Enantioselective Michael Addition Reaction Catalysed by Enantiopure Binuclear Nickel(II) Close-Ended Helicates

Article abstract of DOI:10.1002/adsc.201901350

The enantiopure Ni(II) helicates [Ni₂L₁^RR.Cl₂] (1), [Ni₂L₁^SS.Cl₂] (1′), [Ni₂L₂^RR.Cl₂] (2), [Ni₂L₂^SS.Cl₂] (2′) were synthesized by one-pot self-assembly technique from R-(+)- or S-(?)-1,1′-binaphthyl-2,2′-diamine, with 4-methyl-2,6-diformyl phenol or 4-tert-butyl-2,6-diformyl phenol and nickel salts. This binuclear double stranded Ni(II) helicates were characterized by ESI-MS, IR and single crystal X-ray structure wherever applicable. The extensive chiroptical studies suggest that the complexes are enantiopure in nature. The chirality transfer from ligand L₁^RR & L₂^RR to Ni(II) metal centre produced ΔΔ geometrical chirality, while their enantiomeric counterpart L₁^SS & L₂^SS produced ΛΛ chirality in their respective complexes.These enantiopure helicates were applied as catalysts in asymmetric Michael addition of 1,3-dicarbonyl compounds with β-nitrostyrene to produce nitroalkanes in good yield (96–98%) and ee (78–94%). (Figure presented.).

Full text of DOI:10.1002/adsc.201901350

Title: Enantioselective Michael Addition Reaction Catalysed by
Enantiopure Binuclear Nickel(II) Close-Ended Helicates
Authors: Palani Subramanian, Eswaran Chinnaraja, Rajendran
Arunachalam, Krishanu samanta, and Ramalingam Natarajan
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To be cited as: Adv. Synth. Catal. 10.1002/adsc.201901350
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10.1002/adsc.201901350
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201901350
Enantioselective Michael Addition Reaction Catalysed by
Enantiopure Binuclear Nickel(II) Close-Ended Helicates
Eswaran Chinnaraja,a,b Rajendran Arunachalam,a,b Krishanu Samanta,b,c Ramalingam
Natarajan,b,c and Palani S. Subramanian,*a,b
a
Inorganic Materials and Catalysis Division, CSIR-Central Salt and Marine Chemicals Research Institute (CSIR-
CSMCRI), Bhavnagar- 364 002, Gujarat, India. * E-mail: siva@csmcri.res.in; Fax.0091-278-2567562; Tel. 0091-278-
2471793
Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
b
c
Organic & Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology, Kolkata, India.
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract. The enantiopure Ni(II) helicates [Ni2L1RR.Cl2] (1), enantiomeric counterpart L1SS & L2SS producedchirality
[Ni2L1SS.Cl2] (1’), [Ni2L2RR.Cl2] (2), [Ni2L2SS.Cl2] (2’) were in their respective complexes.These enantiopure helicates
synthesized by one-pot self-assembly technique from R-(+)- were applied as catalysts in asymmetric Michael addition of
or S-(-)-1,1’-binaphthyl-2,2’-diamine, with 4-methyl-2,6- 1,3-dicorbonyl compounds with -nitrostyrene to produce
diformyl phenol or 4-tert-butyl-2,6-diformyl phenol and nitroalkanes in good yield (96-98%) and ee (78-90%).
nickel salts. This binuclear double stranded Ni(II) helicates
were characterized by ESI-MS, IR and single crystal x-ray
structure wherever applicable. The extensive chiroptical Keywords: Asymmetric catalysis; Binuclear nickel(II)
studies suggest that the complexes are enantiopure in nature. complexes; Chiroptical properties; Enantiopure helicate;
The chirality transfer from ligand L1RR & L2RR to Ni(II) metal Michael addition reaction
centre produced geometrical chirality, while their
conformation of the catalysts.[10] With in-built
Introduction
enantiopure BINOL, Shibasaki has constructed
various binuclear metal catalysts with N2O4
chromophores for diverse reactions.
Asymmetric catalysis[1] is one of the most powerful
and economical method to achieve enantiorich
compounds compared to kinetic resolution. In such
reaction although metal catalysts,[2] organocatalysts[3]
and enzymatic catalysts[4] are used, the metal catalysts
continue to be a potential player owing to its high
efficiency, stability and broad substrate scope.
Conventionally, such metal catalysts are generally
monometallic with in-built chiral component.[5]
Tethering two such catalytic units through covalent or
non-covalent bond was found to enhance their
cooperative catalytic function. In this direction,
compared to monometallic, the bimetallic catalysts are
considered superior because of such existence in
enzyme based biocatalysts e.g., superoxide
dismutase,[6] urease[7] etc. Inspired by such dimeric
system in various biocatalysts, there have been a
growing interest to develop various homo and hetero
binuclear catalysts as evidenced from the literature.[8]
Binuclear catalysts thus emerging as a powerful tool,
their applications in asymmetric transformation
reactions[9] has gained significance.
Scheme 1. Enantiomeric [2+2] close-ended macrocyclic
Ni(II)-helicates.
Various homo-(Ni2, Mn2, Co2)[11] and hetero-
bimetallic catalysts (La-Yb, Ga-Yb, Cu-La, Cu-Pr,
Cu-Sm, Cu-Eu, Cu-Dy, Zn-Sm, Mg-Sm and Ni-Sm)[12]
were studied for their catalytic applications in
Nitroaldol,[13] Michael addition,[14] and Mannich
reaction[15] etc. Michael addition reaction thus known
for its stereo-controlled C-C bond formation, its
influence on total synthesis of optically active natural
Similarly, BINOL a well-known compound for its
axial chirality is of extensive investigation adapting in
various binuclear metal complexes to control the
1
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10.1002/adsc.201901350
Advanced Synthesis & Catalysis
RR
products e.g., hexahydropyrrolo-indole alkaloids, (+)-
chimonanthine, (+)-folicanthine, and (-)-calycanthine)
pharmaceuticals and materials are well documented in
the literature.[16-18]
peak at m/z = 991.46 correspond to [Ni2L1 Cl.H2O]+
(calc. m/Z = 991.15) is appeared with isotopic peaks
as depicted in Figure 1.
In this series, the Ni2-schiff base complex with open
ended N2O4 chromophore containing endogenous
naptholate phenolic oxygen treated with Li, Na, K, or
Cs has been extensively investigated.[19] The
incremental enantioselectivity obtained upon
introduction of metal ions with napthoxide hydroxide
salts were correlated with increased atomic radius and
polarizability of the napthoxide-Cs pair.[20] In such
system the introduction of large sized Cesium
enhancing the selectivity, the consequent change in the
twist angle associated with conformational change
may not be ignored. In this direction, we in the present
study report binuclear double-stranded close-ended
helicates where the twist angle between the N2O2
chromophore is locked by their helical architecture.
Ever since the term helicate was coined by Lehn[21]
(1987), the subsequent reports on helicate has
increased tremendously for its various applications on
sensors,[22] biological applications[23] and catalysis[24]
etc. Thus, the double helical structure in the helicate
inspired us to implement them as catalyst.[25] Although
the enantiopure helicates are known for their appealing
architecture and chiral properties, their catalytic
application in asymmetric catalysis was less explored.
The combined effect of helical chirality and metal
centred chirality on enantioselective catalysis has been
of keen interest.[26] In this series recently, we have
reported a series of binuclear double-stranded Cu2 and
Zn2 helicates and their catalysis in asymmetric
reactions.[27] With that encouragements, we here report
the synthesis of few important close-ended nickel(II)
helicates and their catalytic application in Michael
addition reaction. In this endeavour, this report
demonstrate the synthesis of series of chiral
nitroalkane from -nitroalkene and 1,3-dicarbonyl
compounds. In addition to investigating the
enantioselective catalytic role of this Ni2 helicate for
wide variety of substrates, we also tested them for the
enantioselective synthesis of a pharmaceutically
important chiral drug (S)-Warfarin.
