Binuclear Cu(II) chiral complexes: Synthesis, characterization and application in enantioselective nitroaldol (Henry) reaction

Article abstract of DOI:10.1002/aoc.3404

Enantiopure macrocyclic ligands were synthesized from (1R,2R)-(+)- and (1S,2S)-(-)-diphenylethylenediamine with 3,3'-methylenebis(5-(tert-butyl)-2-hydroxybenzaldehyde) and characterized. The chirality transfer and chiral inversion from ligand to copper(II

Full text of DOI:10.1002/aoc.3404

Full paper
Received: 23 June 2015
Revised: 29 September 2015
Accepted: 9 October 2015
Published online in Wiley Online Library: 25 November 2015
(wileyonlinelibrary.com) DOI 10.1002/aoc.3404
Binuclear Cu(II) chiral complexes: synthesis,
characterization and application in
enantioselective nitroaldol (Henry) reaction
E. Chinnarajaa,b, R. Arunachalama,b, Manoj K. Choudharya,b, R. I. Kureshya,b
and P. S. Subramaniana,b*
Enantiopure macrocyclic ligands were synthesized from (1R,2R)-(+)- and (1S,2S)-(ꢀ)-diphenylethylenediamine with 3,3’-
methylenebis(5-(tert-butyl)-2-hydroxybenzaldehyde) and characterized. The chirality transfer and chiral inversion from ligand
to copper(II) metal centre were studied using circular dichroism spectroscopy. The enantiopure binuclear copper(II) complexes
(ΔΔ and ΛΛ) were used as catalysts for asymmetric nitroaldol reaction to generate β-nitroalcohol with 88% yield and 67%
enantioselectivity. Copyright © 2015 John Wiley & Sons, Ltd.
Additional supporting information may be found in the online version of this article at the publisher’s web site.
Keywords: chiral copper(II) complexes; chirality transfer; chiroptical property; nitroaldol; β-nitroalcohol
respectively, the enantiopure nature enables them to act with effi-
cient enantioselectivity in asymmetric reactions. Thus the helicates
possessing intrinsic chirality, the addition of enantiopure ligands
can provide important catalytic capability. Accordingly, in the work
reported here, we synthesized enantiopure macrocyclic chiral
ligands 1 and 2 (Scheme 1). These enantiopure ligands were pre-
pared by treating (1R,2R)-(+)- or (1S,2S)-(ꢀ)-diphenylethylenediamine
with 3,3′-methylenebis(5-(tert-butyl)-2-hydroxybenzaldehyde). Both
ligands having four asymmetric carbons exist in the RRRR or the SSSS
form, respectively.
The structures of the ligands are designed to create discrete
metal binding domains which are doubly linked with each other
by methylene spacers. Both ligands 1 and 2 and the complexes
Cu21 and Cu22 were characterized using UV–visible, Fourier trans-
form infrared (FT-IR) and NMR spectroscopies, elemental analysis,
ESI-MS and MALDI-TOF MS wherever applicable. The enantiopure
copper(II) helicates were demonstrated for the synthesis of a series
of β-nitroalcohols via asymmetric nitroaldol reaction using nitro-
methane and various substituted benzaldehydes as substrates.
Introduction
Chirality is a key phenomenon for a variety of stereo- and regiose-
lective catalytic and biological reactions. The term ‘helicate’ intro-
duced by Lehn defines metal complexes that contain one or
more ligand strands wrapped around two or more metal centres.
The spatial arrangement of chelating ligands around the metal ions
in double- or triple-stranded helicates[1] provides geometrical or
metal-centred chirality (Δ/Λ). A helicate, thus formed, gains chiral
property due to such a spatial arrangement of the helicands. These
intrinsically chiral compounds possess two different enantiomers
and remain racemic because of their PP, MM and PM mixtures.[2]
This intrinsic chiral property of helicates is considered in parallel
to the chirality associated with asymmetric chiral carbons.
