Enantiomeric Resolution of Asymmetric-Carbon-Free Binuclear Double-Stranded Cobalt(III) Helicates and Their Application as Catalysts in Asymmetric Reactions

Article abstract of DOI:10.1021/acs.inorgchem.8b01204

A series of double-stranded binuclear helicates [Co₂(H1)₂]⁴⁺, [Co₂(H2)₂]⁴⁺, and [Co₂(H3)₂]⁴⁺, derived from monodeprotonated bis-pyridyl hydrazine-based liga

Full text of DOI:10.1021/acs.inorgchem.8b01204

Article
pubs.acs.org/IC
Cite This: Inorg. Chem. XXXX, XXX, XXX−XXX
Enantiomeric Resolution of Asymmetric-Carbon-Free Binuclear
Double-Stranded Cobalt(III) Helicates and Their Application as
Catalysts in Asymmetric Reactions
Rajendran Arunachalam,†,‡ Eswaran Chinnaraja,†,‡ Arto Valkonen,§ Kari Rissanen,§ Shovan K. Sen,‡,∥
Ramalingam Natarajan,‡,∥ and Palani S. Subramanian*,†,‡
†Inorganic Materials and Catalysis Division, CSIR-Central Salt and Marine Chemicals Research Institute, Bhavnagar, 364021,
Gujarat, India
‡Academy of Scientific and Innovative Research (AcSIR), Bhavnagar, 364021, Gujarat, India
§
̈
̈
Department of Chemistry, University of Jyvaskyla, Jyvaskyla, FI-40014, Finland
∥Organic & Medicinal Chemistry Division, CSIR-Indian Institute of Chemical Biology, 4, Raja S. C. Mullick Road, Kolkata, 700032,
India
S
* Supporting Information
ABSTRACT: A series of double-stranded binuclear helicates [Co2-
(H1)2]4+, [Co2(H2)2]4+, and [Co2(H3)2]4+, derived from mono-
deprotonated bis-pyridyl hydrazine-based ligands of H21, H22, and H23
with one, two, and three −CH2 spacers, were obtained. These
asymmetric-carbon-free racemic helicates were separated into their ΔΔ
and ΛΛ enantiomers. The resolved helicates were examined for the first
time as enantioselective catalysts in asymmetric benzoylation and
nitroaldol reactions.
results in a situation where the system is CD silent; viz. the
chirality of the helicates cannot be observed. Even though
there are abundant reports on the synthesis of helical
complexes, the reports on their enantiomeric separation are
quite rare. The research groups of Knee,12−15 Lacour,16
Hannon,17,18 Lehn,19,20 Williams,21 and Piguet22 have already
demonstrated the enantiomeric resolution of helicates, yet
none of these resolved helicates have been examined as
enantioselective catalysts. Herein, we describe the synthesis of
a series of binuclear Co(III) double-stranded helicates and
their resolution into the ΔΔ and ΛΛ enantiomers. Further, we
demonstrate, for the first time, that the asymmetric-carbon-free
helicates can act as enantioselective catalysts in selected
organic transformations such as nitroaldol and benzoylation
reactions.
INTRODUCTION
■
Werner resolved the first asymmetric-carbon-free inorganic
chiral complexes of “Hexol” and [Co(NH3)6]3+ more than a
century ago.1 Later, a series of other metal complexes, e.g.,
[Co(en)3]3+, were resolved into their optical isomers.2 In the
last three decades, helicates,3,4 which are discrete and
intrinsically chiral double-, triple-, and multistranded com-
plexes, have emerged as a fascinating class of complex
structures in supramolecular chemistry. When the bis- or
tris-chelating ligands establish coordination by wrapping
around the metal ions, the resulting helical chirality observed
is denoted as P (positive) and M (minus) or alternatively Δ
(delta) and Λ (lambda). The corresponding binuclear double-
stranded helicates form homochiral helicates (ΔΔ, ΛΛ)5−7
and achiral mesocates (ΔΛ).8 Harris and McKenzie9 have
reported a binuclear Cu2L3 complex and suggested the
existence of all above-mentioned three isomers. Raymond
and co-workers10,11 have reported a series of binuclear triple-
stranded complexes with rhodotorulic acid and confirmed the
chiral ΔΔ and ΛΛ isomers through circular dichroism (CD)
and single crystal X-ray structures, and studied the mechanism
of interconversion between the isomers. Despite the fact that
metal-ion helicates are intrinsically chiral, the spontaneous
formation of ΔΔ, ΛΛ, and ΔΛ isomers in the same mixture
RESULTS AND DISCUSSION
■
The bis-pyridylhydrazone based multidentate ligands H21−
H23 (Scheme 1) with one, two, and three −CH2 spacers were
synthesized via a condensation reaction of pyridine-2-
carboxaldehyde with malonic, succinic, and glutaric dihydra-
Received: May 2, 2018
© XXXX American Chemical Society
A
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Article
S17). Similar observations were made with [Co2(H2)2]Cl4 and
[Co2(H3)2]Cl4. The absorption spectra of ligands and their
complexes were recorded in DMF, and both the ligand and
metal-centered transitions were well-resolved (Figure 1). The
band at 310 nm of the ligand represents the ligand-centered
transition, and the corresponding signals on the complexes
appeared at 380−390 nm, which manifest the ligand to metal
charge transfer band. The two well-resolved bands observed
from 600 to 675 nm are attributed to the d−d transitions of
Scheme 1. Synthesis of Co(III) Helicates from H21 (n = 1),
H22 (n = 2), and H23 (n = 3)
4
4
3
4T1g(F) → A2g(F) (610 nm) and T1g(F) → T2g(F) (675
nm), supportive for a distorted octahedral geometry of the
Co(III) ion.
