Efficient Ru(II)-catalyzed asymmetric hydrogenation of simple ketones with C2-symmetric planar chiral metallocenyl phosphinooxazoline ligands

Article abstract of DOI:10.1016/j.tet.2012.02.075

C₂-symmetric metallocenyl planar phosphinooxazoline ligands (2 and 3) have been applied in the Ru(II)-catalyzed asymmetric hydrogenation of simple ketones. This type of ligands enjoys the advantages of dual reaction sites as well as larger steric hindrance than their corresponding C ₁-symmetric counterparts. As a result, almost quantitative conversions and excellent enantioselectivities were obtained for a series of simple ketones. Under the optimal reaction conditions, up to 99.7% ee was obtained in many cases. It was also confirmed that hydrogen rather than reaction solvent i-PrOH is at work in the hydrogenation procedure.

Full text of DOI:10.1016/j.tet.2012.02.075

Tetrahedron 68 (2012) 3295e3299
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Tetrahedron
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Efficient Ru(II)-catalyzed asymmetric hydrogenation of simple ketones with
C2-symmetric planar chiral metallocenyl phosphinooxazoline ligands
,b,
Hui Guo a, Delong Liu a, Nicholas A. Butt b, Yangang Liu a, Wanbin Zhang a
*
a School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China
b School of Chemistry and Chemical Engineering, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai 200240, PR China
a r t i c l e i n f o
a b s t r a c t
Article history:
C2-symmetric metallocenyl planar phosphinooxazoline ligands (2 and 3) have been applied in the Ru(II)-
catalyzed asymmetric hydrogenation of simple ketones. This type of ligands enjoys the advantages of
dual reaction sites as well as larger steric hindrance than their corresponding C1-symmetric counterparts.
As a result, almost quantitative conversions and excellent enantioselectivities were obtained for a series
of simple ketones. Under the optimal reaction conditions, up to 99.7% ee was obtained in many cases. It
was also confirmed that hydrogen rather than reaction solvent i-PrOH is at work in the hydrogenation
procedure.
Received 19 October 2011
Received in revised form 22 February 2012
Accepted 28 February 2012
Available online 5 March 2012
Keywords:
Ketone
Planar chirality
Ó 2012 Elsevier Ltd. All rights reserved.
Phosphinooxazoline ligands
Ru-catalyzed asymmetric hydrogenation
1. Introduction
Because of its high atom economy and satisfactory activity ad-
vantages, the Ru(II)-catalyzed asymmetric hydrogenation of simple
High quality chiral ligands are the critical factor for the de-
velopment of efficient metal-catalyzed asymmetric trans-
formations.1 Of the various chiral ligands reported, planar chiral
metallocenyl ligands have attracted tremendous attention over the
last decade.2 Specifically, ferrocenyl and/or ruthenocenyl phosphi-
nooxazoline ligands play an important role due to their excellent
catalytic behavior in many kinds of asymmetric reactions. Recently,
our group has focused on the development of novel planar chiral
metallocenyl ligands and their applications in different types of
asymmetric synthesis (Fig. 1).3
ketones is one of the simplest and most powerful ways to produce
chiral alcohols and as a core technology has attracted much at-
tention not only in academia but also in industry.4 In our previous
work, C1-symmetric ruthenocenyl phosphinooxazoline ligands (1)
were found to be efficient in this asymmetric hydrogenation.3f,g
Various ketones, including both aromatic and heteroaromatic,
were examined and the reaction proceeded with consistently high
enantioselectivity. This time, our attention has focused on the
C2-symmetric metallocenyl planar phosphinooxazoline ligands for
their excellent catalytic behavior in many kinds of asymmetric ca-
talysis (23hej and 35). Meanwhile, this type of ligands enjoys dual
reaction sites as well as larger steric hindrance than 1. Conse-
quently, higher catalytic efficiency and enantioselectivity should be
achieved by applying them in the asymmetric catalysis. Herein, we
report the excellent catalytic behavior of C2-symmetric phosphi-
nooxazoline ruthenocenes in the Ru(II)-catalyzed asymmetric hy-
drogenation of simple ketones.
