Highly asymmetric hetero-Diels-Alder reaction using helical silica-supported Mn(III)-salen catalysts

Article abstract of DOI:10.1016/j.tet.2015.08.045

Helical silica were prepared and functionalized by Mn(III)-salen complexes in order to catalyze asymmetric hetero-Diels-Alder reactions. Characterizations revealed doping of sodium lactate facilitated porosity, hydrolysis resistance and chiral configurati

Full text of DOI:10.1016/j.tet.2015.08.045

Accepted Manuscript
Highly asymmetric hetero-Diels-Alder reaction using helical silica-supported Mn(III)-
salen catalysts
Le Li, Yu Li, Di Pang, Fei Liu, Aqun Zheng, Guangbin Zhang, Yang Sun
PII:
S0040-4020(15)01237-5
10.1016/j.tet.2015.08.045
TET 27067
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 6 July 2015
Revised Date: 13 August 2015
Accepted Date: 17 August 2015
Please cite this article as: Li L, Li Y, Pang D, Liu F, Zheng A, Zhang G, Sun Y, Highly asymmetric
hetero-Diels-Alder reaction using helical silica-supported Mn(III)-salen catalysts, Tetrahedron (2015),
doi: 10.1016/j.tet.2015.08.045.
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ACCEPTED MANUSCRIPT
Revised Graphical Abstract

ACCEPTED MANUSCRIPT
Highly asymmetric hetero-Diels-Alder reaction using helical silica-supported
Mn(III)-salen catalysts
a
a
b
b
a
c
a,
Le Li , Yu Li , Di Pang , Fei Liu , Aqun Zheng , Guangbin Zhang , Yang Sun *
Department of Applied Chemistry, School of Science, Xi’an Jiaotong University, No. 28,
Xianning West Road, Xi’an 710049, PR China
a
b
School of Materials & Chemical Engineering, Xi’an Technological University, No. 2, Xuefu
Road, Xi’an 710021, PR China
c
School of Pharmacy, Health Science Center, Xi’an Jiaotong University, No. 76, Yanta West Road,
Xi’an 710061, PR China
Abstract
Helical silica were prepared and functionalized by Mn(III)-salen complexes in order to
catalyze asymmetric hetero-Diels-Alder reactions. Characterizations revealed doping of sodium
lactate facilitated porosity, hydrolysis resistance and chiral configuration of silica matrix. Catalysis
revealed the combination of Mn(III)-salen with helical silica had excellent chiral induction. Major
product configuration was affected by temperature and solvent. Loading imidazolium ionic liquid
as solvent improved both enantioselectivity and catalyst recycling.
Keywords: Helical silica; Mn(III)-salen; Immobilization; hetero-Diels-Alder.
1
. Introduction
*
Corresponding author. E-mail address: sunyang79@mail.xjtu.edu.cn (Y. Sun).
1

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Asymmetric hetero-Diels-Alder (hDA) reaction of 1,3-diene with carbonyl compound
provided a strategy for synthesis of chiral six-membered heterocycles, which had showed great
1
,2
values in both synthetic and pharmaceutical fields. In view of reaction rate and scale, optical
purity of product, as well as environmental protection, the application of efficient catalysts for
3
,4
hDA reaction had become an important selection for academic and industrial concerns.
Previously, metal complexes afforded excellent stereoselectivity and conversion for asymmetric
5
6
7
8
hDA, including chromium-salen, copper-Schiff-base, titanium-binol, zirconium-binol,
9
10
gold-phosphoramidite or rare earth-phosphate . Organocatalysts also attracted attentions due to
11
avoidance of metal toxicity, tolerance of air, and convenient manipulation. TADDOL
1
2
13
14
(
α,α,α’,α’-tetraaryl-1,3-dioxolane-4,5-dimethanol), oxazoline or bis-sulfonamide were typical
examples. Even so, some key issues involving optical yield, catalyst recycling, cost of route and
environmental burden still demanded endeavors for promotion.
1
5
Synthesis and application of chiral silica materials had aroused interests in recent years.
Immobilization of chiral metal complexes into chiral silica was an interesting alternative for
heterogeneous asymmetric catalysis, because the synergy of two components might affect outputs,
1
6
including conversion and stereoselectivity. On the other hand, ionic liquids were chemically
1
7
stable, non-volatile and nonflammable, but not very viscous. Dispersion of metal catalysts into
1
7
ionic liquid could avoid leaching of metal ions in some cases. Therefore, ionic liquids were
1
8
promising solvents in heterogeneous catalysis.
In this work, a series of helical silica were prepared in a sol-gel procedure, where sodium
lactate was doped in order to affect chirality. The Mn(III)-salen complexes (Jacobsen’s catalyst)
were immobilized into helical silica to catalyze asymmetric hDA reactions of Danishefsky’s diene
2

