Cyclodextrin-[RuCl2(Arene)]2 conjugates: Another way to enhance the enantioselectivity of aromatic ketones reduction by aromatic ligands' volume

Article abstract of DOI:10.1016/j.tet.2013.07.077

Eight amino alcohol-modified β-CDs CD-1-CD-8 have been synthesized in acceptable yields and were employed to form artificial metalloenzymes with [RuCl₂(Benzene)]₂ and [RuCl₂(Mesitylene)] ₂, respectively. All the conformations of CD-1-CD-8, the complexes between CD-1-CD-8 and [RuCl₂(Arene)]₂, and the inclusion complexes between CD-1-CD-8 and acetophenone were characterized by UV, ¹H NMR, ¹H ROESY NMR, and quantum calculation. The catalytic activity of the formed artificial metalloenzymes in the asymmetric hydrogenation of aromatic ketones, especially the effect of the aromatic ligands' volume on the enantioselectivity were investigated in detail, in which it was obvious that the enantioselectivity increased as the increase in the aromatic ligands' volume. For the best artificial metalloenzyme constructed from the complex between CD-8 and [RuCl₂(Mesitylene)]₂, which not only exhibits a good tolerance to a wide range of substrates but also demonstrates some substrate selectivity, 76.39% ee was obtained for acetophenone and 79.67% ee for 2-acetylnaphthalene. A strategy to improve the enantioselectivity in the asymmetric reactions catalyzed by the artificial metalloenzymes based on CDs has been provided.

Full text of DOI:10.1016/j.tet.2013.07.077

Tetrahedron 69 (2013) 8360e8367
Contents lists available at SciVerse ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Cyclodextrine[RuCl (Arene)] conjugates: another way to enhance
2
2
the enantioselectivity of aromatic ketones reduction by aromatic
ligands’ volume
Hai-Min Shen, Hong-Bing Ji *
School of Chemistry and Chemical Engineering, Sun Yat-sen University, Guangzhou 510275, China
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 18 April 2013
Received in revised form 14 July 2013
Accepted 22 July 2013
Available online 31 July 2013
Eight amino alcohol-modified
employed to form artificial metalloenzymes with [RuCl
b
-CDs CD-1eCD-8 have been synthesized in acceptable yields and were
(Benzene)] and [RuCl (Mesitylene)] , re-
spectively. All the conformations of CD-1eCD-8, the complexes between CD-1eCD-8 and [RuCl (Ar-
2
2
2
2
2
2
ene)] , and the inclusion complexes between CD-1eCD-8 and acetophenone were characterized by UV,
1
H NMR, 1H ROESY NMR, and quantum calculation. The catalytic activity of the formed artificial met-
alloenzymes in the asymmetric hydrogenation of aromatic ketones, especially the effect of the aromatic
ligands’ volume on the enantioselectivity were investigated in detail, in which it was obvious that the
enantioselectivity increased as the increase in the aromatic ligands’ volume. For the best artificial
Keywords:
Cyclodextrin
Artificial metalloenzyme
Asymmetric hydrogenation
Enantioselectivity
Ligand’s volume
2 2
metalloenzyme constructed from the complex between CD-8 and [RuCl (Mesitylene)] , which not only
exhibits a good tolerance to a wide range of substrates but also demonstrates some substrate selectivity,
76.39% ee was obtained for acetophenone and 79.67% ee for 2-acetylnaphthalene. A strategy to improve
the enantioselectivity in the asymmetric reactions catalyzed by the artificial metalloenzymes based on
CDs has been provided.
Ó 2013 Elsevier Ltd. All rights reserved.
1. Introduction
substrate molecule would be immobilized near the modifying
groups of CDs, which play the role of catalytic active center. Hence,
Cyclodextrins (CDs) obtained from enzymatic degradation
of starch, are a family of water-soluble macrocyclic oligomers of
enhanced catalytic activity, obvious acceleration in reaction rate,
and excellent regioselectivity can usually be achieved in the organic
reaction catalyzed by the artificial enzymes and artificial metal-
loenzymes based on CDs, such as the cytochrome P-450 oxidase
D
-(þ)-glucopyranosyl units linked by
possess a hydrophilic exterior and a hydrophobic cavity. Among
them, three main members are known widely as -CD, -CD (Fig. 1),
and -CD with six, seven, and eight glucose units, respectively.
a-1,4-glycosidic bonds, which
15e18
a
b
mimics reported by Breslow and co-workers,
dioxygenases mimics reported by French and co-workers,
the carotene
1e4
19,20
g
the
21e25
Because of their hydrophilic exteriors and hydrophobic cavities,
CDs can form inclusion complexes with a wide range of guest
molecules possessing suitable shape and size in water like the hy-
drophobic pockets in enzymes, and catalyze or promote organic
reactions through weak interactions between CDs and substrate
molecules.5 CDs have become important catalysts and additives in
aqueous organic reactions. Modification of CDs expands the appli-
cation of CDs in aqueous organic reactions, and a lot of artificial
enzymes and artificial metalloenzymes were constructed based on
glutathione peroxidase mimics reported by Liu and Jin
and the
2
6e30
hydrolase mimics reported by Mao.
e9
10e14
CDs, especially
b-CD for its ready availability in commerce.
In
the artificial enzymes and artificial metalloenzymes based on CDs,
the CDs units can function as the hydrophobic pockets in enzymes
and form inclusion complex with the substrate molecule, thus the
Fig. 1. Schematic structure of b-cyclodextrin (b-CD).
However, when applied in the asymmetric organic reaction, the
artificial enzymes and artificial metalloenzymes based on CDs
usually could not give so satisfactory results, such as the artificial
*
Corresponding author. Tel.: þ86 20 8411 3658; fax: þ86 20 8411 3654; e-mail
address: jihb@mail.sysu.edu.cn (H.-B. Ji).
