Asymmetric borane reduction of prochiral ketones using imidazolium-tagged sulfonamide catalyst

Article abstract of DOI:10.1016/j.tetasy.2006.07.003

A novel sulfonamide catalyst based on a room temperature ionic liquid (RTIL) has been developed for the enantioselective reduction of ketones in refluxing toluene. The optically active secondary alcohol products were obtained in good enantiomeric excess and excellent yields. The imidazolium-tagged sulfonamide catalyst can be readily recovered and reused four times without any significant loss of catalytic activity.

Full text of DOI:10.1016/j.tetasy.2006.07.003

Tetrahedron: Asymmetry 17 (2006) 1895–1900
Asymmetric borane reduction of prochiral ketones using
imidazolium-tagged sulfonamide catalyst
Shang-Dong Yang,a Yun Shi,a Zhen-Hua Sun,a Ya-Bin Zhaoa and Yong-Min Lianga,b,
*
aState Key Laboratory of Applied Organic Chemistry, Lanzhou University, Lanzhou 730000, PR China
bState Key Laboratory of Solid Lubrication, Lanzhou Institute of Chemical Physics, Chinese Academy of Science,
Lanzhou 730000, PR China
Received 9 June 2006; accepted 3 July 2006
Abstract—A novel sulfonamide catalyst based on a room temperature ionic liquid (RTIL) has been developed for the enantioselective
reduction of ketones in refluxing toluene. The optically active secondary alcohol products were obtained in good enantiomeric excess and
excellent yields. The imidazolium-tagged sulfonamide catalyst can be readily recovered and reused four times without any significant loss
of catalytic activity.
ꢀ 2006 Elsevier Ltd. All rights reserved.
1. Introduction
to their tunable features for various chemical tasks and
their advantages as reusable homogeneous supports,6,7
such as olefin metathesis,8 hydrogenation,9 cyanosilylation
of aldehydes,10 hydroformylation,11 Negishi cross-coupling
reaction,12 Heck reaction,13 Suzuki and Stille coupling
reactions,14 Morita–Baylis–Hillman reaction,15 Friedel–
Crafts alkylations or Beckman rearrangements, etc.16
The enantioselective reduction of prochiral ketones to the
corresponding optically active secondary alcohols plays
an important role in asymmetric synthesis.1 One of the
most popular methods using chiral 1,3,2-oxazaborolidines
as catalysts was developed by Itsuno et al. and further im-
proved by Corey et al.2,3 Numerous examples describing
the application of this homogeneous catalyst have been re-
ported,4 but the development of efficient methods of recov-
ering the catalyst is still a challenging target. Over the past
20 years, several groups have reported the preparation and
application of heterogeneous catalysts for the enantioselec-
tive reduction of ketones.5 However, only a few of the
reducing agents displayed high reactivity and enantioselec-
tivity owing to the diffusion limitations caused by the poly-
mer matrix.5j,k
Herein, we report the synthesis of an alkyl imidazolium
salt-tagged chiral sulfonamide IL-1 and its application
and recycling in the enantioselective reduction of prochiral
ketones to optically active secondary alcohols. To compare
the sulfonamide S-1, catalyst IL-1 gave the better enantio-
selectivity (Fig. 1).
BF4
O
S
O
N
O
O
S N
N
N
H3C
C
H3C
H2
To integrate the advantages of homogeneous and heteroge-
neous catalysis into one process, a conceptual solution in-
volves the use of ‘separation tags’, which are chosen such
that they dominate over tagged molecules in a complemen-
tary separation technique. Ionic liquids, especially task-
specific ionic liquids (TSIL), have recently received growing
attention and have been introduced as ligands in recover-
able catalysts in a series of chemical transformations due
HO
HO
IL-1
S-1
Figure 1.
2. Results and discussion
*
The route for the synthesis of IL-1 is illustrated in Scheme 1.
