Asymmetric borane reduction of prochiral ketones catalyzed by C3-symmetric sulfonamide

Article abstract of DOI:10.1016/j.tetasy.2008.03.012

A novel, recoverable, C₃-symmetric sulfonamide L-1 has been developed for the asymmetric borane reduction of prochiral ketones in refluxing THF. The optically active secondary alcohols were obtained in excellent enantiometric excesses (up to 97% ee) and good yields. The C₃-symmetric sulfonamide L-1 can be easily recovered and reused four times without any significant loss of catalytic activity.

Full text of DOI:10.1016/j.tetasy.2008.03.012

Available online at www.sciencedirect.com
Tetrahedron: Asymmetry 19 (2008) 816–821
Asymmetric borane reduction of prochiral ketones
catalyzed by C3-symmetric sulfonamide
Gao-Qiang Li,a Ze-Yi Yan,b Yan-Ning Niu,a Lu-Yong Wu,a Hai-Long Weia
and Yong-Min Lianga,*
aState Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, PR China
bLaboratory of Radiochemistry, School of Nuclear Science and Technology, Lanzhou University, Lanzhou 730000, PR China
Received 14 January 2008; accepted 5 March 2008
Available online 15 April 2008
Abstract—A novel, recoverable, C3-symmetric sulfonamide L-1 has been developed for the asymmetric borane reduction of prochiral
ketones in refluxing THF. The optically active secondary alcohols were obtained in excellent enantiometric excesses (up to 97% ee)
and good yields. The C3-symmetric sulfonamide L-1 can be easily recovered and reused four times without any significant loss of catalytic
activity.
Ó 2008 Elsevier Ltd. All rights reserved.
1. Introduction
enantioselectivities (up to 98% ee).6 Therefore, there is a
need to synthesize the versatile C3-symmetric ligands for
asymmetric reactions.
C3 symmetry is an interesting subject in synthetic chemis-
try, with a number of C3-symmetric chiral ligands and their
applications in asymmetric catalysis being reported.1 For
example, C3-symmetric tris(phospine) ligands have been
reported to act as efficient catalysts in the enantioselective
hydrogenation of various unsaturated substrates (up to
95% ee).2 Chan et al. have synthesized the C3-symmetric
oxazolinyl ligands, which catalyzed the addition of diethyl-
zinc to aromatic aldehydes to give secondary alcohols with
high enantiomeric excesses (up to 90%).3 Katsuki and co-
workers have employed tridentate tris(oxazoline) ligands
as chiral auxiliaries in copper-mediated asymmetric allylic
oxidation of cycloalkenes to give the corresponding prod-
ucts with moderate to high enantioselectivities (up to 93%
ee).4 Tang et al. also developed pseudo-C3-symmetric
trisoxazolines, and successfully applied them into the
copper-catalyzed indole alkylation (up to 93% ee), the
kinugasa reaction (up to 85% ee), and copper-catalyzed
Diels–Alder reaction (up to 82% ee).5 Very recently, Du
et al. synthesized a series of C3-symmetric tripodal tris
(b-hydroxyamide) ligands to the complete asymmetric
borane reduction of prochiral ketones with excellent
On the other hand, the separation and recycling of chiral
catalysts has attracted much attention.7 The enantioselec-
tive reduction of prochiral ketones to the corresponding
optically active secondary alcohols is still an important
methodology. One of the most popular methods using chi-
ral 1,3,2-oxazaborolidines as catalysts was firstly developed
by Itsuno et al.8 and further improved upon by Corey,
Bakshi, and Shibata, known as the CBS catalyst.9 Many
applications of this homogeneous catalysts have been
reported in the literature.10 However, the development of
efficient methods for recovering the catalysts remains a
challenging target. In the recent years, chiral sulfonamides
acting as robust catalysts for the reduction of ketones have
been reported.11 In our previous study, we have reported
an imidazolium-tagged sulfonamide catalyst L-2 for the
enantioselective reduction of ketones in refluxing toluene.12
Our ongoing interest is to explore and synthesize a new chi-
ral sulfonamide catalyst with a C3-symmetric structure.
Herein, we report the synthesis of a novel, recoverable
C3-symmetric sulfonamide L-1 and its application in the
enantioselective borane reduction of prochiral ketones.
Compared with the imidazolium-tagged sulfonamide L-2
and the C1-symmetric sulfonamide L-3, the present ligand
L-1 gives a better enantioselectivity (Fig. 1).