Figure 1. ESI-MS spectra of [Ni2L1RR.Cl2] (1) helicate.
Similarly, the m/Z peak at 1027.24 (Calc.1027.13)
attributed to the monocationic species to this
enantiomeric counterpart [1’.H2O]H+ confirms the
formation of binuclear double-stranded helicate.
Similarly
the
complexation
of
L2
with
nickel(II)chloride provide an intense peak at m/Z =
1111.29 and 1111.31 (Calc: 1111.22) correspond to
[2.H2O.H+]+, [2’.H2O.H+]+ respectively and confirms
their dimeric association (Figure S1-Figure S4).
The IR spectra (S2) recorded for these complexes
depict an intense band in the range 1630-1638 cm-1 are
attributed to C=N stretching frequencies in all four
double stranded-helicates (Figure S5). Electronic
spectra of the Ni(II) helicates recorded in THF reveals
three set of bands as shown in Figure 2. The two
intense and a narrow band in the Uv region 257±5nm
and 290±5 nm represents σ-π*, π-π* type intraligand
transitions. The prominent band at 419 ± 2 nm
attributable to LMCT (ligand centred charge transfer)
unveils the coordination of phenolate oxygen to the
nickel(II) centre. The additional d-d band at 616±3 nm
matching well with various reported d-d transitions of
similar nickel(II) complexes supports
a
five-
coordinated square-pyramidal geometry around the
nickel centre in all these complexes.
Results and Discussion
We report here the synthesis of series of binuclear
double-stranded helicates 1, 1’, 2, and 2’ using
nickel(II) chloride and enantiopure ligands L1 and L2.
These ligands were obtained using (R)-(+)-1,1’-
BNDA or (S)-(-)-1,1’-BNDA with 4-methyl-2,6-
diformylphenol or 4-tert-butyl-2,6-diformylphenol
following our recent report.[27] As a result we produced
SS
four different hexadentate helical ligands L1RR, L1 ,
L2RR & L2SS as shown in scheme 1. These enantiomeric
helical ligands efficiently formed a series of binuclear
double-stranded Ni(II) helicates (scheme 1).
The ESI-MS spectra (S1) depict a peak at m/Z =
RR
Figure 2. UV-Visible spectra of all the nickel helicates
recorded in THF (1x10-5M). The inset shows d-d band (1x
10-3M).
973.43 of monocationic species [Ni2L1 Cl]+ matching
with the calculated value 973.14 along with an intense
2
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10.1002/adsc.201901350
Advanced Synthesis & Catalysis
Chiroptical studies
Figure 4 (Figure S7- Figure S9). Thus, each Ni(II) ion
adapts an identical distorted square pyramidal
geometry by coordinating to two azomethine nitrogens
and two phenolate oxygens with the Ni atom sitting
0.416 Å above the square base and a chloride ion at the
apex. The relevant bond distances and angles are
presented in Table S1. The axially chiral BNDA units,
incorporated in the (L1SS) backbone coordinate to the
Ni-atoms via their azomethine nitrogens and are
twisted in an angle of ca. 71.38 and 69.29 in respect
to the biphenyl planes. The unit cell contains two
molecules of enantiopure nickel helicate (Figure S10)
consisting of S-BNDA in both sides confirm that chiral
self-sorting[28] persist in the chirality. The Flack
parameter 0.14(4) obtained for this complex indicates
the chiral nature of the complex.
Since these complexes are composed with enantiopure
BNDA, we inspired to investigate their chiroptical
properties. Accordingly, the CD spectra recorded for
all these complexes in THF are presented in Figure 3.
The CD spectra for 1 in Figure 3 revealed ligand
centred transitions at 271±4 (-ve cotton), 299±3 (+ve
cotton) nm and a broad band at 416±3 (+ve cotton) nm
attributable to LMCT matching to the electronic
ss
spectra. A similar spectra for [Ni2L1 Cl2] depicting an
opposite optical pattern the opposite optical signature
obtained for these enantiomeric counterparts
unambiguously attributed to the retention of chirality
of the ligand in the respective Ni(II) helicates. A
similar trend has been observed in 2 and 2’ helicates
(Figure S6). The retention of the chirality, thus infers
that the chirality of the ligand is transferred to the
metal centre resulting  geometrical chirality in 1
and 2, while in the respective enantiomeric
counterparts 1’, 2’, the nickel(II) metal center gains
chirality as revealed from their d-d band shown in
Figure 3.
Figure 4. Thermal ellipsoid plot with partial atom labelling
depicting the neutral dimeric complex 1’ (50% probability
factor for the thermal ellipsoids).
As indicated in the CD spectra (Figure 3), each dimeric
unit in the complex containing two enantiomeric
BNDA units, the RR isomers in the dimer promotes
 metal centred chirality around the Ni(II) metal
center is witnessed from their chromophoric rotation.
This observation in the crystallographic analysis gives
confidence that the opposite complex would certainly
have  from the respective SS–BNDA unit is
understandable from their CD spectra as stated above.
The  and  in the respective helicate is shown
below in Figure 5.
Figure 3. CD spectra of 1 & 1’ recorded in THF (1 x 10-5M).
Inset shows d-d band (1 x 10-3M)
Single Crystal X-ray structure analysis
Acetonitrile solution of complex 1’ upon slow
evaporation at room temperature yield a dark brownish
crystal suitable for single crystal x-ray analysis (S4) in
two weeks (Table 1). The crystal structure was solved
in a P21 space group. The structural analysis shows a
neutral binuclear double-stranded Ni(II) helicate
complex 1’, which possesses two binaphthyl diamine
and two 4-MDFP units that incorporate two Ni(II)–Cl
centers (Figure 4). The helically twisted macrocycle-
type ligand (L1SS) in 1’ possesses two metal binding
domains, each consisting of an N2O2 chromophoric
compartments with two azomethine nitrogens, N1 and
N2, [d(Ni1–N1) = 1.96(2)Å, d(Ni1–N2) = 2.03(3)Å]
and two phenolate oxygens, O1 and O2 [d(Ni1–O1) =
1.952(18) Å and d(Ni1–O2) = 2.04(3) Å]. The selected
bond distances and bond angles are presented in table
S1. These central phenolate oxygens bridge the Ni(II)
centers and form a planar Ni2O2 core as shown in
Figure 5. Schematic representation of P and M close-ended
[2+2]-helicates.
3
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10.1002/adsc.201901350
Advanced Synthesis & Catalysis
Table 1. Summary of the crystal data for 1’.
better homogeneous mixing. Accordingly, the solvent
variation like dichloromethane (Table 2, entry 6),
acetonitrile (Table 2, entry 7), chloroform (Table 2,
entry 8), methanol (Table 2, entry 9), tetrahydofuran
(Table 2, entry 10) and dichloroethane (Table 2, entry
11) are carried out. All these reactions were monitored
by TLC for complete consumption of substrate. This
systematic observation suggests that the reaction takes
14 h for complete conversion. All the solvents are
giving yield in the range of 65 - 85% and a moderate
ee upto 40-75% range. However among them DCM
giving best results than the other solvents i.e., 85 yield
and 75% ee, we have chosen DCM as suitable solvent
for this catalyst system and moved ahead for further
optimisation (Table 2, entry 6).
