Chemo-enzymatic preparation of optically active thiiranes

Article abstract of DOI:10.1016/j.tetasy.2007.01.024

A simple method for the preparation of optically active 2-(arylsulfanylmethyl)thiiranes and 2-(aryloxymethyl)thiiranes from the corresponding 3-thiocyanatopropan-2-ols and their acetates was developed. The starting enantiomerically enriched β-thiocyanatoa

Full text of DOI:10.1016/j.tetasy.2007.01.024

Tetrahedron: Asymmetry 18 (2007) 493–499
Chemo-enzymatic preparation of optically active thiiranes
Edyta Łukowska and Jan Plenkiewicz*
Chemistry Faculty, Warsaw University of Technology, ul. Noakowskiego 3, 00-664 Warsaw, Poland
Received 9 January 2007; accepted 22 January 2007
Available online 21 February 2007
Abstract—A simple method for the preparation of optically active 2-(arylsulfanylmethyl)thiiranes and 2-(aryloxymethyl)thiiranes from
the corresponding 3-thiocyanatopropan-2-ols and their acetates was developed. The starting enantiomerically enriched b-thiocyanato-
alcohols and the acetates were obtained by a lipase-catalyzed hydrolysis of the appropriate racemic acetates.
ꢀ 2007 Elsevier Ltd. All rights reserved.
1. Introduction
mixed chemo-enzymatic procedure seems to be a promising
route to optically active thiiranes.
Several methods of thiirane preparation have been
reported in the literature. The most efficient route consists
of the conversion of oxiranes into the corresponding thiir-
anes by an oxygen–sulfur exchange reaction. Various sulfur
reagents such as inorganic thiocyanates,1–3 thiourea,3,4
phosphine sulfide,5 potassium thiocyanate6 supported on
silica gel or dimethylthioformamide7 were used to this
end. However, all these methods lead to the preparation
of racemic mixtures. Optically active thiiranes were ob-
tained almost quantitatively in a similar reaction of enantio-
merically enriched oxiranes with thiourea in methanol
solution at room temperature. This procedure does not
affect the chirality of the stereogenic center since no epimer-
ization is observed.8 Another known procedure involves
the Ru(III)-catalyzed9 conversion of optically active oxir-
anes into the corresponding thiiranes in the presence of
ammonium thiocyanate. In this case, (S)-(ꢀ)-styrene
sulfide was obtained from (R)-(+)-styrene oxide in high
enantiomeric excess and excellent yield.
Herein, new acetates of 1-arylsulfanyl-3-thiocyanatopro-
pan-2-ols were used as starting compounds. It was supposed
that the intermediate 1-arylsulfanyl-3-thiocyanatopropan-
2-ols 1 as well as acetates 2 might turn out to be better
substrates in lipase-catalyzed racemate separations and thus
ensure better overall results and higher enzyme
enantioselectivity.
1-Arylsulfanyl-3-thiocyanatopropan-2-ols 1 were prepared
according to a two-step procedure reported10,11 previously
for the preparation of 1-aryloxy-3-thiocyanatopropan-2-
ols. It consisted in the crown ether-catalyzed reaction of
the appropriate 2-(arylsulfanylmethyl)oxiranes with ammo-
nium thiocyanate in an acetonitrile solution (Scheme 1).
Because of low stability ( )-1a–d were not isolated. Instead
they were converted in situ into the corresponding acetates
( )-2a–d by reaction with acetyl chloride. As could be
expected, addition of trace amounts of hydroquinone
stabilized11 ( )-1a–d in the reaction medium and increased
the yields of ( )-2a–d. The latter were stable enough to be
separated and purified.
2. Results and discussion
In recent work,10 we have described an attempt to prepare
optically active thiiranes from enantiomerically enriched 1-
aryloxy-3-thiocyanatopropan-2-ols. In our studies, how-
ever, only optically active polymers were obtained instead
of the expected monomeric thiiranes. Nevertheless, the
According to the literature data,12 Selectfluor can be used
to replace the crown ether as the catalyst in the epoxide
cleavage reaction. In our experiments, Selectfluor was used
in the ring opening reactions of 2-(arylsulfanylmethyl)oxir-
anes by ammonium thiocyanate with no hydroquinone
added. The reactions were carried out at reflux since at
room temperature the reaction rate was very low and some
substrate was still present in the mixture even after 48 h.
*
Corresponding author. Tel.: +48 22 234 7570; fax: +48 22 628 2741;
e-mail: plenki@ch.pw.edu.pl
0957-4166/$ - see front matter ꢀ 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2007.01.024

494
E. Łukowska, J. Plenkiewicz / Tetrahedron: Asymmetry 18 (2007) 493–499
OH
OAc
CH3COCl
reflux
O
NH4SCN, CH3CN
Ar
S
CH2Cl2, catalyst,
reflux
S
SCN
S
SCN
Ar
Ar
( )-1a-d
( )-2a-d
a-Ar= Ph-,
b-Ar= p-Cl-Ph-,
c-Ar= p-Br-Ph-,
d-Ar= p-CH3-Ph-
Scheme 1.
The racemic mixtures of 2a–d were then used as the sub-
strates in a lipase-catalyzed hydrolysis, which was carried
out at 30 ꢁC in a two-phase tert-butyl methyl ether-phos-
phate buffer of pH 7 system, as shown in Scheme 2 (Table 2).
