Enantioselective ring-opening reaction of meso-epoxides with ArSH catalyzed by a C2-symmetric chiral bipyridyldiol-titanium complex

Article abstract of DOI:10.1016/j.tetasy.2007.04.030

This study describes a C₂-symmetric ligand comprising a central bipyridine-pinene-derived core and two functionalized diphenylmethanol subunits. [8′-(Hydroxy-diphenyl-methyl)-10,10,10′,10′-tetramethy l-[5,5′]bi[6-aza-tricyclo[7.1.1.0^2,7

Full text of DOI:10.1016/j.tetasy.2007.04.030

Tetrahedron: Asymmetry 18 (2007) 1313–1319
Enantioselective ring-opening reaction of meso-epoxides with ArSH
catalyzed by a C2-symmetric chiral bipyridyldiol-titanium complex
Yi-Jing Chen and Chinpiao Chen*
Department of Chemistry, National Dong Hwa University, Soufeng, Hualien 974, Taiwan, ROC
Received 29 March 2007; accepted 27 April 2007
Abstract—This study describes a C2-symmetric ligand comprising a central bipyridine-pinene-derived core and two functionalized
diphenylmethanol subunits. [80-(Hydroxy-diphenyl-methyl)-10,10,100,100-tetramethyl-[5,50]bi[6-aza-tricyclo[7.1.1.02,7]undecyl]-2(7),3,5,
20(70),30,50-hexaen-8-yl]-diphenyl-methanol 1 is an effective catalyst in the asymmetric ring opening (ARO) of meso-epoxides with PhSH
and inductions of up to 69% ee. Importantly, there was a correlation between Hammett substituent constants and enantiomeric excesses;
the electron-donating substituents at the meta- and para-positions of the substituted stilbene oxides had good enantioselectivity during
the epoxide ring opening using PhSH.
Ó 2007 Elsevier Ltd. All rights reserved.
1. Introduction
tiomeric excess.7b,c However, the nucleophile was limited to
t-BuSH. Conversely, Hou et al. reported the catalytic
asymmetric ring opening of epoxides with ArSH using a
(salen)Ti(IV) complex as a catalyst. Although the enantio-
selectivity was unsatisfactory, Hou’s approach was a facile
and convenient method for synthesizing chiral b-hydroxy
sulfide compounds.7d We have reported that the catalytic
addition of diethylzinc11a and trimethylsilyl cyanide11b to
various substituted benzaldehydes obtains alcohols with
enantiomeric excess, typically ranging from 2% to 99%
using catalytic amounts of titanium tetraisopropoxide
and chiral bipyridyl-diol 1 derived from (1R)-(+)-a-pinene
(Scheme 1). In this study, a Ti-ligand 1 complex was
utilized as the enantioselective catalyst of asymmetric ring
opening of meso-epoxides with PhSH.
The asymmetric ring opening (ARO) of meso-epoxides
with diverse nucleophiles is an important transformation
in organic synthesis because it is a potent strategy for the
formation of 1,2-bifunctionalized systems, while at the
same time, it establishes two contiguous stereogenic cen-
ters.1 Manifold nucleophiles have been successfully utilized
in the asymmetric ring opening reactions, with most being
heteroatom-based. These methodologies have provided
practical access to enantioenriched b-azido alcohols,2,3
b-halohydrins,4,5 b-cyanohydrins,3a,6 b-hydroxy sulfides,7
b-benzoyloxy alcohols,8 b-aryloxy alcohols,9 and b-amino
alcohols.10 Of these, sulfur nucleophiles are useful and lead
to the construction of synthetically valuable b-hydroxy
mercaptans or b-hydroxy sulfides. Few studies have inves-
tigated the desymmetrization reaction of meso-epoxides by
using a thiol as a nucleophile.7 This ring-opening reaction
is generally performed in the presence of a catalyst, such
as Zn(II) D-tartrates,7a Ga/Li bis(binaphthoxide) com-
plex7b or metal salen complexes.7c,d The products,
b-hydroxysulfides, can be obtained with high regio- and
stereoselectivity. Shibasaki and Jacobsen et al. reported a
catalytic asymmetric ring opening of epoxides with t-BuSH
using gallium–lithium-bis(binaphthoxide) (GaLB) complex
and (salen)Cr(III) complex as a catalyst in prominent enan-
N
N
OH
HO
Ph
Ph
Ph
Ph
1
Scheme 1.
2. Results and discussion
*
All substituted stilbene oxides were prepared from substi-
tuted benzaldehydes and substituted benzylbromide via a
Corresponding author. Tel.: +886 3 863 3597; fax: +886 3 863 0475;
e-mail: chinpiao@mail.ndhu.edu.tw
0957-4166/$ - see front matter Ó 2007 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2007.04.030

1314
Y.-J. Chen, C. Chen / Tetrahedron: Asymmetry 18 (2007) 1313–1319
Wittig reaction,12 followed by epoxidation using mCPBA.13
The preparation of 2,3-bis-(4-methoxy-phenyl)-oxirane was
unsuccessful. 2,3-Di-o-tolyl-oxirane, 2,3-bis-(2-chloro-phen-
yl)-oxirane, 2,3-bis-(2-cyano-phenyl)-oxirane, 2,3-bis-(2-
nitro-phenyl)-oxirane, and 2,3-bis-(4-nitro-phenyl)-oxirane
cannot perform the corresponding ring-opening reaction
of epoxides with PhSH, in the presence of catalyst or
without catalyst at room temperature or refluxing in
acetonitrile.
PhS
OH
PhS
OH
m-CPBA
+
CH2Cl2, rt.
(1R,2R)-ent-3c
(1S,2S)-3c
PhO2S
OH
PhO2S
OH
+
Asymmetric ring-opening of a meso-epoxide with thio-
phenol was performed in the presence of catalyst Ti(IV)-1
complex as described below. The Ti(O-i-Pr)4 was added
to a stirred solution of ligand 1 in acetonitrile under nitro-
gen. The resulting mixture was stirred at room temperature
for 1 h, then epoxide and PhSH were added. The reaction
mixture was stirred at room temperature for 30 h, then
filtered through a plug of silica gel, and washed with
dichloromethane. Following purification by flash column
chromatography, the enantiomeric excesses of 2-phenyl-
sulfanyl-cyclohexanol were determined by HPLC analysis
using a chiral column (Chiralcel OD-H column).