[Ni2L1SSCl2] 1’
C58 H38 Cl2 N4 Ni2 O2
1011.24
100
monoclinic
P21
17.5098(17)
10.6620(9)
17.5153(16)
90
Identification code
Empirical formula
Formula weight
Temperature/K
Crystal system
Space group
a/Å
b/Å
c/Å
α/°
β/°
γ/°
105.807(5)
90
3146.27
Volume/Å3
Z
2
Table 2. Screening of catalyst and solvent[a]
ρcalcg/cm3
μ/mm-1
1.067
0.720
F(000)
1040
Crystal size/mm3
Radiation
0.21 0.13 0.11
Mo-Kα (λ = 0.71073)
2Θ range for data collection/° 2.26 to 23.588
Reflections collected
Independent reflections
48356
Entry Catalyst Solvent
Yield[b] (%)
ee[c](%)
14249 [Rint = 0. 1478,
Rsigma = 0.1967]
14249/3110/1184
0.926
R1 = 0.0915, wR2 =
0.2273
1
2
3
4
5
6
7
8
Blank
Toluene
Toluene
Toluene
Toluene
Toluene
CH2Cl2
CH3CN
CHCl3
42
81
80
78
77
85
78
79
70
65
76
---
Data/restraints/parameters
Goodness-of-fit on F2
Final R indexes [I>=2σ (I)]
1
1’
2
2’
1
60(S)
59(R)
56(S)
55(R)
75(S)
50(S)
65(S)
50(S)
40(S)
64(S)
Final R indexes [all data]
R1 = 0.1860, wR2 =
0.2891
1
1
Largest diff. peak/hole / e Å-3 0.68/-0.60
Flack parameter
CCDC
0.14(4)
1957380
9
10
11
Methanol
THF
CH3CHCl2
1
1
1
Catalysis
[a]
All the reactions were carried out by 0.5mmol of
The successful synthesis of these enantiopure Ni(II)
helicates and their detailed chiroptical studies,
encouraged us to apply them as catalysts for
enantioselective Michael addition reactions of
nitroalkenes to nitroalkanes using 1,3-dicarbonyl
compounds. Initially, we have screened all four
complexes as catalysts for this reaction with various
solvents. We first checked the reaction without
catalyst, but in the presence of lutidine as a base,
toluene as solvent, diethyl malonate as nucleophile and
-nitrostyrene as electrophile. This reaction produced
racemic 1b with 42% yield (Table 2, entry 1).
Following the progress of the reaction, we inspired to
use all these enantiopure helicates as catalysts aiming
to achieve high enantioselectivity. Accordingly all
these enantiopure nickel(II) double stranded - helicates
1, 1’, 2 and 2’ were adapted as catalysts (Table 2, entry
2-5). Interestingly all these complexes have produced
1b with good yield ranging 77-81% and moderate ee
with a range of 55-60%. All these catalysts producing
almost similar catalytic results, the products differ in
their stereoisomer. Among all, the catalyst 1, has
produced good yield (81%) and ee (60%). Hence 1 has
been chosen as catalyst for further screening of
reaction conditions (Table 2, entry 2). Then we
screened the reaction with different solvents for the
nitrostyrene, 1 equivalant of diethylmalonate, 1 mmol of
DIPEA and 3mL solvent used and the reaction time is 14h,
[b] isolated yield, [c] calculated by using UFLC phenomenox
Lux cellulose-1 column.
Then we checked the reaction without base but we did
not get better results (Table 3, entry 1) suggesting that
the external base is necessary to facilitate the
deprotonation of active methylene group of the
substrate. Hence, we moved to screening of various
bases, the tributylamine produced 1b with 80% yield
and 55% ee (Table 3, entry 2), triethylamine (Table 3,
entry 3) gave 90% yield
tertamethylethylene diamine (TMEDA) gave 85%
yield 56% ee (Table 3, entry 4), 4-
&
40% ee,
&
dimethylaminopyridine (4-DMAP) gave 85% yield &
45% ee (Table 3, entry 5), diisopropylethylamine
(DIPEA) gives good yield 93% and 80% ee (Table 3,
entry 6). Use of some inorganic base such as CaCO3
(Table 3, entry 7), K2CO3 (Table 3, entry 8) gave
moderate yields 65 & 50 % and ee 33 & 25%
respectively. Amongst all, DIPEA (Table 3, entry 6)
giving best results (93% yield and 80% ee), it has been
chosen as a best deprotonating agent for this reaction
with the catalyst 1.
4
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10.1002/adsc.201901350
Advanced Synthesis & Catalysis
Table 3. Screening of base[a]
7
8
9
10
11
12
10
2
2
2
2
RT
60
40
20
10
0
88
90
95
96
80
70
85
75
85
88
87
86
2
[a]
Entry
Base
Yield[b] (%) ee[c] (%)(S)
All the reactions were carried out by 0.5mmol of
nitrostyrene, 1mmol of diethylmalonate, 1mmol of
DIPEA and 3mL solvent used and the reaction time is 14h
1
2
3
4
5
6
7
8
--
10
80
90
85
85
93
65
50
40
55
40
56
45
80
33
25
Tributylamine
Triethylamine
TMEDA
4-DMAP
DIPEA
all the substrate were monitored by TLC and completely
consumed, [b] isolated yield,
calculated by using UFLC
[c]
phenomenox Lux cellulose-1 column.
CaCO3
K2CO3
Temperature being one of the important parameter on
such enantioselective reaction, next we optimised the
reaction temperature. Accordingly, we screened the
reaction varying temperatures from 60 to 0oC and the
respective data are presented in Table 4 (entry 8-12).
The rise in temperature from RT to 40C and 60C
(Table 4, entry 8, 9) showed significant loss in ee (85
& 75% respectively) yield (95 & 90% respectively).
[a]
All the reactions were carried out by 0.5mmol of -
nitrostyrene, 1mmol of diethylmalonate, 1mmol of base and
3mL solvent used and the reaction time is 14h. [b]isolated
[c]
yield,
calculated by using UFLC phenomenox Lux
cellulose-1 column.
o
While reducing the temperature from RT to 20 C
(Table 4, entry 10), 10 oC (Table 4, entry 11), and 0 oC
(Table 4, entry 12), the yield falling 96%, 80% and
70% respectively, the ee is maintained to remain 87-
88%. Hence, we have chosen RT (25±2C) as
optimized temperature as both on higher as well as
lowering from RT caused significant loss of yield and
ee. Finally, the optimised conditions derived from the
above systematic experiments suggests that DCM as
solvent, DIPEA as base, 2mol% catalyst load and RT
as optimised temperature.
Next in order to optimise the catalyst amount, we
varied different amount of catalyst from 1 – 10 mol%.
In our first attempt, we increased the loading from 0.5
to 1 mol% which gave better yield 94% & ee 83%
(Table 4, entry 1). Then 1.5 mol% (Table 4, entry 2)
gave 96% yield and 85% ee. Similarly, 2 mol% (Table
4, entry 3) gave 98% yield and 90% ee. Thus the
increase in the catalyst load was found to increase the
yield and ee of 1b. Hence, we thought to increase
further like 2.5 mol% gave 98% yield, 89% ee (Table
4, entry 4), 3 mol% produce 95% yield, 87% ee (Table
4, entry 5), 4 mol% produce 92% yield, 86% ee (Table
4, entry 6). In this series, the 10 mol% catalyst load
produced 88% yield, 85% ee (Table 4, entry 7). From
this series of experiments, it is concluded that the
increasing of the catalyst amount in the range 1 mol%
to 2mol% show an increasing trend of yield and ee. But
beyond 2.5 mol% upto 4 mol% reveals a gradual
decline in the yield cum ee is visible (Table 4, entries
4-6). A further increase in the catalyst load upto 10
mol% depict a dramatic fall in the yield and ee. Hence
the 2 mol% was chosen as an optimum amount of
catalyst for this reaction (Table 4, entry 3).