Furthermore, a chiral ligand upon coordination with a metal centre
transfers chirality to the metal centre, making the latter gain chirality
(Δ/Λ).[3] Thus the synthesis of new enantiopure chiral helicates
and the chirality transfer from chiral ligand to metal centre and the
consequent geometrical chirality (Δ/Λ) are considered potential
contributors in smart chiroptical devices, enantioselective catalysis,
materials science and pharmaceuticals. In this regard we have
recently demonstrated the application of a double-stranded dicopper
catalyst and its diastereoselective catalysis in nitroaldol (Henry)
reaction.[4] The Henry reaction, known as one of the important C–C
bond forming reactions, provides a number of interesting intermedi-
ates useful for industrial applications. Examples of such are 1,2-
diaminoalcohols,[5] aminosugars,[6] nitroketones[7] and α,β-unsatu-
rated nitro compounds.[8] Both organocatalysts[9] and metal
catalysts[10] have been reported for the Henry reaction. However,
among the metal complexes employed as catalysts, homo-
bimetallic[11] and heterobimetallic[12] complexes deserve special
attention due to the significant contribution made by Shibasaki.
While the homo- and heterobimetallic complexes are active as
diastereoselective catalysts and render syn or anti selectivity,
Results and discussion
The macrocyclic N2O2 chromophoric ligands 1 and 2 were prepared
by reacting (1R,2R)-(+)- and (1S,2S)-(ꢀ)-diphenylethylenediamine,
*
Correspondence to: P. S. Subramanian, Inorganic Materials and Catalysis Division,
CSIR-Central Salt and Marine Chemicals Research Institute (CSIR-CSMCRI),
Bhavnagar – 364 002, Gujarat, India. E-mail: siva@csmcri.org
a Inorganic Materials and Catalysis Division, CSIR-Central Salt and Marine
Chemicals Research Institute (CSIR-CSMCRI), Bhavnagar– 364 002, Gujarat, India
b Academy of Scientific and Innovative Research (AcSIR), CSIR-CSMCRI, Bhavnagar,
Gujarat, –364 002, India
Appl. Organometal. Chem. 2016, 30, 95–101
Copyright © 2015 John Wiley & Sons, Ltd.

E. Chinnaraja et al.
is assigned to Cu22 + Na+ (Figs S9 and S11). FT-IR spectra of ligands
have peaks at 1629 and 1626 cmꢀ1 for 1 and 2, attributable to C¼N
stretching, which shift to 1612 and 1610 cmꢀ1 in the spectra of the
respective complexes Cu21 (Fig. S13(a)) and Cu22 (Fig. S13(b)), an
approximately 16 cmꢀ1 shift, confirming the coordination with Cu
(II). Likewise, a sharp band in the region of 1464 cmꢀ1 appearing
in the spectra of both the ligands, attributable to νC–O, is found to
be shifted to 1528 and 1518 cmꢀ1 in the respective Cu(II) com-
plexes Cu21 and Cu22.
Electronic spectra of ligands 1 and 2 and their respective com-
plexes Cu21 and Cu22 (Fig. 1) show nearly similar spectral patterns.
However, in addition to the d–d band appearing at 568 nm, the
consequent shift observed in the ligand-centred transition confirms
the complexation with Cu(II). The ligand-centred bands at 239 and
264 nm are attributed to the σ–π* and π–π* transitions. The peak at
338 nm of the ligands is found to be shifted to 395 nm in their re-
spective complexes. This may be assigned to a ligand-to-metal
charge transfer transition caused by phenolate oxygen to Cu(II)
centre[14] as evidenced by a bathochromic shift of approximately
57 nm. The d–d band at 568 nm of complexes Cu21 and Cu22 re-
veals a distorted square planar geometry of the Cu(II) centre. The
UV–visible data for the ligands and their complexes are summa-
rized in Table 1.
Scheme 1. Synthesis of macrocyclic ligands 1 (RRRR) and 2 (SSSS) and their
copper(II) helicates Cu21 and Cu22.
In addition to obtaining UV spectra, we performed a titration of
ligand versus cupric acetate monohydrate using a 1:1 (v/v) ratio
of tetrahydrofuran THF:CH3CN solvent mixture (Fig. S12). The
respectively, with 3,3′-methylenebis(5-(tert-butyl)-2-hydroxybenzal-
dehyde) using boric acid as a template[13] and were obtained in
1
90% yield (Scheme 1). The H NMR spectra (Figs S1 and S5) of li-
gands 1 and 2 each show a peak at 8.4 ppm corresponding to four
hydrogens and confirming the formation of azomethine moiety
(CH¼N).