(1S,2S)-6
major
(1R,2R)-ent-6
Scheme 2. Absolute configurations of the major isomers of 3c and 6.
The enantiomeric excesses of the ARO of meso-epoxides in
the presence of Ti(IV)-1 complex were cis-stilbene oxide
(66% ee), cyclohexene oxide (17% ee) and cyclopentene
oxide (0% ee). Notably, cis-stilbene oxide for the ARO
reaction gave a better result than the other epoxides. The
desymmetrization of stilbene oxides using PhSH, in the
presence of various amounts of ligand 1 and 1.5 equiv
Ti(O-i-Pr)4, the enantiomeric excesses of 1,2-diphenyl-2-
phenylsulfanyl-ethanol were acquired (Table 1, entries
8–11). The optimal amount of catalyst was 20 mol % of
ligand 1 (69% ee).
Sharpless reported that a stoichiometric amount of Ti(O-i-
Pr)4 was necessary for the reaction to proceed.14 The ring
opening reaction of cis-stilbene oxide with PhSH 5 mol %
of chiral ligand 1 and Ti(O-i-Pr)4 was performed under var-
ious reaction conditions. Table 1 displays the enantiomeric
excesses of 1,2-diphenyl-2-phenylsulfanyl-ethanol. The
optimal amount of Ti(O-i-Pr)4 was 1.5 equiv in acetonitrile
with 51% ee. The desymmetrization of stilbene oxides was
performed by using PhSH, in the presence of various
amounts of ligand 1 and 1.5 equiv Ti(O-i-Pr)4. The enan-
tiomeric excesses of 1,2-diphenyl-2-phenylsulfanyl-ethanol
are shown in Table 1 which clearly shows that using
20 mol % of ligand gave best ee (69%). The configuration
of 3c was determined by comparing the literature’s15 spe-
cific rotation, retention time of HPLC and NMR spectrum
of sulfone 6 (Scheme 2).
The electronic effects in asymmetric hydroborations,16
epoxidations,17 and alkylations11 have been reported. In
our previous study,11 the Hammett substituent constants
were strongly correlated with enantiomeric excesses of the
alkylation of meta-substituted benzaldehydes using diethyl-
zinc in the presence of Ti(IV)-bipyridyldiol 1. Additionally,
Ti(IV)-bipyridyldiol 1 acted as an interesting chiral catalyst
for the enantioselective addition of TMSCN to various
Table 1. Enantiomeric excess (%) of ARO of cis-stilbene oxide in the presence of Ti(IV)-1 complex in various reaction conditions
SH
5 mol % ligand 1,
O
PhS
Ph
OH
Ph
Ti(O-
i-Pr)4
+
Ph
Ph
2c
30 hr
3c
Entry
Solvents
Ti(O-i-Pr)4 (mol %)/ligand (mol %)
Yield (%)
ee (%)
Config.b
1
2
3
4
5
6c
7c
8
Hexane
Toluene
5/5
5/5
5/5
5/5
5/5
5/5
5/5
150/5
150/10
150/10
150/20
12
4
4
2
29
0
11
10
11
51
66
66
69
(1S,2S)
(1S,2S)
(1S,2S)
(1S,2S)
(1S,2S)
(1S,2S)
(1S,2S)
(1S,2S)
(1S,2S)
(1S,2S)
(1S,2S)
Acetonitrile
Tetrahydrofuran
p-Xylene
Acetonitrile
Acetonitrile
Acetonitrile
Acetonitrile
Acetonitrile
Acetonitrile
43
23
24
28
8
41
73
51
76
9
10a
11
a PhSH was added dropwise over 6 h.
b Compared with Ref. 15.
c Reaction temperature: entry 6 (0 °C), entry 7 (ꢀ20 °C) and others (25 °C).

Y.-J. Chen, C. Chen / Tetrahedron: Asymmetry 18 (2007) 1313–1319
1315
Table 2. Enantiomeric excess (%) of ARO of substituted stilbene oxides in the presence of Ti(IV)-1 complex
PhS
OH
O
SH
10 mol % ligand 1
+
1.5 eq Ti(O-i-Pr)4
R
R
R
R
CH3CN, rt.
5a-h
4a-h
Entry
Ra
Product
Yieldb (%)
eec (%)
Substituent constants18
1
2
3
4
5
6
7
8
m-OMe
m-Me
p-Me
m-Cl
p-Cl
m-CN
p-CN
m-NO2
5a
5b
5c
5d
5e
5f
77
18
76
96
87
50
40
53
45
60
45
64
36
48
23
20
+0.12
ꢀ0.07
ꢀ0.17
+0.37
+0.23
+0.56
+0.66
+0.71
5g
5h
a All the substituted stilbene oxides were prepared from substituted benzaldehydes and substituted benzylbromide via a Wittig reaction12 followed by
epoxidation by mCPBA.13
b Isolated yield.
c The ee values were determined by HPLC on a chiral Chiralcel OD-H column.
70
60
50
40
30
20
10
0
substituted benzaldehydes, yielding cyanohydrins with (S)-
configurations with enantiomeric excesses, generally rang-
ing from 2% to 98% ee. Notably, electron-releasing substi-
tuents at the meta- and para-positions of the substituted
benzaldehydes were highly enantioselective during cyana-
tion using TMSCN.
H
p-Me
p
-Cl
p-CN
This study examined the reactions of substituted stilbene
oxides with thiophenol at 25 °C in the presence of ligand
1 (10 mmol %) and Ti(O-i-Pr)4 (1.5 equiv) in acetonitrile
(Table 2). Hammett substituent constants were highly cor-
related with the enantiomeric excesses produced by the
asymmetric ring opening of para- and meta-substituted stil-
bene oxides using PhSH. Electron-donating substituents on
the meta-position exhibited high enantiomeric excesses,
whereas electron-withdrawing substituents on the meta-
position gave low enantiomeric excesses (Fig. 1). On the
other hand, electron-donating substituents at the para-
position exhibited high enantiomeric excesses, whereas
relatively strong electron-withdrawing substituents at the
para-position displayed low enantiomeric excesses
(Fig. 2). The electron-donating substituents of substituted
stilbene oxides can enhance the p–p interaction between
-0.1
0
0.1
0.2
0.3
σp
0.4
0.5
0.6
0.7
Figure 2. The correlation of substituent constants (rp) and the enantio-
meric excesses of the ARO of para-substituted stilbene oxides in the
presence of Ti(IV)-1 complex.
the phenyl group of ligand 1 and the aromatic ring of
substituted stilbene oxides. Therefore, the aromatic ring
of substituted stilbene oxides can be fixed tightly and
induced a highly enantioselective ring opening reaction.