X-ray Structures of [Co222]Cl2 and [Co232](NO3)2.
Despite our rigorous efforts, we were able to obtain single
crystals suitable for XRD only from two of the helicates,
namely, [Co222]Cl2 and [Co232](NO3)2. A dark brown single
crystal of [Co222]Cl2 was obtained by diffusing acetone into
the aqueous solution of the complex. The [Co222]Cl2
crystallizes in the centrosymmetric monoclinic system with
P21/c space group (Table 1, S18). The complex has two
Co(III) centers coordinated by two deprotonated 22− ligands
to form a double-stranded [Co222]2+ dication with chloride
anions in the lattice. Both ligands coordinate through their
N2O site to two Co(III) centers (Figure 2) in [Co222]Cl2 with
a Co···Co distance of 6.05 Å. The symmetrically oriented
ligands have a torsion angle of 66.15° through the spacer
carbons C7-C8-C9-C10 and provide a C-type conformation to
define the complex mesocate. The pyridyl nitrogens (N1, N6)
and azomethine nitrogens (N2, N5) of opposite strands form
the four Co−N bonds, while the hydrazone carbonyl oxygens
(O1 and O2) form the two Co−O bonds. Thus, the Co(III)
centers have a distorted octahedral geometry with bond
distances ranging from 1.845 to 1.923 Å with the N1−Co1−
O1 angle of 165.18°, N5−Co1−N2 of 176.14°, and N6−
Co1−O2 of 165.63°. The acylhydrazone moieties in the ligand
have nearly equal Co−O bond distances [Co1−O1 = 1.902(2)
Å, Co1−O2 = 1.893(2) Å] with similar iminic C−N bond
distances [1.320 and 1.318 Å], in accordance with the
deprotonated enol form of the carbonyl groups.
zides, respectively, following the procedure recently reported
by us.23,24 The molecular structure of the ligands were
characterized by mass spectrometry, NMR, IR spectroscopy,
and elemental analysis. The negative-mode electrospray
ionization (ESI) mass spectrometry of the newly synthesized
ligands H21−H23 exhibited the expected signals for (M − H)−
ions at m/z = 309.16 (H1−), 323.12 (H2−), 337.33 (H3−),
respectively (Figures S1−S3).
1
The H NMR spectroscopy confirmed the presence of the
characteristic resonances at δ = 8.23 and 8.05 ppm (for H21), δ
= 8.18 and 8.05 ppm (for H22), and δ = 8.16 and 8.04 ppm
(for H23) for the azomethine protons, thus confirming the
successful Schiff base condensation reaction (Figures S4−S9).
Also, the IR spectroscopy revealed the azomethine groups at
1550−1580 cm−1 (νCN) (Figure S10).
The helicates were prepared by treating the ligands H21−
H23 with CoCl2 in a 1:1 ratio, in methanol, providing the
expected double-stranded [M2L2]Cl4 type helicates, [Co2-
(H1)2]Cl4, [Co2(H2)2]Cl4, and [Co2(H3)2]Cl4, in reasonable
yields. The basic monoanionic ligands facilitate the oxidation
of Co(II) to Co(III) without any additional oxidizing agents
during the helicate formation, as reported earlier.25 The
positive-mode ESI mass spectra of the helicates showed the
presence of the expected peaks for the dicationic (M2+) ions of
[Co212]2+ [Co222]2+, and [Co232]2+ at m/z = 367.80, 381.27,
,
and 395.45, respectively (Figures S11−S13), and confirms the
1
dinuclear helicate formation. The H NMR spectra of these
A similar binuclear double-stranded helicate [Co232](NO3)2
was obtained using H23 and Co(NO3)2. The single crystals
were obtained by diffusing isopropyl alcohol into the aqueous
solution of the helicate. The X-ray structural analysis of the
helicate revealed a similar structure with deprotonated
dianionic ligands as for [Co222]Cl2. The ligands adopt a
similar C-type conformation to possess cis−cis coordination
with two cobalt ions and is a mesocate as [Co222]Cl2. In
complexes span over a narrow spectral range, 0−15 ppm, in
accordance with the presence of Co(III) ions (Figures S14−
S16). The broad IR bands observed around 3400 cm−1 are
attributed to the hydroxyl group of water molecules in
helicates. The −CO stretching frequency at 1665 cm−1 in
H21 is shifted to 1619 cm−1 in the [Co2(H1)2]Cl4 helicate;
also a small shift from 1558 to 1544 cm−1 in the azomethine
band was observed, in accord with the complexation (Figure
Figure 1. (a) UV−vis spectra of the ligands and the helicates in DMF; (a′) d−d transitions (1 × 10−4 M).
