Synthesis of novel chiral Schiff bases and their application in asymmetric transfer hydrogenation of prochiral ketones

Article abstract of DOI:10.1002/hc.20494

Novel chiral Schiff bases were synthesized from (+)-camphor, and their application to asymmetric transfer hydrogenation of prochiral ketones is described. The asymmetric transfer hydrogenation reaction could afford excellent conversion rates (up to 97.3%) and up to 27.3% enantiomeric excess.

Full text of DOI:10.1002/hc.20494

Heteroatom Chemistry
Volume 19, Number 7, 2008
Synthesis of Novel Chiral Schiff Bases and
Their Application in Asymmetric Transfer
Hydrogenation of Prochiral Ketones
Zhongqiang Zhou and Yongjun Bian
Key Laboratory of Catalysis and Materials Science of Hubei Province,
College of Chemistry and Materials Science, South-Central University for Nationalities,
Wuhan 430074, People’s Republic of China
Received 17 April 2008; revised 6 July 2008, 24 July 2008
genation of ketones [9–12]. To date, many modified
ABSTRACT: Novel chiral Schiff bases were syn-
thesized from (+)-camphor, and their application
to asymmetric transfer hydrogenation of prochiral ke-
tones is described. The asymmetric transfer hydro-
genation reaction could afford excellent conversion
rates (up to 97.3%) and up to 27.3% enantiomeric
excess. 2008 Wiley Periodicals, Inc. Heteroatom Chem
19:682–687, 2008; Published online in Wiley InterScience
(www.interscience.wiley.com). DOI 10.1002/hc.20494
TsDPEN ligands have been developed and applied
to this reaction, providing good conversion rates
and enantioselectivities [13–27]. Monosulfonamide-
cyclohexane-1,2-diamine [28,29], amino alcohols
[30], and amino amides [31–36] have been found
to be efficient ligands for the asymmetric transfer
hydrogenation of ketones, too. The design and syn-
thesis of new chiral ligands for transition metals
have played a significant role in the development of
the asymmetric transfer hydrogenation reaction. To
the best of our knowledge, there are no reports on the
use of ligand derived from camphor in the ATH re-
action. In the present work, novel chiral Schiff bases
were synthesized from (+)-camphor, and their ap-
plication to asymmetric transfer hydrogenation of
prochiral ketones is described.
ꢀ
C
INTRODUCTION
Chiral alcohols are very important synthetic in-
termediates and building blocks in organic syn-
thesis and the pharmaceutical industry. Asym-
metric transfer hydrogenation (ATH) of prochiral
ketones to enantiomerically pure secondary alco-
hols provides an attractive alternative to asymmet-
ric hydrogenation due to its operational simplic-
ity, the easy availability of hydrogen sources, lower
cost, and safety [1–8]. Noyori’s ruthenium com-
plexes containing arene and N-(p-toluenesulfonyl)-
1,2-diphenylethylenediamine (TsDPEN) ligands are
efficient catalysts for the asymmetric transfer hydro-
RESULTS AND DISCUSSION
The synthetic route for chiral Schiff bases is sum-
marized in Scheme 1. The reaction of (+)-ketopinic
acid [37] 3 that was easily derived from camphor
with thionyl chloride followed by the addition of am-
monium hydroxide produced compound 4a. Simi-
larly, 4b and 4c were prepared by the reaction of
acid chloride with amine in the presence of tri-
ethylamine. Amide 4 (1.0 equiv) and benzylamine
(3 equiv) were mixed in refluxing toluene with cat-
alytic BF3·Et2O (10 mol%), followed by azeotropic
removal of water (12 h), giving the chiral Schiff bases
5a–5c in excellent yields. The reaction of amine with
Correspondence to: Zhongqiang Zhou; e-mail: zhou-zq@
hotmail.com.
Contract grant sponsor: The Natural Science Foundation of
Hubei Province.
Contract grant number: 2007ABA291.
