Preparation of highly enantiomerically pure linear secondary alcohols via asymmetric reduction of prochiral ketones with borane

Article abstract of DOI:10.1016/S0957-4166(03)00373-2

An efficient and practical preparation of homochiral linear secondary alcohols, 1-(4-alkylphenyl) and 1-(4-alkoxylphenyl) alcohols, via the asymmetric oxazaborolidine-catalyzed borane reduction of prochiral ketones is described. The phenomenon of the enan

Full text of DOI:10.1016/S0957-4166(03)00373-2

TETRAHEDRON:
ASYMMETRY
Pergamon
Tetrahedron: Asymmetry 14 (2003) 1781–1786
Preparation of highly enantiomerically pure linear secondary
alcohols via asymmetric reduction of prochiral ketones with
borane
Jiaxi Xu,* Xianbin Su and Qihan Zhang
Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Department of Chemical Biology,
College of Chemistry and Molecular Engineering, Peking University, Beijing 100871, China
Received 9 December 2002; accepted 15 April 2003
Abstract—An efficient and practical preparation of homochiral linear secondary alcohols, 1-(4-alkylphenyl) and 1-(4-
alkoxylphenyl) alcohols, via the asymmetric oxazaborolidine-catalyzed borane reduction of prochiral ketones is described. The
phenomenon of the enantioselectivity of 1-(4-alkoxylphenyl) alcohols lower than that of 1-(4-alkylphenyl) alcohols was found and
rationalized to the coordination of the oxygen atom in the alkoxy groups to the catalyst and borane. Based on the rationale, the
enantioselectivity of 1-(4-alkoxylphenyl) alcohols in the asymmetric reduction was improved with increasing the amount of the
catalyst. © 2003 Elsevier Science Ltd. All rights reserved.
1
. Introduction
borane reduction with chiral oxazaborolidines as cata-
lysts is one of the most useful methods to synthesize
optically active secondary alcohols. This method, pio-
3
Homochiral secondary alcohols are very important
intermediates in organic synthesis. They are generally
prepared via chemical or enzymatic resolution of
racemic secondary alcohols, chemical or enzymatic
asymmetric reduction of prochiral ketones, or asym-
metric addition of dialkylzinc to aldehydes. Optically
active linear secondary alcohols are widely used in the
preparation of chiral liquid crystal materials and other
neered by Itsuno, was developed by Corey et al., and
called as the CBS (named after Corey, Bakshi, and
1
,2
3
Shibata) reduction. Herein, we report the preparation
3
,4
of highly enantiomerically pure linear secondary alco-
hols via the asymmetric reduction of prochiral ketones
by borane.
5
6
chiral optical materials.
2
. Results and discussion
Recently we prepared highly enantiomerically pure lin-
ear secondary alcohols, 1-(4-alkylphenyl) alcohols, in
satisfactory yields through chemical resolution. How-
ever, the method was unsuccessful for the resolution of
(
S)-(Diphenylhydroxymethyl)pyrrolidine is one of the
1c
best amino alcohols used in the CBS process, and is
commercially available or conveniently prepared from
L-proline. The oxazaborolidine catalysts 1 derivated
from (S)-(diphenylhydroxymethyl)pyrrolidine is an
effective kind of catalyst, which behave like an enzyme
since they bind both a ketone and a hydride and release
them after the reaction. Corey’s group introduced,
isolated, and identified the chiral oxazaborolidines 1a–
c. Though the catalysts 1a–c have been proved to be
effective catalysts in the asymmetric borane reduction
of ketones with excellent yields and enantioselectivities
for a wide variety of ketones, they have not been
entirely satisfactory, particularly for large-scale produc-
tions, owing to the necessity of relatively expensive
reagents, such as trimethyl boroxine, methylboronic
acid or n-butylboronic acid, to prepare the oxazaboro-
1
-(4-alkoxyphenyl) alcohols. As part of a program
directed towards the preparation of highly enantiomeri-
cally pure linear secondary alcohols, we sought to
prepare homochiral 1-(4-alkoxyphenyl) alcohols.