*
Corresponding author. Tel.: +86 931 891 2596; fax: +86 931 891 2582;
e-mail: liangym@lzu.edu.cn
0957-4166/$ - see front matter Ó 2008 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2008.03.012

G.-Q. Li et al. / Tetrahedron: Asymmetry 19 (2008) 816–821
817
and compared the catalytic activities and enantioselectivi-
ties of ligands L-2 and L-3. The results are summarized
in Table 1.
Ph
Ph
N
S
HO
O
O
After being extensively reviewed, we chose the reaction
media of toluene and THF to examine the solvent effects.
At room temperature, the reduction was completed within
10 h in THF and 16 h in toluene with moderate ee values
(entries 1 and 2). When the reaction temperature reached
50 °C, the ee values were 85% in THF and 76% in toluene
(entries 3 and 4), respectively. By increasing the tempera-
ture to reflux, the reaction was completed within 4 h and
90% ee was obtained. The results showed that THF is a
more effective solvent for the present reduction and the
level of enantiometric excess is sensitive to the reaction
temperature. Subsequently, the catalyst loading was inves-
tigated. It was observed that a decrease in the catalyst load-
ing from 10 to 5 mol % at reflux temperature resulted in a
slight decrease in the enantioselectivity and a slight loss of
yield (entries 5 and 6). By further reducing the amount of
catalyst to 3 mol %, a large decrease in the ee value was
seen (entry 7). As a compromise between catalyst loading
and the ee value, a ligand L-1 loading of 5 mol % provided
the optimum level of enantioselectivity, which is presum-
ably because the rate of the catalyzed reaction in the pres-
ence of 5 mol % catalyst is sufficiently faster than the non-
catalytic reduction with only BH3ꢀSMe2.13 We also exam-
ined the effects of ligands L-2 and L-3 on the reduction
of acetophenone, and lower enantiometric excesses were
obtained. It was important to note that only 82% ee and
73% ee were obtained respectively, although 15 mol % of
L-3 and L-2 was loaded (entries 8 and 11). These results
indicate that the structural effect of C3-symmetric sulfon-
amide L-1 increases the enantioselectivity of the catalyst
greatly.
O
Ph
O
O
OH
N
Ph
O
S
O
S
O
HO
N
O
L-1
Ph
Ph
O
BF4
N
O
O
N
C
S N
H3C
H2
Ph
OH
HO
Ph
SO2
N
L-2
L-3
Figure 1.
2. Results and discussion
The synthetic procedure for the C3-symmetric sulfonamide
L-1 and the C1-symmetric sulfonamide L-3 is shown in
Scheme 1. Imidazolium-tagged sulfonamide L-2 is pre-
pared according to our previous work.12 Compound 2
was directly grafted onto 1,1,1-tris(4-hydroxyphenyl)-
ethane and phenol in refluxing acetone in the presence of
K2CO3 and 18-crown-6 to give L-1 as a white solid in
94% yield and L-3 as a white solid in 96% yield,
respectively.
Under the optimized reaction conditions, the C3-symmetric
sulfonamide L-1 was applied to the asymmetric borane
reduction of a variety of aromatic ketones (Table 2).
Compared to the reaction of L-2, ligand L-1 provided good
scope and generality of substrates. High yields and enantio-
selectivities were obtained not only for the prochiral
ketones containing electron-withdrawing group (entries 2,
4–6) but also for those with a substitution at the ortho-
position (entries 10 and 13), unlike ligand L-2, of which
the enantioselectivity was highly dependent on steric
effects. Slightly decreasing ee values were observed for pro-
chiral ketones with electron-donating groups, and therefore
electron-withdrawing groups are relatively beneficial for
the enantioselectivity. We also extended the reaction to
the reduction of a-haloacetophenone under the same
conditions, which also gave the high yields and excellent
ee values (entries 11–13). This indicated that the reactivity
and enantioselectivity were not significantly affected by a
halogen atom. However, moderate enantioselectivity was
given for the reduction of cyclic aryl ketone and aryl ethyl
ketone, which was presumably due to electronic effects
(entries 15 and 16).
O
O
S N
C6H5OH
O
BrH2C
K2CO3/18-crown-6
acetone/reflux
2
Ph
HO
Ph
Ph
OH
Ph
SO2
K2CO3/18-crown-6
acetone/reflux
CH3C(C6H4OH)3
N
L-1
L-3
Scheme 1. The synthesis of C3-symmetric sulfonamide L-1 and C1-
symmetric sulfonamide L-3.
