Lipase catalyzed desymmetrization of roof shape cis-11,12-bis(hydroxymethyl)-9,10-dihydro-9,10-ethanoanthracene

Article abstract of DOI:10.1039/c5ra11626k

Biocatalyzed desymmetrization of roof shape meso cis-11,12-bis(hydroxymethyl)-9,10-dihydro-9,10-ethanoanthracene has been achieved. The absolute configuration of the product is established by single crystal X-ray analysis of its diastereomer prepared with R-chloropropionic acid. Single crystal analysis of the chiral roof shape monoacetate shows a P-helical motif due to the extended intramolecular hydrogen bonding while the racemic sample exhibits intermolecular double hydrogen bonding holding two molecules together as a dimmer.

Full text of DOI:10.1039/c5ra11626k

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Lipase catalyzed desymmetrization of roof shape cis-11,12-
bis(hydroxymethyl)-9,10-dihydro-9,10-ethanoanthracene
Nilesh Jain and Ashutosh V. Bedekar*
Department of Chemistry, Faculty of Science
M.S. University of Baroda, Vadodara 390 002, India
Tel. No. +91ꢀ265ꢀ2795552; Email: avbedekar@yahoo.co.in
Abstract:
Biocatalyzed desymmetrization of roof shape meso cisꢀ11,12ꢀbis(hydroxymethyl)ꢀ9,10ꢀ
dihydroꢀ9,10ꢀethanoanthracene has been achieved. The absolute configuration of the product is
established by single crystal Xꢀray analysis of its diastereomer prepared with Rꢀchloropropionic
acid. Single crystal analysis of the chiral roof shape monoacetate shows a Pꢀhelical motif due to the
extended intramolecular hydrogen bonding while the racemic sample exhibits intermolecular
double hydrogen bonding holding two molecules together as a dimmer.
OH
OH
OAc
OH
desymmetrization
acyl donor
biocatalyst
meso-diol
chiral alcohol

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Introduction:
Synthesis of chiral molecules with different shape and size in optically pure form is an
important aspect of modern organic chemistry. Applications of chiral molecules, natural and
unnatural, are found in wide range of areas covering medicinal, supramolecular, material, analytical
chemistry, agro and food industry and in asymmetric synthesis of other chiral compounds. The
strategy of chiral pool synthesis is widely explored to access chiral starting materials for useful
1
synthesis, but it has its limitations. Scope of applications of unnatural chiral compounds is widely
being recognized. Recent focus is on the use of efficient synthetic methodologies to access such
chiral molecules from achiral or prochiral materials. Along with several elegant methods of
generation of chiral elements by synthetic operations, it is also possible to separate enantiomers of
the chiral compounds. Separation of isomers of chiral compounds can be achieved by metal based
catalytic reactions or by nonꢀmetal based organocatalytic and enzymatic reactions. Enzymes are
generally recognized as effective, mild, selective, environment friendly catalysts for accessing
2
optically active compounds, mostly by separating the isomers. The development is also helped by
availability of immobilized enzymes which can tolerate nonꢀaqueous reaction conditions for
3
practical applications. Although biocatalysts can target several functional groups like esters, acids,
amines they are often studied for effecting conversion of alcohols to esters by suitable
transesterification reactions. Racemic alcohols can be selectively converted to the esters of one
4
enantiomer while keeping the other unaffected, based on the kinetic resolution process. The
drawback of limited yield, maximum 50 %, of the product and unchanged starting material in this
5
process is overcome by dynamic kinetic resolution which consists of carrying out continuous
interconversion or racemization of the substrate molecule. At the same time the process of
desymmetrization which effectively removes the element of symmetry from suitable molecules is
an attractive option to access chiral molecules. Basically molecules with two identical functional

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groups are subjected to selective conversion of one of them to different functionality, theoretically
giving quantitative yield of the product. Such desymmetrization has been known to be achieved by
6
7
metal catalytic or nonꢀenzymatic reactions or by biocatalyzed conversions. The protocol of
biocatalyzed desymmetrization has been applied on mesoꢀdiols for the preparation of chiral
8
9
molecules and for the synthesis of complex natural products. The most common arrangement of
mesoꢀdiol A and B which can be subjected to enzymatic desymmetrization are presented in Figure
1.
R1
R1
R1
R2
OH
OH
OH
OH
R2
R2
A
B
FIGURE 1. Basic types of meso diols.
Some molecules which posses shape similar to a roof of a hut or a house, called as “Roof
Shape” molecules, were introduced by Weber for the study of inclusion properties as clathrate
10
11
hosts. Similarly other known molecules which are structurally analogues, such as iptacene,
1
2
13
triptacene, and molecular tweezers have shown useful applications. Structurally similar roof
1
4
shape molecules have been well studied for their various properties and applications. The roof
shape molecules are synthesized by DielsꢀAlder cycloaddition of anthracene with electron deficient
dienophile. Further functional group modifications have lead to a number such derivatives with
1
5
16
wide applications in fields such as medicinal chemistry, as ligands in catalytic transformations,
17
18
for organocatalytic reactions, for preparation of chiral selectors, and in the synthesis of
1
9
functional polymers. The optically pure isomers of such anthracene derived roof shape molecules
1
6a,20
have been obtained by asymmetric synthesis utilizing chiral fumaric acid derivatives
or by
2
1
separating the enantiomers by fractional crystallization with chiral resolving agens.

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In our continuing interests in the roof shape molecules we have prepared and resolved
2
2
alcohol 1 and diol 2 by enzymatic selective esterification reactions (Chart 1). These molecules
were prepared from anthracene by DielsꢀAlder cycloaddition reaction with suitable dienophiles
such as methyl acrylate and dimethyl fumarate, followed by the reduction of the roof shape adducts.
The alcohol 1 and diol 2 were subjected to enzymatic transesterification reaction with appropriate
acylating agents in presence of biocatalysts. The optically pure alcohol and diol were then
converted to a series of amines by simple chemical operations. The resulting optically pure roof
2
2b
shape amines were screened as chiral solvating agents for discrimination of signals in nuclear
magnetic resonance spectroscopy.
OH
OH
HO
1
2
OH
OH
3
CHART 1. Roof shape alcohol and diols.
In the present study we extend the scope of such molecules by studying the meso isomer of
cisꢀdiol 3, which was synthesized and resolved using biocatalytic approach. The separation of cisꢀ
diol 3 involving enantioselective acylation and hence may give theoretically up to quantitative yield
as against the case of transꢀdiol 2.
Result and Discussion:
The synthesis of cisꢀdiol 3 is outlined in Scheme 1. The roof shape framework is
constructed by Lewis acid catalyzed DielsꢀAlder cycloaddition of anthracene and maleic anhydride

