Synthesis of optically active β-aryloxy alcohols and β-arylthiol alcohols via asymmetric transfer hydrogenation reaction

Article abstract of DOI:10.2174/157017811799304197

A series of optically active β-aryloxy alcohols and β-arylthiol alcohols were synthesized directly by asymmetric transfer hydrogenation of the corresponding β-carbonyl ethers or β-carbonyl sulfides in excellent yields (up to 99%) and excellent enantiosele

Full text of DOI:10.2174/157017811799304197

Letters in Organic Chemistry, 2011, 8, 737-742
737
Synthesis of Optically Active ꢀ-Aryloxy Alcohols and ꢀ-Arylthiol Alcohols
via Asymmetric Transfer Hydrogenation Reaction
Zhou Xu*,a, Wei Yinb, Nan Wuc, Jingjing Shib, Ting Liua, Yu Wanb and Hui Wu*,b
aDepartment of Chemistry, Xuzhou Medical College, Xuzhou 221004, P.R. China
bCollege of Chemistry and Chemical Engineering, Xuzhou Normal University, 221116, P.R. China
cDepartment of Aviation Oil and Material, Xuzhou Airforce College, Xuzhou 221110, P. R. China
Received April 22, 2011: Revised August 04, 2011: Accepted August 04, 2011
Abstract: A series of optically active ꢀ-aryloxy alcohols and ꢀ-arylthiol alcohols were synthesized directly by asymmetric
transfer hydrogenation of the corresponding ꢀ-carbonyl ethers or ꢀ-carbonyl sulfides in excellent yields (up to 99%) and
excellent enantioselectivity (up to 100% ee) under mild reaction conditions.
Keywords: Asymmetric transfer hydrogenation, ꢀ-aryloxy alcohols, ꢀ-arylthiol alcohols, ꢀ-ketosulfide, ꢀ-ketoether.
INTRODUCTION
[4–10]. Chiral ꢀ-aryloxy alcohols and ꢀ-arylthiol alcohols
are important building blocks for many chiral compounds,
such as chiral oxiranes, aziridines, thiiranes, tetrahydrofurans
and ꢀ-hydroxy esters [11–17]. Few papers reported the
synthesis of these compounds by biological method and the
scope was limited [18, 19]. Herein, we report a highly
efficient synthesis of optical acitive ꢀ-aryloxy alcohols and
The asymmetric transfer hydrogenation (ATH) reaction
of prochiral ketones and imines is a pivotal reaction for the
synthesis of chiral secondary alcohols or amines which has
attracted much attention in recent years [1]. The easily
available hydrogen sources, mild reaction conditions and
simple experimental setup have made it an area of interest
NH2
Ph
Ph
Ph
Ph
Ph
Ph
OH
H2N
NHTs
HO
NHTs
N
OH
H
2
1
3
4
N
N
H
H
HO
HO
O
N
N
5
6
Fig. (1). Ligands chosen for the ATH reactions.
for both industrial and academic researchers [2, 3]. Many
catalysts have been developed for the hydrogenation process
of various ketones, providing the corresponding products
with high ee values, such as the reduction of acetophenones
bearing CN, N3, Cl, RNH, SO2NH and NO2 at the ꢁ-position
ꢀ-arylthiol alcohols with high enantiomeric purity via ATH
reaction. Most of the products are new compounds.
RESULTS AND DISCUSSION
Initially, 2-pehnoxy-1-phenylethanone was used as the
model substrate and the asymmetric catalytic activities of six
chiral amino alcohols (Fig. 1) were examined for the ATH
reaction. The results are summumrized in Table 1.
*Address correspondence to these authors at the Department of Chemistry,
Xuzhou Medical College, Xuzhou 221004, P.R. China; Tel: +86-516-
83403163; Fax: 0516-83500065; E-mail: xuzhou@xzmc.edu.cn
College of Chemistry and Chemical Engineering, Xuzhou Normal
University, 221116, P.R. China; Tel: +86-516-83500349; Fax: 83500065;
E-mail: wuhui72@xznu.edu.cn
As expected, (1R, 2R)-Ts-DPEN, the well known ligand,
gave the best result (Table 1, entries 1-6). The product was
1875-6255/11 $58.00+.00
© 2011 Bentham Science Publishers

738 Letters in Organic Chemistry, 2011, Vol. 8, No. 10
Xu et al.
