Humicola lanuginosa lipase-catalyzed enantioselective resolution of β-hydroxy sulfides: Versatile synthons for enantiopure β-hydroxy sulfoxides

Article abstract of DOI:10.1016/S0957-4166(01)00434-7

Humicola lanuginosa lipase-catalyzed acylation of β-hydroxy sulfides provides both the (R)- and (S)-enantiomers in high enantiomeric purity. In two cases the resolved hydroxy sulfides were oxidized to give β-hydroxy sulfoxides in >99% e.e. The effect of substituents on enantioselectivity is discussed.

Full text of DOI:10.1016/S0957-4166(01)00434-7

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 12 (2001) 2457–2462
Humicola lanuginosa lipase-catalyzed enantioselective resolution
of b-hydroxy sulfides: versatile synthons for enantiopure
b-hydroxy sulfoxides
Satwinder Singh, Subodh Kumar and Swapandeep Singh Chimni*
Department of Chemistry, Guru Nanak Dev University, Amritsar 143 005, India
Received 4 September 2001; accepted 1 October 2001
Abstract—Humicola lanuginosa lipase-catalyzed acylation of b-hydroxy sulfides provides both the (R)- and (S)-enantiomers in
high enantiomeric purity. In two cases the resolved hydroxy sulfides were oxidized to give b-hydroxy sulfoxides in >99% e.e. The
effect of substituents on enantioselectivity is discussed. © 2001 Elsevier Science Ltd. All rights reserved.
1. Introduction
lyzed resolution of hydroxy sulfides or their esters
provides an alternative approach10 and have found that
Humicola lanuginosa lipase (HLL), a cheap detergent
lipase, rarely used for resolution of organic molecules
resolves b-hydroxy sulfides to give both the (R)- and
(S)-enantiomers of 1a–1g in high enantiomeric purity.
Enantiopure functionalized secondary alcohols are
important synthetic intermediates and useful chiral aux-
iliaries both for analytical and synthetic applications.1
The presence of a sulfur atom placed at an appropriate
position from the hydroxy group provides unique syn-
thetic versatility.2 Thus, enantiopure hydroxy sulfides
serve as intermediates in the synthesis of naturally
occurring spiroketal pheromones,3 chiral oxiranes,4 thi-
iranes,5 tetrahydrofurans,6 and 4-acetoxyazetidinone.7
The available synthetic approaches for obtaining enan-
tiopure hydroxy sulfides involve stereoselective reduc-
tion of phenylthio ketones using baker’s yeast3,8 or
asymmetric chiral ruthenium complexes9 and are
plagued with either the availability of only one enan-
tiomer or moderate enantioselectivity. The lipase-cata-
Furthermore, oxidation of the enzymatically-resolved
enantiomers 1a–1b with m-CPBA, followed by frac-
tional crystallization provides a convenient route to the
enantiopure b-hydroxy sulfoxides (Scheme 1), which
find widespread application as chiral intermediates11
and chiral catalysts.12 Generally, b-hydroxy sulfoxides
are synthesized by the stereoselective reduction13,14 of
chiral b-ketosulfoxides, which are obtained through an
approach requiring several steps, starting with
Andersen’s resolution.15 This method, in addition to
Scheme 1. (i) Lipase/VA; (ii) base; (iii) m-CPBA; (iv) fractional crystallization.
* Corresponding author. Fax: +91-183-258820; e-mail: sschimni@angelfire.com
0957-4166/01/$ - see front matter © 2001 Elsevier Science Ltd. All rights reserved.
PII: S0957-4166(01)00434-7

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S. Singh et al. / Tetrahedron: Asymmetry 12 (2001) 2457–2462
Table 1. Enantioselective acylation of alcohols (R,S)-1 and (R,S)-3 with HLLa
Entry
Substrate
Timeb (h)
Conv. (%)c
Yieldd of (S)-alc.
E.e.e (S)-alc.
Yieldd,f of (R)-alc. E.e.e (R)-alc.
