Facile Synthesis of a New Chiral BINOL–Silica Hybrid Catalyst for Asymmetric Diels–Alder and Aza Michael Reactions

Article abstract of DOI:10.1007/s10562-018-2346-z

Abstract: A novel chiral BINOL–silica hybrid has been successfully prepared by the reaction of (S)-BINOL and SiCl₄ following by gel polymerization under atmosphere condition. The synthesized catalyst was characterized by elemental analysis, Fourier-transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy and energy-dispersive X-ray spectroscopy. Catalytic activity of the chiral BINOL–silica hybrid for diastereo- and enantioselective Diels–Alder and aza Michael reactions has been investigated. Mild reaction conditions, high yields, excellent diastereo- and enantiomeric excess make this powerful and effective catalyst as an attractive option for the synthesis of chiral organic compounds. Graphical Abstract: [Figure not available: see fulltext.]

Full text of DOI:10.1007/s10562-018-2346-z

Catalysis Letters
https://doi.org/10.1007/s10562-018-2346-z
Facile Synthesis of a New Chiral BINOL–Silica Hybrid Catalyst
for Asymmetric Diels–Alder and Aza Michael Reactions
Hamid Saeidian1 · Hossein Paghandeh1 · Zahra Parvin2 · Zohreh Mirjafary3 · Mohammad Ghaffarzadeh2
Received: 4 October 2017 / Accepted: 24 February 2018
© Springer Science+Business Media, LLC, part of Springer Nature 2018
Abstract
A novel chiral BINOL–silica hybrid has been successfully prepared by the reaction of (S)-BINOL and SiCl4 following by
gel polymerization under atmosphere condition. The synthesized catalyst was characterized by elemental analysis, Fourier-
transform infrared spectroscopy, X-ray diffraction, scanning electron microscopy and energy-dispersive X-ray spectroscopy.
Catalytic activity of the chiral BINOL–silica hybrid for diastereo- and enantioselective Diels–Alder and aza Michael reac-
tions has been investigated. Mild reaction conditions, high yields, excellent diastereo- and enantiomeric excess make this
powerful and effective catalyst as an attractive option for the synthesis of chiral organic compounds.
Graphical Abstract
O
= (S)-BINOL
O
SiO2
SiO2
SiO2
HO
O
O
O
CH2Cl2, r.t
+
SiO2
Si
O
EWG
Si
O
Si
O
O
HO
SiO2
OH
O
Diels-Alder cycloaddition
O
SiO2
SiO2
O
OH
Si
EWG
SiO2
O
O
O
SiO2
Si
O
O
O
O
SiO2
SiO2
O
O
Si
O
Si
O
R2
O
O
R1
H
O
O
O
OH
O
N
CH2Cl2, 40 °C
R2
SiO2
O
N
+
R1
N
SiO2
O
N
SiO2
aza Michael addition
A sketch of the chemical structure of the (S)-BINOL-silica hybrid (BSH)
1. High yields
2. Excellent diastereoselectivity
3. Excellent enantioselectivity
5. Reusable chiral catalyst
4. Inexpensive chiral catalyst
6. Short reaction times
Keywords Heterogeneous chiral catalyst · Sol–gel process · Organic–inorganic hybrids · BINOL–silica hybrid · Diels–
Alder cycloaddition · Aza Michael addition
Electronic supplementary material The online version of this
article (https://doi.org/10.1007/s10562-018-2346-z) contains
supplementary material, which is available to authorized users.
Extended author information available on the last page of the article
Vol.:(0123456789)
1 3