The reaction of stilbene oxide with thiophenol at 25 °C in
the presence of ligand 1 (10 mmol %) and Ti(O-i-Pr)4
(1.5 equiv) in acetonitrile gave a highly enantioselective
product (66% ee). Substituted stilbene oxides with a small
substituent induced a high enantioselectivity.
80
70
60
3. Conclusion
H
m-Cl
50
40
30
20
10
0
m-Me
m
-CN
In this study, a chiral bipyridinyldiol 1 was prepared from
highly enantiopure (1R)-(+)-a-pinene (>97% ee).11a The
Ti(IV)-bipyridinyldiol complex acted as a chiral catalyst
for the enantioselective addition of PhSH to various substi-
tuted stilbene oxides, and attained synthetically versatile
b-hydroxy sulfides in optically active forms, generally
ranging from 20% to 69% ee. Notably, electron-releasing
substituents at the meta- and para-positions of the substi-
tuted stilbene oxides gave good enantioselectivity during
epoxide ring opening using PhSH.
m
-OMe
m
-NO2
-0.2 -0.1
0
0.1 0.2 0.3 0.4 0.5 0.6 0.7 0.8
σm
Figure 1. The correlation of substituent constants (rm) and the enantio-
meric excesses of the ARO of meta-substituted stilbene oxides in the
presence of Ti(IV)-1 complex.

1316
Y.-J. Chen, C. Chen / Tetrahedron: Asymmetry 18 (2007) 1313–1319
4. Experimental
129.6, 128.0, 127.8, 125.9, 21.3. IR (KBr): 3010, 2919,
1918, 1598, 771, 734 cmꢀ1. MS m/z: 208 (M+, 100), 193
(50), 178 (50), 165 (11), 115 (15), 91 (9). HRMS-EI (m/z):
[M]+ calcd for C16H16, 208.1252; found, 208.1247.
4.1. General
All reactions were carried out in anhydrous solvents. THF
and diethyl ether were distilled from sodium-benzophenone
under argon. Toluene, CH3CN, CH2Cl2, xylene, and
4.2.4. trans-3,30-Dimethylstilbene. 1H NMR (300 MHz,
CDCl3, d): 7.42–7.24 (m, 6H), 7.11–7.08 (m, 4H), 2.40 (s,
6H). 13C NMR (75.5 MHz, CDCl3, d): 138.2, 137.4,
128.6, 128.4, 127.2, 123.7, 21.4. IR (KBr): 3025, 2915,
1
hexane were distilled from CaH2. H NMR spectra were
obtained at 300 or 400 MHz (as indicated), and 13C
NMR spectra were obtained at 75.5 or 100.6 MHz using
a Bruker NMR spectrometer. Chemical shifts (d) are
reported in ppm relative to CDCl3 (7.26 and 77.0 ppm).
Mass spectra (MS) and high resolution mass spectra
(HRMS) were determined on a Finnigan/Thermo Quest
MAT 95XL mass spectrometer. Infrared spectra were
recorded using a JASCO FT/IR 410 spectrometer. All
asymmetric reactions were conducted in dry glassware
under nitrogen using a standard glovebox. Enantiomeric
excesses were determined using Lab Alliance Series III
high performance liquid chromatography (HPLC) with a
Chiracel OD-H chiral column (Daicel Chemical Industries,
LTD). Optical rotations were measured using a JASCO
P-1010 polarimeter at the indicated temperature using a
sodium lamp (D line, 589 nm). Flash column chromatogra-
phy was performed using MN silica gel 60 (70–230 mesh)
purchased from Macherey-Nagel.
1600, 1488, 968, 788, 696 cmꢀ1
.
4.2.5. cis-4,40-Dimethylstilbene. 1H NMR (300 MHz,
CDCl3, d): 7.17 (d, J = 8.0 Hz, 4H), 7.04 (d, J = 7.9 Hz,
4H), 6.51 (s, 2H), 2.31 (s, 6H). 13C NMR (100.6 MHz,
CDCl3, d): 136.7, 134.5, 129.5, 128.9, 128.7, 21.2. IR
(KBr): 3010, 2915, 1909, 1508, 823, 777 cmꢀ1. MS m/z:
208 (M+, 100), 193 (63), 178 (33), 165 (11), 115 (28), 91
(10). HRMS-EI (m/z): [M]+ calcd for C16H16, 208.1252;
found, 208.1253.
4.2.6. trans-4,40-Dimethylstilbene. 1H NMR (300 MHz,
CDCl3, d): 7.41 (d, J = 8.0 Hz, 4H), 7.17 (d, J = 8.0 Hz,
4H), 7.03 (s, 2H), 2.35 (s, 6H). 13C NMR (100.6 MHz,
CDCl3, d): 137.2, 134.7, 129.3, 127.6, 126.3, 21.2. IR
(KBr): 3018, 2910, 1909, 1513, 970, 819 cmꢀ1
.
4.2.7. cis-3,30-Dichlorostilbene. 1H NMR (300 MHz,
CDCl3, d): 7.21–7.06 (m, 8H), 6.57 (s, 2H). 13C NMR
(100.6 MHz, CDCl3, d): 138.5, 134.2, 130.0, 129.5, 128.8,
127.5, 126.9. IR (KBr): 3066, 3016, 1940, 1870, 1702,
1589, 1473, 1425, 798, 678 cmꢀ1. MS m/z: 252 (M++4,
6), 250 (M++2, 41), 248 (M+, 64), 212 (23), 178 (100),
106 (11), 88 (25). HRMS-EI (m/z): [M]+ calcd for
C14H10Cl2, 248.0160; found, 248.0151.