Table 1. The yields of acetates ( )-2a–d obtained with or without the
addition of hydroquinone in the presence of a crown ether or Selectfluor
catalyst
Entry
Ar–
Catalyst
18-Crown-6
Selectfluor
Yield (%)
Three lipase preparations were tested in the reactions:
Amano AK from Pseudomonas sp., Amano PS from Pseu-
domonas cepacia, and Novozym SP 435 from Candida ant-
arctica. Only the last enzyme was capable of hydrolyzing
( )-2a–d with high stereoselectivity. In the case of ( )-2c,
a satisfactory enantiomeric excess was also obtained with
the Amano PS lipase. The progress of the reactions was
monitored on TLC plates and the reactions were stopped
at a conversion level of approximately 50%. In these
reactions alcohols and esters of high enantiomeric purity
were obtained. The (R)-configuration of the separated
enantiomer of 1-phenylsulfanyl-3-thiocyanatopropan-2-yl
acetate (ꢀ)-4a was determined by X-ray crystallography
(Fig. 1).
Yield (%)
Yield (%) with
hydroquinone
a
b
c
Ph–
30
36
64
40
83
69
80
68
80
68
65
70.5
p-Cl–Ph–
p-Br–Ph–
p-CH3–Ph–
d
Also in this case, ( )-1a–d were not isolated but converted
in situ into ( )-2a–d. The yields were satisfactory and com-
parable with those obtained in the presence of 18-crown-6
with added hydroquinone. The relevant data are presented
in Table 1.
OH
OAc
OAc
Enzyme, T=30 °C
+
t-BuOMe
phosphate buffer pH=7
S
SCN
S
SCN
S
SCN
Ar
Ar
Ar
(S)-(+)-3a-d
( )-2a-d
(R)-(-)-4a-d
Scheme 2.
Table 2. Results of lipase-catalyzed hydrolysisa of esters ( )-2a–d
cb (%)
eesc (%)
eep (%)
Eb
c
Entry
Ar–
Enzyme
Time (h)
a
b
c
Ph–
116
72
165
91
48
37.5
42
90
58
61
NDd
96
98
85
80
>100
>100
23
p-Cl–Ph–
p-Br–Ph–
p-CH3–Ph–
Novozym SP 435
d
—
—
a
b
c
Ph–
96
120
73
44
43
20
—
21
24
95
NDd
27
32
38
90
2
2
2
p-Cl–Ph–
p-Br–Ph–
p-CH3–Ph–
Amano AK
d
120
—
a
b
c
Ph–
96
96
48
89
71
71.5
40
94
95
58
NDd
38
38
85
95
7
7
22
p-Cl–Ph–
p-Br–Ph–
p-CH3–Ph–
Amano PS
d
—
—
a Conditions: 1 g of ( )-2a–d, 40 mL of TBME (tert-butyl methyl ether), 200 mL of 0.1 M phosphate buffer KH2PO4–K2HPO4 (pH 7), 1 g of enzyme
(Novozym SP 435, Amano AK or Amano PS lipase), temperature 30 ꢁC.
b Conversion (c) and E values were calculated from the enantiomeric excess of substrate (acetate) (ꢀ)-3a–d (ees) and product (alcohol) (+)-4a–d (eep) using
the formula: E = Ln[(1 ꢀ ees) (eep/(ees + eep))]/Ln[(1 + ees) (eep/(ees + eep))], conv. = ees/(ees + eep).
*
*
c Determined by HPLC analysis using Chiralcel OD-H column.
d ND—not determined.

E. Łukowska, J. Plenkiewicz / Tetrahedron: Asymmetry 18 (2007) 493–499
495
the contact time of the formed thiirane and the base was
considerably reduced. With those changes in procedure
we were able to prepare the requested monomeric optically
active 2-(arylsulfanylmethyl)thiiranes in good yields. Also,
optically active 2-(aryloxymethyl)thiiranes 6e–g were
obtained from the previously described10 1-aryloxy-3-thio-
cyanatopropan-2-yl acetates (R)-(ꢀ)-4e–g by the same
procedure (Scheme 4).
S
OAc
THF, LiOH
H2O
X
X
SCN
Ar
Ar
(R)-(-)-4a-g
(S)-6a-g
e-Ar-X= Ph-O-,
f-Ar-X= p-Cl-Ph-O-,
g-Ar-X= p-CH3-Ph-O-
Figure 1. An ORTEP plot of (R)-(ꢀ)-1-phenylsulfanyl-3-thiocyanatopro-
pan-2-yl acetate 4a with thermal ellipsoids drawn at 50% probability level.
Scheme 4.
In an attempt to prepare 2-(arylsulfanylmethyl)thiiranes
the solutions of optically active alcohols (S)-(+)-3a and
(S)-(+)-3b were treated in ethanol with a few drops of a
60% aqueous solution of potassium hydroxide at room
temperature. Upon a routine workup, optically active poly-
mers (S)-(ꢀ)-5a and (S)-(ꢀ)-5b were isolated as the prod-
ucts (Scheme 3). The result is similar to that described
earlier in our attempts to prepare 2-(aryloxymethyl)thiir-
anes from 1-aryloxy-3-thiocyanatopropan-2-ols.10 Poly-
merization proceeds very fast under this condition,
meaning that we were not able to isolate thiirane mono-
mers. The results are in accordance with literature1 data
reporting the instability of thiiranes in the presence of both
acids and bases. With nucleophiles, thiiranes are even more
reactive than oxiranes13 while ring opening at either the
primary or the secondary carbon atom leads to a mixture
of polymer isomers.
On the basis of the reaction mechanism proposed by Price
and Kirk14 (Scheme 5), it seems reasonable to assume that
the optically active thiiranes prepared possess the opposite
configuration to the starting 1-aryloxy- and 1-arylsulfanyl-
3-thiocyanatopropan-2-ols or the corresponding acetates.