Upon succeeding the optimisation of reaction
conditions, then we have screened scope of the
substrates of Michael donors containing different
active methylene groups by keeping the -nitro styrene
as shown in chart-1 (1a - 9a). Consequently, we have
screened various active methylene substrates covering
diethylmalonate
1a,
malonyl
chloride
2a,
malononitrile 3a, adapting the above optimised
conditions. The diethyl substituted active-methylene
group in diethylmalonate 1a gave product 1b with
good yield 98% and ee 90% (Chart-1, 1b). The
malonyl chloride 2a gave 2b with 96% yield and 89%
ee (Chart-1, 2b). Then the malononitrile 3a produced
3b with yield of 98%, generated ee 78% (Chart-1, 3b).
Using ethyl cyanoacetate, (4a) ethyl bromoacetate(5a)
as substrates produced 4b & 5b in 90 & 92% yield and
Table 4. Screening of Catalyst loading and temperature[a]
80
& 78% ee respectively. The methyl 2-
pyridylacetate (6a) and ethyl 2-pyridylacetate (7a)
produced 6b & 7b in 88, 86% yield and 74, 76% ee
respectively. Then we extended our substrate scope to
barbituric acid (8a) and dimedone (9a) which
produced (8b) and (9b) with good yield (78 & 90%)
and ee (72 & 86%). The screening of substrates thus
suggested that the catalyst 1 is catalysing all the
substrates almost equally, but provide the best results
in the case of diethylmalonate (Chart-1, 1b) than the
other substrates.
Entry
Catalyst
Temp
Yield[b]
%
ee[c](S)
%
load (mol%)
C
1
2
3
4
5
6
1
1.5
2
2.5
3
RT
RT
RT
RT
RT
RT
94
96
98
98
95
92
83
85
90
89
87
86
4
5
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10.1002/adsc.201901350
Advanced Synthesis & Catalysis
Chart 1. Screening of substrate[a]
Then we moved to screen the Michael acceptors and
the results are depicted in Table 5 (entry 1-10). Initally,
we used chalcone (10a) as a Michael acceptor with
diethylmalonate (1a) leads to 10b (Table 5, entry 1) in
better yield (95%) and moderate ee (76%) which is
lesser than the β-nitrostyrene product (1b). Hence we
have screened different substituted β-nitrostyrenes
(11a-19a) as shown in Table 5. The electron
withdrawing (11a-14a), donating (15a), different
aromatic (16a-17a) and aliphatic nitroalkenes (18a-
19a) were adapted. The electron withdrawing group at
the nitrostyrene provides (Table 5, entry 2-5) better
yield in the range of 90-98% and ee in 86-94%. While
the electron donating methoxy substituted nitrostyrene
15a leads to produce 15b in 88% yield and 80 % ee
(Table 5, entry 6). Then the use of
nitrovinyl)anthracene (16a) and
9-(2-
2-(2-
nitrovinyl)pyridine (17a) as Michael acceptors (Table
5, entry 7-8) leads to 16b & 17b in 92 & 93 % yield
and 88 & 85 % ee respectively. We also used aliphatic
olefins (Table 5, entry 9-10) such as 1-nitropent-1-ene
(18a) and 1-nitrohept-1-ene (19a) leading to 18b and
19b in 82 & 80% yield and 66 & 60 ee respectively.
As a result of screening different Michael acceptors,
the 4-flouro substitued β-nitrostyrene (11a) produced
11b in good yield (98%) and ee (94%) suggesting that
electron withdrawing group in the phenyl ring of
niitrostyrene supporting the formation of carbocation
which further facilitates the interaction of carbanion of
diethylamalonate. However, the aromatic Michael
acceptors are found to give better results than the
aliphatics suggesting the possible strong -
interaction between the aromatic nitrostyrenes and
catalyst matching to our earlier observation derived in
our earlier work.[27]
Table 5. Screening of Michael acceptor[a]
Entry
1
R’‘-X
Yield[b]
ee[c] (S)
95 (10b)
76
2
3
4
5
98 (11b)
95(12b)
90 (13b)
92(14b)
94
92
90
86
[a]All the reactions were carried out by 0.5mmol of
nitrostyrene, 1mmol of dialkylmalonate, 1mmol of
DIPEA and 3mL solvent used and the reaction time is 14h
all the substrate were monitored by TLC and completely
consumed. [b](1:2) ratio of DCM:Toluene used. Yield shown
here is isolated yield, ee calculated by using UFLC
phenomenox Lux cellulose-1 column & amylose-2 column.
6
7
88(15b)
92(16b)
80
88
6
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10.1002/adsc.201901350
Advanced Synthesis & Catalysis
8
93(17b)
85
9
10
82(18b)
80(19b)
66
60
[a]
All the reactions were carried out by 0.5mmol of
Michael acceptor, 1mmol of diethylmalonate, 1mmol of
DIPEA and 3mL solvent used and the reaction time is 14h
all the substrate were monitored by TLC and completely
[c]
consumed, [b] isolated yield,
calculated by using UFLC
phenomenox Lux cellulose-1 column & amylose-2 column.
Figure 6. Stereochemical model of catalyst-substrate
interactions, (a) Catalyst 1 and 1’ involve in the favour of
Re and Si face attack respectively, (b) Catalyst 1’ favoured
Re face stereo induction to R-Product.
At this juncture, a comparative analysis was carried
out in view of gaining better understanding about the
efficiency of the present catalyst. In this regard we
have screened few important catalysts 3-7 comprising
both Ni(II)-bimetallic and monometallic complexes
incorporating the respective ligands,[26,30] La, Lb, Lc, Ld
and Le (Figure S12). Incorporating Ni(II), the
complexes 3-5 are monometallic while 6 &7 are
obtained as bimetallic. Adapting the above optimized
reaction condition, the catalytic reaction between the
substrates 1a &12a, produce 12b as product. All the
bimetallic complexes (5-7) provides yield 80-85%
with ee ranging 70-86%, while the monomeric
complexes (3 & 4) are giving yield 90, 75% with ee
80,85% respectively. This detailed comparative
catalytic study again re-establish that the present
bimetallic helicate catalyst 1 is superior. Thus the
encouraging yield and ee, and the comparative study
together inspired us to undertake the recyclability test
for the catalyst 1. Accordingly, the catalyst 1 was
tested for its catalytic stability adapting 4-Fluoro--
nitrostyrene and diethylmalonate as standard
substrates adapting the above optimised conditions.
The catalyst was recycled upto nine times, where
significant retention of yield and ee were maintained
as shown in Figure 7. The recovered catalyst was
analysed by FT-IR studies and was found to match
with fresh catalyst (Figure S13) at the end of the 9th
cycle.
Scheme 2. Probable mechanism for asymmetric Michael
addition reaction catalysed by nickel helicate.
Based on the results and the literature studies we
propose here a probable mechanism for the Michael
[29]
addition reaction
in scheme 2. The Ni-complex
initially interact with diethyl malonate via carbonyl
group as shown in TS-1. Following this, the organic
base DIPEA remove the hydrogen ion from active
methylene compound as shown in TS-2 (Figure S11).
The deprotonated diethyl malonate in its resonance
structures existing in both carbanion and enolate forms
are known to associate with the delocalisation of
electron pair. On the other hand, the nitrostyrene
approaches to Ni(II) center simultaneously weakening
the Ni-Cl bond. Upon establishing the strong
interaction of nitrostyrene, the chloride ion is detached
from the Ni(II) center (TS-3). The carbanion attacks
the -carbon of nitrostyrene through Si face attack as
illustrated in the Figure 6a which lead to S-11b while
on the other hand the opposite isomer catalyst 1’ leads
to Re face attack leads to R-11b (Figure 6a). The
crystal structure of catalyst 1’ is used for depicting the
stereochemical induction model shown in figure 6b.
This clearly suggest that the Re face attack favoured
the formation of R-11b.