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the present study, we have attempted to separate the
enantiomers from each other and from the mesocate through
column chromatography. In this challenging process, the
choice of the mobile and stationary phases is of crucial
importance. The chiral mobile and stationary phases were
chosen in such a way that their interaction with one
enantiomer will be stronger than the other. In this respect,
we have examined as the chiral stationary either cellulose or
SP-Sephadex and as the mobile phases L-potassium antimony-
(III)-tartrate, sodium-D-gluconate, dibasic L-(+)-potassium
tartrate, dibasic D-(−)-potassium tartrate, (+)-O,O′-di-p-
toluoyl-D-tartaric acid, (−)-O,O′-di-p-toluoyl-L-tartaric acid,
dibenzoyl-L-tartaric acid, and (+)-2,3-dibenzoyl-D-tartaric
acid. The initial thin layer chromatography (TLC) analysis
suggested that the 2:8 ratio of 0.02 M of dibasic L-
(+)-potassium-tartrate (aq) with acetonitrile would be the
suitable mobile phase and cellulose as the suitable stationary
phase. Accordingly, the columns were loaded with cellulose
using acetonitrile and a slurry made of [Co2L2]Cl4 helicate, [L
= H1, H2, H3], were placed on the column. Initially, the
columns were eluted with acetonitrile alone after which the
polarity of the mobile phase was raised by incremental
amounts of 0.2% potassium-tartrate dibasic(aq) (0.01M) with
acetonitrile. Due to the selective interaction of tartrate ions
with one of the enantiomers, differential elutions of the
enantiomeric helicates were observed. We postulate that the
chloride ions in the [Co2(H2)2]Cl4 are replaced by the chiral
tartrate ions during the elution. The chiral tartrate ion forms
two diastereomeric helicates, leading to the separation of the
enantiomeric helicates. The separation process is very slow.
Thus, with flow rates being low, the elution process consumes
a very long elution time of around 25−30 days. If the
separation was attempted by increasing the flow rate of the
mobile phase, it only led to no or poor separation. Apart from
the exorbitant duration for one enantiomer to elute from the
column, the other enantiomer was found to bind so strongly to
the cellulose stationary phase that it was difficult to isolate. As
we wanted to resolve both enantiomers, we were motivated to
modify the protocol, which would facilitate to achieve
separation of both of the enantiomers. Accordingly, by keeping
the choice of cellulose as stationary phase unchanged, the
slurry was made by mixing 0.02 M aq. NaCl, cellulose, and the
helicate (dissolved in a minimum amount of water). This
slurry was placed on the column top for a few minutes and
then eluted with fresh acetonitrile. A pale brown band eluted
Table 1. Crystal Data for [Co222]Cl2(H2O)4 and
[Co232](NO3)2
parameters
[Co222]Cl2(H2O)4
[Co232](NO3)2
chemical formula
formula weight
crystal size (mm)
temperature (K)
crystal system
space group
a (Å)
b (Å)
c (Å)
α (Å)
C32H28Cl2Co2N12O8
897.42
0.28 × 0.14 × 0.12
100
monoclinic
P21/c
12.5772(6)
17.0364(8)
9.0254(5)
90
C68H64Co4N28O21
1845.19
0.19 × 0.11 × 0.06
123
monoclinic
C2/c
16.9666(9)
25.1732(13)
9.1054(5)
90
β (Å)
γ (Å)
97.906(2)
90
101.658(5)
90
Z
2
2
ρcalc (g/cm3)
1.556
1.609
μ (mm−1
F(000)
)
1.071
912
0.950
1888
reflections collected
independent reflections
Rint
25637
4437
0.0459
6456
3434
0.0187
restraints/parameters
GOF on F2
262/305
1.906
296/411
1.062
final R1/wR2 [I ≥ 2σ(I)]
R1/wR2 (all data)
0.0547/0.1420
0.0658/0.1420
0.0511/0.1342
0.0642/0.1438
0.904/−0.611
1832297
largest diff. peak/hole (e Å3) 1.02/−0.65
CCDC
1835264
[Co232](NO3)2, the Co···Co distance is 7.32 Å (Figure 3); the
longer distance is caused by the additional CH2 group in the
spacer. The octahedral coordination geometry in [Co232]-
(NO3)2 [Co−O = 1.893−1.945 Å; 1.902−1.906 Å] and C−O
= [1.291, 1.307 Å] is very similar to that of [Co222]Cl2.
The Enantiomeric Resolution of [Co2(H1)2]Cl4, [Co2-
(H2)2]Cl4, and [Co2(H3)2]Cl4. Although the helicates do not
have asymmetric carbons, they are intrinsically chiral due to
the helical arrangement of ligands and the induced chirality
around the metal centers upon complexation. Thus, the
synthesis of double-stranded helicates leads to a mixture
consisting a pair of chiral helicates (ΔΔ, ΛΛ) and achiral
mesocate (ΔΛ), as shown in the Scheme 2. Since the structural
differences between the chiral helicates and the mesocate are
small, the separation of them is difficult and rarely reported. In
Figure 2. X-ray structure of [Co222]2+. The chloride counterions are omitted for clarity.