0
040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.07.077

H.-M. Shen, H.-B. Ji / Tetrahedron 69 (2013) 8360e8367
8361
metalloenzymes in the asymmetric oxidation of thioanisole re-
Thus, in order to investigate the effect of the aromatic ligands on
the enantioselectivity in the asymmetric organic reaction, herein
we employed the asymmetric hydrogenation of aromatic ketones
31,32
ported by Bonchio and Sakuraba,
the ee just being 50e60%. We
also have reported the asymmetric oxidation of thioanisole cata-
lyzed by the artificial metalloenzymes formed by the complexation
as model reaction, used [RuCl
2 2 2
(Benzene)] and [RuCl (Mesity-
of
b
-CD derivatives CD-1eCD-7 (Fig. 2) and Na
2
MoO
4
and just
lene)] (Fig. 4), which had different volume in aromatic ligands as
2
3
3
moderate ee (56%) was achieved. With the aid of quantum cal-
culation, the moderate enantioselectivity was ascribed to the two
different binding models of CDs and thioanisole (Fig. 3), which
existed concurrently. In model A, thioanisole conducted intra-
molecular catalytic oxidation giving the chiral product and in
model B thioanisole conducted intermolecular catalytic oxidation
giving the racemic product, resulting in the moderate ee. Thus in
the asymmetric oxidation of thioanisole catalyzed by the complex
precursor metal ion forming complex with CD-1eCD-8 to construct
artificial metalloenzymes and investigated the effect of the aro-
matic ligands’ volume on the enantioselectivity in the model re-
action systematically. The formation of the complex between
[RuCl
2 2
(Arene)] and CDs, the inclusion complex of aromatic ketones
and CDs, and the reaction mechanism were also studied in detail, in
1
1
which UV, H NMR, H ROESY NMR, and quantum calculation were
employed. In addition, a practicable strategy to improve the
enantioselectivity in the asymmetric reactions catalyzed by the
artificial metalloenzymes based on CDs has been provided in this
study, in which, besides the induction effect of the CDs, the enan-
tioselectivity could also be enhanced through providing a second-
ary ligand for the metal ion and increasing its molecular volume,
because of the increase in the steric hindrance around the metal
ion.
3
3
of CD-5 and Na
Schlatter had reported the complex of [RuCl
2
MoO
4
, the ee just being 53% is rational. But
(Benzene)] and -CD
2
2
b
derivative CD-5 as artificial metalloenzyme to catalyze the asym-
metric hydrogenation of prochiral aromatic and aliphatic ketones,
higher ee were achieved, up to 77% for the substrate acetophe-
none, which inspired us that besides CD-5, the existence of aro-
matic ligands of the metal ion might play a favorable role in the
enhancement of the ee, because in the complex of CD-5 and
3
4
2 4
Na MoO , the ligand of the metal ion was just CD-5. The existence
of the aromatic ligands might increase the steric hindrance around
the metal ion and prevent substrate from conducting in-
termolecular catalytic oxidation in model B.
2 2 2 2
Fig. 4. Schematic structures of [RuCl (Benzene)] and [RuCl (Mesitylene)] .
2
2
. Results and discussion
.1. Synthesis of CD-1eCD-8 and [RuCl
2 2
(Arene)]
The synthesis of CD-1eCD-7 has been illustrated in our previous
3
3
report, and CD-8 was synthesized following the similar procedure
illustrated in Scheme 1. Mono(6-O-p-tolylsulfonyl)- -CD was syn-
thesized by tosylation of -CD with p-toluenesulfonyl chloride in
b
b
basic aqueous solution according to literature procedure, which
could be obtained in a large scale after filtration and washing with
3
5
acetone and water. Then CD-8 was smoothly synthesized by nu-
cleophilic substitution of mono(6-O-p-tolylsulfonyl)-
b
-CD with an
ꢀ
excess of (R)-1-amino-2-propanol at 80 C in DMF. All of CD-1eCD-
Fig. 2. Schematic structures of the amino alcohol-modified
b-cyclodextrins (
b-CDs).
1
13
8
were characterized by H NMR, C NMR, ESIMS, and quantum
calculation. When the conformation of CD-8 in aqueous solution
was optimized by Gaussian 03 program at the level of B3LYP/6-
3
6
3
1G(d)(Fig. 5), the result is in good consistency with the confor-
mations of CD-1eCD-7 as the modifying group pointing to the
outside of the parent -CD in their optimized conformations, which
were due to the high solubility of the modifying groups in water.
b
3
3
To a certain extent, it could be concluded that when CD-8 combines
with a metal ion without secondary ligand to form artificial met-
alloenzyme, the substrate might conduct intermolecular catalytic
Fig. 3. Two schematic binding models for CD-1eCD-7 and thioanisole.
Scheme 1. Schematic synthesis of the CD-8.

8362
H.-M. Shen, H.-B. Ji / Tetrahedron 69 (2013) 8360e8367
1
transformation in model B giving the racemic product, resulting in
the moderate ee, because the modifying group pointing to the
H atoms in the modifying group of CD-8. In the H NMR spectrum of
the complex between CD-8 and [RuCl (Benzene)] , the chemical-
2
2
outside of the parent
termolecular catalytic transformation of substrate in model B as
reported in our previous study.
b
-CD was the main origin for the in-
shift of the H atoms in the modifying group shifted downfield by
0.43 ppm because of the effect of metal ion Ru and benzene. But at
the same time, no obvious chemical-shift change was observed
3
3
Fig. 5. Optimized conformation of CD-8 in aqueous solution (a, side view; b, vertical view) obtained at the level of B3LYP/6-31G(d).
[
RuCl
2
(Benzene)]
2
and [RuCl
2
(Mesitylene)]
2
were synthesized
from the H atoms belonged to the parent
remained at the same chemical-shift. Thus, it could be concluded
that CD-8 formed complex with [RuCl (Benzene)] mainly through
its modifying group, the hydroxyls in the parent -CD did not
participate in the complexation with [RuCl (Benzene)]
Besides H NMR study, the formation of the complex between
CD-8 and [RuCl (Benzene)] has also been characterized by UV
spectrum (Fig. 7). At the same concentration of [RuCl (Benzene)]
in the mixture of H O and DMF, when CD-8 was added, which had
no obvious UV absorption to form complex with [RuCl (Benzene)]
an enhancement in UV absorption was observed, different from the
UV absorption of [RuCl (Benzene)] . UV spectrum also provided an
evidence for the formation of the complex between CD-8 and
b-CD, which nearly
according to literature procedure through refluxing the mixture of
hydrated ruthenium(III) trichloride and 1,4-cyclohexadiene or
,3,5-trimethylcyclohexa-1,4-diene in ethanol. The brown pre-
cipitate was filtered off, washed with methanol, and dried in vac-
2
2
3
7
1
b
2
2
.
1
uum to give the target product in high purity.