The broad signals at 13.38 and 13.40 ppm in the spectra of 1 and
2, respectively, disappear on deuterium exchange (Fig. S2), indicat-
ing that they correspond to phenolic OH protons. Similarly two dis-
tinguishable singlets appear at 4.0 and 4.7 ppm corresponding to
four hydrogens each. These resonances are attributable to the
methylene (CH2) and asymmetric methine (CH) groups, respec-
tively, and together they confirm the formation of the macrocyclic
ligands 1 and 2, respectively. Because of the symmetry, both these
ligands are anticipated to give 15 peaks in the 13C NMR spectra
(Figs S3 and S6) as observed. Furthermore DEPT-135° NMR spectra
(Figs S4 and S7) recorded for 1 and 2 each have one peak pointing
down at 29.14 and 29.16 ppm, respectively. These are attributed to
CH2 groups. The remaining signals pointing up confirm the CH
carbons. The ESI-MS (Figs S8 and S10) of 1 and 2 show dominant
peaks at m/z = 1090.40 and 1089.97, respectively, indicating the
formation of the [M + H]+ ion (calculated: 1090.63). FT-IR spectra
reveal the presence of characteristic OH, aliphatic C–H and C¼N
stretching frequencies at, respectively, 3433, 2960 and 1629 cmꢀ1
for 1 (Fig. S13(a)) and 3435, 2955 and 1626 cmꢀ1 for 2 (Fig. S13(b)).
After the successful synthesis of these ligands, we next prepared
the respective Cu(II) binuclear complexes Cu21 and Cu22. Each of
these complexes possesses two sets of N2O2 chromophoric do-
mains arranged in a tetradentate manner. The binuclear Cu(II) com-
plexes were synthesized by treating cupric acetate monohydrate
with 1 or 2 in a 2:1 metal-to-ligand stoichiometry using acetoni-
trile–chloroform solvent mixture (80:20 ratio) at room temperature.
After reaction for 1 h, a green-coloured precipitate appeared which
was isolated by filtration and dried to afford 82% yield. ESI-MS and
MALDI-TOF MS confirm the formation of binuclear complexes. The
peak at m/z = 1211.95 is attributed to Cu21 + H+ and that at 1233.49
Figure 1. UV–visible spectra of ligands and complexes recorded in THF
(1 × 10ꢀ5 M). The inset shows the d–d band region for complexes Cu21
and Cu22.
Table 1. UV–visible spectral data for ligands 1 and 2 and complexes
Cu21 and Cu22
Species
Wavelength, nm (ε)
Ligand-centred transitions
d–d band
1
239 (56 000), 264 (73 000), 338 (24 000)
239 (56 000), 264 (73 000), 338 (24 000)
244 (86 000), 290 (68 000), 395(28 100),
420 (21 700)
—
—
2
Cu21
568 (1060)
Cu22
242 (73 000), 291 (53 000), 396 (22 200),
427 (15 300)
569 (2300)
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Asymmetric henry reaction catalyzed by binuclear Cu(II) complex
intensity at 395 nm is found to increase with an increasing amount
of cupric acetate monohydrate. The highest intensity obtained at a
2:1 (metal-to-ligand) ratio confirms the formation of binuclear com-
plexes (Fig. 2). Beyond this ratio, there is no increase in absorbance
at 395 nm.
Circular dichroism (CD) spectra recorded for both ligands 1 and 2
and the respective complexes Cu21 and Cu22 are shown in Fig. 3.
Showing exactly opposite CD patterns, it is obvious to understand
that ligands 1 and 2 and their respective complexes exist in
enantiopure form. Ligands 1 and 2, each having four asymmetric
carbons, possess RRRR and SSSS configurations, respectively. In ad-
dition to evidencing opposite optical sign in their respective CD
patterns, the complexes show metal-centred chirality: ligand 1 with
RRRR configuration shows metal-centred chirality ΔΔ in Cu21 and
ligand 2 with SSSS configuration shows ΛΛ chirality in Cu22 (Fig. 3).
A systematic titration carried out using UV–visible spectra of li-
gands with an increasing concentration of cupric salt suggests a
Figure 4. Titration of Cu(CH3COO)2ꢁH2O against ligand performed using CD
spectra recorded in THF (1 × 10ꢀ4 M). Inset shows Δε measured at λ = 430 nm.