2. Results and discussion
2.1. Screening of ligands
Fig. 1. Ligands 1, 2, and 3.
Initially, C2-symmetric phosphinooxazolines were applied in the
Ru(II)-catalyzed asymmetric hydrogenation of acetophenone under
10 atm hydrogen pressure at 25 ꢀC in i-PrOH with t-BuOK as a base
(Table 1).
* Corresponding author. Tel./fax: þ86 21 54743265; e-mail address: wanbin@
sjtu.edu.cn (W. Zhang).
0040-4020/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2012.02.075

3296
H. Guo et al. / Tetrahedron 68 (2012) 3295e3299
Table 1
Since the reaction conditions here were almost identical to
those in asymmetric transfer hydrogenation except for the pres-
ence of hydrogen and the difference of the reaction temperature,
we wanted to determine whether the reaction proceeded via
transfer hydrogenation or a combination of transfer hydrogenation
and H2 hydrogenation. Thus, we conducted a number of transfer
hydrogenation experiments in order to inspect this process and
optimize the reaction conditions (Table 3).
Asymmetric hydrogenation of acetophenone with planar chiral metallocenyl
phosphinooxazoline ligandsa
As shown in Table 3, no reaction was observed at 0 ꢀC even after
2 days (entry 1). With the temperature increasing, the reaction
activity and conversion improved quickly and up to 100% conver-
sion could be obtained within 5 min under reflux conditions (en-
tries 2e5). The reactions showed excellent enantioselectivities and
the best result was obtained at 45 ꢀC (96.8% ee). This phenomenon
provided evidence that it was H2 rather than i-PrOH providing the
hydrogen source in our previous asymmetric hydrogenation at 0 ꢀC.
Entry
Ligand
Conv.b (%)
eec (%) (config.d)
1
2
3
4
2a
2b
3a
3b
100
100
100
100
97.0 (R)
98.8 (R)
96.8 (R)
95.9 (R)
a
Reactions were conducted using 0.4 mmol of acetophenone in i-PrOH (5 mL)
containing 0.65 mol % of the ligands, 1 mol % of Ru(II)(PPh3)3Cl2, and 10 mol % of
t-BuOK/i-PrOH (0.2 M), under H2 atmosphere (10 atm) at 25 ꢀC for 24 h.
b
The conversions were determined by 1H NMR.
Determined by GC using a CP-Chirasil-Dex CB column.
The absolute configuration of product was assigned through comparison of the
c
Table 3
Asymmetric transfer hydrogenation of acetophenone catalyzed by ligand 2ba
d
sign of specific rotation with the literature datum.4n
As shown in Table 1, both 2a and 2b bearing the ruthenoceyl
backbone presented high catalytic activity and excellent enantio-
selectivity (entries 1 and 2). Ligand 2b with relatively larger steric
hindrance in the oxazoline group provided up to 98.8% ee value. For
comparison, the corresponding ferrocenyl ligands 3a and 3b were
also examined in this asymmetric synthesis and somewhat lower
results were obtained. It was interesting that the steric hindrance in
the oxazoline group of the two kinds of metallocenyl ligands
showed a different effect on enantioselectivities. According to the
catalytic behavior, ligand 2b was selected for use in further hy-
drogenation reactions.
Entry
Temp (ꢀC)
Time (min)
Conv.b (%)
eec (%) (config.d)
1
2
3
4
5
0
25
45
65
2 d
15 h
30
10
5
0
79
100
100
100
d
86.1 (R)
96.8 (R)
94.2 (R)
92.4 (R)
Reflux
a
Reactions were conducted using 0.4 mmol of acetophenone in i-PrOH (8 mL)
containing 0.65 mol % of 2b, 1 mol % of Ru(II)(PPh3)3Cl2, and 10 mol % of t-BuOK/i-
PrOH (0.2 M), at designated temperature for a certain time.
b
The conversions were determined by 1H NMR.
Determined by GC using a CP-Chirasil-Dex CB column.