It is well known that the enantioselectivity of borane reduc-
tion is greatly affected by solvent, temperature, and the
amount of catalyst. In order to evaluate the above effects,
we investigated the reduction of acetophenone with the
C3-symmetric ligand L-1 under various reaction conditions
Meanwhile, it is worth noting that the C3-symmetric sulf-
onamide L-1 can be easily separated and recycled. After

818
G.-Q. Li et al. / Tetrahedron: Asymmetry 19 (2008) 816–821
Table 1. Enantioselective borane reduction of acetophenonea
Ligand
BH3 SMe2
OH
O
.
*
CH3
Ph
Ph
CH3
Solvent
Entry
Solvent
Ligand (mol %)
Temperature (°C)
Yieldb (%)
eec (%)
Configurationd
1
2
3
4
5
6
7
8
9e
10e
11e
THF
Toluene
THF
Toluene
THF
THF
THF
THF
THF
Toluene
Toluene
L-1 (10)
L-1 (10)
L-1 (10)
L-1 (10)
L-1 (10)
L-1 (5)
rt
rt
50
50
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
92
90
93
90
96
95
93
95
94
95
95
66
55
85
76
90
88
80
82
52
65
73
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
L-1 (3)
L-3 (15)
L-2 (10)
L-2 (10)
L-2 (15)
a Reaction was carried out on a 1.0 mmol scale in 5 mL of solvent, molar ratio of PhCOCH3/BH3ꢀSMe2 = 1.0:1.1.
b Isolated yield by column chromatography.
c Determined by HPLC analysis using a Daicel Chiralcel OJ column.
d The absolute configuration was determined by comparison with the literature.
e Obtained from the literature data.12
Table 2. Catalytic asymmetric reduction of ketonesa
O
OH
R2
L-1 5 mol%
THF/reflux
.
+
BH3 SMe2
R1
R2
R1
*
Entry
Ketone
Yieldb (%)
eec (%)
Configurationd
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
Acetophenone
95
94
91
95
95
94
93
90
92
90
94
92
94
93
86
80
88
90
82
90
92
91
86
86
86
97
89
81
92
87
77
73
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(R)
(S)
(S)
(S)
(R)
(R)
(R)
1-(4-Chlorophenyl)ethanone
1-(4-Methoxyphenyl)ethanone
1-(4-Nitrophenyl)ethanone
1-(4-Bromophenyl)ethanone
1-(4-Fluorophenyl)ethanone
1-(3-Bromophenyl)ethanone
1-(3-Methoxylphenyl)ethanone
1-(3-Methylphenyl)ethanone
1-(2-Fluorophenyl)ethanone
2-Bromo-1-phenylethanone
2-Chloro-1-(4-methoxyphenyl)ethanone
2-Bromo-1-(2,4-dimethylphenyl)ethanone
b-Acetonaphthone
1-Tetralone
Propiophenone
a Reaction was carried out with 1.0 mmol scale in 5 mL of solvent, molar ratio of ketone/BH3ꢀSMe2 = 1.0:1.1.
b Isolated yield by column chromatography.
c Determined by HPLC analysis using a Daicel Chiralcel OJ column.
d The absolute configuration was determined by comparison with the literature.
the reduction was completed, the reaction was quenched
Table 3. Recycling of C3-symmetric sulfonamide L-1 (reduction of
with water and extracted. After evaporating the solvent,
the product was isolated by being redissolved in diethyl
ether resulting in the precipitate ligand L-1 being obtained.
Next, the C3-symmetric sulfonamide L-1 was washed sev-
eral times with diethyl ether and dried. Recycling of the
C3-symmetric sulfonamide L-1 was tested by the reduction
of acetophenone (Table 3). The results show that ligand L-
1 could be reused at least four times with little or no loss of
performance.
acetophenone)
Cycle
1
2
3
4
Liganda (%)
Yieldb (%)
eec (%)
94
93
85
90
90
87
92
89
87
96
91
84
a Isolated yield by precipitation.
b Isolated yield by column chromatography.
c Determined by HPLC analysis using a Daicel Chiralcel OJ column.

G.-Q. Li et al. / Tetrahedron: Asymmetry 19 (2008) 816–821
819
3. Conclusion
701 cmꢁ1. Anal. Calcd for C92H87N3O12S3: C, 72.56; H,
5.76; N, 2.76. Found: C, 72.08, H, 5.73, N, 2.75.