2
2
2
2
2
.2. Preparation and characterization of complexes between
CD-1eCD-8 and [RuCl -(Arene)]
2
2
2
2
2
,
With CD-1eCD-8 in hand, we prepared the complexes of CD-
eCD-8 and [RuCl (Arene)] in situ prior to catalytic experiments
2
2
1
2
2
by stirring CD-1eCD-8 and [RuCl
2
(Arene)]
2
in the mixture of H
(Ar-
O) and
UV spectrum. The H NMR spectra of CD-8 and its complex with
2
O
1
ꢀ
[RuCl
spectrum and related literature,
formed by CD-8 and [RuCl (Benzene)] was surmised as shown in
2 2
(Benzene)] to some extent. Based on the H NMR study, UV
and DMF at 25 C. The complexes of CD-1eCD-8 and [RuCl
2
3
4
1
the structure of complexes
2 2
ene)] were characterized by H NMR studies (400 MHz, D
1
2
2
1
2 2
Fig. 8. CD-8 coordinated to the [RuCl (Benzene)] through its
[
RuCl
2 2
(Benzene)] were shown in Fig. 6. Compared the two H NMR
modifying group, combining the catalytic active center and modi-
fied -CD together, forming artificial metalloenzyme.
spectra, significant chemical-shift changes were observed from the
b
1
1
1
0
0
0
0
0
.4
.2
.0
.8
.6
.4
.2
.0
0
.32mmol/L CD-8
0.16mmol/L RuCl (Benzene)
2
2
2
0
+
.16mmol/L RuCl (Benzene)
0.32mmol/L CD-8
2
2
00
300
400
Wavelength
500
(nm)
600
λ
Fig. 7. UV absorption spectra of CD-8, [RuCl
in vH2 O=vDMF ¼ 3 : 1:
2
(Benzene)]
2
, and CD-8þ[RuCl
2 2
(Benzene)]
Fig. 6. 1H NMR spectra of CD-8 and CD-8þ[RuCl
2 2 2
(Benzene)] in D O.

H.-M. Shen, H.-B. Ji / Tetrahedron 69 (2013) 8360e8367
8363
respectively. And then the binding energy (BE) at the level of
ONIOM(B3LYP/6-31G(d):PM3) was obtained according to Eq. 1:
OPT
ONIOM
OPT
PM3
OPT
BE ¼ E½Cꢁ
ꢂ E½Hꢁ
ꢂ E½Gꢁ
(1)
B3LYP=6ꢂ31GðdÞ
OPT
OPT
OPT
where E½Cꢁ
; E½Hꢁ
; and E½Gꢁ represented the
B3LYP=6ꢂ31GðdÞ
ONIOM
PM3
total optimized energy of the inclusion complex at the level of
ONIOM(B3LYP/6-31G(d):PM3), the free CD-8 at the level of PM3,
and the free acetophenone at the level of B3LYP/6-31G(d).
The optimized geometry of the inclusion complex between CD-
8
and acetophenone in model A and model B is shown in Fig.10, and
Fig. 8. Schematic structure of the complex between CD-8 and [RuCl
2
(Benzene)]
2
.
the binding energies in model A and B are ꢂ40.9452 kJ/mol and
ꢂ45.0176 kJ/mol, respectively. The negative binding energy in-
dicated the formation of inclusion complex between CD-8 and
acetophenone is thermodynamically favorable and spontaneous. In
addition, we also obtained that the difference in the binding en-
ergies between model A and B was just 4.0724 kJ/mol, a very low
energy barrier. Two binding models exist in the inclusion complex
of CD-8 and acetophenone simultaneously and can transform to
each other freely. Thus, as reported in our previous study, when
CD-8 combines with a metal ion without secondary ligand to form
artificial metalloenzyme, the substrate might conduct in-
termolecular catalytic transformation in model B giving the race-
mic product, just resulting in the moderate ee, because the
2
.3. Preparation and characterization of the inclusion com-
plexes between CD-1eCD-8 and aromatic ketones
The formation of inclusion complex is the critical step in the
biomimetic catalysis based on artificial metalloenzyme constructed
from CDs. In this study, the inclusion complexes between CD-
3
3
1
eCD-8 and aromatic ketones were prepared by stirring the mix-
ture of CD-1eCD-8 and aromatic ketones in water and character-
1
ized by H ROESY NMR and quantum calculation. Set CD-8 as
example, the 1H ROESY NMR spectrum of the inclusion complex
between CD-8 and acetophenone was illustrated in Fig. 9. In Fig. 9,
obvious correlation peaks between the H atoms located in the
phenyl ring of acetophenone and the H-3, H-5 in the cavity of the
modifying group of CD-8 pointing to the outside of the parent b-CD
has been proved in the optimization of the conformation of CD-8 in
aqueous solution employing quantum calculation.
parent b-CD could be observed, which illustrated the formation of
inclusion complex between CD-8 and acetophenone. Meanwhile,
there is no correlation peak observed between the H atoms located
in the phenyl ring of acetophenone and the H-2, H-4 in the outside
of the parent
acetophenone, almost all the acetophenone molecules are included
into the cavity of the parent -CD, no acetophenone absorbed on
the outside of the parent -CD. But whether the inclusion complex
b-CD. Thus, in the inclusion complex of CD-8 and
b
b
between CD-8 and acetophenone had two binding models as
shown in Fig. 3 could not be determined, for what the quantum
calculation was employed to calculate the binding energy of CD-8
and acetophenone in model A and model B. The geometry of the
inclusion complex between CD-8 and acetophenone was firstly
optimized by Gaussian 03 program at the level of PM3, and then the
output files were employed as input files for optimization at the
level of ONIOM(B3LYP/6-31G(d):PM3), in which CD-8 and aceto-
phenone were optimized at the level of PM3 and B3LYP/6-31G(d),
Fig. 10. Two optimized conformations of the inclusion complexes formed by CD-8 and
acetophenone, and the binding energy (1: side view; 2: vertical view).
2.4. Asymmetric reduction of aromatic ketones
To evaluate the effect of the aromatic ligands on the enantio-
selectivity in the asymmetric organic reaction, the complexes be-
tween CD-1eCD-8 and [RuCl (Benzene)] or [RuCl (Mesitylene)]
were applied to the asymmetric hydrogenation of aromatic ketones
Fig. 9. Partial 1H ROESY NMR spectrum of the inclusion complex formed by CD-8 and
acetophenone in D O.
2
2
2
2
2

8364
H.-M. Shen, H.-B. Ji / Tetrahedron 69 (2013) 8360e8367
as artificial metalloenzymes. And the effect of the aromatic ligands’
volume on the enantioselectivity was our research focus. The re-
sults of the asymmetric hydrogenation of acetophenone were listed
in Table 1. Obviously, the CDs play an important role in the catalytic
property of the artificial metalloenzymes constructed from CD-
1
eCD-8 and [RuCl
2 2 2 2
(Benzene)] or [RuCl (Mesitylene)] . When CD-
3
, CD-6, and CD-7 were employed, the formed artificial metal-
loenzymes did not possess catalytic activity in the asymmetric
hydrogenation of acetophenone. CD-2 being employed, the formed
artificial metalloenzyme possessed catalytic activity, but no enan-
tioselectivity being observed. Only when CD-1, CD-4, CD-5, and CD-
8
were employed to form artificial metalloenzymes with [RuCl
2
(-
Benzene)] or [RuCl (Mesitylene)] , there were both expected cat-
2
2
2
alytic activity and enantioselectivity being observed. Besides the
effect of CDs on the catalytic activity and enantioselectivity, espe-
cially from the results of the artificial metalloenzymes based on CD-
Fig. 11. Schematic intermolecular catalytic transformation of substrate in model B.