The absolute configuration of product was assigned through comparison of the
2.2. Optimization of reaction conditions
c
d
Accordingly, the effect of base on the reaction was examined
(Table 2). All the bases showed high reaction activity and excellent
enantioselectivity (entries 1e3). Excellent results were also afforded
from 5 to 20 atm H2 pressure (entries 3e5). Temperature had only
a slight influence on the reaction too. From 0 ꢀC to 50 ꢀC, all reactions
showed excellent results and 99.1% ee was obtained at 0 ꢀC (entries
5e7). Therefore, furtherreactionswerecarriedout using 2basa chiral
ligand under a H2 atmosphere of 10 atm at 0 ꢀC with t-BuOK as a base.
sign of specific rotation with the literature datum.4n
In order to obtain more evidence concerning the hydrogen source
in the above hydrogenation, we performed the same reaction in d7-i-
PrOD with either t-BuOK or Na2CO3 as a base. Correspondingly, the
hydrogenation product with H2 as hydrogen source was obtained.
Interestingly, the methyl and hydroxyl groups of hydrogenation
product were deuterated (Scheme 1), which was confirmed by 1H
NMR and MS. To determine the deuteration phenomenon, we ran
a 1H NMR spectrum of acetophenone in d7-i-PrOD immediately after
the addition of t-BuOK or Na2CO3, finding that the methyl group of
acetophenone had already been deuterated. The result further il-
lustrated that only H2 was at work in our hydrogenation conditions.
Table 2
Optimization of the reaction conditions in asymmetric hydrogenation of aceto-
phenone catalyzed by ligand 2ba
Entry
Temp (ꢀC)
Pres. (atm)
Base
Conv.b (%)
eec (%) (config.d)
1
2
3
4
5
6
7
25
25
25
25
25
0
10
10
10
5
20
10
10
KOH
100
100
100
100
100
100
100
98.6 (R)
98.5 (R)
98.8 (R)
98.3 (R)
98.8 (R)
99.1 (R)
98.2 (R)
Na2CO3
t-BuOK
t-BuOK
t-BuOK
t-BuOK
t-BuOK
Scheme 1. Asymmetric hydrogenation of 4a in d7-i-PrOD.
50
2.3. The scope of substrates
a
Reactions were conducted using 0.4 mmol of acetophenone in i-PrOH (5 ml)
containing 0.65 mol % of 2b, 1 mol % of Ru(II)(PPh3)3Cl2, and 10 mol % of base/i-PrOH
(0.2 M), under designated H2 pressure at designated temperature for 24 h.
With the optimal reaction conditions in hand, we explored the
scope of substrates to further investigate the applicability of this
catalytic system. Thus, a number of simple ketones have been
tested in the Ru(II)-catalyzed asymmetric hydrogenation using 2b
as a chiral ligand at 0 ꢀC with t-BuOK as a base (Table 4).
b
The conversions were determined by 1H NMR.
Determined by GC using a CP-Chirasil-Dex CB column.
The absolute configuration of product was assigned through comparison of the
c
d
sign of specific rotations with the literature data.4n

H. Guo et al. / Tetrahedron 68 (2012) 3295e3299
3297
Table 4
asymmetric hydrogenation of a series of simple ketones. This type
of ligands enjoys the advantages of dual reaction sites and relative
larger steric hindrance than their corresponding C1-symmetric
counterparts. As a result, they showed high efficiency in the afore-
mentioned reactions. In many cases, quantitative conversions and up
to 99.7% ee was obtained under optimal reaction conditions. We can
also confirmthat H2 rather than i-PrOHserved asthehydrogensource
in the hydrogenation procedure. These results greatly broaden the
scope and utility of the planar chiral ruthenocenyl phosphinooxazo-
line ligands and the Ru(II)-catalyzed asymmetric hydrogenation.