H. Saeidian et al.
of silica resulted hybrid inorganic–organic silica, which
was applied widely in chemical industry [19, 20]. Sol–gel
process is the known method for fabrication of hybrid sil-
ica-organic materials which are receiving much attention
due to their well-defined structure and stability [21–25].
Hydrolysis and condensation of organosilicates in typi-
cal sol–gel reactions lead to a wide variety of particulate
hybrid gels in crystalline or amorphous structures [26].
Strong covalent bonds between silica and organic com-
pound leads to a 3D network which can be described
as siloxane chains cross-linked by bridging organic
subunits [27, 28]. Synthesis of chiral organic–inorganic
hybrid material by the sol–gel process is an interesting
idea for preparation of a heterogeneous chiral catalyst.
2,2′-Binaphthol (BINOL) has generated particular inter-
est because of its versatile backbone [29–32]. Nowadays
SiCl4 is one of the most common used raw material for the
fabrication of silica. In the present study, synthesis of a
chiral BINOL–silica hybrid (BSH) was investigated by the
reaction of (S)-BINOL with an excess amount of SiCl4 fol-
lowed by gel formation under atmosphere condition. The
synthesized BSH was characterized by elemental analysis
(CHN), Fourier-transform infrared spectroscopy (FT-IR),
X-ray diffraction (XRD), scanning electron microscopy
(SEM) and energy-dispersive X-ray spectroscopy (EDS),
and then was used in the asymmetric Diels–Alder and
1 Introduction
The need for diastereo- and enantiomerically pure organic
molecules and pharmaceuticals, propels chemists to design
and preparation of new chiral catalysts which can per-
form asymmetric reactions in high stereoselectivity [1].
A myriad of catalytic asymmetric transformations in the
presence of homogeneous and heterogeneous chiral cata-
lysts have been reported in literature [2–5]. Application of
heterogeneous chiral catalysts for asymmetric synthesis
is often preferable to homogeneous chiral catalysts due
to their easy handling and separation from the reaction
mixture and reusability [6–9]. Several informative review
papers summarized the latest developments on heteroge-
neous chiral catalysts assisted chemical reactions [9–15].
Design and synthesis of a heterogeneous chiral catalyst
in high levels of catalytic efficiency and stereoselectiv-
ity in a target asymmetric reaction is very difficult and
needs numerous trial-and-error attempts. The anchoring
of chiral ligands on the surface of inorganic polymers
such as silica, opens the new window to heterogeneous
chiral catalysts [16]. The silica has been widely used as
support material because of its high surface area, large
pore volume, rich hydroxyl groups and it is also relatively
cheap [17, 18]. Organic functionalization and modification
Cl
O
OH
Et2O
Si
+ SiCl4
+
SiCl4
O
OH
Reflux, 2 h
Cl
10 equivalent
(S)-BINOL
O
O
2) H2O
= (S)-BINOL
3) sol-gel polymerization
SiO2
SiO2
HO
O
O
O
CH2Cl2, r.t
+
SiO2
Si
O
SiO2
SiO2
EWG
Si
O
Si
O
O
HO
OH
O
Diels-Alder cycloaddition
O
SiO2
O
Si
OH
O
EWG
SiO2
O
O
SiO2
SiO2
O
O
Si
O
O
O
SiO2
Si
Si
O
O
O
R2
O
O
O
R1
H
O
O
O
OH
N
SiO2
CH2Cl2, 40 °C
R2
O
N
+
R1
N
SiO2
A sketch of the chemical structure of the (S)-BINOL-silica hybrid (BSH)
O
N
aza Michael addition
Scheme 1 Synthesis of (S)-BINOL–silica hybrid and its catalytic activity in the asymmetric Diels–Alder and aza Michael reactions
1 3