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Figure 3. X-ray structure of [Co232]2+. The nitrate counterions are omitted for clarity.
Scheme 2. Possible Enantiomers in the Co(III) Helicates
(Each Racemic Helicate Contains Two Enantiomers and
a
One Mesocate)
Figure 4. Photograph of resolved enantiomers (ΛΛ enantiomer,
green band, in acetonitrile) and (ΔΔ enantiomer, brown band, in
acetonitrile−0.02 M NaCl (aq)).
a
The n indicates the number of −CH2 groups of ligands 1, 2, and 3.
out first, and the elemental and MS analyses match well with
those of the parent dinuclear helicate. However, the absence of
CD for this fraction suggested that this band consists of achiral
mesocate (ΔΛ).
Following the elution of this band, an additional two intense
bands, green and brown in color, appeared, and both were
collected separately (Figure 4). Initially, the green band was
collected using acetonitrile alone. Subsequently, the brown
band was collected by raising the polarity by using 0.02 M
NaCl(aq) solution. The isolated complexes from the both
green and brown bands exhibited similar elemental analysis
data (S19) and MS spectra (Figure S20). The CD spectra
recorded revealed positive and negative Cotton effects (Figure
5) and confirm that they are enantiomers. The respective CD
spectra in Figure 5 reveal the ligand-centered [Figure 5a−c]
and d−d transitions [Figure 5(a′−c′)], which are resolved at
lower concentration (≈1 × 10−4 M) and higher concentration
(≈5 × 10−2 M), respectively.
The opposite optical behavior of the green and the brown
bands at 700−600 nm is associated with the opposite helical
chiralities of the respective metal centers (ΔΔ and ΛΛ). This
observation matches with Hannon’s report18 suggesting that
the green and brown bands correspond to the (M)-helicate
Figure 5. CD spectra recorded in DMF for resolved green and brown
bands of tetracationic (a) ΛΛ-[Co2(H1)2] and ΔΔ-[Co2(H1)2], (b)
ΛΛ-[Co2(H2)2] and ΔΔ-[Co2(H2)2], (c) ΛΛ-[Co2(H3)2] and ΔΔ-
[Co2(H3)2]. The a′, b′, and c′ represent the d−d band.
D
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and (P)-helicates, respectively. The ligand centered bands in
the CD spectral range of 260−350 nm of all three helicates
show an opposite optical pattern of λmax at around 290 nm for
the green bands attributable to ΛΛ-[Co2(H1)2], ΛΛ-[Co2-
(H2)2], and ΛΛ-[Co2(H3)2] helicates and for the brown
bands to their ΔΔ-[Co2(H1)2], ΔΔ-[Co2(H2)2], and ΔΔ-
[Co2(H3)2] enantiomers (Figure 5).
Although the yields are encouraging (80−90%, Table 2), the
enantioselectivities observed were only modest. However, the
14% ee obtained (Table 2: entries 5 and 6) in the reactions are
certainly due to the chirality associated with the enantiomeric
helicate catalyst. The optical nature of the enantiomeric
products (Table 2: entries 5 and 6) obtained using the catalytic
ΔΔ and ΛΛ enantiomeric helicates of [Co2(H2)2]4+ was
analyzed by HPLC using a Lux-cellulose column, and they
were confirmed to be enantiomers (Figures S23 and S24).
Similar studies with an asymmetric nitroaldol reaction were
also carried out using benzaldehyde and nitromethane as a
model substrate, with DIPEA as the base in acetonitrile at 0 °C
for 16 h, using 2 mol % of the resolved enantiomers as catalysts
(S25). The completion of the reaction was monitored by TLC.
Subsequently, the catalysts were separated as described in the
general procedure (S25), and the products (S26) were purified
by flash column chromatography (Figure S27). As shown in
the Table 3, the yields are again high, but the respective ee’s
Since the cobalt ions are in the +3 oxidation state in all of
1
these complexes, we were inspired to investigate their H
1
NMR spectra. The representative H NMR recorded for the
[Co2(H2)2]Cl4 complex using D2O as solvent shows two well
distinguishable doublets corresponding to the CH2 protons of
the succinate spacer in the mixture of enantiomers (Figure
S21). Upon separation of the enantiomers from the mesocate,
they show only a small change in their chemical shift with
reference to the racemic mixture. Further, the 1H NMR
spectrum of [Co2(H2)2]Cl4 shows the coexistence of two sets
of doublets attributable to the enantiomers and one singlet for
mesocate; it allowed us to establish the relative ratio of
helicate:mesocate population in the complex as 71:29%.
Asymmetric Synthesis with the Helicates as Cata-
lysts. Having successfully isolated the asymmetric-carbon-free
enantiomeric helicates, we aimed to examine their hitherto
unexplored ability to function as enantioselective catalysts.
