Desymmetrization of meso diols using enantiopure zinc (II) dimers: Synthesis and chiroptical properties

Article abstract of DOI:10.1002/aoc.4827

The one-pot metal templated synthesis of enantiopure binuclear Zn (II) complexes Zn₂L¹–Zn₂L⁴ were obtained by treating (1R,2R)-diphenylethylenediamine or (1S,2S)-diphenylethylenediamine with 2-hydroxy-5-methyl-1

Full text of DOI:10.1002/aoc.4827

Received: 12 October 2018
DOI: 10.1002/aoc.4827
Revised: 3 December 2018
Accepted: 6 December 2018
F U L L P A P E R
Desymmetrization of meso diols using enantiopure zinc (II)
dimers: Synthesis and chiroptical properties
Eswaran Chinnaraja1,2 | Rajendran Arunachalam1,2 | Jayanta Samanta2,3
Ramalingam Natarajan2,3 | Palani S. Subramanian1,2
|
1 Inorganic Materials and Catalysis
The one‐pot metal templated synthesis of enantiopure binuclear Zn (II)
complexes were obtained by treating (1R,2R)‐
Zn2L1–Zn2L4
Division, CSIR‐Central Salt and Marine
Chemicals Research Institute (CSIR‐
CSMCRI), Bhavnagar 364 021Gujarat,
India
2 Academy of Scientific and Innovative
research (AcSIR), Ghaziabad 201 002,
India
3 Organic & Medicinal Chemistry Division,
CSIR‐Indian Institute of Chemical
Biology, Kolkata, India
diphenylethylenediamine or (1S,2S)‐diphenylethylenediamine with 2‐hydroxy‐
5‐methyl‐1,3‐benzenedicarboxaldehyde or 4‐tert‐butyl‐2,6‐diformylphenol and
zinc acetate. The chiroptical properties of the complexes were studied by using
circular dichroism spectroscopy. These ΔΔ and ΛΛ complexes were used as
enantioselective catalysts for desymmetrization of meso diol to achieve
monobenzoylated product with 96% yield and 88% ee.
Correspondence
KEYWORDS
Palani S. Subramanian, Inorganic
Materials and Catalysis Division, CSIR‐
Central Salt and Marine Chemicals
Research Institute (CSIR‐CSMCRI),
Bhavnagar‐ 364 021, Gujarat, India.
Email: siva140@yahoo.co.in
binuclear zinc complexes, chiroptical properties, desymmetrization, macrocycle, one‐pot synthesis
Funding information
DST‐SERB New Delhi, Grant/Award
Numbers: SB/S1/IC‐26/2013 and SR/S1/
IC‐23/2011
1 | INTRODUCTION
complexes,[6] phosphine[7] and phosphinite catalysts.[8]
Enzymatic[9] and kinetic resolution methods[10] were also
Meso diols of cyclopentane, cyclohexane, cyclooctane and
1,2‐diphenylethylene, etc. are known to possess C2 sym-
metry. Such diols are widely used in their symmetrical
and unsymmetrical forms as building blocks in various
pharma and organic compounds.[1] Nadolol, the well‐
known β‐blocker, contains a meso diol.[2] Conversion of
an achiral or meso compound to an enantiorich chiral
product by destructing the C2 symmetry is known to be
explored extensively. As desymmetrization of meso diols
is considered one of the highly challenging reactions,
the metal‐based chiral catalysts are considered superior.
Stereoselective acylation products are important compo-
nents in the preparation of various precursors in pharma-
ceutical and organic industries, and natural product
synthesis.[11] In this regard, although many catalysts are
reported,[12,13] a need for the development of a new cata-
lyst that aims to achieve high ee and yield depending
upon the stereochemical‐fit between the catalyst–
substrates and the lack of recyclability, etc. is considered
essential. In this regard, many homo‐ and heteronuclear
complexes that are reported for their selectivity,
copper‐[14] and zinc‐based homodimers[15] are found to
one of the highly challenging steps in such
a
desymmetrization reaction.[3] Desymmetrized diols are
generally obtained by implying biocatalysis, for example,
BCL (Burkholderia capacia lipase) enzyme.[4] Further,
the enantiorich desymmetrized products of monoesters
were also achieved by adapting various organo,[5] metal
Appl Organometal Chem. 2019;e4827.
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© 2019 John Wiley & Sons, Ltd.