2008 Wiley Periodicals, Inc.
c
ꢀ
682

Novel Chiral Schiff Bases and Their Application in Asymmetric Transfer Hydrogenation of Prochiral Ketones 683
1. SOCl2
2. RNH2
PhCH2NH2
BF3·Et2O
O
O
COOH
O
NCH2Ph
CONHR
CONHR
5a R=H
4a R=H
(+)-camphor
3
5b R=CH(CH3)Ph
4b R=CH(CH3)Ph
4c R=Ph
5c R=Ph
Ac2O, H2SO4
KMnO4
PhCH2NH2
BF3·Et2O
SOCl2
RNH2
O
O
O
NCH2Ph
SO2NHR
SO3H
SO2Cl
SO2NHR
6a R=cyclohexyl
6b R=CH2Ph
1
2
7a R=cyclohexyl
7b R=CH2Ph
SCHEME 1
TABLE 1 Asymmetric Transfer Hydrogenation of Acetophe-
(1S)-(+)-10-camphorsulfonyl chloride [38] 2, which
was prepared from the commercially available (+)-
camphor, catalyzed by triethylamine gave camphor-
sulfonamides 6a and 6b with good yields. Sulfon-
amides 6 (1.0 equiv) and benzylamine (3 equiv) were
mixed in refluxing toluene with catalytic BF3·Et2O
(10 mol%), followed by azeotropic removal of water
(12 h), giving the chiral Schiff bases 7a and 7b in
good to excellent yields.
none with Chiral Schiff Basesa
Entry Ligand Ru/L T (◦C) Conversion (%)d e.e. (%)e
1
5a
5a
5a
5b
5c
7a
7b
5c
5c
5c
5c
5c
5c
5c
5c
5c
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:1
1:2
1:1
1:2
1:2
1:1
1:2
1:2
1:3
40
40
60
60
60
60
60
25
25
40
40
60
80
80
60
60
13
17
0
0
0
0
11.8
0
2b
3
49.3
51.6
83.5
51.2
61.8
5.2
5.7
5.6
26
51.5
2.8
4
5
6
7
8
9
10
11
12
13c
14c
15b
16b
First, acetophenone was tested as model sub-
strate in the ATH reaction using 5a as ligand. The re-
sults are listed in Table 1. The catalyst was generated
in situ by reacting chiral Schiff base with [RuCl2(p-
cymene)]2 in isoprapanol. Following the addition of
0.1 M of KOH in isopropanol and acetophenone
with a substrate/catalyst/KOH (S/C/KOH) ratio of
100:1:2.5, the ketone was converted into racemic
1-phenylethanol in 13% conversion rate at 40◦C
in 48 h reaction time. When S/C/KOH ratio
was changed to S/C/KOH = 50:1:2.5, racemic
phenylethanol was obtained in 17% conversion rate.
When the reaction temperature was increased to
60◦C, acetophenone was converted into racemic
phenylethanol in a moderate conversion rate (entry
3). The other chiral Schiff bases were tested under
the same reaction condition; acetophenone was con-
verted into (R)-1-phenylethanol in 83.5% conversion
rate with 11.8% enantiomeric excess (e.e.) (entry 5)
when chiral Schiff base 5c was used as ligand.
We studied the influence of the reaction temper-
ature on the reduction of acetophenone, using 5c
as ligand with a molar ratio of Ru/L = 1:1. An in-
crease in the temperature leads to an improvement
in the catalytic activity. The increase of the reaction
temperature from 25 to 60◦C notably increased the
reaction rate. However, when the reaction temper-
ature was increased to 80◦C under the same reac-
0
ndf
ndf
ndf
11.4
17
ndf
20.2
20.2
23.5
15.2
64.7
67.4
aUnless otherwise indicated, the reaction was carried out in 19.5 mL
of isopropanol under argon atmosphere for 48 h, using 2 mmol ace-
tophenone, S/C/KOH = 100:1:2.5. Molar ratio of Ru/L = 1:1 corre-
sponds to one molecule of ligand per one atom of Ru.
bS/C/KOH = 50:1:2.5.
cThe reaction was carried out for 30 h.
dDetermined by GC-MS analysis on a HP-5ms column.
eDetermined by comparison of the specific rotation with the literature
[39]. The alcohol configuration was determined by comparison of the
sign of the optical rotation with literature [39] data; acetophenone was
converted into (R)-1- phenylethanol.
f Not determined.
tion conditions, acetophenone was converted into
1-phenylethanol only in 2.8% conversion rate (entry
13). Thus, the optimum reaction temperature is at
60◦C.