ACCEPTED MANUSCRIPT
with carbonyl compounds. In addition to regular solvents, two imidazolium ionic liquids BMImX
+
-
-
-
(
BMIm = 1-n-butyl-3-methylimidazolium; X = NO or BF ) were introduced to improve
3 4
recycling of catalysts. Overall, this work would provide new chiral silica materials as well as an
efficient catalytic system for asymmetric hDA reactions.
2
2
. Results and discussion
.1. Synthesis of catalysts
Synthesis of catalysts was shown in Scheme 1. Helical silica N was synthesized according to
1
9
the method established by Ying and co-workers. L and D were prepared according to the same
process, except for the doping of chiral sodium lactate. Formation of helical silica would be
discussed in Section 2.8.. Phenylsulfonylation of helical silica was performed according to
2
0
literature with modifications. At last, immobilization of Mn(III)-salen complexes into functional
helical silica was performed in dichloromethane.
PhSO H(p-)
Ph
Si
3
Si
OH OH OH
O
O
O O O
O
H SO (10 wt%)
PTMS
2
4
NaHCO
3
4
0 o
C
Toluene
N: no chiral additive
L: L-sodium lactate
D: D-sodium lactate
(a)
(b)
R2
1
R1
R
R2
N
N
Mn
O
t-Bu
O
O
t-Bu
O
O
t-Bu
t-Bu
R
2
R1
R2
R
1
S
Mn1, Cat1: R1 = R2 = H; from Y;
Cat2: R1 = R2 = H; from YL;
Cat3: R = R = H; from YD;
Mn2, Cat4: R1 + R1 = -(CH ) -; R = H; from Y;
N
Mn
O Cl
N
PhSO Na(p-)
3
Ph
Si
O
Si
t-Bu
O
t-Bu
1
2
O O O
2 4
2
t-Bu
t-Bu
(
Mn)
O
O
Cat5: R1 + R1 = -(CH ) -; R = H; from YL;
2 4
2
Cat6: R1 + R1 = -(CH ) -; R = H; from YD;
2 4
2
CH Cl2
2
Y: from N
YL: from L
YD: from D
Mn3, Cat7: R1 = H; R2 + R2 = -(CH ) -; from Y;
(
Cat)
2 4
Cat8: R1 = H; R2 + R2 = -(CH ) -; from YL;
2 4
Cat9: R1 = H; R2 + R2 = -(CH ) -; from YD;
2 4
Scheme 1. Immobilization of Mn(III)-salen complexes into helical silica.
3

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2
.2. FT-IR study
Fig. 1. FT-IR of L (a), YL (b), Cat5 (c) and Cat6 (d).
-1
Sample L showed the stretching vibration of SiO-H at 3426 cm , which was sharply degraded
-1
and moved to 3439 cm after functionalization, proving PTMS were attached to L (a vs. b, Fig. 1).
-1
-
Furthermore, the vibration at 1136 cm represented anti-symmetric stretching of -SO , indicating
3
2
1
phenylsulfonylation of L was available (b, Fig. 1).
-1
The 3447 cm on Cat5 could be ascribed to the stretching of non-substituted silanol groups,
-1
while 3121 cm illustrated C-H stretching of benzene on Mn2 (c, Fig. 1). Both 2959 and 2868
-
1
-1
cm characterized stretching of C-H on methyl. The 1614 cm demonstrated C=N stretching,
-
1
22
while a new peak at 543 cm could be assigned to Mn-O stretching. Although symmetric
-
-1
-1
stretching of -SO3 might be overlapped by Si-O stretching at 1088 cm , the 1136 cm still
-
21,22
characterized anti-symmetric stretching of -SO (c, Fig. 1).
All these data proved linkage of
3
Mn2 with YL was available.
4

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There were no significant differences among Cat4-6, indicating sodium lactate would not
change linking mode between Mn(III)-salen and helical silica (Fig. S1, Supplementary data; c and
d, Fig. 1).
2
.3. Nitrogen adsorption-desorption
Fig. 2. Nitrogen adsorption-desorption isotherms and pore size distribution of L (a and a’), YL (b
and b’) and Cat6 (c and c’).
Both N and L showed type II isotherms, ordered pore size distributions, along with large
surface areas, proving they had uniform channel-like mesopores (Fig. S2, Supplementary data; a
1
9,23
and a’, Fig. 2; Table 1).
L showed larger BET surface area and pore volume than N, proving
sodium lactate had unique template effects on porosity. Phenylsulfonylation of L decreased BET
surface area and pore volume (YL vs. L, Table 1), but type of isotherms was basically preserved
5

ACCEPTED MANUSCRIPT
(b vs. a, Fig. 2), indicating PTMS entered channels of L.
Immobilization of Mn2 into L gave a poor porosity (Cat5 vs. L, Table 1), so did that of Mn2
into Y (Cat4 vs. N, Table 1). However, attachment of Mn2 to D showed a promising BET surface
area (Cat6 vs. D, Table 1), as well as type II isotherms and ordered pore size distribution (c and c’,
Fig. 2). Therefore, the porous silica matrixes should be degraded to some extent during
functionalization or immobilization.
Table 1
Textural parameters of samples
a
b
c
d
e
f
Sample
N
SBET
PV
PR
ρ
dS
dW
-
-
-
-
-
-
-
1
1
1
1
2
2
1
958.2
1372.9
1190.7
770.6
59.3
6.4 × 10
8.6 × 10
7.5 × 10
2.2 × 10
6.8 × 10
7.6 × 10
1.9 × 10
12.9
12.9
13.0
13.4
44.6
64.0
13.9
0.2
1.0
0.9
1.0
0.5
0.5
0.4
31.3
4.3
175.7
89.6
L
D
5.5
206.9
418.1
161.5
173.2
117.0
YL
7.7
Cat5
Cat4
Cat6
202.3
600.0
22.6
20.0
660.8
a
2
-1
Surface area (m g ) determined by BET method based on N adsorption.
2
b
c
d
e
f
3
-1
Pore volume (cm g ), BJH method on N adsorption.
2
Pore radius (nm), BJH method on N adsorption.
2
-3
Bulk density (g cm ).
Crystallite size (nm) based on BET surface area: d = 6/(SBET·ρ), ρ bulk density.
S
Diameter of particle in CH Cl (nm).
2
2
2
.4. Low-angle X-ray diffraction
6