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https://doi.org/10.1002/aoc.4827

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CHINNARAJA ET AL.
be efficient. Keeping this in mind, aiming to develop a
new chiral catalyst with an enhanced stereoselectivity
and recyclability at ambient conditions, we have recently
reported similar binuclear copper complexes[16] and
mononuclear zinc complexes[17] as efficient catalysts with
high yield, ee and recyclability. In the present manuscript,
we report very simple and easy‐to‐synthesize binuclear
chiral complexes, which are efficient at catalysing such
desymmetric acylation reactions. This procedure, thus
by‐passing the multistep synthetic complexities in the
previous reports, provides a very simple and single‐step
synthetic approach[18] to achieve enantiopure catalysts
for such desymmetric acylation.
et al.[19] enhanced the yield to 80–82% (Scheme 1), and sim-
plified the synthetic complexity into a single step as
described in the Experimental section. The m/z values of
ESI‐MS for 1 (m/z = 975.66), 1' (m/z = 865.99), 2 (m/z =
951.11) and 2' (m/z = 951.44) that are observed correspond
to monocations calculated as m/z = 975.23, 865.97, 951.26
well, respectively.
The 1H‐NMR spectra of the complexes showed two dis-
tinguishable singlets at δ = 8.25, 8.05 ppm corresponding
2 | RESULTS AND DISCUSSION
The binuclear enantiopure complexes [Zn2(RRRR)‐
L1(OAc)2] (1), [Zn2(SSSS)‐L2(OAc)2] (1'), [Zn2(RRRR)‐
L3(OAc)2] (2) and [Zn2(SSSS)‐L4(OAc)2] (2') were
prepared by the one‐pot metal template method by treating
stepwise2‐hydroxy‐5‐methyl‐1,3‐benzenedicarboxaldehyde
(4‐MDFP), or 4‐tert‐butyl‐2,6‐diformylphenol (4‐tBDFP)
with zinc (II) acetate followed by either (1R,2R)‐
diphenylethylenediamine [(1R,2R)‐DPEN] or (1S,2S)‐
diphenylethylenediamine [(1S,2S)‐DPEN], as shown in
Scheme 1. A minor modification in the approach of Gao
FIGURE 1 UV–Vis spectra of 1, 1', 2 and 2' in THF (1 × 10−5 M)
SCHEME 1 Enantiopure Zn (II) dimers by metal template method

CHINNARAJA ET AL.
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to the CH=N group, which fits well with the integral
value of two hydrogens; and a multiplet at δ = 7.3–7.40
ppm corresponds to 24 hydrogens in the aromatic region
and a singlet at δ = 2.14 ppm is attributable to the methyl
group, which together confirm the formation of macrocy-
clic zinc (II) dimeric complex (Figures S5–S7). Electronic
absorption spectra of the complexes 1, 1', 2 and 2' almost
resemble each other, with two well‐resolved bands at
256–257 and 375‐381 nm attributed to the σ‐π*, π‐π* tran-
sitions and LMCT transitions [phenolate oxygen to Zn
(II) centre], respectively (Figure 1).
The circular dichroism (CD) spectra of 1, 1' and 2, 2' in
Figure 2 reveal an opposite cotton effect at 400 nm with
positive and negative signs. The equal and opposite opti-
cal behaviour obviously indicate that the complexes are
in enantiopure form. The ligands L1 and L3 constructed
with an enantiopure 1,2‐diphenylethylenediamine pos-
sess RRRR components and produce a macrocyclic com-
plex with ΛMRC = ΛΛ‐[Zn2(RRRR)‐L1,3] in 1 and 2,
while the other ligands L2 and L4 holding the opposite
enantiomer possess SSSS configuration and produce
ΔMSC = ΔΔ‐[Zn2(SSSS)‐L2,4] in the complexes 1' and
2'. Having used enantiopure (1R,2R)‐DPEN or (1S,2S)‐
DPEN, the enantiopurity of the complexes 1, 1', 2 and 2'
is beyond doubt. All the metal centres in these complexes
possess pentacoordinated geometry, and the assignment
of the chiral descriptors Δ and Λ is possible in principle.
FIGURE 2 Circular dichroism (CD) spectra of enantiopure
dinuclear zinc complexes 1 & 1', 2 & 2' we(1 × 10−4 M)
FIGURE 3 Schematic representation
of: (i) Λ and Δ metal‐centred chirality; (ii)
ΛΛ in complex 1 and ΔΔ in complex 1'
(phenylmoieties are removed for clarity)

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CHINNARAJA ET AL.
However, such descriptors are generally described for
square‐planar and octahedral complexes in the literature.
Although the assignment is not that straightforward for
pentacoordinated complexes, there are a good number
of reports availabe in the literature.[20] The chromo-
phoric arrangement of N2O3 around the metal centre
Zn1 and Zn2 is assigned as Λ and Δ depending upon
clockwise and counterclockwise rotation, as shown in
Figure 3. The chromophore O1‐N1‐N1'‐O1'‐O2 of Zn2
and O1‐N2‐N2'‐O1'‐O3 around Zn1 revolve in the coun-
terclockwise direction in complex 1, in which the ligands
possessing RRRR chiral carbon are assigned ΛΛ descrip-
tor. Following this, complex 1' having SSSS conformer of
complex 1' produces the ΔΔ enantiomer, as shown in
Figure 3.
