Structural, kinetics and mechanistic studies of transfer hydrogenation of ketones catalyzed by chiral (pyridyl)imine nickel(ii) complexes

Article abstract of DOI:10.1039/c9dt00024k

The chiral synthons (S-)-1-phenyl-N-(pyridine-2-yl)ethylidine)ethanamine (L1), (R-)-1phenyl-N-(pyridine-2-yl)ethylidine))ethanamine (L2) (S)-1-phenyl-N-(pyridine-2-yl methylene) ethanamine (L3), and (R)-1-phenyl-N-(pyridine-2-yl methylene) ethanamine (L4) were synthesized in good yields. Treatments of L1-L4 with NiBr₂(DME) and NiCl₂ precursor afforded dinuclear complexes [Ni₂(L1)₄-μ-Br₂]NiBr₄ (Ni1), [Ni₂(L2)₄-μ-Br₂]NiBr₄ (Ni2), [Ni₂(L3)₄-μBr₂]Br₂ (Ni3), [Ni₂(L4)₄-μ-Br₂]NiBr₄ (Ni4) and [Ni(L4)₂Cl₂] (Ni5). The identities of the compounds were established using NMR, FT-IR and EPR spectroscopy, mass spectrometry, magnetic moments, elemental analysis and single crystal X-ray crystallography. The dinuclear dibromide nickel complexes dissociate into mononuclear species in the presence of strongly coordinating solvents. Compounds Ni1-Ni5 displayed moderate catalytic activities in the asymmetric transfer hydrogenation (ATH) of ketones, but with low enantiomeric excess (ee%). Both mercury and substoichiometric poisoning tests pointed to the homogeneous nature of the active species with the partial formation of catalytically active Ni(0) nanoparticles. Low resolution mass spectrometry analyses of the intermediates supported a dihydride mechanistic pathway for the transfer of hydrogenation reactions.

Full text of DOI:10.1039/c9dt00024k

View Article Online
View Journal
Dalton
Transactions
An international journal of inorganic chemistry
Accepted Manuscript
This article can be cited before page numbers have been issued, to do this please use: R. T. Kumah, N.
Tsaulwayo, B. Xulu and S. O. Ojwach, Dalton Trans., 2019, DOI: 10.1039/C9DT00024K.
Volume 46
Number 10
14 March 2017
Pages 3073-3412
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Dalton
Transactions
An international journal of inorganic chemistry
Accepted Manuscripts are published online shortly after acceptance,
before technical editing, formatting and proof reading. Using this free
rsc.li/dalton
service, authors can make their results available to the community, in
citable form, before we publish the edited article. We will replace this
Accepted Manuscript with the edited and formatted Advance Article as
soon as it is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes to the
text and/or graphics, which may alter content. The journal’s standard
Terms & Conditions and the Ethical guidelines still apply. In no event
ISSN 0306-0012
COMMUNICATION
Douglas W. Stephen et al.
shall the Royal Society of Chemistry be held responsible for any errors
N-Heterocyclic carbene stabilized parent sulfenyl, selenenyl,
and tellurenyl cations (XH+, X = S, Se, Te)
or omissions in this Accepted Manuscript or any consequences arising
from the use of any information it contains.
rsc.li/dalton

Page 1 of 32
Dalton Transactions
Dalton Transactions
View Article Online
Structural, kinetics and mechanistic studies of transfer hydrogenation ofDkOeI:t1o0n.10e3s9/C9DT00024K
catalyzed by chiral (pyridyl)imine nickel(II) complexes
Robert T. Kumah, Nokwanda Tsaulwayo, Bheki A. Xulu, Stephen O. Ojwach*
School of Chemistry and physics, University of KwaZulu-Natal, Pietermaritzburg Campus,
Private Bag X01 Scottsville, 3209, South Africa
ABSTRACT
The chiral synthons (S-)-1-phenyl-N-(pyridine-2-yl)ethylidine) ethanamine (L1), (R-)-
1phenyl-N-(pyridine-2-yl)ethylidine) ethanamine (L2) (S)-1-phenyl-N-(pyridine-2-yl
methylene) ethanamine (L3), and (R)-1-phenyl-N-(pyridine-2-yl methylene) ethanamine (L4)
were synthesized in good yields. Treatments of L1-L4 with NiBr2(DME) and NiCl2 precursor
afforded dinuclear complexes [Ni2(L1)4-μ-Br2]NiBr4 (Ni1), [Ni2(L2)4-μ-Br2]NiBr4 (Ni2),
[Ni2(L3)4-μBr2]Br2 (Ni3), [Ni2(L4)4-μ-Br2]NiBr4 (Ni4) and [Ni(L4)2Cl2] (Ni5). The identities
of the compounds were established using NMR, FT-IR and EPR spectroscopies, mass
spectrometry, magnetic moments, elemental analysis and single crystal X-ray crystallography.
The dinuclear dibromide nickel complexes dissociate into mononuclear species in the presence
of strongly coordinating solvents. Compounds Ni1-Ni5 displayed moderate catalytic activities
in the asymmetric transfer hydrogenation (ATH) of ketones, but with low enantiomeric excess
(ee%). Both mercury and substoichiometric poisoning tests pointed to homogeneous nature of
the active with partial formation of catalytically active Ni(0) nanoparticles. Low resolution
mass spectrometry analyses of the intermediates supported a dihydride mechanistic pathway
for the transfer hydrogenation reactions.
*Corresponding author: E-mail: ojwach@ukzn.ac.za (S. O. Ojwach)
1 | P a g e

Dalton Transactions
Page 2 of 32
Dalton Transactions
View Article Online
DOI: 10.1039/C9DT00024K
1. Introduction
Asymmetric catalysis is one of the emerging disciplines in the chemical industry due to
the versatility and importance of chiral intermediates in the production of a wide range of fine
chemicals such as pharmaceuticals, perfumes, pesticides among others.1-2 A classic example is
the asymmetric transfer of hydrogenation (ATH) of ketones to produce chiral alcohols, which
form useful intermediates for the syntheses of a number of domestically and industrial relevant
products.1, 3-5 To date, a number of transition metal catalysts derived from chiral ruthenium(II),
rhodium(III), iridium(II), and osmium(II) metal complexes have been found to show high
catalytic activities and enantioselectivities in asymmetric transfer hydrogenation of ketones.6-
12 Despite the efficiency of these catalytic systems in these reactions, their industrial application
have been limited by their high costs and instability under normal conditions.13-14
This has led to the design and development of alternative catalysts which are less
expensive but can parallel the catalytic activities of the well-established ruthenium(II) and
iridium(II) analogues. On this trajectory, nickel(II) complexes have emerged as good
candidates due to their relative cheaper costs and stability.15-16 It is thus not surprising that in
recent years, a number of nickel(II) catalysts containing nitrogen-donor ligands have been
reported as catalysts8 in the asymmetric transfer hydrogenation of ketones 17-18 The results
have not been disappointing as high catalytic activities with excellent enantioselectivities have
been reported in some cases. A notable example is the work of Gao and co-workers, which
demonstrated that Ni(PPh3)2Cl2 in combination with P^N^O-type ligands could catalyse ATH
of simple ketones achieving 10-84 ee%.19 We recently investigated the application of some
(pyrazolylmethyl)pyridine nickel(II) complexes as catalysts in the transfer hydrogenation of
ketones with some promising results.20-21 Herein, we report the syntheses of chiral
2 | P a g e