7
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10.1002/adsc.201901350
Advanced Synthesis & Catalysis
template method. This helically structured dinuclear
double-stranded Ni(II) complexes were characterised
by ESI-MS, FT-IR and CD. The detailed chiroptical
spectral investigation suggest that these helicates
retains the chirality of the ligand in its complexes; A
transfer of chirality from ligand to metal center has
also been established without any ambiguity. This
detailed study shows that the chirality transfer from
ligand to metal produced in the case of 1, 2 where
the ligand is in RR form. A similar approach in the case
of 1’, 2’ complexes has produced metal centered
chirality. This chirally active binuclear helicates were
further applied as catalysts in asymmetric Michael
addition of 1,3-dicorabonyl compound with 4-Fluoro-
-nitrostyrene and was found to produce maximum
yield of 98% and 94% ee in the case of
diethylmalonate. Further, the catalyst 1 giving better
result the respective recyclability experiment has
proven to run upto nine cycles without any significant
loss in the yield and ee. The catalytic system also been
applied to synthesis of S-warfarin an anti-coagulant
drug in good yield (98%) and ee (96%).
Figure 7. Recyclability of the catalyst 1
Synthesis of S-Warfarin and its derivatives
In a view to understand the impact of the present
catalyst, we inspired to investigate the efficiency of the
catalyst 1 on the synthesis of enantioselective warfarin.
In addition the enantioselective Michael addition of 4-
hydroxy coumarin and 4-phenylbut-3-en-2-one was
adapted to achieve (S)-Warfarin (Scheme 3) which is
an effective anticoagulnt for preventing thrombosis
and embolism. The literature survey suggests that
there are various organcatalyts mainly functionalized
with amine and imine motiefs[31] and metal[32] complex.
Adapting catalyst 1 and using the above optimized
reaction condition, the substrate benzylideneacetone
(20a) and chalcone (21a) with 4-hydroxycoumarin, we
could achieve the respective warfarin derivates with
excellent enantioselectivity shown in scheme 3. The
(20b) was obtained in good yield (98%) and ee (96%),
and the (21b) with 95% yield and 76% ee.
Experimental Section
Materials and methods
2-hydroxy-5-methyl-1,3-benzenedicarboxaldehyde, 4-tert-
Butyl-2,6-diformylphenol,
(R)-(+)-1,1’-Binaphyl-2,2’-
diamine, (S)-(-)-1,1’-Binaphyl-2,2’-diamine Nickel(II)
chloride hexahydrate were purchased from Aldrich & Co.
All these chemicals were used as received without any
further purification. IR spectra were recorded using KBr
pellets (1% w/w) on a Perkin-Elmer Spectrum GX FT-IR
spectrophotometer. Electronic spectra were recorded on a
Shimadzu UV 3101 PC spectrophotometer. Mass analyses
were performed using the positive electron spray ionization
(ESI+) technique on a waters Q TOF-micro mass
1
spectrometer. H, 13C NMR spectra were recorded on a
Bruker Avance DPX 200 and 500 MHz FT-NMR
spectrometer. Chemical shifts for proton resonances are
reported in ppm (δ) relative to tetramethylsilane (TMS). The
CD spectra were recorded on a JASCO 815 Spectrometer.
The enantioselectivity of the monobenzoylated product was
determined by UFLC (Shimadzu SCL-10AVP) and
ThermoFisher Scientific ultimate 3000 UHPLC using chiral
columns (Phenomenox Lux cellulose-1 and Amylose-2
column).
Scheme 3. Enantioselective synthesis of (S)-warfarins[a]
Synthesis of Ni(II) helicate: The 5-methyl-2-
hydroxyisophthalaldehyde
(16.4mg,
0.1mmol)
in
acetonitrile (5mL), then 0.1mmol of triethylamine (13.9l)
and Nickel(II) chloride hexahydrate (0.1mmol, 23.8mg)
were added to the solution with constant stirring at room
temperature for 30mniutes. To this R-(+)-1, 1’-Binaphthyl-
2, 2’-diamine (28.4 mg, 0.1mmol) was added drop by drop.
After the complete addition of amine, the mixture has
refluxed for 36 h. The solvent was removed by rotavapour,
and the resulting solid material dissolved with
dichloromethane, was washed with water (3x10ml), the
organic layer separated and dried. [Ni2(L1RR)Cl2] (1).
C58H38Cl2Ni2N4O2, Yield 80 %. UV vis.  (ε, cm-1) = 256
(11,229), 289 (7,553), 419(4,072), 617(14) nm. FT-IR
(KBr) ν = 3148, 1632, 1538, 1503, 1401, 1343, 1327, 1269,
1218, 1202, 1146, 1055, 999, 980, 941, 870, 824, 771, 747,
696, 665, 621, 577, 530, 513, 482, 437 cm-1. [ESI-MS]+
Chemical formula for [Ni2(L1RR)Cl]+ C58H38ClN4Ni2O2 m/z
Cal(found): 973.13(973.45) and [Ni2(L1RR)Cl.H2O]+
C58H40ClN4Ni2O3 m/z Cal(found): 991.15(991.47).
Elemental Analysis: Mol. Formula. C58H44Cl2N4 Ni2O5.
[a]
All the reactions were carried out by 0.5mmol of
hydroxycoumarin, 0.55mmol of enone, 0.5mmol of
DIPEA and 3mL solvent used and the reaction time is 16h
all the substrate were monitored by TLC and completely
consumed, Yield presented here are isolated yield and the
ee calculated by using UFLC phenomenox amylose-2
column.
Conclusion
In conclusion a series of enantiopure Ni(II) helicates
were successfully synthesised by simple one pot metal
8
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10.1002/adsc.201901350
Advanced Synthesis & Catalysis
Calc(found) C, 65.39(65.02), H, 4.16(4.32), N,
5.26(5.45) %.
References
[1] a) K. Mikami, M. Yamanaka, Chem. Rev. 2003, 103,
3369-3400; b) P. J. Walsh, H. Li, C. A. de Parrodi, Chem.
Rev. 2007, 107, 2503-2545; c) M. Shibasaki, N.
Yoshikawa, Chem. Rev. 2002, 102, 2187-2209; d) A. J.
Boersma, R. P. Megens, B. L. Feringa, G. Roelfes, Chem.
Soc. Rev. 2010, 39, 2083–2092; e) J. T. Mohr, M. R.
Krout, B. M. Stoltz, Nature, 2008, 455, 323-3322008; f)
D. Yang, L. Wang, F. Han, D. Zhao, B. Zhang, R. Wang,
Angew. Chem. Int. Ed. 2013, 52, 6739-6742.
[Ni2(L1SS)Cl2], (1’). Similar procedure followed from above
procedure except S-BNDA used instead of R-BNDA. The
single crystal obtained by room temperature slow
evaporation of acetonitrile solution of [Ni2(L1SS)Cl2] to
yield dark brown needle type crystals suitable for X-ray
analysis. C58H38Cl2Ni2N4O2, Yield 82 %. UV vis.  (ε, cm-
1) = 256 (16,650), 290 (11,333), 420 (6038), 615 (15) nm.
FT-IR (KBr) ν =3420, 3148, 1631, 1542, 1507, 1404, 1326,
1222, 1202, 1120, 1066, 1005, 870, 822, 773, 751, 701, 658,
625, 568, 486 cm-1. [ESI-MS]+ Chemical formula for
+
[Ni2(L1SS)Cl2.H2O.H+]+
C58H41Cl2N4Ni2O3
m/z
Cal(found): 1027.13(1027.24. Elemental Analysis: Mol.
Formula. C60H42Cl6N4Ni2O2. Calc(found) C, 61.02(61.26),
H, 3.58(3.74), N, 4.74(4.89) %.
[2] a) Z. Du, Z. Shao, Chem. Soc. Rev. 2013,42, 1337-1378;
b) Y. Yamashita, T. Yasukawa, W. J. Yoo, T.