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Fig. 3. Low-angle XRD of powdered L (a), Cat5 (b), D (c), YD (d) and Cat6 (e).
Both N and L as well as D showed hexagonal symmetry because 10, 11, 20 diffractions were
o
detectable. Lattice constant (a) had an order as N (3.74 nm, 2θ = 2.360 ) > D (3.63 nm, 2θ =
o
o
2
.428 ) > L (3.55 nm, 2θ = 2.488 ), which revealed doping of sodium lactate maintained
1
9
hexagonal phase (Fig. S3, Supplementary data; Fig. 3).
Attachment of PTMS and Mn2 to N destroyed hexagonal symmetry completely (b vs. a, Fig.
S3), but immobilizations of L and D looked much better, where only small diffractions such as 11
and 20 were degraded (b vs. a, e vs. c, Fig. 3), indicating doping of sodium lactate improved
24
hydrolysis resistance of silica matrixes. In particular, YD showed hexagonal symmetry similar to
D, but had a narrower basal spacing (d vs. c, Fig. 3), demonstrating PTMS entered internal
channels of D (Scheme 1). Furthermore, YD and Cat6 shared an identical basal spacing of 3.40
o
nm at 2θ = 2.596 (d and e, Fig. 3), but 11 and 20 diffractions of Cat6 disappeared, proving Mn2
were mainly attached to 11 and 20 lattice planes of YD (e vs. d, Fig. 3).
7

ACCEPTED MANUSCRIPT
2
.5. X-ray photoelectron spectroscopy
Neither N nor L showed 1s photoelectron of nitrogen that demonstrated nitrogen-containing
templates were completely removed after calcination (Table 2). Sodium lactate reduced content of
carbon and doubled that of Si and O simultaneously, while binding energies were preserved, both
proving sodium lactate accelerated removal of organic templates under calcination (L vs. N, Table
2
).
After immobilization of PTMS and Mn2 into N, contents and binding energies of Si and O on
N were decreased, but content of carbon was increased, suggesting Mn2 were attached to N (Cat4
vs. N, Table 2). Similar tendency was found in variation of L to Cat5, and detection of sodium
ions on YL proved salification was available (Table 2 and Scheme 1).
Table 2
Binding energy and atomic composition of Si, O, C, N and Mn on sample surface
Sample
N
Si (2p)
O (1s)
C (1s)
N (1s) / Na (1s)
Mn (2p)
a
104.0 (17.7)
103.0 (8.0)
104.0 (34.1)
103.0 (31.3)
103.0 (5.9)
103.0 (27.6)
533.0 (26.7)
532.0 (12.7)
533.0 (42.3)
533.0 (35.4)
532.0 (10.1)
533.0 (31.3)
285.0 (55.2)
285.0 (77.3)
285.0 (23.4)
285.0 (33.1)
285.0 (81.1)
285.0 (40.6)
-
-
Cat4
L
399.0 (0.63)
-
642.0 (0.28)
-
b
YL
1072.0 (0.12)
-
Cat5
Cat6
399.0 (0.99)
399.0 (0.16)
642.0 (0.36)
644.0 (0.11)
a
Binding energy (eV), along with atomic percentage (at%) in parentheses.
Above parameters of Na.
b
2
.6. SEM and TEM
8

ACCEPTED MANUSCRIPT
Fig. 4. SEM of L (a), D (b), Cat5 (c), Cat6 (d) and TEM of Cat5 (e), Cat6 (f).
The N was composed of helical rods having length of 0.5-5 ꢀm, pitch of 0.5-1.5 ꢀm, and offset
distance from spiral axis to center of rod) of 20-200 nm (a’’, Fig. S4, Supplementary data). The N
(
had both right- and left-handed morphologies, along with a small amount of amorphous blocks
a’’, Fig. S4). Moreover, L and D showed the same appearance as N (a, b, Fig. 4; b’, c’, Fig. S4).
(
Therefore, sodium lactate had little influences on morphology of helical silica.
Only phenylsulfonylation did not destroy morphology and porosity of helical silica (Scheme 1;
9

ACCEPTED MANUSCRIPT
d’ vs. e’, Fig. S4; YL, Table 1), but subsequent immobilization of Mn2 degraded silica matrixes
sometimes. For example, Cat4 was degraded into large sticky blocks (f’ and f’’, Fig. S4), which
was proved by a poor surface area (Cat4, Table 1). Cat5 looked better owing to a small extent of
degradation (c, Fig. 4). Cat6 appeared to be unaffected on appearance (d, Fig. 4), being approved
2
-1
by a surface area of 660.8 m g (Cat6, Table 1). Thus, sodium lactate improved hydrolysis
resistance of helical silica. In addition, Cat4-6 were all solid rods rather than hollow tubes based
on TEM observations (f’’, Fig. S4; e and f, Fig. 4).
2
.7. Configuration of internal channels
The N preferred L-valine rather than D-valine, but both L and D showed the contrary
adsorption priority, indicating channels of N were left-handed on average, while those of L and D
2
5
were right-handed (b and c vs. a, Fig. S5, Supplementary data). Y, YL and YD had the same
chiral configuration as their precursors N, L and D, respectively (d vs. a, e vs. b, f vs. c, Fig. S5).
Meanwhile, adsorbed amount of Y, YL and YD were larger than N, L and D, mainly because
sodium benzene sulfonate groups had been fixed on silica surface (d vs. a, e vs. b, and f vs. c, Fig.
S5).
Cat4 maintained configuration of channels derived from N to Y (g vs. d and a, Fig. S5), but
Cat5 changed configuration of YL (h vs. e, Fig. S5), probably because Mn(III)-(R,R)salen (Mn2)
preferred L-valine more than D-valine, which might take effects on enantioselective adsorption
when content of Mn-salen units was high enough in catalyst (Cat5, Table S1, Supplementary data).
Accordingly, perhaps because Cat6 had a lower Mn content than Cat5 (Table S1),
enantioselective adsorption of valine on Cat6 was still dominated by YD more than Mn2 (i vs. f,
1
0