We also examined the influence of the ruthe-
nium/ligand ratio (Ru/5c) both on the conversion
rate and on the e.e. The reaction was performed with
a Ru/5c ratio = 2 at 60◦C, in comparison with Ru/5c
Heteroatom Chemistry DOI 10.1002/hc

684 Zhou and Bian
OH
O
In summary, novel chiral Schiff bases have been
conveniently synthesized from readily available (+)-
camphor in good yields and are used as ligands for
asymmetric transfer hydrogenation of prochiral ke-
tones, affording excellent conversion rates and low
enantiomeric excesses. The further application of
these chiral Schiff bases on a variety of asymmet-
ric reactions is under investigation.
[RuCl2(p-cymene)]2/ligand
R2
R2
isopropanol/KOH
R1
R1
SCHEME 2
ratio = 1, the e.e. value slightly increased, but the
conversion rate was notably decreased (entry 12).
The increased or decreased temperature caused a
decrease in the conversion rate. The S/C ratio was
changed to 50; after the reaction, 64.7% of the con-
version rate and 20.2% of the e.e. value were ob-
tained (entry 15). The reaction could be run at a
higher Ru/5c ratio of 3 without a notable increase of
the conversion and enantioselectivity (entry 16).
We subsequently explored the scope of the asym-
metric transfer hydrogenation of prochiral ketones,
using the best performing ligand 5c (Scheme 2).
As shown in Table 2, for the examined ketones,
the ligand 5c gave 0%–27.3% e.e. and 12.8%–97.3%
chemical conversion rates. The reaction of the sub-
stituted acetophenone showed that the chemical
conversion rate was significantly affected by the
type of substituent. The substituted acetophenones
(methyl at p- or α-position) were reduced in excellent
conversion rates (entries 2 and 3). The p-haloketones
(chloride or bromide at p-position) were reduced
in excellent conversion rates (entries 4 and 5), too.
However, α-haloketones (chloride or bromide at
α-position) were reduced in low conversion rates
(entries 6–9). The results show that the reduction of
prochiral ketones could give a low enantioselectivity.
Moreover, the results also show that α-haloketones
were reduced to the corresponding alcohols with (S)-
configuration, whereas other ketones provided alco-
hols with (R)-configuration.
EXPERIMENTAL
Melting points were determined on a melting point
apparatus and are uncorrected. Specific rotations
were recorded in a WZZ-3 digital polarimeter. IR
spectra were recorded on a Nicolet Nexus 470 FTIR
spectrometer. 1H NMR spectra were recorded on
a Varian mercury 300, using TMS as an internal
standard. Elemental analyses were carried out on a
PE-2400 elemental analyzer. The conversions were
measured by GC-MS on an Agilent 5973N (HP-
5ms capillary column). [RuCl2(p-cymene)]2 was pur-
chased from the Alfa Aesar Chemical. Other chemi-
cal reagents were obtained from Sinopharm Chemi-
cal Reagent Co. Ltd. (Shanghai, People’s Republic of
China).