Determination of the enantiomeric excesses of the prepared
thiiranes (S)-6e–g indicated that the conversion of acetates
(R)-(ꢀ)-4e–g into the corresponding thiiranes did not affect
the compounds enantiomeric purity; and no trace amounts
of racemization were observed (Table 3). On the contrary,
conversion of acetates (R)-(ꢀ)-4a–d into thiiranes 6a–d is
not so selective and some racemization was observed in
the reaction (Table 3). The yields of the final step of thiir-
anes preparation ranged from 67% to 87% depending on
the substrate used.
The following values of specific rotation were measured for
24
24:6
5a: ½aꢁD = ꢀ8.7 (c 1.61, CHCl3), for 5b: ½aꢁD = ꢀ7.5 (c 2,
CHCl3). Molecular weights of the polymers measured by
GPC in THF and referred to the polystyrene standard were
Mn = 1905.65 and Mw = 2701.50 for 5a; Mn = 1139.22 and
Mw = 2083.04 for 5b.
The opposite (R)-enantiomers of thiiranes 6a–g are also
directly available from alcohols (S)-(+)-3a–g obtained from a
lipase-catalyzed hydrolyses of racemic thiocyanatoacetates
4a–g (Scheme 6), or through the intermediate acetates. For
example, (S)-(+)-3a (ee = 96%) reacted with lithium
hydroxide, as described earlier gave the appropriate thii-
rane (R)-(ꢀ)-6a of 86% enantiomeric excess in 70% yield.
Acetylation of the optically active alcohol (S)-(+)-3a
(ee = 96%) with acetyl chloride gave the corresponding
acetate (S)-(+)-4a in 81% yield with no change of enantio-
meric excess; and the further reaction of (S)-(+)-4a with
lithium hydroxide afforded thiirane (R)-(ꢀ)-6a in 65% yield
and enantiomeric excess 82%.
In order to avoid the thiirane polymerization, we changed
the procedure and made the base react not with the alco-
hols (S)-(+)-3a–d but with their more stable acetates (R)-
(ꢀ)-4a–d. Moreover, considering relatively small volume
of the lithium cation, we used a solution of lithium hydrox-
ide instead of potassium hydroxide. The reaction was car-
ried out in a two-phase aqueous LiOH/THF system, thus
S
OH
60% KOH,
EtOH
POLYMER
S
S
SCN
Ar
Ar
(-)-5a,b
(S)-(+)-3a,b
Scheme 3.

496
E. Łukowska, J. Plenkiewicz / Tetrahedron: Asymmetry 18 (2007) 493–499
N
R
N
H
S
W. I.
O
R
H
H
H
SCN
H
+
H
H
R
HO
S
O
H
O
R
S
N
W. I.
H
R
OCN
+
H
S
Scheme 5.
Table 3. Yields and properties of thiiranes (S)-6a–g
23
24
Entry
Ar–X–
ees (%)
eep (%)
½aꢁD
½aꢁD
Yield (%)
s
p
a
b
c
d
e
f
Ph–S–
90
58
61
NDa
97
86
53
59
32
97
90
86
ꢀ8.4
ꢀ0.65
0
ꢀ1.9
ꢀ49.3
ꢀ37.5
ꢀ63.4
+71.4
+35.2
+33.0
+24.2
ꢀ13.6
ꢀ12.5
ꢀ10.7
79
67
84
71
87
83
76
p-Cl–Ph–S–
p-Br–Ph–S–
p-CH3–Ph–S–
Ph–O–
p-Cl–Ph–O–
p-CH3–Ph–O–
90
86
g
a ND—not determined.
Chiralpak AD-H column (in hexane:iso-propanol 95:5).
Optical rotations were measured in a CDCl3 solution with
PolAAr 32 polarimeter. Elemental analyses were per-
formed on a CHNSCl/O Perkin Elmer type 2400 instru-
ment. The reactions were monitored by TLC on silica gel
60 (230–400 mesh). The arylsulfanylglycidyl ethers were
prepared in high yields (80–85%) from the corresponding
thiophenols and epichlorohydrin in a NaOH/THF suspen-
sion according to the described15 method. The optically ac-
tive 1-aryloxy-3-thiocyanatopropan-2-yl acetates (ꢀ)-4f–g
were prepared by the lipase-catalyzed hydrolysis in a two-
phase tert-butyl methyl ether-phosphate buffer system from
the racemic mixtures.10 Amano AK, Amano PS, and Nov-
ozym SP 435 (immobilized C. antarctica-B lipase) were
kindly granted by Novo-Nordisk.
S
OH
THF, LiOH
H2O
X
X
SCN
Ar
Ar
(S)-(+)-3a-g
(R)-6a-g
Scheme 6.
3. Conclusions
Lipase catalyzed enantiomer separation of 1-arylsulfanyl-3-
thiocyanatopropan-2-yl acetates yields alcohols and esters
of high enantiomeric purity. The highest enantioselectivities
of the reaction (E > 20) were obtained with Novozym SP
435 from C. antarctica. Transformations of the optically
active b-hydroxythiocyanatopropane derivatives into the
corresponding enantiomerically enriched thiiranes were
carried out in two phase aqueous LiOH/THF system.
4.2. Preparation of 1-arylsulfanyl-3-thiocyanatopropan-2-yl
acetates ( )-2a–d. General procedure
To the mixture of 2-(arylsulfanylmethyl)oxiranes
(10 mmol) and NH4SCN (10 mmol, 1.52 g) in acetonitrile
(30 mL) a solution of 18-crown-6 ether in CH2Cl2
(0.1 mmol, 0.0264 g in 5 mL and traces of hydroquinone)
or selectfluor (1 mmol, 0.39 g) was added, and the mixture
stirred under reflux conditions. The progress of the reac-
tion was monitored by TLC, using n-hexane–ethyl acetate
(3:1 v/v) as the eluent. After completion of the reaction,
the precipitate was filtered off and the solvent evaporated.