2:1 metal-to-ligand complexation (Fig. S12). Similarly, the
enantiopure ligands 1 and 2 were titrated with cupric acetate
monohydrate and the CD responses are depicted in Fig. 4. Each
of these ligands contains four asymmetric carbons, each generating
either RRRR or SSSS stereochemical configuration. Each enantiopure
ligand upon complexation with Cu(II) metal centre gains a distorted
square planar geometry. As evident from the UV–visible spectral
data (Table 1), the position of the d–d band indicates distorted
square planar geometry; the respective optical signs in the CD spec-
tra further confirm that ligand 1 with (RRRR) isomer produces ΔΔ
chirality, while ligand 2 with (SSSS) isomer generates ΛΛ chirality
in their respective binuclear complexes, as is evident from Figs. 3
and 4. Following the intensity enhancement observed in the li-
gand-to-metal charge transfer band at λ = 430 nm, a plot of the ra-
tio of concentration of cupric acetate versus Δε of CD intensity, as
shown in the inset of Fig. 4, reaffirms the formation of a 2:1 ratio
of metal to ligand. In order to study the effect of temperature on
chirality, we obtained variable-temperature CD spectra ranging
from ꢀ10 to 65°C at 5°C intervals using THF as solvent for Cu21
(Fig. S14). In this temperature range, the complex shows no change
in the dichroic pattern, illustrating that the chirality of this complex
is thermally stable. Further a detailed investigation carried out
in combination with CD and optical rotatory dispersion (ORD)
(Fig. S15)[15] suggests the optical sign of the ligands and complexes.
Accordingly CD and ORD indicate that complex Cu21 shows a
positive Cotton effect, while Cu22 exhibits a negative Cotton effect.
Figure 2. Nonlinear curve fitting for titration of ligand versus Cu(CH3COO)
2ꢁH2O (1 × 10ꢀ4 M) for UV–visible spectral data derived from λ = 395 nm.
Cyclic voltammetry
The electrochemical behaviour of complexes Cu21 and Cu22 were
studied using cyclic voltammetry with dimethylformamide (DMF)
as solvent, tetrabutylammonium perchlorate (TBAP) as supporting
electrolyte and Ag/AgCl as reference electrode in the potential
range ꢀ1.5 to 1.5 V. Separate cyclic voltammograms were recorded
for ligands 1 and 2 giving similar cyclic voltammetry patterns stud-
ied in the region 0.25–1.5 V; the range ꢀ1.5 to 0.25 V is considered
to represent Cu(II)/Cu(I) redox couple in the complexes. The reduc-
tion of Cu(II) to Cu(I) takes place at much lower potential of ꢀ1.02 V
and is weakly reversible. Various electrochemical parameters,
namely Epc, Epa, ΔEp and E01/2, derived from cyclic voltammograms
at various scan rates of 600, 700, 800, 900 and 1000 mV sꢀ1 are
Figure 3. CD spectra of ligands 1 and 2 and complexes Cu21 and Cu22
recorded in THF (1 × 10ꢀ4 M). Inset shows the expanded d–d band region.
Appl. Organometal. Chem. 2016, 30, 95–101
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E. Chinnaraja et al.
Table 2. Electrochemical data for complexes Cu21 and Cu22a
Complex Scan rate (mV sꢀ1 Epa (V) Epc (V) ΔEp (V) E01/2 (V)
without any additional base or additive, but, unfortunately, there is no
conversion even after 72 h at RT (Table 3, entry 1).
)
To determine the appropriate base, we screened various addi-
tives (Table 3). In the process of optimization, additives N,N-
diisopropylethylamine (DIPEA), lutidine (2,6-dimethylpyridine),
triethylamine, tributylamine and N,N,N′,N′-tetramethylethylenedi-
amine (TMEDA) were examined (Table 3, entries 2–6). Among these
additives, lutidine gives better efficiency by reducing the reaction
time to 48 h in THF at RT and by giving better enantioselectivity
(Table 3, entry 6). Hence lutidine was chosen as nucleophilic base
for this reaction for further optimization. The two methyl groups
in lutidine might favour it to act as a moderate base leading to bet-
ter selectivity than the other strong bases. To further identify the
best catalyst among complexes Cu21 and Cu22, both were
screened and found to provide similar enantioselectivities and
yields, but with opposite configuration of β-nitroalcohol (Table 3,
entries 6 and 7). So, all further reactions are carried out only with
catalyst Cu21. To identify a suitable solvent, various solvents were
checked for homogeneous reaction mixtures. However, limited sol-
ubility of the complexes in common solvents like THF, chloroform,
dichloromethane, toluene, ethylacetate and acetone prompted us
to also check binary solvents such as THF–methanol, THF–ethanol
and THF–water. The respective yield and enantiomeric excess (ee)
are presented in Table 4 (entries 1–10). All these attempts suggest
THF as the appropriate solvent rendering a high yield of 88% and
highest ee of 67% (Table 4, entry 11). There are a significant number
of reports[21] suggesting alcohol and aqueous medium being better
solvents for this reaction. However, utilizing these solvent systems,
no significant change in the yield and selectivity is observed in the
present case. Binary solvent mixtures such as THF with methanol,
ethanol and water in 1:1 (v/v) ratio give no encouraging
enantioselectivities or yields (Table 4, entries 7–9).
