Highly enantioselective kinetic resolution of trans-2-(phenylthio) cyclohexanol derivatives by immobilized Candida antartica B lipase

Article abstract of DOI:10.1016/j.molcatb.2013.06.006

Candida antartica B (immobilized CAL-B) mediated resolutions of trans-2-(phenylthio)cyclohexanol derivatives using vinyl acetate as acylating agent and MTBE as solvent provide excellent enantioselectivity (up to >99%) and high yield of both the enantiomer

Full text of DOI:10.1016/j.molcatb.2013.06.006

Journal of Molecular Catalysis B: Enzymatic 96 (2013) 67–74
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Journal of Molecular Catalysis B: Enzymatic
journal homepage: www.elsevier.com/locate/molcatb
Highly enantioselective kinetic resolution of
trans-2-(phenylthio)cyclohexanol derivatives by immobilized Candida
antartica B lipase
Swapandeep Singh Chimni∗, Kirandeep Kaur, Neeraj Bala
Department of Chemistry, Guru Nanak Dev University, Amritsar 143005, India
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 20 April 2013
Received in revised form 10 June 2013
Accepted 12 June 2013
Available online 27 June 2013
Candida antartica B (immobilized CAL-B) mediated resolutions of trans-2-(phenylthio)cyclohexanol
derivatives using vinyl acetate as acylating agent and MTBE as solvent provide excellent enantioselectivity
(up to >99%) and high yield of both the enantiomers in short reaction time.
© 2013 Elsevier B.V. All rights reserved.
Keywords:
␤-Hydroxy sulfides
Kinetic resolution
Immobilized Candida antartica B
Hydrolases
1. Introduction
Due to the importance of chiral ␤-hydroxy sulfides a num-
ber of methods have been developed for their synthesis such as;
Organosulfur compounds are of great significance in synthetic
organic chemistry as they are widely used for the synthesis
of potentially bioactive molecules, which find applications as
agrochemicals [1], pharmaceuticals [2–4], chiral auxiliaries for ana-
lytical as well as synthetic applications [6–8] and in numerous
selective organic synthesis [5].
asymmetric ring opening of epoxides [20], asymmetric reduction
of ␤-ketosulfides using Baker’s yeast [21] and fungal whole cells
[22], and kinetic resolution of racemic ␤-hydroxy sulfides with
chiral 1,2-diamines [23] and enzymes [24,25]. The requirement of
expensive or toxic metal catalysts [26], long reaction times [27],
elevated temperature [28] and difficulty in handling cell mass
in the above mentioned methods and our interest in the kinetic
resolution [29] lead us to seek an effective and environmentally
benign approach for the synthesis of enantiomerically pure trans-
2-(phenylthio)cyclohexanol derivatives.
The enantioselective kinetic resolution of secondary alcohols
with lipases provides an environmentally benign approach
to obtain optically pure alcohols. Herein we report our
results on the lipase mediated kinetic resolution of trans-2-
(phenylthio)cyclohexanol derivatives and their functionalization
to optically pure ␤-hydroxy sulfoxides.
Chiral hydroxy sulfides occupy a special place among the enan-
tiopure organosulfur compounds, since the sulfur atom placed at
an appropriate position from the hydroxy group provides unique
synthetic versatility. Hence, they can be used as synthons for a
variety of chiral organic compounds, such as chiral oxiranes [9],
allylic alcohols [10], lactones [11], macrolides [12], pheromones
[13] and tetrahydrofurans [14]. In particular, the asymmetric motifs
obtained from relatively rigid cyclic structures, cyclic ␤-hydroxy
sulfides have been employed as organocatalysts in Baylis–Hillman
reaction [15]. Their transformation to hydroxy sulfoxides [16] or
sulfones [17], provides useful chiral building blocks and chiral lig-
ands, for example, ␤-hydroxy sulfoxides have been used as chiral
ligands in the enantioselective addition of diethylzinc to benz-
aldehyde [18] and also in the synthesis of naturally occurring
compounds such as leukotrienes [19].
2. Results and discussions
In the preliminary study, Humicola lanuginosa lipase was used to
resolve trans-2-(phenylthio)cyclohexanol, ( )-1 using vinyl acetate
as acylating agent under solvent free conditions at room temper-
ature (Scheme 1). The progress of the reactions was monitored
at regular intervals for 24 h by chiral HPLC using chiralcel OD-H
column (Fig. 1, Table 1, entry 1).
∗
Corresponding author. Tel.: +91 183 2258809; fax: +91 1883 2258820.
E-mail address: sschimni@yahoo.com (S.S. Chimni).
1381-1177/$ – see front matter © 2013 Elsevier B.V. All rights reserved.
http://dx.doi.org/10.1016/j.molcatb.2013.06.006

68
S.S. Chimni et al. / Journal of Molecular Catalysis B: Enzymatic 96 (2013) 67–74
Table 2
SPh
SPh
SPh
OH
OAc
Solvent screening for resolution of trans-2-(Phenylthio)cyclohexanol.
+
Lipase
a
a
Eb
OH
(1S, 2S)-1
S. no.
Solvent
Conversion (%)
eep (%)
ees (%)
OAc
(1R, 2R)-1a
1
2
3
4
5
6
7
8
9
10
11
12
13
NEAT
THF
DCM
50
37
48
43
48
50
30
41
18
10
11
9
>99
>99
>99
>99
>99
>99
71.5
81
>99
>99
>99
>99
>99
92
64
86
97
95
>99
37
69
26
>500
>500
>500
>500
>500
>500
8
19
66
87
63
trans-(+)- 1
Scheme 1. Lipase mediated kinetic resolution of trans-2-(phenylthio)cyclohexanol,
)-1.
Hexane
Acetonitrile
MTBE
Toluene
Dioxane
Ethyl acetate
Methanol
DMSO
(
14
16.5
69
DMF
Dichloroethane
>500
>500
24
61
a
ees and eep are calculated from HPLC.
E = ln[(1 − c)(1 − ees)]/ln[(1 − c)(1 + ees)] where c = ees/ees + eep.
b
>99% ee while the conversion was observed at 50%. Thus, MTBE
(1 mL) was added in all further optimization reactions. The study
for time of resolution was carried out in order to obtain the exact
time in which 50% of resolution was achieved. It was observed that
enantioselectivity of (1R, 2R)-1a and conversion increase with reac-
tion time till 4 h and no further change was observed (Fig. 2, graph
I). So, the reaction time of 4 h was taken as optimum.