Page 3 of 32
Dalton Transactions
Dalton Transactions
View Article Online
DOI: 10.1039/C9DT00024K
(pyridyl)imine complexes and their application as ATH catalysts for a range of selected
aromatic ketones. Structural elucidation of the complexes has been extensively performed
using a combination of techniques such as mass spectrometry, electron paramagnetic
resonance, single crystal X-ray crystallography and elemental analyses. Detailed studies on
the true identity of the active species using substoichiometric and mercury poisoning tests and
investigation of the mechanistic pathways of ATH reactions have also been carried out and
are herein discussed.
2. Results and discussion
2.1.
Synthesis and characterization Ni(II) complexes Ni1-Ni5
The reactions of synthons L1-L4 with NiBr2(DME) and NiCl2 in CH2Cl2 afforded the
corresponding complexes Ni1-Ni5 as green solids (Scheme 1) in moderate yields (50-70%).
All the complexes were characterized by IR spectroscopy, mass spectrometry, magnetic
moment measurements, elemental analyses and single crystal X-ray analyses in some cases.
Comparison of FT-IR signal shifts of the ligands in L1-L4 to their corresponding Ni(II)
complexes Ni1-Ni5 allowed us to establish the successful formation of the complexes. For
instance, (ѵC=N imine
signals were observed at 1618 cm-1 for L3 and 1637cm-1 for the
)
corresponding complex Ni3 respectively (Figs. S18 and S21). The ESI-MS spectral data
were also used to establish the identity of the complexes Ni1- Ni5 (Figs. S11-S15). In general,
ESI MS (low resolution) data of complexes Ni1-Ni4 showed m/z signals corresponding to the
cationic mononuclear units, containing two ligand units. The absence of molecular mass peaks
corresponding to the dinuclear complexes hint to their instability, hence ease of dissociation
to form the mononuclear compounds (vide infra). For instance, the positive and negative
mode mass spectrum of complex Ni4 showed signals at m/z = 559 amu and m/z = 373 amu,
corresponding to the fragment (M+-Br-) of the mononuclear species and the counter ion
3 | P a g e

Dalton Transactions
Page 4 of 32
Dalton Transactions
View Article Online
DOI: 10.1039/C9DT00024K
[NiBr4]2- respectively (Fig. S21). In all cases, the experimental and simulated isotopic mass
distributions showed correlations (Figs. S18-S22).
X
Br
R
N
N
*
*
R
[NiBr2(DME)]
CH2Cl2
N
Ni
N
N
N
Ni
R
*
*
R
N
N
Br
R
R = CH3, X = [NiBr4]2-, (S-) (Ni1); R = CH3, X = [NiBr4]2- (R-) (Ni2);
R = H, X = [2Br-], ( ) (Ni3); R = H, X = [NiBr ]2-, ( ) (Ni4)
S-
R-
N*
N
4
L1: R = H (S)
L2: R = H (R)
L3: R = Me (S)
L4: R =Me (R)
H
NiCl2
CH
N*
N
2Cl2
Cl
Ni
Cl
*
N
N
H
(S-);Ni5
Scheme 1. Synthesis of chiral (pyridyl)imine Ni(II) complexes Ni1-Ni5.
The effective magnetic moments of complexes Ni1-Ni5 were recorded in the range 3.52
BM - 3.97 BM and were generally higher than the expected spin-only magnetic moment of 2.83
BM for a nickel(II) ion.22 This large variation could be attributed to the spin-orbital magnetic
moment contribution from the (pyridyl)imine and halide ligands.23 However, all the values
were comparable, signifying similar ligand-field splitting of L1-L4. Elemental analyses data of
complexes Ni1-Ni5 were in good agreement with two ligand units per metal atom and
established the purity of the bulk materials.
2.2. Molecular structure of compound Ni3 and Ni 4.
4 | P a g e

Page 5 of 32
Dalton Transactions
Dalton Transactions
View Article Online
Single crystals suitable for X-ray crystallography analyses of complexes Ni3a (a monomeric
DOI: 10.1039/C9DT00024K
form of Ni3) and Ni4 were grown by slow evaporation of the CH2Cl2/hexanesolutions at room
temperature, while crystals of compound Ni5 were obtained by slow diffusion of diethyl ether
into a solution of Ni5 in acetonitrile. Table 1 shows the data collection and structural
refinement parameters for complexes Ni3a, Ni4 and Ni5, while Figs. 1-3 show the respective
molecular structures and bond parameters. The solid state of complex Ni4 is dinuclear
containing two bidentate ligand units on each nickel atom, two bridging bromide ligands and
a [NiBr4]2- counter anion, in good agreement with the mass spectral and elemental analyses
data (Scheme 2). On the other hand, the molecular structure of Ni3a (derivative of Ni3), is
cationic, containing two ligand L3 units per nickel atom (Fig. 1) and two coordinated water
molecules. It is therefore evident that in the presence of strongly coordinating solvents such
as H2O, the dinuclear Ni3 complex dissociates via nucleophilic substitution of the bridging
bromides to form the mononuclear species (Ni3a) as shown in Scheme 3. The transformation
is not unique and has been reported by Schlemper24 and may be useful in generation of the
activation species (creation of vacant coordination sites). Interestingly, the mononuclear
dichloride complex Ni5, is neutral and contains two ligand (L3) units and two chloride ligands
in the coordination sphere. The monomeric nature of Ni5 thus indicate, unfavourable bridging
by the chloride ligand, while the lack of substitution of the chlorides by the water molecules
can be attributed to the poor nucleophilic displacement of the chloride ligands in comparison
to the bromide ligand.25
5 | P a g e

Dalton Transactions
Page 6 of 32
Dalton Transactions
View Article Online
DOI: 10.1039/C9DT00024K
-
2Br
N
NiBr4
N
N
N
N
N
Br
Br
+ 2H2O
2
- H2O
N
N
N
Ni
H2O
Ni
OH2
+
NiBr2
Ni
N
N
N
Ni3a
Ni3
Scheme 3. Transformation of the dinuclear complex Ni3 to the mononuclear species Ni3a in
the presence of H2O molecules via nucleophilic attack.
The average Ni-O, Ni-Br and Ni-Cl bond lengths of 2.068 Å, 2.595 Å and 2.417 Å for
Ni3a, Ni4 and Ni5 are within the bond distances of 2.07±0.12 Å, 2.58 ± 0.08 Å and 2.42 ±0.06
Å respectively reported in 98-172 structures when subjected to online check CID routine
data.26-27 Similarly, the average Ni-Nimine bond lengths for Ni3a, Ni4 and Ni5 of 2.089 Å 2.079
Å, and 2.147 Å respectively, agree well with the average Ni-Nimine bond length of 2.123 Å
reported in literature.27 Furthermore, the Ni-Npy bond lengths of Ni3a, Ni4 and Ni5 of 2.06 Å,
2.088 Å and 2.033Å respectively are within the maximum range of 2.065 Å reported in
literature.27 The slight differences in for example, the averaged Ni-Nimine bond distances for
Ni3a, Ni4 and Ni5 of 2.094(4) Å, 2.079 Å, and 2.150 (14) Å respectively may be attributed to
the varied trans influence of the H2O, bromide and chloride ligands. Interestingly, the bond
distances of the Ni(1)-Nimine in the structure of Ni3a are quite different,despite having the
same H2O ligand in the trans-position. The reason for this variation is not clear, though steric
factors may be implicated.
6 | P a g e