Cu21
600
700
800
900
1000
600
700
800
900
1000
ꢀ0.44
ꢀ0.34
ꢀ0.25
ꢀ0.28
ꢀ0.25
ꢀ0.19
ꢀ0.14
ꢀ0.10
ꢀ0.09
ꢀ0.06
ꢀ1.02
ꢀ1.10
ꢀ1.13
ꢀ1.14
ꢀ1.16
ꢀ0.78
ꢀ0.90
ꢀ0.91
ꢀ0.91
ꢀ0.83
0.58
0.76
0.88
0.86
0.91
0.59
0.76
0.81
0.82
0.86
0.29
0.38
0.44
0.43
0.45
0.29
0.38
0.40
0.41
0.43
Cu22
aΔEp = Epa ꢀ Epc; E10/2 = (Epa ꢀ Epc)/2.
To optimize the reaction temperature, we performed the catalytic
reaction at various temperatures from RT to 60°C (Table 4, entries
10–12). Better enantioselectivity is observed at 45°C (Table 4, entry
11). Although the yield is enhanced to 90% at 60°C, the correspond-
ing enantioselectivity is lower (Table 4, entry12) and hence 45°C is
fixed as the appropriate temperature. Furthermore, optimization
of the catalyst loading was performed by varying the catalyst
amount from 0.5 to 10 mol% (Table 4, entries 13–16). As the loading
Figure 5. Cyclic voltammogram for Cu21 in DMF + 0.5 M TBAP, with Pt as a
working electrode versus Ag/AgCl (scan rate: 600 mV sꢀ1).
listed in Table 2. The cyclic voltammogram shown in Fig. 5,
depicting a single redox couple, is assigned to the two-electron sin-
gle-step redox judged from ΔEp. Cathodic peak (Epc), anodic peak
(Epa) and redox (E1/2) potentials are within the reported range of
those of similar dicopper systems.[16] The peak-to-peak separation
(ΔEp) is sensitive towards the Cu(II) environment and its Cu–Cu
interactions.[17] The single redox couple indicates the reduction of
Cu2+Cu2+ → Cu1+Cu1+, two-electron redox process, and suggests
that both metal centres exist in a similar environment which agrees
with our observation of electronic spectra. The ligands being
ditopic, both complexes each contain two Cu(II) ions.
Table 3. Screening of catalysts and additives using benzaldehyde with
nitromethanea
To understand the intermetallic magnetic interactions, and their
impact on the catalytic efficiency, we determined the magnetic mo-
ment using Evans’ method[18] in solution state. Accordingly, the
magnetic moments for 1 and 2 are obtained as 0.886 and 0.883
BM against the calculated value of 1.93 BM for Cu(II) ion. Such a re-
duction in the magnetic moment may be possible in a dimeric sys-
tem with a strong intermetallic exchange interaction, further
confirming the dinuclear Cu–Cu association.[19]
Entry
Catalystb
Additive
Yield (%)c
ee (%)d
1
2
3
4
5
6
7
Cu21
Cu21
Cu21
Cu21
Cu21
Cu21
Cu22
—
10
71
88
85
89
82
80
—
DIPEA
24 (S)
13 (S)
10 (S)
15 (S)
50 (S)
50 (R)
triethylamine
Tributylamine
TMEDA
Lutidine
Lutidine
Catalysis
aAll reactions were carried out with 0.5 mmol of benzaldehyde, 5 mmol
of nitromethane and 0.5 mmol of of additives.
bCatalyst at RT, 48 h.
cIsolated after column chromatography.
dDetermined using HPLC (Chiralcel OD).