2.1 | Structural description by
single‐crystal X‐ray diffraction
All these zinc (II) dimeric complexes were yellow in col-
our, and slow evaporation of their DCM/CH3CN solvent
mixture provided a suitable single crystal for 1, 1' and
2'. Summary of the crystallographic data for all the com-
plexes are given in Table 1. The neutral binuclear zinc
(II) complex consisting of two DPEN and two 4‐MDFP
units incorporates two Zn (II) metals. The DPEN used
in the synthesis was of enatiopure form either in (1R,
2R) or (1S, 2S), the respective ligand thus gains four chi-
ral centres in each complex.
The enantiopure dimeric complexes of zinc (II) acetate
are crystallized in chiral space groups P21 in 1 and 1' and
TABLE 1 Summary of the crystal data for 1, 1' and 2'
Identification code
(1)
(1')
(2')
Empirical formula
C56H54Cl4N6O6Zn2
1179.59
C50H48N4O8Zn2
963.66
C56H57N4O6.5Zn2
Formula weight
1020.79
Temp./K
100
100
100
Crystal size/mm3
0.16 × 0.16 × 0.12
monoclinic
P21
0.24 × 0.18 × 0.12
monoclinic
P21
0.18 × 0.12 × 0.12
Crystal system
orthorhombic
Space group
P212121
a/Å
11.2314(5)
10.7745(4)
22.2565(9)
90
12.4061(8)
10.8649(7)
16.7263(13)
90
10.6782(4)
b/Å
20.1147(8)
c/Å
24.4386(9)
α/°
90
β/°
96.386(3)
90
101.323(5)
90
90
γ/°
90
Volume/Å3
2676.61(19)
2
2210.7(3)
2
5249.1(3)
Z
4
ρ
calcg/cm3
1.464
1.448
1.292
μ/mm−1
1.152
1.146
0.967
F (000)
1216.0
1000.0
2132.0
Radiation
MoKα (λ = 0.71073)
19 532
MoKα (λ = 0.71073)
37 601
MoKα (λ = 0.71073)
91 000
Reflections collected
Independent reflections
Data/restraints/parameters
Goodness‐of‐fit on F 2
Final R indexes [I ≥ 2σ (I)]
Final R indexes [all data]
8475 [Rint = 0.0514, Rσ = 0.0868] 9058 [Rint = 0.0768, Rσ = 0.0817] 10 753 [Rint = 0.0540, Rσ = 0.0381]
8475/33/601
9058/5/587
10 753/295/711
1.040
1.045
1.027
R1 = 0.0645, wR2 = 0.1618
R1 = 0.0903, wR2 = 0.1794
R1 = 0.0513, wR2 = 0.1101
R1 = 0.0793, wR2 = 0.1233
1.41/−0.52
R1 = 0.0323, wR2 = 0.0707
R1 = 0.0420, wR2 = 0.0738
0.38/−0.51
Largest diff. peak/hole/e Å−3 1.16/−1.26
Flack parameter
CCDC
0.006(13)
1867277
−0.032(10)
0.009(4)
1867278
1867279

CHINNARAJA ET AL.
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P212121 in 2' with two and four molecules in the unit cell,
respectively. The selected bond distances and bond angles
are presented in Figure S15 and Table S2. The macrocyclic
ligand containing N2O2N2 metal‐binding domain accom-
modates two Zn (II) ions. All the ligands in [Zn2L1(OAc)2]
to [Zn2L4(OAc)2] possess two metal‐binding domains,
each containing N2O2 chromophoric compartments with
two azomethine nitrogens and two phenolic oxygens.
The central phenolate oxygens (O1, O2) bridge both the
Zn (II) centres and adopt a star‐like conformation, as
shown in Figures 4–6. Thus, each Zn (II) ion coordinating
to two azomethine nitrogens N1, N2 and two phenolate
oxygens O1, O2 form a distorted square base, with the fifth
coordination occupied by acetate ions in its axial site,
revealing a distorted square‐pyramidal geometry of Zn
(II) metals in all the complexes.
The Zn (II) metal in 1 (Figure 4) sitting on the N2O2
square base coordinated to N1N2O2O1 chromophoric
atoms with bond distances Zn1‐N1 = 2.043(8) Å, Zn1‐
N2 = 2.047(9) Å, Zn1‐O1 = 1.996(8) Å and Zn1‐O2 =
2.072(8) Å. The Zn1 is moved up slightly by 0.764 Å and
the Zn2 is moved down by 0.767 Å from their respective
FIGURE 4 ORTEP diagram of 1
showing atom numbering (solvents were
removed for better clarity)
FIGURE 5 ORTEP diagram of 1'
showing atom numbering (solvents were
removed for better clarity)

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CHINNARAJA ET AL.