Accordingly, we have chosen two well-established reactions,
the desymmetrization of a meso diol26 and the nitroaldol27,28
reactions. Accordingly, using 2 mol % of the above-resolved
enantiomers as catalysts, we treated the meso-hydrobenzoin
(model substrate) with benzoyl chloride (acylating reagent)
with DIPEA as the base in a MeCN−DCM solvent mixture at
−30 °C for 8 h. The results are presented in Table 2. The
reaction mixtures were purified following the general
procedure (S22) by flash column, and their ee’s were
determined (S23) using chiral HPLC (Figure S24).
Table 3. Screening of the Helicate Catalysts for the
a
Asymmetric Nitroaldol Reaction
entry
catalyst
blank
yield (%)
ee (%)
1
2
3
4
5
6
7
8
9
56
92
90
90
95
92
92
90
86
92
ΔΔ-[Co2(H1)2]
ΛΛ-[Co2(H1)2]
rac-[Co2(H1)2]
ΔΔ-[Co2(H2)2]
ΛΛ-[Co2(H2)2]
rac-[Co2(H2)2]
ΔΔ-[Co2(H3)2]
ΛΛ-[Co2(H3)2]
rac-[Co2(H3)2]
24
20
26
22
20
18
10
a
All reactions were carried out using 2 mol % (0.007 mmol) of
Table 2. Screening of the Helicate Catalyst for the
Asymmetric Benzoylation Reaction
catalyst, 0.37 mmol of the substrate, 0.4 mmol of DIPEA (di-isopropyl
ethylamine), and 3.76 mmol of CH3NO2 at 0 °C, for 16 h. The ee’s
were determined using UFLC, Lux-cellulose-1 in an IPA−Hexane
system. *The Co(III) in the catalyst is balanced with chloride
counterions. The HPLC profile for the nitroaldol product is given in
the Supporting Information (Figure S27a−f).
a
observed are only modest, ranging from 18% to 26%. As in the
benzoylation reaction, the enantiomeric excess obtained here
also accounts for the chirality associated with the enantiomeri-
cally pure helicate catalyst.
The poor enantioselectivities of the reactions urged us to
revisit the CD experiments of the resolved helicates. Hence, we
observed that the CD signal intensities are reducing as a
function of time and suggest that, in solution, the enantiomeri-
cally pure helicates racemize through the mesocate (ΔΔ ↔
ΛΔ ↔ ΛΛ), and thus results in the low ee’s observed in the
asymmetric catalysis.
In order to examine the recyclability of the catalyst, we
performed the nitroaldol reaction using ΔΔ-[Co2(H2)2]
helicate, under the same catalytic conditions. We found that
the catalytic activity remained excellent up to the third cycle,
but the ee’s were found to be decreasing systematically from
26% to 10%, and finally to zero. This again confirms that the
catalyst is undergoing racemization during the course of the
reaction, causing the poor enantioselectivity.
entry
catalyst
blank
yield (%)
ee (%)
major
1
2
3
4
5
6
7
8
9
42
85
88
90
92
90
90
82
86
86
ΔΔ-[Co2(H1)2]
ΛΛ-[Co2(H1)2]
rac-[Co2(H1)2]
ΔΔ-[Co2(H2)2]
ΛΛ-[Co2(H2)2]
rac-[Co2(H2)2]
ΔΔ-[Co2(H3)2]
ΛΛ-[Co2(H3)2]
rac-[Co2(H3)2]
4
2
14
14
1R, 2S
1S, 2R
2
6
10
a
All reactions were carried out using 0.004 mmol of catalyst, 0.2
mmol of the substrate, 0.4 mmol of DIPEA (di-isopropyl ethylamine),
0.2 mmol of benzoyl chloride at −30 °C for 8 h. The
enantioselectivities were determined using UFLC, Lux-cellulose-1 in
an IPA−Hexane system. The Co(III) in the catalyst is balanced with
chloride counterions. The HPLC profile for the benzoylation product
is given in the Supporting Information (Figure S24a−f).
E
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26.59. IR(KBr) ν = 3440 (OH), 3076 (C-H), 2951, 2902 (N-H),
2362, 1680 (int, CO), 1581 (int, CN), 1448 (ar CC), 1210
(C-N), 1160 (m), 944, 780 (C-H) cm−1. UV−vis [DMF, λ, nm, (ε/
M−1)]: 310 (10682), 300 (10183). Anal. Calcd (%) for C16H16N6O2:
C, 59.25; H, 4.97; N, 25.91. Found: C, 58.42; H, 5.36; N, 25.11. ESI-
MS: m/z (−) found 323.12 [H2]− (Calcd 323.13).
CONCLUSION
■
In summary, three binuclear Co(III) helicates [Co2(H1)2]Cl4,
[Co2(H2)2]Cl4, and [Co2(H3)2]Cl4 were synthesized and
resolved into their ΔΔ and ΛΛ enantiomers. The mirror image
CD spectra of the column chromatographically separated
enantiomers confirm the resolution of the helicates into their
respective ΔΔ and ΛΛ enantiomers. The resolved enantiomers
were examined as catalysts for asymmetric organic trans-
formation for the first time and led to the expected products in
excellent yields, but disappointedly only with moderate
enantioselectivities. The results presented here encourage us
to look for a better design strategy of the ligands for enantio-
stable helicates, and upon resolution, for efficient enantiose-
lective catalysis.
