric transfer hydrogenation reactions. Various bases
such as KOH, NaOH, tBuOK, KOiPr, tBuONa, NaOiPr were employed
under the same conditions. Among the bases used, KOH showed
the highest activity with 98% conversion and 44% ee. (Table 1, entry
(conversion) is concerned with cone angle (
q
) of the PR
2
group.
ꢂ
PPh
2
moiety with
q: 141 angle exhibits the highest catalytic ac-
tivity [20]. Therefore, in this study, the catalytic activity in terms of
conversion in the reduction of acetophenone catalyzed by complex
4 (PR
2
; R:Ph) was higher than those of complexes 5 (PR
2
; R: i-Pr)
and 6 (PR
2
; R: Cy).
Encouraged by the good enantioselectivities attained in these
initial studies, we next extended our researches to involve asym-
metric hydrogenation of substituted acetophenone derivatives. The
findings summarized in Table 2 demonstrate that a variety of ace-
tophenone derivatives can be hydrogenated with moderate to good
enantioselectivities. Thus, the reaction of several aromatic ketones
with different electronic and steric variations on the substrate
backbone was investigated and found that the position and
1
). It should be noted that without base no significant conversion
Table 2
Asymmetric transfer hydrogenation results for substituted acetophenones catalyzed by C
2
-symmetric half sandwich h6-p-cymene-Ru(II) complexes (4, 5 and 6).3
Conv.(%)b
ee(%)c
TOF (h )[d]
ꢁ1
Conf.[e]
Entry
Cat.
R
Time
1
2
3
4
5
6
7
8
9
4
5
6
4
5
6
4
5
6
4
5
6
4
5
6
4
5
6
4
5
6
4
5
6
2-F
30 min
2 h
3 h
30 min
2 h
3 h
30 min
2 h
3 h
45 min
2 h
3 h
45 min
2 h
3 h
3 h
5 h
5 h
3 h
3 h
3 h
99
99
98
97
98
96
97
97
96
98
98
96
97
96
94
98
99
90
98
92
92
96
96
90
45
21
22
54
23
24
49
24
23
48
19
25
42
21
20
59
22
21
60
32
28
57
29
25
198
50
33
194
49
32
194
49
32
130
46
32
129
48
31
33
20
18
33
31
31
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
R
4-F
4-Cl
2-Br
4-Br
4-NO
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
2
2-MeO
4-MeO
2 h
3 h
3 h
48
32
30
Reaction conditions.
ꢂ
a Catalyst (0.005 mmol), substrate (0.5 mmol), iso-PrOH (5 mL), KOH (0.025 mmol %), 82 C, respectively, the concentration of acetophenone derivatives is 0.1 M.
b
Purity of compounds is checked by NMR and GC (three independent catalytic experiments), yields are based on methyl aryl ketone.
c
TOF ¼ (mol product/mol Cat.) x hꢁ1
.

8
N.A. Saleh et al. / Journal of Molecular Structure 1200 (2020) 127146
electronic property of the substituents present in the substrates
influenced hydrogenation results. As expected, we observed that
the introduction of electron withdrawing substituents, such as F, Cl
and Br to the o- or p-position of the aryl ring of the ketone increased
the electron deficiency in the carbonyl group so that the activity
was enhanced leading to easier hydrogenation. An electron-
withdrawing group such as fluoro or nitro group to the p-position
of the aryl ring of the ketone was useful to achieve excellent con-
version and moderate enantioselectivity (up to 54% ee, Table 2). On
the other hand, the introducing electron donating substituent such
as methoxy to the o- or p-position make the ketone substrate more
electron rich and thus, it needs longer time to obtain higher con-
version. However, methoxy substituent at o-position of the phenyl
ring increases the rate and improves the enantioselectivity
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