3
During the last decade, there has been a large number
of papers on the enantioselective reduction of ketones
by a wide variety of reagents made by mixing alu-
minum or boron hydrides and various homochiral diols
8
3,7
or amino alcohols. Among these systems asymmetric
*
0
Corresponding author. E-mail: jxxu@chem.pku.edu.cn
957-4166/03/$ - see front matter © 2003 Elsevier Science Ltd. All rights reserved.
doi:10.1016/S0957-4166(03)00373-2

1
782
J. Xu et al. / Tetrahedron: Asymmetry 14 (2003) 1781–1786
3
lidine catalysts 1a–c. On the other hand, they need to
be prepared first before catalytic reactions in order to
get excellent and stable enantioselectivity, and the cata-
prepared from (S)-(diphenylhydroxymethyl)pyrrolidine
and inexpensive trimethyl borate, and used directly in
asymmetric reduction without any further separation
and purification. To develop a practical and efficient
method to the preparation of homochiral linear sec-
ondary alcohols, we selected Masui’s procedure to pre-
pare our chiral alcohols in good yields and satisfactory
enantioselectivities (Scheme 1 and Table 1).
3
lyst 1a is air and moisture sensitive. Masui et al.
modified the catalysts, developed and applied the cata-
lyst 1d successfully in enantioselective reduction of
9
ketones. They supposed that the B-methoxy oxaza-
borolidine 1d should be a more efficient catalyst than
the B-methyl oxazaborolidine 1b due to its stronger
Lewis acidity of the boron in the oxazaborolidine,
produced by a stronger electron-withdrawing methoxy
group. The advantage of the catalyst 1d is that it can be
From Table 1, relatively higher e.e. values were
obtained for alkylphenyl ketones 2a–f (entries 1–6 in
Table 1), while lower e.e. values were obtained for
Scheme 1. Asymmetric borane reduction of ketones catalyzed by chiral oxazaborolidine 1d.
Table 1. Asymmetric reduction of ketones catalyzed by 0.1 equivalent of the catalyst 1d
Entry
Ketone
Time (h)
Yield (%)a
e.e. (%)b
95c
Config.
h
1
2
3
4
5
6
7
8
9
2a
2b
2c
2d
2e
2f
2g
2h
2i
2
2
3
3
3
95
99
92
95
98
97
97
95
95
96
94
91
96
R
R
R
R
R
R
R
R
R
R
R
R
d
h
93
89
91
91
85
81
80
76
e
h
e
h
e
i
f
i
5
g
i
12
14
14
14
14
14
14
f
i
g
i
f
i
10
11
12
13
2j
2k
2l
75
73
71
f
i
g
i
c
i
2m
69
R
a
Isolated yields after the column chromatography.
E.e. values were determined by HPLC analysis using OD or OJ chiral columns (Chiralcel) and a mixture of n-hexane and 2-propanol as an
b
eluent.
c
d
e
f
OD column, n-hexane: 2-propanol (99: 1, v/v).
OD column, n-hexane: 2-propanol (97: 3, v/v).
OJ column, n-hexane: 2-propanol (98: 2, v/v).
OJ column, n-hexane: 2-propanol (98: 2, v/v).
g
h
OJ column, n-hexane: 2-propanol (97: 3, v/v).
Configuration was assigned according to the rotation value. In each case a positive rotation was obtained, indicating that the selectivity was for
the (R)-enantiomer in agreement with reported work (Refs. 1a,c, 2b, 8 and 9).
Configuration was tentatively assumed according to the mechanism and their optical rotation signs.
i

J. Xu et al. / Tetrahedron: Asymmetry 14 (2003) 1781–1786
1783
Scheme 2. Rationale for enantioselective decrease of 1-(4-alkoxyphenyl) ketones.
3
c
alkoxyphenyl ketones 2g–l (entries 7–12 in Table 1). In
dimethyl sulfide at very low rates through pathway 3.
each case decreased enantioselectivity was reached with
In most cases, the reduction occurs through pathway 1
to afford chiral alcohols with excellent enantioselectivity
at a high reduction rate. However, for alkyl 1-(4-
alkoxylphenyl) ketones 2g–l, the reaction rate of pathway
1 is decreased because the ether-linked oxygen atom
could coordinate with the boron atom in the oxazaboro-
lidine 1d and the amount of the oxazaborolidine 1d
participated in pathway 1 is decreased. Thus, the reduc-
tion needs longer and the reductive rates through path-
ways 3–5 are increased relatively as decrease of the rate
in pathway 1. As the results, the enantioselectivity is
decreased in these cases (Scheme 2).