In conclusion, a novel, recoverable, C3-symmetric sulfon-
amide L-1 has been synthesized, which was used as an effi-
cient catalyst in the enantioselective borane reduction of
prochiral ketones with good to excellent enantioselectivities
have been obtained (up to 97% ee). The reduction permits
extensive recycling of the C3-symmetric sulfonamide cata-
lyst without substantial loss in the activity within four
cycles.
4.1.2. Synthesis of C1-symmetric sulfonamide L-3. To a
stirred solution of 2 (4.85 g, 10 mmol) and phenol (0.93 g,
9.9 mmol) in acetone (20 mL) were added potassium
carbonate (1.52 g, 11 mmol) and 18-crown-6 (10 mg,
0.04 mmol). The reaction mixture was heated at reflux for
24 h under argon. After cooling to room temperature, the
reaction was quenched with water (15 mL) and extracted
with CH2Cl2 (3 ꢂ 15 mL). The combined organic extracts
were washed with brine and dried over MgSO4. After evap-
orating the solvent under reduced pressure, the residue was
purified by flash column chromatography on silica gel
4. Experimental
All the reactions were carried out under a dry argon atmo-
sphere. THF was freshly distilled over sodium before use.
All the ketones were prepared according to the reported
procedure and further purified by crystallization or distilla-
tion. Borane-dimethyl sulfide was obtained from Aldrich
Chemical Co. The purity of all reagents was checked by
NMR spectroscopy.
(hexane/EtOAc = 2:1 as eluent) to give the product as a
20
white solid. Yield: 4.74 g (96%). Mp: 135–137 °C; ½aꢃD
¼
ꢁ66:5 ðc 2:0; CH2Cl2Þ; 1H NMR (400 MHz, CDCl3): d
7.76 (d, J = 8 Hz, 2H), 7.55 (d, J = 8 Hz, 2H), 7.19–7.43
(m, 13H), 6.95–6.99 (m, 2H), 5.01 (s, 2H), 4.85–4.88 (m,
1H), 4.44 (s, 1H), 3.25–3.32 (m, 1H), 2.78–2.85 (m, 1H),
1.74–1.88 (m, 2H), 1.15–1.26 (m, 1H), 0.76–0.88 (m, 1H);
13C NMR (75 MHz, CDCl3): d 158.5, 145.9, 143.9, 143.0,
137.7, 129.9, 128.4, 128.3, 128.1, 127.9 (two peaks), 127.8,
127.7, 127.6, 121.7, 115.1, 80.2, 69.1, 67.8, 50.3, 29.9,
24.2. IR (KBr): 3463, 2929, 1494, 1343, 1237, 1155, 758,
686, 619 cmꢁ1. Anal. Calcd for C30H29NO4S: C, 72.12;
H, 5.85; N, 2.80. Found: C, 72.46; H, 5.88; N, 2.79.
HRMS-FAB: m/z calcd for C30H29NO4SNa: 522.1710.
Found: 522.1704.
Melting points were determined on a microscopic appara-
1
tus and are uncorrected. H NMR spectra were recorded
at 300 MHz and 400 MHz in CDCl3 and 13C NMR spectra
were recorded at 75 MHz in CDCl3 using TMS as an inter-
nal standard. IR spectra were obtained using a Nicolet
NEXUS 670 FT-IR spectrometer and only major peaks
are reported in cmꢁ1. HRMS spectra were performed on
a Bruker APEX instrument. Elemental analyses were per-
formed on Perkin–Elmer 240-C. Optical rotation value
was measured on a Perkin–Elmer 341MC polarimeter.
Enantiometric excesses were determined by HPLC with a
Chiralcel OJ column.