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at ambient conditions. The adduct anhydride 4 separated by crystallization was then subjected to
23
reduction under mild conditions of I ꢀNaBH to afford cisꢀdiol 3 in good yield.
2
4
O
O
O
AlCl3
I2-NaBH4
O
+
O
3
CH Cl2
THF
2
reflux, 18 h
r.t., 6 h
O
4
71 %
95 %
SCHEME 1. Synthesis of meso diol 3
The cisꢀdiol 3 was then subjected to desymmetrization reaction involving enzyme mediated
transesterification reaction (Scheme 2). In our earlier study on resolution of roof shape alcohols we
2
2b
had successfully screened Novozymeꢀ435 for alcohol 1, while Steapsin lipase was effective for
22a
transꢀdiol 2 and THF was found to be a good solvent for both reactions. The optically pure
materials were obtained in high purity and efficiency, particularly at low temperature. Our
2
4
observation of higher selectivity at lower temperature is consistent with the literature reports.
Hence, we started our initial screening with these conditions for the desymmetrization of diol 3
(Table 1).
OH
OH
*
OH
OAc
*
Conditions
see Table 1
3
5
SCHEME 2. Desymmetrization of 3.
The reaction of diol 3 with vinyl acetate as acyl donor in presence of Steapsin lipase in THF
was clean and only one product of mono acylation 5 was detected in the reaction mixture. The
product could be easily separated and analyzed. The optical purity of the product 5 was established

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by HPLC analysis on ChiralpakꢀODH column. As can be observed acylation was more effective
with higher amount of acylating reagent. Comparison of amount of vinyl acetate and the reaction
time indicated the optimum condition was achieved with its use in large excess and much shorter
reaction time (entry 4). The other enzymes Novozymeꢀ435 and Candida rugasa were ineffective in
chiral discrimination. We scanned two more solvents, DME and toluene, although conversion was
notable the selectivity was moderate (entry 8 & 9). We also scanned different acyl donors, where
ethyl acetate was found effective when used as solvent. Although the selectivity was good the
conversion was quite poor (entry 10 to 12).
a
Table-1. Condition for Enzymatic desymmetrization of 3.
a
b
c
No Enzyme
Solvent Time Acyl donor
Yield (%)
d
(h)
(eq.)
[ee (%)] of 5
1
2
3
4
5
6
7
8
9
SL
SL
THF
THF
72
72
60
30
60
60
60
60
60
120
60
60
VA (3)
VA (15)
VA (30)
VA (60)
VA (7)
VA (7)
VA (7)
VA (30)
VA (30)
35 [13]
71 [48]
93 [72]
90 [79]
29 [0]
SL
THF
SL
THF
Nꢀ435
Nꢀ435
CR
THF
THF
35 [0]
THF
12 [0]
SL
DME
Toluene
THF
75 [55]
53 [55]
27 [71]
35 [52]
SL
e
1
0
1
2
SL
EA
1
SL
THF
IPA (30)
BA (30)
f
1
SL
THF
ꢀꢀ [ꢀꢀ]
a
o
a
All reaction run at 8ꢀ9 C; SL = Steapsin lipase; Nꢀ435 = Novozymeꢀ435; CR =
b
Candida rugasa. VA = vinyl acetate; IPA = isopropenyl acetate; . EA = ethyl
c
c
acetate; BA = butyl acetate. Isolated. Determined by HPLC on ChiralpakꢀODH.
e
f
As solvent. No reaction.
The enzyme mediated reactions on structurally demanding substrates are often found
8
b,8c,25
difficult and challenging.
The present cisꢀdiol 3 in comparison with the other two roof shape
substrates 1 and 2 may also pose difficulty due to the similar considerations. This was addressed by

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studying the increased ratio of enzyme to substrate (Table 2). Although there was not much
improvement in the conversion, the selectivity was considerably improved when high amounts
were used with excess of acyl donor. Significantly no product of diacetylation was observed in any
of the experiments investigated in the present study.
Table 2. Effect of substrate: enzyme (Steapsin lipase) ratio.
a
No Substrate: Enzyme Time (h)
Yield (%)
b
[
ee (%)] of 5
1
2
3
1 : 1
1 : 2
1 : 3
72
60
60
90 [48]
93 [72]
95 [73]
a
b
Isolated. Determined by HPLC on ChiralpakꢀODH.
Molecules pose some additional issues where the two groups capable of chemically
undergoing acylation reactions are juxtaposed in the manner where the internal acyl transfer
reactions are feasible. When the two alcohol groups are placed close to each other the acyl group
may migrate leading to the interconversion of the mono acyl derivative. Such problem leads to low
8
b
8c,26
selectivity as discussed by Fadel and Arzel and others.
In the course of our present study we
envisaged similar possibility as the two hydroxymethyl arms in cisꢀdiol 3 are protruding in the
same direction and are placed close to each other. The possibility may attribute to the observed low
selectivity in some of the experiments we had studied. To confirm this possibility a sample of
optically pure mono acetate 5 was refluxed in isopropanol and its purity was checked periodically
(Table 3). Within a relatively short time the product lost its optical purity to a considerable extent
confirming the isomerization of mono acetate 5. The possible mode of internal transfer of acyl unit
in 5 may be explained in Scheme 3. Attack of free hydroxyl group on the acetate can give a meso
intermediate 1,3ꢀdioxolanꢀ2ꢀol derivative 6, which can open from two sides, ‘pathꢀa’ giving one

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isomer 5a, while ‘pathꢀb’ may lead to the other isomer 5b, both the steps can be promoted at higher
temperature.
a
Table 3. Racemization study.
b
No
1
Time (h)
Ee (%)
83
2
2
6
81
3
12
15
18
24
30
48
72
4
52
5
33
6
30
7
29
8
22
a
b
The sample was heated in reflux isopropanol.
Determined by HPLC on ChiralpakꢀODH.
a
O
O
O
O
O
O
H
b
H
Me
Me
6
5
path a
path b
OH
OAc
OAc
OH
5
a
5b
SCHEME 3. Mode of racemization of 5.
Optically active compounds, particularly with more than one chiral center, are often
subjected to enrichment by recrystallization under proper conditions. Right from the pioneering
27
work of Louis Pasteur such observations are well studied. The procedure of enrichment of chiral
isomers during the process of crystallization appears to be more of an art than science and success