Corresponding author. Tel./fax: +86 0931 8912581; e-mail: liangym@
lzu.edu.cn
In the first step, sulfonylation of the diphenylprolinol
0957-4166/$ - see front matter ꢀ 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetasy.2006.07.003

1896
S.-D. Yang et al. / Tetrahedron: Asymmetry 17 (2006) 1895–1900
Br
O
S
O
N
O
S
O
N
N
NH
N
N
H3C
H3C
BrH2C
C
BrH2C
SO2Cl
H2
CH3CN/ reflux
N
H
NEt3/Et2O 0 °C
HO
HO
OH
2
3
TsCl NEt3/Et2O 0 °C
H2O
NaBF4
BF4
O
S
O
N
O
O
S N
N
N
H3C
C
H3C
H2
HO
HO
S-1
IL-1
Scheme 1. Synthesis of IL-tagged sulfonamide IL-1 and sulfonamide S-1.
amino group with 4-(bromomethyl)benzene-sulfonyl chlo-
ride in the presence of Et3N at 0 ꢁC over 4 h afforded 2
in 86% yield. In the second step, compound 2 was grafted
onto the 1-methylimidazole in refluxing acetonitrile to give
3 in 92% yield. Following anion exchange in water with
NaBF4, the desired tetrafluoroborate imidazolium salt
IL-1 was obtained in 98% yield, which was purified by
redissolving in a mixture of THF and ethanol, then filtrated
to remove the by-product of NaBr and afforded pure ionic
liquid (IL)-tagged catalyst IL-1 as an air-stable colorless
and transparent liquid. According to the literature proce-
dures,17 the sulfonamide catalyst S-1 was prepared directly
from diphenylprolinol and 4-methylbenzene sulfonyl chlo-
ride in the presence of Et3N at 0 ꢁC in 92% yield as the
white solid.
pared the catalytic activity and enantioselectivity of
catalyst S-1. The results are summarized in Table 1.
Firstly, solvent effects were observed. At room temperature
(entries 1 and 2), the reduction was completed within 10 h
in toluene and 16 h in THF. When the reaction tempera-
ture was raised from room temperature to reflux, the reduc-
tion was complete in 1.5 h and the ee value was 52% in
THF and 65% in toluene (entries 3 and 4), respectively.
The results show that toluene is a more effective solvent
for the reduction and the level of enantiomeric excess is
sensitive to the reaction temperature. The best result could
be achieved if the reaction mixture was at reflux.4d,5,10
Apart from the reaction temperature and solvent, the ratio
of the catalysts has an impact on the reduction. When the
amount of catalyst was increased from 10 to 15 mol %, the
enantiomeric excess increased from 65% to 73% (entries 4
and 5). By increasing further the amount of catalyst to
20 mol %, the ee had only slightly changed (entries 6).
We also investigated the effect of catalyst S-1 on the reduc-
tion of acetophenone, and lower enantiomeric excesses
It is well known that the stereoselectivity of reduction is af-
fected greatly by solvent, temperature and the amount of
catalyst. To find the optimum reaction conditions, we
examined the reduction of acetophenone with chiral cata-
lyst IL-1 under various experimental conditions and com-
Table 1. Effect of temperature, solvent and catalysta,d
O
OH
Catalyst
CH3
CH3
.
BH3 S(CH3)2
+
Solvent
Entry
Solvent
Catalyst
Catalyst (mol %)
Temperature (ꢁC)
Yieldb (%)
eec (%)
1
2
3
4
5
6
7
8
9
THF
Toluene
THF
Toluene
Toluene
Toluene
THF
Toluene
Toluene
IL-1
IL-1
IL-1
IL-1
IL-1
IL-1
S-1
10
10
10
10
15
20
10
10
15
rt
rt
94
92
94
95
95
95
94
93
94
13
7
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
Reflux
52
65
73
75
49
57
66
S-1
S-1
a Molar ratio, PhCOCH3/BH3ÆSMe2 1.0:1.1.
b Isolated yield after column purification.
c Determined by HPLC analysis using Diacel Chiralcel OJ column (eluent: hexane/2-propanol = 9:1).
d The absolute configuration was determined by optical rotation.

S.-D. Yang et al. / Tetrahedron: Asymmetry 17 (2006) 1895–1900
1897
Table 4. Recycling of chiral catalyst IL-1 (reduction of acetophenone)
Cycle
were observed. It is noted that the ionic liquid not only aids
the separation, but also increases the enantioselectivity of
the catalyst (entries 4, 5, and 7–9).
1
2
3
4
Liganda (%)
Yielda (%)
eeb (%)
98
96
72.6
99
96
72.1
97
95
71.4
98
96
64.9
Having established the best reaction conditions, the appli-
cation of catalyst IL-1 to the reduction of other prochiral
ketones was investigated using
a catalytic amount
a Yields of isolated products.
b Determined by using chiral HPLC.