4.2. Synthesis of substituted stilbenes
The typical procedure for preparing substituted stilbenes is
as follows. Aromatic aldehydes (5 mmol) and 18-crown-6
(0.5 mmol) were added to a solution of phosphonium salt
(5 mmol) in dichloromethane (25 mL). The mixture was
cooled to ꢀ78 °C, and freshly powdered potassium hydr-
oxide (10 mmol) was added under magnetic stirring. After
stirring at ꢀ78 °C for 6 h, the mixture was diluted with
dichloromethane, filtered off, and washed with water. The
organic phase was dried over anhydrous magnesium sul-
fate. After filtration and concentration of the organic
phase, the residue was purified by flash column chromato-
graphy using silica gel as the stationary phase and ethyl
acetate–hexane (1:49) as mobile phase. Thus, substituted
stilbenes were produced.
4.2.8. trans-3,30-Dichlorostilbene. 1H NMR (300 MHz,
CDCl3, d): 7.50 (s, 2H), 7.38–7.23 (m, 6H), 7.03 (s, 2H).
13C NMR (100.6 MHz, CDCl3, d): 138.7, 134.7, 129.9,
128.6, 127.9, 126.4, 124.8. IR (KBr): 3434, 3056, 1592,
1565, 966, 887, 771, 684 cmꢀ1
.
4.2.9. cis-4,40-Dichlorostilbene. 1H NMR (300 MHz,
CDCl3, d): 7.21 (d, J = 6.5 Hz, 4H), 7.15 (d, J = 6.5 Hz,
4H), 6.63 (s, 2H). 13C NMR (100.6 MHz, CDCl3, d):
135.2, 133.0, 130.1, 129.6, 128.5. IR (KBr): 3415, 3021,
2923, 1895, 1486, 1083, 1012, 877, 821, 736 cmꢀ1. MS
m/z: 252 (M++4, 8), 250 (M++2, 53), 248 (M+, 83), 212
(20), 178 (100), 151 (10), 88 (19). HRMS-EI (m/z): [M]+
calcd for C14H10Cl2, 248.0160; found, 248.0152.
4.2.1. cis-3,30-Dimethoxystilbene. 1H NMR (300 MHz,
CDCl3, d): 7.18 (t, J = 7.8 Hz, 2H), 6.86–6.73 (m, 6H),
6.58 (s, 2H), 3.66 (s, 6H). 13C NMR (75.5 MHz, CDCl3,
d): 159.4, 138.6, 130.4, 129.2, 121.5, 113.9, 113.3, 55.1. IR
(KBr): 3066, 2946, 2834, 1930, 1845, 1598, 1045, 781,
686 cmꢀ1. MS m/z: 240 (M+, 100), 209 (21), 165 (45), 153
(23), 91 (2). HRMS-EI (m/z): [M]+ calcd for C16H16O2,
240.1150; found, 240.1142.
4.2.10. cis-3,30-Dicyanostilbene. 1H NMR (300 MHz,
CDCl3, d): 7.54–7.32 (m, 8H), 6.75 (s, 2H). 13C NMR
(75.5 MHz, CDCl3, d): 137.4, 132.9, 132.2, 131.2, 130.2,
129.3, 118.3, 112.9. IR (KBr): 3430, 3056, 2227, 1722,
1596, 1477, 813, 678 cmꢀ1. MS m/z: 230 (M+, 100), 215
(16), 203 (16), 190 (14), 115 (6), 88 (8). HRMS-EI (m/z):
[M]+ calcd for C16H10N2, 230.0844; found, 230.0848.
4.2.2. trans-3,30-Dimethoxystilbene. 1H NMR (300 MHz,
CDCl3, d): 7.31–7.05 (m, 8H), 6.8 (d, J = 7.4 Hz, 2H),
3.85 (s, 6H). 13C NMR (100.6 MHz, CDCl3, d): 159.9,
138.7, 129.6, 128.9, 119.3, 113.4, 111.8, 55.2. IR (KBr):
2960, 2933, 1954, 781, 692 cmꢀ1
.
4.2.11. cis-4,40-Dicyanostilbene. 1H NMR (300 MHz,
CDCl3, d): 7.55 (d, J = 6.6 Hz, 4H), 7.29 (d, J = 6.7 Hz,
4H), 6.74 (s, 2H). 13C NMR (100.6 MHz, CDCl3, d):
140.9, 132.3, 131.2, 129.4, 118.5, 111.4. IR (KBr): 3052,
4.2.3. cis-3,30-Dimethylstilbene. 1H NMR (300 MHz,
CDCl3, d): 7.19–7.02 (m, 8H), 6.54 (s, 2H), 2.27 (s, 6H).
13C NMR (100.6 MHz, CDCl3, d): 137.6, 137.2, 130.2,

Y.-J. Chen, C. Chen / Tetrahedron: Asymmetry 18 (2007) 1313–1319
1317
2223, 1602, 1504, 1411, 1180, 892, 831, 576, 545 cmꢀ1. MS
m/z: 230 (M+, 100), 215 (17), 202 (11), 190 (18), 127 (7), 88
(7). HRMS-EI (m/z): [M]+ calcd for C16H10N2, 230.0844;
found, 230.0842.
(21), 229 (36), 201 (12), 194 (33), 165 (48), 139 (31), 89
(100), 75 (13). HRMS-EI (m/z): [M]+ calcd for
C16H10Cl2O, 264.0109; found, 264.0110.
4.3.5. 2,3-Bis-(4-chloro-phenyl)-oxirane 4e. 1H NMR
(300 MHz, CDCl3, d): 7.18 (d, J = 8.4 Hz, 4H), 7.09 (d,
J = 9.0 Hz, 4H), 4.31 (s, 2H). 13C NMR (75.4 MHz,
CDCl3, d): 133.6, 132.5, 128.3, 59.1. IR (KBr): 3430,
1917, 1598, 1492, 1419, 1087, 1012, 875, 798, 763,
501 cmꢀ1. MS m/z: 268 (M++4, 1), 266 (M++4, 7), 264
(M+, 13), 250 (26), 237 (40), 235 (73), 229 (26), 165 (49),
141 (100), 139 (70), 89 (56), 77 (46). HRMS-EI (m/z):
[M]+ calcd for C16H10Cl2O, 264.0109; found, 264.0114.