Next, the variation in the amount of vinyl acetate for kinetic res-
olution of ( )-1 was studied, the results illustrated in Fig. 2. Both the
resolved products (1R, 2R)-1a and (1S, 2S)-1 were obtained in >99%
ee on using 10 equiv. of the vinyl acetate with respect to 1 equiv. of
the substrate. Using lower amounts of vinyl acetate provided prod-
ucts with slightly lower enantiomeric excess. So, 10 equiv. of vinyl
acetate was used for all further optimizations (Fig. 2, graph IV). The
optimization for amount of lipase with respect to substrate was
studied by varying lipase-substrate ratios (w/w) from 0.2 to 2.00
(Fig. 2, graph III). It was found that conversion as well as enantio-
selectivity increases from 0.2 to 1.00 of lipase:substrate ratio while
the lipase substrate ratio 1:1 was optimum to achieve 50% conver-
sion and obtained (1R, 2R)-1a and (1S, 2S)-1 in >99% ee. There was
no change in results using higher amounts of lipase with respect to
substrate. Since, enzyme catalysis is sensitive to changes in temper-
ature, thus the reaction was performed at different temperatures. It
was found that the best results, i.e. >99% ee for both (1R, 2R)-1a and
(1S, 2S)-1 with 50% conversion was obtained on running the reac-
tion at temperatures 30 ◦C and 40 ◦C (Fig. 2, graph II). The reaction
temperature of was selected for running all further reactions.
Thus, the optimized condition for the resolution of trans-2-
(phenylthio)cyclohexanol ( )-1 consist of stirring a mixture of
Fig. 1. An overlay of HPLC traces of (a) racemic acetylated product, 1a; (b) racemic
alcohol, ( )-1; (c) after resolution of 24 h with HLL lipase.
After workup and purification on silica gel column, the acety-
lated product, (1R, 2R)-1a was obtained in >99% enantiomeric
excess and the unreacted alcohol, (1S, 2S)-1 was obtained with
55% ee (Table 1, entry 1). Similarly other lipases were screened
for resolution of trans-2-(phenylthio)cyclohexanol [( )-1]. Most of
the lipases were found to be less efficient in resolving ( )-1 but
Burkholderia cepacia lipase resolved the substrate in 8 h to provide
1a in >99% ee and 1 in 90% ee (Table 1 entry 8). Candida antartica
B lipase (CAL B) was found to be most efficient in resolving ( )-1
in 4 h to provide (1R, 2R)-1a in >99% ee and (1S, 2S)-1 in 92% ee
(Table 1 entry 5), so it was selected for further optimization.
Further, the effect of different solvents was studied on the res-
olution of ( )-1 by CAL-B. The reaction was performed by using
1 mL solvent (Table 2). It was observed that polar solvents result
in a lower conversion of ( )-1 as well as lower enantioselectivity
of (1S, 2S)-1 in comparison to non-polar solvents. The reaction run
in methyl tert-butyl ether (MTBE) resolved both the products with
(
)-1 (100 mg) in MTBE (1 mL) and vinyl acetate (412 ␮L, 10 equiv.)
with CAL-B (100 mg) as the catalyst (Scheme 2). Further, the scope
of this resolution was observed by screening different derivatives of
trans-2-(phenylthio)cyclohexanol using the optimized conditions
(Table 3, entry 1–13).
Table 1
Results of lipases screening for resolution of trans-2-(phenylthio)cyclohexanol.
a
a
S. no.
Lipase
Conversion (%)
Time taken (h)
24
24
24
24
4
24
24
8
eep (%)
ee s (%)
Eb
1
2
3
4
5
6
7
8
9
Humicola lanuginosa
Pseudomonas stutzeri
Pseudomonas fluorescens
Candida rugosa
Immobilized Candida antartica B
Aspergillus niger
Burkholderia cepacia
Burkholderia cepacia (immobilized on ceramic)
Burkholderia cepacia (immobilized diatomite)
34
46
39
11
50
31
18
48
48
99
>99
>99
99
>99
99
99
>99
>99
55
82
65
15
92
50
29
90
89
155
>500
238
604
>500
110
10
246
246
8
a
ees and eep are calculated from HPLC.
E = ln[(1 − c)(1 − ees)]/ln[(1 − c)(1 + ees)] where c = ees/ees + eep.
b

S.S. Chimni et al. / Journal of Molecular Catalysis B: Enzymatic 96 (2013) 67–74
69
Fig. 2. Optimizing reaction conditions: (I) reaction time; (II) Temperature; (III) lipase-substrate ratio; (IV) equivalents of vinyl acetate.
It had been observed that conversion of 50% and >99% enan-
tioselectivity with E > 500 was achieved for both the acetylated and
unreacted enantiomers in all substrates ranging from 1 to 13. How-
ever, a slight variation in reaction times (3–9 h) was observed. It has
been found that the resolution of trans-2-(phenylthio)cyclohexanol
(Table 3, entry 1) can be obtained with >99% ee in 4 h while the
trans-2-(phenylthio)cyclopentanol (Table 3, entry 11) was resolved
in 3 h affording (1R, 2R)-2-(phenylthio)cyclopentyl acetate and(1S,
2S)-2-(phenylthio)cyclopentanol in >99% ee. Varying the substitu-
tion at phenyl ring of the thiol part of the molecule, it was observed
that p-halo substituted ␤-hydroxy sulfides took longer time for
the transformation than p-methyl- and p-methoxy-substituted
derivatives. However, the substitution pattern of ortho-, meta-
and para- was studied by using the three derivatives of trans-
2-(chlorophenylthio)cyclohexanol (Table 3, entry 2, 3, 4). It was
observed that ortho substituted derivative took 9 h to resolve while
meta and para were resolved in 7 h and 6 h, respectively. trans-2-
(Cyclohexylthio)cyclohexanol provided the corresponding acetate
and alcohol in 50% conversion in 8 h (Table 3, entry 10). However,
the acyclic hydroxy sulfides (Table 3, entry 12 and 13) undergo
resolution with >99% ee of both the products in 4 h and 5 h, respec-
tively.
14a. The fractional crystallization of this diastereomeric mixture
provided (1R, 2R, Ss)-14a as pure colorless crystals (>99% ee, m.p.
153 ◦C) having [␣]D27 = +112.9◦ (c 0.50, CH2Cl2) and mother liquor
(14a) as a colorless liquid with [␣]D27 = −110.0◦ (c 1.0, CH2Cl2). The
crystalline diastereomer (1R, 2R, Ss)-14a was assigned the config-
uration on the basis of its X-ray data (Fig. 2) as well on comparison
of the specific rotation values as reported in literature [30].