H23. Yield 72% (7.60 g). 1H NMR (DMSO-d6, TMS, 500 MHz): δ
= 11.64 (s, 1H, NH), 11.50 (s, 1H, −NH), 8.60 (s, 2H, −CH), 8.18−
8.15 (d, J = 6 Hz, 1H, CH), 8.04−8.01 (d, J = 7 Hz, 1H, CH), 7.94−
7.66 (m, 4H, −CH), 7.39 (t, J = 7 Hz, 2H, −CH), 2.77 (t, 2H), 2.36
(m, 2H), 1.94 (t, 2H). 13C NMR (DMSO-d6, 600 MHz): δ = 174.37,
174.23, 168.68, 168.54, 153.30, 153.18, 153.14, 149.43, 146.21,
146.10, 143.16, 143.04, 136.86, 136.82, 136.75, 124.30, 124.26,
124.06, 119.79, 119.47, 119.38, 33.48, 33.36, 31.36, 31.12, 20.62,
20.01, 19.42. IR (KBr) ν = 3435 (OH), 3191 (C-H), 3053, 3005
(N-H), 2365, 1680 (int, CO), 1566 (int, CN), 1388 (CC, ar),
1249 (C-N), 1150(m), 778 (C-H) cm−1. UV−vis [DMF, λ, nm, (ε/
M−1)]: 311 (10590), 300 (10105). Anal. Calcd (%) for C17H18N6O2:
C, 60.22; H, 5.34; N, 24.19. Found: C, 60.34; H,5.36; N, 24.84. ESI-
MS: m/z (−) found 337.33 [H3]− (Calcd 337.14).
EXPERIMENTAL SECTION
■
Materials and General Methods. All the chemicals were
purchased from Aldrich & Co. IR spectra were recorded using KBr
pellets (1% w/w) on a PerkinElmer Spectrum GX FT-IR
spectrophotometer. Electronic spectra were recorded on a Shimadzu
UV 3101PC spectrophotometer. Electrospray ionization mass
spectrometry (ESI MS) measurements were carried out on a Waters
QTof-micro instrument for all of these complexes upon dissolving in
methanol−water solvents. CHNS analyses were done using a
PerkinElmer 2400 CHNS/O analyzer. Single crystal data for
[Co222]Cl2(H2O)4 were collected at 100 K on a Bruker Kappa
APEX2 CCD diffractometer with Mo−Kα (λ = 0.71073 Å) radiation.
The X-ray data for [Co232](NO3)2O were collected on an Agilent
SuperNova single-source diffractometer equipped with an Eos CCD
detector using mirror-monochromated Mo-Kα (λ = 0.71073 Å)
radiation. 1H and 13C NMR spectra were recorded on a Bruker
Avance II 500 or 600 MHz FT-NMR spectrometer. Chemical shifts
for proton resonances are reported in ppm (δ) relative to
tetramethylsilane, and 13C spectra are calibrated with reference to
Synthesis of Helicates. [Co2(H1)2]Cl4 (H2O)5. To a methanolic
solution of ligand H21 (1241 mg, 4 mmol), cobalt(II) chloride
hexahydrate (952 mg, 4 mmol) in methanol was added dropwise. The
colorless solution of the ligand turns into yellow to orange and then
blackish red. The reaction mixture is heated to 60 °C for 2 h and then
allowed to stir at RT for 14 h. The solution was evaporated under
reduced pressure. Black crystalline solid. Yield: 45% (1.70 g). IR
(KBr) ν = 3402 (−OH), 1619 (int, CO), 1544 (int, CN), 1470
(ar CC), 1361, 1222 (C-N), 1153, 773 (C-H) cm−1. UV−vis
[DMF, λ, nm, (ε/M−1)]: 675 (452), 655 (429), 600 (481), 486
(2082), 368 (8460), 315 (10034). Anal. Calcd (%) for C30H36-
Cl4Co2N12O9: C, 37.21; H, 3.75; N, 17.36. Found: C, 37.23; H, 3.45;
N, 17.36. ESI-MS: m/z (+) found 734.61 [Co212]2+ (Calcd 734.07);
and the corresponding M2+/2 found 367.80 (calcd 367.03).
[Co2(H2)2]Cl4(H2O)5. A similar procedure adapted by following the
above and using H22 in place of H21. Black solid. Yield: 48% (0.456
g). IR (KBr): ν = 3405 (−OH), 3080 (C-H), 2916, 2834 (N-H),
2365, 1616 (int, CO), 1536 (int, CN), 1238 (C-N), 1175 (m),
938, 780 (C-H) cm−1. UV−vis [DMF, λ, nm, (ε/M−1)]: 676 (549),
657 (492), 631 (372), 607 (320), 367 (7590), 316 (10188). Anal.
Calcd (%) for C32H40Cl4Co2N12O9: C, 38.57; H, 4.05; N, 16.87.