4.2.12. cis-3,30-Dinitrostilbene. 1H NMR (300 MHz,
CDCl3, d): 8.10–8.06 (m, 4H), 7.54–7.25 (m, 4H), 6.80 (s,
2H). 13C NMR (75.5 MHz, CDCl3, d): 148.5, 137.7,
134.6, 130.4, 129.5, 123.7, 122.6. IR (KBr): 3070, 2863,
1702, 1515, 1348, 1083, 809, 765, 719, 669 cmꢀ1. MS m/z:
270 (M+, 100), 176 (62), 165 (63), 151 (25), 76 (12).
HRMS-EI (m/z): [M]+ calcd for C14H10N2O4, 270.0641;
found, 270.0637.
4.3. Synthesis of substituted stilbene oxides
4.3.6. 2,3-Bis-(3-cyano-phenyl)-oxirane 4f. 1H NMR
(300 MHz, CDCl3, d): 7.57–7.30 (m, 8H), 4.42 (s, 2H).
13C NMR (100.6 MHz, CDCl3, d): 135.2, 131.7, 130.8,
130.2, 129.0, 118.1, 112.5, 58.6. IR (KBr): 3066, 2227,
1481, 917, 806, 690 cmꢀ1. MS m/z: 246 (M+, 95), 228
(59), 217 (100), 190 (44), 130 (24), 115 (86), 102 (18), 88
(36), 63 (12). HRMS-EI (m/z): [M]+ calcd for
C16H10N2O, 246.0793; found, 246.0802.
The typical procedure for preparing substituted stilbene
oxides is as follows. To a solution of substituted stilbene
(2 mmol) in dichloromethane (20 mL) was added mCPBA
(5 mmol) at 0 °C. After stirring at room temperature for
15 h, the mixture was diluted with diethyl ether, and
washed with 5% NaHCO3. The organic phase was dried
over anhydrous magnesium sulfate. Following filtration
and concentration, the residue was purified by column
chromatography using silica gel as the stationary phase
and ethyl acetate/hexane (1:19) as mobile phase to yield
the stilbene oxides.
4.3.7. 2,3-Bis-(4-cyano-phenyl)-oxirane 4g. 1H NMR
(300 MHz, CDCl3, d): 7.51 (d, J = 5.6 Hz, 4H), 7.29 (d,
J = 8.1 Hz, 4H), 4.45 (s, 2H). 13C NMR (100.6 MHz,
CDCl3, d): 138.8, 132.2, 131.9, 129.4, 127.3, 59.1. IR
(KBr): 3438, 3056, 2225, 1608, 1506, 1417, 1182, 894,
833, 813, 584 cmꢀ1. MS m/z: 246 (M+, 100), 230 (85),
217 (74), 190 (54), 130 (29), 115 (98), 102 (24), 88 (42), 63
(15). HRMS-EI (m/z): [M]+ calcd for C16H10N2O,
246.0793; found, 246.0787.
4.3.1. 2,3-Bis-(3-methoxy-phenyl)-oxirane 4a. 1H NMR
(300 MHz, CDCl3, d): 7.13–7.07 (t, J = 7.3 Hz, 2H), 6.82
(d, J = 7.5 Hz, 2H), 6.71–6.68 (m, 4H), 4.32 (s, 2H), 3.67
(s, 6H). 13C NMR (100.6 MHz, CDCl3, d): 159.1, 135.9,
128.8, 119.3, 113.6, 112.0, 59.7, 55.1. IR (KBr): 2957,
2834, 1585, 1491, 1044, 795, 694 cmꢀ1. MS m/z: 256 (M+,
100), 238 (86), 227 (75), 149 (42), 135 (54), 121 (48), 91
(58), 77 (63). HRMS-EI (m/z): [M]+ calcd for C16H16O3,
256.1099; found, 256.1106.
4.3.8. 2,3-Bis-(3-nitro-phenyl)-oxirane 4h. 1H NMR
(300 MHz, CDCl3, d): 8.23–8.01 (m, 4H), 7.55 (d,
J = 7.7 Hz, 2H), 7.42–7.37 (t, J = 7.9 Hz, 2H), 4.53 (s,
2H). 13C NMR (75.4 MHz, CDCl3, d): 135.6, 132.5,
129.2, 123.1, 121.7, 58.8. IR (KBr): 3079, 1697, 1531,
1349, 1309, 1089, 935, 744 cmꢀ1. MS m/z: 286 (M+, 3),
269 (5), 257 (2), 239 (7), 193 (4), 165 (22), 135 (100), 105
(75), 89 (65), 77 (12), 63 (28). HRMS-EI (m/z): [M]+ calcd
for C14H10N2O5, 286.0590; found, 286.0593.
4.3.2. 2,3-Di-m-tolyl-oxirane 4b. 1H NMR (300 MHz,
CDCl3, d): 7.09–6.94 (m, 8H), 4.30 (s, 2H), 2.19 (s, 6H).
13C NMR (75.4 MHz, CDCl3, d): 137.3, 134.5, 129.0,
128.4, 123.9, 59.9, 21.4. IR (KBr): 3031, 2921, 1094,
1770, 1608, 1418, 1216, 800, 754, 698 cmꢀ1. MS m/z: 224
(M+, 49), 209 (38), 195 (100), 180 (28), 165 (37), 119 (77),
103 (34), 91 (52), 77 (26). HRMS-EI (m/z): [M]+ calcd
for C16H16O, 224.1201; found, 224.1203.
4.4. Representative procedure for the asymmetric ring
opening of epoxides by Ti-ligand 1 complex
To a stirred solution of ligand 1 (7.0 mg, 0.01 mmol) in
CH3CN (1.0 mL) under nitrogen, Ti(O-i-Pr)4 (43 lL,
0.15 mmol) was added. The resulting mixture was stirred
at room temperature for 1 h, then epoxide (0.1 mmol) and
PhSH (0.1 mmol) were added. The reaction mixture was
stirred at room temperature for 30 h, filtered through a plug
of silica gel, and washed with 5 mL CH2Cl2. The solvent was
removed under reduced pressure, and the residue was
purified by flash column chromatography to furnish the cor-
responding asymmetric ring opening product. Enantiomeric
excess was determined by HPLC analysis using a chiral
column (Chiralcel OD-H column, flow rate 0.25 mL/min).