Page 7 of 32
Dalton Transactions
Dalton Transactions
View Article Online
DOI: 10.1039/C9DT00024K
Table 1: Crystal data and structure refinement parameters for complexes Ni3a and Ni4.
Parameter
Empirical
formula
Ni 3a
Ni 4
Ni5
2(C28H32N4NiO2),4(Br),H2O C56 H56 Br6 N8 C28H28N4NiCl2
Ni3
Formula weight
1368.22
1496.67
550.15
Temperature(K)
Wavelength (Å)
100
0.71073
100(2)
0.71073 Å
100
0.71073
Crystal system
Space group
Monoclinic
P 21
Orthorhombic
P 21 21 21
Monoclinic
P1 21 1
a(Å)
b(Å)
c(Å)
(◦)
9.4714(5)
15.4585(7)
19.8142(10)
90
13.3668(9)
24.1182(16)
24.2402(16)
90
8.4920(7)
18.0236(14)
8.5613(7)
90
β(◦)
γ (◦)
91.8 (3)
90
90
90
99.564
90
Volume
Z
2899.6(2)
2
7814.6(9)
4
1292.15(18)
2
Dcalcd (mg/m3
)
1.567
1.272
1.414
Absorption
coefficient
(mm-1)
F(000)
Number
reflections
Goodness-of-fit
on
3.459
3.816
3.448
1388.0
0.0254( 10895)
2968
56652
572
6204
1.001
1.060
1.002
F2
R indices (all
data)
R1=0.0254, wR2=0.0555
0.660 and -0.265
R1=0.0394,wR2= R1=0.0173,
wR2=0.044
0.1433 and -
0.254
0.0707
1.403 and -0.773
Largest diff.
peak and hole
(e Å−3)
The bond angles of 79.86(14)°, 90.17(13)° and 91.50(13)° for N(1)-Ni(1)-N(2), N(1)-
Ni(1)-O(1), O(1)-Ni-O(1) respectively for Ni3a deviate slightly from the expected 90° and
7 | P a g e

Dalton Transactions
Page 8 of 32
Dalton Transactions
View Article Online
DOI: 10.1039/C9DT00024K
thus reveal a distorted octahedral geometry. Similar distortion is observed in complex Ni5,
with most bond angles recorded within the range 78°-98°. In general, the presence of two
ligand units around each nickel(II) atom in complex Ni4 is not common for dinuclear
nickel(II) complexes and may largely be attributed to the less steric demands of ligands L1-
L4.
Fig. 1: Symmetric unit of compound Ni3a with thermal ellipsoids drawn at 50% probability
level. H, Br and H2O atoms were omitted for clarity. Bond lengths (Å); Ni(1)-N(1), 2.121(4);
Ni(1)-N(2), 2.064; Ni(1)-N(3), 2.067(4); Ni(1)-N(4), 2.073(4); Ni(1)-O(1), 2.055(4); Ni(1)-
O(2), 2.092(3); Ni(1)-N(4), 2.055(4); Bond angle (°); N(2)Ni(1)-N(3), 99.4 (14); N(2)-Ni(1)-
O(2), 89.9(14); N(3)-Ni(1)-O(2), 88.4(13); N(4)-Ni(1)-O(2), 86.0(13); N(3)-Ni(1)-N(4),
80.3(14); N(2)-Ni(1)-N(4), 175.9(14).
8 | P a g e

Page 9 of 32
Dalton Transactions
Dalton Transactions
View Article Online
DOI: 10.1039/C9DT00024K
Fig. 2. Thermal ellipsoids (40% probability) plot of complex Ni4. H atoms and
[NiBr4]2- were omitted for clarity. Bond lengths (Å); Ni(1)–N(1), 2.089(4); Ni(1)–
N(2), 2.079(4); Ni(1)–N(3), 2.084(4); Ni(1)–N(4), 2.081(4); Ni(1)–Br(1), 2.568(7);
Br(3)–Ni(2), 2.546(7); Br(6)–Ni(3), 2.379(9). Bond angle (°): Ni(1)–Br(1)-Ni(2),
91.4(2); Ni(2)-Br(2)-Ni(1), 92.4(2); N(1)-Ni(1)N(2), 79.9(14; N(1)-Ni(1)-Br(1),
94.9(10), N(3)-Ni(2)-Br(2), 90.2(10); N(5)-Ni(2)-N(7), 79.5(17).
9 | P a g e

Dalton Transactions
Page 10 of 32
Dalton Transactions
View Article Online
DOI: 10.1039/C9DT00024K
Fig. 3. Molecular structure of complex Ni5 draw with thermal ellipsoids (50%
probability). Hydrogen atoms were omitted for clarity. Bond lengths (Å); Ni(1)–
N(1), 2.033(15); Ni(1)– N(2), 2.147 (14); Ni(1)–N(3), 2.153 (13); Ni(1)–N(4),
2.0361(16); Ni(1)–Cl(1), 2.396(5); Cl(2)–Ni(1), 2.438 (5). Bond angle (°): N(1)–
Ni(1)-Cl(1), 90.41(4); N(1)-Ni(1)-N(3), 98.05(6); N(1)-Ni(1)-N(2), 78.67(6);
N(1)-Ni(1)-Cl(2), 169.42(42), N(4)-Ni(1)-N(3), 78.76(10); N(4)-Ni(1)-N(2),
95.40(6).
2.3. Electron paramagnetic resonance (EPR)
The X-band EPR spectra of nickel(II) complexes, Ni3, Ni4 and Ni5 were recorded at
room temperature and 77 K. Both powder and frozen solutions of Ni3, Ni4 and Ni5 exhibited
broad isotropic signals (Fig. 4(a) and (b)). The giso values measured for these complexes (2.20-
2.32) are much higher than those expected for nickel(II) species and organic radicals of g
2.00.28 However, the giso values in the range 2.20-2.32 are typical for paramagnetic nickel(II)
centers.29 Surprisingly, the ESR spectrum of Ni4 in DMSO (a strong coordinating solvent) at
room temperature is similar to that of iPrOH (a weakly coordinating solvent) suggesting non-
coordination (Fig. 4(a)). The use of CH3CN, a moderately strong coordinating solvent only
10 | P a g e