1, CD-4, CD-5, and CD-8, we also could observe the effect of the
aromatic ligands’ volume on the enantioselectivity in the asym-
metric hydrogenation of acetophenone. The enantioselectivity in-
creased as the aromatic ligands being changed from ‘Benzene’ to
as shown in Table 2. The constructed artificial metalloenzyme not
only exhibits a good tolerance to a wide range of substrates but also
demonstrates some substrate selectivity. For 2-acetylnaphthalene,
which has most suitable molecular shape and size, the highest ee in
this study was obtained, 79.67%. The complex between CD-8 and
[RuCl (Mesitylene)] can be accounted as an effective artificial
metalloenzyme in the asymmetric hydrogenation of aromatic ke-
tones. In order to investigate the reaction mechanism, the control
experiments were conducted as shown in Table 3. From Table 3, we
‘Mesitylene’, which had larger molecular volume except for CD-5.
Although it could not be applicable to all the CDs, for CD-1, CD-4,
and CD-8, the enantioselectivity increased as the increase in the
aromatic ligands’ volume from 4.76% to 47.89%, 5.73% to 55.81%,
and 30.26% to 76.39%, respectively, which could be attributed to the
increase in the aromatic ligands’ volume increased the steric hin-
drance around the metal ion and prevented substrate from con-
ducting intermolecular catalytic hydrogenation in model B as
shown in Fig. 11, which would give the racemic products. The ex-
periment result about the relation between enantioselectivity and
the aromatic ligands’ volume is in good consistency with our
speculation to some extent. Based on Table 1, the best artificial
metalloenzyme in this study is the complex between CD-8 and
2
2
Table 2
The asymmetric reduction of typical aromatic ketones catalyzed by
CD-8þ[RuCl
2
(Mesitylene)]
2
Entry
Ketones
Conversion Yield ee
%) (%) (%)
Configuration
(
2 2
[RuCl (Mesitylene)] , the ee being 76.39% for acetophenone.
1
2
85.41
76.25
70.36 76.39
67.33 75.51
R
Table 1
Effect of the aromatic ligands of Ru on the asymmetric reduction of acetophenone
Entry
1
CDs
Ru precursors
Conversion (%)
Yield (%)
ee (%)
R
R
S
a
4.76d
47.89d
0.00
CD-1
[RuCl
RuCl
[RuCl
RuCl
[RuCl
RuCl
[RuCl
RuCl
[RuCl
RuCl
[RuCl
RuCl
[RuCl
RuCl
[RuCl
RuCl
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
2
(Benzene)]
(Mesitylene)]
2
99.86
74.19
54.59
54.51
N.D.
70.51
62.63
36.48
46.36
<5
b
b
b
b
b
b
b
b
[
2
2
2
2
2
2
2
2
a
2
3
4
5
6
7
8
CD-2
CD-3
CD-4
CD-5
CD-6
CD-7
CD-8
(Benzene)]
(Mesitylene)]
2
[
0.00
N.D.
N.D.
5.73
55.81
67.07
18.29
N.D.
a
(Benzene)]
(Mesitylene)]
2
3
4
72.44
47.71
53.39 60.94
39.21 73.69
[
N.D.
<5
a
c
(Benzene)]
(Mesitylene)]
2
99.54
69.14
89.24
43.45
N.D,
N.D.
N.D.
N.D.
99.89
85.41
71.06
58.97
58.99
24.14
<5
<5
<5
<5
68.16
70.36
d
[
a
c
(Benzene)]
(Mesitylene)]
2
c
[
a
(Benzene)]
(Mesitylene)]
2
[
N.D.
N.D.
a
(Benzene)]
(Mesitylene)]
2
[
N.D.
a
30.26d
76.39d
(Benzene)]
(Mesitylene)]
2
[
Reaction conditions: acetophenone (0.2 mmol), modified CDs (0.02 mmol), Ru
5
6
75.79
49.88
63.68 79.67
28.49 76.61
R
R
precursors (0.01 mmol), HCOONa$2H
2
O (2.0 mmol) in the mixture of H
2
O and DMF
ꢀ
ðvDMF=v 2
H
O
¼ 1 : 1; 1:0 mLÞ at 25 C.
The ee and absolute isomer were determined by HPLC analysis with a Chiralcel OD-
H column and comparison of the eluting sequence of the enantiomers with the
authentic sample.
a
Reaction 24.0 h.
Reaction 96.0 h.
S-Isomer.
b
c
d
R-Isomer.
Reaction conditions: aromatic ketones (0.2 mmol), CD-8 (0.02 mmol), [RuCl
2
(Me-
sitylene)]
ðvDMF=vH2
2
(0.01 mmol), HCOONa$2H
2
O (2.0 mmol) in the mixture of H
2
O and DMF
Then the complex between CD-8 and [RuCl
employed as the best artificial metalloenzyme to catalyze the
asymmetric hydrogenation of a variety of typical aromatic ketones
2
(Mesitylene)]
2
was
ꢀ
O
¼ 1 : 1; 1:0 mLÞ at 25 C for 96.0 h. The ee and absolute isomer were
determined by HPLC analysis with a Chiralcel OD-H or AS-H column and comparison
of the eluting sequence of the enantiomers with the authentic sample.

H.-M. Shen, H.-B. Ji / Tetrahedron 69 (2013) 8360e8367
8365
could see that it was necessary to attach (R)-1-amino-2-propanol to
parent -CD covalently, and then to form complex with [RuCl (-
Mesitylene)] to construct the effective artificial metalloenzyme in
this study. Any one of [RuCl (Mesitylene)] , CD-8, the mixture of
CD and [RuCl (Mesitylene)] the mixture of (R)-1-amino-2-
propanol and [RuCl (Mesitylene)], the mixture of -CD, (R)-1-
amino-2-propanol, and [RuCl (Mesitylene)] could not catalyze the
b
2
2
2
2
b-
2
2
,
2
b
2
2
asymmetric hydrogenation of aromatic ketones effectively. The
delicate cooperation between the modifying groups in CD-8, metal
ion Ru, the aromatic ligand of Ru, and the hydrophobic cavity of the
parent b-CD is the origin of the catalytic activity and the enantio-
selectivity in our constructed artificial metalloenzyme.
Table 3
Control experiments
Entry Catalysts
Conversion (%) Yield (%) ee (%)
1
2
3
4
5
[RuCl
CD-8
2
(Mesitylene)]
2
N.D.
N.D.
85.41
N.D.
50.46
<2
N.D.
N.D.