4.3.3. 2,3-Di-p-tolyl-oxirane 4c. 1H NMR (300 MHz,
CDCl3, d): 7.07 (d, J = 6.3 Hz, 4H), 7.00 (d, J = 8.0 Hz,
4H), 4.29 (s, 2H), 2.24 (s, 6H). 13C NMR (75.4 MHz,
CDCl3, d): 137.1, 131.5, 128.5, 126.8, 59.8, 21.1. IR
(KBr): 2921, 1911, 1725, 1515, 1172, 900, 804, 765 cmꢀ1
.
MS m/z: 224 (M+, 38), 209 (31), 195 (100), 180 (16), 165
(18), 119 (28), 103 (33), 91 (18), 77 (13). HRMS-EI (m/z):
[M]+ calcd for C16H16O, 224.1201; found, 224.1202.
4.3.4. 2,3-Bis-(3-chloro-phenyl)-oxirane 4d. 1H NMR
(300 MHz, CDCl3, d): 7.19–7.02 (m, 8H), 4.32 (s, 2H).
13C NMR (75.4 MHz, CDCl3, d): 135.9, 134.0, 129.2,
128.0, 126.9, 124.8, 59.0. IR (KBr): 3424, 2962, 2927,
2764, 1596, 1569, 1479, 1429, 788, 678, 593 cmꢀ1. MS
m/z: 268 (M++4, 3), 266 (M++4, 17), 264 (M+, 26), 246
4.4.1. 1,2-Diphenyl-2-phenylsulfanyl-ethanol 3c.15 Yield:
21
66%. ½aꢁD ¼ þ54:8 (c 1.1, CH3Cl). HPLC (Daicel Chiralcel
OD-H, hexane/i-PrOH = 90:10, flow rate 0.25 mL/min) tR

1318
Y.-J. Chen, C. Chen / Tetrahedron: Asymmetry 18 (2007) 1313–1319
1
21.2 and 25.1 min. H NMR (400 MHz, CDCl3, d): 7.30–
7.13 (m, 13H), 7.01 (m, 2H), 4.95 (d, J = 8.5 Hz, 1H), 4.36
(d, J = 8.6 Hz, 1H), 3.29 (br, 1H). 13C NMR (100.6 MHz,
CDCl3, d): 140.4, 139.2, 132.4, 128.8, 128.5, 128.1, 127.9,
127.7, 127.4, 127.2, 126.9, 77.3, 63.9.
IR (KBr): 3422, 3058, 2919, 1594, 1476, 741, 692 cmꢀ1
.
MS m/z: 374 (M+, 0.02), 356 (0.1), 265 (0.1), 233 (100),
197 (24), 165 (21), 139 (15), 125 (23), 105 (17), 91 (2), 77
(22). HRMS-EI (m/z): [M]+ calcd for C20H16Cl2OS,
374.0299; found, 374.0307.
4.4.2. 1,2-Bis-(3-methoxy-phenyl)-2-phenylsulfanyl-ethanol
4.4.6. 1,2-Bis-(4-chloro-phenyl)-2-phenylsulfanyl-ethanol 5e.
21
21
5a. Yield: 77%. ½aꢁD ¼ þ45:6 (c 1.1, CH3Cl). HPLC (Dai-
Yield: 87%. ½aꢁD ¼ þ6:9 (c 1.5, CH3Cl). HPLC (Daicel
cel Chiralcel OD-H, hexane/i-PrOH = 90:10, flow rate
Chiralcel OD-H, hexane/i-PrOH = 90:10, flow rate
1
1
0.25 mL/min) tR 32.8 and 44.0 min. H NMR (300 MHz,
0.25 mL/min) tR 19.2 and 33.6 min. H NMR (400 MHz,
CDCl3, d): 7.30–7.19 (m, 5H), 7.09–7.06 (m, 2H), 6.72–
6.58 (m, 6H), 4.92 (d, J = 8.3 Hz, 1H), 4.32 (d,
J = 8.3 Hz, 1H), 3.68 (s, 3H), 3.66 (s, 3H), 3.22 (br, 1H).
13C NMR (100.6 MHz, CDCl3, d): 159.3, 142.0, 140.7,
134.2, 132.3, 129.1, 128.9, 128.8, 127.4, 121.0, 119.2,
114.0, 113.6, 113.0, 112.2, 63.7, 55.1. IR (KBr): 3457,
3057, 2835, 1599, 1488, 1436, 1043, 692 cmꢀ1. MS m/z:
366 (M+, 0.01), 348 (0.7), 241 (0.8), 230 (100), 197 (12),
135 (18), 121 (30), 109 (14), 91 (10), 77 (15). HRMS-EI
(m/z): [M]+ calcd for C22H22O3S, 366.1290; found,
366.1290.
CDCl3, d): 7.26–7.11 (m, 9H), 7.06 (d, J = 6.5 Hz, 2H),
6.93 (d, J = 6.6 Hz, 2H), 4.87 (d, J = 7.9 Hz, 1H), 4.25
(d, J = 7.8 Hz, 1H), 3.12 (br, 1H). 13C NMR
(100.6 MHz, CDCl3, d): 138.6, 137.4, 133.7, 133.2, 132.8,
129.8, 129.0, 128.4, 128.2, 127.9, 75.9, 63.2. IR (KBr):
3356, 3096, 1489, 1089, 741, 690 cmꢀ1. MS m/z: 374 (M+,
0.1), 356 (0.1), 265 (0.2), 233 (100), 197 (25), 165 (22),
139 (16), 125 (19), 111 (11), 91 (2), 77 (23). HRMS-EI
(m/z): [M]+ calcd for C20H16Cl2OS, 374.0299; found,
374.0300.
4.4.7. 1,2-Bis-(3-cyano-phenyl)-2-phenylsulfanyl-ethanol 5f.
4.4.3. 2-Phenylsulfanyl-1,2-di-m-tolyl-ethanol 5b. Yield:
21
Yield: 50%. ½aꢁD ¼ þ13:8 (c 0.7, CH3Cl). HPLC (Daicel
21
18%. ½aꢁD ¼ þ57:7 (c 0.3, CH3Cl). HPLC (Daicel Chiralcel
Chiralcel OD-H, hexane/i-PrOH = 90:10, flow rate
OD-H, hexane/i-PrOH = 90:10, flow rate 0.25 mL/min) tR
1
1.00 mL/min) tR 39.0 and 52.0 min. H NMR (300 MHz,
1
14.6 and 18.3 min. H NMR (300 MHz, CDCl3, d): 7.36–
CDCl3, d): 7.51–7.46 (m, 3H), 7.31–7.22 (m, 8H), 4.98 (d,
J = 7.9 Hz, 1H), 4.24 (d, J = 7.9 Hz, 1H), 3.35 (br, 1H).