Page 11 of 32
Dalton Transactions
Dalton Transactions
View Article Online
resulted in broader line widths and no significant change in the g value recorded DcOoIm: 10p.1a0r3e9d/C9tDoT00024K
weakly coordinating iPrOH solvent (Fig. 4). The simulated epr spectra in the solid state of
complexes Ni4 and Ni5 compare well with the experimental spectra (Fig. 4(c) and (d)).
(C)
(d)
Fig 4. EPR spectra data of (a) Ni4; solid at room temperature (g=2.24), frozen in iPrOH (g
= 2.21), Frozen in DMSO (g=2.28), frozen at 77 (g=2.25) and (b) Ni5; solid at room
temperature (g=2.24), Frozen in iPrOH (g =2.22) (g =2.20). Simulated and experimental
epr spectra of complexes Ni4 (c) and Ni5 (d) respectively.
11 | P a g e

Dalton Transactions
Page 12 of 32
Dalton Transactions
View Article Online
DOI: 10.1039/C9DT00024K
2.4. Asymmetric transfer hydrogenation of ketones.
2.4.1. Screening of Ni(II) complexes Ni1-Ni5 in asymmetric transfer hydrogenation of
acetophenone.
The Ni(II) complexes Ni1-Ni5 were evaluated in catalytic transfer hydrogenation of
i
ketones using acetophenone, KOH and PrOH as the model substrate, base and hydrogen
donor respectively. Percentage conversions and enantiomeric excess of the substrate to the
respective R/S-alcohols were determined by 1H NMR spectroscopy (Fig. S23) and chiral GC
analyses (Fig. S24). All the complexes showed modest conversions between 54% and 98%
(TOF = 7.50 and 13.61 h-1) within 24 h (Fig. S25 and S26) though with very low ee of
between11% to 16% (Table 2). Based on these findings, we thus carried out detailed
investigations of the kinetics, insights into the mechanistic pathways, deactivation profiles
and nature of the active species of these ATH reactions.
2.4.2 .Effects of complex/ ligand structure on ATH of acetophenone
To understand the effects of ligand/complex structure on the kinetics of the ATH of
acetophenone catalyzed by complexes Ni1-Ni5, plots of In[Acetoph.]o/[Acetoph.]t versus time
(Fig S26) were used to deduce the initial rate constants, kob for each complex and the order of
reaction with respect to acetophenone substrate. A pseudo-first order kinetics with respect to
acetophenone substrate was deduced from the linear section of the plots (Fig. S26 inset) as
shown in equation 1.30 The rate constants (kob) and the corresponding TOFs for complexes Ni1-
Ni5 are given in Table 2 and the initial rate constants were in the order
Ni4>Ni3>Ni5>Ni1>Ni2.
12 | P a g e

Page 13 of 32
Dalton Transactions
Dalton Transactions
View Article Online
DOI: 10.1039/C9DT00024K
Rate = kob[acetoph.]1……………………………………… (Eq. 1)
From the catalytic activity trends obtained with respect to the ligand architecture, complexes
bearing methyl substituent on the imine carbon showed lower catalytic activities compared to
the unsubstituted counterparts. For example, complex Ni1 bearingamethylsubstituent recorded
a lower kob of 4.0 x 10-5s-1 compared to the unsubstituted analogous complex Ni3, which
achieved kob of 4.7 x 10-5s-1 (Table 2, entries 1 and 3). While it is much easier to assign this
trend to steric effects (CH3 vs H), a closer examination of the structures reveals that this groups
are remotely located away from the metal atoms hence unlikely to confer any significant steric
control. Thus, we believe that the lower reactivity of complex Ni1, bearing the methyl
substituents may be due to reduced electophilicity of the Ni(II) atom (since CH3 is more
electron donating than H group). This has the net effect of limiting substrate coordination to
the active metal centre. These results are in agreement with literature findings of Chirik et al,31
where diimine Fe(II) complexes bearing methyl substituent at the imine carbon in the ligand
backbone showed lower catalytic than unsubstituted diimine Fe(II) complexes in asymmetric
hydrosilylation of acetophenone.
Table 2. Kinetic data of catalytic asymmetric transfer hydrogenation of acetophenone
catalyzed by complexes Ni1-Ni5
Entry Catalyst Conversion Initial rate constant R2
TOF/h-1 Enantiomeric
-5
[%]b
kob x 10 /s-1
excess (ee %)
1
2
3
4
Ni1
Ni2
Ni3
Ni4
54
4.00±0.04
5.52±0.06
4.73±0.03
7.55±0.11
0.98
0.98
0.98
0.99
7.86
11(S-)
16(R-)
6(S-)
72
84
98
10.00
11.66
13.60
11(R-)
5
88
7.02±0.08
0.97
11.79
14 (R-)
Ni5
a
Conditions: acetophenone, 2.00 mmol; catalyst; 0.057 mmol (0.3 mmol%); base, (100
mmol%) KOH in 2-propanol (5.0 ml); time, 24 h, temperature, 82 oC. b Determined by 1H NMR
spectroscopy. c Turn over frequency (TOF) = (mmol of substrate)/(mmol of catalyst)/(h).
13 | P a g e

Dalton Transactions
Page 14 of 32
Dalton Transactions
View Article Online
The stereochemistry of the complexes was also observed to influence the catalytic
DOI: 10.1039/C9DT00024K
activities of the resultant catalysts. For example, complex Ni4 (R-) showed high kob of 7.55 x
10-5/s-1 compared to the corresponding complex Ni3 (S-) of 4.73 x 10-5/s-1 (Table 2, entries
34). Thus for the (S-) isomer (Ni3), the close proximity of the bulkier phenyl groups to the Ni
atom is likely to hinder coordination of acetophenone substrate, accounting for the lower
catalytic activity observed. This observation is consistent with those of Morris et al where
(R,R)-trans-[Fe(CO)Me(CN)-CyP2N2)[BF4] catalysts were observed to show high catalytic
activity than (S,S)-trans-[Fe(CO)Me(CN)-CyP2N2)[BF4] (R,R).13 While the remote location of
the chiral centre outside metal coordination may be implicated in the low ee% recorded for
these catalysts, it is also possible that dissociation of the complexes into ligandless nickel(0)
salts, may play a major role in their poor enantiaoselectiviy.
In comparison to the previously reported nickel-based catalysts in the transfer
hydrogenation of ketones, these present catalysts display moderate catalysts. For example, the
kob observed for the nickel complexes Ni1-Ni4 of between 4.00 to 7.02 x 105 s-1 are slightly
higher than the values of 2.5 to 5.0 x 105 S-1 reported for the (pyrazolylmethyl)pyridine nickel
complexes.20 In addition, the complexes Ni1-N4 showed better catalytic activities compared
to the template Ni(0) systems of Ni(COD)2/dppe which gave conversions of 96% only after 48
h at elevated temperatures of 130 0C.32 In terms of enantioselectivity, the complexes Ni1-N4
(ee% < 11%) fared poorly compared to Ni(PPh3)2Cl2/P^N^O- systems that could catalyse ATH
of simple ketones to achieve 10-84 ee%.19
2.4.3. Optimization of reaction conditions on transfer hydrogenation
Upon establishing the catalytic efficacy of the nickel complexes Ni1-Ni5 in the transfer
hydrogenation of acetophenone, we then optimized the reaction conditions by investigating the
effect of base and catalyst loading using the most active complex Ni4. Generally, an increase
in catalyst loading was observed to result in diminished catalytic activities. For example, an
14 | P a g e