Asymmetric hydrogenation of simple ketones catalyzed by ligand 2ba,b
Entry
Substrate
R
R0
Product
eec(%)
1
2
3
4
5
6
7
8
4a
4b
4c
4d
4e
4f
4g
4h
4i
Ph
CH3
CH3
CH3
CH3
CH3
CH3
CH3
CH3
5a
5b
5c
5d
5e
5f
5g
5h
5i
99.1 (þ)
99.0 (þ)
99.0 (þ)
97.6 (þ)
98.1 (þ)
99.0 (þ)
98.8 (þ)
98.5 (þ)
98.3 (þ)
99.0 (þ)
97.9 (þ)
99.1 (þ)
96.3 (þ)
97.3 (þ)
98.4 (þ)
98.3 (þ)
99.2 (þ)
99.6 (þ)
99.5 (ꢁ)
99.7 (ꢁ)
91.9 (þ)
95.1 (þ)
40.7 (ꢁ)
2-MePh
3-MePh
4-MePh
2-MeOPh
3-MeOPh
4-MeOPh
4-FPh
4. Experimental
4.1. General procedure for the asymmetric hydrogenation of
acetophenone
9
3-ClPh
CH3
Under an atmosphere of argon, 1 mol % of [RuCl2(PPh3)3] and
0.65 mol % of chiral ligand 2b were dissolved by heating at reflux in
degassed dry 2-propanol (3 mL) for 1 h. After quickly cooling to
0 ꢀC, a solution of acetophenone (0.4 mmol) in degassed dry
2-propanol (2 mL) was added. A solution of t-BuOK in degassed dry
2-propanol (0.2 M, 0.2 mL) was added to the mixture. The above
reaction mixture was stirred under a H2 atmosphere (10 atm) at
0 ꢀC for 24 h in an autoclave. The reaction mixture was concen-
trated under reduced pressure. The residue was determined by 1H
NMR directly to give the percentage conversion of product. The
mixture was purified via flash chromatography with ethyl acetate/
petrol ether (1:5) to give pure product for the determination of the
ee value by GC using a CP-Chirasil-Dex CB column.
10
11
12
13
14
15
16
17
18
19
20
21
22
23
4j
4-ClPh
CH3
5j
4k
4l
4-BrPh
CH3
CH3
CH3
CH3
CH3
CH3
C2H5
(CH2)3CH3
5k
5l
4-PhPh
3,4-diMeOPh
3,4-diClPh
1-Naph
2-Naph
Ph
4m
4n
4o
4p
4q
4r
5m
5n
5o
5p
5q
5r
Ph
4s
4t
4u
4v
4w
1-Indanone
1-Tetralone
2-Furyl
3-Pyridyl
n-Pr
5s
5t
5u
5v
5w
CH3
CH3
CH3
a
All reactions were conducted using 0.4 mmol of simple ketone in i-PrOH (5 mL)
containing 0.65 mol % of 2b, 1 mol % of Ru(II)(PPh3)3Cl2, 10 mol % of t-BuOK/i-PrOH
(0.2 M), under a H2 atmosphere (10 atm) at 0 ꢀC for 24 h.
4.2. General procedure for the asymmetric transfer
hydrogenation of acetophenone
b
Quantitative conversions were obtained.
Determined by GC using a CP-Chirasil-Dex CB column.
c
Under an atmosphere of argon, 1 mol % of [RuCl2(PPh3)3] and
0.65 mol % of chiral ligand 2b were dissolved by heating to reflux in
degassed dry 2-propanol (5 mL) for 1 h. After quickly cooling to
a suitable temperature, a solution of the acetophenone (4 mmol) in
degassed dry 2-propanol (3 mL) was added and the mixture was
stirred at the designated temperature for 15 min. The reaction was
started by addition of a solution of t-BuOK in 2-propanol (0.2 M,
0.2 mL). The reaction mixture was stirred at the designated tem-
perature for a certain time. The reaction mixture was then con-
centrated under reduced pressure. The residue was determined by
1H NMR directly to give the percentage conversion of product. The
mixture was purified by flash chromatography with ethyl acetate/
petrol ether (1:5) to afford pure product for the determination of
the ee value using a CP-Chirasil-Dex CB column.
An electron-donating group, such as CH3 or CH3O, located in any
position of the phenyl ring showed quantitative conversion and
excellent enantioselectivities (entries 2e7). Ketones employing an
electron-withdrawing group, such as F, Cl, and Br also showed
similar reactivity (entries 8e11). Interestingly, p-phenyl acetophe-
none gave 99.0% ee value (entry 12). Multisubstituted acetophe-
nones, such as 3,4-dimethoxyl acetophenone and 3,4-dichloro
acetophenone, also gave excellent but somewhat lower ee than
others (entries 13 and 14). It was shown that steric and/or elec-
tronic factors had little effect on the reaction and all the products of
substituted acetophenones presented quantitative conversions and
excellent enantioselectivities.