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depends on certain structural arrangement responsible for definite supramolecular interactions.
There are frequent reports in the literature where the technique of recrystallization has been utilized
2
8
to improve the optical purity of the compounds. The isolated optically enriched sample of the
product 5 was crystallized from different solvents in order to purify as well as to further improve
the ratio of its diastereomers. Different solvents were investigated to recrystallize optically pure
samples of 5 (~70 % ee). In dichoromethane ꢀ hexane mixture (10:90) we observed formation of
crystals of two distinct shapes. Careful observation indicated that few crystals were of plate like
shape and more transparent in nature. These crystals, though seen in very few numbers, were
physically separated and characterized by single crystal Xꢀray diffraction analysis and their optical
purity was established by chiral phase HPLC analysis (Chiralpak ODH). The optical purity was
observed to be enriched and on average seen to be in the rage of 93ꢀ95 %. The Xꢀray analysis of
2
9
these crystals showed unique features (Figure 2). The crystal showed packing of only one
stereoisomer with a chiral space group of P2 2 2 . Moreover intermolecular hydrogen bonding
1
1 1
between the carbonyl oxygen of ꢀOC(O)CH of one molecule and the hydroxyl group of the other
3
was observed. The hydrogen bond distance was found to be 2.138 Å, typical of such a case.
FIGURE 2. ORTEP Diagram of optically pure mono acetate 5.

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The intermolecular hydrogen bonding in the optically pure crystal of 5 was observed in an
extended linear way between the series of molecules (Figure 3). Moreover it is noteworthy to see a
Pꢀhelical motif along with the a axis (marked by yellow rod in Figure 3) with a helical pitch of
15.782 Å. Such molecular assembly formed due to weak hydrogen bond network to form a helix
3
0
with particular stereoisomer is known in the literature.
FIGURE 3. Diagram showing topology formed in crystal due to extended intermolecular Hꢀbond
network for optically pure mono acetate 5. Right side is space filled picture where the alternate
molecules are shown in green and blue colour.
However, the majority of crystals of 5 were colorless and more like cube shape. These
crystals were racemic in nature, established by specific optical rotation as well as by HPLC

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2
9
analysis. The single crystal analysis indicated a completely different arrangement (Figure 4). The
analysis revealed the unit cell was consisting of two molecules of opposite stereochemistry held
together by two sets of intermolecular hydrogen bonding between the same functionalities. The
hydrogen bond distance was seen to be 2.308 Å in the case of racemic sample. Slightly weaker
hydrogen bond in racemic sample may be attributed to quite a large macrocycle of eighteen atoms.
The space group of the racemic crystal was observed to be Pꢀ1 and a well organized dimmeric
arrangement was detected. No extended hydrogen bond network was observed in the crystal of
racemic mono acetate 5. Such contrasting crystal behavior between the optically pure and racemic
sample of same molecule is a rare phenomena. However, the recrystallization of initial racemic
sample of 5 in various solvents under different conditions yielded racemic crystals; hence the
31
possibility of spontaneous resolution may be low. It was also observed that the melting points of
the chiral and racemic samples of 5 differ, as also observed earlier for similar roof shape transꢀ
20a
diol. The thermal analysis TGꢀDTA indicated the m.p. of chiral 5 (sample of 95 % ee) was 104.5
o
o
C while the racemic sample melted at higher temperature of 119.3 C.
FIGURE 4. ORTEP Diagram of racemic mono acetate 5 showing dimmer formation.

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The absolute configuration of enantiomerically enriched sample of 5 was established by
preparing its ester with (R)ꢀ2ꢀchloropropionic acid. The chirally pure mono acetate 5 obtained
during the resolution was converted to the diastereomerically pure ester 7 (Scheme 4). The single
2
9
crystal Xꢀray diffraction analysis of 7 clearly established the absolute configuration of the
stereogenic carbons of the original sample of 5 (Figure 5).
O
Cl
Cl
S
OH
OAc
O
OAc
H
R
R
HOOC R CH3
CH3
DCC, CH Cl2
2
0 oC, 3 h
5
7
71 %
SCHEME 4. Conversion of 5 to ester of known absolute configuration.
FIGURE 5. ORTEP Diagram of 7.
The present roof shape chiral molecules are good candidates to be used in asymmetric
synthesis, catalysis and in molecular recognition studies. To increase their utility we need to
develop their conversion to other functional groups. Our studies have also established the cisꢀ
isomers undergoes loss of its optical purity due to the internal acyl transfer process. In order to
address these issues we consider conversion the free hydroxyl group of optically pure sample of

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3
2
mono acetate 5a to its azide by Mitsunobu reaction with DPPA. We followed the standard
3
3
procedure to convert sample of 5a with optical purity of 79 % ee under ultrasonic irradiation to
afford azidoꢀacetate 8, which was converted to azidoꢀalcohol 9 by acid catalyzed hydrolysis. The
optical purity of 9 remained unchanged during the procedure as both the products were stable and
no isomerisation was observed (Scheme 5).
OH
OAc
N3
OAc
Mitsunobu
DEAD, PPh3
DPPA, THF
30 min, 60 %
5
a
8
(
79 % ee)
HCl, MeOH
reflux
2
h, 90 %
N3
OH
9
79 % ee)
(
SCHEME 5. Synthesis of azidoꢀacetate 8 and azidoꢀalcohol 9.
In the earlier part of the study we have established the thermal isomerisation of optically
pure sample of monoꢀacetate 5a (Table 3). During the course of workꢀup and purification by
column chromatography, concentration of the fractions etc. there was a chance of isomerisation of
the compound and may contribute in the lowering of optical purity. In order to ascertain this aspect
we performed a separate set of lipase mediated resolution of cisꢀdiol 3, where the crude sample,
after just filtration of the immobilized enzyme, was subjected to the above sequence of Mitsunobu
reaction and hydrolysis (Scheme 6). The final product 9 was purified by column chromatography
and analyzed for its optical purity. The product 9 obtained here showed higher optical purity (85 %
ee) and the process can be extended for practical applications.