76.39
N.D.
39.56
<0.2
70.36
<2
a
a
CD-8þ[RuCl
2
(Mesitylene)]
(Mesitylene)]
2
b
-CDþ[RuCl
2
2
(R)-1-Amino-2-propanolþ
RuCl (Mesitylene)]
-CDþ(R)-1-Amino-
-propanolþ[RuCl (Mesitylene)]
38.01
[
b
2
2
2
6
55.10
37.26
38.69a
2
2
Reaction conditions: acetophenone (0.2 mmol), catalyst (0.02 mmol), HCOO-
Na$2H
2
O (2.0 mmol) in the mixture of H
2
O and DMF ðvDMF=v 2
H
O
¼ 1 : 1; 1:0 mLÞ at
ꢀ
25
C for 96.0 h.
The ee and absolute isomer were determined by HPLC analysis with a Chiralcel OD-
H column and comparison of the eluting sequence of the enantiomers with the
authentic sample.
a
R-Isomer.
At last, on the basis of our study and related literature,34,38,39 the
catalytic cycle in the asymmetric hydrogenation of aromatic ke-
tones catalyzed by the complex between CD-8 and [RuCl
2
(Mesity-
lene)] was proposed as illustrated in Scheme 2: (1) activation and
2
Scheme 2. Proposed catalytic cycle for complex between CD-8 and [RuCl
lene)] in asymmetric hydrogenation of acetophenone.
2
(Mesity-
2
complexation of H from formate (I); (2) formation of inclusion
complex between formed artificial metalloenzyme and substrate
acetophenone in model A (II); (3) hydrogenation of substrate ace-
tophenone and liberation of the generated product (III); (4) re-
covery of the coordination number for metal ion Ru (IV); (5)
activation and complexation of H from formate (V). This is also the
reaction mechanism and the origin of the catalytic activity and
enantioselectivity in our study.
been provided in this study too, which is, in addition to the CDs,
providing a secondary ligand for the metal ion and increasing its
molecular volume, because of the increase in the steric hindrance
around the metal ion. Additionally, a strategy in the construction of
artificial metalloenzymes also has been illustrated in our study
through employing CDs to simulate the hydrophobic pockets in
enzymes. At last, quantum calculation has been proved to be
a powerful tool in the investigation of the supramolecular catalysts’
conformation and their complexes with substrate.
3
. Conclusion
In summary, eight amino alcohol-modified b-CDs CD-1eCD-8
have been synthesized to form artificial metalloenzymes with
RuCl (Benzene)] and [RuCl (Mesitylene)] , respectively. And the
4. Experimental
[
2
2
2
2
formed artificial metalloenzymes being applied in the asymmetric
hydrogenation of aromatic ketones, it was found that the enan-
tioselectivity increased as the increase in the aromatic ligands’
volume because the increase in the aromatic ligands’ volume in-
creased the steric hindrance around the metal ion and prevented
substrate from conducting intermolecular catalytic hydrogenation
in model B, which would give the racemic products. Among the
constructed artificial metalloenzymes, the best one was the com-
4.1. Materials and methods
b-CD in 99% purity was purchased from Shanghai Boao Biological
Technology Co. Ltd., China. p-Toluenesulfonyl chloride, 3-amino-1-
propanol, (R,S)-1-amino-2-propanol, (S)-1-amino-2-propanol, (R)-
0
1-amino-2-propanol, 1,1 -iminodi-2-propanol, 2-methylamino-1-
ethanol, and acetophenone in 98% purity were purchased from
Aladdin. 2-Amino-1-ethanol and 2,2 -iminodiethanol of analytical
0
bination of CD-8 and [RuCl
2
(Mesitylene)]
2
, which not only exhibits
grade were purchased from Tianjin Damao Chemical Reagent fac-
tory, China. (R)-1-Phenyethanol was obtained from Alfa Aesar. All
the other common reagents were analytical grade. All of the reagents
were used as received without further purification unless otherwise
noted. NMR spectra were recorded on a Bruker Avance 400 spec-
6 2
trometer in DMSO-d or D O. The quantum calculation was carried
a good tolerance to a wide range of substrates but also demon-
strates some substrate selectivity, 76.39% ee being obtained for
acetophenone and 79.67% ee for 2-acetylnaphthalene. A successful
artificial metalloenzyme in the asymmetric hydrogenation of aro-
matic ketones was reported in our study. More importantly,
a strategy to improve the enantioselectivity in the asymmetric re-
actions catalyzed by the artificial metalloenzymes based on CDs has
III
out by using Gaussian 03 program at the level of PM3 and B3LYP/6-
31G(d). The ee value was determined by HPLC analysis (SHIMADZU

8366
H.-M. Shen, H.-B. Ji / Tetrahedron 69 (2013) 8360e8367
LC-20AT chromatography, UVevis detector, 254 nm, Chiralcel OD-H
or AS-H column, eluted with the mixture of n-hexane and isopropyl
alcohol). The absolute configuration was determined by comparison
of the eluting sequence of the enantiomers with the authentic
sample.
4.02e3.88 (m, 26H), 3.69e3.58 (m, 14H), 3.46 (t, J¼9.4 Hz, 1H),
3.14e3.06 (m, 1H), 2.89e2.77 (m, 1H), 2.67e2.55 (m, 2H),
13
1.21e1.17 ppm (m, 3H); C NMR (400 MHz, D
83.58, 81.21e81.02 (m), 80.68, 73.10e72.89 (m), 72.04e71.78 (m),
70.51, 70.23, 66.40, 65.75, 60.29e60.07 (m), 55.88, 55.52, 20.33,
2
O):
d
¼101.85, 100.34,
þ
þ
2
0.09 ppm; MS (ESI): m/z: 1214.5 [MþNa] , 1192.4 [MþH] .
25
ꢀ
4
.2. Synthesis of mono[6-O-(p-toluenesulfonyl)]-
b-CD
CD-5: Yield: 59.75%; [
a
]
D
þ151.07 (c 0.3248, H
2
O); mp>250 C
1
(decomp.); H NMR (400 MHz, D O):
2
d
¼5.10 (d, J¼3.4 Hz, 7H),
A solution of sodium hydroxide (6.0000 g, 150 mmol) in water
4.02e3.88 (m, 26H), 3.69e3.59 (m, 14H), 3.48 (dd, J¼21.4, 12.1 Hz,
(
5
20 mL) was added dropwise to a solution of
0 mmol) in water (500 mL) with magnetic stirring at 10e15
b
-CD (56.7490 g,
1H), 3.08 (d, J¼12.3 Hz, 1H), 2.90e2.84 (m, 1H), 2.66e2.60 (m, 2H),
ꢀ
13
C
1.19 ppm (d, J¼6.3 Hz, 3H); C NMR (400 MHz, D
2
O):
d¼101.84,
over about 15 min. The solution became homogeneous, and then
101.32, 99.00, 82.79, 81.15e80.66 (m), 73.04e72.87 (m),
72.03e71.78 (m), 65.61, 60.24, 55.44, 20.07 ppm; MS (ESI): m/z:
a solution of p-toluenesulfonyl chloride (11.4384 g, 60 mmol) in
ꢀ
þ
þ
acetonitrile (30 mL) was added dropwise at 10e15 C over about
1214.5 [MþNa] , 1192.4 [MþH] .