Facile Synthesis of a New Chiral BINOL–Silica Hybrid Catalyst for Asymmetric Diels–Alder and…
aza Michael reactions as a heterogeneous chiral catalyst
(Scheme 1). It should be noted that developing of more
efficient reactions for the construction of organic com-
pounds is a topic of immense importance. Cyclization and
Michael reactions have emerged as powerful tools in syn-
thetic organic chemistry due to their wide range of applica-
tions in chemistry and biochemistry [33–36].
2.3 General Procedure for the Asymmetric
Diels–Alder Cycloaddition in the Presence
of the Catalyst (BSH)
Dienophile (1 mmol) and 0.15 g of the catalyst (BSH) were
added to CH2Cl2 (5 mL) and the mixture was stirred at room
temperature. After 10 min, 6 mmol cyclopentadien (Cp) was
added to the mixture. 2 h later, the reaction mixture was
filtered and the solid was washed with CH2Cl2. The organic
phase was evaporated in vacuo and purified by column chro-
matography to afford the pure cycloadduct 3, 5 and 7.
2 Experimental
2.1 General Information
All the chemicals required for the synthesis of (S)-BINOL–sil-
ica hybrid and Diels–Alder cycloaddition and aza Michael
addition products were purchased from Sigma-Aldrich (St.
Louis, MO, USA), Fluka (Neu-Ulm, Germany) and Merck
(Darmstadt, Germany) companies and were used as received.
A Bruker (DRX-400 Avance) NMR was used to record the
1H NMR spectra (supporting information). All NMR spec-
tra were determined in CDCl3 at ambient temperature. The
GC–MS analysis were performed using an Agilent 6890N
gas chromatograph coupled to a 5973 Mass Selective Detec-
tor, a HP-5MS capillary column (30 m, 320 µm i.d. and 0.25
µm film thickness). FT-IR spectra were taken using KBr pel-
lets by a Nicolet spectrometer (Magna 550). XRD patterns
of the catalyst were determined by a Siemens D5000 X-ray
diffractometer using graphite-monochromatized high-intensity
Cu K⍺ radiation (λ=1.5406 Å). SEM images were obtained
using a Stereo Scan 3360 Leica Cambridge. The enantiomeric
excesses (ee %) were determined by chiral High-performance
liquid chromatography (HPLC: Knaur HPLC system with a
pump K-1001, an UV detector K-2600 and column Chiralcel
OD-H).
2.4 General Procedure for the Asymmetric Aza
Michael Addition in the Presence of the Catalyst
(BSH)
To a stirred solution of Michael acceptor (1 mmol) and
0.15 g of the catalyst (BSH) in CH2Cl2 (5 mL), 2 mmol of
amine was added. The mixture was refluxed for 20 h. Upon
completion as judged by TLC, the mixture was filtered and
solid was washed with CH2Cl2. The organic phase was con-
centrated and the desired aza-Michael product 9, 10, 11, 12
were purified by recrystallization in petroleum ether:ethyl
acetate mixture (1:1).
2.5 Spectroscopic Data of the Selected Major
Products of Diels–Alder and Aza‑Michael
Products (Supporting Information)
(3): 1H NMR (400 MHz, CDCl3) δ=6.14 (1H), 5.84 (1H),
3.11 (1H), 3.05 (1H), 2.89 (1H), 2.11 (3H), 1.73 (1H), 1.45
1
(2H), 1.33 (1H); MS (CI): m/z 137 (M + 1); (5) H NMR
2.2 General Procedure for the Preparation
of (S)‑BINOL–Silica Hybrid (BSH)
(400 MHz, CDCl3) δ=9.40 (1H), 6.20 (1H), 5.98 (1H), 3.23
(1H), 2.91 (1H), 2.88 (1H), 1.90 (1H), 1.41 (2H), 1.25 (1H);
MS (CI): m/z 123 (M+1); (7): 1H NMR (400 MHz, CDCl3)
δ=6.36 (2H), 3.62 (2H), 3.56 (2H), 1.83 (1H), 1.61 (1H);
MS (CI): m/z 165 (M+1); (9): 1H NMR (400 MHz, CDCl3)
δ=7.14 (2H), 6.69 (1H), 6.65 (2H), 4.30 (2H), 4.10 (1H),
3.86 (2H), 3.33 (1H), 2.99 (1H), 1.29 (3H); MS (EI): m/z
248 (M+); (10): 1H NMR (400 MHz, CDCl3) δ=6.72 (2H),
6.61 (2H), 4.60 (2H), 4.02 (1H), 3.89 (2H), 3.71 (3H), 3.30
(1H), 2.95 (1H), 1.25 (3H); MS (EI): m/z 278 (M+); (12):
1H NMR (400 MHz, CDCl3) δ=7.25 (2H), 7.18 (3H), 4.06
(1H), 3.86 (2H), 3.65 (2H), 3.13 (2H), 2.86 (2H), 2.55 (1H),
2.30 (1H), 1.06 (3H); MS (EI): m/z 276 (M+).
To a refluxing solution of (S)-BINOL in diethyl ether (0.2 M),
10 equiv. of SiCl4 was added dropwise. The reaction mixture
was stirred at refluxing temperature for 2 h and quenched with
distilled water, while stirring. Afterwards the heating was
stopped and distilled water was added. The reaction mixture
was transferred to a crystallizer and gel formation was com-
pleted overnight. The precipitate was washed with CH2Cl2 to
remove unreacted (S)-BINOL and dried at room temperature
overnight. The resulting white solid was analyzed by CHN,
EDS, XRD, FT-IR and SEM techniques.
1 3