Replacement of the phenyl ring by a naphthalene ring, such as
either 1-(naphthalen-1-yl)ethanone or 1-(naphthalen-2-yl)etha-
none, quantitative conversion and more than 98% ee value were
obtained (entries 15 and 16). The aliphatic R group had an obvious
effect on the reaction (entries 17e20). When the CH3 moiety was
replaced by C2H5 or (CH2)3CH3, more than 99% ee value was obtained
(entries 17 and 18). The best results were obtained in the asymmetric
hydrogenation of cyclic aromatic ketones and up to 99.7% ee were
obtained (entries 19 and 20). In addition, this method also allowed
the asymmetric hydrogenation of heteroaromatic ketones in excel-
lent conversion and enantioselectivity (entries 21 and 22). Quanti-
tative conversion but moderate enantioselectivity was obtained with
dialkyl ketone 2-pentanone as a substrate (entry 23). It is obvious
that the present catalytic system is suitable for the Ru(II)-catalyzed
asymmetric hydrogenation of a series of simple aryl alkyl ketones.
4.3. Analytical data
4.3.1. 1-Phenylethanol (5a).6 1H NMR (400 MHz, CDCl3)
d 7.44e7.27
(m, 5H), 4.89 (q, J¼6.4 Hz, 1H), 1.96 (br s, 1H), 1.51 (d, J¼6.4 Hz, 3H).
GC analysis: CP-Chirasil-Dex CB column; 105 ꢀC; isothermal; tR
(major)¼8.9 min, tR (minor)¼10.1 min, 99.1% ee.
4.3.2. 1-Phenylethanol (5a0).6 1H NMR (400 MHz, CDCl3)
d
7.40e7.27 (m, 5H), 4.89 (s, 1H). MS (EI): m/z 108 [Mꢁ18þ] (100).
4.3.3. 1-(o-Tolyl)ethanol (5b).7 1H NMR (400 MHz, CDCl3)
d
7.54e7.49 (m, 1H), 7.30e7.11 (m, 3H), 5.13 (q, J¼6.2 Hz, 1H), 2.38
(s, 3H), 1.84 (br s, 1H), 1.48 (d, J¼6.2 Hz, 3H). GC analysis:
CP-Chirasil-Dex CB column; 110 ꢀC; isothermal; tR (major)¼
17.7 min, tR (minor)¼20.3 min, 99.0% ee.
3. Conclusions
In conclusion, C2-symmetric metallocenyl planar phosphinoox-
azoline ligands (2 and 3) have been applied in the Ru(II)-catalyzed
4.3.4. 1-(m-Tolyl)ethanol (5c).7 1H NMR (400 MHz, CDCl3)
d
7.31e6.98 (m, 4H), 4.85 (q, J¼6.4 Hz, 1H), 2.38 (s, 3H), 2.17 (br s,

3298
H. Guo et al. / Tetrahedron 68 (2012) 3295e3299
1H), 1.47 (d, J¼6.4 Hz, 3H). GC analysis: CP-Chirasil-Dex CB column;
110 ꢀC; isothermal; tR (major)¼18.6 min, tR (minor)¼25.0 min,
99.0% ee.
3H). GC analysis: CP-Chirasil-Dex CB column; 135 ꢀC; isothermal; tR
(major)¼17.2 min, tR (minor)¼18.9 min, 97.3% ee.
4.3.16. 1-(Naphthalen-1-yl)ethanol (5o).6 1H NMR (400 MHz,
CDCl3) d 8.13e8.07 (m, 1H), 7.91e7.86 (m, 1H), 7.81e7.77 (m, 1H),
4.3.5. 1-(p-Tolyl)ethanol (5d).8 1H NMR (400 MHz, CDCl3)
d
7.27 (d,
J¼8.1 Hz, 2H), 7.19 (d, J¼8.1 Hz, 2H), 4.83 (q, J¼6.4 Hz,1H), 2.82 (br s,
1H), 2.39 (s, 3H), 1.47 (d, J¼6.4 Hz, 3H). GC analysis: CP-Chirasil-Dex
CB column; 110 ꢀC; isothermal; tR (major)¼9.7 min, tR (minor)¼
11.0 min, 97.6% ee.