Esg
1
2
3
4
5
6
7
8
1a
1b
1c
1d
1e
1f
1g
3
12.5
11
11
12
7
12
28
8
46
46
37
48
33
43
42
44
49
50
51
51
56
52
53
52
81
76
41
78
40
66
70
62
45
44
36
46
30
43
39
42
99
92
95
88
88
90
88
84
500
62
61
37
23
38
124
23
a The substrate:enzyme ratio is 1:2 w/w.
b Reaction performed with HLL preincubated at 39 1°C for 72 h.
c Percentage conversion was calculated with the help of 1H NMR.
d Yields refer to pure isolated products after column chromatography.
e E.e. calculated by 1H NMR analysis of the corresponding acetylmandelic acid ester of the alcohol.
f Overall yield of alcohol derived from hydrolysis of the initially formed chiral acetate.
g Enantiomeric ratio (E) values were determined from the e.e. of residual substrate and extent of conversion. (Chen, Ch-Sh; Fujimoto, Y.;
Girdaukas, G.; Sih, J. C. J. Am. Chem. Soc. 1982, 104, 7294).
being inconvenient provides only the (R)-configured
sulfinyl compound. Herein, we report the first-time
synthesis of enantiomerically pure (R,Ss)- and (S,Rs)-b-
hydroxy sulfoxides without using an optically active
starting material through lipase-catalyzed kinetic
resolution.
The replacement of the sulfide with an ether linkage
lowers the enantioselectivity. Thus, both of these obser-
vations show that the phenylthio group present b- to
the hydroxy group increases the enantiopreference of
HLL in favor of the (R)-enantiomer. Therefore, Humi-
cola lanuginosa lipase (HLL) catalyzes the acylation of
1-alkyl/aryl-thiopropan-2-ols in vinyl acetate to provide
the (S)-enantiomers (40–81% e.e.) and the (R)-enan-
tiomers (88–99% e.e.) with E values ranging from 23 to
500.
2. Results and discussion
Optimization of the conditions for the resolution of
b-hydroxy sulfide 1a with different lipases showed HLL
to be a better catalyst.16 A typical procedure involves
stirring a solution of 1a (840 mg, 5 mmol) and HLL
(1.68 g, 2 equiv. w/w) with vinyl acetate (4.5 mL, 10
equiv.) used both as reagent and solvent, at 25 1°C.
The reaction was monitored by recording 1H NMR
spectra of aliquots of the reaction mixture taken at
regular intervals. The reaction was stopped at 46%
conversion (12.5 h) by filtration of the enzyme and
(R)-2a and (S)-1a were separated by column chro-
matography. (R)-2a was hydrolyzed with 1N methano-
lic NaOH to give (R)-1a. The e.e. of (R)-1a was found
to be 99% and (S)-1a had e.e. of 81% (Table 1).17 This
reaction has enantiomeric ratio (E value) of 500.
On stirring (R)-1b with m-CPBA in dichloromethane
(Scheme 3) at −20°C afforded a mixture of the
Scheme 2.
All other b-hydroxy sulfides 1b–1g were then resolved
under similar conditions (Scheme 2). It was observed
that aryl sulfide derivatives (entries 1 and 2) show better
enantioselectivity than alkyl derivatives (entries 5 and
6). Also, in the case of aryl group-containing substrates
(entries 1, 3, and 4), the placement of the phenyl ring
away from the sulfur atom decreases the E progres-
sively from 500 (entry 1) to 61 (entry 3) to 37 (entry 4).
Clearly, increasing spacer length between the phenyl
ring
and
the
sulfur
atom
decreases
the
enantioselectivity.
To investigate the role of the sulfur atom in enantiose-
lective recognition of the (R)-enantiomer by HLL, reso-
lution of ( )-1-phenoxypropan-2-ol 3 was carried out to
obtain (R)-3 (84% e.e.) and (S)-3 in 62% e.e. (E=23).
Scheme 3.

S. Singh et al. / Tetrahedron: Asymmetry 12 (2001) 2457–2462
2459
Table 2. Synthesis of b-hydroxy sulfoxides by m-CPBA oxidation
oxidation
b-Hydroxy sulfide
b-Hydroxy sulfoxide
[h]2D7
Yield (%)
Mp (°C)
% E.e.
Config.