13C NMR (100.6 MHz, CDCl3, d): 141.4, 140.2, 133.0,
132.2, 132.0, 131.8, 131.2, 130.4, 129.3, 129.1, 128.5,
118.3, 112.5, 75.4, 62.9. IR (KBr): 3447, 3056, 2918,
2229, 1581, 1480, 744, 690 cmꢀ1. MS m/z: 356 (M+, 0.1),
271 (0.8), 247 (0.6), 224 (62), 190 (40), 146 (22), 132 (40),
104 (57), 91 (5), 77 (100). HRMS-EI (m/z): [M]+ calcd
for C22H16N2OS, 356.0983; found, 356.0989.
7.19 (m, 6H), 7.08–6.83 (m, 7H), 4.91 (d, J = 8.2 Hz,
1H), 4.34 (d, J = 8.2 Hz, 1H), 3.23 (br, 1H), 2.24 (s, 3H),
2.22 (s, 3H). 13C NMR (75.4 MHz, CDCl3, d): 140.3,
139.1, 137.6, 134.4, 132.2, 129.2, 128.8, 128.4, 138.3,
128.0, 127.7, 127.4, 127.3, 125.6, 124.0, 63.6, 21.3. IR
(KBr): 3438, 3052, 3023, 2918, 1605, 1479, 742, 693 cmꢀ1
.
MS m/z: 334 (M+, 0.01), 316 (0.8), 225 (0.7), 214 (100),
179 (6), 165 (12), 135 (5), 119 (23), 105 (44), 91 (31), 77
(13). HRMS-EI (m/z): [M]+ calcd for C22H22OS,
334.1391; found, 334.1397.
4.4.8. 1,2-Bis-(4-cyano-phenyl)-2-phenylsulfanyl-ethanol 5g.
21
Yield: 40%. ½aꢁD ¼ þ5:0 (c 0.6, CH3Cl). HPLC (Daicel
4.4.4. 2-Phenylsulfanyl-1,2-di-p-tolyl-ethanol 5c. Yield:
21
Chiralcel OD-H, hexane/i-PrOH = 90:10, flow rate
76%. ½aꢁD ¼ þ35:9 (c 1.1, CH3Cl). HPLC (Daicel Chiralcel
1
0.75 mL/min) tR 43.8 and 72.0 min. H NMR (300 MHz,
OD-H, hexane/i-PrOH = 90:10, flow rate 0.25 mL/min) tR
1
CDCl3, d): 7.63–6.69 (m, 13H), 5.00 (d, J = 8.1 Hz, 1H),
4.29 (d, J = 8.1 Hz, 1H), 3.38 (br, 1H). 13C NMR
(75.4 MHz, CDCl3, d): 145.1, 144.0, 133.1, 132.8, 132.2,
132.1, 132.0, 131.9, 129.9, 129.4, 129.3, 128.5, 128.4,
128.3, 127.5, 127.0, 118.3, 112.1, 111.6, 74.5, 63.4. IR
15.6 and 22.3 min. H NMR (300 MHz, CDCl3, d): 7.30–
7.20 (m, 6H), 7.06 (d, J = 8.1 Hz, 2H), 7.00 (d,
J = 8.3 Hz, 2H), 6.8 (s, 3H), 4.92 (d, J = 8.5 Hz, 1H),
4.36 (d, J = 8.5 Hz, 1H), 3.21 (br, 1H), 2.26 (s, 3H), 2.25
(s, 3H). 13C NMR (100.6 MHz, CDCl3, d): 137.5, 137.3,
136.8, 136.2, 134.4, 132.2, 128.8, 128.6, 128.5, 128.4,
128.3, 127.2, 126.8, 63.4, 21.1. IR (KBr): 3502, 3052,
3023, 2918, 1511, 1438, 1173, 813, 689 cmꢀ1. MS m/z:
334 (M+, 0.05), 316 (0.9), 233 (1), 213 (100), 195 (8), 165
(14), 135 (6), 128 (23), 105 (58), 91 (42), 77 (22). HRMS-
EI (m/z): [M]+ calcd for C22H22OS, 334.1391; found,
334.1385.
(KBr): 3447, 3061, 2922, 2227, 1606, 1064, 472, 690 cmꢀ1
.
MS m/z: 356 (M+, 0.03), 338 (0.6), 246 (0.6), 224 (100),
190 (13), 146 (6), 130 (21), 116 (23), 89 (6), 77 (18).
HRMS-EI (m/z): [M]+ calcd for C22H16N2OS, 356.0983;
found, 356.0984.
4.4.9. 1,2-Bis-(3-nitro-phenyl)-2-phenylsulfanyl-ethanol 5h.
21
Yield: 53%. ½aꢁD ¼ ꢀ6:8 (c 0.7, CH3Cl). HPLC (Daicel
4.4.5. 1,2-Bis-(3-chloro-phenyl)-2-phenylsulfanyl-ethanol 5d.
Chiralcel OD-H, hexane/i-PrOH = 90:10, flow rate
21
1
Yield: 96%. ½aꢁD ¼ þ43:6 (c 1.5, CH3Cl). HPLC (Daicel
1.00 mL/min) tR 36.0 and 46.0 min. H NMR (300 MHz,
Chiralcel OD-H, hexane/i-PrOH = 90:10, flow rate
CDCl3, d): 8.20–8.03 (m, 3H), 7.9 (s, 1H), 7.42–7.25 (m,
9H), 5.12 (d, J = 7.8 Hz, 1H), 4.43 (d, J = 7.8 Hz, 1H).