Table 1. Screening of Optimum Conditions for ATH Reactiona
OH
O
OPh
[Ru(cymene)Cl2]2/Ligand
solvent/r.t
OPh
Entrya
Ligand
Solvent
Yield (%)
ee (%)e
1
2
1
2
3
4
5
6
1
1
1
1
1
1
1
1
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
DMF
96
93
-
No reduction
3b
76
trace
trace
trace
92
86
-
4b
5b
-
6b
-
7
89
91
96
88
85
89
88
91
8
CH3OH
THF
95
9
97
10
11
12
13[c]
14[d]
DCM
99
Et2O
99
Toluene
THF
95
96
THF
94
aReactions were performed at room temperature for 24 h, using 0.5 mmol substrate, 1.0 ml solvent, 0.25 mol% ligand, 3.8 mg [Ru(cymene)Cl2]2 and 0.2 ml HCOOH/Et3N (5 : 2).
bThe reaction was carried out in iPrOH/KOH system.
cThe amount of the ligand is 0.50 mol%.
dThe amount of the ligand is 0.125 mol%.
eThe enantiomeric excess was determined by chiral HPLC analysis of the corresponding products on a Chiralpak AD-H column. The absolute configuration is S according to the
literature (see ref. [17]).
obtained with 96% yield and 93% ee in acetonitrile.
Encouraged by the excellent result, we attempted to identify
the optimal conditions for the ATH reaction using (1R, 2R)-
Ts-DPEN as the chiral ligand. Solvent effect was firstly
examined. Among the solvents explored, the best result was
obtained when THF was used as the solvent (Table 1, entry
9). Then, the influence of the substrate/catalyst ratio on the
ATH was investigated. Decreasing or increasing the amount
of the ligand had no benefit on the reaction. Thus, the
optimal conditions for the ATH reaction of 2-pehnoxy-1-
phenylethanone required 0.25 mol% ligand and formic acid as
the hydrogen donor in THF at room temperature.
in Table 3. As can be seen from the table, most of the
reactions were completed within 24 h with excellent yields
(88%–99%) and excellent enantioselectivities (79% to 100%
ee).
In summary, we have presented the first asymmetric
reduction of ꢀ-carbonyl ethers or ꢀ-carbonyl sulfides using
chiral [RuCl2(p-cymene)]-TsDPEN as the catalyst, and
HCOOH/Et3N as the hydrogen source. A series of optically
active ꢀ-aryloxy alcohols and ꢀ-arylthiol alcohols were
synthesized with good to excellent yields (up to 99% yield)
and excellent enantioselectivity (up to 100% ee).
With the optimized reaction conditions in hand, the scope
of the reaction was investigated and the results are
summarized in Table 2. Various substrates (1a-1j) were
reacted in the presence of chiral catalyst Ru(p-
cymene)TsDPEN using the HCOOH/Et3N = 5 : 2 as
hydrogen source in THF at ambient temperature. Regardless
of the types of substituents on the R1 ring or R2 ring, be it
electron-withdrawing or electron-donating, the reactions
proceeded well to afford highly enantioselective adducts (up
to 99%). When R1 is heteroatomic ring, the product can aslo
obtained with high ee (up to 98%, Table 2, entry 10).
EXPERIMENTAL
All manipulations were carried out under an argon in
degassed solvents. The reactions were monitored by TLC.
NMR spectra were measured in CDCl3 on a Varian-Inova-
400 NMR spectrometer with TMS as an internal reference.
Optical rotations were measured with a HORIBA SEPA-200
high-sensitivity polarimeter. The enantiomeric excess (ee)
was determined by using a Chiralpak AD-H column or a
Chiralpak IA column with hexane–iPrOH as the solvent at a
flow rate of 1 mL/min (unless otherwise stated), and UV
detection at 254 nm (unless otherwise stated). MS spectra
were recorded under EI conditions. IR spectra were recorded
on a Varian FT-1000 IR spectrophotometer using KBr disks
in the 4000–400 cm–1 region.
When the substrates were broaden to ꢀ-ketosulfides, the
reaction can hardly react at the same conditions. However,
the reaction can proceed smoothly with the reaction
temperature enhancing to 40 oC. The results are summarized

Synthesis of Optically Active ꢀ-Aryloxy Alcohols
Letters in Organic Chemistry, 2011, Vol. 8, No. 10
739
Table 2. Scopes of Reactiona
OH
O
[Ru(cymene)Cl2]2
O
O
R1
R2
R1
R2
(1R,2R)-Ts-DPEN
THF, rt, 24h
1a-1j
2a-2j
Entry
R1
R2
Product
Yield (%)b
Ee (%)c
1
2
C6H5
p-MeC6H4
p-MeOC6H4
p-MeC6H4
C6H5
C6H5
C6H5
C6H5
2a
2b
2c
2d
2e
2f
97
86
89
89
92
94
90
87
90
86
96
98
97
99
99
93
93
98
92
98
3
4
2-Naphthyl
5
p-C6H4CHO
2-Naphthyl
C6H5
6
p-ClC6H4
p-ClC6H4
p-MeOC6H4
C6H5
7
2g
2h
2i
8
2-Naphthyl
2-Naphthyl
C6H5
9
10
thiophene
2k
aReactions were performed at room temperature for 24 h, using 0.5 mmol substrate, 1.0 ml THF, 0.25 mol% (1R, 2R)-Ts-DPEN , 3.8 mg [Ru(cymene)Cl2]2 and 0.2 ml HCOOH/Et3N
(5 : 2).