Similarly oxidation of (1S, 2S)-2-(phenylthio)cyclohexanol (1)
followed by crystallization afforded (1S, 2S, Ss)-14 and (1S, 2S, Rs)-
14 (>99% ee, mp: 156 ◦C) having [␣]D27 = −129.2 (c 1.0, CH2Cl2)
(Table 4).
The absolute configurations of the sulfoxides have been assigned
on the basis of X-ray data [31] (Fig. 3) as well as the specific rotation
values compared to literature [30].
2.1. Reusability of enzyme
The lipase reused for next cycle was filtered from the previ-
ous reaction, washed with ethyl acetate, dried and the weighed.
For carrying out the next cycle, the amount of substrate was taken
with respect to the amount of enzyme recovered from earlier cycle,
Further, sulfoxidation of the isolated enantiopure (1R, 2R)-1a
and (1S, 2S)-1 was studied with m-CPBA in CH2Cl2 at −20 ◦C
(Scheme 3). The oxidation of (1R, 2R)-1a provided a mixture of
(1R, 2R, Ss)- and (1R, 2R, Rs)-2-(phenylsulfinyl)cyclohexyl acetate
O
O
S
S
S
Ph
Ph
OAc
1R, 2R-1a
m-CPBA/ CH2Cl2
-20oC
Ph
+
+
OAc
OAc
(1R, 2R, Ss)-14a
(1R, 2R, Rs)-14a
SR
SR
SR
O
OAc
CAL-B, MTBE
O
+
S
S
S
Ph
Ph
OH
1S, 2S-1
m-CPBA/ CH2Cl2
-20oC
Ph
OH
1S, 2S-(1-13)
OAc
OH
OH
1R, 2R-(1-13)a
OH
trans-(+)- 1-13
(1S, 2S, Ss)- 14
(1S, 2S, Rs)-14
Scheme 2. Optimized condition for carrying out resolution of different derivatives
of trans-2-(phenylthio)cyclohexanol.
Scheme 3.

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S.S. Chimni et al. / Journal of Molecular Catalysis B: Enzymatic 96 (2013) 67–74
Table 3
Kinetic resolution of different derivatives of ␤-hydroxy sulfides with Candida antartica lipase B.
Entry
Substrate trans-( )-1-13
Reaction time (h)
Conv (%)
(1-13)a
eep (%)
(1-13)
ees (%)
E
Yield (%)
42
Yield (%)
46
S
1
2
3
4
6
7
50
50
48
>99
>99
>99
>99
>99
>99
>500
>500
>500
OH
S
47
42
37
44
OH
S
Cl
Cl
OH
S
Cl
4
9
48
>99
47
>99
42
>500
OH
S
5
6
7
5
8
5
50
47
50
>99
>99
>99
35
44
45
>99
>99
>99
41
41
43
>500
>500
>500
OH
S
Br
OH
S
F
OH
S
CH3
8
9
6
6
8
3
50
50
47
50
>99
>99
>99
>99
47
46
38
43
>99
>99
>99
>99
42
40
35
45
>500
>500
>500
>500
OH
S
OCH3
OH
S
10
11
OH
S
OH
OH
S
12
13
4
5
50
50
>99
>99
40
41
>99
>99
44
46
>500
>500
OH
S
Table 4
␤-Hydroxy sulfoxides obtained from chiral products of ␤-hydroxy sulfide (1).
27
␤-Hydroxy sulfide
␤-Hydroxy sulfoxide
m.p. (◦C)
[␣]D
ee (%)
(1R, 2R)-1a
(1R, 2R)-1a
(1S, 2S)-1
(1S, 2S)-1
(1R, 2R, Ss)-14a
(1R, 2R, Rs)-14a
(1S, 2S, Ss)-14
(1S, 2S, Rs)-14
153–156
+112.9 (c = 0.50, CH2Cl2).
−110.0 (c = 1.0, CH2Cl2).
−129.2 (c = 1.0, CH2Cl2)
+132.1 (c = 0.75, CH2Cl2)
>99
>99
>99
>99
–
156–157
–

S.S. Chimni et al. / Journal of Molecular Catalysis B: Enzymatic 96 (2013) 67–74
71
exposing to UV light or iodine vapors. Column chromatography
was performed using silica gel 60–120 and 100–200. HPLC anal-
yses were carried out in a Hewlett Packard 1100 chromatograph,
UV detector using a SPD-M20A prominence diode array detec-
tor (25 cm × 4.6 mm), Daicel Chiralpak OD-H (25 cm × 4.6 mm),
Chiralpak AS-H (25 cm × 4.6 mm), Chiralcell IB (25 cm × 4.6 mm)
columns, varying the conditions according to the specific sub-
strate. Measurements of the optical rotation values were done in a
PerkinElmer 241 polarimeter.
4.2. General method for preparation of substrates
To a stirred solution of epoxide (3 mmol) and potassium car-
bonate (0.04 g) in a round bottom flask was added water (2 mL)
and corresponding thiophenol (3 mmol) and the resulting mix-
ture was stirred at room temperature for 30–240 min. In case of
solid ␤-hydroxy sulfides, pure product was isolated by filtration.
The liquid ␤-hydroxy sulfides were extracted with ethyl acetate
and dried over anhydrous sodium sulphate. Evaporation of solvent
under reduced pressure afforded pure product.
Fig. 3. X-ray structure of 14a.
trans-( )-2-(Phenylthio)cyclohexanol (1): Yield: 82%, White
solid 1H NMR (CDCl3, 300 MHz), ı [ppm]: 1.23–1.35 (m, 4H),
1.66–1.70 (m, 2H), 2.07–2.11 (m, 1H), 2.95 (m, 1H), 7.24–7.31 (m,
3H), 7.44–7.48 (m, 2H); 13C NMR (CDCl3, 75 MHz) ı [ppm]: 24.2,
26.1, 32.7, 33.8, 56.5, 72.1, 127.7, 128.8, 133.7; HPLC analysis: Daicel
chiralpak OD-H, hexane/i-PrOH 95/5, 0.5 mL/min, 220 nm, reten-
tion time: 14.89 min (1R, 2R), 21.66 (1S, 2S) min; HRMS (M+Na)
calcd. for C12H16OS: 231.0838, found: 231.0814.
Table 5
Reusability of enzyme up to 4 cycles.