H. Saeidian et al.
SiCl4 in 46 mL diethyl ether for 2 h, following by addition
of 0.63 mL of distilled water. Gel formation was completed
at room temperature overnight. CHN analysis of obtained
white solid showed loading of 11.51% of carbon on the silica
network. Energy-dispersive X-ray spectroscopy (EDS) was
also used for chemical characterization of the catalyst and
exhibited the existence of carbon, oxygen and silicon atoms
in catalytic system (Fig. 1).
3 Results and Discussion
3.1 Synthesis and Characterization of the Catalyst
(BSH)
Tetrachlorosilane and (S)-BINOL as starting materials were
used to functionalize the silica network by sol–gel method.
The obtained white mass was firstly analyzed by elemental
analysis to determine the loading amount of (S)-BINOL on
silica network. High loading of (S)-BINOL on silica network
was achieved by refluxing of 2.65 g (S)-BINOL, 11.60 mL
The positions of FT-IR bands (Fig. 2) provide good hints
regarding the bonding sites of (S)-BINOL by grafting to
silica network. Infrared transmission spectrum of the cat-
alyst was recorded to be in the range of 4000–500 cm−1.
The υ(Si–O–Si) and υ(Si–O–H) bands are observed
at 1000–1200 and 3100–3500 cm−1, respectively. The
υ(Si–O–C) can be seen at 1000–1200 cm−1 which over-
lapped with υ(Si–O–Si).
Comparing the XRD spectra of (S)-BINOL and the cata-
lyst (BSH) confirmed that (S)-BINOL was attached to silica
network (Fig. 3).
The morphology of the catalyst was also investigated by
SEM. As shown in Fig. 4, the catalyst (BSH) has amorphous
structure.
3.2 The Asymmetric Diels–Alder Cycloaddition
in the Presence of the Catalyst (BSH)
With the catalyst in hand, attention was focused on the
asymmetric Diels–Alder cycloaddition of cyclopentadien
1 with methyl vinyl ketone 2 as a model reaction (Table 1).
Fig. 1 EDS analysis of the catalyst (BSH)
Fig. 2 FT-IR spectrum of the catalyst (BSH)
1 3

Facile Synthesis of a New Chiral BINOL–Silica Hybrid Catalyst for Asymmetric Diels–Alder and…
Fig. 3 The XRD patterns of (S)-BINOL (SBI) and the catalyst (BSH)
In short reaction time, the yield was increased as the
reaction temperature was raised to room temperature along
with only a slight loss in stereoselectivity (Table 1). In
the absence of the catalyst, the product 3 was obtained in
low yield and low diastereoselectivity after 2 h (Table 1,
entry 5), while good results were obtained in the pres-
ence of the catalyst (BSH). Clearly, using THF as solvent,
diastereoselectivity has been reduced along with lower
yield and long reaction time rather than CH2Cl2 (Table 1,
entry 6). The reusability of the catalyst was also studied for
the model reaction. The catalyst was recovered by simple
filtration, washed with CH2Cl2 and reused with consistent
activity even after fourth catalytic cycles (Table 1, entry
9). The exo/endo ratio was determined by GC–MS analysis
1 3