7.68e7.64 (m,1H), 7.56e7.45 (m, 3H), 5.62 (q, J¼6.4 Hz,1H), 2.35 (br
s, 1H), 1.66 (d, J¼6.4 Hz, 3H). GC analysis: CP-Chirasil-Dex CB col-
umn; 150 ꢀC; isothermal; tR (major)¼18.8 min, tR (minor)¼
18.0 min, 98.4% ee.
4.3.6. 1-(2-Methoxyphenyl)ethanol (5e).9 1H NMR (400 MHz,
4.3.17. 1-(Naphthalen-2-yl)ethanol (5p).6 1H NMR (400 MHz,
CDCl3)
d
7.33e7.20 (m, 2H), 7.00e6.86 (m, 2H), 5.10 (q, J¼6.3 Hz,
CDCl3)
d
7.88e7.75 (m, 4H), 7.53e7.41 (m, 3H), 5.01 (q, J¼6.5 Hz,
1H), 3.87 (s, 3H), 2.68 (br s, 1H), 1.52 (d, 3H). GC analysis: CP-
Chirasil-Dex CB column; 110 ꢀC; isothermal; tR (major)¼18.2 min,
tR (minor)¼16.9 min, 98.1% ee.
1H), 2.66 (br s, 1H), 1.65 (d, J¼6.5 Hz, 3H). GC analysis: CP-Chirasil-
Dex CB column; 140 ꢀC; isothermal; tR (major)¼26.4 min, tR
(minor)¼28.0 min, 98.3% ee.
4.3.7. 1-(3-Methoxyphenyl)ethanol (5f).7 1H NMR (400 MHz, CDCl3)
4.3.18. 1-Phenylpropan-1-ol (5q).6 1H NMR (400 MHz, CDCl3)
d
7.35e7.18 (m, 1H), 6.93e6.75 (m, 3H), 4.86 (q, J¼6.4 Hz, 1H), 3.85
d
7.38e7.25 (m, 5H), 4.58 (t, J¼6.6 Hz, 1H), 2.11 (br s, 1H), 1.89e1.68
(s, 3H), 1.97 (br s, 1H), 1.47 (d, J¼6.4 Hz, 3H). GC analysis: CP-
Chirasil-Dex CB column; 115 ꢀC; isothermal; tR (major)¼27.4 min,
tR (minor)¼32.0 min, 99.0% ee.
(m, 2H), 0.92 (t, J¼7.2 Hz, 3H). GC analysis: CP-Chirasil-Dex CB
column; 105 ꢀC; isothermal; tR (major)¼20.4 min, tR (minor)¼
22.2 min, 99.2% ee.
4.3.8. 1-(4-Methoxyphenyl)ethanol (5g).6 1H NMR (400 MHz,
4.3.19. 1-Phenylpentan-1-ol (5r).12 1H NMR (400 MHz, CDCl3)
CDCl3)
d
7.31e7.26 (m, 2H), 6.91e6.85 (m, 2H), 4.84 (q, J¼6.4 Hz,
d
7.40e7.23 (m, 5H), 4.64 (t, J¼6.6 Hz, 1H), 2.15 (br s, 1H), 1.87e1.63
1H), 3.80 (s, 3H), 1.96 (br s, 1H), 1.47 (d, J¼6.4 Hz, 3H). GC analysis:
CP-Chirasil-Dex CB column; 115 ꢀC; isothermal; tR (major)¼
25.6 min, tR (minor)¼28.6 min, 98.8% ee.
(m, 2H), 1.47e1.16 (m, 4H), 0.90 (t, J¼7.2 Hz, 3H). GC analysis: CP-
Chirasil-Dex CB column; 110 ꢀC; isothermal; tR (major)¼32.0 min,
tR (minor)¼31.4 min, 99.6% ee.