1
2
increasing length(s) of either R and/or R chain(s) of the
ketones. The only difference between alkyl 1-(4-
alkoxylphenyl) ketones 2g–l and alkyl 1-(4-alkylphenyl)
ketones 2a–f is that the former have an ether-linked
oxygen atom in the molecules. It was also found that the
reduction rate of ketones 2g–l is slower than that of
ketones 2a–f because the reduction of ketones 2g–l needs
longer. The enantioselective decrease of the reduction
ketones 2g–l could be rationalized as following (Scheme
2
). In the reaction mixture there are several pathways to
reduce ketones to alcohols. Generally pathway 1 cata-
lyzed by the oxazaborolidine 1d is a fast process to afford
(
R)-alcohols. Although pathway 2 is also catalyzed by
To verify the rationale, a thioether-link containing
ketone, 1-(4-butylthiophenyl)propanone 2m, was
designed and synthesized from thiophenol via alkylation
with butyl bromide and acylation with propionyl chlo-
ride. The ketone 2m should show a stronger coordi-
the oxazoborolidine 1d, it is disfavored because a larger
1
group Ar (R XPh) occupies an axial position in a
six-membered ring chair conformation in the transition
state. Ketones could also be reduced directly by borane-
Table 2. Asymmetric reduction of alkyl alkoxylphenyl ketones 2g–l and 1-(4-alkythiophenyl)propanone 2m catalyzed by 0.5
equiv. of the catalyst 1d
Entry
Ketone
Time (h)
Yield (%)a
E.e. (%)b
Config.c
1
2
3
4
5
6
7
2g
2h
2i
2j
2k
2l
12
12
12
12
12
12
12
97
96
95
95
96
93
96
89
86
86
85
83
81
83
R
R
R
R
R
R
R
2m
a
Isolated yields after the column chromatography.
E.e. values were determined as shown in Table 1.
Configuration was assigned as shown in Table 1.
b
c

1
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J. Xu et al. / Tetrahedron: Asymmetry 14 (2003) 1781–1786
nation with the Lewis acid boron atom in the catalyst
Varian Mercury 200 (200 MHz) spectrometer in CDCl3
solution with TMS as an internal standard and chemi-
cal shifts are reported in ppm. Mass spectra were
obtained on a VG-ZAB-HS spectrometer. CH analyses
were performed on an Elementar Vario EL analyzer.
Optical rotations were measured on a Perkin–Elmer
model 341LC polarimeter with a thermally jacketed 10
cm cell (concentration c given as g/100 mL). HPLC
analyses were performed on an HP1100 HPLC equip-
ment. The e.e. values were determined by HPLC analy-
sis with chiralcel OD or OJ columns (4.6×250 mm) with
a mixture of hexane–isopropanol as an eluent at an
eluent rate of 0.6 mL/min at monitoring wave 228 nm.
All the starting materials were prepared according to
1
d than the corresponding ether-link containing ketones
g–l because a sulfur atom is a much softer Lewis base
2
than an oxygen atom. Coordination between a sulfur
atom in a thioether and borane, and its effect on
enantioselectivity was observed and reported in the
1
0
literature. The experimental results indicate that the
asymmetric reduction enantioselectivity of ketone 2m is
lower than those of ketones 2e and 2f, which were
selected as samples in the verification experiments since
the length of their chains is same (entries 5, 6 and 13 in
Table 1). The results support our rationale.
Based on the rationale, the reduction enantioselectivity
of the alkyl 1-(4-alkoxylphenyl) ketones 2g–l could be
improved by increasing the amount of the catalyst 1d
because the increasing amount of the catalyst will
decrease the partition of the ether oxygen coordinated
catalyst relatively, the reduction rate of pathway 1 will
be increased and the reaction rates in the pathways 3–5
will be decreased relatively. The experimental results
indicated that the e.e. values were increased 8% and
1c
the literature procedure.
Trimethyl borate and
borane–dimethyl sulfide complex were purchased from
Acros Chemicals Co. Tetrahydrofuran was heated
under reflux over sodium and distilled prior to use.