(1S)-7,7-Dimethylbicyclo[2.2.1]heptane-1-
carboxylamide-2-one 4a
To a flask containing 3.64 g (20 mmol) of (+)-
ketopinic acid, 8 mL thionyl chloride was added. The
mixture was stirred at room temperature for 2 h and
then at reflux temperature for 1 h. The excess thionyl
chloride was removed under reduced pressure, and
the crude acid chloride was obtained. Ammonium
hydroxide (10 mL, 28%) was added slowly to the so-
lution of acid chloride obtained above in 10 mL of
benzene with vigorous stirring at 0◦C. After the stir-
ring was continued at 0◦C for 8 h, 10 mL benzene
was added. The organic layer was separated, and the
aqueous layer was extracted with benzene (10 mL ×
3). The combined organic layers were washed with
saturated brine, dried over anhydrous MgSO4. The
solvent was removed under reduced pressure, and
the crude product was purified by recrystallization
from ethyl acetate to afford 4a. Yield 86.2%; mp 194–
195◦C; [α]D = + 120 (c = 0.65, CHCl3). IR (KBr) νmax
(cm−1): 3380, 3170, 2960, 1736, 1669, 1598, 1398.
1H NMR (300 MHz, CDCl3), δ (ppm): 1.01 (s, 3H,
CH3), 1.24 (s, 3H, CH3), 1.42–1.69 (m, 2H), 1.96–2.20
(m, 3H), 2.50–2.56 (m, 2H), 6.41 (s, 1H, NH), 7.44 (s,
1H, NH). Anal. Calcd for C10H15NO2: C 66.27, H 8.34,
N 7.73; Found: C 66.13, H 8.39, N 7.81.
TABLE 2 Asymmetric Transfer Hydrogenation of Prochiral
Ketones with Ligand 5ca
Entry
R1
R2
Conv. (%)b
e.e. (%)c
Conf.d
1
2
3
4
5
6
7
8
9
H
H
CH3
Cl
Br
CH3
Cl
H
CH3
H
H
H
Cl
Cl
Cl
Br
83.5
93.7
95.6
93.2
97.3
35.4
12.8
16.9
21.5
11.8
0
0
R
–
–
0
–
4.1
4.5
0
0
27.3
R
S
–
–
S
H
H
aThe reaction conditions were the same as used in entry 5 of Table 1.
bDetermined by GC-MS analysis on a HP-5ms column.
cDetermined by comparison of the optical rotation value with the
literature [39–42] value.
dDetermined by comparison of the specific rotation with the literature
[39–42].
Heteroatom Chemistry DOI 10.1002/hc

Novel Chiral Schiff Bases and Their Application in Asymmetric Transfer Hydrogenation of Prochiral Ketones 685
(1S,1ꢁS)-7,7-Dimethylbicyclo[2.2.1]heptane-1-N-
(1S)-N-(Benzyl)-7,7-dimethylbicyclo[2.2.1]hept-
1-yl-methanesulfonamide 6b
(1ꢁ-pheny)lethylcarboxylamide-2-one 4b
To a flask containing 3.64 g (20 mmol) of (+)-
ketopinic acid, 8 mL thionyl chloride was added.
The mixture was stirred at room temperature for 2 h
and then at reflux temperature for 1 h. The excess
thionyl chloride was removed under reduced pres-
sure, and the crude acid chloride was obtained. Tri-
ethylamine (7 mL) was added to the solution of (S)-
1-phenylethylamine (2.42 g, 20 mmol) in 20 mL of
benzene at 0◦C, and then, with vigorous stirring, the
solution of acid chloride obtained above in 10 mL of
benzene was added dropwise. After the stirring was
continued at room temperature for 20 h, 20 mL ethyl
acetate was added. The organic layer was washed
with saturated brine, dried over anhydrous MgSO4.
The solvent was removed under reduced pressure,
and the crude product was suitable for the next re-
action without purification, yielding 98.2%.
Compound 6b was prepared using the same proce-
dure as discussed for 6a. After the usual workup,
the crude product was suitable for the next reaction
without purification, yielding 96.6%.
General Procedure for Preparation of Chiral
Schiff Bases
A solution of benzylamine (5 mL, 45 mmol), amide 4
(or sulfonamide 6) (15 mmol), and BF3·Et2O (0.2 mL,
1.5 mmol) in toluene (50 mL) was heated under re-
flux, using a Dean-Stark trap for 12 h. Toluene was
removed, and the residue was purified by recrystal-
lization.