Entry
Cycle
Time taken (h)
1
2
3
4
1st
4
12
24
32
2nd
3rd
4th
trans-( )-2-(p-Tolylthio)cyclohexanol (2): Yield: 79%; 1H
NMR (CDCl3, 300 MHz), ı [ppm]: 1.20–1.33 (m, 4H), 1.59–1.72 (m,
2H), 2.05–2.14 (m, 2H), 2.34 (s, 3H) 2.63–2.70 (m, 1H), 3.04–3.29
(m, 1H), 7.10–7.25 (m, 2H), 7.35–7.38 (m, 2H); 13C NMR (CDCl3,
75 MHz) ı [ppm]: 24.2, 26.1, 32.7, 33.8, 56.5, 72.1, 127.7, 128.8,
133.7; HPLC analysis: Daicel Chiralcel OD-H, hexane/i-PrOH = 9/1,
flow rate = 0.5 mL/min, 220 nm, retention time: 11.23 min (1R, 2R),
18.72 min (1S, 2S); HRMS (M+Na) calcd. for C13H18OS: 245.0974,
found: 245.0971.
trans-( )-2-(4-Chlorophenylthio)cyclohexanol (3): Yield:
83%; 1H NMR (CDCl3, 300 MHz), ı [ppm]: 1.23–1.27 (m, 1H),
1.66–1.70 (m, 2H), 2.07–2.11 (m, 1H), 2.95 (m, 1H), 7.24–7.31 (m,
5H), 7.44–7.48 (m, H); 13C NMR (CDCl3, 75 MHz) ı [ppm]: 20.9,
23.4, 24.9, 31.3, 31.5, 50.2, 75.2, 126.8, 129.6, 129.7, 131.1; HPLC
analysis: Daicel chiralpak OD-H, hexane/i-PrOH 95/5, 1.0 mL/min,
220 nm, retention times: 9.45 min (1R, 2R), 13.26 min (1S, 2S);
HRMS (M+Na) calcd. for C12H15ClOS: 265.0453, found: 265.0452.
trans-( )-2-(3-Chlorophenylthio)cyclohexanol (4): Yield:
74%; HPLC analysis: Daicel chiralpak OD-H, hexane/i-PrOH 95/5,
1.0 mL/min, 220 nm, retention time: 8.56 min (1R, 2R), 11.55 min
(1S, 2S); HRMS (M+Na) calcd. for C12H15ClOS: 265.0442, found:
265.0447.
maintaining the enzyme-substrate ratio 1:1. Immobilized CAL-B
gave reproducible results with 50% conversion and >99% enantio-
selectivity for the kinetic resolution of ( )-1a with vinyl acetate in
MTBE over the four reuse cycles investigated. The same enantio-
selectivity and conversion was observed over the four sequentially
performed reactions, however the time taken to achieve 50% con-
version was longer. The second cycle requires 12 h in order to reach
the full 50% conversion instead of 4 h in the first cycle while the third
cycle requires almost 24 h to achieve complete conversion. The
slow rate of conversion could be attributed to the possible leaching
of the enzyme [32] from the immobilization support (acrylic resin)
(Table 5).
3. Conclusions
In this study, a series of ␤-hydroxy sulfides were successfully
resolved with excellent enantioselectivity (up to ≥99% ee) via
immobilized CAL-B catalyzed kinetic hydrolysis of the correspond-
ing ␤-hydroxy phenylthiocyclohexanols. The method developed is
simple, environmentally benign and highly enantioselective.
trans-( )-2-(2-Chlorophenylthio)cyclohexanol (5): Yield:
77%; 1H NMR (CDCl3, 300 MHz), ı [ppm]: 1.27–1.39 (m, 4H),
1.72–1.73 (m, 2H), 2.12–2.16 (m, 2H), 2.89–2.94 (m, 2H), 3.43
(m, 1H), 7.18–7.54 (m, 5H); 13C NMR (CDCl3, 75 MHz) ı [ppm]:
24.1, 25.9, 32.4, 33.9, 55.8, 72.6, 127.0, 128.4, 129.9, 132.8, 133.9,
136.8. HPLC analysis: Daicel chiralpak OD-H, hexane/i-PrOH 95/5,
1.0 mL/min, 220 nm, retention time: 10.13 min (1R, 2R), 12.40 min
(1S, 2S); HRMS (M+Na) calcd. for C12H15ClOS: 265.0438, found:
265.0434.
trans-( )-2-(4-Bromophenylthio)cyclohexanol (6): Yield:
89%; 1H NMR (CDCl3, 300 MHz), ı [ppm]: 1.39 (m, 4H), 1.73 (m,
2H), 2.08 (m,2H), 3.18 (m, 1H), 4.78 (m, 1H), 7.19–7.30 (m, 4H);
13C NMR (CDCl3, 75 MHz) ı [ppm]: 20.9, 23.4, 24.9, 31.3, 50.2, 75.2,
126.8, 129.7, 131.1, 134.3, 137.1. HPLC analysis: Daicel chiralpak
OD-H, hexane/i-PrOH 95/5, 0.3 mL/min, 220 nm, retention times:
4. Experimental
4.1. Materials and methods
NMR spectra were obtained at 300 MHz (JEOL AL-300) using
either CDCl3 or DMSO as solvents with Me4Si in CDCl3 as the
internal standard. The chemical shifts are given in delta (ı) val-
ues and the coupling constants (J) in Hertz (Hz). Spectral patterns
are designated as s = singlet; d = doublet; dd = doublet of dou-
blets; q = quartet; t = triplet; br = broad; m = multiplet. Analytical
thin layer chromatography (TLC) was performed on either (i) alu-
minum sheets pre-coated with silica gel GF254 (Merck, India) or (ii)
glass plates (7.5 cm × 2.5 cm) coated with silica gel GF-254 (Spec-
trochem, India). Visualization of the spots was accomplished by

72
S.S. Chimni et al. / Journal of Molecular Catalysis B: Enzymatic 96 (2013) 67–74
15.24 min (1R, 2R), 20.33 min (1S, 2S); HRMS (M+Na) calcd. for
70.3, 74.6, 125.2, 126.8, 129.0, 136.4; HPLC analysis: Daicel chi-
ralpak OD-H, hexane/i-PrOH 95/5, 0.5 mL/min, 220 nm, retention
time: 10.65 min (1S, 2S), 11.23 min (1R, 2R); HRMS (M+Na) calcd.
for C14H18O2S: 273.0913, found: 273.0912.
trans-( )-2-(p-Tolylthio)cyclohexyl acetate (2a): Yield: 72%;
1H NMR (CDCl3, 300 MHz), ı [ppm]: 1.32–1.47 (m, 4H), 1.53–1.87
(m, 4H), 2.01 (s, 3H), 2.35 (s, 1H), 3.07 (m, 1H), 4.18 (m, 1H),
6.92–7.10 (m, 4H); 13C NMR (CDCl3, 75 MHz) ı [ppm]: 21.0, 21.6,
24.3, 28.2, 29.9, 58.9, 74.6, 126.7, 129.3, 133.4, 134.8, 170.3; HPLC
analysis: Daicel chiralpak OD-H, hexane/i-PrOH 95/5, 0.5 mL/min,
220 nm, retention time: 5.94 min (1S, 2S), 6.63 min (1R, 2R); HRMS
(M+Na) calcd. for C15H20O2S: 287.1075 found: 287.1100.