bIsolated yield.
cDetermined by chiral HPLC analysis using a Chiralpak AD–H or IA column. Absolute configuration probably S based on comparison of the elution order of HPLC analysis and/or
the sign of the specific rotation value with those of the analogues reported. see ref. [17, 20-22].
Table 3. Scopes of the ATH Reaction for Ketosulfidesa
OH
O
[Ru(cymene)Cl2]2
S
S
R1
R2
R1
R2
(1S, 2S)-Ts-DPEN
THF,40oC, 24h
4a-4g
3a-3g
Entry
R1
R2
Product
Yield (%)b
Ee (%)c
1
2
3
4
5
6
7
C6H5
C6H5
C6H5
4a
4b
4c
4d
4e
4f
90
91
91
99
92
90
88
100
79
95
95
91
98
95
p-MeOC6H4
p-MeC6H4
p-MeC6H4
p-ClC6H4
p-MeC6H4
C6H5
C6H5
p-ClC6H4
p-MeC6H4
p-MeC6H4
p-MeOC6H4
4g
aReactions were performed at 40 oC for 24 h, using 0.5 mmol substrate, 1.0 ml THF, 0.25 mol% (1S, 2S)-Ts-DPEN , 3.8 mg [Ru(cymene)Cl2]2 and 0.2 ml HCOOH/Et3N (5 : 2).
bIsolated yield.
cDetermined by chiral HPLC analysis using a Chiralpak AD–H or IA column. Absolute configuration except for 4a is unknown, but probably S based on comparison of the elution
order of HPLC analysis and/or the sign of the specific rotation value with those of the p-tolyl- analogues reported. See ref. [11, 12 and 22].
Gereral Experimental Procedure
6)] to give the pure product. For ketosulfieds 3a–3g, the
reaction conditions were identical, except that the ligand was
(1S,2S)-Ts-DPEN and the reaction temperature was 40 oC.
A suspension of [RuCl2(p-cymene)]2 (3.8 mg) and (1R,
2R)-Ts-DPEN ligand (4.5 mg) in THF (1.0 mL) was stirred
at r.t. for 2 h. HCOOH/Et3N (5 : 2; 0.2 mL) and substrate
(0.5 mmol) were added, and the mixture was stirred for 24 h.
The product was then extracted with EtOAc (3 ꢀ 10 mL),
and the combined extracts were dried (Na2SO4) and
concentrated under vacuum. The residue was purified by
flash column chromatography [silica gel H, EtOAc–PE (1 :
Spectral Data
(S)-2-phenoxy-1-phenylethanol (2a)
25
o
[ꢁ]D = + 35.4 (c 0.97, CH2Cl2); 97% yield. 96% ee
determined by HPLC analysis (Chiralcel AD-H column, IPA

740 Letters in Organic Chemistry, 2011, Vol. 8, No. 10
Xu et al.
: hexane = 15 : 85). Retention time: tminor = 8.65 min, tmajor
=11.25 min. 1H NMR (400 MHz, CDCl3) ꢀ 7.47 (d, J = 7.6
Hz, 2H), 7.40 (t, J = 7.2 Hz, 2H), 7.36–7.28 (m, 3H), 6.98 (t,
J = 7.0 Hz, 1H), 6.93 (d, J = 8.0 Hz, 2H), 5.14 (d, J = 8.8 Hz,
1H), 4.12 (dd, J1 = 2.8 Hz, J2 = 9.6 Hz, 1H), 4.01 (t, J = 9.2
Hz, 1H), 2.78 (d, J = 2.4 Hz, 1H); 13C NMR (100 MHz,
CDCl3) ꢀ 139.6, 129.6, 128.6, 128.2, 126.3, 121.3, 114.7,
96.4, 73.32, 72.63; IR (cm–1) : 3219, 1598, 1585, 1498,
1456, 1243; MS [ESI] m/z for [C14H14O2 +H]+ found
(exceped): 215.0928 (215.1027).