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OH
OH
OH
OAc
Lipase
VA, THF
3
0 h
3
5a
Mitsunobu
conditions
same as in
Scheme 5
(
35 %)
N3
OH
N3
OAc
HCl, MeOH
reflux
2
h, 90 %
9
85 % ee)
8
(
SCHEME 6. One step synthesis of azidoꢀalcohol 9.
The conversion of meso cisꢀdiol 3 to optically pure azidoꢀalcohol 9 will open further
possibilities to study applications of functionalized roof shape chiral compounds.
Experimental section:
Thin Layer Chromatography was performed on silica gel plates quoted on aluminium
sheets. The spots were visualized under UV light or with iodine vapor. All the compounds were
purified by column chromatography on silica gel (60ꢀ120 mesh). All reactions were carried out
under an inert atmosphere (nitrogen) unless other conditions are specified. NMR Spectra were
1
13
recorded on Bruker Avance 400 Spectrometer (400 MHz for HꢀNMR, 100 MHz for CꢀNMR)
with CDCl as solvent and TMS as internal standard. Mass spectra were recorded on Thermoꢀ
3
Fischer DSQ II GCMS instrument; IR spectra were recorded on a PerkinꢀElmer FTIR RXI
spectrometer as KBr pallets. Melting points were recorded in Thiele’s tube using paraffin oil and
are uncorrected.

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9,10ꢀDihydroanthraceneꢀ9,10ꢀ α,βꢀsuccinic acid anhydride (4):
To a suspension of anthracene (10.0 g, 56.2 mmol) in dry dichloromethane (100 mL) under
o
nitrogen atmosphere kept in ice bath (0 to 3 C), aluminum chloride (7.47 g, 56.2 mmol) was added
portion wise. After stirring for 15 min, maleic anhydride (5.5 g, 56.2 mmol) was added. The
resulting mixture was stirred at room temperature (6 h), and poured into iceꢀwater (200 mL), the
separated organic layer was collected and the aqueous layer was extracted with dichloromethane
(3X150 mL). The combined organic extracts were washed with water (2X50 mL), dried over
anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified
by crystallization with ethyl acetate (14.2 g, 91 %).
34
M.p. = 255 ºC (lit. 257ꢀ258 ºC).
1
H NMR (400 MHz, CDCl ): δ 3.557 (s, 2H) 4.854 (s, 2H), 7.21ꢀ7.24 (m, 4H), 7.34ꢀ7.42 (m, 4H).
3
1
3
C NMR (100 MHz, CDCl ): δ 47.4, 47.9, 124.4, 125.2, 127.2, 127.7, 138.1, 140.6, 170.5.
3
ꢀ1
IR (KBr): υ 2977, 1783, 1706, 1463, 1258, 1065, 751 cm.
cisꢀ11,12ꢀbis(hydroxymethyl)ꢀ9,10ꢀdihydroꢀ9,10ꢀethanoanthracene (3)
An assembly of three necked round bottom 500 mL flask with magnetic stir bar, a reflux condenser
and an addition funnel is prepared. The flask was charged with sodium borohydride (2.7 g, 72.4
o
mmol) and dry THF (50 mL). To this mixture kept at 0 C, the above anhydride (4) (5.0 g, 18.1
mmol) was added in one portion. A solution of iodine (9.2 g, 36.2 mmol dissolved in 50 mL THF),
was added drop wise over 30 min resulting in vigorous evolution of hydrogen. After addition of
iodine was complete the flask was heated to reflux (18 h) and then cooled to room temperature. Dry
methanol was added cautiously, until the mixture became clear. After stirring for 30 min, the
solvent was removed by rotary evaporation leaving a white paste which was dissolved by addition
of aqueous KOH solution (5 %, 150 mL) was stirred (1 h) and extracted with ethyl acetate (3X250
mL). The organic extracts were dried over anhydrous sodium sulfate and concentrated in vacuum,

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which was further purified by column chromatography on silica gel (CH Cl / MeOH, gradient
2
2
elution: 95/5). R = 0.4 (CH Cl ꢀMeOH, 4:1) (3.81 g, 71 %).
f
2
2
35
o
M.p. 224 °C (lit. = 222ꢀ225 C).
1
H NMR (400 MHz, CDCl ): 2.35ꢀ2.42 (m, 2H), 2.67 (br signal, 2H), 3.28ꢀ3.36 (dd, 11.2, 4.0 Hz,
3
2H), 3.55ꢀ3.58 (dd, J = 12.2, 4.0 Hz, 2H), 4.21 (s, 2H), 7.01ꢀ7.13 (m, 4H), 7.20ꢀ7.31 (m, 4H).
1
3
C NMR (100 MHz, CDCl ): δ 43.5, 47.9, 64.4, 123.3, 124.7, 125.8, 125.9, 140.8, 143.4.
3
ꢀ1
IR (KBr): υ 3325, 3235, 3017, 1466, 1359, 1040, 1022, 749 cm.
Standard procedure for enzymatic reaction:
The lipase (0.30 g) was added to a solution of 3 (0.150 g, 0.56 mmol) in dry THF (10 mL) and
o
vinyl acetate (1.55 mL, 16.9 mmol) and the mixture was stirred at 8ꢀ9 C. The course of reaction
was monitored by TLC. After the period indicated in Table 1, the reaction mixture was filtered
through a pad of celite and washed with THF. The filtrate was concentrated in vacuum and purified
by short column chromatography. (light petroleum ether (PE)/EtOAc, gradient elution: 80/20.
R 0.45 (PE/EtOAc, 1:1).
f
cisꢀ9,10ꢀDihydroꢀ9,10ꢀethanoanthraceneꢀ11ꢀacetoxymethylꢀ12ꢀmethanol (5).
M.p. =119.3 ºC for racemic, 104.5 ºC for (11R, 12S)
=
30.4 (c = 0.5, MeOH for 95% ee)
HPLC condition Chiralpak ODꢀH column: 10% IPAꢀHexane, UV = 254nm, Flow= 0.8 mL/min Rt
st
nd
=
15.8 min (1 Peak) [11R, 12Sꢀisomer] and R – 18.1 min (2 peak) [11S, 12R isomer].
t
1
H NMR (400 MHz, CDCl ): δ 2.12 (s, 3H), 2.31ꢀ2.44 (m, 2H), 3.13ꢀ3.17 (dd, J = 9.2, 5.6 Hz, 1H),
3
3.49ꢀ3.60 (m, 2H), 3.93ꢀ3.97 (dd, J = 10.8, 5.6 Hz), 4.32 (d, J = 2 Hz, 1H), 4.45 (d, J = 1.8 Hz, 1H),
7.13ꢀ7.27 (m, 4H), 7.28ꢀ7.33 (m, 4H).
1
3
C NMR (100 MHz, CDCl ): δ 21.1, 39.6, 43.1, 46.2, 46.7, 62.3, 64.3, 123.5(2C), 125.2, 125.3,
3
125.8, 126.0, 126.1(2C), 140.5, 140.8, 143.1, 143.5, 170.9.