(15 mol %) of IL-1 in refluxing toluene (Table 2). All reduc-
tions gave excellent yields and good enantiomeric excesses.
The results demonstrate that the steric effects have a signi-
ficant impact on the enantioselectivity (entries 3, 5, and 6).
Comparison of the results obtained from p-methoxy-
acetophenone and p-nitroacetophenone indicated that
electron-withdrawing groups are relatively beneficial for
enantioselectivity.
the reduction of 2,4-dimethyl-a-bromoacetophenone and
2,4-dimethyl-a-chloroacetophenone was obtained in 95%
and 96% ee, respectively.
The obvious predominance of IL-tagged catalyst IL-1 can
be easily separated and recycled. After the reduction was
complete, the reaction was quenched with water and the
product isolated by extraction with diethyl ether with the
catalyst IL-1 remaining in the aqueous media. After water
was removed at reduced pressure, catalyst IL-1 was redis-
solved in ethyl acetate, then washed with water and dried.
Ethyl acetate was removed and the catalyst IL-1 was reused
for the next cycle of reduction. Excellent conversions were
obtained for four consecutive cycles with little or no loss of
performance (Table 4). These results showed the impor-
tance of grafting onto an imidazolium ionic liquid pattern
to the catalyst to obtain its recycling from the reaction
system.
We also investigated the reduction of a-haloacetophenone
under the same conditions. Much higher enantiomeric
excesses were observed. Similarly, the results (summarized
in Table 3) showed that the enantioselectivity of the reduc-
tion was highly dependent on steric effects. The 2,4-disub-
stituted substrates afforded excellent ees. For example,
Table 2. Asymmetric reduction of prochiral ketonesa
O
OH
CH3
IL-1 15 mol%
toluene/reflux
CH3
.
BH3 S(CH3)2
+
R
R
Entry
R
Yieldb (%)
eec (%)
Config.d
1
2
3
4
5
6
7
8
9
H
4-Cl
2-Cl
4-OCH3
2-OCH3
2-CH3
4-F
94
96
95
92
93
94
95
96
94
73
75
94
65
89
91
75
75
76
R
R
R
R
R
R
R
R
R
3. Conclusion
In conclusion, we have developed a new catalyst of IL-
tagged sulfonamides for the enantioselective borane reduc-
tion of prochiral ketones. The catalyst can be recycled four
times with minimal loss of catalytic performance.
b-Acetonaphthone
4-NO2
a Experiments were performed on a 1.0 mmol scale.
4. Experimental
b Yields of isolated products after purification by column chromatography.
c Determined by using chiral HPLC.
All reactions were carried out under an argon atmosphere.
THF was dried over sodium and freshly distilled before
use. Toluene was distilled over calcium hydride. Acetophe-
none was dried and distilled over calcium hydride. Other
ketones were further purified by recrystallization before
use. (S)-Diphenylprolinol was prepared according to the
literature procedures.18 Borane–dimethyl sulfide was
obtained from Aldrich Chemical Co. The purity of all
reagents was checked by NMR spectroscopy.
d The absolute configurations were determined by optical rotation.
Table 3. Asymmetric reduction of prochiral a-haloacetophenonea
O
OH
CH2X
IL-1 15 mol%
toluene/reflux
CH2X
.
BH3 S(CH3)2
+
R
R
4.1. General procedure for preparation of IL-sulfonamide
catalyst
Entry
R
X
Yieldb (%)
eec (%)
Config.d
1
2
3b
4
5
6
H
H
Br
Cl
Cl
Br
Cl
Br
92
93
91
94
93
94
71
77
96
95
64
67
S
S
S
S
S
S
4.1.1. Synthesis of (S)-4-bromomethylbenzene-sulfonyldi-
phenylprolinol 2. (S)-Diphenyprolinol (2.53 g, 10 mmol)
and Et3N (1.55 mL, 11 mmol) were dissolved in Et2O
(30 mL). The solution was stirred at 0 ꢁC and 4-bromo-
methylbenzene-sulfonyl chloride (2.95 g, 11 mmol) in Et2O
(30 mL) was slowly added. The mixture was stirred for
6 h. The reaction mixture was filtered and the solvent evap-
orated and purified by flash chromatography on silica gel
2,4-Dimethyl
2,4-Dimethyl
4-OCH3
4-OCH3
a Experiments were performed on a 1.0 mmol scale.
b Yields of isolated products after purification by column chromatography.
c Determined by using chiral HPLC.
d The absolute configurations were determined by optical rotation.