13C NMR (100.6 MHz, CDCl3, d): 148.1, 142.0, 140.6,
134.5, 133.2, 131.9, 129.3, 129.1, 128.6, 123.4, 123.2,
122.7, 121.8, 75.3, 62.7. IR (KBr): 3465, 3070, 1526,
1348, 737, 688 cmꢀ1. MS m/z: 396 (M+, 0.1), 378 (0.2),
287 (0.3), 244 (100), 228 (62), 198 (42), 165 (20), 121 (12),
1
0.25 mL/min) tR 20.1 and 26.3 min. H NMR (400 MHz,
CDCl3, d): 7.24–7.05 (m, 11H), 6.95 (d, J = 7.3 Hz, 1H),
6.88 (d, J = 7.3 Hz, 1H), 4.88 (d, J = 8.2 Hz, 1H), 4.24
(d, J = 8.3 Hz, 1H). 13C NMR (100.6 MHz, CDCl3, d):
142.1, 140.9, 134.1, 133.1, 132.8, 129.4, 129.2, 129.0,
128.6, 128.1, 128.0, 127.7, 126.8, 126.7, 125.1, 75.9, 63.3.

Y.-J. Chen, C. Chen / Tetrahedron: Asymmetry 18 (2007) 1313–1319
1319
110 (8), 89 (5), 77 (12). HRMS-EI (m/z): [M]+ calcd for
C20H16N2O5S, 396.0780; found, 396.0781.
2000, 11, 4441–4445; (e) Nakajima, M.; Saito, M.; Uemura,
M.; Hashimoto, S. Tetrahedron Lett. 2002, 43, 8827–8829.
5. (a) Wang, L.-S.; Hollis, T. K. Org. Lett. 2003, 5, 2543–2545;
(b) Tokuoka, E.; Kotani, S.; Matsunaga, H.; Ishizuka, T.;
Hashimoto, S.; Nakajima, M. Tetrahedron: Asymmetry 2005,
16, 2391–2392; (c) Roy, C. D.; Brown, H. C. Tetrahedron:
Asymmetry 2006, 17, 1931–1936.
6. (a) Schaus, S. E.; Jacobsen, E. N. Org. Lett. 2000, 2, 1001–
1004; (b) Zhu, C.; Yuan, F.; Gu, W.; Pan, Y. Chem. Commun.
2003, 692–693; (c) Belokon, Y. N.; Chusov, D.; Borkin, D.
A.; Yashkina, L. V.; Dmitriev, A. V.; Katayeva, D.; North,
M. Tetrahedron: Asymmetry 2006, 17, 2328–2333.
7. (a) Yamashita, H. Bull. Chem. Soc. Jpn. 1988, 61, 1213–1220;
(b) Iida, T.; Yamamoto, N.; Sasai, H.; Shibasaki, M. J. Am.
Chem. Soc. 1997, 119, 4783–4784; (c) Wu, M. H.; Jacobsen,
E. N. J. Org. Chem. 1998, 63, 5252–5254; (d) Wu, J.; Hou,
X.-L.; Dai, L.-X.; Xia, L.-J.; Tang, M.-H. Tetrahedron:
Asymmetry 1998, 9, 3431–3436.
4.5. 2-Benzenesulfonyl-1,2-diphenyl-ethanol 615
To a solution of 3c (62 mg, 0.20 mmol) in 5 mL CH2Cl2
was added mCPBA (ꢂ70%, 120 mg, 0.49 mmol) at 0 °C.
After stirring at room temperature for 15 h, the mixture
was diluted with CH2Cl2 and washed with water. The
organic phase was dried over anhydrous magnesium
sulfate. Following filtration and concentration, the residue
was purified by column chromatography using silica gel as
the stationary phase and ethyl acetate/hexane (2:8) as a
22
mobile phase to give product 6 (60 mg, 90%). ½aꢁD
¼
þ35:8 (c 0.8, CH3Cl). HPLC (Daicel Chiralcel OD-H,
hexane/i-PrOH = 70:30, flow rate 1.20 mL/min) tR 10.8
1
and 25.5 min. H NMR (400 MHz, CDCl3, d): 7.98–6.89
8. Jacobsen, E. N.; Kakiuchi, F.; Konsler, R. G.; Larrow, J. F.;
Tokunaga, M. Tetrahedron Lett. 1997, 38, 773–776.
(m, 15H), 5.77 (d, J = 9.6 Hz, 1H), 4.48 (d, J = 9.6 Hz,
1H). 13C NMR (100.6 MHz, CDCl3, d): 139.5, 137.6,
133.8, 130.8, 130.3, 128.9, 128.7, 128.5, 128.1, 127.3, 77.6,
73.9.
9. (a) Iida, T.; Yamamoto, N.; Matsunaga, S.; Woo, H.-G.;
Shibasaki, M. Angew. Chem., Int. Ed. 1998, 37, 2223–2226;
(b) Matsunaga, S.; Das, J.; Roels, J.; Vogl, E. M.; Yama-
moto, N.; Iida, T.; Yamaguchi, K.; Shibasaki, M. J. Am.
Chem. Soc. 2000, 122, 2252–2260.
10. (a) Sekine, A.; Ohshima, T.; Shibasaki, M. Tetrahedron 2002,
Acknowledgements
´
58, 75–82; (b) Carree, F.; Gil, R.; Collin, J. Tetrahedron Lett.
´
2004, 45, 7749–7751; (c) Carree, F.; Gil, R.; Collin, J. Org.
The authors thank Ms. L. M. Hsu, at the Instruments
Center, National Chung Hsing University, for her help
in obtaining HRMS, and the National Science Council of
the Republic of China, for financially supporting this
research under Contract NSC 94-2113-M-259-006.
Lett. 2005, 7, 1023–1026; (d) Azoulay, S.; Manabe, K.;
Kobayashi, S. Org. Lett. 2005, 7, 4593–4595; (e) Kureshy, R.
I.; Singh, S.; Khan, N. H.; Abdi, S. H. R.; Agrawal, S.;
Mayani, V. J.; Jasra, R. V. Tetrahedron Lett. 2006, 47, 5277–
5279.
11. (a) Chen, Y.-J.; Lin, R.-X.; Chen, C. Tetrahedron: Asymmetry
2004, 15, 3561–3571; (b) Lee, P.-T.; Chen, C. Tetrahedron:
Asymmetry 2005, 16, 2704–2710; (c) Lin, R.-X.; Chen, C. J.
Mol. Catal. A: Chem. 2006, 243, 89–98.
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