Found: C, 38.35; H, 4.34; N, 15.39. ESI-MS m/z (+) found 762.57
[Co222]2+ (Calcd 762.10), and the corresponding M2+/2 found
381.27 (calcd 381.05).
[Co2(H3)2]Cl4(H2O)3. A similar procedure was adapted using H23 in
place of H21. Blackish brown crystalline solid. Yield: 40% (0.77 g). IR
(KBr): ν = 3395 (br, −OH), 3024, 2941 (−NH), 2360, 1626 (int,
CO), 1540 (int, CN), 1350 (ar CC), 1228 (C-N), 1153, 935,
778 (C-H) cm−1. UV−vis [DMF, λ, nm, (ε/M−1)]: 675 (554), 661
(531), 631 (352), 605 (408), 367 (10602), 350 (10280), 308
(11072). Anal. Calcd (%) for C34H40Cl4Co2N12O7: C, 41.32; H, 4.08;
N, 17.01. Found: C, 41.47; H, 4.17; N, 17.31. ESI-MS m/z (+) found
789.92 [Co232]2+ (Calcd 790.13) and the corresponding M2+/2 found
395.45 (calcd 395.07).
[Co2(H3)2](NO3)4(H2O)6. A similar procedure adapted by following
the above and except H23 (465 mg, 1.374 mmol) and cobalt(II)
nitrate (400 mg, 1.374 mmol). The crude complex was washed with
diethyl ether to remove trace solvent impurities to yield a fine
crystalline blackish brown solid. Yield: 56% (0.86 g). IR(KBr): ν =
3418 (br, −OH), 2926, 2855 (−NH), 1622 (int, CO), 1536 (int,
CN), 1350 (ar CC), 1151 (C-N), 1016, 776 (C-H) cm−1. UV−
vis [DMF, λ, nm, (ε/M−1)]: 675 (1184), 654 (1059), 605 (956), 389
(8624), 356 (8998), 322 (8434). Anal. Calcd (%) for C34H48-
Co2N16O22: C, 35.49; H, 4.20; N, 19.48. Found: C, 35.29; H, 3.89; N,
19.41. ESI-MS m/z (+) found 790.52 [Co232]2+ (calcd 790.13) and
the corresponding M2+/2 found 396.26 (calcd 395.56).
1
DMSO-d6. All the catalytic products were established based on H
NMR spectra. The CD spectra were recorded on a JASCO 815
Spectrometer. The enantioselectivity of the Henry product was
determined by UFLC (Shimadzu SCL-10AVP) using chiral columns
(Phenomenox Lux cellulose-1 and Amylose-2 column).
Synthesis of Ligands H21−H23. To a methanolic suspension of
malonohydrazide (5.0 g, 0.034 mol), 2-pyridine carboxaldehyde (7.32
g, 0.068 mol) was added, and the mixture was allowed to stir at 0 °C
for 8 h. The suspension changed into a clear solution, and a
precipitate slowly formed during the course of the reaction. In the
case of H21 and H22, the colorless solid obtained was filtered, washed
with methanol, and dried. In the case of ligand H23, a pale yellow
product was obtained.
H21. Yield 84% (9.86 g). 1H NMR (DMSO-d6, TMS, 500 MHz): δ
= 11.94, 11.73 (s, 1H each, −NH), 8.58 (s, 2H), 8.26 (s, 1H), 8.04 (s,
2H), 7.87−7.85 (d, J = 8 Hz, 2H), 7.70−7.67 (t, J = 8 Hz, 2H), 7.37−
7.35 (t, J = 6 Hz, 2H), 4.01 (s, 2H). 13C NMR (DMSO-d6, 600
MHz): δ = 169.45, 168.93, 163.40, 162.95, 153.12, 153.01, 149.53,
149.48, 147.18, 146.64, 143.58, 143.31, 136.92, 136.63, 136.58,
124.52, 124.44, 124.26, 124.19, 120.01, 119.90, 119.58, 119.49, 41.19.
IR(KBr): ν = 3445 (−OH), 3200, 3068 (−NH), 1665 (int, CO),
1558 (int, −CN), 1465 (ar CC), 1360, 1214 (C-N), 1151, 780
(C-H) cm−1 UV−vis [DMF, λ, nm, (ε/M−1)]: 305 (8614), 296
.
(8200). Anal. Calcd (%) for C15H14N6O2: C, 58.06; H, 4.55; N,
27.08. Found: C, 57.51; H, 4.74; N, 27.40. ESI-MS: m/z (−) found
309.16 [H1]− (Calcd 309.11).