25
ꢀ
2
O); mp>260 C
4
5 min forming white precipitate immediately. The resultant so-
CD-6: Yield: 36.86%; [
a
]
D
þ140.75 (c 0.1132, H
1
lution was kept stirring for 3.0 h, and rose to room temperature. The
precipitate formed was collected by suction filtration and then
suspended in water (300 mL) with magnetic stirring at room
temperature for 3.0 h. The precipitate collected by suction filtration
(decomp.); H NMR (400 MHz, D O):
2
d
¼5.21e5.08 (m, 7H), 4.01e3.85
(m, 26H), 3.71e3.64 (m, 14H), 3.42 (t, J¼8.6 Hz, 1H), 3.13e2.99 (m,
1H), 2.86e2.77 (m, 2H), 2.67e2.53 (m, 4H), 1.17 ppm (d, J¼5.9 Hz,
13
6H); C NMR (400 MHz, DMSO-d
6
):
d
¼102.09e100.72 (m), 84.37,
was washed successively with acetone (100 mL) and water
81.32e80.49 (m), 73.22e71.57 (m) 70.21, 69.56, 64.38e63.08 (m),
59.71e59.30 (m), 56.83e56.36 (m), 21.14e20.57 ppm (m); MS (ESI):
ꢀ
(
160 mL), and then dried in vacuum at 80 C for 8.0 h to afford white
þ
þ
solid powder 8.1746 g in 12.68% yield.
m/z: 1272.5 [MþNa] , 1250.5 [MþH] .
2
5
ꢀ
1
25
ꢀ
2
O); mp>250 C
[a
]
D
þ124.15 (c 0.8044, DMF); mp>160 C (decomp.); H NMR
400 MHz, DMSO-d ):
¼7.76 (d, J¼8.3 Hz, 2H), 7.44 (d, J¼8.2 Hz,
H), 5.83e5.63 (m, 14H), 4.85e4.76 (m, 7H), 4.50e4.44 (m, 5H),
.37e4.32 (m, 2H), 4.21e4.17 (m, 1H), 3.70e3.43 (m, 26H),
CD-7: Yield: 61.13%; [
a
]
D
þ149.90 (c 0.4136, H
(decomp.); H NMR (400 MHz, D O):
¼5.16e5.09 (m, 7H),
4.10e3.92 (m, 26H), 3.78e3.60 (m, 14H), 3.45 (t, J¼9.2 Hz, 1H),
1
(
6
d
2
d
2
4
3
13
2.97e2.88 (m, 1H), 2.77e2.53 (m, 4H), 2.35 ppm (s, 3H); C NMR
(400 MHz, D O):
13
.40e3.19 (m, 14H, overlaps with H
2
O), 2.43 ppm (s, 3H); C NMR
2
d
¼101.77, 100.91, 83.74, 81.14e80.94 (m), 80.13,
(
1
5
400 MHz, DMSO-d
02.09e101.14 (m), 81.51e80.63 (m), 72.88e71.69 (m), 69.56, 68.76,
6
):
d
¼144.67, 132.53, 129.75, 127.44,
73.12e72.76 (m), 72.09e71.68 (m), 69.34, 60.28e60.16 (m), 58.50,
þ
58.26, 57.98, 42.18 ppm (m); MS (ESI): m/z: 1214.5 [MþNa] , 1192.4
þ
þ
9.74e59.04 (m), 21.06 ppm; MS (ESI): m/z: 1311.3 [MþNa] ,
[MþH] .
þ
17
ꢀ
2
O); mp>250 C
1
289.0 [MþH] .
CD-8: Yield: 34.07%; [
a
]
D
þ147.25 (c 0.5012, H
NMR(400 MHz, O):
¼5.22e5.16 (m, 7H),
4.09e3.94 (m, 26H), 3.78e3.65 (m, 14H), 3.53 (t, 1H), 3.18 (d, 1H),
1
(decomp.);
H
D
2
d
4
.3. Typical procedure for the synthesis of CD-1 to CD-8
13
2
.91e2.85 (m, 1H), 2.73e2.63 (m, 2H), 1.26 ppm (d, 3H); C NMR
(400 MHz, D O):
¼101.82, 101.33, 83.55, 81.17, 80.65, 73.02e72.86
(m), 71.99e71.73 (m), 70.42, 66.32, 60.24e60.03 (m), 55.82, 49.55,
A solution of mono[6-O-(p-toluenesulfonyl)]-
mmol) in amino alcohol (375 mmol) was stirred at 70 C or 80 C
b
-CD (6.4459 g,
2
d
ꢀ
ꢀ
5
þ
þ
for 12.0 h, and then cooled to room temperature. Water (20 mL)
was added to dilute the mixture, and resultant solution was poured
into a mixture of acetone (200 mL) and ethanol (200 mL) slowly
forming white precipitate immediately. The white precipitate was
20.30, 16.73 ppm; MS (ESI): m/z: 1214.5 [MþNa] , 1192.4 [MþH] .
4.4. Typical procedure for the asymmetric hydrogenation of
aromatic ketones
collected by suction filtration and recrystallized two times in water
ꢀ
(
2ꢃ10 mL), dried in vacuum at 80 C for 8.0 h to afford white crystal.
A solution of modified
b
-CD (0.02 mmol) and [RuCl
2
(Arene)]
2
2
5
ꢀ
CD-1: Yield: 60.15%; [
a]
D
þ150.54 (c 0.8020, H
O):
¼5.11e5.09 (dd, J¼6.9,
.4 Hz, 7H), 4.02e3.88 (m, 26H), 3.76e3.58 (m, 14H), 3.49e3.44 (m,
2
O); mp>250 C
(0.01 mmol) in the mixture of H
2
O and DMF (1 mL) was stirred at
decomp.); 1H NMR (400 MHz, D
d
25 C for 1.0 h, and then HCOONa$2H
ꢀ
O (2.0 mmol) was added.