Page 15 of 32
Dalton Transactions
Dalton Transactions
View Article Online
increase in catalyst loading from 0.30 mmol% to 1.14 mmol%, was followed DbOyI: 1a0.1d03r9a/sCt9iDcT00024K
decrease in TOF from 13.47 to 2.19 h-1 (Table 3, entries 1 and 4 and Fig. S27). Decrease in
catalytic activity with increase in catalyst loading may be associated with the aggregation of
the pre-catalysts20, 33-34 which have the net effect of reducing the number of active species. This
agrees with the literature reports by Rupesh et al where an increase in catalyst/substrate ratio
from 1:400 to 1:1600 resulted in drop in catalytic activities from 90% to 46% within 3 h for
Ru(II) carbonyl benzoylhydrazone complex.35 On the other hand, lower catalytic activities
observed at lower catalyst loadings of 0.14 mmol% pointed to possible insufficient amount of
the active species, thus rendering 0.30 mmol% as the optimum catalyst loading (Fig. S27). The
impact of the nature of the base on the ATH of acetophenone was also studied by using tBuOK,
KOH, NaOH, and Na2CO3 (Table 3, entries 5-8). The highest catalytic activity was observed
in tBuOK, while the lowest catalytic activity was recorded in Na2CO3. This is consistent with
the order of pKb values (base strength) and stability of the bases in good agreement with
literature findings.36
Table 3. Effect of catalyst loading and nature of base in ATH of acetophenone using
complex Ni4
15 | P a g e

Dalton Transactions
Page 16 of 32
Dalton Transactions
View Article Online
DOI: 10.1039/C9DT00024K
Entry
Catalyst
loading/mmol %
Base
KOH
Conversion[%]
97
TOF/h-1
1
0.30
13.47
2
3
4
5
6
7
8
KOH
KOH
KOH
KOH
NaOH
tBuOK
0.14
0.43
0.86
1.14
0.30
0.30
0.30
53
72
64
60
96
99
66
15.80
6.98
3.10
2.19
13.33
13.75
9.16
Na2CO3
aConditions: acetophenone, 2.00 mmol; catalyst, 0.0057 mmol (0.30 mmol%);
o
100 mmol% of base in 2-propanol (5.0 mL), time, 24 h; temperature, 82 C.
bDetermined by 1H NMR spectroscopy; cTurn over frequency (TOF) = (mmol of
substrate)/(mmol of catalyst)/time.
2.4.4. Variation of ketones substrates
Having established the optimum reactions conditions for the TH reactions, we turned
our attention to the scope of ketone substrates that can be reduced by nickel complex Ni4
(Table 4). In general, acetophenone derivatives bearing electron donating or withdrawing
groups appeared to exhibit lower reactivities (Tables 4, entries 1-4). For example, 2-
methylacetophenone and 2-chloroacetophenone displayed conversions of 87% and 91%
compared to 98% respectively reported for acetophenone (Table 4, entries 1-3). This trend
contradicts previous literature findings for Ni-N^P^O and Fe(II) (NH)2P2 catalysts where
higher reactivities (>95%) were observed for acetophenone derivatives bearing electron
donating or withdrawing groups compared to acetophenone (81%).19, 37-38 The observed trend
could be attributed to steric effects, since the substituents are at the ortho position, which is
close to the carbonyl centre. The argument is supported by the lower reactivities observed for
the more sterically demanding 2-aminophenyl acetophenone and cyclohexyl acetophenone of
80% and 86% respectively (Table 4, entries 1, 5 and 6). Indeed, the less sterically hindered 1-
16 | P a g e

Page 17 of 32
Dalton Transactions
Dalton Transactions
View Article Online
(naththalen-2-yl) ethan-1-one recorded relatively higher percentage conversion of 93%
DOI: 10.1039/C9DT00024K
conversions (Table 4, entry 8). These results compare well with those reported by Ikariya et al.
using oxo-tethered Ru(II) complexes where sterically hindered benzophenone, gave lower
catalytic activities >59 % compared to conversions of >99% for the unsubstituted
benzophenones. We also studied para-substituted acetophenones using 4-methylacetophenone
and 4-chloroacetophenone substrates (Table 4, entries 4 and 5). Interestingly, lower reactivities
of 57% and 87% were recorded for 4-methylacetophenone and 4-chloroacetophenone
respectively, a phenomenon that can be largely attributed to electronic effects. Heterocyclic
aromatic ketones also exhibited lower conversions. For example, conversions of 56% and 49%
were recorded for the pyrazine and pyrrole derivatives respectively (Table 4, entries 1 vs 11-
14
13) in line with irreversible coordination of the heteroatoms to the metal center.39
Interestingly, there was no significant drop in catalytic activity for the aliphatic 1-cylcohexyl
ethanone ketone (93%) (Table 4, entry 10).
Table 4. Effect of substrate scope variation on the TH reactions catalyzed by complex Ni4
Enter
Substrate
Conversion[%]
TOF/h-1
17 | P a g e

Dalton Transactions
Page 18 of 32
Dalton Transactions
O
View Article Online
1
2
98
87
13.68
DOI: 10.1039/C9DT00024K
O
12.08
O
3
91
12.63
Cl
O
4
5
6
57
87
92
7.97
12.08
12.77
O
Cl
O
OH
O
7
86
11.94
NH2
O
8
9
93
80
12.91
11.10
O
O
O
10
63
8.74
11
12
89
56
12.35
7.77
N
O
N
N
O
13
49
6.80
N
aConditions: acetophenone,2.00 mmol;0.0057 mmol (0.3 mmol%); base, tButOK(100 mmol%)
in 2-propanol (5.0 ml); time, 24 h, temperature, 82 oC. b Determined by 1H NMR spectroscopy.
c Turn over frequency (TOF) = (mmol of substrate)/(mmol of catalyst)/(h).
2.5 Determination of the nature of the active species
In modern catalytic practises, determination of the true nature of the active species is a
ubiquitous exercise and regarded as a bare minimum. In distinguishing between homogeneous
18 | P a g e

Page 19 of 32
Dalton Transactions
Dalton Transactions
View Article Online
and heterogeneous catalysts, a number of experiments such a catalyst poisoning tests and
DOI: 10.1039/C9DT00024K
identification of nanoparticle formation are employed.40-43 We thus employed sub-
stoichiometric and mercury poisoning experiments to determine the true active intermediate.44-
46
Using 20% (mol. equivalent to Ni4 complex) of tricyclohexyl phosphine (PCy3),
triphenylphosphine (PPh3), and carbon disulfide (CS2), we observed appreciable reduction in
conversions of complex Ni4 from 85% to about 65%, 60% and 45% respectively (Fig. 5). This
diminished catalytic activity upon addition of 20% of the poisoning ligands provided points to
a possible existence of catalytic active Ni(0) nanoparticles, i.e heterogeneity of the system.
However, the significant percentage conversions retained in the presence of the poisons of 45%
- 65% (representing about 50% to 75% of the original catalytic activity) is a strong indicator
of largely homogeneous species.41 Indeed, the observation of catalytic activities (conversions
of 55%) even upon addition of 100% mol equivalent of PPh3 (Fig. S29) corroborates this
assertion.
Fig. 5. Kinetics of the deactivation profiles of catalyst Ni4 using 20% (mol
equivalent to the Ni4 catalyst) phosphine ligands PCy3, PPh3 and CS2.
19 | P a g e