5a: The crude product was recrystallized from
ethyl acetate to give a white solid. Yield 93.8%; mp
132–134◦C; [α]D = +99.4 (c = 0.5, CHCl3). IR (KBr)
νmax (cm−1): 3235, 3029, 2966, 1680, 1658, 1596, 1489,
1452, 1394, 1030, 731, 694. 1H NMR (300 MHz,
CDCl3), δ (ppm): 0.94 (s, 3H, CH3), 1.26 (s, 3H, CH3),
1.31–1.68 (m, 2H), 2.00–2.06 (m, 2H), 2.08–2.10 (m,
1H), 2.55–2.59 (m, 2H), 4.49 (q, J = 8.4, 24 Hz, 2H),
5.56 (s, 1H, NH), 7.26–7.36 (m, 5H, Ar-H), 9.32 (s,
1H, NH). Anal. Calcd for C17H22N2O: C 75.52, H 8.20,
N 10.36; Found: C 75.41, H 8.13, N 10.41.
5b: The crude product was recrystallized from
ethyl acetate/petroleum ether to give a white solid.
Yield 89.8%; mp 110–112◦C; [α]D = +78 (c = 0.5,
CHCl3). IR (KBr) νmax (cm−1): 3155, 2960, 1674, 1652,
1551, 1495, 1450, 1378, 1322, 1137, 1078, 1026, 752.
1H NMR (300 MHz, CDCl3), δ (ppm): 0.83 (s, 3H,
CH3), 1.23 (s, 3H, CH3), 1.31–1.35 (m, 1H), 1.43 (d,
J = 3.6 Hz, 3H, CH3), 1.65–1.66 (m, 1H), 1.96 (s,
1H), 2.03–2.12 (m, 2H), 2.54–2.60 (m, 2H), 4.45–4.50
(m, 2H), 5.13–5.15 (m, 1H), 7.21–7.33 (m, 10H, Ar-
H), 10.07 (s, 1H, NH). Anal. Calcd for C25H30N2O: C
80.17, H 8.07, N 7.48; Found: C 80.28, H 8.11, N 7.41.
5c: The crude product was recrystallized from
ethanol to give a white solid. Yield 98%; mp 100–
102◦C; [α]D = +45.5(c = 0.56, CHCl3). IR (KBr) νmax
(cm−1): 3446, 3026, 2971, 2880, 1681, 1590, 1557,
1494, 1447, 1323, 1256. 1H NMR (300 MHz, CDCl3),
δ (ppm): 0.96 (s, 3H, CH3), 1.36 (s, 3H, CH3), 1.39–
1.74 (m, 2H), 2.01–2.10 (m, 2H), 2.13–2.18 (m, 1H),
2.61–2.66 (m 2H), 4.56 (q, J = 6.6, 22.2 Hz, 2H),
7.02–7.05 (t, J = 3.6 Hz, 1H, Ar-H), 7.26 (t, J = 4.2
Hz, 2H, Ar-H), 7.32–7.33 (m, 2H, Ar-H), 7.39–7.42
(m, 3H, Ar-H), 7.54 (d, J = 3.9 Hz, 2H, Ar-H), 9.7
(s, 1H, NH). Anal. Calcd for C23H26N2O: C 79.73, H
7.56, N 8.09; Found: C 79.99, H 7.51, N 8.01.
(1S)-7,7-Dimethylbicyclo[2.2.1]heptane-1-N-
phenylcarboxylamide-2-one 4c
Compound 4c was prepared using the same proce-
dure as 4b. After the usual workup, the crude prod-
uct was purified by recrystallization from ethanol to
afford 4c. Yield 89.5%; mp 88–90◦C; [α]D = +40.2
(c = 0.55, CHCl3). IR (KBr) νmax (cm−1): 3297, 2967,
1727, 1670, 1597, 1538, 1442, 1325, 1249, 756, 694.