1898
S.-D. Yang et al. / Tetrahedron: Asymmetry 17 (2006) 1895–1900
(ethyl acetate/hexane = 1:4 as eluent) to give 2 as the white
solid (4.17 g, 86% yield), mp 286–288 ꢁC; 1H NMR
(300 MHz, CDCl3): d 7.76 (d, J = 8.0 Hz, 2H), 7.53 (d,
J = 8.0 Hz, 2H), 7.44–7.26 (m, 10H), 4.92 (t, J = 11.0 Hz,
1H), 4.63 (s, 1H), 4.31 (d, J = 1.2 Hz, 1H), 3.30 (m, 1H),
2.84 (m, 1H), 1.87 (m, 2H), 1.26 (m, 1H), 0.83 (m, 1H);
13C NMR (75 MHz, CDCl3): d 145.4, 143.4, 137.9, 129.7,
128.0, 127.4 (two peaks overlap), 79.9, 67.3, 49.9, 31.5,
29.6, 23.9; IR (neat) 3455, 2969, 1600, 1491, 1336, 1556,
1156, 1091, 1047, 757, 672, 974, 607 cmꢀ1; MS (CI) calcd
for C24H25BrNSO3: 486.0, 488.0 (m/z), found: 468.0,
470.0 (Mꢀ18).
pressure. Catalyst IL-1 was redissolved in ethylacetate,
then washed with water and dried. Ethyl acetate was re-
moved and the catalyst IL-1 was reused for the next cycle
of reduction.
4.2.1. (R)-1-Phenyl-ethanol. Purified by flash chromato-
graphy on silica gel (eluent: hexanes/EtOAc = 9:1); yield
25
94%, as colorless oil; ½aꢁD ¼ ꢀ38:4 (c 1.32, CHCl3); ee
1
73%. H NMR (300 MHz, CDCl3): d 7.36 (t, J = 8.9 Hz,
4H), 7.28 (m, 1H), 4.89 (q, J = 6.6 Hz, 1H), 2.04 (s, 1H),
1.49 (d, J = 6.6 Hz, 3H); 13C NMR (75 MHz, CDCl3): d
145.7, 128.4, 125.3, 70.1, 25.1; m/z (EI) 122 (M+, 12.2%),
107 (62.9%), 79 (100%).
4.1.2. Synthesis of IL supported sulfonamide 3. To a solu-
tion of 2 (2.42 g, 5.0 mmol) in CH3CN was added
N-methylimidazole (0.49 g, 6.0 mmol). The mixture was
stirred for 6 h at reflux temperature. After cooling to room
temperature, the reaction mixture was concentrated. The
residue was purified by flash column chromatography on
silica gel (methanol/dichloromethane = 1:10 as eluent) to
give the desired product 3 as a colorless transparent liquid
4.2.2. (R)-1-(4-Chloro-phenyl)-ethanol. Purified by flash
chromatography on silica gel (eluent: hexanes/EtOAc =
25
9:1); yield 96%, as colorless oil; ½aꢁD ¼ ꢀ39:5 (c 1.21,
1
CHCl3); ee 75%; H NMR (300 MHz, CDCl3): d 7.30 (d,
J = 12 Hz, 4H), 4.86 (q, J = 6.4 Hz, 1H), 1.99 (s, 1H),
1.46 (d, J = 6.0 Hz, 3H); 13C NMR (75 MHz, CDCl3): d
144.2, 128.5, 126.7, 69.6, 25.2; m/z (EI) 156 (M+, 13.4%),
141 (56.3%), 113 (26.2%), 77 (100%), 43 (60.8%).