ACCEPTED MANUSCRIPT
Fig. S5).
2
.8. Proposed formation of helical silica
TEOS
C TAB
+
L-Sodium lactate
1
6
NH (aq. 25 wt.%)
3
Chiral
Micelle
HO
EtO
OEt
OEt
O
Si
-O
Alkali-promoted hydrolysis of TEOS
Self-polymerization
N
HO
+
-
HO
Si
Na Br
O
OEt
OEt
EtO
-O
N
N
HO
+
-
Na Br
O
HO
OEt
-O
Si
EtO
OEt
HO
+
Na Br-
TEOS, H O
2
O
(guest collision)
OH
Si
N
+ -
EtO
O
OEt
+
Na Br-
EtO
(helical packing)
HO
Helical composite
O
N
OH
Si
-O
EtO
+
-
Na Br
OEt
Calcination
HO
EtO
O
N
-O
+
-
Na Br
HO
OH
EtO
Si
OEt
EtO
Porous helical silica
Fig. 5. Proposed formation of helical silica.
According to the above discussions, formation mechanism of helical silica was proposed in
Fig. 5. Herein, lactate anions would attract C TAB cations that constructed framework of micelle.
1
6
Under alkaline environment, TEOS would be hydrolyzed and polymerized, providing shell and
stuff of micelle.
In view of a theory on entropy-driven formation of helices, a chain-like and flexible
macromolecule or agglomerate might be twisted in a crowded environment in order for maximum
11

ACCEPTED MANUSCRIPT
2
6
entropy of guest molecules. In this work, due to effects of entropy, packing of micelles would be
twisted by collision of guest molecules such as TEOS and water, then be wrapped by
self-polymerization of TEOS (Fig. 5).
Probably because collision of guest molecules was disordered, N and L as well as D had both
left-handed and right-handed morphologies (Fig. 4 and Fig. S4). However, N was internally
left-handed, while L and D were both right-handed (a, b, c, Fig. S5), proving chiral sodium lactate
facilitated internal chirality of micelles in sol-gel (Fig. 5), and interestingly two enantiomers of
sodium lactate had the same effects on internal configuration (b and c, Fig. S5).
2
.9. Catalysis
Catalyst blank provided conversion of 3%, indicating molecular sieve (4Å) was catalytically
active to some extent (entry 1, Table 3). YL showed conversion of 2 %, proving Mn(III)-salen
would be catalytic center if positive results were obtained (entry 2). All other reactions proceeded
smoothly during the entire work (Tables 3 and 4).
Because Mn1 was achiral, asymmetric induction of Cat1-3 depended on Y, YL and YD
16
respectively (Scheme 1). N was left-handed (a, Fig. S5), L and D were both right-handed (b and
c, Fig. S5), but their combinations with Mn1 showed good to excellent e.e. values for
transformation of benzaldehyde (entries 3-5). Association of L with Mn1 (Cat2) provided
excellent e.e. for heptaldehyde too (entry 28). In addition, Cat2 showed moderate to poor e.e. for
acetophenone (entry 17), ethyl glyoxylate (entry 35) and cyclohexanecarboxaldehyde (entry 24).
Therefore, chiral induction of helical silica was affirmative.
1
2

ACCEPTED MANUSCRIPT
Table 3
Catalytic asymmetric hDA reactions of Danishefsky’s diene with various carbonyl compounds
OCH3
(1) Catalyst (2 mol%)
MS 4 angstrom
O
O
*
solvent, T, 6 h
+
R'
(
H C) Si
3 3
R
R'
(2) CF COOH
O
3
O
R
a
o
b
c
d
-1
Entry
Carbonyl
Catalyst
blank
YL
Solvent
T ( C)
Yield (%) E.e. (%)
TOF (h )
1
2
3
4
5
6
7
8
9
1
CH Cl2
0
3
0
-
2
O
a
CH Cl2
0
2
0
-
2
Ph
H
Cat1
Cat2
Cat3
Mn2
Cat4
Cat5
Cat5
Cat6
Cat6
Cat6
Cat6
Cat7
Cat8
Cat9
Cat2
Mn2
Cat4
Cat5
Cat5
Cat6
Cat7
Cat2
Mn2
Cat5
Cat5
Cat2
Mn2
Cat4
Cat5
Cat5
Cat6
Cat7
CH Cl2
2
0
83
100 (S)
100 (S)
84 (S)
45 (R)
82 (R)
57 (R)
73 (S)
70 (R)
93 (S)
95 (S)
97 (S)
100 (S)
91 (S)
87 (S)
-39
3.2
5.4
3.0
3.3
5.4
7.9
6.6
7.4
8.2
7.4
7.4
8.3
8.3
8.3
6.4
3.0
6.7
7.5
5.5
6.9
7.9
8.3
8.3
8.3
8.3
7.4
8.3
8.3
8.3
6.8
8.3
8.3
CH Cl2
0
65
2
CH Cl2
0
36
2
CH Cl2
0
40
2
CH Cl2
0
65
2
CH Cl2
0
94
2
CH Cl2
-78
0
79
2
0
CH Cl2
89
2
11
toluene
0
98
1
1
1
1
1
1
1
1
2
2
2
2
2
2
2
2
2
2
3
3
3
3
3
2
3
4
5
6
7
8
9
0
1
2
3
4
5
6
7
8
9
0
1
2
3
4
CH CN
0
89
3
C H OH
0
88
2
5
CH Cl2
0
100
100
99
2
CH Cl2
0
2
CH Cl2
0
2
CH Cl2
0
77
2
O
CH Cl2
0
36
25
2
Ph
CH3
CH Cl2
0
81
-50
2
CH Cl2
0
90
58
2
CH Cl2
-78
0
66
-96
2
CH Cl2
83
48
2
CH Cl2
0
95
-67
2
CH Cl2
0
100
100
100
100
89
1 (R)
29 (S)
20 (S)
23 (R)
-100
56
2
O
CH Cl2
0
2
H
CH Cl2
0
2
CH Cl2
-78
0
2
CH Cl2
2
O
CH Cl2
0
100
100
100
82
5
H
2
CH Cl2
0
-10
2
CH Cl2
0
84
2
CH Cl2
-78
0
-95
2
CH Cl2
100
100
67
2
CH Cl2
0
-66
2
1
3