Dalton Transactions
Page 20 of 32
Dalton Transactions
View Article Online
To gain further insight in the nature of the active species of complex Ni4, we carried
DOI: 10.1039/C9DT00024K
out mercury poisoning tests using 3, 5 and 10 drops at the beginning of the reaction (after pre-
generation of the active species) and at about 50% conversion (Fig. 6 and Fig. S29). Both
experiments were run for 24 h and compared to the control experiments without mercury (Fig.
6).40, 47-49 Lower conversions of about 60% (initial addition) and 66% (50% addition) were
observed in comparison to conversions of 98% reported in the absence of mercury. The partial
reduction in catalytic activity of complex Ni4 points to the presence of both homogeneous and
Ni(0) nanoparticles as the active species, in good agreement with the sub-stoichiometric data.41,
50 From the the poisoning data and smooth kinetics curves (Figs. S25 and S26), we can conclude
that active species are largely homogenous in nature but accompanied by the formation of
catalytic active Ni(0) nanoparticles during the course of the reaction.41
Fig. 6. Kinetic plots showing deactivation profiles of complex Ni4 with excess mercury. The
deactivation experiment was carried out using 5 drops of Hg at the beginning and at 50%
percentage conversions and compared with the standard kinetic profiles.
2.6 Proposed mechanism of asymmetric transfer hydrogenation of ketones
catalyzed by complex Ni4
20 | P a g e

Page 21 of 32
Dalton Transactions
Dalton Transactions
View Article Online
Having established the homogeneity of the active species of complexes Ni1-Ni5, we
DOI: 10.1039/C9DT00024K
therefore employed low resolution mass spectrometry to support the plausible mechanism for
the ATH reactions of complex Ni4 (Fig. S28) as given in Scheme 4 as previously reported in
literature.51-52 This was accomplished by withdrawing aliquots from the reaction mixture at
regular time intervals and subjecting the sample ESI-MS analyses. From the data obtained, the
ATH mechanism is proposed to begin with the homolytic cleavage of the dinuclear complex
Ni4 in iPrOH to give the mononuclear species (4a) as detected from mass spectrum (m/z =
559.06 amu). This structural rearrangement may explain the relatively longer induction profiles
observed in the kinetic plots (Fig. S28) and absence of molecular mass of the dinuclear complex
Ni4 in the spectrum (Fig. S28). The formation of the mononuclear aqua Ni3a complex also
supports this transformation. Coordination of iPrOK to 4a via substitution of the bromides to
afford the Ni(L4)2-(iPrO)2 adduct (4b) was deduced from the m/z signal at 599 amu. Generation
of the dihydride intermediate (4c), believed to be the active species followed by elimination of
the acetone molecule could be hypothesized from the presence of the signal at m/z = 481 amu.
Subsequent coordination of acetophenone substrate to form adduct (4d) prior to hydride
migration to give the expected 1-phenyl ethanol product is evident from the signal at m/z =
657.14 amu corresponding to (4e). Elimination of the product from the metal coordination
sphere is believed to complete the catalytic cycles leading to re-generation of the solvated
complex (4b).
21 | P a g e

Dalton Transactions
Page 22 of 32
Dalton Transactions
View Article Online
DOI: 10.1039/C9DT00024K
Scheme 4. Proposed mechanism of asymmetric transfer hydrogenation of ketones catalyzed by
complex Ni4 based on intermediates as identified from low resolution mass spectrometry.
Conclusions
In summary, chiral (pyridyl)imine Ni(II) complexes have been synthesized and
structurally characterized using IR spectroscopy, mass spectrometry, single crystal X-ray
crystallography and electron paramagnetic resonance. The complexes demonstrate some
unprecedented diverse coordination chemistry controlled largely by the lability of the
coordinated halides. The presence of two ligand units per Ni(II) atom in the dinuclear core
22 | P a g e

Page 23 of 32
Dalton Transactions
Dalton Transactions
View Article Online
DOI: 10.1039/C9DT00024K
is unusual and highlight the less steric demands of the ligands. All the complexes showed
moderate catalytic activities in the asymmetric transfer hydrogenation of ketones though
with low enantioselectivity. The catalytic activities of the complexes were influenced by
the ligand motif and nature of the base employed. The reactivities of the ketone substrates
are controlled by both steric parameters and electronic factors. Kinetics data, sub-
stoichiometric and mercury poisoning tests point to the homogeneity of the complexes with
the formation of Ni(0) nanocluster particles. From low resolution mass spectrometry
analyses of the reaction intermediates, a dihydride mechanism can be proposed.
3. Experimental sections
3.1 Materials and instrumentation
All synthetic manipulations especially reactions involving air and moisture sensitive
materials were performed under nitrogen atmosphere using standard Schlenk techniques in a
vacuum line. All solvents were of analytical grade. Toluene, hexane, dichloromethane
(CH2Cl2), isopropanol (iPrOH), diethyl ether, ethyl acetate and ethanol were purified by
distillation and dried over sodium/ benzophenone, CaCl2 and molecular sieves prior to use.
Starting materials: Nickel(II) bromide ethylene glycol dimethyl ether [NiBr2(DME)] ( :
99.99%); Nickel Chloride (NiCl2) (≥ 99.99%), The ligands (S-)-1-phenyl-N-(pyridine-2-yl)
ethylidene) ethanamine (L1), (R-)-1-phenyl-N-(pyridine-2-yl) ethylidine) ethanamine (L2),
(S)-1-phenyl-N-(pyridine-2-yl methylene) ethanamine (L3) and (R)-1-phenyl-N-(pyridine-2yl
methylene) ethanamine (L4) were synthesised by following literature procedure.53
2acetylpyridine (≥ 99.99%), ( 99.9%)2-propanol (iPrOH), acetophenone (≥99.99%), KOH,
NaOH, potassium tert-butoxide, Na2CO3, 2-chloro-acetophenol (≥ 99.99%), 2-methyl
acetophenone (≥ 99.99%), 2-hydroxyacetophenone (≥ 99.99%), 2-acetyl pyridine (≥99.99%),
acetyl pyrizine (≥99.99%), 1-cyclohexyl-2-enyl) ethanone (≥99.99%), cyclohexyl(phenyl)
23 | P a g e