FIGURE 6 ORTEP diagram of 2'
showing atom numbering (solvents were
removed for better clarity)
mean plane. The Zn1‐Zn2 distance within the dimer is
measured as 3.167 Å. The trans angles <O2Zn1N1 =
ion is moved down slightly by 0.786 Å and the Zn2 is moved
up by 0.779 Å from their respective mean planes. The Zn1‐
Zn2 distance is 3.170 Å. The trans angles <O2Zn1N1 =
147.7(2)° and < O1Zn1N2 = 121.2(2)°; and the cis angles
<N2Zn1O2, N2Zn1N1, O1Zn1O2, O1Zn1N1 are found to
be 86.7(2), 81.6(2), 78.07(19), 82.4(2)°.
The Zn (II) metal in 2' (Figure 6) sitting on the N2O2
square base coordinated to N1N2O2O1 atoms with bond
distances Zn1‐N3 = 2.085(3) Å, Zn1‐N4 = 2.041(3) Å,
131.8(3)° and
<
O1Zn1N2 = 139.5(4)°; cis angles
<N2Zn1O2, N2Zn1N1, O1Zn1O2, O1Zn1N1 are found
to be 80.9(3), 81.8(3), 76.7(3), 88.5(3)°.
The Zn (II) metal in 1' (Figure 5) sitting on the N2O2
square base coordinated to N1N2O2O1 atoms with bond
distances Zn1‐N1 = 2.051(6) Å, Zn1‐N2 = 2.061(6) Å,
Zn1‐O1 = 2.076(5) Å and Zn1‐O2 = 1.993(5) Å. The Zn1
TABLE 2 Screening of catalysta
Entry
Catalyst
Catalyst, X mol%
Yield,b
%
ee,c %
1
2
3
4
5
6
7
8
9
1
1'
2
2'
1
1
1
1
1
5
75
73
74
75
65
75
80
85
80
65(1S,2R)
64(1R,2S)
60(1S,2R)
61(1R,2S)
50
5
5
5
2
8
69
10
15
20
75
70
66
aAll the reactions were carried out with 0.2 mmol of mesohydrobenzoin, 0.2 mmol of PhCOCl, 0.4 mmol of lutidine and 2 ml of solvent.
bIsolated yield.
cDetermined by HPLC (Lux cellulose‐1 column). Reaction time 12 hr.

CHINNARAJA ET AL.
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Zn1‐O1 = 2.030(2) Å and Zn1‐O2 = 1.939(8) Å. The Zn1
and Zn2 atoms in the dimer with an intradimer M‐M dis-
tance 3.185 Å are moved down slightly by 0.686 Å (Zn1)
and up by 0.859 Å (Zn2), respectively, from their respec-
tive mean planes towards their fifth axial coordination.
The trans angles <O2Zn1N4 = 144.0(4)° and < O1Zn1N3
= 136.85(10)°, and the cis angles <O2Zn1N3, N4Zn1N3,
O1Zn1O2, O1Zn1N4 are found to be 88.8(2), 81.41(10),
75.48(15), 86.18(9)°. In all these cases, the phenolate
oxygen bridging both the metal centres provides a μ2‐
phenoxo bridge. Having used an enantiopure 1,2‐
diphenylethylenediamine, the respective complexes in
their crystallographic structures illustrate a ΛΛ configura-
tion in 1 and 2, and a ΔΔ metal‐centred chirality in 1' and
2'. After the successful synthesis of these complexes, their
enantiopurity inspired us to investigate their catalytic
ability in converting meso‐hydrobenzoin 3a to corre-
sponding monobenzoylated products (1S,2R)‐3b and
1R,2S)‐3b, and the respective data are shown in Table 2.
Initially, we tested all the catalysts (1, 1', 2 and 2') with
5 mol% catalyst loading, 0.5 equivalence of lutidine, using
benzoyl chloride (PhCOCl, 0.5 eq.) as acylating agent and
dichloroethane as a solvent at room temperature (RT;
Table 2, entries 1–4). The reaction time was monitored
by thin‐layer chromatography (TLC) following the con-
sumption of the substrate. All the catalysts gave 74 1%
yields and ee ranges of 60–65% (Table 2, entries 1–4).