1
(2.60 g, 92% yield). H NMR (300 MHz, CDCl3): d 9.53
(s, 1H), 7.52 (d, J = 8.9 Hz, 4H), 7.46 (s, 1H), 7.29–7.17
(m, 5H), 7.11–7.05 (m, 6H), 7.03 (s, 1H), 5.47 (s, 2H),
4.68 (s, 1H), 3.74 (s, 2H), 3.21 (s, 3H), 2.76 (br s, 1H),
1.64 (d, J = 7.8 Hz, 1H), 1.13 (br s, 1H), 0.88 (br s, 1H);
13C NMR (75 MHz, CDCl3): d 144.7, 143.2, 138.1, 136.1,
129.2, 127.2 (four peaks overlap), 123.4, 122.0, 79.7, 67.0,
51.3, 49.3 (two peaks overlap), 36.0, 28.5, 23.3; IR (neat)
3365, 3155, 3060, 2977, 2198, 1663, 1569, 1448, 1336,
1158, 1091, 1027, 989, 917, 731, 598, 565 cmꢀ1; MS (CI)
4.2.3. (R)-1-(2-Chloro-phenyl)-ethanol. Purified by flash
chromatography on silica gel (eluent: hexanes/EtOAc =
25
8:1); yield 95%, as colorless oil; ½aꢁD ¼ ꢀ49:3 (c 1.12,
1
CHCl3); ee 94%; H NMR (300 MHz, CDCl3): d 7.58 (d,
J = 8.7 Hz, 1H), 7.29 (m, 2H), 7.19 (d, J = 9.3 Hz, 1H),
5.29 (q, J = 12 Hz, 1H), 2.21 (s, 1H), 1.47 (d, J = 6.3 Hz,
3H); 13C NMR (75 MHz, CDCl3): d 143.0, 129.3, 128.3,
127.2, 126.3, 66.9, 23.5; m/z (EI) 156 (M+, 9.6%), 141
(54.6%), 113 (22.8%), 77 (100%), 51 (39.3%), 43 (47.5%).
calcd for C28H31BrN3SO3: 488.2, (m/z), found: 488.2
20
(m/z); ½aꢁD ¼ ꢀ34:6 (c 1.14, MeOH).
4.2.4. (R)-1-(4-Methoxy-phenyl)-ethanol. Purified by flash
4.1.3. Anion exchange of sulfonamide 3. To a solution of 3
(2.60 g, 4.6 mmol) in H2O (20 mL) was added NaBF4
(1.0 g, 9.2 mmol). The mixture stirred for 5 h at room tem-
perature. After evaporation of H2O and purification of the
residue, it was redissolved in a mixture of THF and ethanol
(1:1), then filtered and the solid thoroughly washed with
medley liquids. The filtrate and wash liquids were evapo-
rated at reduced pressure, the residue then redissolved in
dichloromethane and again filtrated, to remove the rudi-
mental salt. The sulfonamide catalyst IL-1 was obtained
as a colorless transparent liquid.
chromatography on silica gel (eluent: hexanes/EtOAc =
25
9:1); yield 92%, as colorless oil; ½aꢁD ¼ ꢀ29:3 (c 1.34,
1
MeOH); ee 65%; H NMR (300 MHz, CDCl3): d 7.33 (d,
J = 27 Hz, 2H), 6.90 (d, J = 27 Hz, 2H), 5.10 (br, 1H),
3.85 (s, 3H), 2.88 (s, 1H), 1.49 (d, J = 6.0 Hz, 3H); 13C
NMR (75 MHz, CDCl3): d 156.3, 133.4, 128.1, 125.9,
120.6, 66.2, 55.1, 22.8; m/z (EI) 152 (M+, 14.5%), 137
(60.7%), 107 (100%), 79 (73.5%), 43 (36.6%).
4.2.5. (R)-1-(2-Methoxy-phenyl)-ethanol. Purified by flash
chromatography on silica gel (eluent: hexanes/EtOAc =
25
8:1); yield 93%, as colorless oil; ½aꢁD ¼ ꢀ46:8 (c 1.28,
4.2. General procedure for asymmetric reduction of prochiral
CHCl3); ee 89%; 1H NMR (300 MHz, CDCl3): d 7.35
(d, J = 7.2 Hz, 1H), 7.28 (q, J = 15 Hz, 1H), 6.97 (t,
J = 15 Hz, 2H), 6.88 (d, J = 8.4 Hz, 1H), 5.10 (q,
J = 12 Hz, 1H), 3.86 (s, 3H), 2.74 (s, 1H), 1.51 (d, J =
6.6 Hz, 3H); 13C NMR (75 MHz, CDCl3): d 156.4, 134.6,
133.3, 128.2, 126.0, 120.7, 110.3, 66.4, 55.2, 22.8; m/z (EI)
152 (M+, 25.3%), 137 (100%), 107 (82.3%), 94 (19.2%),
77 (42.9%), 51 (30.3%), 43 (48.4%).