Dalton Transactions
Page 24 of 32
Dalton Transactions
methanone (≥99.99%), 1-naphthalen-3-yl) ethanone, (2- and aminophenyl) methanone, anVdiew(RAr)ticle Online
DOI: 10.1039/C9DT00024K
and (S-) 1-phenyl ethanol (≥ 99.99%), tricyclohexylphosphine (≥99.99%), triphenylphosphine
(PPh3) (≥ 99.99%), mercury (Hg), and Carbon disulfide (CS2) (≥ 99.99%) were purchased from
Sigma-Aldrich., and NMR solvents (deuterated chloroform, CDCl3) were purchased from
Sigma-Aldrich and used as received without further purification.
1H and 13C NMR spectra were recorded on a Bruker Ultrashield 400 (1H NMR
400MHz, 13C NMR 100 MHz) spectrometer in CDCl3 solution at room temperature and
chemical shifts (δ) were determined relative to internal TMS and recorded in ppm relative to
CHCl3 δ1 : 7.26 ppm and δ13C: 77.6 ppm and DMSO-d6 δ1H; 2.50 ppm. Coupling constants
H
(J) are reported in Hertz (Hz) and splitting patterns are indicated as s (singlet), d (doublet), dd
(doublet of doublet), t (triplet), and m (multiplet). Elemental analyses were performed on
Thermal Scientific Flash 2000, and ESI mass spectra were recorded on an LC premier micro-
mass spectrometer. The infra-red spectra were recorded on a PerkinElmer spectrum 100 in the
4000 – 650 cm-1 range. EPR measurements were performed in the optical ERP cavity (ER
41040R, Bruker, Germany) employing a customly designed flat EPR cell equipped with a
laminated Pt-mesh working electrode, Pt-wire as a counter electrode, and Agwire as a pseudo-
reference electrode. The measurements were performed at X-band using a Bruker EPR
spectrometer. The asymmetric transfer hydrogenation reaction of ketone was carried out in a
two-necked round bottom flask fitted with a reflux condenser under nitrogen gas. GC analyses
for enantiomeric excess were performed under the following chromatography conditions:
Varian CP-3800, ga 265/ 51nm/ pst2, 5µl capillary 30m x 0.250 x 0.25 µm. Nitrogen carrier
o
O
column gas 5psi, injector temperature 250 C, oven programmed at isotherm 120 C, 150:1
split ratio, flow rate = 1.5, velocity = 38cm/sec, 1uL sample and mobile phase (N2) gas, internal
standard: decane.
24 | P a g e

Page 25 of 32
Dalton Transactions
Dalton Transactions
View Article Online
DOI: 10.1039/C9DT00024K
3.2. Synthesis and characterization of Ni(II) complexes
3.2.1. [Ni2(L1)4-µ-Br2] [NiBr4] (Ni1)
To a solution of [NiBr2(DME)] (0.20 g, 0.65 mmol) in CH2Cl2 (15 mL), was added to
solution of ligand (L1) (0.30 g, 1.30 mmol) in CH2Cl2 (15 mL) and the reaction was stirred at
room temperature for 24 h to give a pink solution. After the specified reaction period, the
resulting solution was concentrated under reduced pressure followed by addition hexane (20
ml) to precipitate crude product. The crude product was washed then with hexane (15 mL) and
dried under vacuum to afford complex 1 as a green powder. Yield = 0.41 g, (50%). ESI-MS:
m/z (%) 587 [1/2M – Br, 45%]+, 362 [1/2M – (L1+Br), 100%]+. FT-IR (cm-1): (ѵC=N imine
)
=1649, µeff = 3.97 BM. Anal. Calc. for C60H64N8Ni3Br6: C, 46.28; H, 4.15; N, 7.22 Found: C,
46.29; H, 4.18; N, 7.26.
Complexes Ni2- Ni5 were synthesised following the protocol described for Ni1.
3.2.2. Ni2(L2)4-µ-Br2] [NiBr4] (Ni2)
[NiBr2(DME)] (0.20 g, 0.65 mmol) in CH2Cl2 (15 mL) and L2 (0.30 g, 1.30 mmol) in
CH2Cl2 (15 mL) to afford green powder. Yield = 0.48 g (58%). ESI-MS: m/z (%) 587 [1/2M –
Br, 100%]+, 362 [1/2M – (L1+Br), 60%]+. FT-IR (cm-1): (ѵC=N imine
= 1639, µeff = 3.76 BM.
)
Anal. Calc. for C60H64N8Ni3Br6. C, 46.41; H, 4.15; N, 7.22 Found: C, 46.46; H, 4.20; N, 7.24.
3.2.2. [Ni2(L3)4-µ-Br2] [Br2] (Ni3)
[NiBr2(DME)] (0.10 g, 0.33 mmol) in CH2Cl2 (15 mL) and L3 (0.14 g, 0.65 mmol) in CH2Cl2
(15 mL) to afford lemon green powder. Yield = 0.43g (52%). ESI-MS: m/z (%) 559 [1/2M –
Br, 100%]+, FT-IR (cm-1): (ѵC=N imine
= 1650, (ѵC=N)py = 3291. EPR (CH2Cl2, liquid N2
)
25 | P a g e

Dalton Transactions
Page 26 of 32
Dalton Transactions
View Article Online
temperature): g = 2.2836. µeff = 3.52 BM. Recrystallization from a mixture of CHD2COI:l210:.1h0e39x/aCn9DeT00024K
solution afforded single crystals suitable for single crystal X-ray crystallography.
C56H56N8Ni2Br4: C, 52.62; H, 4.42; N, 8.77. Found: C, 52.60; H, 4.49; N, 8.81.
3.2.4. [Ni2(L4)4-µ-Br2] [NiBr4] (Ni4)
[NiBr2(DME)] (0.20 g, 0.65 mmol) in CH2Cl2 (10 mL) and L4 (0.28 g, 1.30 mmol) in
CH2Cl2 (10 mL) to afford lemon green powder. Yield = 0.51g (56 %). ESI-MS: m/z (%) 559
[1/2M – Br, 100%]+. FT-IR (cm-1): (ѵC=N imine
= 1641, (ѵC=N)py = 3388. EPR (CH2Cl2, liquid
)
N2 temperature): g = 2.28. µeff = 3.66 BM. Recrystallization from a mixture of CH2Cl2: hexane
solution afforded single crystals suitable for single crystal x-ray crystallography. Anal. Calc.
for Anal. Calc. for C56H56N8Ni3Br6: C, 44.94; H, 3.77; N, 7.49. Found: C, 44.81; H, 3.91; N,
7.65.
3.2.5. [Ni(L3)2Cl2] (Ni5)
NiCl2 (0.20 g, 1.5 mmol) in CH2Cl2 (10 mL) and L4 (0.63 g, 3.00 mmol) in CH2Cl2 (10 mL)
to afford a lemon green powder. Yield = 0.51g (58 %). ESI-MS: m/z (%) 483 [M –2Cl, 100%]+.
FT-IR (cm-1): (ѵC=N imine
= 1631, EPR (CH3N, liquid N2 temperature): g = 2.2. µeff = 3.62 BM.
)
Recrystallization from a mixture of CH3CN: (CH3CH3)2O solution afforded single crystals
suitable for single crystal x-ray crystallography. Anal. Calc. for Anal. Calc. for
C28H28N4NiCl2: C, 61.13; H, 5.13; N, 10.18. Found: C, 61.14; H, 5.21; N, 10.15.
3.3. Single crystal X-ray crystallography
Single crystal X-ray diffraction data collection and structure refinement for Ni3, Ni4 and Ni5
were recorded on a Bruker Apex Duo equipped with an Oxford Instrument Cryo jet operating
at 100(2) K and an uncoated micro source operating at 30 W power. The data were collected
26 | P a g e