The Henry reaction[20] is a base-catalysed nucleophilic reaction. Initially
we optimized various reaction parameters, namely additive variation,
solvent, temperature and catalyst loading, using complex Cu21 with
benzaldehyde and nitromethane as model substrates using THF as sol-
vent, at room temperature (RT; 25°C). Initially the reaction was assessed
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Asymmetric henry reaction catalyzed by binuclear Cu(II) complex
Table 4. Screening of solvents, catalyst loading and temperature using
1b, 1c) and electron-withdrawing groups (Chart 1: 2a, 2b, 2c).
Electron-donating substituted substrates such as 4-methoxyben-
zaldehyde and 3-methoxybenzaldehyde give better selectivity
(Chart 1: 1b, 1c) than electron-withdrawing substituents like 4-
fluorobenzaldehyde, 4-bromobenzaldehyde and 4-nitrobenzal-
dehyde (Chart 1: 2a, 2b, 2c). The highest enantioselectivity is ob-
served for benzaldehyde, i.e. 67% ee with 88% yield (Chart 1: 1a).
In the case of 9-anthracenaldehyde, a 68% yield and 55% ee is ob-
tained (Chart 1: 3).
In order to check the stability of the catalyst, we performed a cat-
alytic recycling study using benzaldehyde and nitromethane as rep-
resentative substrates under the optimized reaction conditions.
After completion of the reaction, the solvent was evaporated under
vacuum and the products were extracted using hexane. The cata-
lyst was washed with hexane, dried and reused without any further
purification. The catalyst is found to be efficient for up to five cycles
without loss of activity and enantioselectivity (Fig. 6).
To understand the probable catalytic mechanism, we recorded
stepwise UV–visible spectra with (i) catalyst Cu21 alone, (ii) catalyst
with benzaldehyde, (iii) catalyst with benzaldehyde and nitrometh-
ane and (iv) catalyst, benzaldehyde, nitromethane and base, the
d–d band of the spectra being monitored (Fig. 7). Based on the
UV–visible spectral changes, the catalytic mechanism is proposed
as depicted in Scheme 2. Initially, the substrate interacts with cop-
per, followed by the nitronate anion which stereoselectively attacks
the carbonyl carbon to give β-nitroalcohol.
benzaldehyde with nitromethanea
Entry Solvent
Catalyst loading Temp. (°C) Yield (%)b ee (%)c
(mol%)
1
Chloroform
1
1
1
1
1
1
1
1
1
1
1
1
0.5
3
5
RT
RT
RT
RT
RT
RT
RT
RT
RT
30
45
60
45
45
45
45
75
88
73
84
76
74
79
78
68
80
88
90
80
88
88
88
—
2
THF
51 (S)
10 (S)
36 (S)
—
3
DCM
4
Toluene
Acetone
EtOAc
THF–EtOHd
THF–MeOHd
THF–waterd
THF
5
6
50 (S)
28 (S)
25 (S)
—
7
8
9
10
11
12
13
14
15
16
45 (S)
67 (S)
40 (S)
60 (S)
43 (S)
42 (S)
42 (S)
THF
THF
THF
THF
THF
THF
10
aAll reactions were carried out with 0.5 mmol of benzaldehyde, 5 mmol
of nitromethane and 0.5 mmol of lutidine.
bIsolated after column chromatography.
cDetermined using HPLC (Chiralcel OD).
d1:1 binary solvent.
increases, the enantioselectivity decreases, although the yield re-
mains nearly the same. The highest enantioselectivity is obtained
by using 1 mol% catalyst at 45°C in THF with lutidine as additive
(Table 4, entry 11), considered as optimized conditions.
Using the optimized conditions as discussed above, we screened
various substrates with different electron-donating groups (Chart 1:
Figure 6. Recyclability of catalyst Cu21 using benzaldehyde and
nitromethane.
Chart 1. Screening of substrate. All reactions were carried out with 0.5
mmol of substrates and
5 mmol of nitromethane. Isolated yield
determined after flash column chromatography. Enantioselectivity
determined using HPLC (Chiralcel OD, Lux cellulose-1 column).
Figure 7. Stepwise UV–visible spectra obtained in THF in the presence of
Cu21, benzaldehyde, nitromethane and lutidine.