4.2. General procedure for asymmetric reduction of
ketones
1
4%, respectively, for ketones 2g and 2m when the
To a solution of (S)-2-diphenylhydroxymethylpyrro-
lidine (25 mg, 0.1 mmol) in dry THF (5 mL) was added
trimethyl borate (12 mg, 0.12 mmol), and the mixture
was stirred under nitrogen atmosphere at room temper-
ature for 1 h. After 2 M borane–dimethyl sulfide com-
plex in THF (0.75 mL, 1.5 mmol) was added, a solution
of ketone (1 mmol) in dry THF (5 mL) was added
dropwise over 30 min. The mixture was stirred at 0–5°C
in an ice bath until the ketone disappeared on a thin
layer chromatographic monitoring. The resulting mix-
ture was quenched with 2 M HCl and extracted with
diethyl ether (3×25 mL). The combined organic layers
were successively washed with 2 M HCl and brine,
dried over MgSO4 and concentrated under reduced
pressure. The residue was purified on a silica gel
column with a mixture of petroleum ether (30–60°C)
and acetone (10: 1, v/v) as an eluent to give a colorless
oil chiral secondary alcohol.
catalyst was increased to 0.5 equivalent from 0.1 equiv-
alent (entries 1 and 7 in Table 2). The e.e. value of
ketone 2m is still lower than that of ketone 2g under
this reaction conditions due to the stronger coordina-
tion of the sulfur atom. The results also support our
rationale. Alkyl 1-(4-alkoxylphenyl) ketones 2f–l were
reduced under 0.5 equivalent of the catalyst 1d and
their e.e. values were improved significantly to 4–10%
(
as shown in Table 2).
3. Conclusion
Highly enantiomerically pure linear secondary alcohols,
-(4-alkylphenyl)- and 1-(4-alkoxylphenyl)alcohols,
1
were prepared in excellent yields via a practical and
efficient one-pot borane asymmetric reduction of alkyl
4
-alkylphenyl and 4-alkoxyphenyl ketones, catalyzed by
an oxazaborolidine derivative, (S)-2-methoxy-4,4-
diphenyl-3,1,2-oxazaboro[3.3.0]octane, prepared in situ
from
4.2.1. (R)-1-(4-Ethylphenyl)ethanol 3a. Colorless liquid;
20
1c
20
[h] =+36.9 (c 2.2, MeOH), e.e. 95%; Lit.: [h] =
D
D
(S)-(diphenylhydroxymethyl)pyrrolidine
and
+47.0 (c 1.2, CHCl ), e.e. 98%.
3
trimethyl borate without further separation and purifi-
cation. The phenomenon of the enantioselectivity of
4.2.2. (R)-1-(4-Propylphenyl)ethanol 3b. Colorless liq-
20
1c
20
1
-(4-alkoxylphenyl) alcohols lower than that of 1-(4-
uid; [h] =+33.2 (c 2.2, MeOH), e.e. 93%; Lit.: [h] =
D
D
alkylphenyl) alcohols was found and rationalized to the
coordination of the oxygen atom in the alkoxy groups
to the catalyst and borane. The rationale was confirmed
by the asymmetric reduction of a designed substrate
+40.9 (c 1.7, CHCl ), e.e. 96%.
3
4.2.3. (R)-1-(4-Butylphenyl)ethanol 3c. Colorless liquid;
2
0
1c
20
D
[h] =+31.5 (c 1.4, MeOH), e.e. 89%; Lit.: [h] =
D
1-(4-butylthiophenyl)propanone. Based on the ratio-
+42.1 (c 1.4, CHCl ), e.e. 98%.
3
nale, the enantioselectivity of 1-(4-alkoxylphenyl) alco-
hols in the asymmetric reduction was improved with
increasing amount of the catalyst.
4.2.4. (R)-1-(4-Pentylphenyl)ethanol 3d. Colorless liquid;
20
1c
20
[h] =+29.3 (c 1.2, MeOH), e.e. 91%; Lit.: [h] =
D
D
+
33.2 (c 1.5, CHCl ), e.e. 92%.