Page 27 of 32
Dalton Transactions
Dalton Transactions
View Article Online
DOI: 10.1039/C9DT00024K
with Mo Kα (λ = 0.71073 (Å)) radiation at a crystal-to-detector distance of 50 mm. The
following conditions were used for the data collection: omega and phi scans with exposures
taken at 30 W X-ray power and 0.50 frame widths using APEX2.54 The data were reduced
with the programme SAINT55 using outlier rejection, scan speed scaling, as well as standard
Lorentz and polarisation correction factors. A SADABS semi-empirical multi-scan
absorption correction was applied to the data. Direct methods, SHELXS-2014 and WinGX
were used to solve both structures. All non-hydrogen atoms were located in the difference
density map and refined anisotropically with SHELX-2014.56 All hydrogen atoms were
included as idealized contributors in the least squares process. Their positions were calculated
using a standard riding model with C-Haromatic distances of 0.93 Å and Uiso = 1.2Ueq and
CHmethylene distances of o.99 Å and Uiso =1.2 Ueq and C-Hmethyl distances of 0.98 Å and Uiso
=1.5 Ueq.
3.4. General procedure for asymmetric transfer hydrogenation of ketones
For catalytic asymmetric transfer hydrogenation of ketones, a typical procedure was
as followed. A solution of 5 mL of KOH (100 mmol %) in iPrOH and catalysts Ni1-Ni5 (0.3.0
mmol %) were mixed and stirred at 82 oC for 30 min, 2.0 mmol of ketone was introduced in
drop wise into the reaction mixture. During the process of reaction, about 0.5 mL of the
mixture was sampled at regular time intervals, cooled, and percentage conversion of
acetophenone to 1-phenyl ethanol was analysed using 1H NMR spectroscopy by comparing
the intensity of methyl signals of acetophenone (s, δ 2.59 ppm) and 1-phenyl ethanol (d, δ
1.49 ppm) of the crude products. In addition, GC was used as a standard to validate the results
and also to determine the enantiomeric excess (ee %). Kinetic data were analysed using 64-
bit Origin Pro 9.1. A standard nonlinear first order monomolecular exponential growth model,
y = ea(1 - e(k(x-xc) ), where a = amplitude, x = time, xc = centre, and k = rate, was used to fit the
kinetic data for Ni1–Ni5.
27 | P a g e

Dalton Transactions
Page 28 of 32
Dalton Transactions
View Article Online
DOI: 10.1039/C9DT00024K
3.5. Mercury poisoning tests
In a typical experiment, to a solution of the pre-activated catalyst system (complex Ni4,
0.3% mmol, in 5 mL of KOH,100 mmol%; in iPrOH 5 mL), acetophenone (2.0 mmol) and the
respective amounts of Hg (3, 5 and 10 drops) were added and allowed to reflux at 82 oC for 24
h. During the reaction, about 0.5 mL of the reacting mixture was sampled at regular time
intervals, cooled and analysed for percentage conversion. In the second test, 3 drops of Hg
were added at 50% conversion (time, t = 4.5 h and 8 h respectively) and allowed to proceed for
24 h during which samples were withdrawn at regular time intervals and analysed for
percentage conversion.
3.6. Sub-stoichiometric deactivation studies
To a solution of pre-activated catalyst system (complex Ni4, 0.3% mmol, in 5 mL of
KOH,100 mmol%; in iPrOH 5 mL), acetophenone (2.0 mmol) and 20% mol equivalent of the
appropriate poisoning agent, carbon disulphide (CS2), triphenylphosphine (PPh3), and
tricyclohexyl phosphine (PCy)3 was added and allowed to reflux at 82 oC for 24 h. During thi
period, samples were withdrawn at regular time intervals, cooled and analysed as discussed in
section 3.4.
3.7. Mechanistic studies of ATH of ketones
Mechanistic studies of the transfer hydrogenation of acetophenone catalyzed by nickel
complexes were performed using low resolution ESI-MS technique. Generally, a solution of
the nickel complex (0.3 mol% Ni1-Ni5) in iPrOH were mixed and stirred at 82 oC for 30 min
followed by drop-wise addition of acetophenone (2.0 mmol) in iPrOH (5 mL) into the reaction
mixture and stirred for 24 h. During the course the reaction, about 0.1 mL of the mixture was
sampled at regular time intervals, cooled to about 0 oC and analysed using ESI-MS technique
to identify the respective mass fragments of the intermediates in the catalytic cycle.
28 | P a g e

Page 29 of 32
Dalton Transactions
Dalton Transactions
View Article Online
DOI: 10.1039/C9DT00024K
References
1.
Chen, J.-s.; Li, Y.-y.; Dong, Z.-r.; Li, B.-z.; Gao, J.-x., Tetrahedron Let.2004, 45, 8415-
Wan, K. Y.; Roelfes, F.; Lough, A. J.; Hahn, F. E.; Morris, R. H., Organometallics
8418.
2.
2018, 37, 491-504.
3.
4.
Goldberg, K.; Schroer, K.; Lütz, S.; Liese, A., Appl. Microbio.biotech. 2007, 76, 237.
Hashiguchi, S.; Fujii, A.; Takehara, J.; Ikariya, T.; Noyori, R., J. Am. Chem. Soc. 1995,
117, 7562-7563.
5.
6.
7.
Gao, J.-X.; Ikariya, T.; Noyori, R., Organometallics 1996, 15 1087-1089.
Faller, J.; Lavoie, A. R., Organometallics 2002, 21, 3493-3495.
Bertoli, M.; Choualeb, A.; Lough, A. J.; Moore, B.; Spasyuk, D.; Gusev, D. G.,
Organometallics 2011, 30, 3479-3482.
8.
9.
Wang, D.; Astruc, D., Chem. Rev. 2015, 115, 6621-6686.
Clarke, Z. E.; Maragh, P. T.; Dasgupta, T. P.; Gusev, D. G.; Lough, A. J.; Abdur-
Rashid, K., Organometallics 2006, 25, 4113-4117.
10.
Werkmeister, S.; Neumann, J.; Junge, K.; Beller, M., Chem. Eur. J. 2015, 21, 12226-
Baratta, W.; Ballico, M.; Del Zotto, A.; Siega, K.; Magnolia, S.; Rigo, P., Chem. Eur.
12250.
11.
J. 2008, 14, 2557-2563.
12.
Wu, X.; Li, X.; Zanotti‐Gerosa, A.; Pettman, A.; Liu, J.; Mills, A. J.; Xiao, J., Chem.
Eur. J. 2008, 14, 2209-2222.
13.
14.
15.
16.
Morris, R. H., Chem. Soc. Rev.2009, 38, 2282-2291.
Demmans, K.; Ko, O.; Morris, R., RSC Adv. 2016, 6, 88580-88587.
Malacea, R.; Poli, R.; Manoury, E., Coord. Chem. Rev. 2010, 254, 729-752.
Wu, X.; Xiao, J., Chem. Commun. 2007, , 2449-2466.
29 | P a g e