The catalysts 1 and 1' gave similar yields, they varied only
in the enantiomeric nature of the product of the monoes-
ters. Among the four catalysts screened, the catalysts 1
and 1' showed an enhancement in the enantioselectivity
that encouraged us to consider them for further optimiza-
tion. Because both these catalysts gave similar yields and
enantioselectivity, complex 1 was chosen for further opti-
mization. Initially, we attempted to vary the amount of
catalyst from 2 to 20 mol% (Table 2, entries 5–9). When
the catalyst amount increased from 2 mol% to 10 mol%,
the yield also increased from 65% to 80% (Table 2, entries
7–9) alongwith ee (50–75%). A further increment in the
catalyst loading from 15 mol% to 20 mol% caused a dra-
matic decrease in the enantioselectivity, i.e. 70–66%
(Table 2, entries 8 and 9). Henceforth, we decided to fix
the amount of catalyst as 10 mol%, in which the yield
was obtained as 80% with highest ee 75% (Table 2, entry
7). Then, in an attempt to optimize the temperature, the
yield and ee were monitored at different temperatures,
for example 40ºC, 0ºC, −5ºC, and up to −10°C
(Figure 7a). While increasing the temperature from RT
(30°C) to 40°C, a significant loss in the enantioselectivity
to 45% and yield to 70% (Figure 7a) was observed. Hence,
lowering the temperature from RT to 0°C gave an
enhancement, i.e. yield 85%, ee 78% (Figure 7a). A similar
approach at −5°C gave 86% yield, but the fall in ee to 63%
FIGURE 7 Optimization of reaction conditions. (a) All the
reactions were carried out with 10 mol% of catalyst, 0.2 mmol of
mesohydrobenzoin, 0.2 mmol of PhCOCl, 0.4 mmol of base and 2
ml of solvent. (b) Isolated yield. (c) Determined by high‐
performance liquid chromatography (HPLC; Lux cellulose‐1
column). (d) Reaction time is 12 hr
(Figure 7a) was not encouraging. A further decrease in
temperature to −10°C resulted in 85% yield with a further
fall in the ee to 60% (Figure 7a). Thus, it is convincing
that to obtain a better yield and ee, the temperature of
0°C has been chosen as an optimum temperature for this
reaction. As the yield and enantioselectivity of the prod-
uct depends on the strength of the base, an attempt to
identify the optimum base was also performed. Our initial
analysis without using base provides a very negligible
amount of yield. Hence, we have conducted the reaction
using a variety of bases, such as triethylamine (Et3N;
Figure 7b; yield 60%, ee 55%), diisopropylethylamine
(DIPEA; Figure 7b; yield 88%, ee 80%) and some inor-
ganic bases like Na2CO3 (Figure 7b; yield 50%, ee 35%)
or K2CO3 (Figure 7b; yield 45%, ee 28%). All these bases
act as deprotonating agents; among the bases used,

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CHINNARAJA ET AL.
DIPEA gives better results than the others. Hence, DIPEA
was chosen as the best deprotonating agent. Similarly,
solvent plays a major role in homogeneous catalysis, so
we next examined for a suitable solvent. As most of
the reported benzoylation reactions are conducted in
halogenated solvents, the main emphasis was given for
halogenated solvents, and the results are presented in
Figure 7c. Solvents such as CCl4 (Figure 7c; yield 70%,
ee 65%), DCM (Figure 7c; yield 96%, ee 88%) and a few
non‐halogenated solvents such as toluene (Figure 7c;
yield 76%, ee 58%), THF (Figure 7c; yield 68%, ee 63%)
and EtOAc (Figure 7c; yield 56%, ee 34%) were tested.
Excitingly, DCM gave a good yield of 96% and better
enantioselectivity of 88%.
Adapting the above‐optimized conditions, we next
investigated various meso‐1,2‐diols as substrates (Figure 8
, 3b–13b) using 1 as a catalyst. In the case of 3a, the catalyst
gave 96% yield with 88% ee (Figure 8, 3b). Then we moved
from acyclic diol to cyclic diol containing five‐membered
and eight‐membered rings. The cyclopentane diol (4a)
has converted to the respective monoester (4b) with 92%
yield and 40% ee (Figure 8, 4b), the cyclohexane diol (5a)
produced monoester (5b) with 91% yield and 50% ee
(Figure 8, 5b).
The cyclooctane diol 6a gave 93% yield and 40% ee of
monoester product 6b (Figure 8; 6b). The 2,3‐butane‐diol
7a, which is a methyl‐substituted diol, gave good yield
(90%) but the ee was very poor, i.e. 30% (Figure 8, 7b).
From the substrate variation, the mesohydrobenzoin
(3a) gave the best result (yield 96%, ee 88%) compared
with the other substrates (Figure 8, 3b). This may be
because the 1,2‐diphenyl moiety with a phenyl ring had
a strong π … π interaction between the catalyst and sub-
strates with aromatic moiety that might have favoured
the asymmetric benzoylation. Hence, keeping meso‐
hydrobenzoin as a substrate, we then varied different acyl
and aroyl chlorides with the same optimized conditions,
and the results are presented in Figure 8, 8b–13b. When
4‐methylbenzoylchloride 8a was used, the corresponding
monoester 8b was produced with 90% yield and 78% ee
(Figure 8, 8b). The 4‐nitrobenzoylchloride 9a gave mono-
ester 9b with 96% yield, but the enantioselectivity was
reduced to 20% (Figure 8, 9b), this may be because the
bulky nitro group at the para‐position might interrupt
FIGURE 8 Asymmetric benzoylation of
meso‐1,2‐diol with various aroyl and
acylchloride. (a) All the reactions were
carried out with 10 mol% of catalyst, 0.2
mmol of substrates, 0.2 mmol of PhCOCl,
0.4 mmol of DIPEA and 2 ml of solvent.