(R)-1aa
(S)-1aa
(R)-1bb
(S)-1bb
40
40
38
39
132–133
133–135
122–123
123–124
−367 (c 0.23, CH2Cl2)
+369 (c 0.75, CH2Cl2)
−343 (c 0.60, CH2Cl2)
+343 (c 0.50, CH2Cl2)
\99
\99
\99
\99
(R,Ss)
(S,Rs)
(R,Ss)
(S,Rs)
a Crystallization was carried at 24 1°C (CH2Cl2/hexane).
b Crystallization was carried at 0–5°C (CH2Cl2/hexane).
diastereomeric hydroxy sulfoxides i.e. (R,Ss)-4b and
(R,Rs)-4b. Fractional crystallization of the crude mix-
ture at 0–5°C provided a white crystalline solid (38%,
>99% e.e., mp 122–123°C) having [h]2D7=−343 (c 0.60,
CH2Cl2). The mother liquor afforded a colorless liquid
(62% d.e.), which on comparison of its 1H NMR
reported in literature18 was assigned configuration
(R,Rs)-4b. So, the crystalline diastereomer was assigned
the configuration (R,Ss)-4b on the basis of its spectro-
scopic data. A clear distinction between the two
with Me4Si (in CDCl3) as internal standard. Chemical
shifts are expressed as l downfield from the TMS and
J values are in Hz. When necessary, assignments were
aided by DEPT-135 and decoupling experiments. IR
spectra were obtained with a Nicolet Avatar 320 FTIR.
Mass spectra were recorded on GCMS-QP-2000 mass
spectrometer by EI method. Optical rotations were
measured with a Jasco DIP-360 digital polarimeter.
4.2. Synthesis of the racemic substrates
1
diastereomers could be made from the H NMR spec-
The starting compounds 1a–1g were prepared by a
slight modification of the method given by Crumbie et
al.8a for the preparation of 1a and 1c. To a solution of
sodium ethoxide prepared by dissolving metallic
sodium (2.53 g, 0.11 mol) in absolute alcohol (50 mL),
the respective thiol (0.10 mol) was then added drop-
wise. The solution was stirred for 10 min at 10°C and
finally a solution of chloroacetone (11.1 g, 9.56 mL,
0.12 mol) in absolute alcohol (10 mL) was added over
15 min. Stirring was continued for 2 h then the mixture
was filtered to remove precipitated sodium chloride.
The filtrate was concentrated under reduced pressure
and the resulting viscous oil was diluted with water (10
mL) and extracted with ethyl acetate (3×50 mL). The
organic layer was dried over anhydrous Na2SO4 and
concentrated under reduced pressure to give crude
alkyl/arylthiopropan-2-one, which was reduced with
NaBH4 in ethanol. To a stirred solution of the parent
ketone (0.1 mol) in ethanol (30 mL), 1.85 g (0.05 mol)
of NaBH4 was added in small portions. The mixture
was stirred until the reduction was complete (TLC).
The reaction mixture was neutralized with dil. HCl, and
extracted with ethyl acetate. The organic layer was
dried and evaporated to yield the crude product, which
was purified by a column chromatography with 60–120
mesh silica gel using hexane–ethyl acetate (90:10) as
eluent. The spectroscopic data of 1a and 1c agrees well
with that reported earlier.8
tra, the methyl and methine protons in (R,Ss)-4b res-
onates at l 1.23 and l 4.31–4.38 ppm, and in case of
(R,Rs)-4b at l 1.30 and l 4.38–4.48 ppm. Similar
oxidation of enantiomer (S)-1b followed by crystalliza-
tion afforded (S,Rs)-4b (39%, >99% e.e., mp: 123–
124°C) having [h]D27=+343 (c 0.50, CH2Cl2). Further,
sulfoxidation of (R)-1a and (S)-1a with m-CPBA pro-
vided diastereomeric pairs (R,Ss)-4a, (R,Rs)-4a and
(S,Rs)-4a, (S,Ss)-4a, respectively. The fractional crystal-
lization of respective diastereomeric pairs provided
(R,Ss)-4a and (S,Rs)-4a as pure crystalline solids (Table
2). To the best of our knowledge, (R,Ss)-4a and (R,Ss)-
4b are the first examples of b-hydroxy sulfoxides having
(S)-configuration at sulfur.