Kitanosono, S. Kobayashi, Chem. Soc. Rev. 2018, 47,
4388-4480
[Ni2(L2RR)Cl2] (2). Similar procedure followed from above
procedure
except
4-tert-Butyl-2,6-diformylphenol.
C58H38Cl2Ni2N4O2, Yield 80 %. UV vis.  (ε, cm-1) =
257(18,440), 289(12,533), 418(6716), 616 (16) nm. FT-IR
(KBr) ν = 3441, 3143, 1630, 1542, 1504, 1403, 1327, 1224,
1203, 1165, 1146, 1061, 1025, 974, 946, 891, 865, 830, 802,
774, 747, 692, 668, 619, 576, 510, 481 cm-1. [ESI-MS]+
[3] a) S. Saravanan, N. H. Khan, R. I. Kureshy, S. H. R.
Abdi, H. C. Bajaj, ACS Catal. 2013, 3, 873-2880; b) T.
Miura, K. Imai, M. Ina, N. Tada, N. Imai, A. Itoh, Org.
Lett. 2010, 12, 1620-1623; c) M. P. Carroll, P. J. Guiry,
Chem. Soc. Rev. 2014, 43, 819-833; d) V. Blanco, D. A.
Leigh, V. Marcos, J. A. Morales-Serna, A. L.
Nussbaumer, J. Am. Chem. Soc. 2014, 136, 4905-4908
Chemical
formula
for
[Ni2(L2RR)Cl2(H2O)H+]
+
C64H53Cl2N4Ni2O3 m/z Cal(found): 1111.22(1111.2981).
Elemental Analysis: Mol. Formula. C64H52Cl2N4Ni2O3.
Calc(found) C, 69.04(69.35), H, 4.71(4.54), N,
5.03(4.95) %.
[4] a) M. Hall, A. S. Bommarius, Chem. Rev. 2011, 111,
4088-4110; b) Z. Guan, J. Song, Y. Xue, D. C. Yang, Y.
H. He, J. Mol. Cat. B: Enzym. 2015, 111, 16-20; c) R. Li
Z. L. Li, H. Y. Zhou, Y. H. He, Z. Guan, J. Mol. Cat. B:
Enzym. 2016, 126, 90-98.
[Ni2(L2SS)Cl2] (2’). Similar procedure followed from above
procedure except 4-tert-Butyl-2,6-diformylphenol and S-
BNDA used instead of R-BNDA. C58H38Cl2Ni2N4O2, Yield
80 %. UV vis.  (ε, cm-1) = 256 (21,874), 290 (14,816), 419
(7,986), 617 (23) nm. FT-IR (KBr) ν = 3442, 3148, 1626,
1590, 1539, 1507, 1404, 1327, 1287, 1224, 1203, 1163,
1145, 1059, 1025, 974, 946, 891, 867, 828, 804, 773, 748,
[5] a) Y. Hamashima, D. Sawada, M. Kanai, M. Shibasaki,
J. Am. Chem. Soc.1999, 121, 2641-2642; a) S. Mouri, Z.
Chen, H. Mitsunuma, M. Furutachi, S. Matsunaga, M.
Shibasaki, J. Am. Chem. Soc. 2010, 13, 1255-1257; c) R.
E. Douthwaite, Annu. Rep. Prog. Chem., Sect. A, 2004,
100, 385-406.
692, 324, 574, 510, 477 cm-1. [ESI-MS]+ Chemical formula
+
for [Ni2(L2SS)Cl2(H2O)H+] C64H53Cl2N4Ni2O3
m/z
Cal(found): 1111.22(1111.3111). Elemental Analysis: Mol.
Formula. C64H54Cl2N4Ni2O4. Calc(found) C, 67.94(68.02),
H, 4.81(4.72), N, 4.95(4.68) %.
General procedure for Asymmetric Michael Addition
reaction.
[6] a) J. Wuerges, J. W. Lee, Y. Yim, H. S. Yim, S. Kang,
K. D. Carugo, Proc. Natl. Acad. Sci. U.S.A. 2004, 101,
8569-74; b) V. Pelmenschikov, P. E. M. Siegbahn, J. Am.
Chem. Soc. 2006, 128, 7466-7475; c) Y. Li, D. B.
Zamble, Chem. Rev. 2009, 109, 4617-4643.
A dry 5 mL flask, equipped with a magnetic stirring
bar, was charged with catalyst (2 mol %) and freshly
o
distilled dry DCM (3mL) at RT (25±2 C). Corresponding
malonate (1 mmol), was then added, and the resulting
mixture was stirred at RT. Then the -nitrostyrene
(0.5mmol) and DIPEA (1mmol) were successively added to
a mixture. The mixture was stirred at the same temperature
until the 14 h or complete consumption of substrate through
monitoring by TLC. After completion of reaction, the
solvent was evaporated by rotavapour and the resulting solid
mixture was washed with ethyl acetate: hexane (20:80, 8-10
times) to separate catalyst from the mixture. Finally the
crude product was purified by column chromatography
(silica gel: 100-200 mesh using ethyl acetate and hexanes)
to give corresponding product. Enantiomeric excess was
determined by HPLC using Phenomenox Lux cellulose-1
column and Amylose-2 column using isopropanol and
hexanes (10% and 90%) as eluting agent. The absolute
configuration of the product were assigned by comparison
HPLC profile with reported literature. [33]
[7] a)P. A. Karplus, M. A. Pearson, R. P. Hausinger, Acc.
Chem. Res.1997, 30, 330-337; b) B. Krajewska, R. v.
Eldik, M. Brindell, J. Bio. Inorg. Chem. 2012, 17, 1123-
1134.
[8] S. Matsunaga and M. Shibasaki, Chem. Commun. 2014,
50, 1044-1057.
[9] J. Park, S. Hong, Chem. Soc. Rev. 2012, 41, 6931-6943.
[10] a) J. M. Brunel, Chem. Rev. 2005, 105, 857-898; b) M.
Okada, K. Kaneko, M. Yamanaka, S. Shirakawa, Org.
Biomol. Chem. 2019, 17, 3747-3751; c) V. Annamalai,
E. F. DiMauro, P. J. Carroll, M. C. Kozlowski, J. Org.
Chem. 2003, 68, 1973-1981.
[11] a) Z. Chen, H. Morimoto, S. Matsunaga, M. Shibasaki,
J. Am. Chem. Soc. 2008, 130, 2170-2171; b) Y. Kato, M.
Furutachi, Z. Chen, H. Mitsunuma, S. Matsunaga, M.
Shibasaki, J. Am. Chem. Soc. 2009, 131, 9168-9169.
Acknowledgements
CSMCRI communication number CSIR-CSMCRI 137/2019.
Author EC and RA acknowledge the CSIR for SRF grants. The
authors gratefully acknowledge DST-SERB New Delhi (Project No.
SR/S1/IC-23/2011) for funding. Members of AESDCIF of CSMCRI
are acknowledged for their instrumentation support.
[12] a) H. Egami, T. Oguma, T. Katsuki, J. Am. Chem. Soc.
2010, 132, 5886; b) K. Suyama, Y. Sakai, K. Matsumoto,
B. Saito, T. Katsuki, Angew. Chem., Int. Ed. 2010, 49,
9
This article is protected by copyright. All rights reserved.

10.1002/adsc.201901350
Advanced Synthesis & Catalysis
797; c) K. Matsumoto, T. Oguma, T. Katsuki, Angew.
Larrow, B. A. Stearns, J. M. Vance, Angew. Chem., Int.
Ed. 2000, 39, 213; c) M. Movassaghi, M. A. Schmidt,
Angew. Chem., Int. Ed. 2007, 46, 3725; d) M. A.