Under an argon atmosphere, BH3ÆSMe2 (1.1 mmol) was
added to a suspension of IL-tagged sulfonamide catalyst
IL-1 (0.15 mmol) in toluene (5 mL). The suspension was
stirred and refluxed for 1 h. Then a toluene (5 mL) solution
of ketone (1.0 mmol) was added within 30 min. After the
addition was completed, the reaction was quenched with
water (2 mL) and extracted with diethyl ether (2 ·
5.0 mL). The organic layer was treated with saturated
ammonium chloride solution and brine, then dried over
anhydrous Mg2SO4. After removal of solvent, the residue
was purified by flash column chromatography on silica
gel to give pure product. The ee value was determined by
Chiralcel OJ column (eluent: hexane/2-propanol = 9:1).
Catalyst IL-1 was separated and water removed at reduced
4.2.6. (R)-1-(2-Methyl-phenyl)-ethanol. Purified by flash
chromatography on silica gel (eluent: hexanes/EtOAc =
25
10:1); yield 94%, as colorless oil; ½aꢁD ¼ ꢀ47:9 (c 1.03,
1
CHCl3); ee 91%; H NMR (300 MHz, CDCl3): d 7.51 (d,
J = 7.5 Hz, 1H), 7.24, 7.16 (br, 3H), 5.09 (d, J = 6.0 Hz,
1H), 2.34 (s, 3H), 2.27 (s, 1H), 1.45 (d, J = 6.6 Hz, 3H);
13C NMR (75 MHz, CDCl3): d 143.8, 134.1, 130.2, 127.0,

S.-D. Yang et al. / Tetrahedron: Asymmetry 17 (2006) 1895–1900
1899
126.2, 124.4, 66.6, 23.8, 18.8; m/z (EI) 136 (M+, 18.8%),
4.2.13. (S)-2-Bromo-1-(2,4-dimethyl-phenyl)-ethanol. Purified
121 (70.9%), 91 (98%), 77 (57.8%), 43 (100%).
by flash chromatography on silica gel (eluent: hexanes/
25
EtOAc = 8:1); yield 94%, as colorless oil; ½aꢁD ¼ þ41:5 (c
1
1.06, CHCl3); ee 95%; H NMR (300 MHz, CDCl3): d 7.40
4.2.7. (R)-1-(4-Fluoro-phenyl)-ethanol. Purified by flash
(d, J = 9 Hz, 1H), 7.06 (d, J = 9 Hz, 1H), 6.99 (s, 1H), 5.07 (t,
J = 9 Hz, 1H), 3.63 (m, 2H), 2.31 (s, 6H); 13C NMR
(75 MHz, CDCl3): d 137.9, 134.9, 131.4, 127.1, 125.4, 70.7,
49.9, 21.0, 19.0; m/z (EI) 228 (M+, 3.9%), 135 (100%), 107
(46.8%), 91 (42%), 51 (10.9%).
chromatography on silica gel (eluent: hexanes/EtOAc =
25
10:1); yield 95%, as colorless oil; ½aꢁD ¼ ꢀ35:1 (c 1.24,
1
CHCl3); ee 75%; H NMR (300 MHz, CDCl3): d 7.23 (d,
J = 15 Hz, 2H), 6.96 (d, J = 18 Hz, 2H), 4.74 (q,
J = 18 Hz, 1H), 3.64 (s, 1H), 1.36 (d, J = 9.0 Hz, 3H);
13C NMR (75 MHz, CDCl3): d 163.4, 160.2, 141.5, 126.8,
115.0, 114.7, 69.2, 24.9; m/z (EI) 140 (M+, 17.7%), 125
(92.9%), 97 (100%), 77 (34.5%), 43 (66.8%).