4.3.9. 1-(4-Fluorophenyl)ethanol (5h).9 1H NMR (400 MHz, CDCl3)
4.3.20. 1-Indanol (5s).13 1H NMR (400 MHz, CDCl3)
d 7.43e7.38 (m,
d
7.39e7.32 (m, 2H), 7.07e7.00 (m, 2H), 4.90 (d, J¼6.4 Hz, 1H), 1.76
1H), 7.28e7.22 (m, 3H), 5.23 (t, J¼6.1 Hz, 1H), 3.10e3.01 (m, 1H),
2.87e2.76 (m, 1H), 2.52e2.42 (m, 1H), 2.19 (br s, 1H), 1.98e1.88 (m,
1H). GC analysis: CP-Chirasil-Dex CB column; 110 ꢀC; isothermal; tR
(major)¼45.1 min, tR (minor)¼44.6 min, 99.5% ee.
(br s, 1H), 1.48 (d, J¼6.4 Hz, 4H). GC analysis: CP-Chirasil-Dex CB
column; 110 ꢀC; isothermal; tR (major)¼7.9 min, tR (minor)¼
9.0 min, 98.5% ee.
4.3.10. 1-(3-Chlorophenyl)ethanol (5i).7 1H NMR (400 MHz, CDCl3)
4.3.21. 1,2,3,4-Tetrahydronaphthalen-1-ol (5t).6 1H NMR (400 MHz,
d
7.37e7.35 (m, 1H), 7.29e7.20 (m, 3H), 4.84 (q, J¼6.4 Hz, 1H), 2.20
CDCl3) d 7.47e7.39 (m, 1H), 7.24e7.18 (m, 2H), 7.12 (m, 1H), 4.75 (t,
(br s, 1H), 1.57 (d, J¼6.4 Hz, 3H). GC analysis: CP-Chirasil-Dex CB
column; 115 ꢀC; isothermal; tR (major)¼25.3 min, tR (minor)¼
31.2 min, 98.3% ee.
J¼6.6 Hz 4.7 Hz, 1H), 2.94e2.64 (m, 2H), 2.18 (br s, 1H), 2.08e1.68
(m, 4H). GC analysis: CP-Chirasil-Dex CB column; 110 ꢀC; iso-
thermal; tR (major)¼46.1 min, tR (minor)¼44.8 min, 99.7% ee.
4.3.11. 1-(4-Chlorophenyl)ethanol (5j).9 1H NMR (400 MHz, CDCl3)
4.3.22. 1-(Furan-2-yl)ethanol (5u).10 1H NMR (400 MHz, CDCl3)
d
7.37e7.24 (m, 4H), 4.86 (q, J¼6.4 Hz, 1H), 2.15 (br s, 1H), 1.47 (d,
d
7.37 (s,1H), 6.40e6.19 (m, 2H), 4.88 (q, J¼6.5 Hz,1H), 2.01 (br s,1H),
J¼6.4 Hz, 4H). GC analysis: CP-Chirasil-Dex CB column; 115 ꢀC;
1.54(d, J¼6.5 Hz, 3H). GC analysis: CP-Chirasil-Dex CB column; 80 ꢀC;
isothermal; tR (major)¼24.1 min, tR (minor)¼29.7 min, 99.0% ee.
isothermal; tR (major)¼25.2 min, tR (minor)¼25.7 min, 91.9% ee.
4.3.12. 1-(4-Bromophenyl)ethanol (5k).9 1H NMR (400 MHz, CDCl3)
4.3.23. 1-(Pyridin-3-yl)ethanol (5v).12 1H NMR (400 MHz, CDCl3)
d
7.46 (d, J¼8.4 Hz, 2H), 7.22 (d, J¼8.4 Hz, 2H), 4.82 (q, J¼6.4 Hz, 1H),
d
8.51 (d, J¼2.0 Hz, 1H), 8.43 (dd, J¼4.8, 1.6 Hz, 1H), 7.72 (dt, J¼7.8,
2.25 (br s, 1H), 1.44 (d, J¼6.4 Hz, 3H). GC analysis: CP-Chirasil-Dex
CB column; 135 ꢀC; isothermal; tR (major)¼12.1 min, tR (minor)¼
13.3 min, 97.9% ee.