Schmidt, M. Movassaghi, Synlett. 2008, 313; e) H.
Mitsunuma, M. Shibasaki, M. Kanai, S. Matsunaga,
Angew. Chem., Int. Ed. 2012, 51, 5217; f) H. Mitsunuma,
S. Matsunaga, Chem. Commun. 2011, 47, 469.
Chem., Int. Ed. 2009, 48, 7432; d) B. Saito, H. Egami, T.
Katsuki, J. Am. Chem. Soc. 2007, 129, 1978; e) B. Saito,
T. Katsuki, Angew. Chem., Int. Ed. 2005, 44, 4600; f) M.
Furutachi, S. Mouri, S. Matsunaga, M. Shibasaki, Chem.
Asian. J. 2010, 5, 2351. g) S. Kobayashi, M. Sugiura, H.
Kitagawa, W. W. L. Lam, Chem. Rev. 2002, 102, 2227;
h) S.-X. Wang, M.-X. Wang, D.-X. Wang, J. Zhu, Org.
Lett. 2007, 9, 3615; i) H. Tsuruta, K. Yamaguchi, T.
Imamoto, Chem. Commun. 1999, 1703; j) B. Wu, J. C.
Gallucci, J. R. Parquette, T. V. RajanBabu, Angew.
Chem., Int. Ed. 2009, 48, 1126.
[18] a) X.-T. Li, A.-D. Zhao, L.-P. Mo, Z.-H. Zhang, RSC
Adv. 2014, 4, 51580-51588; b) G. M. Ziarani, F. Aleali,
N. Lashgari, RSC Adv. 2016, 6, 50895-50922; c)H. J. Al-
Najjar, A. Barakat, A. M. Al-Majid, Y. N. Mabkhot, M.
Weber, H. A. Ghabbour, H. K. Fun, Molecules, 2014, 19,
1150-1162; d) S. J. Kalita, H. Mecadon, D. C. Deka,
RSC Adv. 2014, 4, 10402-10411; e) M. Rombola, C. S.
Sumaria, T. D. Montgomery, V. H. Rawal, J. Am. Chem.
Soc. 2017, 139, 5297-5300; f) C. Segovia, A. Lebrêne,
V. Levacher, S. Oudeyer, J. F. Brière, Catalysts, 2019,
9, 13; .g) Q. Wang, W. Wang, L. Ye, X. Yang, X. Li, Z.
Zhao, X. Li, Molecules. 2017, 22, 1096.
[13] a) C. Palomo, M. Oiarbide, A. Laso, Eur. J. Org. Chem.
2007, 2561; b) J. Boruwa, N. Gogoi, P. P. Saikia, N. C.
Barua, Tetrahedron: Asymmetry. 2006, 17, 3315; c) C.
Palomo, M. Oiarbide, A. Mielgo, Angew. Chem., Int. Ed.
2004, 43, 5442; d) T. Ogawa, N. Kumagai, M. Shibasaki,
Angew. Chem., Int. Ed. 2013, 52, 6196; e) D. Uraguchi,
S. Nakamura, T. Ooi, Angew. Chem., Int. Ed. 2010, 49,
7562; e) T. Nitabaru, A. Nojiri, M. Kobayashi, N.
Kumagai, M. Shibasaki, J. Am. Chem. Soc. 2009, 131,
13860; f) D. Uraguchi, S. Sakaki, T. Ooi, J. Am. Chem.
Soc. 2007, 129, 12392. g) S. Handa, K. Nagawa, Y.
Sohtome, S. Matsunaga, M. Shibasaki, Angew. Chem.,
Int. Ed. 2008, 47, 3230; h) Y. Sohtome, Y. Kato, S.
Handa, N. Aoyama, K. Nagawa, S. Matsunaga, M.
Shibasaki, Org. Lett. 2008, 10, 2231.
[19] E. F. DiMauro, M. C. Kozlowski, Organometallics.
2002, 21, 1454-1461.
[20] E. F. DiMauro, M. C. Kozlowski, Org. Lett. 2001, 3,
1641-1644.
[21] a) J.-M. Lehn, A. Rigault, J. Siegel, J. Harrowfield, B.
Chevrier, D. Morast, Proc. Natl. Acad. Sci. USA. 1987,
84, 2565-2569. b) C. Piguet, G. Bernardinelli, G.
Hopfgartner, Chem. Rev. 1997, 97, 2005-2062; c) M.
Albrecht Chem. Rev. 2001, 101, 3457-3497.
[14] a) O.M. Berner, L. Tedeschi, D. Enders, Eur. J. Org.
Chem. 2002, 1877; b) J. Christoffers, G. Koripelly, A.
Rosiak and M. Rössle, Synthesis. 2007, 1279; c) H.
Tanabe, Y. Xu, B. Sun, S. Matsunaga, M. Shibasaki,
Heterocycles, 2012, 86, 611; d) M. Furutachi, Z. Chen,
S. Matsunaga, M. Shibasaki, Molecules. 2010, 15, 532;
e) Z. Chen, M. Furutachi, Y. Kato, S. Matsunaga, M.
Shibasaki, Angew. Chem., Int. Ed. 2009, 48, 2218; f) Y.
Kato, M. Furutachi, Z. Chen, H. Mitsunuma, S.
Matsunaga, M. Shibasaki, J. Am. Chem. Soc. 2009, 131,
9168; g)T. Okino, Y. Hoashi, T. Furukawa, X. Xu, Y.
Takemoto, J. Am. Chem. Soc. 2005, 127, 119-125; h) T.
Okino, Y. Hoashi, Y. Takemoto, J. Am. Chem. Soc. 2003,
125, 12672-12673
[22] a) M. Boiocchia, L. Fabbrizzi, Chem. Soc. Rev. 2014,
43, 1835-1847; b) J Sahoo, R. Arunachalam, P.S.
Subramanian, E. Suresh, A. Valkonen, K. Rissanen, M.
Albrecht. Angew Chem Int Ed Engl. 2016, 55, 9625-
9629.
[23] H. Miyake, H. Tsukube, Chem. Soc. Rev. 2012, 41,
6977-6991.
[24] a) T. D. Owens, F. J. Hollander, A. G. Oliver, J. A.
Ellman, J. Am. Chem. Soc. 2001, 123, 1539-1540; b)Y.
Cui, C. He, J. Am. Chem. Soc. 2003, 125, 16202. b) Y.
Cui and C. He, Angew. Chem. Int. Ed. 2004, 43, 4210;
c) H. L. Kwong, H. L. Yeung, W.S. Lee, W. T. Wong,
Chem. Commun. 2006, 4841-4843; d) C. T. Yeung, H.
L. Yeung, C. S. Tsang, W.Y. Wong, H. L. Kwong, Chem.
Commun. 2007, 5203-5205; e) T. Hasegawa, Y. Furusho,
H. Katagiri, E. Yashima, Angew. Chem. Int. Ed. 2007,
46, 5885 -5888; f) R. K. C. Sham, H. L. Yeung, S. M.
Yiu, T. C. Lau, H. L. Kwong, Dalton Trans. 2010, 39,
9469-9471; g) P. M. Selvakumar, P. Y. Jebaraj, J. Sahoo,
E. Suresh, K. J. Prathap, R. I. Kureshy, P. S.
Subramanian, RSC Adv. 2012, 2, 7689-7692; h) Y. Liu,
X. Xi, C. Ye, T. Gong, Z. Yang, Y. Cui, Angew. Chem.
Int. Ed. 2014, 53, 13821 -13825; h) Y. Fang, W. Gong,
L. Liu, Y. Liu, Y. Cui, Inorg. Chem. 2016, 55, 10102-
10105.
[15] a) S. Handa, V. Gnanadesikan, S. Matsunaga, M.