(
3
1
2
2
ꢀ
After the resultant mixture was stirred at 25 C for another 1.0 h,
aromatic ketone (0.2 mmol) was added. After stirring at 25 C for
13
ꢀ
H), 3.12e3.09 (m, 1H), 2.90e2.75 ppm (m, 4H);
O):
¼101.80, 101.40, 83.58, 81.11, 80.73, 73.06e72.90
m), 72.05e71.77 (m), 70.47, 60.29e60.11 (m), 50.21, 49.25,
C NMR
(
(
400 MHz, D
2
d
24.0 h or 96.0 h, the obtained solution was extracted with n-hexane
(4ꢃ2 mL), and the combined organic phase was dried over anhy-
þ
þ
4
1.96 ppm; MS (ESI): m/z: 1200.5 [MþNa] , 1178.4 [MþH] .
2 4
drous Na SO and analyzed by HPLC to determine the yield and ee
2
5
ꢀ
CD-2: Yield: 42.68%; [
a
]
D
þ140.90 (c 0.8060, H
decomp.); H NMR (400 MHz, D O):
¼5.15e5.06 (m, 7H),
.04e3.87 (m, 26H), 3.74e3.58 (m, 14H), 3.42 (t, J¼9.3 Hz, 1H),
2
O); mp>260 C
value.
1
(
4
3
D
(
2
d
4.5. Quantum calculation
13
.09e3.05 (m, 1H), 2.86e2.69 ppm (m, 8H); C NMR (400 MHz,
O):
¼101.78, 100.95, 83.42, 81.11e80.87 (m), 80.27, 73.19e72.75
m), 72.10e71.69 (m), 70.07, 60.37e60.09 (m), 59.57, 58.94, 55.96,
2
d
All calculations were carried out by using Gaussian 03 program
at the level of PM3, B3LYP, and ONIOM(B3LYP/6-31G(d):PM3). The
initial structure of b-CD was constructed with the aid of the avail-
þ
þ
5
5.58, 49.62 ppm; MS (ESI): m/z: 1244.5 [MþNa] , 1222.4 [[MþH] .
2
5
ꢀ
CD-3: Yield: 55.48%; [
decomp.); 1H NMR (400 MHz, D
.01e3.88 (m, 26H), 3.69e3.59 (m, 14H), 3.45 (t, J¼9.3 Hz, 1H), 3.08
d, J¼11.1 Hz, 1H), 2.89e2.78 (m, 2H), 2.68 (t, J¼7.3 Hz, 2H),
a
]
D
þ149.66 (c 0.8116, H
2
O); mp>250 C
able crystallographic data obtained from XRD without any
40
(
4
(
1
8
6
1
2
O):
d
¼5.10 (t, J¼3.1 Hz, 7H),
optimization. The initial structures of acetophenone and amino
alcohols were constructed with the aid of ChemBioOffice 3D Ultra
(Version 12.0, Cambridge software) and were fully optimized at the
level of B3LYP/6-31G(d). Then the optimized amino alcohols were
attached to the C-6 of b-CD forming amino alcohol-modified b-CDs,
which were fully optimized at the level of PM3 and B3LYP/6-31G(d)
without any symmetrical restrictions. The coordinate system for
.82e1.72 ppm (m, 2H); 1 C NMR (400 MHz, D
3
O):
d¼101.84,101.39,
2
3.64, 81.10, 80.71, 73.07e72.93 (m), 72.05e71.76 (m), 70.28,
0.24e60.03 (m), 59.27, 49.45, 45.91, 31.07 ppm; MS (ESI): m/z:
þ
192.5 [MþH] .
2
5
ꢀ
CD-4: Yield: 50.21%; [
a
]
D
þ147.81 (c 0.4860, H
2
O); mp>250 C
describing the inclusion complexes between native
molecules has been reported in many literature.
b
-CD and guest
In general, all
decomp.); 1H NMR (400 MHz, D
O):
d¼5.09 (t, J¼3.6 Hz, 7H),
41e44
(
2

H.-M. Shen, H.-B. Ji / Tetrahedron 69 (2013) 8360e8367
8367
the glycosidic oxygen atoms in the parent
b
-CD were located onto
19. French, R. R.; Holzer, P.; Leuenberger, M. G.; Woggon, W. D. Angew. Chem., Int.
Ed. 2000, 39, 1267e1269.
the XY plane, and their center was defined as the origin of this
coordinate system. And the C-6 hydroxyls were located pointing to
the positive Z axis. The coordinate of the guest molecule aceto-
phenone was determined with the aid of three dummy atoms, one
in the Z axis and two in the XY plane. The relative position between
20. French, R. R.; Holzer, P.; Leuenberger, M.; Nold, M. C.; Woggon, W. D. J. Inorg.
Biochem. 2002, 88, 295e304.
21. Dong, Z. Y.; Liu, J. Q.; Mao, S. Z.; Huang, X.; Yang, B.; Ren, X. J.; Luo, G. M.; Shen,
J. C. J. Am. Chem. Soc. 2004, 126, 16395e16404.
22. Dong, Z. Y.; Liu, J. Q.; Mao, S. Z.; Huang, X.; Luo, G. M.; Shen, J. C. J. Incl. Phenom.
Macrocycl. Chem. 2006, 56, 179e182.
the modified
b
-CDs and acetophenone was determined by the
23. Dong, Z. Y.; Liang, K.; Wang, C. Y.; Huang, X.; Mao, S.; Li, X. Z.; Xu, J. Q.; Liu, J. Q.;
Luo, G. M.; Shen, J. C. J. Mol. Catal. A: Chem. 2007, 277, 193e201.
distance, angle, and dihedral angle between the labeled carbon
atom in acetophenone and the three dummy atoms. The inclusion
complexes were firstly optimized at the level of PM3, and then the
output files were employed as input files for optimization at the
level of ONIOM(B3LYP/6-31G(d):PM3) to obtain optimized energy.
24. Lin, T.; Ding, Z.; Li, N.; Xu, J.; Luo, G.; Liu, J.; Shen, J. Carcinogenesis 2011, 32,
154e167.
25. Jiao, A. Q.; Yang, N.; Wang, J. P.; Toure, A.; Xu, X. M.; Jin, Z. Y. J. Incl. Phenom.
Macrocycl. Chem. 2012, 74, 335e341.
26. Zhou, Y. H.; Zhao, M.; Mao, Z. W.; Ji, L. N. Chem.dEur. J. 2008, 14, 7193e7201.
27. Tang, S. P.; Zhou, Y. H.; Chen, H. Y.; Zhao, C. Y.; Mao, Z. W.; Ji, L. N. Chem.dAsian J.
2
009, 4, 1354e1360.
28. Zhao, M.; Zhang, L.; Chen, H. Y.; Wang, H. L.; Ji, L. N.; Mao, Z. W. Chem. Commun.
010, 6497e6499.
9. Zhao, M.; Wang, H. L.; Zhang, L.; Zhao, C. Y.; Ji, L. N.; Mao, Z. W. Chem. Commun.
011, 7344e7346.