4.2. General procedure for the asymmetric reduction of
prochiral ketones
Under an argon atmosphere, BH3ꢀSMe2 (1.1 mmol) was
added to a suspension of C3-symmetric sulfonamide L-1
(0.05 mmol) in THF (5 mL) at room temperature. The
mixture was heated at reflux and stirred for 1 h. Then a
THF (5 mL) solution of ketone (1.0 mmol) was added
dropwise over a period of 2 h by a syringe pump, and
the mixture was stirred for another 1 h. The reaction mix-
ture was quenched by the dropwise addition of water
(5 mL) and extracted with CH2Cl2 (3 ꢂ 5 mL). The com-
bined organic extracts were washed with brine and dried
over MgSO4. After evaporating the solvent under reduced
pressure, the alcohol was redissolved in the diethyl ether,
and the ligand L-1 was precipitated. The ether phase
was removed, and the C3-symmetric sulfonamide L-1
was further washed several times with diethyl ether and
dried. The combined diethyl ether was concentrated by
rotatory evaporation, and the product was purified by
flash column chromatography on a silica gel to afford
the corresponding secondary alcohol. The ee value was
determined by HPLC with a Chiralcel OJ column. The
absolute configuration of the product was determined by
the comparison of the specific rotation with the literature
data.6b,14–17
4.1. Synthesis of ligands
4.1.1. Synthesis of C3-symmetric sulfonamide L-1. To a
stirred solution of 212 (4.85 g, 10 mmol) and 1,1,1-tris(4-
hydroxyphenyl)-ethane (1.01 g, 3.3 mmol) in acetone
(20 mL) were added potassium carbonate (1.52 g,
11 mmol) and 18-crown-6 (10 mg, 0.04 mmol). The reac-
tion mixture was heated at reflux for 24 h under argon.
After cooling to room temperature, the reaction was
quenched with water (15 mL) and extracted with CH2Cl2
(3 ꢂ 15 mL). The combined organic extracts were washed
with brine and dried over MgSO4. After evaporating the
solvent under reduced pressure, the residue was purified
by flash column chromatography on a silica gel (metha-
nol/dichloromethane = 1:20 as eluent) to give the C3-sym-
metric sulfonamide L-1 as a white solid. Yield: 4.72 g
20
(94%). Mp: 132–134 °C; ½aꢃD ¼ ꢁ54:8 ðc 2:0; CH2Cl2Þ;
1H NMR (400 MHz, CDCl3): d 7.76 (d, J = 8.0 Hz, 6H),
7.55 (d, J = 8.4 Hz, 6H), 7.37–7.43 (m, 12H), 7.21–7.32
(m, 18H), 7.02 (d, J = 8.8 Hz, 6H), 6.86 (d, J = 8.8 Hz,
6H), 5.09 (s, 6H), 4.86–4.89 (m, 3H), 4.47 (d, J = 2.8 Hz,
3H), 3.25–3.32 (m, 3H), 2.80–2.87 (m, 3H), 1.78–1.87 (m,
6H), 1.17–1.25 (m, 3H), 0.76–0.83 (m, 3H); 13C NMR
(75 MHz, CDCl3): d 156.2, 145.4, 143.5, 142.6, 142.2,
137.3, 129.6, 127.9, 127.8, 127.6, 127.5, 127.4, 127.3,
127.2, 127.1, 113.9, 79.8, 68.7, 67.3, 50.6, 49.8, 30.6, 29.4,
23.7. IR (KBr): 3465, 2975, 1506, 1334, 1245, 1155,
4.2.1. (R)-1-Phenyl-ethanol.6b Colorless oil. 95% Yield;
88% ee determined by HPLC analysis (Daicel Chiralcel
OJ column, hexane/2-propanol = 90:10, 0.5 mL/min,
254 nm). Retention times: 15.202 min [minor (S)-enantio-
20
mer], 16.615 min [major (R)-enantiomer]. ½aꢃD
¼

820
G.-Q. Li et al. / Tetrahedron: Asymmetry 19 (2008) 816–821
þ38:2 ðc 1:0; CH2Cl2Þ. 1H NMR (300 MHz, CDCl3): d
7.22–7.35 (m, 5H), 4.83 (q, J = 6.6 Hz, 1H), 2.35 (s, 1H),
1.45 (d, J = 6.6 Hz, 3H); 13C NMR (75 MHz, CDCl3): d
145.7, 128.4, 127.3, 125.3, 70.2, 25.0.
min, 254nm). Retention times: 13.432 min [minor (S)-
20
enantiomer], 14.958 min [major (R)-enantiomer]. ½aꢃD
¼
þ37:5 ðc 1:5; CH2Cl2Þ. 1H NMR (300 MHz, CDCl3): d
7.49 (s, 1H), 7.36 (d, J = 7.8 Hz, 1H), 7.16–7.25 (m, 2H),
4.79 (q, J = 6.3 Hz, 1H), 2.47 (s, 1H), 1.43 (d, J = 6.6 Hz,
3H); 13C NMR (75 MHz, CDCl3): d 148.1, 130.3, 130.0,
128.5, 124.0, 122.5, 69.6, 25.1.
4.2.2. (R)-1-(4-Chlorophenyl)-ethanol.6b Colorless oil.