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ꢀ1
IR (KBr): υ 3356, 3021, 2957, 1724, 1468, 1368, 1233, 1020, 746 cm.
+
HRMS: HRMS (ESI+) m/z calculated for C H O [M+Na] 331.1304; found 331.1305.
2
0
20
3
cisꢀ9,10ꢀDihydroꢀ9,10ꢀethanoanthraceneꢀ11ꢀyl)methyl 2ꢀchloropropanoate acetoxymethylꢀ12ꢀ
acetoxymethyl (7).
Alcoholꢀ(5) (0.1 g, 0.32 mmol), DCC (0.066 g, 0.32 mmol) was placed in two necked flask under
N atmosphere, dissolved in 5 mL of dichloromethane and cooled (0 °C). A solution of (R)ꢀ2ꢀchloro
2
propionic acid (0.027 mL, 0.32 mmol) in dichloromethane (2 mL) was added drop wise. The
o
reaction mixture was stirred (0 C, 3h). After the reaction was over the reaction mixture was passed
through celite, washed with dichloromethane and purified by column chromatography on silica gel.
(
PE/EtOAc, gradient elution: 90/10. R = 0.7 (PE/EtOAc, 3:1). White solid (0.09 g, 71 %).
f
o
M.p. = 126 C
= 19.7 (c =1.0, CHCl3).
1
H NMR (400 MHz, CDCl ): δ 1.74 (d, J = 6.8 Hz, 3H), 2.10 (s, 3H), 2.42ꢀ2.53 (m, 2H), 3.61ꢀ3.75
3
(m, 2H), 3.88ꢀ3.97 (dd, J = 11.2, 5.6 Hz, 1H), 4.02ꢀ4.05 (dd, J = 10.8, 5.4 Hz, 1H), 4.32 (d, J = 2
Hz, 1H), 4.37 (d, J = 2 Hz, 1H), 4.43ꢀ4.49 (q, J = 6.8 Hz, 1H), 7.14ꢀ7.17 (m, 4H), 7.26ꢀ7.33 (m,
4H).
1
3
C NMR (100 MHz, CDCl ): δ 21.1, 21.3, 39.6, 39.7, 46.3, 46.6, 52.4, 64.0, 65.5, 123.6, 123.7,
3
125.4, 125.8, 126.1(2C), 126.3(2C), 140.1, 140.2, 142.8, 143.0, 169.7, 170.7.
ꢀ1
IR (KBr): υ 2964, 1740, 1696, 1468, 1274, 1234, 1061, 757, 550 cm.
+
HRMS (ESI+) m/z calculated for C H ClO [M+Na] 421.1183; found 421.1177.
2
3
23
4
cisꢀ9,10ꢀDihydroꢀ9,10ꢀethanoanthraceneꢀ11ꢀ(azidomethyl)ꢀ12ꢀyl)methy acetate (8).
A solution of PPh (0.236 g, 0.90 mmol) in dry THF (1.5 mL) was cooled (0 C) under N
o
3
2
atmosphere. To the mixture deithylazodicarboxlate (0.14 mL, 0.90 mmol) was slowly added. Then
solution of monoacetate (5) (0.16 g, 0.60 mmol) in dry THF (2 mL) was added to the reaction

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DOI: 10.1039/C5RA11626K
o
mixture, which was stirred (10 min. at 0 C). To this DPPA (0.16 mL, 0.75 mmol) was added drop
wise. The reaction mixture was then exposed to ultrasonic irradiation (30 min.). The solvent was
removed under reduced pressure and the crude material was purified silica gel column
chromatography on silica gel (PE/EtOAc, gradient elution: 95/5). R = 0.78 (Pet Ether/EtOAc, 4:1).
f
White solid (0.103 g, 60 %).
o
M.p. = 110ꢀ111 C
= 11.01 (c = 1.0, CHCl3)
1
H NMR (400 MHz, CDCl ): δ 2.11 (s, 3H), 2.32ꢀ2.42 (m, 2H), 2.68ꢀ2.72 (dd, J = 10.8, 4.8 Hz,
3
1H) 3.29ꢀ3.34 (dd, J = 9.6, 4.8 Hz, 1H), 3.60ꢀ3.3.65 (dd, 9.6, 8.4 Hz, 1H), 3.78ꢀ3.83 (dd, J = 10.8,
6.0 Hz, 1H), 4.29 (d, J = 2 Hz, 1H), 4.41 (d, J = 2 Hz, 1H), 7.14ꢀ7.28 (m, 2H), 7.30ꢀ7.35 (m, 4H).
1
3
C NMR (100 MHz, CDCl ): 21.0, 39.8, 40.3, 46.5, 46.7, 51.5, 64.1, 123.5, 123.8, 125.4, 125.6,
3
126.1, 126.2, 126.3 (2C), 140.1, 140.3, 142.7, 142.9, 170.7.
ꢀ1
IR (KBr): υ 3024, 2099, 1734, 1468, 1235, 1035, 755 cm.
.
+
HRMS (ESI+) m/z calculated for found C H N O [M+Na] 356.1369; found 356.1370.
2
0
19
3
2
cisꢀ9,10ꢀDihydroꢀ9,10ꢀethanoanthraceneꢀ11ꢀ(azidomethyl)ꢀ12ꢀyl)methanol (9)
To a solution of 8 (0.1 g, 0.3 mmol) in methanol (5 mL), HCl (0.04 mL, 0.5 mmol, 36 %) was
added. The reaction mixture was refluxed (2 h). After completion of reaction (TLC), MeOH was
evaporated under reduce pressure. The residue was taken in ethyl acetate (25 mL) and washed with
water (2X15 mL). The organic layer was dried with sodium sulfate and concentrated to afford (9) as
white solid 0.079 g (90 %). R = 0.60 (Pet Ether/EtOAc, 4:1).
f
o
M.p. = 135 C
= 29.0 (c = 0.5, CHCl for 85 % ee)
3
HPLC Condition Chiralpak ODꢀH column: 20% IPAꢀhexane, UV= 215 nm, Flow= 0.75 mL/min Rt
st
nd
–
8.7 min (1 Peak) and R – 15.7 min (2 peak).
t
1
H NMR (400 MHz, CDCl ): δ 2.31ꢀ2.35 (m, 2H), 2.75ꢀ2.80 (m, 1H), 3.20ꢀ3.24 (m, 1H), 3.33ꢀ3.41
3
(m, 2H), 4.39 (s, 2H) 77.14ꢀ7.34 (m, 4H), 7.29ꢀ7.34 (m, 4H).