3. Conclusion
Our present studies have demonstrated that Humicola
lanuginosa lipase (HLL) catalyzed kinetic resolution of
racemic b-hydroxy sulfides, coupled with subsequent
oxidation with m-CPBA provides an effective method
for synthesis of enantiopure b-hydroxy sulfoxides which
are important chiral intermediates. This method repre-
sents a simple alternative to earlier reports,13,14 as it
provides high e.e. under mild reaction conditions with-
out needing any expensive reagents or special expertise.
Furthermore, no alternative route to our approach
appears to be known for enantiopure sulfoxides (R,Ss)-
4a and (R,Ss)-4b.
(RS)-1-Phenylthiopropan-2-ol 1a: yellow liquid; yield=
79%; IR (film): 3520, 3070, 2970, 2925, 1561, 1030, 690
cm−1; MS (m/z): 168 (M+), 135, 124 (100), 123, 109, 91,
1
77; H NMR (CDCl3): l 1.27 (d, 3H, J=6.2 Hz, CH3),
4. Experimental
4.1. General
1.98 (bs, 1H, OH), 2.85 (dd, 1H, J=13.7 and 8.5 Hz,
CH2), 3.11 (dd, 1H, J=13.7 and 3.7 Hz, CH2), 3.78–
3.90 (m, 1H, CH), 7.17–7.41 (m, 5H, ArH); 13C NMR/
DEPT (CDCl3): l 22.30 (+ve, CH3), 43.20 (-ve, CH2),
66.42 (+ve, CH), 127.17 (+ve, C-Ar), 128.22 (+ve, C-
Ar), 131.52 (+ve, C-Ar), 131.98 (C-Ar).
NMR spectra were obtained at 200 (Bruker AC 200E)
1
or 300 MHz for H and at 50 or 75 MHz for 13C NMR

2460
S. Singh et al. / Tetrahedron: Asymmetry 12 (2001) 2457–2462
1
(RS)-1-(4-Methylphenyl)thiopropan-2-ol 1b: colorless
liquid; yield=82%; IR (film): 3420, 3080, 2972, 1560,
820 cm−1; MS (m/z): 182 (M+), 137, 136, 123, 91 (100),
174, 173, 159, 127, 91, 76; H NMR (CDCl3): l 1.30 (d,
3H, J=6.2 Hz, CH3), 2.80 (bs, 1H, OH), 2.97 (dd, 1H,
J=13.6 and 8.1 Hz, CH2), 3.19 (dd, 1H, J=13.6 and
4.0 Hz, CH2), 3.84–3.97 (m, 1H, CH), 7.17–7.42 (m,
3H, ArH), 7.65–7.92 (m, 4H, ArH); 13C NMR (CDCl3):
l 21.89 (CH3), 43.11 (CH2), 65.62 (CH), 125.78 (C-Ar),
126.51 (C-Ar), 126.98 (C-Ar), 127.58 (C-Ar), 127.87
(C-Ar), 128.50 (C-Ar), 131.80 (C-Ar), 132.67 (C-Ar),
133.55 (C-Ar). Found C, 72.12; H, 5.94; C13H14OS
requires C, 71.56; H, 6.42%.
1
77; H NMR (CDCl3): l 1.24 (d, 3H, J=6.3 Hz, CH3),
2.0 (bs, 1H, OH), 2.33 (s, 3H, CH3), 2.75 (dd, 1H,
J=13.6 and 8.7 Hz, CH2), 3.03 (dd, 1H, J=13.6 and
3.6 Hz, CH2), 3.70–3.85 (m, 1H, CH), 7.08 (d, 2H,
J=8.0 Hz, ArH), 7.28 (d, 2H, J=8.0 Hz, ArH); 13C
NMR/DEPT (CDCl3): l 20.52 (+ve, CH3), 21.56 (+ve,
CH3), 43.12 (-ve, CH2), 65.42 (+ve, CH), 129.26 (+ve,
C-Ar), 129.91 (+ve, C-Ar), 131.70 (C-Ar), 135.67 (C-1).