Hz, 1H), 2.76 (s, 1H); 13C NMR (100 MHz, CDCl3) ꢀ 158.1,
139.7, 133.8, 128.7, 128.6, 128.2, 126.3 114.8, 73.5, 72.6,
65.0; IR (cm–1) : 3254, 2923, 2865, 1610, 1512, 1454, 1249;
MS [ESI] m/z for [C15H16O3+Na]+ found (exceped):
267.0999 (267.0997).
(S)-1-(4-chlorophenyl)-2-(naphthalen-2-ylox y)ethanol (2f)
25
o
[ꢀ]D = + 21.9 (c 0.46, CH2Cl2); 94% yield. 93% ee
determined by HPLC analysis (Chiralcel AD-H column, IPA
: hexane = 15 : 85). Retention time: tminor = 11.65 min, tmajor
1
=23.08 min. H NMR (400 MHz, CDCl3) ꢁ: 7.79–7.76 (m,
(S)-2-phenoxy-1-p-tolylethanol (2b)
2H), 7.69 (d, J = 8.0 Hz, 1H), 7.46–7.34 (m, 6H), 7.20–7.17
(m, 1H), 7.12 (d, J = 2.0 Hz, 1H), 5.30 (td, J1 = 2.8 Hz, J2 =
9.2 Hz, 1H), 4.21 (dd, J1 = 3.2 Hz, J2 = 9.6 Hz, 1H), 4.10 (t, J
= 9.2 Hz, 1H), 2.83 (d, J = 2.4 Hz, 1H); 13C NMR (100
MHz, CDCl3) ꢀ 155.2, 138.2, 134.4, 134.0, 129.7, 129.3,
128.8, 127.7, 127.6, 126.8, 126.6, 124.0, 118.5, 107.2, 73.2,
72.0;
IR (cm–1) : 3559, 1596, 1576, 1487, 1217; MS [ESI] m/z
for [C18H15ClO2+Na]+ found (exceped): 321.0623
(321.0658).
25
o
[ꢀ]D = + 38.6 (c 0.96, CH2Cl2); 86% yield. 98% ee
determined by HPLC analysis (Chiralcel AD-H column, IPA
: hexane = 15 : 85). Retention time: tminor = 9.5 min, tmajor
=
13.8 min. 1H NMR (400 MHz, CDCl3) ꢀ 7.35 (d, J = 7.6 Hz,
2H), 7.29 (t, J = 8.0 Hz, 2H), 7.21 (d, J = 8.0 Hz, 2H), 6.98
(t, J = 7.4 Hz, 1H), 6.92 (d, J = 8.0 Hz, 2H), 5.10 (d, J = 8.8
Hz, 1H), 4.10 (dd, J1 = 3.0 Hz, J2 = 9.4 Hz, 1H), 4.00 (t, J =
8.8 Hz, 1H), 2.73 (d, J = 2.0 Hz, 1H), 2.37 (s, 3H); 13C NMR
(100 MHz, CDCl3) ꢀ 158.4, 138.0, 136.7, 129.6, 129.3,
126.2, 121.3, 114.7, 73.3, 72.5, 21.2; IR (cm–1) : 3197, 2918,
1599, 1586, 1499, 1459, 1242; MS [ESI] m/z for [C15H16O2
+Na]+ found (exceped): 251.1038 (251.1048).
(S)-1-(4-chlorophenyl)-2-phenoxyethanol (2g)
25
o
[ꢀ]D = + 35.8 (c 0.74, CH2Cl2); 90% yield. 93% ee
determined by HPLC analysis (Chiralcel AD-H column, IPA
: hexane = 15 : 85). Retention time: tminor = 9.07 min, tmajor
(S)-1-(4-methoxyphenyl)-2-phenoxyethanol (2c)
25
o
[ꢀ]D = + 36.1 (c 0.28, CH2Cl2); 89% yield. 97% ee
determined by HPLC analysis (Chiralcel AD-H column, IPA
: hexane = 15 : 85). Retention time: tminor = 13.8 min, tmajor
1
=13.86 min. H NMR (400 MHz, CDCl3) ꢁ 7.42–7.36 (m,
4H), 7.30 (t, J = 7.8 Hz, 2H), 6.99 (t, J = 3.4 Hz, 1H), 6.91
(d, J = 8.4 Hz, 2H), 5.11 (d, J = 8.0 Hz, 1H), 4.09 (dd, J1 =
3.4 Hz, J2 = 9.4 Hz, 1H), 3.97 (t, J = 9.2 Hz, 1H), 2.80 (d, J =
2.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) ꢀ 158.3, 138.2,
133.9, 129.6, 128.8, 127.9, 121.5, 114.6, 73.1, 72.0; IR (cm–
1) : 3244, 1601, 1588, 1499, 1243; MS [ESI] m/z for
[C14H13O2Cl+Na]+ found (exceped): 271.0493 (271.0502).