ACCEPTED MANUSCRIPT
3
3
3
3
3
4
4
5
6
7
8
9
0
1
Cat2
Mn2
Cat4
Cat5
Cat5
Cat6
Cat7
CH Cl2
0
100
66
-39
77
8.3
5.5
8.3
8.3
8.3
8.3
8.3
2
O
CH Cl2
0
2
O
O
CH Cl2
0
100
100
100
100
100
-59
71
2
H
CH Cl2
0
2
CH Cl2
-78
0
-98
81
2
CH Cl2
2
CH Cl2
0
-86
2
a
b
c
Conditions same as in section 4.6.. Na of YL surface controlled at 2 mol% based on carbonyl substrate (Table 2).
Molar percentage of hDA product to original carbonyl substrate, but those of entries 24-27 determined by diene.
Enantiomeric excess. Retention time (min) for hDA product of benzaldehyde: 3.664 (R) and 4.040 (S),
27
determined by comparison with literature ; product of acetophenone: 3.578 and 3.938, absolute configuration not
determined, e.e. = ([early (retention time)] – [late]) / ([early] + [late]), also for other cases lack of absolute
28
27
configurations; product of cyclohexanecarboxaldehyde : 3.970 (S) and 6.197 (R); product of heptaldehyde :
29
3
.632 and 3.995, absolute configuration not determined; product of ethyl glyoxylate : 3.621 and 3.970; absolute
configuration not determined.
d
-1
-1
Turnover frequency, molproduct molMn (6 h) .
On the other hand, Cat2 showed very high e.e. value for reaction of heptaldehyde, but showed
very poor e.e. for cyclohexanecarboxaldehyde (entries 24 vs. 28). In the present system, the
hydroxyl of silanol on Cat2 would construct hydrogen bond in association with carbonyl substrate.
Heptaldehyde has a long and flexible alkyl that could be induced by chiral centers on catalyst
easily.
However,
the
boat-to-chair
conformation
change
of
cyclohexyl
on
cyclohexanecarboxaldehyde could be restricted by silanols on Cat2 through hydrogen-bond or
other adsorptions, which might depress enantioselectivity. This phenomenon was different with
2
7
28
those stemmed from strictly homogenous or polymer-facilitated catalysis.
Immobilization of Mn2 into helical silica increased e.e. values, which were observed in
1
4

ACCEPTED MANUSCRIPT
reactions of benzaldehyde (entries 7, 8, 10 vs. 6), acetophenone (entries 19, 20, 22 vs. 18),
heptaldehyde (entries 31, 33 vs. 29) and ethyl glyoxylate (entries 40 vs. 36). On the other hand,
Mn2 dominated major configuration of hDA product of benzaldehyde rather than helical silica
(entries 7 vs. 3; 8 vs. 4; 10 vs. 5), so did Mn3 (entries 14 vs. 7, 15 vs. 8, 16 vs. 10). Similar trends
were observed in transformations of acetophenone (entries 20 and 22 vs. 18; 23 vs. 19),
cyclohexanecarboxaldehyde (entries 26 vs. 25), heptaldehyde (entries 31 and 33 vs. 29; 34 vs. 30)
and ethyl glyoxylate (entries 38 and 40 vs. 36; 41 vs. 37). Therefore, Mn(III)-salen and helical
silica had a synergy on chiral induction, where Mn(III)-salen controlled product configuration and
helical silica took effects in promotion of e.e. values.
Combination of sodium lactate-doped silica (YL or YD) with Mn2 afforded higher e.e. values
than that of non-doped material (Y) for reactions of acetophenone (entries 20 vs. 19),
heptaldehyde (entries 31 and 33 vs. 30) and ethyl glyoxylate (entries 38 and 40 vs. 37). Only a
small deviation was observed in that of benzaldehyde (entries 8 and 10 vs. 7). Therefore, doping
of sodium lactate improved chiral induction of helical silica.
The most significant result was temperature-facilitating major configuration of product, which
was found in all substrates (entries 9 vs. 8; 21 vs. 20; 27 vs. 26; 32 vs. 31; 39 vs. 38). Herein, Cat5
was composed of YL (mesoscopic chirality) and Mn2 (molecular chirality), but they had contrary
o
inducing direction on major configuration of product (entries 4 vs. 6). The 0 C might provide a
reaction of thermodynamic control where Mn2 dominated configuration of product, but a much
o
30
lower temperature (-78 C) probably gave a kinetic control where Mn2 and YL worked together.
Another interesting phenomenon was effects of solvent on major configuration of product and
enantioselectivity. In practice, toluene, acetonitrile and ethanol showed the same major
1
5