4.3. General procedure for resolution
(RS)-1-Benzylthiopropan-2-ol 1c: yellow liquid; yield=
80%; IR (film): 3400, 3082, 2992, 1548, 752 cm−1; MS
A solution of the (RS)-1 (5 mmol) and vinyl acetate
(4.5 mL, 50 mmol) was stirred with HLL (1.68 g, 2
equiv. w/w) at 24 1°C. The reaction was monitored by
1
(m/z): 182 (M+), 138, 137, 123 (100), 91, 77; H NMR
(CDCl3): l 1.12 (d, 3H, J=6.2 Hz, CH3), 2.09 (bs, 1H,
OH), 2.26 (dd, 1H, J=13.7 and 8.8 Hz, CH2), 2.49 (dd,
1H, J=13.7 and 3.6 Hz, CH2), 3.63 (s, 2H, CH2),
3.66–3.74 (m, 1H, CH), 7.14–7.22 (m, 5H, ArH); 13C
NMR/DEPT (CDCl3): l 22.08 (+ve, CH3), 36.19 (-ve,
CH2), 40.09 (-ve, CH2), 65.72 (+ve, CH), 126.84 (+ve,
C-Ar), 128.28 (+ve, C-Ar), 128.72 (+ve, C-Ar), 138.00
(C-Ar).
1
taking H NMR of aliquots taken at regular intervals.
The reaction was stopped by filtering the mixture
through a sintered glass funnel. Concentration of the
filtrate followed by column chromatography provided
(R)-2 and (S)-1. (R)-2 (2.3 mmol) was hydrolyzed with
1N NaOH (2.3 mL) in 10 mL solution of methanol and
water (4:1) to give (R)-1.
(RS)-1-Phenylethylthiopropan-2-ol 1d: pale yellow oil;
yield=77%; IR (film): 3510, 3020, 2980, 1542, 762
cm−1; MS (m/z): 196 (M+), 181, 151, 137, 119, 105, 91
(R)-1-Phenylthiopropan-2-yl acetate 2a: yellow oil:
[h]2D7=−0.9 (c 1.12, CH2Cl2); IR (film): 3055, 2980,
2930, 1735, 1110, 760 cm−1; MS (m/z): 210 (M+), 195,
1
1
(100), 77, 58; H NMR (CDCl3): l 1.24 (d, 3H, J=6.2
168, 135, 124, 109 (100), 77, 58; H NMR (CDCl3): l
Hz, CH3), 2.42 (dd, 2H, J=13.6 and 8.8 Hz, 1H each
1.34 (d, 3H, J=6.3 Hz, CH3), 1.96 (s, 3H, COCH3),
2.93 (dd, 1H, J=13.7 and 6.4 Hz, CH2), 3.15 (dd, 1H,
J=13.7 and 5.9 Hz, CH2), 5.00 (sextet, 1H, J=6.3 Hz,
CH), 7.12–7.39 (m, 5H, ArH); 13C NMR/DEPT
(CDCl3): l 18.50 (+ve, CH3), 20.96 (+ve CH3), 45.22
(−ve, CH2), 65.52 (+ve, CH), 127.56 (+ve, C-Ar), 128.12
(+ve, C-Ar), 131.68 (+ve, C-Ar), 132.26 (C-Ar), 170.24
(CꢀO).
of CH2
6 -CH(OH)-and OH), 2.70 (dd, 1H, J=13.6 and
3.5 Hz, CH2
6
-CH(OH)-), 2.74–2.92 (m, 4H, 2×CH2),
3.76–3.82 (m, 1H, CH), 7.16–7.28 (m, 5H, ArH); 13C
NMR/DEPT (CDCl3): l 21.56 (+ve, CH3), 33.3 (-ve,
CH2), 35.75 (-ve, CH2), 40.75 (-ve, CH2), 65.46 (+ve,
CH), 125.63 (+ve, C-Ar), 127.75 (+ve, C-Ar), 139.66
(C-Ar).