30. Hu, P.; Liu, G. F.; Ji, L. N.; Mao, Z. W. Chem. Commun. 2012, 5515e5517.
Acknowledgements
2
2
The authors thank the National Natural Science Foundation of
China (Nos. 21176268 and 21036009) for providing financial sup-
port to this project.
2
31. Bonchio, M.; Carofiglio, T.; Di Furia, F.; Fornasier, R. J. Org. Chem. 1995, 60,
5986e5988.
3
3
3
2. Sakuraba, H.; Maekawa, H. J. Incl. Phenom. Macrocycl. Chem. 2006, 54, 41e45.
3. Shen, H. M.; Ji, H. B. Carbohydr. Res. 2012, 354, 49e58.
4. Schlatter, A.; Kundu, M. K.; Woggon, W. D. Angew. Chem., Int. Ed. 2004, 43,
Supplementary data
6
731e6734.
5. Petter, R. C.; Salek, J. S.; Sikorski, C. T.; Kumaravel, G.; Lin, F. T. J. Am. Chem. Soc.
990, 112, 3860e3868.
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.tet.2013.07.077.
3
3
1
6. Frisch, M. J.; Trucks, G. W.; Schlegel, H. B.; Scuseria, G. E.; Robb, M. A.; R.
Cheeseman, J.; Montgomery, J. A., Jr.; Vreven, T.; Kudin, K. N.; Burant, J. C.;
Millam, J. M.; Iyengar, S. S.; Tomasi, J.; Barone, V.; Mennucci, B.; Cossi, M.;
Scalmani, G.; Rega, N.; Petersson, G. A.; Nakatsuji, H.; Hada, M.; Ehara, M.;
Toyota, K.; Fukuda, R.; Hasegawa, J.; Ishida, M.; Nakajima, T.; Honda, Y.; Kitao,
O.; Nakai, H.; Klene, M.; Li, X.; Knox, J. E.; Hratchian, H. P.; Cross, J. B.; Bakken,
V.; Adamo, C.; Jaramillo, J.; Gomperts, R.; Stratmann, R. E.; Yazyev, O.; Austin, A.
J.; Cammi, R.; Pomelli, C.; Ochterski, J. W.; Ayala, P. Y.; Morokuma, K.; Voth, G.
A.; Salvador, P.; Dannenberg, J. J.; Zakrzewski, V. G.; Dapprich, S.; Daniels, A. D.;
Strain, M. C.; Farkas, O.; Malick, D. K.; Rabuck, A. D.; Raghavachari, K.; Fores-
man, J. B.; Ortiz, J. V.; Cui, Q.; Baboul, A. G.; Clifford, S.; Cioslowski, J.; Stefanov,
B. B.; Liu, G.; Liashenko, A.; Piskorz, P.; Komaromi, I.; Martin, R. L.; Fox, D. J.;
Keith, T.; Al-Laham, M. A.; Peng, C. Y.; Nanayakkara, A.; Challacombe, M.; Gill, P.
M. W.; Johnson, B.; Chen, W.; Wong, M. W.; Gonzalez, C.; Pople, J. A. Gaussian
03, Revision D.01; Gaussian: Wallingford CT, 2004.
References and notes
1. Szejtli, J. Chem. Rev. 1998, 98, 1743e1753.
2
3
4
. Villalonga, R.; Cao, R.; Fragoso, A. Chem. Rev. 2007, 107, 3088e3116.
. Sallas, F.; Darcy, R. Eur. J. Org. Chem. 2008, 957e969.
. Abdel-Naby, M. A.; El-Refai, H. A.; Abdel-Fattah, A. F. J. Appl. Microbiol. 2011, 111,
1129e1137.
5. Takahashi, K. Chem. Rev. 1998, 98, 2013e2033.
6. Johnson, A. E.; Perchyonok, V. T. Curr. Org. Chem. 2009, 13, 914e918.
7. Chen, H. Y.; Ji, H. B. AIChE J. 2010, 56, 466e476.
8
. Prasantha, P. A.; Sandhya, N. C.; Kempegowda, B. K.; Bhadregowda, D. G.;
Mantelingu, K.; Ananda, S.; Rangappa, K. K. S.; Kumara, M. N. J. Mol. Catal. A:
Chem. 2012, 353, 111e116.
9. Zhao, W.; Zhong, Q. J. Incl. Phenom. Macrocycl. Chem. 2012, 72, 1e14.
1
1
1
1
1
1
0. Breslow, R.; Dong, S. D. Chem. Rev. 1998, 98, 1997e2011.
1. Marinescu, L.; Bols, M. Curr. Org. Chem. 2010, 14, 1380e1398.
2. Woggon, W. D. Curr. Org. Chem. 2010, 14, 1362e1379.
3. Marchetti, L.; Levine, M. ACS Catal. 2011, 1, 1090e1118.
4. Dong, Z. Y.; Luo, Q.; Liu, J. Q. Chem. Soc. Rev. 2012, 41, 7890e7908.
5. Breslow, R.; Zhang, X.; Xu, R.; Maletic, M.; Merger, R. J. Am. Chem. Soc. 1996, 118,
1678e11679.
6. Breslow, R.; Zhang, X.; Huang, Y. J. Am. Chem. Soc. 1997, 119, 4535e4536.
7. Yang, J.; Breslow, R. Angew. Chem., Int. Ed. 2000, 39, 2692e2694.
8. Yang, J.; Gabriele, B.; Belvedere, S.; Huang, Y.; Breslow, R. J. Org. Chem. 2002, 67,
057e5067.
37. Bennett, M. A.; Smith, A. K. J. Chem. Soc., Dalton Trans. 1974, 233e241.
38. Canivet, J.; Suss-Fink, G.; Stepnicka, P. Eur. J. Inorg. Chem. 2007, 4736e4742.
39. Canivet, J.; Suss-Fink, G. Green Chem. 2007, 9, 391e397.
40. Betzel, C.; Saenger, W.; Hingerty, B. E.; Brown, G. M. J. Am. Chem. Soc. 1984, 106,
7545e7557.
41. Yang, E. C.; Zhao, X. J.; Hua, F.; Hao, J. K. J. Mol. Struct.: THEOCHEM 2004, 712,
75e79.
42. Cao, Y. J.; Xiao, X. H.; Ji, S. F.; Lu, R. H.; Guo, Q. X. Spectrochim. Acta, Part A 2004,
60, 815e820.
1
1
1
1
43. Cao, Y. J.; Lu, R. H. Spectrochim. Acta, Part A 2009, 73, 713e718.
44. Yahia, O. A.; Khatmi, D. E. J. Mol. Struct.: THEOCHEM 2009, 912, 38e43.
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