ACCEPTED MANUSCRIPT
configuration in combination with Cat6, but dichloromethane gave different results (entries 11-13
vs. 10). Under Cat5, BMImNO and BMImBF showed a major configuration contrary to that
3
4
from dichloromethane either (Table 4). Thus, the polarity of solvent, along with interaction of
solvent with silica surfaces might play a key role in determination of major configuration of
product. In addition, all polar solvents afforded satisfactory yields in transformation of
benzaldehyde (entries 10-13). The stronger the polarity was, the higher the e.e. value was (entries
1
0 < 11 < 12 < 13 < ionic liquids of Table 4), indicating chiral induction of helical silica-supported
3
1
Mn(III)-salen could be promoted under highly polarized media.
2
.10. Recycling of catalyst
Although fresh cycle achieved satisfactory yield and good enantioselectivity (entry 8), direct
recycling of Cat5 was not very efficient because no product was detected after four cycles
Cat5/CH Cl , Table 4). The weakening of Mn-O bond by valence change of Mn ion, or leaching
(
2
2
3
2
of Mn(III)-salen complexes into n-hexane may take part in it (section 4.6.).
In this work, BMImNO and BMImBF were employed as recycling media, and satisfactory
3
4
e.e. values were obtained (Table 4). Obviously, two ionic liquids prevented degradation of
Mn(III)-salen effectively, perhaps owing to coordination of nitrogen of imidazolyl into manganese
ions. Furthermore, BMImBF showed better yields than BMImNO in recycling, probably because
4
3
-
-
BF4 showed higher affinity to Mn(III)-salen than NO3 (Table 4). In practice, chemical
3
3
modification of Jacobsen’s catalyst could not always guarantee stereoselectivity. However, this
work provided a promising strategy for reusability of Mn(III)-salen catalyst without changing
structure.
1
6

ACCEPTED MANUSCRIPT
Table 4
Recycling of Cat5 in imidazolium ionic liquids for hDA reaction of Danishefsky’s diene with benzaldehyde
OCH3
(1) Cat5 (2 mol%)
MS 4 angstrom
solvent, 0 C, 6 h
O
o
O
*
+
H
(
H C) Si
3 3
Ph
H
(2) CF COOH
O
3
O
Ph
a
Catalyst
Yield (%), E.e. (%)
Cycle fresh
Cycle 1
Cycle 2
Cycle 3
Cycle 4
-
Cycle 5
b
Cat5/CH Cl2
94, 57 (R)
80, 60 (R)
87, 100 (S)
77, 100 (S)
35, 25 (R)
80, 100 (S)
83, 100 (S)
10, 36 (R)
81, 100 (S)
70, 100 (S)
-
2
Cat5/BMImNO3 88, 100 (S)
Cat5/BMImBF4 74, 100 (S)
70, 100 (S)
69, 100 (S)
50, 100 (S)
74, 100 (S)
a
Recycling details same as in section 4.6., other parameters same as in Table 3.
Entry 8, Table 3.
b
3
. Conclusions
In conclusion, doping of sodium lactate significantly changed porosity, internal configuration
and hydrolysis resistance of helical silica. In heterogeneous catalysis, combination of achiral
Mn(III)-salen complex with helical silica provided high enantioselectivity, while the synergy of
Mn(III)-salen with helical silica on chiral induction was present. Secondly, temperature and
solvent showed important influences on major configuration of products as well as
enantioselectivity. At last, imidazolium ionic liquids were efficient media for recycling of catalyst.
This work developed a new series of chiral silica materials, and provided a highly asymmetric,
recyclable, green and low-cost route to catalytic asymmetric hetero-Diels-Alder reaction.
4
4
. Experimental
.1. Starting materials
Hexadecyltrimethylammonium bromide (C TAB), tetraethyl orthosilicate (TEOS), L- and
1
6
1
7

ACCEPTED MANUSCRIPT
D-sodium lactate, ammonia solution (25 wt.%), phenyltrimethoxysilane (PTMS), Danishefsky’s
diene (1-methoxy-3-trimethylsilyloxy-1,3-butadiene, 94 wt.%), benzaldehyde, acetophenone,
cyclohexanecarboxaldehyde, heptaldehyde, ethyl glyoxylate (50 wt.% in toluene) and
trifluoroacetic acid were purchased from Aldrich, Accela or Acros. Jacobsen’s catalyst (Mn1-3,
3
4
+
Scheme 1; Sections 1-2, Supplementary data), and ionic liquid BMImX (BMIm
=
-
- 35
1
-n-butyl-3-methylimidazolium; X = BF ) were synthesized according to literatures (Section 4,
4
-
-
Supplementary data). BMImX (X = NO ) was prepared by the ion-exchanging of commercial
3
BMImCl with AgNO in distilled water (Section 3, Supplementary data).
3
4
.2. Instruments
1
H NMR was recorded on Bruker ADVANCE III (400MHz). ESI-HRMS was detected on
microOTOF-Q II, Bruker.Daltonics. GC-MS was carried out on GCMS-QP2010 Plus, Shimadzu.
Mn contents were measured by inductively coupled plasma atomic emission spectrometry
(ICP-AES) on ICPE-9000, Shimadzu. FT-IR was reported in KBr pellets on Bruker Tensor 27,
-1
with wave numbers of 400-4000 cm .
BET surface area, pore volume, pore radius and pore size distribution were performed on
Micromeritics ASAP 2020, using N adsorption isotherms at 77.35 K. Samples were degassed at
2
o
1
50 C in vacuum before testing. Surface area was calculated on these isotherms using the
multi-point Brunauer-Emmett-Teller (BET) method based on adsorption data in relative pressure
P/P of 0.06-0.3. Total pore volume was obtained from N adsorbed at P/P = 0.97. Pore volume
0
2
0
and pore radius were determined using Barrett-Joyner-Halenda (BJH) method.
Particle size was tested in CH Cl at 298 K on Zetasizer Nano ZS90, Malvern. Low-angle
2
2
1
8