(RS)-1-Ethylthiopropan-2-ol 1e: colorless liquid; yield=
71%; IR (film): 3400, 2969, 2927, 2872, 1454, 1125
(R)-1-(4-Methylphenyl)thiopropan-2-yl
acetate
2b:
yellow liquid: [h]D27=−6.6 (c 1.59, CH2Cl2); IR (film):
3075, 2976, 1735, 1580, 830 cm−1; MS (m/z): 224 (M+),
1
cm−1; MS (m/z): 120 (M+), 105, 76, 75, 61: H NMR
1
(CDCl3): l 1.24 (d, 3H, J=6.2 Hz, CH3), 1.27 (t, 3H,
J=7.4 Hz, CH3), 2.44 (dd, 1H, J=13.6 and 8.8 Hz,
209, 181, 123 (100), 91, 77, 58; H NMR (CDCl3): l
1.33 (d, 3H, J=6.3 Hz, CH3), 1.97 (s, 3H, COCH3),
2.34 (s, 3H, CH3), 2.87 (dd, 1H, J=13.7 and 6.5 Hz,
CH2), 3.09 (dd, 1H, J=13.7 and 6.0 Hz, CH2), 4.98
(sextet, 1H, J=6.3 Hz, CH), 7.08 (d, 2H, J=8.2 Hz,
ArH), 7.19 (d, 2H, J=8.2 Hz, ArH); 13C NMR/DEPT
(CDCl3): l 18.95 (+ve, CH3), 20.70 (+ve, CH3), 20.80
(+ve, CH3), 39.53 (-ve, CH2), 69.24 (+ve, CH), 129.45
(+ve, C-Ar), 130.0 (+ve, C-Ar), 132.23 (C-Ar), 135.99
(C-Ar), 169.24 (CꢀO).
CH2), 2.54 (q, 3H, J=7.4 Hz, CH2
(dd, 1H, J=13.6 and 3.6 Hz, CH2), 3.72–3.86 (m, 1H,
CH); 13C NMR/DEPT (CDCl3):
14.51 (+ve,
CH3CH2), 21.74 (+ve, CH3), 25.85 (-ve, CH2CH3),
40.62 (-ve, CH2), 65.43 (+ve, CH).
6 -CH3 and OH), 2.71
l
6
6
(RS)-1-Cyclohexylthiopropan-2-ol 1f: pale yellow liquid;
yield=74%; IR (film): 3420, 2980, 2950, 1345, 1080
cm−1; MS (m/z): 174 (M+), 130, 129, 115, 83, 69, 55; 1H
NMR (CDCl3): l 1.25 (d, 3H, J=6.2 Hz, CH3), 1.27–
2.05 (complex pattern, 12H, cyclohexyl ring and OH),
2.43 (dd, 1H, J=13.5 and 9.0 Hz, CH2), 2.65 (m, 1H,
SCH), 2.69 (dd, 1H, J=13.6 and 3.6 Hz, CH2), 3.81 (m,
1H, CH); 13C NMR/DEPT (CDCl3): l 21.63 (+ve,
CH3), 25.3 (-ve, CH2), 25.58 (-ve, CH2), 33.31 (-ve,
CH2), 33.46 (-ve, CH2), 38.97 (-ve, CH2), 43.35 (-ve,
CH2), 65.84 (+ve, CH).
(R)-1-Benzylthiopropan-2-yl acetate 2c: yellow liquid;
[h]2D7=+17.2 (c 1.59, CH2Cl2); IR (film): 3084, 2962,
1745, 1540, 760 cm−1; MS (m/z): 224 (M+), 209, 181,
1
123, 91 (100), 77; H NMR (CDCl3): l 1.27 (d, 3H,
J=6.2 Hz, CH3), 2.04 (s, 3H, COCH3), 2.40 (dd, 2H,
J=13.8 and 6.4 Hz, CH2), 2.55 (dd, 1H, J=13.8 and
6.3 Hz, CH2), 3.64 (s, 2H, CH2), 5.0 (sextet, 1H, J=6.3
Hz, CH), 7.16–7.34 (m, 5H, ArH); 13C NMR/DEPT
(CDCl3): l 19.19 (+ve, CH3), 20.96 (+ve, CH3), 36.23
(-ve, CH2), 36.32 (-ve, CH2), 69.11 (+ve, CH), 126.89
(+ve, C-Ar), 128.31 (+ve, C-Ar), 128.87 (+ve, C-Ar),
137.92 (C-Ar), 169.37 (CꢀO).