Shibasaki, J. Am. Chem. Soc. 2010, 132, 4925-4934; b)
M. M. B. Marques, Angew. Chem., Int. Ed. 2006, 45,
348; c) R. Gómez Arrayás, J. C. Carretero, Chem. Soc.
Rev. 2009, 38, 1940; d) B. Weiner, W. Szymanski, D. B.
Janssen, A. J. Minnaard, B. L. Feringa, Chem. Soc. Rev.
2010, 39, 1656; e) N. E. Shepherd, H. Tanabe, Y. Xu, S.
Matsunaga, M. Shibasaki, J. Am. Chem. Soc. 2010, 132,
3666.
[16] a)T. Komnenos, Justus Liebigs Ann. Chem. 1883,
218,145-169; b) H. Pellissier, Adv. Synth. Catal. 2015,
357, 2745 - 2780; c) J. H. Nelson, P. N. Howells, G. C.
DeLullo, G. L. Landen, R. A. Henry, J. Org. Chem. 1980,
45, 1246–1249; d) H. Suga, T. Kitamura, A. Kakehi, T.
Baba, Chem . Commun. 2004 , 1414 - 1415;e) D.
Kühbeck, G. Saidulu, K. R. Reddy, D. D. Díaz, Green
Chem. 2012, 14, 378.
[25] a) L. Wang, C. Xu, Q, Han, X. Tang, P. Zhou, R.
Zhang, G. Gao, B. Xu, W. Qin, W. Liu, Chem. Commun.
2018, 54, 2212-2215; b) L. Wang, R. Zhang, Q. Han, C.
Xu, W. Chen, H. Yang, G. Gao, W. Qin, W. Liu, Green
Chem. 2018, 20, 5311-5317; c) M. A. Gaona, F. Cruz-
[17] a) L. E. Overman, D. V. Paone, B. A. Stearns, J. Am.
Chem. Soc. 1999, 121, 7702; b) L. E. Overman, J. F.
10
This article is protected by copyright. All rights reserved.

10.1002/adsc.201901350
Advanced Synthesis & Catalysis
Martínez, J. Fernández-Baeza, L. F. Sánchez-Barba, C.
[31] a) A. Robinson, H. -Y. Li, Tetrahedron Lett. 1996, 37,
8321-8324; b) N. Halland, T. Hansen, K. A. Jørgensen,
Angew. Chem. Int. Ed. 2003, 42, 4955-4957; c) J. -W.
Xie, L. Yue, W. Chen, W. Du, J. Zhu, J. -G. Deng, Y. -
C. Chen, Org. Lett. 2007, 9, 413-415; d) M. Rogozińska,
A. Adamkiewicz, J. Mlynarski, Green Chem. 2011, 13,
1155-1157; e) R.-Q. Mei, X. -Y. Xu, Y. -C. Li, J. -Y. Fu,
Q. -C. Huang, L. -X. Wang, Tetrahedron Lett. 2011, 52,
1566-1568; f) X. Zhu, A. Lin, Y. Shi, J. Guo, C. Zhu, Y.
Cheng, Org. Lett. 2011, 13, 4382-4385; g) A. S.
Kucherenko, D. E. Siyutkin, A. G. Nigmatov, A. O.
Chizhov, S. G. Zlotin, Adv. Synth. Catal. 2012, 354,
3078-3086; h) S. Sabira, N. Rashid, S. Naz, B. Masood,
Int. J. Pharm. Pharm. Sci. 2013, 5, 177-181; i) M.
Rogozińska-Szymczak, J. Mlynarski, Tetrahedron:
Asymm. 2014, 25, 813-820; j) A. S. Kucherenko, V. G.
Lisnyak, A. O. Chizhov, S. G. Zlotin, Eur. J. Org. Chem.
2014, 3808-3813; k) N. Kausar, P. P. Ghosh, G. Pal, A.
R. Das, RSC Adv. 2015, 5, 60199-60207; l) R. Porta, M.
Benaglia, F. Coccia, S. Rossi, A. Puglisi, Symmetry.
2015, 7, 1395-1409; m) A. N. Shaik, R. Grater, M. Lull,
D. A. Williams, L. L. Ganc, T. Bohnert, B. W. LeDuc, J.
Chrom. B. 2016, 1008, 164-173; n) A. S. Kucherenko,
A. A. Kostenko, G. M. Zhdankina, O. Y. Kuznetsova, S.
G. Zlotin. Green Chem. 2018, 20, 754-759; o) V.
Modrocká, E. Veverková, M. Mečiarová, R Šebesta, J.
Org. Chem. 2018, 83, 13111-13120; p) L. Zhu, L. Zhang,
S. Luo, Org. Lett. 2018, 20, 1672-1675.
Alonso-Moreno, A. M. Rodríguez, A. Rodríguez-
Diéguez, J. A. Castro-Osma, A. Otero, A. Lara-Sánchez,
Dalton Trans. 2019, 48, 4218.
[26] a) E. Chinnaraja, R. Arunachalam, M. K. Choudhary,
R. I. Kureshy, P. S. Subramanian, Appl. Organometal.
Chem. 2016, 30, 95–101; b) E. Chinnaraja, R.
Arunachalam, and P. S. Subramanian, ChemistrySelect
2016, 1, 5331-5338.
[27] E. Chinnaraja, R. Arunachalam, E. Suresh, S. K. Sen,
R. Natarajan, P. S. Subramanian, Inorg. Chem. 2019, 58,
4465-4479.
[28] a) R. Pfukwa, P. H. J. Kouwer, A. E. Rowan, B.
Klumperman, Angew. Chem. 2013, 125, 11246-11250;
b) C. Provent, G. Bernardinelli, A. F. Williams, N.
Vulliermet, Eur. J. Inorg. Chem. 2001, 2001,
1963−1967.
[29] a) T. Saegusa, Y. Ito, S. Tomitra, H. Kinoshita, Bull.
Chem. Soc. Jpn. 1972, 45, 496-499; b) H. Brunner, B.
Hammer, Angew. Chem. 1984, 96, 305-306; Angew.
Chem. Int. Ed. Engl. 1984, 23, 312-313; c) A. G. M.
Barrett, G. G. Graboski, Chem. Rev. 1986, 86, 751-762.
[30] a) P. Muthupandi, S. K. Alamsetti, G. Sekar, Chem.
Commun. 2009, 3288-3290; b) H. Suga, A. Kakehi, S.
Ito, H. Sugimoto, Bull. Chem. Soc. Jpn. 2003, 76, 327-
334; c) N. Takenaka, Y. Huang, V. H. Rawal,
Tetrahedron. 2002, 58, 8299-8305; d) J. Gao, J. H.
Reibenspies, R. A. Zingaro, F.R.Woolley, A. E. Matell,
A. Clearfield, Inorg Chem.2005, 44, 232-241; e) E.
Chinnaraja, R. Arunachalam, J. Samanta, R. Natarajan,
P. S. Subramanian, Appl. Organometal. Chem. 2019, 33,
e4827.
[32] H. -M. Yang, L. Li, K. -Z. Jiang, J. -X. Jiang, G. -Q.
Lai, L. -W. Xu, Tetrahedron. 2010, 66, 9708-9713.
[33] M. Watanabe, A. Ikagawa, H. Wang, K. Murata, T.
Ikariya, J. Am. Chem. Soc. 2004, 126, 11148-11149.
11
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10.1002/adsc.201901350
Advanced Synthesis & Catalysis
FULL PAPER
Enantioselective Michael Addition Reaction
Catalysed by Enantiopure Binuclear Nickel(II)
Close-Ended Helicates
Adv. Synth. Catal. Year, Volume, Page – Page
Eswaran Chinnaraja,a,b Rajendran Arunachalam,a,b
Krishanu Samanta,b,c Ramalingam Natarajan,b,c and
Palani S. Subramanian,*a,b
12
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