94% Yield; 90% ee determined by HPLC analysis (Daicel
Chiralcel OJ column, hexane/2-propanol = 90:10, 0.5 mL/
4.2.8. (R)-1-(3-Methoxylphenyl)-ethanol.15 Colorless oil.
90% Yield; 86% ee determined by HPLC analysis (Daicel
Chiralcel OJ column, hexane/2-propanol = 90:10, 0.5 mL/
min, 254 nm). Retention times: 13.775 min (minor S-enan-
20
tiomer), 14.794 min [major (R)-enantiomer]. ½aꢃD
¼
þ45:8 ðc 1:1; CH2Cl2Þ. 1H NMR (400 MHz, CDCl3): d
7.26–7.32 (m, 4H), 4.85 (q, J = 6.8 Hz, 1H), 2.10 (s, 1H),
1.45 (d, J = 6.4 Hz, 3H); 13C NMR (75 MHz, CDCl3): d
144.5, 133.3, 128.8, 127.0, 69.9, 25.5.
min, 254 nm). Retention times: 20.647 min [minor (S)-
20
enantiomer], 22.378 min [major (R)-enantiomer]. ½aꢃD
¼
þ32:8 ðc 1:0; CH2Cl2Þ. 1H NMR (300 MHz, CDCl3): d
7.21–7.26 (m, 1H), 6.90–6.92 (m, 2H), 6.76–6.80 (m, 1H),
4.81 (q, J = 6.6 Hz, 1H), 3.78 (s, 3H), 2.35 (s, 1H), 1.45
(m, 3H); 13C NMR (75 MHz, CDCl3): d 159.6, 147.6,
129.4, 117.6, 112.7, 110.8, 70.1, 55.1, 25.0.
4.2.3. (R)-1-(4-Methoxylphenyl)-ethanol.6b Colorless oil.
91% Yield; 82% ee determined by HPLC analysis (Daicel
Chiralcel OJ column, hexane/2-propanol = 90:10, 0.5 mL/
min, 254 nm). Retention times: 30.212 min [minor (S)-
20
enantiomer], 32.074 min [major (R)-enantiomer]. ½aꢃD
¼
4.2.9. (R)-1-(3-Methylphenyl)-ethanol.16 Colorless oil.
92% Yield; 86% ee determined by HPLC analysis (Daicel
Chiralcel OJ column, hexane/2-propanol = 90:10, 0.5 mL/
þ46:5 ðc 1:0; CH2Cl2Þ. 1H NMR (300 MHz, CDCl3): d
7.27 (d, J = 8.1 Hz, 2H), 6.85–6.87 (m, 2H), 4.81 (q,
J = 6.6 Hz, 1H), 3.78 (s, 3H), 2.16 (s, 1H), 1.45 (d,
J = 6.6 Hz, 3H); 13C NMR (75 MHz, CDCl3): d 158.8,
138.0, 126.6, 113.7, 69.8, 55.2, 24.9.
min, 254 nm). Retention times: 13.099 [minor (S)-enantio-
20
mer], 13.775 min [major (R)-enantiomer]. ½aꢃD
¼
þ45:8 ðc 1:0; CH2Cl2Þ. 1H NMR (300 MHz, CDCl3): d
7.06–7.25 (m, 4H), 4.82 (q, J = 6.6 Hz, 1H), 2.35 (s, 3H),
2.06 (s, 1H), 1.46 (d, J = 6.3 Hz, 3H). 13C NMR
(75 MHz, CDCl3): d 145.8, 138.1, 128.3, 128.1, 126.0,
122.4, 70.3, 25.0, 21.4.
4.2.4. (R)-1-(4-Nitrophenyl)-ethanol.6b Colorless oil. 95%
Yield; 90% ee determined by HPLC analysis (Daicel
Chiralcel OJ column, hexane/2-propanol = 90:10, 0.5 mL/
min, 254 nm). Retention times: 34.650 min [minor (S)-
20
enantiomer], 37.942 min [major (R)-enantiomer]. ½aꢃD
¼
4.2.10. (R)-1-(2-Fluorophenyl)-ethanol.15 Colorless oil.