1
=19.3 min. H NMR (400 MHz, CDCl3) ꢀ 7.38 (d, J = 8.8
Hz, 2H), 7.31–7.26 (m, 2H), 6.97 (t, J = 7.4 Hz, 1H), 6.95 (d,
J = 8.0 Hz, 4H), 5.08 (td, J1 = 2.0 Hz, J2 = 9.2 Hz, 1H), 4.07
(dd, J1 = 3.2 Hz, J2 = 9.6 Hz, 1H), 4.00 (t, J = 9.2 Hz, 1H),
3.82 (s, 3H), 2.75 (d, J = 2.0 Hz, 1H); 13C NMR (100 MHz,
CDCl3) ꢀ 130.8, 126.7, 126.5, 125.8, 122.9, 117.7, 113.0,
112.2, 72.4, 71.2, 54.4; IR (cm–1) : 3503, 2943, 2834, 1600,
1584, 1510, 1246, 1170; MS [ESI] m/z for [C15H16O3+Na]+
found (exceped): 267.0984 (267.0997).
(S)-1-(4-methoxyphenyl)-2-(naphthalen-2-yloxy)ethanol
(2h)
25
o
[ꢀ]D = + 31.8 (c 0.50, CH2Cl2); 87% yield. 98% ee
determined by HPLC analysis (Chiralcel AD-H column, IPA
: hexane = 15 : 85). Retention time: tminor = 16.91 min, tmajor
(S)-2-(naphthalen-2-yloxy)-1-p-tolylethanol (2d)
25
o
[ꢀ]D = + 31.9 (c 0.48, CH2Cl2); 89% yield. 99% ee
determined by HPLC analysis (Chiralcel AD-H column, IPA
: hexane = 15 : 85). Retention time: tminor = 11.81 min, tmajor
1
=28.15 min. H NMR (400 MHz，CDCl3) ꢁ: 7.78–7.75 (m,
2H), 7.69 (d, J = 8.4 Hz, 1H), 7.43 (d, J = 8.4 Hz, 3H), 7.35
(t, J = 6.8 Hz, 1H), 7.20 (dd, J1 = 3.2 Hz, J2 = 8.8 Hz, 1H),
7.13 (d, J = 2.0 Hz, 1H), 6.95 (d, J = 8.8 Hz, 2H), 5.16 (td, J1
= 2.4 Hz, J2 = 9.2 Hz, 1H), 4.19 (dd, J1 = 3.2 Hz, J2 = 9.6 Hz,
1H), 4.13 (t, J = 9.2 Hz, 1H), 3.84 (s, 3H), 2.76 (d, J = 2.4
Hz, 1H); 13C NMR (100 MHz, CDCl3) ꢀ 159.6, 156.4, 134.5,
131.8, 129.6, 129.2, 127.7, 127.6, 126.8, 126.4, 123.9, 118.7,
114.1, 107.1, 73.4, 72.2 55.4; IR (cm–1) : 3327, 2931, 1628,
1510, 1246, 1218, 1179; MS [ESI] m/z for [C19H18O3+Na]+
found (exceped): 317.1140 (317.1157).
1
= 21.10 min. H NMR (400 MHz, CDCl3) ꢀ 7.78–7.75 (m,
2H), 7.68 (d, J = 8.0 Hz, 1H), 7.45–7.33 (m, 4H), 7.24–7.19
(m, 3H), 7.12 (d, J = 2.0 Hz, 1H), 5.18 (d, J = 8.8 Hz, 1H),
4.21 (dd, J1 = 3.2 Hz, J2 = 9.6 Hz, 1H), 2.76 (d, J = 2.4 Hz,
1H), 2.38 (s, 3H); 13C NMR (100 MHz, CDCl3) ꢀ 156.4,
138.1, 136.7, 134.5, 129.6, 129.3, 127.7, 126.8, 126.5, 126.3,
123.9, 118.7, 113.2, 107.1, 73.4, 72.5, 21.2; IR (cm–1) :
3327, 2931, 1628, 1510, 1454, 1246, 1218, 1179; MS [ESI]
m/z for [C19H18O2 +Na]+ found (exceped): 301.1193
(301.1204).