The resulting crude mixture of b-hydroxythiocyanates
was used as the substrate in the synthesis of acetates by
adding an excess of acetyl chloride (25 mL) and stirring
the mixture for 2.5 h at reflux. After cooling to room
temperature, the traces of solid material were filtered off,
the filtrate cooled in an ice bath and neutralized to pH 7
with K2CO3 solution. The products were extracted with
4. Experimental
4.1. General
1H (400 MHz) and 13C NMR (100 MHz) spectra were
recorded on a Varian Mercury 400 MHz spectrometer in
CDCl3 solution; IR spectra were taken on a Carl Zeiss Spe-
cord M80 instrument. Ee’s of the alcohols, esters, and thi-
iranes 6e–g were determined on a Thermo-Separation
Products P-100 HPLC apparatus with Chiralcel OD-H col-
umn (in hexane:iso-propanol 9:1; 0.8 mL/min for esters
and alcohols and 95:5; 98:2; 99:1; 0.8 mL/min for thiiranes
6e–g) using the corresponding racemic compounds as refer-
ences. Ee’s of thiiranes 6a–d were determined on chromato-
graph fitted with the diode array detector (DAD) and

E. Łukowska, J. Plenkiewicz / Tetrahedron: Asymmetry 18 (2007) 493–499
497
CH2Cl2 (5 · 30 mL), and the organic layer washed with
water (3 · 50 mL), dried over anhydrous MgSO4, and
evaporated. The oily residue was purified by column chro-
matography on a silica gel with n-hexane–ethyl acetate
the solvent was evaporated. The mixture was separated by
chromatography on a silica-gel column with n-hexane–
ethyl acetate (5:1 v/v). NMR spectra of the enantiomeri-
cally enriched acetates (R)-(ꢀ)-4a–d were identical with
those of ( )-2a–d. The specific rotations measured in
CHCl3 solution for the prepared enantiomerically enriched
acetates are as follows:
1
(7:1 v/v) as the eluent. H, 13C NMR spectra, IR data,
and elemental analyses of the prepared esters are reported
below.
28
ðRÞ-ðꢀÞ-4a: ½aꢁD ¼ ꢀ8:4 ðc 5; CHCl3Þ ee ¼ 90%
4.2.1. ( )-1-Phenylsulfanyl-3-thiocyanatopropan-2-yl ace-
tate 2a. Colorless crystals, mp 50–51 ꢁC. 1H NMR
(CDCl3) d ppm: 2.03 (s; 3H (CH3)); 3.11–3.41 (m; 4H
(CH2SPh, CH2SCN)); 5.18 (m; 1H (CH)); 7.22–7.42 (m;
5H (Ph)). 13C NMR (CDCl3) d ppm: 20.57; 35.60; 35.83;
70.44; 111.65; 127.17; 129.26; 130.20; 134.00; 169.98. IR
(Nujol, cmꢀ1) 2150 (CN); 1740 (CO). Anal. Calcd for
C12H13NS2O2: C, 53.91; H, 4.90; N, 5.24; S, 23.98. Found:
C, 53.95; H, 5.00; N, 5.16; S, 23.89.
23
ðRÞ-ðꢀÞ-4b: ½aꢁD ¼ ꢀ0:65 ðc 9:21; CHCl3Þ ee ¼ 58%
23:5
ðRÞ-4c: ½aꢁD ¼ 0 ðc 4:30; CHCl3Þ ee ¼ 61%
23
ðRÞ-ðꢀÞ-4d: ½aꢁD ¼ ꢀ1:9 ðc 5:14; CHCl3Þ ee ¼ ND
1H and 13C NMR spectra, as well as IR data and elemental
analyses of the prepared optically active alcohols (+)-3a–d
are reported below.
4.3.1. (S)-(+)-1-Phenylsulfanyl-3-thiocyanatopropan-2-ol 3a.
Oil, yield 19%. 1H NMR (CDCl3) d ppm: 2.96 (s; 1H
4.2.2. ( )-1-(4-Chlorophenylsulfanyl)-3-thiocyanatopropan-
2-yl acetate 2b. Oil, H NMR (CDCl3) d ppm: 2.05 (s;
1
(OH)); 3.02 (dd; 1H (CHaHbSCN); JH CH ¼ 2:8 Hz;
3H (CH3)); 3.08–3.40 (m; 4H (CH2SPh, CH2SCN)); 5.16
(m; 1H (CH)); 7.26–7.35 (m; 4H (Ph)). 13C NMR (CDCl3)
d ppm: 20.57; 35.82; 35.89; 70.76; 111.53; 129.40; 131.54;
132.53; 133.31; 169.96. IR (film, cmꢀ1) 2150 (CN); 1740
(CO). Anal. Calcd for C12H12NClS2O2: C, 47.76; H, 4.01;
N, 4.64; S, 21.25. Found: C, 47.83; H, 4.10; N, 4.75; S, 21.21.
a
JH H ¼ 7:6 Hz); 3.06 (dd; 1H (CHaHbSCN); JH CH
¼
a
b
b
2:4 Hz); 3.17 (dd; 1H (CHcHdSPh) JH CH ¼ 4:8 Hz;
c
JH H ¼ 14 Hz); 3.23 (dd; 1H (CHcHdSPh); JH CH
¼
c
d
d
4 Hz); 3.99 (m; 1H (CH)); 7.30–7.42 (m; 5H (Ph)). 13C
NMR (CDCl3) d ppm: 39.08; 40.18; 68.38; 112.32;
127.38; 129.33; 130.64; 133.83. IR (film, cmꢀ1) 3450
25
(OH); 2150 (CN). ½aꢁD = +7.2 (c 9.76, CHCl3) ee 96%.