3
4. Experimental
4.2.5. (R)-1-(4-Pentylphenyl)propanol 3e. Colorless liq-
20
1
uid; [h] =+28.4 (c 2.3, MeOH), e.e. 91%; H NMR
D
4.1. General
(200 MHz, CDCl : l 0.89 (t, J=6.4 Hz, 3H, CH ), 0.92
3
3
(
t, J=7.4 Hz, 3H, CH ), 1.26–1.36 (m, 4H, 2CH ),
3
2
IR spectra were recorded on a Bruker Vector 22 FT-IR
spectrophotometer. H spectra were recorded on a
1.57–1.90 (m, 5H, OH, 2CH ), 2.59 (t, J=7.6 Hz, 2H,
2
1
ArCH ), 4.57 (t, J=6.6 Hz, 1H, CH), 7.14–7.27 (m, 4H,
2

J. Xu et al. / Tetrahedron: Asymmetry 14 (2003) 1781–1786
1785
+
ArH). MS (EI) m/z: 206 (M ), 177, 91, 71, 43, 29; IR w
CH ), 0.91 (t, J=6.4 Hz, 3H, CH ), 1.33–1.48 (m, 6H,
3 3
−
1
(
cm ): 3362 (OH), 1099. Anal. calcd for C H O
3CH ), 1.60–1.89 (m, 5H, OH, 2CH ), 3.94 (t, J=6.6
14
22
2
2
(
1
206.32): C, 81.50; H, 10.75. Found: C, 81.21; H,
0.71%.
Hz, 2H, OCH ), 4.52 (t, J=6.6 Hz, 1H, CH), 6.83–7.26
2
+
(m, 4H, ArH). MS (EI) m/z: 236 (M ), 207, 123, 95, 77,
−
1
4
3; IR w (cm ): 3381 (OH), 1245, 1098. Anal. calcd for
4
.2.6. (R)-1-(4-Pentylphenyl)-n-butanol 3f. Colorless liq-
C H O (236.35): C, 76.23; H, 10.24. Found: C, 75.89;
H, 10.57%.
15
24
2
2
0
1
uid; [h] =+27.6 (c 2.1, MeOH), e.e. 85%; H NMR
D
(200 MHz, CDCl ): l 0.88 (t, J=6.4 Hz, 3H, CH ),
3
3
0
2
2
4
4
.92 (t, J=7.2 Hz, 3H, CH ), 1.24–1.46 (m, 5H, OH,
4.2.12. (R)-1-(4-Hexoxyphenyl)-n-pentanol 3l. Colorless
3
20
1
CH ), 1.57–1.84 (m, 4H, 2CH ), 2.59 (t, J=7.6 Hz,
liquid; [h] =+19.6 (c 1.9, MeOH), e.e. 81%; H NMR
2
2
D
H, ArCH ), 4.64 (t, J=6.6 Hz, 1H, CH), 7.13–7.27 (m,
(200 MHz, CDCl ): l 0.88 (t, J=6.4 Hz, 3H, CH ),
2
3
3
+
H, ArH). MS (EI) m/z: 220 (M ), 177, 149, 91, 71, 56,
3; IR w (cm ): 3363 (OH), 1106. Anal. calcd for
0.91 (t, J=6.4 Hz, 3H, CH ), 1.22–1.53 (m, 10H,
3
−
1
5CH ), 1.60–1.83 (m, 5H, OH and 2CH ), 3.94 (t,
2
2
C H O (220.35): C, 81.76; H, 10.98. Found: C, 81.76;
H, 11.02%.
J=6.6 Hz, 2H, OCH ), 4.60 (t, J=6.2 Hz, 1H, CH),
15
24
2
+
6.84–7.27 (m, 4H, ArH). MS (EI) m/z: 264 (M ), 246,
07, 162, 133, 123, 95, 77, 57; IR w (cm ): 3374 (OH),
−
1
2
4
.2.7. (R)-1-(4-Butoxyphenyl)-n-propanol 3g. Colorless
1245, 1111. Anal. calcd for C H O (264.40): C, 77.22;
H, 10.67. Found: C, 77.04; H, 10.66%.
17
28
2
2
0
1
liquid; [h] =+29.9 (c 2.2, MeOH), e.e. 89%; H NMR
D
(200 MHz, CDCl ): l 0.89 (t, J=7.4 Hz, 3H, CH ),
3
3
0
1
.97 (t, J=7.2 Hz, 3H, CH ), 1.40–1.60 (m, 2H, CH ),
4.3. Synthesis of 1-(4-butylthiophenyl)propanone 2m
3
2
.63–1.90 (m, 5H, OH, 3CH ), 3.95 (t, J=6.6 Hz, 2H,
2
OCH ), 4.52 (t, J=6.6 Hz, 1H, CH), 6.83–7.26 (m, 4H,
ArH). MS (EI) m/z: 208 (M ), 179, 123, 95, 77, 57, 43;
IR w (cm ): 3380 (OH), 1264, 1119. Anal. calcd for
C H O (208.30): C, 74.96; H, 9.68. Found: C, 74.80;
4.4 g (40 mmol) of thiophenol was dissolved in 20 mL
of 50% NaOH. To the resulting solution was added
dropwise 5.48 g (40 mmol) of butyl bromide and was
kept stirring for 4 h. The reaction mixture was
extracted with diethyl ether (2×20 mL), washed with
2
+
−
1
13
20
2
H, 9.79%.