trans-( )-2-(4-Chlorophenylthio)cyclohexyl acetate (3a):
Yield: 71%; 1H NMR (CDCl3, 300 MHz), ı [ppm]: 1.31–1.49 (m,
4H), 1.57–1.92 (m, 4H), 2.01 (s, 3H), 3.07 (m, 1H), 4.18 (m, 1H),
7.12–7.24 (m, 4H); 13C NMR (CDCl3, 75 MHz) ı [ppm]: 21.0, 21.6,
24.7, 28.2, 29.9, 58.9, 74.6, 128.2, 129.1, 130.7, 134.5, 170.3; HPLC
analysis: Daicel chiralpak OD-H, hexane/i-PrOH 95/5, 1.0 mL/min,
220 nm, retention times: 5.05 min (1S, 2S), 5.78 min (1R, 2R).
trans-( )-2-(3-Chlorophenylthio)cyclohexyl acetate (4a):
Yield 67%; 1H NMR (CDCl3, 300 MHz), ı [ppm]: 1.30–1.48 (m,
4H), 1.60–1.91 (m, 4H), 2.01 (s, 3H), 3.09 (m, 1H), 4.20 (m, 1H),
7.02–7.21 (m, 4H); 13C NMR (CDCl3, 75 MHz) ı [ppm]: 21.2, 24.5,
28.0, 29.7, 58.4, 74.2, 124.9, 125.2, 130.5, 136.6, 170.1; HPLC
analysis: Daicel chiralpak OD-H, hexane/i-PrOH 95/5, 1.0 mL/min,
220 nm, retention time: 4.80 min (1S, 2S), 5.14 min (1R, 2R).
trans-( )-2-(2-Chlorophenylthio)cyclohexyl acetate (5a):
Yield: 64%; 1H NMR (CDCl3, 300 MHz), ı [ppm]: 1.32–1.47 (m,
4H), 1.59–1.89 (m, 4H), 2.12 (s, 3H), 3.09 (m, 1H), 4.16 (m, 1H)
6.92–7.22 (m, 4H); 13C NMR (CDCl3, 75 MHz) ı [ppm]: 21.5, 22.0,
24.6, 28.0, 29.8, 58.4, 74.6, 126.6, 127.1, 128.9, 136.0, 170.4; HPLC
analysis: Daicel chiralpak OD-H, hexane/i-PrOH 95:5, 1.0 mL/min,
220 nm, retention time: 3.69 min (1S, 2S), 4.36 min (1R, 2R).
trans-( )-2-(4-Bromophenylthio)cyclohexyl acetate (6a):
Yield: 84%; 1H NMR (CDCl3, 300 MHz), ı [ppm]: 1.27–1.49 (m,
4H), 1.52–1.89 (m, 4H), 2.01 (s, 3H), 3.07 (m, 1H), 4.18 (m, 1H),
7.07–7.33 (m, 4H); 13C NMR (CDCl3, 75 MHz) ı [ppm]: 21.0, 21.6,
24.7, 28.2, 29.9, 58.9, 74.6, 119.5, 129.0, 131.9, 135.4, 170.3; HPLC
analysis: Daicel chiralpak OD-H, hexane/i-PrOH 95:5, 0.3 mL/min,
220 nm, retention time: 5.72 min (1S, 2S), 6.41 min (1R, 2R); HRMS
(M+K) calcd. for C14H17O2BrS: 369.0069, found: 368.0074.
C12H15BrOS: 309.0254, found: 309.0249.
trans-( )-2-(4-Fluorophenylthio)cyclohexanol (7): Yield:
87%; 1H NMR (CDCl3, 300 MHz), ı [ppm]: 1.20–1.34 (m, 6H),
1.66–1.74 (m, 2H), 2.03–2.15 (m, 1H), 2.66–3.28 (m, 1H), 6.98–7.04
(m, 2H), 7.44–7.48 (m, 2H); HPLC analysis: Daicel chiralpak
OD-H, hexane/i-PrOH 95/5, 0.5 mL/min, 254 nm, retention times:
14.98 min (1R, 2R), 17.20 min (1S, 2S); HRMS (M+K) calcd. for
C12H15FOS: 265.1474, found: 265.1473.
trans-( )-2-(4-Methoxyphenylthio)cyclohexanol (8): Yield:
75%; 1H NMR (CDCl3, 300 MHz), ı [ppm]: 1.32–1.45 (m, 4H),
1.50–1.86 (m, 4H), 3.71 (s, 3H) 2.52–2.69 (m, 1H), 3.23–3.47 (m,
1H), 6.65–7.38 (m, 4H); 13C NMR (CDCl3, 75 MHz) ı [ppm]: 21.7,
25.4, 28.2, 56.1, 61.9, 72.6, 114.7, 127.6, 128.9, 157.0; HPLC analysis:
Daicel Chiralcel OD-H, hexane/i-PrOH = 9/1, flow rate = 0.5 mL/min,
220 nm, retention time: 12.13 min (1R, 2R), 17.82 min (1S, 2S);
HRMS (M+Na) calcd. for C13H18O2S: 261.3349, found: 261.3350.
trans-( )-2-(Naphthalen-3-ylthio)cyclohexanol (9): Yield:
82%; 1H NMR (CDCl3, 300 MHz), ı [ppm]: 1.27–1.39 (m, 4H),
1.72–1.73 (m, 2H), 2.12–2.16 (m, 2H), 2.89–2.94 (m, 2H), 3.43 (m,
1H), 7.18–7.54 (m, 5H); 13C NMR (CDCl3, 75 MHz) ı [ppm]: 24.2,
26.1, 32.6, 33.8, 56.5, 72.1, 126.4, 126.5, 126.7, 127.4, 127.6, 128.4,
129.9, 130.9, 132.5, 132.7, 133.5; HPLC analysis: Daicel chiralpak
AS-H, hexane/i-PrOH 97/3, 1.0 mL/min, 220 nm, retention time:
9.87 min (1R, 2R), 11.04 min (1S, 2S); 11.04 min; HRMS (M+Na)
calcd. for C16H18OS: 281.0977, found: 281.0980.