90% Yield; 97% ee determined by HPLC analysis (Daicel
Chiralcel OJ column, hexane/2-propanol = 95:5, 0.5 mL/
þ26:5 ðc 1:5; CH2Cl2Þ. 1H NMR (400 MHz, CDCl3): d
8.18 (d, J = 8.8 Hz, 2H), 7.54 (d, J = 8.8 Hz, 2H), 5.01
(q, J = 6.4 Hz, 1H), 2.36 (s, 1H), 1.51–1.52 (m, 3H); 13C
NMR (75 MHz, CDCl3): d 153.1, 147.1, 126.1, 123.7,
69.4, 25.4.
min, 254 nm). Retention times: 10.184 min [minor (S)-
20
enantiomer], 11.424 min [major (R)-enantiomer]. ½aꢃD
¼
þ34:1 ðc 2:0; CH2Cl2Þ. 1H NMR (300 MHz, CDCl3): d
7.45–7.50 (m, 1H), 7.20–7.26 (m, 1H), 7.11–7.16 (m, 1H),
6.97–7.04 (m, 1H), 5.18 (q, J = 6.6 Hz, 1H), 2.13 (s, 1H),
1.50 (d, J = 6.3 Hz, 3H); 13C NMR (75 MHz, CDCl3): d
137.8, 128.7, 126.6, 124.2, 115.4, 115.1, 64.5, 24.0.
4.2.5. (R)-1-(4-Bromophenyl)-ethanol.6b Colorless oil.
95% Yield; 92% ee determined by HPLC analysis (Daicel
Chiralcel OJ column, hexane/2-propanol = 90:10, 0.5 mL/
min, 254 nm). Retention times: 14.705 min [minor (S)-
20
enantiomer], 15.748 min [major (R)-enantiomer]. ½aꢃD
¼
4.2.11. (S)-2-Bromo-1-phenylethanol.6b Colorless oil. 94%
Yield; 89% ee determined by HPLC analysis (Daicel Chi-
ralcel OJ column, hexane/2-propanol = 90:10, 0.5 mL/
þ31:5 ðc 1:0; CH2Cl2Þ. 1H NMR (300 MHz, CDCl3): d
7.43–7.46 (m, 2H), 7.20–7.26 (m, 2H), 4.81 (q,
J = 6.6 Hz, 1H), 2.20 (s, 1H), 1.42–1.45 (m, 3H); 13C
NMR (75 MHz, CDCl3): d 144.7, 131.5, 127.1, 121.1,
69.7, 25.2.
min, 254 nm). Retention times: 30.005 min [minor (R)-
20
enantiomer], 32.256 min [major (S)-enantiomer]. ½aꢃD
¼
þ34:9 ðc 1:7; CH2Cl2Þ. 1H NMR (400 MHz, CDCl3): d
7.25–7.40 (m, 5H), 4.91 (dd, J = 3.2, 8.8 Hz, 1H), 3.51–
3.64 (m, 2H), 2.72 (s, 1H); 13C NMR (75 MHz, CDCl3):
d 146.9, 141.5, 130.1, 126.9, 126.4, 21.7.
4.2.6. (R)-1-(4-Fluorophenyl)-ethanol.6b Colorless oil.
94% Yield; 91% ee determined by HPLC analysis (Daicel
Chiralcel OJ column, hexane/2-propanol = 95:5, 0.5 mL/
min, 254 nm). Retention times: 14.961 min [minor (S)-
20
enantiomer], 15.697 min [major (R)-enantiomer]. ½aꢃD
¼
4.2.12. (S)-2-Chloro-1-(4-methoxyphenyl)-ethanol.12 Col-
orless oil. 92% Yield; 81% ee determined by HPLC analysis
(Daicel Chiralcel OJ column, hexane/2-propanol = 90:10,
0.5 mL/min, 254 nm). Retention times: 13.766 min [minor
þ34:5 ðc 2:0; CH2Cl2Þ. 1H NMR (300 MHz, CDCl3): d
7.26–7.36 (m, 2H), 7.00–7.06 (m, 2H), 4.88 (q, J =
6.6 Hz, 1H), 1.84 (s, 1H), 1.48 (d, J = 6.6 Hz, 3H); 13C
NMR (75 MHz, CDCl3): d 164.4, 160.9, 142.3, 127.0,
115.4, 115.1, 69.8, 25.3.
(R)-enantiomer], 15.761 min [major (S)-enantiomer].
20
½aꢃD ¼ þ32:5 ðc 1:0; CH2Cl2Þ. 1H NMR (400 MHz,
CDCl3): d 7.25–7.29 (m, 2H), 6.85–6.90 (m, 2H), 4.80
(dd, J = 5.6, 11.2 Hz, 1H), 3.78 (s, 3H), 3.56–3.69 (m,
2H), 2.83 (s, 1H). 13C NMR (75 MHz, CDCl3): d 159.5,
132.1, 127.2, 113.9, 73.6, 55.2, 50.6.