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1
3
C NMR (100 MHz, CDCl ): δ 40.4, 43.3, 46.6, 46.9, 51.2, 62.7, 123.5, 123.7, 125.1, 125.5, 125.9,
3
126.1, 140.3, 140.8, 142.8, 143.4.
ꢀ1
IR (KBr): υ 3370, 3041, 2933, 2099, 1468, 1273, 1002, 750 cm.
.
+
HRMS (ESI+) m/z calculated for C H N O [M+Na] 314.1269; found 314.1264.
1
8
17
3
Conclusions:
Thus we have presented our efforts to resolve the meso isomer of novel roof shape cisꢀ
1,12ꢀbis(hydroxymethyl)ꢀ9,10ꢀdihydroꢀ9,10ꢀethanoanthracene by enzyme mediated
1
desymmetrization. The absolute configuration of the product was established by single crystal Xꢀ
ray analysis of its diastereomer prepared with Rꢀchloropropionic acid. Single crystal analysis of the
chiral roof shape monoacetate shows an interesting helical motif of Pꢀconformation due to the
intramolecular hydrogen bonding. Similar arrangement was not seen in the racemic sample of the
same compound, where its two molecules of opposite chirality were nicely held together by
intermolecular hydrogen bonding.
Acknowledgments:
We thank Council of Scientific and Industrial Research (CSIR), New Delhi for the award of Senior
Research Fellowship to NJ. We are also grateful to DSTꢀPURSE for the single crystal Xꢀray
diffraction facility of the Faculty of Science.
Supporting Material: Copies of the spectra, Xꢀray data, TGꢀDTA are available in the supporting
material.

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References and Notes:
1
. (a) H.U. Blaser, Chem. Rev. 1992, 92, 935ꢀ952. (b) S. Haleema, P.V. Sasi, I. Ibnusaud, P.L.
Polavarapu and H.B. Kagan, RSC Adv. 2012, 2, 9257ꢀ9285. (c) P. Singh, K. Samanta, S.K.
Das and G. Panda, Org. Biomol. Chem. 2014, 12, 6297ꢀ6339. (d) C. Bhat and S.G. Tilve,
RSC Adv. 2014, 4, 5405ꢀ5452.
2
. (a) R.D. Schmid and R. Verger, Angew. Chem., Int. Ed. 1998, 37, 1608. (b) S.M. Roberts, J.
Chem. Soc., Perkin Trans. 1, 1999, 1ꢀ21. (c) R.P. Patel, Stereoselective biocatalysis, Marcel
Dekker, New York, 2000. (d) A.S. Bommarius and B.R. Riebel, Biocatalysis, WileyꢀVCH,
Weinheim, 2004. (e) K. Faber, Biotransformations in organic chemistry, SpringerꢀVerlag,
Heidelberg, 2004.
3
4
. (a) G. Carrea and S. Riva, Angew. Chem., Int. Ed. 2000, 39, 2226. (b) A.M. Klibanov,
Nature 2001, 409, 241. (c) L. Cao, L. van Langen and R.A. Sheldon, Curr. Opin.
Biotechnol. 2003, 14, 387. (d) G. Carrea and S. Riva, Organic synthesis with enzymes in
non-aqueous media, WileyꢀVCH, Weinheim, 2008.
. (a) E. Schoffers, A. Golebiowski and C.R. Johnson, Tetrahedron 1996, 52, 3769ꢀ3826. (b)
A. Ghanem and H.Y. AboulꢀEnein, Chirality 2005, 17, 1ꢀ15.
5
. O. Pàmies and J.ꢀE. Bäckvall, Chem. Rev. 2003, 103, 3247.
6
. (a) T. Harada, K. Sekiguchi, T. Nakamura, J. Suzuki and A. Oku, Org. Lett. 2001, 3, 3309ꢀ
3
312. (b) A.J. Blake, S.C. Hume, W.ꢀS. Li and N.S. Simpkins, Tetrahedron 2002, 58, 4589ꢀ
602. (c) S.E. de Sousa, P. O’Brien and C.D. Pilgram, Tetrahedron 2002, 58, 4643ꢀ4654.
4
(d) Y. Matsumura, T. Maki, S. Murakami and O. Onumura, J. Am. Chem. Soc. 2003, 125,
2
052ꢀ2053. (e) H. Shimizu, S. Onitsuka, H. Egami and T. Katsuki, J. Am. Chem. Soc. 2005,
27, 5396ꢀ5413. (f) V.B. Birman, H. Jiang, X. Li, Org. Lett. 2007, 9, 3237ꢀ3240. (g) E.P.
1
Kündig, A. Enriquez Garcia, T. Lomberget, P. Perez Garcia and P. Romanens, Chem.