(b) Isolated yield. (c) Determined by high‐
performance liquid chromatography
(HPLC; Lux cellulose‐1 column). (d)
Reaction time is 12 hr

CHINNARAJA ET AL.
9 of 12
the catalyst–substrate interactions. The remaining 2‐
fluorobenzoyl‐chloride 10a and 4‐fluorobenzoylchloride
11a gave good yield (96% and 92%, respectively) and ee
(74% and 75%, respectively; Figure 8, 10b and 11b). The
aroyl chlorides thus gave encouraging results, so we then
screened non‐aroyl acyclic (acetyl chloride, 12a) and
cyclic chlorides (cyclohexanecarbonyl chloride, 13a) that
are found to produce monoesters (12b and 13b) with
enhanced yield (92% and 86%, respectively) but a dra-
matic decrease in ee (10% and 40%, respectively;
Figure 8, 12b and 13b). These two non‐aroyl chlorides
thus produced a good yield but poor enantioselectivity.
The variation on the acylating agent suggests that the
unsubstituted benzoyl chloride (Figure 8, 3b) is a better
acylating agent compared with the others.
Based on the results, we proposed a probable mecha-
nism for the desymmetrization of meso diol (Scheme 2).
In the first step, the substrate interacted with the catalyst
at a vacant site opposite the acetyl group attached in the
metal for an octahedral complex (TS‐I), then the alcoholic
proton deprotonated by DIPEA interacted with benzoyl
chloride (TS‐II) to form a stereoselective monoester. High
stereoselectivity was observed only in mesohydrobenzoin
compared with the other diols. The phenyl moiety in the
mesohydrobenzoin had a strong π … π interaction with
the catalyst, leading to the formation of the stereoselective
product. Although the Zn‐Zn intermetallic distance in all
three complexes ranged from 3.167 Å to 3.185 Å, similar
to that observed in the dimeric zinc reported[16,21] (Zn‐Zn
= 3.178 Å), the present complex in its chiral space group
differs in its desymmetrization mechanism. The binuclear
complex possessed ΛΛ or ΔΔ homochiral geometry in the
dimeric association, and each Zn (II) centre possessed a
pentacoordinated geometry. Hence, we propose that there
is no possibility for the bidentate or chelate coordination
of the diol with the Zn (II) dimeric centres in the present
complexes. Instead, one of the two hydroxyl groups of the
diol might have selectively coordinated through the sixth
coordination site in a monodentate fashion with each Zn
(II) centre, while the other hydroxyl group remained undis-
turbed. Thus, the non‐superimposable ΛΛ chirality in the
dimer does not permit the diol to establish bimetallic coor-
dination from the same side. Hence, each Zn (II) centre in
the homochiral dimer selectively binds one of the two
hydroxyls of the diol and establishes a sixth coordination
site from the opposite side, and thus both the Zn (II) centres
in their homochiral nature promote a stereoselective prod-
uct. To support this mechanism, we used 1H‐NMR to mon-
itor a model experiment that followed successive additions
of mesohydrobenzoin, DIPEA and benzoylchloride and cat-
alyst (i) [Zn2(RRRR‐L1)(OAc)2]; (ii) [Zn2(RRRR‐L1)(OAc)2]
+ mesohydrobenzoin;
(iii)
[Zn2(RRRR‐L1)(OAc)2] +
mesohydrobenzoin + DIPEA; and (iv) [Zn2(RRRR‐L1)
(OAc)2] + mesohydrobenzoin + DIPEA + benzoyl chlo-
1
ride. The H‐NMR for all these experiments (Figure S18)
and the follow‐up analysis strongly reconfirm the above‐
proposed mechanism.
The recyclability of the catalyst was tested to under-
stand its efficiency. Adapting 1, the mesohydrobenzoin
was chosen as a substrate and benzoyl chloride as acylat-
ing agent at optimized reaction conditions. The yield and
ee were monitored for up to six cycles, and the respective
data are shown in Figure 9. Interestingly, the catalyst was
found to be efficient by showing no loss of
enantioselectivity and yield up to the sixth cycle. The
recycled catalyst was checked by Fourier transform‐
infrared (FT‐IR) spectra. Encouragingly, the spectra
clearly matching with the fresh catalyst, suggest that even
after six cycles the catalyst is stable (Figure S19).
SCHEME 2 Proposed mechanism for the desymmetrization of
meso diol by catalyst 1
FIGURE 9 The recyclability of the catalyst 1 mesohydrobenzoin
with benzoyl chloride in optimized conditions

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CHINNARAJA ET AL.