1H NMR (300 MHz, CDCl3), δ (ppm): 1.04 (s, 3H,
CH3), 1.34 (s, 3H, CH3), 1.46–1.74 (m, 2H), 2.04–2.13
(m, 2H), 2.19–2.23 (m, 1H), 2.58–2.63 (m, 2H), 7.09–
7.62 (m, 5H, Ar-H), 9.70 (s, 1H, NH). Anal. Calcd for
C16H19NO2: C 74.68, H 7.44, N 5.44; Found: C 74.81,
H 7.41, N 5.49.
(1S)-N-(Cyclohexyl)-7,7-dimethylbicyclo[2.2.1]-
hept-1-yl-methanesulfonamide 6a
(1S)-(+)-10-Camphorsulfonyl chloride 1 (2.6 g, 10.4
mmol) in CH2Cl2 (10 mL) was added to a stirred
solution of triethylamine (2.1 g, 21 mmol) and cy-
clohexylamine (1.1 mL, 10 mmol) in CH2Cl2 (10 mL)
at 0◦C over 0.5 h period. The reaction was then al-
lowed to come to room temperature and stirred for
additional 24 h. The organic layer was washed with
HCl (5%), saturated sodium bicarbonate, and satu-
rated brine in turn, dried over anhydrous MgSO4.
The solvent was removed under the reduced pres-
sure, the crude camphorsulfonamide was purified
by recrystallization from ethanol/petroleum ether to
afford 6a. Yield 86%; mp 112–124◦C; lit. [43] 103◦C;
[α]D = +20.9 (c = 1, CHCl3); lit. [43] +20.82 (c = 1,
CHCl3).
7a: The crude product was recrystallized from
ethanol to give a white solid. Yield 92.4%; mp
Heteroatom Chemistry DOI 10.1002/hc

686 Zhou and Bian
106–108◦C; [α]D = +20.4 (c = 0.5, CHCl3). IR (KBr)
νmax (cm−1): 3445, 3031, 2937, 1672, 1457, 1321, 1147,
1081, 742, 700. 1H NMR (300 MHz, CDCl3), δ (ppm):
0.80–0.88 (m, 3H, CH3), 0.90–0.96 (m, 3H, CH3),
1.09–1.18 (m, 2H), 1.30–1.35 (m, 2H), 1.42–1.44 (m,
1H), 1.48–1.53 (m, 1H), 1.61–1.69 (m, 1H), 1.75–1.77
(m, 1H), 1.93–2.04 (m, 2H), 2.04–2.16 (m, 2H), 2.50
(t, J = 9.9 Hz, 2H), 2.92 (d, J = 7.5 Hz, 1H), 3.05–
3.19 (m, 2H), 3.42 (d, J = 7.5 Hz, 1H), 4.00–4.09 (m,
2H), 4.29–4.39 (m, 2H), 6.97 (s, 1H, Ar-H), 7.18–7.36
(m, 3H, Ar-H), 7.61 (s, 1H, Ar-H), 8.26 (s, 1H, NH).
Anal. Calcd for C23H34N2O2S: C 68.62, H 8.51, N 6.96;
Found: C 68.77, H 8.46, N 6.89.
7b: The crude product was recrystallized from
ethyl acetate to give a white solid. Yield 78.3%; mp
122–124◦C; [α]D = +36.6 (c = 0.5, CHCl3). IR (KBr)
νmax (cm−1): 3424, 2970, 2946, 1667, 1454, 1323, 1148,
1083, 741, 701. 1H NMR (300 MHz, CDCl3), δ (ppm):
0.70 (s, 3H, CH3), 0.90 (s, 3H, CH3), 1.32 (t, J = 4.8
Hz, 1H), 1.93–1.96 (m, 2H), 2.00–2.04 (m, 2H), 2.16
(s, 1H), 2.50 (d, J = 8.7 Hz, 1H), 2.92 (d, J = 7.2
Hz, 1H), 3.09 (d, J = 7.8 Hz, 1H), 4.00–4.08 (m, 2H),
4.28–4.35 (m, 2H), 6.97–7.29 (m, 10H, Ar-H), 8.26 (s,
1H, NH). Anal. Calcd for C24H30N2O2S: C 70.21, H
7.36, N 6.82; Found: C 70.33, H 7.29, N 6.77.