Appl. Organometal. Chem. 2016, 30, 95–101
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E. Chinnaraja et al.
Syntheses of ligands 1 and 2
Ligands 1 and 2 were synthesized using boronic acid as a template
following a simple modification of a reported proceedure.[22] 3,3′-
Methylenebis(5-(tert-butyl)-2-hydroxybenzaldehyde) (1.357 mmol,
500 mg) dissolved in 5 ml of chloroform was mixed with a dry
methanolic solution (5 ml) of boric acid (0.6785 mmol, 42 mg). This
reaction mixture was constantly stirred for 1 h at room temperature.
To this reaction mixture 10 ml of a methanolic solution of (1R,2R)-
(+)- or (1S,2S)-(ꢀ)-1,2-diphenylethylenediamine (1.357 mmol, 288
mg) was added dropwise. During the reaction, a colour change
from colourless to yellow was observed after stirring for 7 h. The
conversion of the aldehyde was monitored using TLC. Finally a yel-
low-coloured crystalline compound was isolated by simple filtration
and washed with dry methanol.
26
Ligand 1. Yield 90%; ½αꢂD = ꢀ126.6 (c 0.1, CHCl3). 1H NMR (CDCl3,
200 MHz, TMS, δ, ppm): 13.38 (s, 4H, phenolic OH), 8.4 (s, 4H, –
CH¼N), 7.27 (m, 4H, –CH), 7.17–7.10 (m, 20H, –CH), 7.02–7.0 (d, J
= 4 Hz, 4H, –CH), 4.7 (s, 4H, –CH), 4.08 (s, 4H, –CH2), 1.17 (s, 36H, –
CH3). 13C NMR (CDCl3, 500 MHz, δ, ppm): 166.51, 156.9, 140.69,
139.73, 131.40, 128.15, 127.94, 127.33, 127.14, 126.19, 117.40,
80.42, 33.85, 31.34, 29.15. FT-IR (KBr, ν, cmꢀ1): 3433, 3061, 3026,
2960, 2904, 2867, 1629, 1464, 1459, 1388, 1363, 1272, 1125, 1041,
752, 699. MALDI-TOF MS (ES+) m/z: 1090.40 [M + 2H+]. Elemental
analysis: calcd (found) for C74H80N4O4 (%): C, 81.58 (81.64); H, 7.40
(7.90); N, 5.14 (4.89).
Scheme 2. Plausible mechanism for nitroaldol reaction.
Conclusions
26
Ligand 2. Yield 90%; ½αꢂD = +126.5 (c 0.1, CHCl3). 1H NMR (CDCl3,
Binuclear Cu(II) complexes Cu21 and Cu22 were synthesized using
enantiomerically pure ligands (1 and 2) and were characterized.
The chiroptical properties of the ligands and their respective com-
plexes were thoroughly studied using CD and ORD.
Enantiomerically pure ligands 1 and 2, upon coordination with Cu
(II) metal centre, demonstrate transfer of chirality from ligand to
Cu(II) metal centre by generating ΔΔ and ΛΛ geometrical chirality
in their respective binuclear complexes. The enantiopure binuclear
Cu(II) helicate was successfully demonstrated as an enanitoselective
catalyst for asymmetric nitroalodol reaction giving 88% yield and
67% ee for benzaldehyde. The catalyst can be effectively recycled
up to five times without loss in activity.
500 MHz, TMS, δ, ppm): 13.4 (s, 4H, –OH), 8.4 (s, 4H, CH¼N), 7.27–
7.28 (m, 4H, –CH), 7.12–7.10 (m, 20H, –CH), 7.01–7.02 (d, J = 5 Hz,
4H, –CH), 4.7 (s, 4H, –CH), 4.08 (s, 4H, –CH2), 1.17 (s, 36H, –CH3).
13C NMR (CDCl3, 500 MHz, TMS, δ, ppm): 166.52, 156.9, 140.69,
139.73, 131.4, 128.15, 127.94, 127.33, 127.14, 126.2, 117.4, 80.44,
33.86, 31.34, 29.15. FT-IR (KBr, ν, cmꢀ1): 3435, 3063, 3025, 2955,
2905, 2863, 1626, 1464, 1425, 1387, 1353, 1263, 1125, 1047, 756,
696. MALDI-TOF MS (ES+) m/z: 1090.2 [M + 2H+]. Elemental analysis:
calcd (found) for C74H80N4O4 (%): C, 81.58 (81.25); H, 7.40 (7.80); N,
5.14 (5.38).