(S)-2-(naphthalen-2-yloxy)-1-phenylethanol (2i)
[ꢀ]D = + 26.1 o (c 0.93, CH2Cl2); 90% yield. 92% ee
25
(S)-2-(4-(hydroxymethyl)phenoxy)-1-phenylethanol (2e)
determined by HPLC analysis (Chiralcel AD-H column, IPA
: hexane = 15 : 85). Retention time: tminor = 11.31 min, tmajor
=16.21 min. H NMR (400 MHz, CDCl3) ꢁ 7.79–7.76 (m,
2H), 7.69 (d, J = 8.0 Hz, 1H), 7.51 (d, J = 7.6 Hz, 2H), 7.45–
7.41 (m, 3H), 7.38–7.33 (m, 2H), 7.22–7.19 (m, 1H), 7.13
(d, J = 2.4 Hz, 1H), 5.21 (td, J1 = 2.4 Hz, J2 = 9.2 Hz, 1H),
4.24 (dd, J1 = 2.8 Hz, J2 = 9.2 Hz, 1H), 4.14 (t, J = 9.2 Hz,
1H), 2.81 (d, J = 2.4 Hz, 1H); 13C NMR (100 MHz, CDCl3)
[ꢀ]D = + 17.6 o (c 0.46, CH2Cl2);; 92% yield. 99% ee
25
determined by HPLC analysis (Chiralcel AD-H column, IPA
1
: hexane = 15 : 85). Retention time: tminor = 25.93 min, tmajor
1
=28.70 min. H NMR (400 MHz, CDCl3) ꢀ 7.46 (d, J = 6.8
Hz, 2H), 7.40 (t, J = 7.2 Hz, 2H), 7.36–7.28 (m, 3H), 6.91 (d,
J = 8.8 Hz, 2H), 5.15 (dd, J1 = 3.2 Hz, J2 = 8.8 Hz, 1H), 4.63
(s, 2H), 4.1 (dd, J1 = 3.2 Hz, J2 = 9.6 Hz, 1H), 4.03 (t, J = 9.2

Synthesis of Optically Active ꢀ-Aryloxy Alcohols
Letters in Organic Chemistry, 2011, Vol. 8, No. 10
741
ꢀ 155.3, 138.6, 133.4, 128.6, 127.6, 127.3, 126.7, 125.8,
125.5, 125.3, 122.9, 117.6, 106.0, 72.4, 71.6, 57.2; IR (cm–1)
: 3229, 1630, 1601, 1456, 1258, 1218, 1183; MS [ESI] m/z
for [C18H16O2 +Na]+ found (exceped): 287.1027 (287.1048).
hexane = 3 : 97). Retention time: tmajor = 17.71 min, tmajor
1
=18.75 min. H NMR (400 MHz, CDCl3) ꢀ 7.43－7.41 (m,
2H), 7.33－7.29 (m, 2H), 7.24 (s, 2H), 7.16 (d, J = 7.6 Hz,
3H), 4.71 (dd, J1 = 3.6 Hz, J2 = 9.2 Hz, 1H), 3.31 (dd, J1 =
3.6 Hz, J2 = 13.6 Hz, 1H), 3.10 (dd, J1 = 9.6 Hz, J2 = 14.0 Hz,
1H), 2.76 (s, 1H), 2.34 (s, 3H); 13C NMR (100 MHz, CDCl3)
ꢀ 134.0, 132.5, 129.8, 124.9, 124.0, 123.9, 121.5, 120.6,
66.4, 38.7, 15.9; IR (cm–1) : 3396, 2921, 1583, 1514, 1480,
1439, 1179, 1058, 1025, 739; MS [ESI] m/z for
[C15H16OS+Na]+ found (exceped): 283.0983 (267.0820).
(S)-2-phenoxy-1-(thiophen-2-yl)ethanol (2j)
25
o
[ꢁ]D = － 1.98 (c 0.66, acetone); 86% yield. 98% ee
determined by HPLC analysis (Chiralcel AD-H column, IPA
: hexane = 10 : 90). Retention time: tminor = 11.72 min, tmajor
1
= 19.22 min. H NMR (400 MHz, CDCl3) ꢀ 7.30 (t, J = 8.0
Hz, 3H), 7.10 (d, J = 3.2 Hz, 1H), 7.04–7.94 (m, 4H), 5.38
(dd, J1 = 3.2 Hz, J2 = 8.0 Hz, 1H), 4.21 (dd, J1 = 3.6 Hz, J2 =
9.6 Hz, 1H), 4.14 (t, J = 8.8 Hz, 1H), 2.86 (s, 1H); 13C NMR
(100 MHz, CDCl3) ꢀ 158.1, 143.1, 129.6, 126.8, 125.3,
124.7, 121.5, 114.7, 72.9, 68.9; IR (cm–1) : 3496, 1599,
1498, 1243; MS [ESI] m/z for [C12H12O2 S+Na]+ found
(exceped): 243.0432 (243.0456).