4.2.3. ( )-1-(4-Bromophenylsulfanyl)-3-thiocyanatopropan-
2-yl acetate 2c. Oil, 1H NMR (CDCl3) d ppm: 2.06
(s; 3H (CH3)); 3.08–3.41 (m; 4H (CH2SPh, CH2SCN));
5.17 (m; 1H (CH)); 7.26–7.45 (m; 4H (Ph)). 13C NMR
(CDCl3) d ppm: 20.62; 35.69; 35.83; 70.76; 111.55;
Anal. Calcd for C10H11NS2O: C, 53.30; H, 4.92; N, 6.22;
S, 28.46. Found: C, 53.34; H, 5.22; N, 6.40; S, 28.23.
4.3.2.
(S)-(+)-1-(4-Chlorophenylsulfanyl)-3-thiocyanato-
121.24; 131.66; 132.35; 133.21; 170.00. IR (film, cmꢀ1
)
propan-2-ol 3b. Colorless crystals; mp 52–53 ꢁC, yield
1
15%. H NMR (CDCl3) d ppm: 2.87 (s; 1H (OH)); 3.01
2140 (CN); 1735 (CO). Anal. Calcd for C12H12NBrS2O2:
C, 41.63; H, 3.49; N, 4.05; S, 18.52; Br, 23.08. Found: C,
41.65; H, 3.70; N, 4.11; S, 18.20; Br, 22.98.
(dd; 1H (CHaHbSCN); JH CH ¼ 6:4 Hz; JH H ¼ 7:6 Hz);
a
a
b
3.05 (dd; 1H (CH H SCN); JH
¼ 5:6 Hz); 3.15 (dd;
c
d
bCH
a
b
1H (CHcCHdSPh); JH CH ¼ 4:8 Hz; JH H ¼ 14 Hz); 3.23
c
(dd; 1H (CHcHdSPh); JH CH ¼ 4 Hz); 3.99 (m; 1H (CH));
4.2.4. ( )-3-Thiocyanato-1-(p-tolylsulfanyl)propan-2-yl ace-
tate 2d. Oil, 1H NMR (CDCl3) d ppm: 2.04 (s; 3H
(COCH3)); 2.32 (s; 3H (CH3C6H4)); 3.05–3.41 (m; 4H
(CH2SPh, CH2SCN)); 5.15 (m; 1H (CH)); 7.11–7.32 (m;
4H (Ph)). 13C NMR (CDCl3) d ppm: 20.57; 20.97; 35.82;
36.23; 70.94; 111.71; 123.89; 130.01; 130.20; 134.09;
169.96. IR (Nujol, cmꢀ1) 2140 (CN); 1730 (CO). Anal.
Calcd for C13H15NS2O2: C, 55.49; H, 5.37; N, 4.98; S,
22.79. Found: C, 55.60; H, 5.51; N, 4.93; S, 22.71.
d
7.26–7.35 (m; 4H (Ph)). 13C NMR (CDCl3) d ppm: 39.05;
40.39; 68.41; 112.21; 129.47; 131.96; 132.46; 133.53. IR
23
(film, cmꢀ1) 3445 (OH); 2150 (CN). ½aꢁD = +9.42 (CHCl3,
c 4.67; ee 98%). Anal. Calcd for C10H10NS2ClO: C, 46.24;
H, 3.88; N, 5.39; S, 24.69; Cl, 13.65. Found: C, 46.04; H,
3.89; N, 5.30; S, 24.70; Cl, 13.57.
4.3.3. (S)-(+)-1-(4-Bromophenylsulfanyl)-3-thiocyanatopro-
1
pan-2-ol 3c. Oil, yield 12%. H NMR (CDCl3) d ppm:
2.99 (s; 1H (OH)); 3.02 (dd; 1H (CHaHbSCN); JH CH
¼
4.3. General procedure for enzyme-catalyzed hydrolysis of
acetates ( )-2a–d
a
3:6 Hz; JH H ¼ 7:2 Hz); 3.05 (dd; 1H (CHaHbSCN);
a
b
JH CH ¼ 3:2 Hz); 3.15 (dd; 1H (CHcCHdSPh); JH CH
¼
c
b
5:2 Hz; JH H ¼ 13:6 Hz); 3.24 (dd; 1H (CHcHdSPh);
In a typical experiment, acetate ( )-2a–d (1 g) was dis-
solved in 40 mL of TBME (tert-butyl methyl ether). The
solution was mixed with 0.1 M phosphate buffer
KH2PO4–K2HPO4 (200 mL, pH 7), and 1 g of enzyme
(Novozym SP 435, Amano AK or Amano PS lipase) was
added. The mixture was stirred at 30 ꢁC, and the conver-
sion was monitored by TLC with n-hexane–ethyl acetate
(3:1 v/v) as the eluent. After an appropriate time, the reac-
tion was arrested by filtering off the enzyme and the prod-
ucts were extracted with diethyl ether (5 · 30 mL). The
organic layers were combined, washed with water
(3 · 50 mL), and dried over anhydrous MgSO4, whereupon
c
d
JH CH ¼ 4 Hz); 4.00 (m; 1H (CH)); 7.26–7.45 (m; 4H
d
(Ph)). 13C NMR (CDCl3) d ppm: 39.05; 40.09; 68.42;
112.26; 121.33; 131.98; 132.35; 133.24. IR (film, cmꢀ1
)
23:5
3445 (OH); 2150 (CN). ½aꢁD = +6.4 (c 1.71, CHCl3) ee
85%. Anal. Calcd for C10H10NS2BrO: C, 39.48; H, 3.31;
N, 4.60; S, 21.08; Br, 26.26. Found: C, 39.60; H, 3.27; N,
4.58; S, 21.13; Br, 26.17.