[6] Fan, Q. H.; Li, Y. M.; Chan, A. S. C. Chem Rev 2002,
102, 3385–3466.
[7] Palmer, M. J.; Wills, M. Tetrahedron: Asymmetry
1999, 10, 2045–2061.
[8] Noyori, R.; Hashiguchi, S. Acc Chem Res 1997, 30,
97–102.
[9] Hashiguchi, S.; Fujii, A.; Takehara, J.; Ikariya, T.;
Noyori, R. J Am Chem Soc 1995, 117, 7562–7563.
[10] Sandoval, C.; Ohkuma, T.; Utsumi, N.; Tsutsumi, K.;
Murata, K.; Noyori, R. Chem Asian J 2006, 1–2, 102–
110.
[11] Matsumura, K.; Hashiguchi, S.; Ikariya, T.; Noyori,
R. J Am Chem Soc 1997, 119, 8738–8739.
[12] Hamada, T.; Torii, T.; Onishi, T.; Izawa, K.; Ikariya,
T. J Org Chem 2004, 69, 7391–7394.
[13] Hannedouche, J.; Clarkson, G. J.; Wills, M. J Am
Chem Soc 2004, 126, 986–987.
[14] Hayes, A. M.; Morris, D. J.; Clarkson, G. J.; Wills, M.
J Am Chem Soc 2005, 127, 7318–7319.
[15] Matharu, D. S.; Morris, D. J.; Kawamoto, A. M.;
Clarkson, G. J.; Wills, M. Org Lett 2005, 7, 5489–5491.
[16] Wang, F.; Liu, H.; Cun, L.; Zhu, J.; Deng, J.; Jiang, Y.
J Org Chem 2005, 70, 9424–9429.
[17] Ma, Y.; Liu, H.; Chen, L.; Cui, X.; Zhu, J.; Deng, J.
Org Lett 2003, 5, 2103–2106.
[18] Liu, P.-N.; Gu, P.-M.; Deng, J.-G.; Tu Y.-Q.; Ma, Y.-P.
Eur J Org Chem 2005, 3221–3227.
[19] Liu, P. N.; Gu, P. M.; Wang, F.; Tu, Y. Q. Org Lett
2004, 6, 169–172.
[20] Li, X.; Chen, W.; Hems, W.; King, F.; Xiao, J. Tetra-
hedron Lett 2004, 45, 951–953.
[21] Arakawa, Y.; Haraguchi, N.; Itsuno, S. Tetrahedron
Lett 2006, 47, 3239–3243.
[22] Peach, P.; Cross, D. J.; Kenny, J. A.; Mann, I.; Houson,
I.; Campbell, L.; Walsgrove, T.; Wills, M. Tetrahedron
2006, 62, 1864–1876.
Typical Procedure for Asymmetric Transfer
Hydrogenation of Ketones
5c (0.02 mmol), [RuCl2(p-cymene)]2 (6.1 mg,
0.01 mmol) and 19.5 mL of isopropanol were added
to a flask under argon, and the mixture was stirred
at 60◦C for 1 h. A solution of 0.1 M of KOH in
isopropanol following acetophenone (2 mmol) was
added to the solution. The mixture was stirred un-
der argon at 60◦C for 48 h, acidified to pH 2 with
hydrochloric acid (1 M) and then was extracted
with ethyl acetate (15 mL × 3). The organic phase
was washed with brine and dried over anhydrous
Na2SO4. The conversion was determined by GC-MS.
The pure product was obtained by preparative TLC.
[23] Sterk, D.; Stephanb, M. S.; Mohar, B. Tetrahedron
Lett 2004, 45, 535–537.