ACCEPTED MANUSCRIPT
o
o
X-ray diffractions (2θ at 0.5 to 10 ) of powdered samples were reported on Philips X’Pert Pro
o
-1
diffractometer using Cu-Ka radiation (λ, 1.5418 Å), with interval of 0.05 second , scattering
o
o
signals of 0.5 -2.0 were omitted for clarity. X-ray photoelectron spectroscopy (XPS) was carried
out on Kratos Axis Ultra DLD, using monochromatic Al Kα X-ray (1486.6 eV) as irradiation
source, the binding energy scale was calibrated by using C 1s peak at 285.0 eV. Scanning electron
microscopy (SEM) was performed on JEOL JSM-6700F at 20.0 kV with Au coating. Transmission
electron microscopy (TEM) was tested on JEOL JEM-200CX at 120 kV.
Internal chirality of samples was characterized by enantioselective adsorption of valine in
25
water. In practice, sample (20 mg) and L-(or D-)valine (50 mg) were added to distilled water (20
o
mL), then stirred at 25 C for 120 minutes. Concentration of L-(or D-)valine was monitored at
regular intervals by UV (210 nm, UV 1800, Shimadzu). Adsorption percentage was determined by
Lambert-Beer’s Law, then plotted as a function of time.
Thin layer chromatography (TLC) was performed on glass plates coated with GF254 silica gel,
with coloration in phosphomolybdic acid (PMA)/ethanol solution (5 wt.%). Yield and e.e. were
determined by HPLC (Section 12, Supplementary data). System controller: Waters 1525, binary
hplc pump; UV-Vis detector: Waters 2998, photodiode array detector; UV: 254 nm for
2
2
2
2
2
,3-dihydro-2-phenyl-4H-pyran-4-one
,3-dihydro-2-methyl-2-phenyl-4H-pyran-4-one
-cyclohexyl-2,3-dihydro-4H-pyran-4-one
-hexyl-2,3-dihydro-4H-pyran-4-one
(from
benzaldehyde),
(acetophenone),
(cyclohexanecarboxaldehyde),
(heptaldehyde)
and
-ethoxyformyl-2,3-dihydro-4H-pyran-4-one (ethyl glyoxylate), obtained by scanning 200-400
nm. Daicel Chiralcel OD-H, size: 150 mm × 4.6 mm; particle: 5 ꢀm; mobile phase:
1
9

ACCEPTED MANUSCRIPT
-1
n-hexane/2-propanol, 90/10, v/v; rate: 0.5 mL min ; column temperature: 300 K, pressure: 3.0-3.5
-1
MPa; sample concentration: 0.5 mg mL in n-hexane; injection: 10 ꢀL.
4
.3. Synthesis of helical silica
Sample N was synthesized according to literature. L and D were prepared as follows.
C TAB (0.40 g, 1.09 mmol) and L-(or D-)sodium lactate (0.06 g, 0.54 mmol) were dissolved in
1
9
1
6
o
aqueous ammonia (25 wt.%, 100 mL) at 40 C. TEOS (2.0 mL, 1.86 g, 8.95 mmol) was
o
o
introduced. The mixture was slowly stirred (800 rpm) at 40 C for 3 h, then aged at 100 C for 24
o
h in autoclave. White solids (L or D) were filtered, dried in air, calcined at 550 C for 5 h to
remove templates.
4
.4. Phenylsulfonylation of helical silica
o
N (L or D, 0.9 g) was dehydrated at 60 C for 24 h, then added to dry toluene (150 mL), and
o
dispersed by ultrasound at 25 C for 3 h. PTMS (2.1 mL, 2.2 g, 11.3 mmol) was introduced. The
o
o
o
mixture was stirred at 25 C for 1 h, then refluxed at 120 C for 18 h. After being cooled to 25 C,
o
compound a was filtered, washed with ethanol (3×20 mL), dried at 60 C for 12 h.
o
The a (3.0 g) was added to H SO (10 wt.%, 10 mL), then stirred at 40 C for 2 h. The
2
4
resulting b was filtered and washed with water until pH was 7, further with ethanol (3×20 mL),
-1
o
dried in air. Next, NaHCO solution (0.195 mol L , 20 mL) was added, stirred for 3 h at 25 C. Y
3
(YL or YD) was filtered, washed to neutral with water, dried in air.
4
.5. Synthesis of helical silica-supported Mn(III)-salen complexes
2
0

ACCEPTED MANUSCRIPT
Mn1 (-2, -3; 100 mg) and Y (YL, YD; 300 mg) were added to dichloromethane (20 mL), then
o
stirred at 40 C for 3 h. The solids were collected by filtration and washed by distilled water (3×30
mL) and ethanol (3×30 mL), then dried in air.
4
.6. Catalytic asymmetric hetero-Diels-Alder reaction
Carbonyl compound (1.0 mmol), Danishefsky’s diene (1.0 mmol), molecular sieve (50 mg, 4Å)
and catalyst (2 mol% Mn based on carbonyl) were added to solvent (including ionic liquid, 3.0
o
o
mL), then stirred at 0 C (or at -78 C, in Dewar bottle of 250 mL, filled with liquid nitrogen and
acetone), and monitored by TLC/PMA (petroleum ether; R of Danishefsky’s diene: 0.3; R of
f
f
benzaldehyde, acetophenone, cyclohexanecarboxaldehyde, heptaldehyde, ethyl glyoxylate,: 0.48,
0
.43, invisible, 0.5, 0.64; R of above hDA products: 0.56, 0.87, 0.71, 0.72, 0.70, accordingly). The
f
1
hDA products were further characterized by H NMR and mass spectra (Section 11,
Supplementary data). After 6 h, trifluoroacetic acid (50 ꢀL) was added and stirred for 1 h. Mixture
was concentrated, extracted by n-hexane (3×5 mL), the left catalyst (including ionic liquid layer)
was reloaded with consumables for recycling. Hexane layer was concentrated. The crude product
was purified by flash chromatography (SiO , 200-300 mesh, pure petroleum ether), then tested on
2
chiral HPLC (Section 12, Supplementary data).
Acknowledgements
This study was supported by Shaanxi Higher Education Teaching Reform Project (No.
1
3BY02, Cultivation of Creative Ability of Scientific Research for the Undergraduate), and the
Fundamental Research Funds for the Central Universities (No. xjj2014005, Application of Porous
2
1