4.3.4. (S)-(+)-1-Thiocyanato-3-(p-tolylsulfanyl)propan-2-ol
1
3d. Oil, yield 13%. H NMR (CDCl3) d ppm: 2.33 (s;
3H (CH3)); 2.86 (d; 1H (OH); JOHCH = 3.6 Hz); 2.98 (dd;

498
E. Łukowska, J. Plenkiewicz / Tetrahedron: Asymmetry 18 (2007) 493–499
24
1H (CHaHbSCN); JH CH ¼ 7:6 Hz; JH H ¼ 13:2 Hz); 3.03
132.42; 134.26. ½aꢁD = +33.02 (c 4.36, CHCl3) ee = 59%.
Anal. Calcd for C9H9S2Br: C, 41.39; H, 43.47; S, 24.55;
Br, 30.59. Found: C, 41.63; H, 3.26; S, 24.67; Br, 30.49.
a
a
b
(dd; 1H (CHaHbSCN); JH CH ¼ 7:2 Hz); 3.12 (dd; 1H
b
(CHcCHdSPh); JH CH ¼ 4:4 Hz; JH H ¼ 14 Hz); 3.22 (dd;
c
c
d
1H (CHcHdSPh); JH CH ¼ 4 Hz); 3.96 (m; 1H (CH));
d
7.13–7.33 (m; 4H (Ph)). 13C NMR (CDCl3) d ppm: 21.05;
4.4.4. (S)-(+)-2-(p-Tolylsulfanylmethyl)thiirane 6d. Oil,
yield 71%. 1H NMR (CDCl3) d ppm: 2.06 (dd; 1H
(CHCHaHbS); JH CH ¼ 1:2 Hz; JH H ¼ 5:2 Hz); 2.34 (s;
39.10; 41.04; 68.29; 112.30; 129.87; 130.16; 131.56;
137.91. IR (film, cmꢀ1
½aꢁD = +5.7 (c 0.87, CHCl3) ee 80%. Anal. Calcd for
C11H13NS2O: C, 55.20; H, 5.47; N, 5.85; S, 26.79. Found:
C, 55.48; H, 5.53; N, 5.68; S, 26.78.
)
3400 (OH); 2170 (CN).
a
a
b
27
3H (CH3)); 2.46 (dd; 1H (CHCHaHbS); JH CH ¼ 2:4 Hz);
b
2.73 (dd; 1H (PhSCHcHdCH); JH CH ¼ 8:8 Hz; JH H
¼
c
c
d
13:6 Hz); 3.09 (m; 1H (CH)); 3.40 (dd; 1H (PhSCHc-
HdCH); JH CH ¼ 4:4 Hz); 7.11–7.37 (m; 4H (Ph)). 13C
d
4.4. General procedure for the conversion of acetates 4a–g to
thiiranes 6a–g
NMR (CDCl3) d ppm: 21.06; 26.06; 33.73; 41.81; 129.84;
24
131.17; 131.88; 137.38. ½aꢁD = +24.2 (c 4.54, CHCl3)
ee = 32%. Anal. Calcd for C10H12S2: C, 61.18; H, 6,16; S,
32.66. Found: C, 61.34; H, 6.20.
In a typical experiment, optically active acetate 4a–d
(1 mmol) was dissolved in 17 mL of THF and a solution
of LiOHÆH2O (4 mmol) in 5 mL H2O was added. For com-
pounds 4e–f, 2 mmol of the acetate was dissolved in 28 mL
of THF and a solution of LiOHÆH2O (4 mmol) in 5 mL
H2O was added. The mixture was stirred at room temper-
ature and the progress of the reaction was monitored by
TLC using n-hexane–ethyl acetate (3:1 v/v) as the eluent.
After completion of the reaction (about 2 h), the organic
layer was separated and the solvent was evaporated. The
crude mixture was purified by chromatography on a short
silica gel column with hexane–ethyl acetate (15:1 for thiir-
4.4.5. (S)-(ꢀ)-2-(Phenoxymethyl)thiirane 6e. Oil, yield
87%. 1H NMR (CDCl3) d ppm: 2.33–2.63 (m; 2H
(CHCH2S)); 3.28 (m; 1H (CH)); 3.91 (dd; 1H
(OCHaHbCH); JH CH ¼ 7:2 Hz; JH H ¼ 10 Hz); 4.22 (dd;
a
a
b
1H (OCHaHbCH); JH CH ¼ 5:2 Hz); 6.91–7.32 (m; 5H
b
(Ph)). 13C NMR (CDCl3)
d
ppm: 24.00; 31.37;
25
72.53; 114.62; 121.21; 129.53; 158.20. ½aꢁD = ꢀ13.6 (c 2.8,
1
CHCl3) ee = 97%. H NMR and 13C NMR spectra are
identical with those given in the literature.10
1
anes 6a–d and 7:1 for thiiranes 6e–g) as the eluent. H,
4.4.6. (S)-(ꢀ)-2-(4-Chlorophenoxymethyl)thiirane 6f. Oil,
13C NMR spectra, and elemental analyses of the prepared
yield 83%. H NMR (CDCl3) d ppm: 2.31–2.61 (m; 2H
1
thiiranes 6a–g are reported below.