4.2.7. (R)-1-(3-Bromophenyl)-ethanol.14 Colorless oil.
93% Yield; 86% ee determined by HPLC analysis (Daicel
Chiralcel OJ column, hexane/2-propanol = 90:10, 0.5 mL/

G.-Q. Li et al. / Tetrahedron: Asymmetry 19 (2008) 816–821
821
4.2.13.
(S)-2-Bromo-1-(2,4-dimethylphenyl)-ethanol.12
References
White solid. 94% Yield; 92% ee determined by HPLC anal-
ysis (Daicel Chiralcel OJ column, hexane/2-propanol =
90:10, 0.5 mL/min, 254 nm). Retention times: 16.647 min
[minor (R)-enantiomer], 18.059 min [major (S)-enantio-
mer]. ½aꢃD ¼ þ37:4 ðc 1:0; CH2Cl2Þ. H NMR (300 MHz,
CDCl3): d 7.37 (d, J = 8.7 Hz, 1H), 7.04 (d, J = 8.8 Hz,
1H), 6.97 (s, 1H), 5.07 (d, J = 8.7 Hz, 1H), 3.42–3.56 (m,
2H), 2.68 (s, 1H), 2.29 (m, 6H); 13C NMR (75 MHz,
CDCl3): d 137.9, 135.3, 134.5, 131.3, 127.1, 125.3, 70.6,
39.1, 21.0, 18.9.
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4.2.14. (R)-1-(2-Naphthyl)-ethanol.6b White solid. 93%
yield; 87% ee determined by HPLC analysis (Daicel Chiral-
cel OJ column, hexane/2-propanol = 90:10, 0.5 mL/min,
254 nm). Retention times: 22.904 min [minor (S)-enantio-
20
mer], 27.917 min [major (R)-enantiomer]. ½aꢃD ¼ þ36:5
ðc 2:0; CH2Cl2Þ. 1H NMR (400 MHz, CDCl3): d 7.79–
7.83 (m, 4H), 7.43–7.50 (m, 3H), 5.04 (q, J = 6.8 Hz,
1H), 2.07 (s, 1H), 1.56 (d, J = 6.4 Hz, 3H); 13C NMR
(75 MHz, CDCl3): d 143.4, 133.5, 133.2, 128.5, 128.2,
127.9, 126.4, 126.0, 124.0, 70.7, 29.9, 25.3.
4.2.15. (R)-1,2,3,4-Tetrahydronaphthalen-1-ol.17 Color-
less oil. 86% Yield; 77% ee determined by HPLC analysis
(Daicel Chiralcel OJ column, hexane/2-propanol = 90:10,
0.5 mL/min, 254 nm). Retention times: 13.169 min [minor
20
(S)-enantiomer], 15.630 min [major (R)-enantiomer]. ½aꢃD
¼
ꢁ21:3 ðc 1:5; CH2Cl2Þ. 1H NMR (300 MHz, CDCl3): d
7.40–7.43 (m, 1H), 7.16–7.24 (m, 2H), 7.08–7.10 (m, 1H),
4.76 (br s, 1H), 2.66–2.86 (m, 2H), 1.71–1.99 (m, 5H);
13C NMR (75 MHz, CDCl3): d 138.7, 137.0, 128.9, 128.6,
127.5, 126.1, 68.0, 32.2, 29.2, 18.7.
4.2.16. (R)-1-Phenyl-propanol.17 Colorless oil. 80%
Yield; 73% ee determined by HPLC analysis (Daicel Chi-
ralcel OJ column, hexane/2-propanol = 95:5, 0.5 mL/min,
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254 nm). Retention times: 14.578 min [minor (S)-enantio-
20
mer], 16.285 min [major (R)-enantiomer]. ½aꢃD ¼ þ24:6
ðc 1:0; CH2Cl2Þ. 1H NMR (300 MHz, CDCl3): d 7.24–
7.34 (m, 5H), 4.57 (t, J = 6.9 Hz, 1H), 2.01 (s, 1H),
1.70–1.84 (m, 2H), 0.90 (t, J = 7.8 Hz, 3H); 13C NMR
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10.1.
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Acknowledgments
We are grateful to the NSFC-20021001 and the NSFC-
20572038 for the financial support of this work.
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