(RS)-1-(2-Naphthyl)thiopropan-2-ol 1g: pink solid;
yield=84%; mp 36–38°C (CHCl3/hexane); IR (KBr):
3500, 3080, 2976, 1080, 720 cm−1; MS (m/z): 218 (M+),

S. Singh et al. / Tetrahedron: Asymmetry 12 (2001) 2457–2462
2461
(R)-1-Phenylethylthiopropan-2-yl acetate 2d: colorless
liquid; [h]2D7=+8.26 (c 2.31, CH2Cl2); IR (film): 2974,
1572, 752 cm−1; MS (m/z): 238 (M+), 223, 195, 119,
(R,Ss)-4a and (R,Rs)-4a (280 mg, 91%); mp 95–97°C.
Recrystallization from CH2Cl2/hexane (0–5°C) afforded
(R,Ss)-4a (123 mg, 40%) as white solid (ee >99%); mp:
132–133°C (CH2Cl2/hexane); [h]2D7=−367 (c 0.23,
CH2Cl2); MS (m/z): 184 (M+), 182, 166, 139, 125, 78
(100); 1H NMR (CDCl3, 200 MHz): l 1.25 (d, 3H,
J=6.3 Hz, CH3), 2.64 (dd, 1H, J=13.4 and 1.9 Hz,
CH2), 3.00 (dd, 1H, J=13.4 and 8.8 Hz, CH2), 4.04 (bs,
1H, OH), 4.29–4.42 (m, 1H, CH), 7.52–7.65 (m, 5H,
ArH); 13C NMR (CDCl3): l 23.35 (CH3), 62.84 (CH2),
62.91 (CH), 124.05 (C-Ar), 129.37 (C-Ar), 130.99 (C-
Ar), 143.13 (C-Ar). Found C, 59.05; H, 6.69; C9H12O2S
requires C, 58.70; H, 6.53%.
1
105, 91 (100), 77, 58; H NMR (CDCl3): l 1.30 (d, 3H,
J=6.2 Hz, CH3), 2.05 (s, 3H, COCH3), 2.58 (dd, 1H,
J=13.7 and 6.4 Hz, CH2
J=13.8 and 6.1 Hz, CH2-CH(OH)-), 2.81–2.94 (m, 4H,
6 -CH(OH)-), 2.73 (dd, 1H,
6
2×CH2), 5.01 (sextet, 1H, J=6.2, CH), 7.19–7.33 (m,
5H, ArH); 13C NMR/DEPT (CDCl3): l 18.75 (+ve,
OAc), 20.83 (+ve, CH3), 33.69 (-ve, CH2), 35.93 (-ve,
CH2), 36.99 (-ve, CH2), 69.54 (+ve, CH), 125.97 (+ve,
C-Ar), 128.10 (+ve, C-Ar), 140.00 (C-Ar), 169.87
(CꢀO).
(R)-1-Ethylthio-propan-2-yl acetate 2e: colorless liquid;
[h]2D7=+14.5 (c 1.71 CH2Cl2); IR (film): 2980, 2866,
1750, 1410, 1180 cm−1; MS (m/z): 162 (M+), 147, 119,
The following b-hydroxy sulfoxides were synthesized
similarly.
1
60; H NMR (CDCl3): l 1.28 (t, 3H, J=7.4 Hz, CH3),
(S,Rs)-1-Phenylsulfinyl-2-propanol 4a: white solid;
yield=40%; mp 122–123°C (CH2Cl2/hexane); [h]2D7=
+369 (c 0.75, CH2Cl2). The spectroscopic data (1H
NMR, 13C NMR, MS) of (S,Rs)-4a is identical with
(R,Ss)-4a.
1.33 (d, 3H, J=6.1 Hz), 2.05 (s, 3H, COCH3), 2.49–
2.63 (overlapping q and AB protons, 3H, CH6 2CH3 and
CH2), 2.70 (dd, 1H, J=13.6 and 5.8 Hz, CH2), 4.93–
5.02 (m, 1H, CH); 13C NMR/DEPT (CDCl3): l 15.62
(+ve, CH3), 20.56 (+ve, CH3), 22.84 (+ve, CH3), 24.62
(-ve, CH2), 42.24 (-ve, CH2), 64.62 (+ve, CH), 168.54
(CꢀO).