water, dried over Na SO4 and concentrated under
2
4
.2.8. (R)-1-(4-Butoxyphenyl)-n-pentanol 3h. Colorless
reduced pressure. The residue was distilled at boiling
point 140–142°C/50 mmHg to afford a colorless oil
butyl phenyl thioether 5.71 g in the yield of 86%.
2
0
1
liquid; [h] =+26.6 (c 2.0, MeOH), e.e. 86%; H NMR
D
(200 MHz, CDCl ): l 0.88 (t, J=6.8 Hz, 3H, CH ),
3
3
0
1
.97 (t, J=7.6 Hz, 3H, CH ), 1.20–1.58 (m, 6H, 3CH ),
3 2
.63–1.83 (m, 5H, OH, 2CH ), 3.95 (t, J=6.4 Hz, 2H,
To a mixture of butyl phenyl thioether (3.32 g, 20
mmol) and anhydrous aluminum trichloride (2.94 g, 22
mmol) was added propionyl chloride (1.85 g, 20 mmol)
dropwise in an ice–water bath and the resulting mixture
was stirred at room temperature for 1 h. The reaction
mixture was quenched with 20 mL of ice–water and
extracted with diethyl ether (2×20 mL). The combined
organic layers were successively washed with water to
neutration, dried over Na SO and concentrated under
2
OCH ), 4.60 (t, J=6.6 Hz, 1H, CH), 6.83–7.27 (m, 4H,
ArH). MS (EI) m/z: 236 (M ), 218, 189, 179, 133, 123,
2
+
−
1
95, 77, 57; IR w (cm ): 3372 (OH), 1245, 1111. Anal.
calcd for C H O (236.35): C, 76.23; H, 10.24. Found:
C, 76.10; H, 10.31%.
1
5
24
2
4
.2.9. (R)-1-(4-Pentoxyphenyl)-n-propanol 3i. Colorless
2
0
1
liquid; [h] =+26.8 (c 1.7, MeOH), e.e. 86%; H NMR
D
2
4
(200 MHz, CDCl ): l 0.88 (t, J=7.2 Hz, 3H, CH ),
reduced pressure. The residue was crystallized from
3
3
0
1
.92 (t, J=6.8 Hz, 3H, CH ), 1.33–1.50 (m, 4H, 2CH ),
petroleum ether (30–60°C) to give colorless crystallines
2.87 g, yield 65%, mp 37–38°C; H NMR (200 MHz,
3
2
1
.60–1.85 (m, 5H, OH, 2CH ), 3.94 (t, J=6.6 Hz, 2H,
2
OCH ), 4.52 (t, J=6.6 Hz, 1H, CH), 6.85–7.26 (m, 4H,
ArH). MS (EI) m/z: 222 (M ), 204, 193, 123, 95, 77, 43,
2
CDCl ): l 0.95 (t, J=7.2 Hz, 3H, CH ), 1.22 (t, J=7.4
2
3
3
+
Hz, 3H, CH ), 1.48 (tq, 2H, CH ), 1.67 (tt, 2H, CH ),
3 2 2
−
1
9; IR w (cm ): 3372 (OH), 1246, 1098. Anal. calcd for
2.96 (q, J=7.4 Hz, 2H, CH ), 2.99 (t, J=7.6, 2H, CH ),
2 2
C H O (222.32): C, 75.63; H, 9.97. Found: C, 75.36;
H, 10.01%.
7.29 (d, J=8.2 Hz, 2H, ArH), 7.86 (d, J=8.2 Hz, 2H,
14
22
2
−
1
ArH); IR (KBr) w 2960, 1681 (CꢀO), 1592, 1555 cm ;
+
EI-MS (70 eV) m/z (%): 222 (M , 30), 193 (100), 137
4
.2.10. (R)-1-(4-Pentoxyphenyl)-n-pentanol 3j. Colorless
(48), 109 (17), 57 (13), 43 (17), 29 (24). Anal. calcd for
2
0
1
liquid; [h] =+23.6 (c 2.2, MeOH), e.e. 85%; H NMR
C H OS (222.35): C, 70.22; H, 8.16; Found: C, 70.19;
D
13 18
(200 MHz, CDCl ): l 0.88 (t, J=6.6 Hz, 3H, CH ),
H, 8.63%.