(CHCH2S)); 3.25 (m; 1H (OCH2CHCH2S)); 3.89 (dd; 1H
(OCHaHbCH); JH CH ¼ 6:8 Hz; JH H ¼ 10 Hz); 4.14 (dd;
a
a
b
4.4.1. (S)-(+)-2-(Phenylsulfanylmethyl)thiirane 6a. Oil,
yield 71%. 1H NMR (CDCl3) d ppm: 2.10 (dd; 1H
(CHCHaHbS); JH CH ¼ 1:6 Hz; JH H ¼ 5:2 Hz); 2.48 (dd;
1H (OCHaHbCH); JH CH ¼ 5:6 Hz); 6.82–7.24 (m; 4H
b
(Ph)). 13C NMR (CDCl3) d ppm: 24.01; 31.40; 72.62;
25
114.92; 126.59; 129.50; 156.45. ½aꢁD = ꢀ12.5 (c 4.64,
a
a
b
1
1H (CHCHaHbS); JH CH ¼ 2:4 Hz); 2.79 (dd; 1H
CHCl3) ee = 90%. H NMR and 13C NMR spectra are
b
(PhSCHcHdCH); JH CH ¼ 8:8 Hz; JH H ¼ 14 Hz); 3.11
identical with those given in the literature.10
c
c
d
(m; 1H (CH)); 3.45 (dd; 1H (PhSCHcHdCH); JH CH
¼
d
5:6 Hz); 7.25–7.45 (m; 5H (Ph)). 13C NMR (CDCl3) d
4.4.7. (S)-(ꢀ)-2-(p-Tolyloxymethyl)thiirane 6g. Oil, yield
1
ppm: 26.04; 33.57; 41.15; 127.07; 129.09; 131.05; 135.02.
76%. H NMR (CDCl3) d ppm: 2.29 (s; 3H (CH3)); 2.32–
24
½aꢁD = +71.4 (c 6.78, CHCl3) ee = 86%. Anal. Calcd for
2.61 (m; 2H (CHCH2S)); 3.26 (m; 1H (CHaHbCHCH2));
C9H10S2: C, 59.30; H, 5.53; S, 35.18. Found: C, 59.55; H,
5.72; S, 34.98.
3.86 (dd; 1H (OCHaHbCH); JH CH ¼ 7:2 Hz; JH H
6.80–7.10 (m; 4H (Ph)). 13C NMR (CDCl3) d ppm:
¼
a
a
b
10 Hz); 4.19 (dd; 1H (OCHaHbCH); JH CH ¼ 5:6 Hz);
b
4.4.2. (S)-(+)-2-(4-Chlorophenylsulfanylmethyl)thiirane 6b.
Oil, yield 67%. H NMR (CDCl3) d ppm: 2.10 (dd; 1H
20.46; 24.02; 31.45; 72.76; 114.57; 129.95; 130.51; 156.27.
25
1
½aꢁD = ꢀ10.7 (c 4.48, CHCl3) ee = 86%. 1H NMR and
(CHCHaHbS); JH CH ¼ 1:6 Hz; JH H ¼ 5:2 Hz); 2.48 (dd;
13C NMR spectra are identical with those given in the
literature.10
a
a
b
1H (CHCHaHbS); JH CH ¼ 2:4 Hz); 2.80 (dd; 1H
b
(PhSCHcHdCH); JH CH ¼ 8:4 Hz; JH H ¼ 13:6 Hz); 3.07
c
c
d
(m; 1H (CH)); 3.39 (dd; 1H (PhSCHcHdCH);
4.5. Assignment of absolute configuration of 1-phenylsulfan-
yl-3-thiocyanatopropan-2-yl acetate 4a
JH CH ¼ 4:8 Hz); 7.26–7.38 (m; 4H (Ph)). 13C NMR
d
(CDCl3) d ppm: 25.91; 33.33; 41.30; 129.21; 132.36;
24
133.17; 133.54. ½aꢁD = +35.2 (c 5.47, CHCl3) ee = 53%.
Crystal data concerning the structure of (ꢀ)-1-phenylsulfan-
yl-3-thiocyanatopropan-2-yl acetate and the pertinent
refinement details are given in Table 4. All measurements
were performed on a Kuma KM4CCD j-axis diffracto-
meter with graphite-monochromated MoKa radiation. The
crystal was positioned at 62.25 mm from the KM4CCD
camera. 512 frames were measured at 1.2ꢁ intervals with
a counting time of 12 s. The data were corrected for Lor-
entz and polarization effects. No absorption correction
was applied. Data reduction and analysis were carried
out with the Kuma Diffraction programs: CrysAlis CCD
and CrysAlis RED.16 The structure was solved by direct
Anal. Calcd for C9H9S2Cl: C, 49.87; H, 4.19; S, 29.59;
Cl, 16.36. Found: C, 49.97; H, 4.23; S, 29.40.
4.4.3. (S)-(+)-2-(4-Bromophenylsulfanylmethyl)thiirane 6c.
1
Oil, yield 84%. H NMR (CDCl3) d ppm: 2.11 (dd; 1H
(CHCHaHbS); JH CH ¼ 0:8 Hz; JH H ¼ 5:6 Hz); 2.48 (dd;
a
a
b
1H (CHCHaHbS); JH CH ¼ 1:2 Hz); 2.81 (dd; 1H
b
(PhSCHcHdCH); JH CH ¼ 8:4 Hz; JH H ¼ 13:6 Hz); 3.07
c
c
d
(m; 1H (CH)); 3.39 (dd; 1H (PhSCHcHdCH);
JH CH ¼ 4:8 Hz); 7.28–7.45 (m; 4H (Ph)). 13C NMR
d
(CDCl3) d ppm: 25.92; 33.29; 41.08; 121.05; 132.12;

E. Łukowska, J. Plenkiewicz / Tetrahedron: Asymmetry 18 (2007) 493–499
499
Table 4. Crystal data and structure refinement details
tre as Supplementary Publication No. CCDC 626648. Cop-
ies of the data can be obtained on application to CCDC, 12
Union Road, Cambridge CB2 1EZ, UK (e-mail: deposit@
ccdc.cam.ac.uk).