1.8 Hz, 1H), 7.29 (t, J¼6.0 Hz, 1H), 4.90 (q, J¼6.5 Hz, 1H), 4.12 (br s,
1H), 1.49 (d, J¼6.5 Hz, 3H). GC analysis: CP-Chirasil-Dex CB column;
110 ꢀC; isothermal; tR (major)¼17.2 min, tR (minor)¼19.9 min,
95.1% ee.
4.3.13. 1-(4-Biphenyl)ethanol (5l).10 1H NMR (400 MHz, CDCl3)
d
7.68e7.57 (m, 4H), 7.51e7.42 (m, 4H), 7.42e7.35 (m, 1H), 4.95 (q,
4.3.24. 2-Pentanol (5w).14 1H NMR (400 MHz, CDCl3)
d 3.86e3.71
J¼6.4 Hz, 1H), 2.40 (br s, 1H), 1.56 (d, J¼6.4 Hz, 3H). GC analysis: CP-
Chirasil-Dex CB column; 145 ꢀC; isothermal; tR (major)¼41.4 min,
tR (minor)¼45.1 min, 99.1% ee.
(m, 1H), 2.01 (br s,1H), 1.51e1.31 (m, 4H), 1.19 (d, J¼6.4 Hz, 3H), 0.94
(t, J¼6.4 Hz, 3H). GC analysis: CP-Chirasil-Dex CB column; 30 ꢀC;
isothermal; tR (major)¼11.7 min, tR (minor)¼10.6 min, 40.7% ee.
4.3.14. 1-(3,4-Dimethoxyphenyl)ethanol (5m).11 1H NMR (400 MHz,
Acknowledgements
CDCl3)
d
6.79e6.91 (m, 3H), 4.81 (q, J¼6.5 Hz, 1H), 3.89 (s, 3H), 3.85
(s, 3H), 2.04 (br s, 1H), 1.46 (d, J¼6.5 Hz, 3H). GC analysis: CP-
Chirasil-Dex CB column; 105 ꢀC; isothermal; tR (major)¼82.6 min,
tR (minor)¼92.9 min, 96.3% ee.
This work was supported by the National Nature Science
Foundation of China (No. 20972095 and 21172145), Science and
Technology Commission of Shanghai Municipality (No.
10dz1910105), Nippon Chemical Industrial Co., Ltd and In-
strumental Analysis Center of Shanghai Jiao Tong University. We
thank Prof. Tsuneo Imamoto and Dr. Masashi Sugiya for helpful
discussion.
4.3.15. 1-(3,4-Dichlorophenyl)ethanol (5n).12 1H NMR (400 MHz,
CDCl3)
d
7.46 (d, J¼2.1 Hz, 1H), 7.40 (d, J¼8.3 Hz, 1H), 7.18 (dd, J¼8.3,
2.1 Hz, 1H), 4.85 (q, J¼6.5 Hz, 1H), 2.04 (br s, 1H), 1.46 (d, J¼6.5 Hz,

H. Guo et al. / Tetrahedron 68 (2012) 3295e3299
3299
2008, 49, 1012e1015; (g) Wang, Y.; Liu, D.; Meng, Q.; Zhang, W. Tetrahedron:
Asymmetry 2009, 20, 2510e2512; (h) Zhao, X.; Liu, D.; Xie, F.; Zhang, W. Tet-
rahedron 2009, 65, 512e517; (i) Zhang, W.; Liu, D. In Chiral Ferrocenes in
Asymmetric Catalysis: Synthesis and Applications; Dai, L.-X., Hou, X.-L., Eds.;
VCH: Weinheim, Germany, 2010; Vol. 14, pp 175e214; (j) Zhao, X.; Liu, D.; Xie,
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Supplementary data
Supplementary data related to this article can be found in the
online version, at doi:10.1016/j.tet.2012.02.075.
4. For selected papers: (a) Abdur-Rashid, K.; Faatz, M.; Lough, A. J.; Morris, R. H. J.
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