trans-( )-2-(Cyclohexylthio)cyclohexanol (10): Yield: 69%;
1H NMR (CDCl3, 300 MHz), ı [ppm]: 1.37–1.46 (m, 10H), 1.47–1.92
(m, 6H), 2.48–2.56 (m,2H), 3.44 (m, 1H); 13C NMR (CDCl3, 75 MHz)
ı [ppm]: 24.2, 24.4, 25.2, 25.5, 26.1, 26.3, 26.4, 33.6,34.4, 34.6,
34.9, 37.8, 38.4, 43.63, 52.6, 72.5. HPLC analysis: Daicel chiralpak
OD-H, hexane/i-PrOH 95/5, 0.5 mL/min, 220 nm, retention time:
14.78 min (1R, 2R), 19.93 min (1S, 2S); HRMS (M+Na) calcd. for
C
12H22OS: 237.1247, found: 237.1239.
trans-( )-2-(Phenylthio)cyclopentanol (11): Yield: 75%; 1H
NMR (CDCl3, 300 MHz), ı [ppm]: 1.59–1.80 (m, 6H), 3.39–3.40
(m, 1H), 4.10–4.12 (m, 1H), 7.20–7.42 (m, 5H); 13C NMR (CDCl3,
75 MHz) ı [ppm]: 20.8, 28.2, 34.1, 47.9, 88.7, 125.4, 126.7, 129.2,
135.9; HPLC analysis: Daicel chiralpak OD-H, hexane/i-PrOH 90/10,
0.5 mL/min, 220 nm, retention time: 10.35 min (1R, 2R), 12.51 min
(1S, 2S); HRMS (M+K) calcd. for C11H14OS: 233.0630, found:
233.0632.
trans-( )-2-(4-Fluorophenylthio)cyclohexyl acetate (7a):
Yield: 79%; 1H NMR (CDCl3, 300 MHz), ı [ppm]: 1.25–1.43 (m, 4H),
1.58–1.71 (m, 2H), 1.97 (m,3H), 2.03–2.42 (m, 2H), 2.97–3.05 (m,
(
)-1-(Phenylthio)butan-2-ol (12): Yield: 74%; 1H NMR
(CDCl3, 300 MHz), ı [ppm]: 0.94–0.99 (m, 2H), 1.49–1.61 (m, 3H),
2.80–2.88 (m, 1H), 3.12–3.18 (m, 1H), 3.56–3.64 (m, 1H), 7.18–7.39
(m, 5H); HPLC analysis: Daicel chiralpak OD-H, hexane/i-PrOH 95/5,
0.5 mL/min, 220 nm, retention times: 9.78 min (R); 10.93 min (S);
HRMS (M+K) calcd. for C10H14OS: 221.1160, found: 221.1159.
trans-( )-3-(Phenylthio)butan-2-ol (13): Yield: 72%; 1H NMR
(CDCl3, 300 MHz), ı [ppm]: 1.22–1.29 (m, 6H), 3.04–3.09 (m, 1H),
3.66–3.68 (m, 1H), 7.25–7.64 (m, 5H); HPLC analysis: Daicel chi-
ralpak OD-H, hexane/i-PrOH 95/5, 0.5 mL/min, 220 nm, retention
times: 9.43 min (1R, 2R), 11.80 min (1S, 2S); HRMS (M+K) calcd. for
1H), 4.70–4.76 (m, 1H), 6.96–7.02 (m, 2H), 7.40–7.45 (m, 2H); 13
C
NMR (CDCl3, 75 MHz) ı [ppm]: 21.1, 23.5, 25.0, 31.3, 31.5, 50.8,
74.8, 115.6, 115.9, 135.3, 135.4; HPLC analysis: Daicel chiralpak
OD-H, hexane/i-PrOH 95:5, 0.5 mL/min, 254 nm, retention times:
10.45 min (1S, 2S), 11.50 min (1R, 2R); HRMS (M+Na) calcd. for
C14H17FO2S: 291.0929 found: 291.0933.
trans-( )-2-(4-Methoxyphenylthio)cyclohexyl acetate (8a):
Yield: 69%; 1H NMR (CDCl3, 300 MHz), ı [ppm]: 1.37–1.48 (m, 4H),
1.55–1.85 (m, 4H), 2.03 (s, 3H), 3.01–3.10 (m, 1H), 4.09–4.20 (m,
1H), 3.69 (s, 3H), 6.65–7.10 (m, 5H); 13C NMR (CDCl3, 75 MHz)
ı [ppm]: 21.1, 22.6, 24.5, 28.0, 29.8, 55.4, 58.7, 74.4, 114.0,
127.5, 128.9, 156.9, 170.6; HPLC analysis: Daicel chiralpak OD-H,
hexane/i-PrOH 97/3, 1.0 mL/min, 220 nm, retention times: 3.58 min
(1S, 2S), 4.56 min (1R, 2R); HRMS (M+Na) calcd. for C15H20O3S:
303.3716, found: 303.3712.
trans-( )-2-(Naphthalen-3-ylthio)cyclohexyl acetate (9a):
Yield: 73%; 1H NMR (CDCl3, 300 MHz), ı [ppm]: 1.27–1.39 (m, 4H),
1.72–1.73 (m, 2H), 2.12–2.16 (m, 2H), 2.89–2.94 (m, 2H), 3.43 (m,
1H), 7.18–7.54 (m, 5H); 13C NMR (CDCl3, 75 MHz) ı [ppm]: 22.1,
25.2, 28.2, 33.8, 58.9, 74.6, 127.3, 128.1, 128.9, 129.9, 130.2, 133.0,
134.2, 170.2; HPLC analysis: Yield: 46%; Daicel chiralpak OD-H,
hexane/i-PrOH 97/3, 1.0 mL/min, 220 nm, retention times: 4.68 min
C10H14OS: 221.0621, found: 221.0623.
4.3. General method for preparation of racemic acetates
To a stirred solution of ␤-hydroxy sulfide (1 equiv.), 5 equiv. of
acetyl chloride was added at 0 ◦C. The reaction mixture was stirred
at 0 ◦C for 10–30 min. The excess acetyl chloride was removed
under reduced pressure. The racemic acetates were purified by
column chromatography.
trans-( )-2-(Phenylthio)cyclohexyl acetate (1a): Yield: 68%;
1H NMR (CDCl3, 300 MHz), ı [ppm]: 1.39–1.50 (m, 4H), 1.55–1.87
(m, 4H), 2.01 (s, 3H), 3.07 (m, 1H), 4.18 (m, 1H), 7.02–7.18 (m,
5H); 13C NMR (CDCl3, 75 MHz) ı [ppm]: 21.0, 21.6, 24.7, 28.2, 58.9,

S.S. Chimni et al. / Journal of Molecular Catalysis B: Enzymatic 96 (2013) 67–74
73
(1S, 2S), 5.38 min (1R, 2R); HRMS (M+Na) calcd. for C18H20O2S:
323.1179, found: 323.1184.