Empirical formula
Formula weight
Temperature
C12H13NO2S2
267.35
293(2) K
˚
Wavelength
0.71073 A
Crystal system
Space group
Unit cell dimensions
Orthorombic
P2(1)2(1)2(1)
a = 7.9426(9) A, a = 90ꢁ
b = 12.1238(16) A, b = 90ꢁ
Acknowledgements
˚
˚
˚
This work was financially supported by the Warsaw Uni-
versity of Technology. The X-ray measurements were done
in the Crystallographic Unit of the Physical Chemistry
Laboratory at the Chemistry Department of the University
of Warsaw. Warmest thanks are directed to Professor
Janusz Jurczak and Dr. Piotr Kwiatkowski (Institute of
Organic Chemistry PAN) for determination of optical
purity of the thiiranes, as well as to Mrs. Renata Pawlak-
Morka for her interest in our studies and fruitful
cooperation.
c = 12.8644(15) A, c = 90ꢁ
3
˚
Volume
Z
1238.8(3) A
2
Calculated density
Absorption coefficient
F(000)
Crystal size
Theta range for data collection
Limiting indices
1.434 Mg/m3
0.418 mmꢀ1
560
0.70 mm · 0.53 mm · 0.44 mm
3.01–28.58ꢁ
ꢀ10 6 h 6 10, ꢀ16 6 k 6 12,
ꢀ16 6 l 6 16
Reflections collected/unique
Completeness to theta = 28.58
Absorption correction
Refinement method
Data/restraints/parameters
Goodness-of-fit on F2
11,354/2956 [R(int) = 0.0333]
95.3%
None
Full-matrix least-squares on F2
2956/12/207
References
1. Sander, M. Chem. Rev. 1966, 66, 297.
1.108
2. Vedejs, E.; Kraffi, G. A. Tetrahedron 1982, 38, 2857.
3. Bouda, H.; Borredon, M. E.; Delman, M.; Gaset, A. Synth.
Commun. 1989, 19, 491.
4. Ketcham, R.; Shah, V. P. J. Org. Chem. 1963, 28, 229.
5. Korn, A. C.; Morder, L. J. Chem. Res. (S) 1995, 102.
6. Brimeyer, M. O.; Mehrota, A.; Quici, S.; Nigman, A.; Regen,
S. L. J. Org. Chem. 1980, 45, 4254.
Final R indices [I > 2r(I)]
R indices (all data)
Absolute structure parameter
Extinction coefficient
R1 = 0.0219, wR2 = 0.0557
R1 = 0.0227, wR2 = 0.0565
ꢀ0.05(5)
0.0121(14)
ꢀ3
˚
Largest diff. peak and hole
0.195 and ꢀ0.219 e A
7. Takido, T.; Kobayashi, Y.; Itabashi, K. Synthesis 1986, 779.
8. Pederson, R. L.; Liu, K. K.-C.; Rutan, J. F.; Chen, L.; Wong,
C.-H. J. Org. Chem. 1990, 55, 4897.
9. Iranpoor, N.; Kazemi, F. Tetrahedron 1997, 53, 11377.
10. Łukowska, E.; Plenkiewicz, J. Tetrahedron: Asymmetry 2005,
16, 2149.
11. Sharghi, H.; Nasseri, A.; Niknam, K. J. Org. Chem. 2001, 66,
7287.
12. Yadav, J. S.; Reddy, B. V. S.; Reddy, S. Ch. Tetrahedron
Lett. 2004, 45, 1291.
13. Spassky, N.; Dumas, P.; Sepulchre, M.; Sigwalt, P. J. Polym.
Sci., Polym. Symp. 1975, 52, 327.
14. Price, C. C.; Kirk, P. F. J. Am. Chem. Soc. 1953, 75, 2396.
15. Wielechowska, M.; Plenkiewicz, J. Tetrahedron: Asymmetry
2005, 16, 1199.
16. Oxford Diffraction (20001). CrysAlis CCD and CrysAlis Red.
Oxford diffraction Poland, Wrocław, Poland.
17. Sheldrick, G. M. Acta Crystallogr. A 1990, 46, 467.
18. Sheldrick, G. M. SHELXL 93. Program for the Refinement of
Crystal Structures, Univ. of Go¨ttingen, Germany.
19. International Tables for Crystallography; Wilson, A. J. C.,
Ed.; Kluwer: Dordrecht, 1992; Vol. C.
methods17 and refined using SHELXL.18 The refinement was
based on F2 for all reflections except those with very nega-
tive F2. The weighted R factors wR and all goodness-of-fit
S values are based on F2. Conventional R factors are based
on F with F set to zero for negative F2. The F o2 > 2rðF o2Þ
criterion was used only for calculating R factors and is
not relevant to the choice of reflections for the refinement.
The R factors based on F2 are about twice as large as those
based on F. All hydrogen atoms were located from a differ-
ential map and refined isotropically and restraints on the
C–H bond lengths were set for all hydrogen atoms. Scatter-
ing factors were taken from Tables 6.1.1.4 and 4.2.4.2 in
Ref. 19. Final results give R1 = 0.0219 and wR2 = 0.557
for 11,354 reflections with I > 2r(I). The absolute structure
was established based on anomalous dispersion using the
Flack parameter x.20 The x refined during the final struc-
ture factor evaluation of the model with the molecule of
the R absolute configuration amounted to a value of
ꢀ0.05(5). Crystallographic data for the structure have been
deposited with the Cambridge Crystallographic Data Cen-
20. Klack, H. D. Acta Crystallogr. A 1983, 39, 876.