(HPLC; Shimadzu SCL‐10AVP) using chiral columns
(Phenomenox Lux cellulose‐1 and Amylose‐2 columns).
3 | CONCLUSIONS
In conclusion, we report here the synthesis of a series of
important macrocyclic binuclear Zn (II) complexes that
are easy‐to‐synthesize and enantiopure. These binuclear
complexes are demonstrated as efficient catalysts for
selective desymmetrization of C2‐symmetric meso diols
to unsymmetrical monoesters with good yield and rich
enantioselectivity (96% yield and 88% ee). The Zn (II)
geometry has ΔΔ and ΛΛ metal‐centred chirality, where
each centre in the dimeric unit is involved efficiently in
desymmetrizing the meso diols, which is otherwise highly
challenging. The intermetallic distance derived from the
crystal structure of the complexes 1, 1' and 2' and the
homochiral nature ΛΛ or ΔΔ at the geometry involves
efficiently promoting enantioselective product is evident
without any ambiguity. The catalyst has been successfully
recycled up to six cycles without any significant loss in its
activity.
4.2 | Synthesis
Acetonitrile (5 ml) solution of the 2‐hydroxy‐5‐methyl‐
1,3‐benzenedicarboxaldehyde (16.4 mg, 0.1 mmol in L1
and L2) or 4‐tert‐butyl‐2,6‐diformylphenol (20.6 mg, 0.1
mmol, in L2 and L3), triethylamine (14 µl, 0.1 mmol)
and zinc acetate dihydrate (21.9 mg, 0.1 mmol) were
mixed together and constantly stirred at RT for 15 min.
To this, acetonitrile solution of (1R,2R)‐ or (1S,2S)‐
diphenylethylenediamine (21.2 mg, 0.1 mmol) was added
drop by drop. After the complete addition of diamine, the
reaction mixture was constantly stirred for 6 hr. A colour
change from pale yellow to an intense yellow was
observed. Finally, the solvent was removed by rotavapor
and the resulting residue was washed with dichlorometh-
ane (50 ml) and water (3 × 10 ml), the organic layer was
separated and treated with anhydrous sodium sulphate
and recrystallized from the DCM/acetonitrile (v/v) mix-
ture to yellow polycrystalline products.
4 | EXPERIMENTAL
4.1 | Materials and methods
4.2.1 | [Zn2(RRRR)‐L1(OAc)2] (1)
2‐Hydroxy‐5‐methyl‐1,3‐benzenedicarboxaldehyde, 4‐tert‐
butyl‐2,6‐diformylphenol,
diphenylethylenediamine,
(1R,2R)‐
(1S,2S)‐
C50H44N4O6Zn2. Yield 80%, UV‐Vis. λmax/nm (ε/dm3 mol
−1
diphenylethylenediamine and zinc acetate dihydrate
were purchased from Aldrich. All the chemicals were
used as received without any further purification. Micro-
analyses were performed by using a Perkin‐Elmer PE
2400 series‐II CHNS/O elemental analyser. 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 spec-
trophotometer. Mass analyses were performed using the
positive electron spray ionization (ESI+) technique on
cm−1): 256 (109 523), 381 (42 078). FT‐IR (KBr): ν =
3446, 2924, 1630, 1384, 1326, 1232, 1121, 1000, 740, 701
cm−1. MS (ESI)+: m/z calcd for [M (CH3OH)·(H2O)] +
H+, [C51H51N4O8Zn2]+, 977.23; found: 977.68. H‐NMR
1
(DMSO‐d6, 600 MHz, δ, ppm): 8.25 (s, 2H, CH=N),
8.05(s, 2H, CH=N), 7.40 (m, 5H, Ar), 7.35–7.37 (m, 11H,
Ar), 7.31–7.33 (m, 8H, Ar), 5.44(s, 2H, Ph*CHN), 5.27 (s,
2H, Ph*CHN), 2.14 (s, 3H, CH3). Elemental analysis:
chemical formula; C50H48N4O8Zn2, calcd (found): C,
62.32 (62.44); H, 5.02 (4.76); N, 5.81 (5.56) %.
1
water Q TOF‐micro mass spectrometer. H‐NMR spectra
were recorded on a Bruker Avance DPX 200, 500 MHz
and JEOL Delta 600 MHz FT‐NMR spectrometer. Chem-
ical shifts for proton resonances are reported in ppm (δ)
relative to tetramethylsilane. The CD spectra were
recorded on a JASCO 815 spectrometer. Suitable crystals
for complex 1, 1' and 2' were selected and mounted on a
Mitegen mesh with paratone oil. Data were collected at
100 K on a Bruker Kappa APEX2 CCD diffractometer
with Mo‐Kα radiation. Preliminary lattice parameters
and orientation matrices were obtained from three sets
of frames. Then full data were collected using the ω and
ɸ scan method with a frame width of 0.5°. The
enantioselectivity of the monobenzoylated product was
determined by high‐performance liquid chromatography
4.2.2 | [Zn2(SSSS)‐L2(OAc)2] (1')
C62H52N4O10Zn2. Yield 80%. UV‐Vis. λmax/nm (ε/dm3 mol
−1
cm−1): 256 (74 624), 380 (25 996). FT‐IR (KBr): ν =
3418, 2835, 1631, 1594, 1384, 1352, 1118, 1002, 762, 701,
618 cm−1
.