3
3
0
1
.92 (t, J=6.8 Hz, 3H, CH ), 1.25–1.47 (m, 8H, 4CH ),
3
2
.58–1.82 (m, 5H, OH, 2CH ), 3.95 (t, J=6.4 Hz, 2H,
4.4. Asymmetric reduction of 1-(4-butylthiophenyl)-
propanone
2
OCH ), 4.60 (t, J=6.6 Hz, 1H, CH), 6.85–7.27 (m, 4H,
ArH). MS (EI) m/z: 250 (M ), 232, 193, 162, 133, 123,
2
+
−
1
95, 77, 43; IR w (cm ): 3371 (OH), 1245, 1111. Anal.
The procedure is the same as described in Section 4.2.
calcd for C H O (250.38): C, 76.75; H, 10.47. Found:
C, 76.69; H, 10.53%.
1
6
26
2
4.4.1. (R)-1-(4-Butylthiophenyl)-n-propanol 3m. Color-
20
1
less liquid; [h] =+18.5 (c 1.0, MeOH), e.e. 83%; H
D
4
.2.11. (R)-1-(4-Hexoxyphenyl)-n-propanol 3k. Color-
NMR (200 MHz, CDCl ): l 0.91 (t, J=7.4 Hz, 3H,
3
2
0
1
less liquid; [h] =+24.5 (c 1.9, MeOH), e.e. 83%; H
CH ), 0.92 (t, J=7.2 Hz, 3H, CH ), 1.39–1.84 (m, 7H,
D
3
3
NMR (200 MHz, CDCl ): l 0.88 (t, J=6.4 Hz, 3H,
OH, 3CH ), 2.91 (t, J=7.2 Hz, 2H, SCH ), 4.56 (dt,
2 2
3

1
786
J. Xu et al. / Tetrahedron: Asymmetry 14 (2003) 1781–1786
J=3.0, 6.4 Hz, 1H, CH), 7.22–7.32 (m, 4H, ArH). MS
Deloux, L.; Srebnik, M. Chem. Rev. 1993, 93, 763; (d)
Corey, E. J.; Helal, C. J. Angew. Chem., Int. Ed. Engl.
1998, 37, 1986.
+
(
(
(
(
EI) m/z: 224 (M , 18), 206 (4), 195 (100), 150 (5), 139
19), 123 (5), 111 (24), 77 (10), 57 (15), 29 (15); IR w
−
1
cm ): 3371 (OH), 1094, 819. Anal. calcd for C H OS
4. (a) Csuk, R.; Glanzer, B. I. Chem. Rev. 1991, 91, 49; (b)
Yadav, J. S.; Reddy, P. T.; Nanda, S.; Rao, A. B.
Tetrahedron: Asymmetry 2001, 12, 63; (c) Yadav, J. S.;
Reddy, P. T.; Nanda, S.; Rao, A. B. Tetrahedron: Asym-
metry 2001, 12, 3381.
13
20
224.36): C, 69.59; H, 8.98. Found: C, 69.38; H, 9.50%.
Acknowledgements
5
. (a) Berger, S.; Langer, F.; Lutz, C.; Knochel, P.; Mobley,
T. A.; Reddy, C. K. Angew. Chem., Int. Ed. Engl. 1997,
The project was supported by National Natural Science
Foundation of China (No. 20272002), Ministry of Edu-
cation of P. R. China (SRF for ROCS and EYTP), and
Peking University.
36, 1496; (b) Zhang, F. Y.; Yip, C. W.; Cao, R.; Chan, A.
S. C. Tetrahedron: Asymmetry 1997, 8, 585; (c) Shan, Z.
X.; Xiong, Y.; Li, W. Z.; Zhao, D. J. Tetrahedron:
Asymmetry 1998, 9, 3985.
6. (a) Ohno, K.; Saito, S.; Miyazawa, K.; Ushioda, M.
Inoue, H.; Yoshida, N. EP270244, 1988 (Chem. Abstr.
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1
2779.