Page 21 of 26
RSC Advances
View Article Online
DOI: 10.1039/C5RA11626K
Commun. 2008, 3519ꢀ3521. (h) Y. Tsuda, M. Kuriyama and O. Onomura, Chem. Eur. J.
2
012, 18, 2481ꢀ2483. (i) S.J. Canipa, A. Stute, P. O’Brien, Tetrahedron 2014, 70, 7395ꢀ
7
403.
7
. E. GarcíaꢀUrdiales, I. Alfonso and V. Gotor, Chem. Rev. 2005, 105, 313ꢀ354. For the update
of this review, see: Chem. Rev. 2011, 111, PR110ꢀPR180.
8
. Select examples of enzyme mediated desymmetrization of mesoꢀdiols: (a) G. Nocolosi, A.
Patti, M. Piattelli and C. Sanfillippo, Tetrahedron: Asymmetry 1994, 5, 283ꢀ288. (b) A.
Fadel and P. Arzel, Tetrahedron: Asymmetry 1997, 8, 283ꢀ291. (c) S. Akai, T. Naka, T.
Fujita, Y. Takebo and Y. Kita, Chem. Commun. 2000, 1461ꢀ1462. (d) I. Borreguero, J.M.
SánchezꢀMontero, J.V. Sinisterra, A. Rumbero, J.A. Hermoso and A.R. Alcántara, J. Mol.
Catal. B. Enzym. 2001, 11, 1013ꢀ1024. (e) C. Neri and J.M.J. Williams, Tetrahedron:
Asymmetry 2002, 13, 2197ꢀ2199. (f) R. Chênavert, G. Courchesne and F. Jacques,
Tetrahedron: Asymmetry 2004, 15, 3587ꢀ3590. (g) D. Acetti, E. Brenna, C. Fuganti, F.G.
Gatti and S. Serra, Tetrahedron Lett. 2009, 50, 2249ꢀ2251. (h) C.M. Sapu, J.ꢀE. Bäckvall
and J. Deska, Angew. Chem., Int. Ed. 2011, 50, 9731ꢀ9734. (i) G. Obame, H. Pellissier, N.
Vanthuyne, J.ꢀB. Bongui and G. Audran, Tetrahedron Lett. 2011, 52, 1082ꢀ1085. (j) N.
RíosꢀLombardía, V. GotorꢀFernández and V. Gotor, J. Org. chem. 2011, 76, 811ꢀ819.
. For some important examples of complex products: (a) A.D. Lebsack, J.T. Link, L.E.
Overman and B.A. Stearns, J. Am. Chem. Soc. 2002, 124, 9008ꢀ9009. (b) M. Lautens, J.T.
Colucci, S. Hiebert, N.D. Smith and G. Bouchain, Org. Lett. 2002, 4, 1879ꢀ1882. (c) U.
Zutter, H. Iding, P. Spurr and B. Wirz, J. Org. Chem. 2008, 73, 4895ꢀ4902. (d) K.C.
Nicolaou, H. Zhang, A. Ortiz and P. Dagneau, Angew. Chem., Int. Ed. 2008, 47, 8605ꢀ8610.
9
(e) M. Candy, G. Audran, H. Bienayme, C. Bressy and J.ꢀM. Pons, Org. Lett. 2009, 11,
4
950ꢀ4953.

RSC Advances
Page 22 of 26
View Article Online
DOI: 10.1039/C5RA11626K
1
0. (a) E. Weber, I. Csöregh, J. Ahrendt, S. Finge and M. Czugler, J. Org. Chem. 1988, 53,
5
831ꢀ5839. (b) E. Weber, T. Hens, O. Gallardo and I. Csöregh, J. Chem. Soc., Perkin Trans.
2
, 1996, 737ꢀ745.
1
1. (a) J. Bouffard, R.F. Eaton, P. Muller and T.M. Swager, J. Org. Chem. 2007, 72, 10166ꢀ
0180. (b) T.M. Swager, Acc. Chem. Res. 2008, 41, 1181ꢀ1189.
1
1
2. L. Zhao, Z. Li and T. Worth, Chem. Lett. 2010, 39, 658ꢀ667.
1
3. M. Marquis, K. Kulikiewicz, S. Lebedkin, M.M. Kappes, C. Mioskowski, S. Meunier and
A. Wagner, Chem. Eur. J. 2009, 15, 11187ꢀ11196.
1
4. (a) J. KarolakꢀWojciechowska, H.B. Trzeźwińska, S. AlibertꢀFranco, C. SantelliꢀRouvier
and J. Barbe, J. Chem. Crystallogr. 1998, 28, 905ꢀ911. (b) M. Smet, D. Corens, L. van
Meervelt and W. Dehaen, Molecules 2000, 5, 179ꢀ188. (c) J.C.C. Atherton and S. Jones,
Tetrahedron 2003, 59, 9039ꢀ9057.
1
5. (a) S. Alibert, C. SantelliꢀRouvier, B. Pradines, C. Houdoin, D. Parzy, J. Karolakꢀ
Wojciechowska and J. Barbe, J. Med. Chem. 2002, 45, 3195ꢀ3209. (b) S. Alibert, C.
SantelliꢀRouvier, M. Castaing, M. Berthelot, G. Spengler, J. Molnar and J. Barbe, Eur. J.
Med. Chem. 2003, 38, 253ꢀ263. (c) J. Millet, M. TorrentinoꢀMadamet, S. Alibert, C. Rogier,
C. SantelliꢀRouvier, J. Mosnier, E. Baret, J. Barbe, D. Parzy and B. Pradines, Antimicrob.
Agents Chemother. 2004, 48, 2753ꢀ2756.
1
6. (a) H. Waldmann, M. Weigerding, C. Dreisbach and C. Wandrey, Helv. Chim. Acta 1994,
7
7, 2111ꢀ2116. (b) J.R. Scheffer and H. Ihmels, Liebigs Ann. Recl. 1997, 1925ꢀ1929. (c) S.
Hoshimoto, H. Matsunaga and T. Kunieda, Chem. Pharm. Bull. 2000, 48, 1541ꢀ1544. (d) S.
Doherty, E.G. Robins, J.G. Knight, C.R. Newman, B. Rhodes, P.A. Chapkin and W. Clegg,
J. Organomet. Chem. 2001, 640, 182ꢀ196. (e) B. Wang, X. Feng, Y. Huang, H. Liu, X. Cui
and Y. Jiang, J. Org. Chem. 2002, 67, 2175ꢀ2182. (f) Z. Zeng, G. Zhao, P. Gao, H. Tang, B.