MS (ESI)+: m/z calcd for [M‐OAc]+,
C48H41N4O4Zn2, 867.17; found: 867.99. 1H‐NMR
(DMSO‐d6, 600 MHz, δ, ppm): 8.20 (s, 2H, CH=N), 8.00
(s, 2H, CH=N), 7.36 (m, 5H, Ar), 7.33–7.31 (m, 11H,
Ar), 7.30–7.28 (m, 8H, Ar), 5.38 (s, 2H, Ph*CHN), 5.21
(s, 2H, Ph*CHN), 2.10 (s, 3H, CH3). Elemental analysis:
chemical formula: C50H50N4O9Zn2, calcd (found): C,
61.17 (61.36); H, 5.13 (5.46); N, 5.71 (5.34) %.

CHINNARAJA ET AL.
11 of 12
4.2.3 | [Zn2(RRRR)‐L3(OAc)2] (2)
C68H60N4O8Zn2. Yield 82%. UV‐Vis. λmax/nm (ε/dm3 mol
of the products were assigned by comparison of HPLC
profiles with reported literature.[22]
−1
cm−1): 257 (133 840), 375 (501 673). FT‐IR (KBr): ν =
ACKNOWLEDGEMENTS
3416, 2815, 2721, 1629, 1595, 1384, 1339, 1124, 767, 617
cm−1
.
MS (ESI)+: m/z calcd for [M‐OAc]+,
CSMCRI communication number CSIR‐CSMCRI‐162/
2018. The authors gratefully acknowledge DST‐SERB
New Delhi (Project nos SR/S1/IC‐23/2011 and SB/S1/
IC‐26/2013) for funding. The authors EC and RA
acknowledge for CSIR‐SRF grand. Members of Analytical
Division & Centralized Instruments Facility (ADCIF) of
CSIR‐CSMCRI are acknowledged for their instrumenta-
tion support.
C54H53N4O4Zn2, 951.26; found: 951.11. 1H‐NMR
(DMSO‐d6, 600 MHz, δ, ppm): 1.20 (s, 18H, ‐C (CH3)3),
5.17 (s, 2H, Ph*CHN), 5.46 (s, 2H, Ph*CHN), 7.30–7.32
(m, 4H, Ar), 7.35–7.37 (m, 8H, Ar), 7.42–7.43 (m, 8H,
Ar), 7.57 (s, 4H, Ar), 8.25 (s, 2H, CH=N), 8.42 (s, 2H,
CH=N). Elemental analysis: chemical formula:
C58H63N5O8Zn2, calcd (found): C, 63.97 (63.78); H, 5.83
(4.7); N, 6.43 (6.18) %.
ORCID
4.2.4 | [Zn2(SSSS)‐L4(OAc)2] (2')
Palani S. Subramanian https://orcid.org/0000-0002-9035-
0973
C68H60N4O8Zn2. Yield 82%. UV‐Vis. λmax/nm (ε/dm3
mol−1 cm−1): 257 (89 011), 375 (29 739). FT‐IR (KBr):
ν = 3413, 2812, 2807, 2729, 1632, 1590, 1384, 1123,
765, 702, 616 cm−1. MS (ESI)+: m/z calcd for [M‐OAc]
+, C54H53N4O4Zn2, 951.26; found: 951.44. 1H‐NMR
(DMSO‐d6, 600 MHz, δ, ppm): 1.19 (s, 18H, ‐C (CH3)3),
1.64(s, 6H, CH3COO), 5.14 (s, 2H, Ph*CHN), 5.73
(s, 2H, Ph*CHN), 7.29–7.30 (m, 4H, Ar), 7.33–7.35
(m, 12H, Ar), 7.49 (m, 8H, Ar), 8.13(s, 2H, CH=N),
8.28 (s, 2H, CH=N). Elemental analysis: chemical for-
mula: C56H62N4O9Zn2, calcd (found): C, 63.10 (63.66);
H, 5.86 (5.47); N, 5.26 (5.92) %.
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SUPPORTING INFORMATION
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How to cite this article: Chinnaraja E,
Arunachalam R, Samanta J, Natarajan R,
Subramanian PS. Desymmetrization of meso diols
using enantiopure zinc (II) dimers: Synthesis and
chiroptical properties. Appl Organometal Chem.
2019;e4827. https://doi.org/10.1002/aoc.4827