H22. Yield 76% (8.43 g). 1H NMR (DMSO-d6, TMS, 500 MHz): δ
= 11.71 (s, 1H, NH), 11.53 (s, 1H, −NH), 8.59 (s, 2H, −CH), 8.19
(s, 1H, CHN), 8.05 (s, 1H, CHN), 7.90 (m, 2H, −CH), 7.88−
7.83 (t, 2H, −CH), 7.40 (t, 2H, J = 7 Hz, −CH), 3.02 (s, 2H, −CH),
2.60−2.57 (s, 2H, −CH). 13C NMR (DMSO-d6, 600 MHz): δ =
173.89, 173.68, 168.46, 168.19, 153.36, 153.31, 153.22, 153.18,
149.54, 146.10, 145.92, 143.30, 143.12, 136.94, 136.90, 124.38,
124.34, 124.22, 124.19, 119.82, 119.60, 119.52, 29.05, 28.52, 27.25,
Resolution of Metallohelicates. The cellulose of particle size 20
μ was purchased from Sigma Aldrich and used as stationary phase.
The cellulose was made into a slurry with 0.02 M aq. sodium chloride
and loaded on the column. The metallohelicates which consist of
F
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Inorganic Chemistry
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mixtures of enantiomers (ΔΔ and ΛΛ) and mesocate (ΔΛ) were
dissolved in water as a saturated solution and added to the column.
The column was eluted with acetonitrile, and the resolution of bands
was observed. Two different bands, one with brown and the other
with green, were collected separately and isolated. The isolated
compounds were made stock solution, and CD spectra were recorded
for their enantiopure nature. The clear resolution of metal centered
transitions was obatined at high concentrations in DMF. The racemic
helicates were resolved into green and brown bands which are
showing similar mass and CHNS data, but opposite pattern in CD
spectra, confirming that they are enantiomers (ΔΔ and ΛΛ).
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ASSOCIATED CONTENT
* Supporting Information
The Supporting Information is available free of charge on the
ACS Publications website at DOI: 10.1021/acs.inorg-
chem.8b01204.
■
S
Characterization data of all the ligands and the
complexes such as ESI-MS, UV−vis, FT-IR, NMR, and
crystal data and the HPLC profile and characterization
of catalytic product (PDF)
Accession Codes
CCDC 1832297 and 1835264 contain the supplementary
crystallographic data for this paper. These data can be obtained
free of charge via www.ccdc.cam.ac.uk/data_request/cif, or by
emailing data_request@ccdc.cam.ac.uk, or by contacting The
Cambridge Crystallographic Data Centre, 12 Union Road,
Cambridge CB2 1EZ, UK; fax: +44 1223 336033.
(16) Jodry, J. J.; Lacour, J. Efficient resolution of a dinuclear triple
helicate by asymmetric extraction/precipitation with TRISPHAT
anions as resolving agents. Chem. - Eur. J. 2000, 6 (23), 4297−4304.
(17) Hannon, M. J.; Meistermann, I.; Isaac, C. J.; Blomme, C.;
Aldrich-Wright, J. R.; Rodger, A. Paper: a cheap yet effective chiral
stationary phase for chromatographic resolution of metallo-supra-
molecular helicates. Chem. Commun. 2001, 1078−1079.
(18) Kerckhoffs, J. M. C. A.; Peberdy, J. C.; Meistermann, I.; Childs,
L. J.; Isaac, C. J.; Pearmund, C. R.; Reudegger, V.; Khalid, S.; Alcock,
N. W.; Hannon, M. J.; Rodger, A. Enantiomeric resolution of
supramolecular helicates with different surface topographies. Dalton
Trans 2007, 734−742.
AUTHOR INFORMATION
Corresponding Author
*E-mail: siva@csmcri.res.in, siva140@yahoo.co.in.
ORCID
Kari Rissanen: 0000-0002-7282-8419
Palani S. Subramanian: 0000-0002-9035-0973
Notes
■
The authors declare no competing financial interest.
ACKNOWLEDGMENTS
■
(19) Hasenknopf, B.; Lehn, J. M. Trinuclear double helicates of
Iron(II) and Nickel(II): self-assembly and resolution into helical
enantiomers. Helv. Chim. Acta 1996, 79, 1643−1650.
CSMCRI communication No. 086/2018. R.A. and E.C.
acknowledge the CSIR for SRF. A.V. kindly acknowledges
the Academy of Finland (grant no. 314343) for financial
support. P.S.S. acknowledges the CSIR for Indus Magic Project
No. CSC-0123 and DST-SERB New Delhi (project Nos. SR/
S1/IC-23/2011 & SR/S2/RJN-62-2012) for financial support.
We are thankful to ADCIF for the instrument support.
(20) Kramer, R.; Lehn, J. M.; De Cian, A.; Fischer, J. Self-Assembly,
structure, and spontaneous resolution of a trinuclear triple helix from
an oligobipyridine ligand and Ni(II) ions. Angew. Chem., Int. Ed. Engl.
1993, 32 (5), 703−706.
(21) Charbonniere, L. J.; Bernardinelli, G.; Piguet, C.; Sargeson, A.
M.; Williams, A. F. Synthesis, structure and resolution of a dinuclear
Co(III) triple helix. J. Chem. Soc., Chem. Commun. 1994, 1419−1420.
(22) Cantuel, M.; Bernardinelli, G.; Muller, G.; Riehl, J. P.; Piguet,
C. The first enantiomerically pure helical noncovalent tripod for
assembling nine-coordinate lanthanide(III) podates. Inorg. Chem.
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