Syntheses of complexes Cu21 and Cu22
Experimental
Ligand 1 or 2 (1 mmol) dissolved in CHCl3 was added to an acetoni-
trile solution of cupric acetate monohydrate (2 mmol) and was con-
stantly stirred at room temperature for 1 h. A colour change from
blue to green occurred indicating the complexation. The precipitate
obtained was collected by filtration and dried in a vacuum desiccator.
Complex Cu21. C74H76Cu2N4O4; yield 82%. UV–visible (nm): 244,
290, 395, 568. FT-IR (KBr, ν, cmꢀ1): 3429, 3061, 3028, 2955, 2904,
2368, 1612, 1528, 1451, 1391, 1328, 1264, 1213, 1050, 833, 699.
Chemical formula for [M + H+]: C74H77Cu2N4O4+; m/z calcd (found):
Materials and methods
5-tert-Butylphenol, boronic acid, paraformaldehyde, stannic chlo-
ride (SnCl4), cupric acetate and (1R,2R)-(+)- and (1S,2S)-(ꢀ)-1,2-
diphenylethylenediamine were purchased from Aldrich & Co. All
these chemicals were used as received without any further purifica-
tion. Microanalysis was done using a PerkinElmer PE 2400 series II
CHNS/O elemental analyser. FT-IR spectra were recorded using
KBr pellets (1% w/w) with a PerkinElmer Spectrum GX FT-IR spectro-
photometer. Electronic spectra were recorded with a Shimadzu UV
3101 PC spectrophotometer. Mass analyses were performed using
the positive electron spray ionization (ESI+) technique with a Waters
Q TOF-micro mass spectrometer. 1H NMR, 13C NMR and DEPT 135°
spectra were recorded with Bruker Advance DPX200 and 500 MHz
FT-NMR spectrometers. Chemical shifts for proton resonances were
measured in ppm (δ) relative to tetramethylsilane (TMS). The CD
spectra were recorded with a JASCO 815 spectrometer. The
enantioselectivity of the Henry product was determined with HPLC
(Shimadzu SCL-10AVP) using chiral columns (Chiralcel OD and
Phenomenox Lux cellulose-1).
1211.45 (1211.95). Chemical formula for [M
+
Na+]:
C74H76Cu2N4NaO+4; m/z calcd (found): 1233.44 (1233.87). Elemental
analysis: calcd (found) for Cu2C74H78N4O5 (%): C, 72.23 (71.77); H,
6.39 (6.65); N, 4.55 (5.08).
Complex Cu22. C74H76Cu2N4O4; yield 82%. UV–visible (nm): 242,
291, 396, 569. FT-IR (KBr, ν, cmꢀ1): 3449, 3060, 3027, 2954, 2906,
2362, 1610, 1518, 1425, 1387, 1325, 1263, 1212, 1125, 1057, 756,
696. Chemical formula for [M + H+]: C74H77Cu2N4O4+; m/z calcd
(found) 1211.45 (1211.95). Chemical formula for [M + Na+]:
C74H76Cu2N4NaO+4; m/z calcd (found) 1233.44 (1233.87). Elemental
analysis: calcd (found) for Cu2C74H78N4O5: C, 72.23 (72.22); H, 6.39
(7.09); N, 4.55 (4.34).
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Appl. Organometal. Chem. 2016, 30, 95–101

Asymmetric henry reaction catalyzed by binuclear Cu(II) complex
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General procedure for Cu(II)-catalysed nitroaldol reaction of
nitromethane with aldehydes
A dry and nitrogen-flushed 5 ml flask, equipped with a magnetic
stirring bar, was charged with Cu(II) catalyst (1 mol%) and freshly
distilled dry THF (1 ml) at 45°C. Corresponding aldehyde (0.5 mmol)
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gel, 100–200 mesh, using ethyl acetate and hexanes) to give the
corresponding Henry product. Enantiomeric excess was deter-
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column using isopropanol and hexane as eluting agent. The abso-
lute configurations of the Henry products were assigned by com-
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CSMCRI communication number CSIR-CSMCRI 088/2015. The au-
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