Page 23 of 26
RSC Advances
View Article Online
DOI: 10.1039/C5RA11626K
Chen, Z. Zhou and C. Tang, Catal. Commun. 2007, 8, 1443ꢀ1446. (g) M.S. Jeletic, M.T.
Jan, I. Ghiviriga, K.A. Abboud and A.S. Veige, Dalton Trans. 2009, 2764ꢀ2776. (h) A.B.
Naidu, E.A. Jaseer and G. Sekar, J. Org. Chem. 2009, 74, 3675ꢀ3679. (i) R.J. Lowry, M.T.
Jan, K.A. Abboud, I. Ghiviriga and A.S. Veige, Polyhedron 2010, 29, 553ꢀ563.
1
7. (a) A. Sasaoka, M. Imam Uddin, A. Shimamoto, Y. Ichikawa, M. Shiro and H. Kotsuki,
Tetrahedron: Asymmetry 2006, 17, 2963ꢀ2969. (b) H.R. Cabrera, G. Huelgas, J.M.
Hernández Pérez, P.J. Walsh, R. Somanathan and A. de Parrodi, Tetrahedron: Asymmetry
2
015, 26, 163ꢀ172.
8. S. Allenmark, U. Skogsberg and L. Thunberg, Tetrahedron: Asymmetry 2000, 11, 3527ꢀ
534.
1
1
2
3
9. (a) M.A. Robjohns, P. Hodge and P.A. Lovell, Polymer 1997, 38, 3395ꢀ3407. (b) S. Zheng
and D.Y. Sogah, Polym. Prepr. (Am. Chem. Soc., Div. Polym. Chem.) 2001, 42, 476ꢀ477.
0. (a) L. Thunberg and S. Allenmark, Tetrahedron: Asymmetry 2003, 14, 1317ꢀ1322. (b) F.C.
Zacconi, L.C. Koll and J.C. Podestá, Tetrahedron: Asymmetry 2011, 22, 40ꢀ46.
2
1. C.R. Ramanathan and M. Periasamy, Tetrahedron: Asymmetry 1998, 9, 2651ꢀ2656.
2. (a) N. Jain and A.V. Bedekar, Tetrahedron: Asymmetry 2011, 22, 1176ꢀ1179. (b) N. Jain,
M.B. Mandal and A.V. Bedekar, Tetrahedron 2014, 70, 4343ꢀ4354.
2
2
3. M.J. McKennon, A.I. Meyers, K. Drauz and M. Schwarm, J. Org. Chem. 1993, 58, 3568ꢀ
3
571.
2
2
4. T. Sakai, Tetrahedron: Asymmetry 2004, 15, 2749ꢀ2756.
5. A. Michaud, C. Lévesque, M. Fila, P. Morin, N. Pelchat and R. Chênevert, Tetrahedron:
Asymmetry 2011, 22, 819ꢀ822.
2
6. (a) K.K.ꢀC. Liu, K. Nozaki and C.ꢀH. Wong, Biocatalysis 1990, 3, 169ꢀ177. (b) S. Akai, T.
Naka, Y. Takebo and Y. Kita, Tetrahedron Lett. 1997, 38, 4243ꢀ4246.

RSC Advances
Page 24 of 26
View Article Online
DOI: 10.1039/C5RA11626K
2
7. H.D. Flack, Acta Cryst. 2009, A65, 371ꢀ389 and references cited therein.
2
8. (a) M. Smrcina, M. Lorenc, V. Hanus, P. Sedmera and P. Kocovsky, J. Org. Chem. 1992,
57, 1917ꢀ1920. (b) H. Mahmoud, Y. Han, B.M. Segal and L. Cai, Tetrahedron: Asymmetry
1998, 9, 2035ꢀ2042. (c) S. Abela, R. Inauen, D. Spielvogel and C. Moessner, J. Org. Chem.
2012, 77, 4765ꢀ4773. (d) K. Konuki and H. Nagai, Tetrahedron: Asymmetry 2014, 25,
1581ꢀ1589.
2
9. Crystallographic data for the structures have been deposited with the Cambridge
Crystallographic Data Centre (CCDC No. 1020854 for optically pure 5, 1020855 for
racemic 5 and 1054141 for the diastereomer 7). Copies of the data can be obtained from
http://www.ccdc.cam.ac.uk/conts/retrieving.html or from the Cambridge Crystallographic
Data Centre, 12 Union Road, Cambridge CD21EZ, UK (fax: +44ꢀ1223ꢀ336ꢀ033; eꢀmail:
deposit@ccdc.cam.ac.uk)
3
0. (a) V.R. Naidu, M.C. Kim, J.ꢀM. Suk, H.ꢀJ. Kim, M. Lee, E. Sim and K.ꢀS. Jeong, Org.
Lett. 2008, 10, 5373ꢀ5376. (b) I. Hisaki, N. Shizuki, T. Sasaki, Y. Ito, N. Tohnai and M.
Miyata, Crystal Growth and Design, 2010, 10, 5262ꢀ5269. (c) K.K. Bisht and E. Suresh, J.
Am. Chem. Soc. 2013, 135, 15690ꢀ15693. (d) B. Sureshbabu, R. Venkatachalam and S.
Sankararaman, CrystEngComm 2014, 16, 6098ꢀ6106, and the references cited therein.
1. L. PérezꢀGarcía and D.B. Amabilino, Chem. Soc. Rev. 2002, 31, 342ꢀ356.
3
3
2. K.C. Swamy, N.N. Kumar, E. Balaraman and K.V. Kumar, Chem. Rev. 2009, 109, 2551ꢀ
2
651.
3. (a) B. Lal, B. Pramanik, M.S. Manhas and A.K. Bose, Tetrahedron Lett. 1977, 23, 1977ꢀ
980. (b) L.E. Overman and D.V. Paone, J. Am. Chem. Soc. 2001, 123, 9465ꢀ9467. (c) S.D.
3
1
Lepore and Y. He, J. Org. Chem. 2003, 68, 8261ꢀ8263.
3
4. W. Kitching, W. Adcock, T.C. Khor and D. Doddrell, J. Org. Chem. 1976, 41, 2055ꢀ2058.

Page 25 of 26
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View Article Online
DOI: 10.1039/C5RA11626K
3
5. J.S. Meek and R.D. Stack J. Org. Chem. 1961, 26, 300ꢀ302.

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Graphical Abstract:
Lipase catalyzed desymmetrization of roof shape cis-11,12-
bis(hydroxymethyl)-9,10-dihydro-9,10-ethanoanthracene
Nilesh Jain and Ashutosh V. Bedekar*
*
OH
OAc
*
9
5 % ee
*
OH
OAc
*
0
% ee