[24] Thorpe, T.; Blacker, J.; Brown, S. M.; Bubert, C.;
Crosby, J.; Fitzjohn, S.; Muxworthy, J. P.; Williams,
J. M. Tetrahedron Lett 2001, 42, 4041–4043.
[25] Huang, X.; Ying, J. Y. Chem Commun 2007, 1825–
1827.
[26] Wu, X.; Li, X.; Zanotti-Gerosa, A.; Pettman, A.; Liu, J.;
Mills, A. J.; Xiao, J. Chem Eur J 2008, 14, 2209–2222.
[27] Li, L.; Wu, J.; Wang, F.; Liao, J.; Zhang, H.; Lian, C.;
Zhu, J.; Deng, J. Green Chem 2007, 9, 23–25.
[28] Cortez, N. A.; Aguirre, G.; Parra-Hake, M.;
Somanathan, R. Tetrahedron Lett 2007, 48, 4335–
4338.
[29] Canivet, J.; Suss-Fink, G. Green Chem 2007, 9, 391–
397.
[30] Xu, Z.; Mao, J.; Zhang, Y.; Guo, J.; Zhu, J. Catal Com-
mun 2008, 9, 618–623.
[31] Kawasaki, I.; Tsunoda, K.; Tsuji, T.; Yamaguchi, T.;
Shibuta, H.; Uchida, N.; Yamashitaab, M.; Ohta, S.
Chem Commun 2005, 2134–2136.
[32] Rhyoo, H. Y.; Park, H.-J.; Suh, W. H.; Chung, Y. K.
Tetrahedron Lett 2002, 43, 269–272.
[33] Rhyoo, H. Y.; Park, H. J.; Chung, Y. K. Chem Com-
mun 2001, 2064–2065.
REFERENCES
[1] Wu, X.; Xiao, J. Chem Commun 2007, 2449–2466.
[2] Gladiali, S.; Alberico, E. Chem Soc Rev 2006, 35, 226–
236.
[3] Blaser, H. U.; Malan, C.; Pugin, B.; Spindler, F.;
Steiner, H.; Studer, M. Adv Synth Catal 2003, 345,
103–151.
[4] Everaere, K.; Mortreux, A.; Carpentier, J.-F. Adv
Synth Catal 2003, 345, 67–77.
[5] Saluzzo, C.; Lemaire, M. Adv Synth Catal 2002, 344,
915–928.
[34] Rhyoo, H. Y.; Yoon, Y.-A.; Park, H.-J.; Chung, Y. K.
Tetrahedron Lett 2001, 42, 5045–5048.
[35] Faller, J. W.; Lavoie, A. R. Organometallics 2001, 20,
5245–5247.
Heteroatom Chemistry DOI 10.1002/hc

Novel Chiral Schiff Bases and Their Application in Asymmetric Transfer Hydrogenation of Prochiral Ketones 687
[36] Marson, C. M.; Schwarz. I. Tetrahedron Lett 2000,
[40] Morris, D. J.; Hayes, A. M.; Wills, M. J Org Chem
2006, 71, 7035–7044.
41, 8999–9003.
[37] Bartlett, P. D.; Knox, L. H. Organic Synthesis; Wiley:
New York, 1965; Vol. 45, pp. 55–56.
[38] Bartlett, P. D.; Knox, L. H. Organic Synthesis; Wiley:
New York, 1965; Vol. 45, pp. 14–16.
[41] Li, K.; Zhou, Z.; Wang, L.; Chen, Q.; Zhao, G.; Zhou,
Q.; Tang, C. Tetrahedron: Asymmetry 2003, 14, 95–
100.
[42] Basavaiah, D.; Reddy, G. J.; Chandrashekar, V.
Tetrahedron: Asymmetry 2004, 15, 47–52.
[43] Yeh, T.; Liao, C.; Uang, B. Tetrahedron 1997, 53,
11141–11152.
[39] Basavaiah, D.; Reddy, G. J.; Rao, K. V.
Tetrahedron:
1888.
Asymmetry
2004,
15,
1881–
Heteroatom Chemistry DOI 10.1002/hc