chiralpak OD-H, hexane/i-PrOH 95/5, 1.0 mL/min, 220 nm, reten-
tion time: 11.55 min (1S, 2S).
trans-( )-2-(Cyclohexylthio)cyclohexyl acetate (10a): Yield:
78%; 1H NMR (CDCl3, 300 MHz), ı [ppm]: 1.39–1.49 (m, 10H),
1.52–1.90 (m, 8H), 2.02–2.48 (m,4H), 3.07 (m, 1H), 4.18 (m, 1H);
13C NMR (CDCl3, 75 MHz) ı [ppm]: 21.0, 21.6, 24.2, 24.4, 24.7, 27.6,
29.9, 34.9, 47.7, 75.3, 170.3. HPLC analysis: Daicel chiralpak OD-H,
hexane/i-PrOH 95/5, 0.5 mL/min, 220 nm, retention times: 4.20 min
(1S, 2S), 5.14 min (1R, 2R).
(1R, 2R)-2-(3-Chlorophenylthio)cyclohexyl acetate (4a): Yield
42%; HPLC analysis: Daicel chiralpak OD-H, hexane/i-PrOH 95/5,
1.0 mL/min, 220 nm, retention time: 5.14 min (1R, 2R).
(1S, 2S)-2-(2-Chlorophenylthio)cyclohexanol (5): Yield: 42%;
HPLC analysis: Daicel chiralpak OD-H, hexane/i-PrOH 95/5,
1.0 mL/min, 220 nm, retention time: 12.40 min (1S, 2S).
(1R, 2R)-2-(2-Chlorophenylthio)cyclohexyl acetate (5a):
Yield: 47%; HPLC analysis: Daicel chiralpak OD-H, hexane/i-PrOH
95:5, 1.0 mL/min, 220 nm, retention time: 4.36 min (1R, 2R).
(1S, 2S)-2-(4-Bromophenylthio)cyclohexanol (6): Yield: 41%;
[␣]D25 = +50.6◦ (c 1.00, CHCl3); 99% ee; HPLC analysis: Daicel chi-
ralpak OD-H, hexane/i-PrOH 95/5, 0.3 mL/min, 220 nm, retention
times: 20.33 min (1S, 2S).
(1R, 2R)-2-(4-Bromophenylthio)cyclohexyl acetate (6a):
Yield: 35%; [␣]D25 = +28.6◦ (c 1.00, CHCl3); 99% ee; HPLC analysis:
Daicel chiralpak OD-H, hexane/i-PrOH 95:5, 0.3 mL/min, 220 nm,
retention time: 6.41 min (1R, 2R).
(1S, 2S)-2-(4-Fluorophenylthio)cyclohexanol (7): Yield: 41%;
[␣]D25 = +48.7◦ (c 1.00, CHCl3); 99% ee; HPLC analysis: Daicel chi-
ralpak OD-H, hexane/i-PrOH 95/5, 0.5 mL/min, 254 nm, retention
times: 17.20 min (1S, 2S).
trans-( )-2-(Phenylthio)cyclopentyl acetate (11a): Yield:
92%; 1H NMR (CDCl3, 300 MHz), ı [ppm]: 1.46–1.94 (m, 6H), 2.03
(s, 3H), 3.10–3.14 (m, 1H), 4.11–4.26 (m, 1H), 7.02–7.22 (m, 5H);
13C NMR (CDCl3, 75 MHz) ı [ppm]: 21.2, 28.0, 30.4, 44.7, 76.1,
126.6, 129.5, 136.3, 170.2; HPLC analysis: Daicel chiralpak OD-H,
hexane/i-PrOH 95:5, 0.5 mL/min, 220 nm, retention times: 4.72 min
(1S, 2S), 5.73 min (1R, 2R); HRMS (M+Na) calcd. for C13H16O2S:
259.0765, found: 259.0799.
(
)-1-(Phenylthio)butan-2-yl acetate (12a): Yield: 83%;1H
NMR (CDCl3, 300 MHz), ı [ppm]: 0.90–0.92 (m, 3H), 1.63–1.96 (m,
5H), 3.01–3.16 (s, 2H), 4.94–4.96 (m, 1H), 7.18–7.40 (m, 5H); HPLC
analysis: Daicel chiralpak OD-H, hexane/i-PrOH 95:5, 0.5 mL/min,
220 nm, retention times: 5.63 min (S), 6.27 min (R).
trans-( )-3-(Phenylthio)butan-2-yl acetate (13a): Yield: 71%;
1H NMR (CDCl3, 300 MHz), ı [ppm]: 0.94–0.99 (m, 2H), 1.49–1.61
(m, 3H), 2.80–2.88 (m, 1H), 3.12–3.18 (m, 1H), 3.56–3.64 (m, 1H),
7.18–7.39 (m, 5H); HPLC analysis: Daicel chiralpak OD-H, hexane/i-
PrOH 95:5, 0.5 mL/min, 220 nm, retention times: 5.02 min (1S, 2S),
5.81 min (1R, 2R).
(1R, 2R)-2-(4-Fluorophenylthio)cyclohexyl acetate (7a):
Yield: 44%; [␣]D25 = +6.8◦ (c 1.00, CHCl3); 99% ee; HPLC analysis:
Daicel chiralpak OD-H, hexane/i-PrOH 95:5, 0.5 mL/min, 254 nm,
retention time: 11.50 min (1R, 2R).
(1S,
2S)-2-(4-Methoxyphenylthio)cyclohexanol
(8):
Yield = 42%; [␣]D25 = +56.2◦ (c 1.00, CHCl3); 99% ee; HPLC analysis:
Daicel Chiralcel OD-H, hexane/i-PrOH = 9/1, flow rate = 0.5 mL/min,
220 nm, retention time: 17.82 min (1S, 2S).
4.4. General procedure for resolution of racemic aryl ˇ-hydroxy
sulfides
(1R, 2R)-2-(4-Methoxyphenylthio)cyclohexyl acetate (8a):
Yield = 47%; [␣]D25 = +7.4◦ (c 1.00, CHCl3); 99% ee; HPLC analysis:
Daicel chiralpak OD-H, hexane/i-PrOH 97/3, 1.0 mL/min, 220 nm,
retention times: 4.56 min (1R, 2R).
(1S, 2S)-2-(Naphthalen-3-ylthio)cyclohexanol (9): Yield: 40%;
[␣]D25 = +53.1◦ (c 1.00, CHCl3); 99% ee; HPLC analysis: Daicel chiral-
pak AS-H, hexane/i-PrOH 97/3, 1.0 mL/min, 220 nm, retention time:
11.04 min (1S, 2S).