ACCEPTED MANUSCRIPT
Helical Materials in Catalytic Asymmetric Reactions).
Supplementary data
Complementary characterizations of synthetic samples and templates of chiral HPLC.
References and notes
1
2
3
. Pellissier, H. Tetrahedron 2009, 65, 2839.
. Gaunt, M. J.; Johansson, C. C. C.; McNally, A.; Vo, N. T. Drug Discov. Today 2007, 12, 8.
. Lanari, D.; Montanari, F.; Marmottini, F.; Piermatti, O.; Orrù, M.; Vaccaro, L. J. Catal. 2011,
2
77, 80.
4
5
6
7
8
9
. Zhao, B.; Loh, T. Org. Lett. 2013, 15, 2914.
. Schaus, S. E.; Brånalt, J.; Jacobsen, E. N. J. Org. Chem. 1998, 63, 403.
. Lin, L.; Fan, Q.; Qin, B.; Feng, X. J. Org. Chem. 2006, 71, 4141.
. Long, J.; Hu, J.; Shen, X.; Ji, B.; Ding, K. J. Am. Chem. Soc. 2002, 124, 10.
. Yamashita, Y.; Saito, S.; Ishitani, H.; Kobayashi, S. Org. Lett. 2002, 4, 1221.
. Liu, B.; Li, K. -N.; Luo, S. -W.; Huang, J. -Z.; Pang, H.; Gong, L. -Z. J. Am. Chem. Soc. 2013,
1
35, 3323.
1
0. Furuno, H.; Hayano, T.; Kambara, T.; Sugimoto, Y.; Hanamoto, T.; Tanaka, Y.; Jin, Y. Z.;
Kagawa, T.; Inanaga, J. Tetrahedron 2003, 59, 10509.
11. Chatelet, B.; Dufaud, V.; Dutasta, J.-P.; Martinez, A. J. Org. Chem. 2014, 79, 8684.
12. Huang, Y.; Unni, A. K.; Thadani, A. N.; Rawal, V. H. Nature 2003, 424, 146.
13. Rajaram, S.; Sigman, M. S. Org. Lett. 2005, 7, 5473.
2
2

ACCEPTED MANUSCRIPT
14. Zhuang, W.; Poulsen, T. B.; Jøgensen, K. A. Org. Biomol. Chem. 2005, 3, 3284.
15. Che, S.; Liu, Z.; Ohsuna, T.; Sakamoto, K.; Terasaki, O.; Tatsumi, T. Nature 2004, 429, 281.
16. Fernandes, C. I.; Saraiva, M. S.; Nunes, T. G.; Vaz, P. D.; Nunes, C. D. J. Catal. 2014, 309,
2
1.
1
1
1
2
2
7. Gu, Y.; Li, G. Adv. Synth. Catal. 2009, 351, 817.
8. Jin, X.; Xu, X.; Zhao, K. Tetrahedron: Asymmetry 2012, 23, 1058.
9. Han, Y.; Zhao, L.; Ying, J.Y. Adv. Mater. 2007, 19, 2454.
0. Zhang, H.; Zhang, Y.; Li, C. J. Catal. 2006, 238, 369.
1. Choudary, B. M.; Ramani, T.; Maheswaran, H.; Prashant, L.; Ranganath, K. V. S.; Kumar, K.
V. Adv. Synth. Catal. 2006, 348, 493.
2
2
2
2. Zhang, Z.; Guan, F.; Huang, X.; Wang, Y.; Sun, Y. J. Mol. Catal. A: Chem. 2012, 363-364,
3
43.
3. Sing, K. S. W.; Everett, D. H.; Haul, R. A. W.; Moscou, L.; Pierotti, R. A.; Rouquérol, J.;
Siemieniewska, T. Pure Appl. Chem. 1985, 57, 603.
4. Galarneau, A.; Nader, M.; Guenneau, F.; Renzo, F. D.; Gedeon, A. J. Phys. Chem. C 2007, 111,
8
268.
2
2
2
2
5. Guo, Z.; Du, Y.; Chen, Y.; Ng, S. -C.; Yang, Y. J. Phys. Chem. C 2010, 114, 14353.
6. Snir, Y.; Kamien, R. D. Science 2005, 307, 1067.
7. Aikawa, K.; Irie, R.; Katsuki, T. Tetrahedron 2001, 57, 845.
8. Mellah, M.; Ansel, B.; Patureau, F.; Voituriez, A.; Schulz, E. J. Mol. Catal. A: Chem. 2007,
2
72, 20.
2
9. Motoyama, Y.; Koga, Y.; Nishiyama, H. Tetrahedron 2001, 57, 853.
2
3

ACCEPTED MANUSCRIPT
3
3
3
3
3
0. Li, H. -B.; Page, A. J.; Irle, S.; Morokuma, K. J. Phys. Chem. Lett. 2013, 4, 3176.
1. Leach, A. G.; Houk, K. N. J. Org. Chem. 2001, 66, 5192.
2. Hoffmann, F.; Cornelius, M.; Morell, J.; Fröba, M. Angew. Chem. Int. Ed. 2006, 45, 3216.
3. Zulauf, A.; Mellah, M.; Hong, X.; Schulz, E. J. Chem. Soc., Dalton Trans. 2010, 39, 6911.
4. Larrow, J. F.; Jacobsen, E. N.; Gao, Y.; Hong, Y.; Nie, X.; Zepp, C. M. J. Org. Chem. 1994, 59,
1
939.
5. Suarez, P. A. Z.; Dullius, J. E. L.; Einloft, S.; De Souza, R. F.; Dupont, J. Polyhedron 1996, 15,
217.
3
1
2
4