(S)-1-(4-chlorophenyl)-2-(phenylthio)ethanol (4e)
[ꢁ]D = －10.83 o (c 2.16, acetone); 92% yield. 91% ee
25
determined by HPLC analysis (Chiralcel IA column, IPA :
hexane = 3 : 97). Retention time: tmajor = 28.47 min, tminor
=
31.67 min. 1H NMR (400 MHz, CDCl3) ꢀ 7.47(d, J = 1.6 Hz,
1H), 7.46(d, J = 2.0 Hz, 1H), 7.43 (d, J = 1.2 Hz, 1H), 7.41
(t, J = 1.2 Hz, 1H), 7.34－7.30 (m, 2H), 7.25－7.22 (m, 3H),
4.67 (dd, J1 = 3.6 Hz, J2 = 9.2 Hz, 1H), 3.29 (dd, J1 = 3.2 Hz,
J2 = 13.8, 1H), 3.04 (dd, J1 = 9.6 Hz, J2 = 14.0 Hz, 1H), 2.88
(s, 1H); 13C NMR (100 MHz, CDCl3) ꢀ 135.9, 129.2, 126.4,
125.3, 124.0, 122.3, 121.8, 116.5, 65.7, 38.9; IR (cm–1) :
3395, 1585, 1481, 1403, 1189, 1070, 1010, 740; MS [ESI]
m/z for [C14H13OS+Na]+ found (exceped): 287.0294
(287.0273).
(S)-1-phenyl-2-(phenylthio)ethanol (4a)
25
o
[ꢁ]D = － 8.69 (c 2.14, acetone); 93% yield. 100% ee
determined by HPLC analysis (Chiralcel IA column, IPA :
hexane = 3 : 97). Retention time: tmajor = 19.54 min, tminor
1
=20.61 min. H NMR (400 MHz, CDCl3) ꢀ 7.44－7.41 (m,
2H), 7.36－7.29 (m, 7H), 7.24－7.22 (m, 1H), 4.73 (dd, J1 =
3.2 Hz, J2 = 9.2 Hz, 1H), 3.33 (dd, J1 = 3.6 Hz, J2 = 13.8 Hz,
1H), 3.10 (dd, J1 = 9.6 Hz, J2 = 14.0 Hz, 1H), 2.83 (s, 1H);
(S)-2-(p-tolylthio)-1-(4-chlorophenyl)ethanol (4f)
13C NMR (100 MHz, CDCl3) ꢀ 136.9, 129.5, 125.0,
123.9, 123.3, 122.8, 121.6, 120.6, 66.4, 38.9; IR (cm–1) :
3405, 1583, 1480, 1195, 1055; MS [ESI] m/z for
[C14H14OS+Na]+ found (exceped): 253.0681 (253.0663).
[ꢁ]D25 = － 107.06 o (c 0.17, acetone); 90% yield. 98% ee
determined by HPLC analysis (Chiralcel IA column, IPA :
hexane = 3 : 97). Retention time: tmajor = 5.19 min, tminor
=
6.18 min. 1H NMR (400 MHz, CDCl3) ꢀ 7.45 (d, J = 8.0 Hz,
2H), 7.33 (d, J = 8.0 Hz, 2H), 7.21 (d, J =8.0 Hz, 2H), 7.14
(d, J = 8.0 Hz, 2H), 4.62 (dd, J1 = 3.4 Hz, J2 = 9.4 Hz, 1H),
3.23 (dd, J1 = 3.6 Hz, J2 = 14.0 Hz, 1H), 2.96 (dd, J1 = 9.6
Hz, J2 = 14.0 Hz, 1H), 2.35 (s, 3H); 13C NMR (100 MHz,
CDCl3) ꢀ 140.6, 137.4, 133.6, 131.3, 130.5, 130.0, 128.6,
127.2, 70.8, 44.9, 21.1; IR (cm–1) : 3300, 1433, 1416, 1182,
1128, 1078, 753; MS [ESI] m/z for [C15H15OS-H]- found
(exceped): 278.0513 (278.0532).