(R,Ss)-1-(4-Methylphenylsulfinyl)-2-propanol 4b: white
solid; yield=38%; mp: 122–123°C (CH2Cl2/ hexane);
[h]2D7=−343 (c 0.60, CH2Cl2); MS (m/z): 198 (M+), 137,
1
(R)-1-Cyclohexylthiopropan-2-yl acetate 2f: yellow liq-
uid: [h]2D7=+17.9 (c 0.68, CH2Cl2); IR (film): 2984,
2960, 1745, 1420 cm−1; MS (m/z): 216 (M+), 201, 173,
123, 91, 83, 71 (100); H NMR (CDCl3): l 1.23 (d, 3H,
J=6.4 Hz, CH3), 2.43 (s, 3H, CH3), 2.61 (dd, 1H,
J=13.5 and 1.7 Hz, CH2), 3.09 (dd, 1H, J=13.8 and
9.6 Hz, CH2), 3.91 (d, 1H, 2.9 Hz, OH), 4.31–4.38 (m,
1H), 7.37 (d, 2H, J=8.1 Hz, ArH), 7.53 (d, 2H, J=8.2
Hz, ArH); 13C NMR (CDCl3): l 21.33 (CH3), 23.25
(CH3), 62.43 (CH2), 64.02 (CH), 123.93 (C-Ar), 130.00
(C-Ar), 139.68 (C-Ar), 141.46 (C-Ar). Found C, 60.86;
7.42 H; C10H14O2S requires C, 60.61; H, 7.07%.
1
115 (100), 83; H NMR (CDCl3): l 1.29 (d, 3H, J=6.1
Hz, CH3), 1.61–1.94 (complex pattern, 11H, cyclohexyl
ring), 2.01 (s, 3H, COCH3), 2.54 (dd, 1H, J=13.4 and
7.0, CH2), 2.65 (dd, 1H, J=13.4 and 5.8 Hz, CH2),
4.86–4.95 (m, 1H, CH); 13C NMR/DEPT (CDCl3): l
20.23 (+ve, CH3), 21.84 (+ve, CH3), 24.53 (-ve, CH2),
25.23 (-ve, CH2), 33.65 (-ve, CH2), 34.68 (-ve, CH2),
39.68 (-ve, CH2), 44.24 (-ve, CH2), 66.44 (+ve, CH),
168.66 (CꢀO).
(S,Rs)-1-(4-Methylphenylsulfinyl)-2-propanol 4b: white
solid; yield=39%; mp: 122–123°C (CH2Cl2/hexane);
[h]2D7=+343° (c 0.50, CH2Cl2). The spectroscopic data
(1H NMR, 13C NMR, MS) of (S,Rs)-4b is identical
with (R,Ss)-4b.
(R)-1-(2-Naphthyl)thiopropan-2-yl acetate 2g: pale
yellow liquid; [h]D27=−8.8 (c 1.11, CH2Cl2); IR (film):
3060, 2974, 1758, 1140, 760 cm−1; MS (m/z): 260 (M+),
1
245, 218, 174, 159, 127, 92; H NMR (CDCl3): l 1.39
Acknowledgements
(d, 3H, J=6.3 Hz, CH3), 1.99 (s, 3H, COCH3), 3.09
(dd, 1H, J=13.8 and 6.3 Hz, CH2), 3.32 (dd, 1H,
J=13.7 and 5.9 Hz, CH2), 5.09–5.19 (m, 1H, CH),
7.45–7.53 (m, 3H, ArH), 7.77–7.88 (m, 4H, ArH); 13C
NMR /DEPT (CDCl3): l 19.59 (+ve, CH3), 21.48 (+ve,
CH3), 39.27 (-ve, CH2), 70.07 (+ve, CH), 126.16 (+ve,
C-Ar), 126.95 (+ve, C-Ar), 127.52 (+ve, C-Ar), 127.85
(+ve, C-Ar), 128.03 (+ve, C-Ar), 128.85 (+ve, C-Ar),
133.62 (C-Ar), 134.11 (C-Ar), 170.42 (CꢀO).
We thank CSIR (India) for financial assistance, Dr. J.
S. Rao (Novo Nordisk, India) for HLL and lipozyme
samples and Professor V.S. Parmar for gift of lipases.
S.S. thanks Professor Harjit Singh for financial
support.
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