(1R, 2R)-2-(Naphthalen-3-ylthio)cyclohexyl acetate (9a):
HPLC analysis: Yield: 46%; Daicel chiralpak OD-H, hexane/i-PrOH
97/3, 1.0 mL/min, 220 nm, retention times: 5.38 min (1R, 2R).
(1S, 2S)-2-(Cyclohexylthio)cyclohexanol (10): Yield: 35%;
[␣]D25 = +44.3◦ (c 1.00, CHCl3); 99% ee; HPLC analysis: Daicel chi-
ralpak OD-H, hexane/i-PrOH 95/5, 0.5 mL/min, 220 nm, retention
time: 19.93 min (1S, 2S).
A solution of the ( )-1 (100 mg) and vinyl acetate (4.5 ml,
50 mmol) was stirred with Immobilized C. antartica B (100 mg, 1 eq.
w/w) at 27 ◦C. The reaction was monitored by taking out aliquots at
regular intervals and analyzed with HPLC. The reaction was stopped
by filtering the enzyme on a sintered glass funnel. Concentration
of the filtrate followed by column chromatography provided (1R,
2R)-1a-13a and (1S, 2S)-1-13.
(1S, 2S)-2-(Phenylthio)cyclohexanol (1): Yield: 46%,
[␣]D25 = +62.4◦ (c 1.00, CHCl3); >99% ee; HPLC analysis: Dai-
cel chiralpak OD-H, hexane/i-PrOH 95/5, 0.5 mL/min, 220 nm,
retention time: 21.66 (1S, 2S) min.
(1R, 2R)-2-(Phenylthio)cyclohexyl acetate (1a): Yield: 42%,
[␣]D25 = +19.6◦ (c 0.50, CHCl3); 99% ee; HPLC analysis: Daicel chi-
ralpak OD-H, hexane/i-PrOH 95/5, 0.5 mL/min, 220 nm, retention
time: 11.23 min (1R, 2R).
(1S, 2S)-2-(p-Tolylthio)cyclohexanol (2): Yield: 43%;
[␣]D25 = +65.8◦ (c 1.00, CHCl3); >99% ee; HPLC analysis: Dai-
cel Chiralcel OD-H, hexane/i-PrOH = 9/1, flow rate = 0.5 mL/min,
220 nm, retention time: 18.72 min (1S, 2S).
(1R, 2R)-2-(p-Tolylthio)cyclohexyl acetate (2a): Yield: 45%;
[␣]D25 = +16.7◦ (c 1.00, CHCl3); 99% ee; HPLC analysis: Daicel chi-
ralpak OD-H, hexane/i-PrOH 95/5, 0.5 mL/min, 220 nm, retention
time: 6.63 min (1R, 2R).
(1S, 2S)-2-(4-Chlorophenylthio)cyclohexanol (3): Yield: 37%;
[␣]D25 = +67.1◦ (c 1.00, CHCl3); >99% ee; HPLC analysis: Daicel
chiralpak OD-H, hexane/i-PrOH 95/5, 1.0 mL/min, 220 nm, reten-
tion times: 13.26 min (1S, 2S).
(1R, 2R)-2-(4-Chlorophenylthio)cyclohexyl acetate (3a):
Yield: 47%; [␣]D25 = +24.3◦ (c 1.00, CHCl3); 99% ee; HPLC analysis:
Daicel chiralpak OD-H, hexane/i-PrOH 95/5, 1.0 mL/min, 220 nm,
retention times: 5.78 min (1R, 2R).
(1R,
2R)-2-(Cyclohexylthio)cyclohexyl
acetate
(10a):
Yield: 38%; HPLC analysis: Daicel chiralpak OD-H, hexane/i-
PrOH 95/5, 0.5 mL/min, 220 nm, retention times: 5.14 min
(1R, 2R).
(1S, 2S)-2-(Phenylthio)cyclopentanol (11): Yield: 45%;
[␣]D25 = +23.2◦ (c 1.00, CHCl3); 99% ee; HPLC analysis: Daicel chi-
ralpak OD-H, hexane/i-PrOH 90/10, 0.5 mL/min, 220 nm, retention
time: 12.51 min (1S, 2S).
(1R, 2R)-2-(Phenylthio)cyclopentyl acetate (11a): Yield: 43%;
HPLC analysis: Daicel chiralpak OD-H, hexane/i-PrOH 95:5,
0.5 mL/min, 220 nm, retention times: 5.73 min (1R, 2R).
(1S,
2S)-1-(Phenylthio)butan-2-ol
(12):
Yield:
44%;
[␣]D25 = +62.6◦ (c 1.00, CHCl3); 99% ee; HPLC analysis: Dai-
cel chiralpak OD-H, hexane/i-PrOH 95/5, 0.5 mL/min, 220 nm,
retention times: 10.93 min (S).
(R)-1-(Phenylthio)butan-2-yl acetate (12a): Yield: 40%; HPLC
analysis: Daicel chiralpak OD-H, hexane/i-PrOH 95:5, 0.5 mL/min,
220 nm, retention times: 6.27 min (R).
(1S, 2S)-2-(3-Chlorophenylthio)cyclohexanol (4): Yield: 37%;
(1S,
2S)-3-(Phenylthio)butan-2-ol
(13):
Yield:
46%;
[␣]D25 = +67.1◦ (c 1.00, CHCl3); >99% ee; HPLC analysis: Daicel
[␣]D25 = +36.7◦ (c 1.00, CHCl3); 99% ee; HPLC analysis: Daicel

74
S.S. Chimni et al. / Journal of Molecular Catalysis B: Enzymatic 96 (2013) 67–74
chiralpak OD-H, hexane/i-PrOH 95/5, 0.5 mL/min, 220 nm,
retention times: 11.80 min (1S, 2S).
(1R, 2R)-3-(Phenylthio)butan-2-yl acetate (13a): Yield: 41%;
HPLC analysis: Daicel chiralpak OD-H, hexane/i-PrOH 95:5,
0.5 mL/min, 220 nm, retention times: 5.81 min (1R, 2R).
[10] V. Kesavan, D. Bonnet-Delpon, J.P. Bégué, Tetrahedron Letters 41 (2000) 2895.
[11] P. Bravo, G. Resnati, F. Viani, A. Arnone, Tetrahedron 43 (1987) 4635.
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The research was supported by funds from DBT, India (Research
Grant BT/PR4694/PID/6/633/2012) and UGC, India (KK). The finan-
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acknowledged. We thank Prof. Geeta Hundal for single crystal X-ray
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