(S)- 1-(4-methoxyphenyl)-2-(phenylthio)ethanol (4b)
25
o
[ꢁ]D = － 21.69 (c 0.83, acetone); 90% yield. 79% ee
determined by HPLC analysis (Chiralcel AD-H column, IPA
: hexane = 10 : 90). Retention time: tminor = 16.70 min, tmajor
=
1
15.10 min. H NMR (400 MHz, CDCl3) ꢀ 7.41 (d, J = 7.2
Hz, 2H), 7.33 7.21 (m, 5H), 6.88 (d,
= 8.4 Hz, 2H), 4.68 (dd, J1 = 3.6 Hz, J2 = 9.4,
－
J
1H), 3.80 (s, 3H), 3.31 (dd, J1 = 3.6 Hz, J2 = 13.8 Hz, 1H),
3.10 (dd, J1 = 9.6 Hz, J2 = 14.0 Hz, 1H), 2.82 (s, 1H); 13C
NMR (100 MHz, CDCl3) ꢀ 154.1, 129.1, 125.0, 123.9,
121.9, 121.5, 112.7, 108.7, 66.1, 50.1, 38.7; IR (cm–1) :
3396, 2912, 1583, 1574, 1480, 1439, 1179, 1058; MS
(S)-2-(p-tolylthio)-1-(4-methoxyphenyl)ethanol (4g)
25
o
[ꢁ]D = － 52.60 (c 1.04, acetone); 88% yield. 95% ee
determined by HPLC analysis (Chiralcel IA column, IPA :
hexane = 3 : 97). Retention time: tmajor = 30.75 min, tminor
=
[ESI] m/z for [C15H16O2S+Na]+
ed): 283.0749 (283.0769).
found
(excep-
1
34.74 min. H NMR (400 MHz, CDCl3) ꢀ 7.34 (d, J = 8.0
Hz, 2H), 7.27 (s, 1H), 7.26 (d, J = 3.2 Hz, 1H), 7.13 (d, J =
8.0 Hz, 2H), 6.87 (d, J = 8.8 Hz, 2H), 4.63 (dd, J1 = 2.6 Hz,
J2 = 9.4 Hz, 1H), 3.80 (s, 3H), 3.24 (d, J = 9.6 Hz, 1H), 3.03
(dd, J1 = 9.6 Hz, J2 = 14.0 Hz, 1H), 2.86 (d, J = 14.8 Hz, 1H),
2.34 (s, 3H); 13C NMR (100 MHz, CDCl3) ꢀ 160.0, 137.8,
135.0, 131.7, 130.6, 127.8, 114.6, 77.8, 55.9, 45.4, 21.7;
(S)-2-(p-tolylthio)-1-p-tolylethanol (4c)
25
o
[ꢁ]D = － 50.20 (c 1.02, acetone); 91% yield. 95% ee
determined by HPLC analysis (Chiralcel IA column, IPA :
hexane = 3 : 97). Retention time: tmajor = 20.44 min, tminor
1
=21.81 min. H NMR (400 MHz, CDCl3) ꢀ 7.34 (d, J = 8.0
IR (cm–1) : 3457, 2835, 1586, 1513, 1248, 1091, 1033;
MS [ESI] m/z for [C16H18O2S-H]- found (exceped): 273.0982
(273.0949).
Hz, 2H), 7.23 (d, J = 8.0 Hz, 2H), 7.14 (t, J = 7.6 Hz, 4H),
4.65 (dd, J1 = 3.2 Hz, J2 = 9.6 Hz, 1H), 3.26 (d, J = 13.6 Hz,
1H), 3.06－3.00 (m, 1H), 2.84 (s, 1H), 2.34 (s, 6H); 13C
NMR (100 MHz, CDCl3) ꢀ 139.2, 137.7, 137.0, 131.0,
129.9, 129.2, 125.8, 71.3, 44.7, 21.1, 21.0; IR (cm–1) : 3418,
1514, 1493, 1056, 1018, 805; MS [ESI] m/z for [C16H17OS-
H]- found (exceped): 257.1003 (257.1000).
ACKNOWLEDGEMENTS
We are grateful to the grants from the Natural Science
Foundation of Higher Education Institutions of Jiangsu
Province, China (No. 10KJB150018) and (No.
(S)-2-(phenylthio)-1-p-tolylethanol (4d)
25
o
[ꢁ]D = － 8.90 (c 3.15, acetone); 99% yield. 95% ee
determined by HPLC analysis (Chiralcel IA column, IPA :

742 Letters in Organic Chemistry, 2011, Vol. 8, No. 10
Xu et al.
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10KJA430050) and the Special Presidential Foundation of
Xuzhou Medical College (2010KJZ24) for financial support.
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