4.2.14. (S)-2-Chloro-1-(4-methoxy-phenyl)-ethanol. Puri-
fied by flash chromatography on silica gel (eluent: hex-
25
anes/EtOAc = 8:1); yield 93%, as colorless oil; ½aꢁD
¼
þ18:9 (c 1.19, CHCl3); ee 64%; 1H NMR (300 MHz,
CDCl3): d 7.30 (d, J = 6.0 Hz, 1H), 6.90 (d, J = 9.0 Hz,
2H), 4.84 (q, J = 12 Hz, 1H), 3.80 (s, 3H), 3.65 (m, 2H),
2.75 (s, 1H); 13C NMR (75 MHz, CDCl3): d 159.6, 132.0,
128.6, 127.3, 126.0, 114.0, 73.7, 55.2, 50.8; m/z (EI) 186
(M+, 6.0%), 137 (100%), 109 (23.8%), 94 (26.4%), 77
(28.9%).
4.2.8. (R)-1-Naphthalen-2-yl-ethanol. Purified by flash
chromatography on silica gel (eluent: hexanes/EtOAc =
25
9:1); yield 96%, as colorless oil; ½aꢁD ¼ ꢀ38:1 (c 1.05,
CHCl3); ee 75%; 1H NMR (300 MHz, CDCl3): d 8.10,
7.45 (br, 7H), 7.09 (s, 3H), 5.64 (d, J = 6.0 Hz, 1H), 2.44
(s, 1H), 1.65 (d, J = 6.0 Hz, 2H); 13C NMR (75 MHz,
CDCl3): d 141.2, 133.6, 130.1, 128.8, 127.8, 125.9, 123.1,
121.9, 66.9, 24.3; m/z (EI) 172 (M+, 29.6%), 157 (38.2%),
129 (100%), 77 (10%).
4.2.15. (S)-2-Bromo-1-(4-methoxy-phenyl)-ethanol. Puri-
fied by flash chromatography on silica gel (eluent: hex-
25
anes/EtOAc = 8:1); yield 94%, as colorless oil; ½aꢁD
¼
þ19:6 (c 1.03, CHCl3); ee 67%; 1H NMR (300 MHz,
CDCl3): d 7.30 (d, J = 6.0 Hz, 1H), 6.90 (d, J = 9.0 Hz,
2H), 4.84 (q, J = 12 Hz, 1H), 3.80 (s, 3 H), 3.65 (m, 2H),
2.75 (s, 1H); 13C NMR (75 MHz, CDCl3): d 159.6, 132.0,
128.6, 127.3, 126.0, 114.0, 73.7, 55.2, 50.8; m/z (EI) 232
(M+, 3.0%), 137 (100%), 109 (15.8%), 94 (16.4%), 77
(21.0%).
4.2.9. (R)-1-(4-Nitro-phenyl)-ethanol. Purified by flash
chromatography on silica gel (eluent: hexanes/EtOAc =
25
6:1); yield 94%, as colorless oil; Mp ½aꢁD ¼ ꢀ30:2 (c 1.13,
1
CHCl3); ee 76%; H NMR (300 MHz, CDCl3): d 8.10 (d,
J = 9 Hz, 2H), 7.48 (d, J = 9 Hz, 2H), 4.97 (q, J = 21 Hz,
1H), 2.80 (s, 1H), 1.46 (d, J = 6.0 Hz, 3H); 13C NMR
(75 MHz, CDCl3): d 153.4, 146.8, 126.0, 123.6, 69.3, 25.3;
m/z (EI) 167 (M+, 0.24%), 152 (100%), 107 (82.2%), 77
(60%), 43 (39.9%).
Acknowledgements
4.2.10. (S)-2-Bromo-1-phenyl-ethanol. Purified by flash
chromatography on silica gel (eluent: hexanes/EtOAc =
We thank the NSFC-20021001, NSFC-20572038 and the
‘Hundred Scientist Program’ from the Chinese Academy
of Sciences for the financial support of this work.
25
8:1); yield 92%, as colorless oil; ½aꢁD ¼ þ41:5 (c 1.16,
CHCl3); ee 71%; 1H NMR (300 MHz, CDCl3): d 7.36
(br, 5H), 4.89 (q, J = 12 Hz, 1H), 3.60 (m, 2H), 2.87 (s,
1H); 13C NMR (75 MHz, CDCl3): d 140.2, 128.4, 125.8,
73.7, 40.0; m/z (EI) 200 (M+, 0.22%), 121 (1.5%), 107
(100%), 79 (62.4%).
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