H. Saeidian et al.
Next, we turned our attention to apply the catalyst (BSH)
in the reaction of cyclopentadien 1 with acrolein 4 and
maleic anhydride 6 as dienophiles to obtain the correspond-
ing Diels–Alder products (Scheme 2). These substrates con-
sistently furnished the desired bicyclic products in excellent
yields and high diastereoselectivity.
3.3 The Asymmetric Aza Michael Addition
in the Presence of the Catalyst (BSH)
With the encouraging results of asymmetric Diels–Alder
cycloaddition, attention was focused on enantioselective aza
Michael addition of aromatic and aliphatic amines to 3-((E)-
but-2-enoyl)oxazolidin-2-one 8 as a Michael acceptor in the
presence of the catalyst (BSH). Reaction of aniline with 8 in
different conditions was used as a model reaction (Table 2).
With no catalyst, the product 9 was obtained in low
yield and low enantioselectivity after 46 h (Table 2, entry
3), while good results were obtained in the presence of the
catalyst (BSH). Clearly, by using THF as solvent, the yield
has been reduced even after long reaction time rather than
CH2Cl2 (Table 2, entry 4). Using 0.15 g of the catalyst and
CH2Cl2 as solvent at 40 °C are the best reaction conditions
for the enantioselective aza Michael addition. Catalytic
Fig. 4 SEM micrograph of the catalyst (BSH)
of the reaction crude. GC chromatogram of exo and endo
isomers of 3 and their CI-MS spectra are shown in Fig. 5.
The structure of the major product 3 was confirmed by 1H
NMR and GC–MS and comparison with authentic sample
prepared by reported methods.
Table 1 Optimization conditions for asymmetric Diels–Alder cycloaddition of the model reaction
O
Cat. BSH, CH2Cl2
+
+
Different conditions
exo
endo
2
1
O
3
O
Entry
T (°C)
Time (h)
Exo/endoa
Yield (%)
1
2
3
4
5
6
7
8
9
−78
−30
−15
r.t
r.t
r.t
r.t
r.t
r.t
20
18
5
2
2
18
2
2
2/98
3/97
3/97
4/96
15/85
17/83
6/94
10/90
12/88
75
100
97
100
28b
95c
97d
86e
83f
2
Reaction condition: (1) 6 mmol; (2) 1 mmol; Cat. 0.15 g and CH2Cl2 5 mL
aRatio obtained by using GC analysis of the reaction crude
bNo catalyst
cTHF was used as solvent
dThe second use of the catalyst
eThe third use
fThe fourth use
1 3

Facile Synthesis of a New Chiral BINOL–Silica Hybrid Catalyst for Asymmetric Diels–Alder and…
Fig. 5 GC chromatogram of 3 (a); CI-MS spectra of exo (b) and endo (c) isomers of 3
Scheme 2 Diels–Alder
O
cycloaddition of cyclopentadien
1 with acrolein 4 and maleic
anhydride 6 in the presence of
the catalyst (BSH)
Cat. BSH (0.15 g)
CH2Cl2, r.t, 2 h
H
+
+
H
exo
endo
4
1
1
O
H
5
O
yield = 81 %, exo/endo = 15/85
O
O
O
O
Cat. BSH (0.15 g)
CH2Cl2, r.t, 2 h
+
O
+
O
O
endo
6
exo
7
O
O
yield = 85 %, exo/endo = 8/92
1 3

H. Saeidian et al.
Table 2 Optimization conditions of enantioselective aza Michael addition of the model reaction
NH2
O
O
O
O
NH
Cat. BSH
N
O
+
Different conditions
8
N
O
9
Entry
T (°C)
Time (h)
ee (%)a
Yield (%)
1
3
4
40
40
40
20
46
48
100
32
100
73
60b
50c
Reaction condition: aniline 2 mmol; (8) 1 mmol; Cat. 0.15 g and CH2Cl2 5 mL
aee obtained by HPLC analysis
bNo catalyst
cTHF was used as solvent
R
NH2
O
n
O
O
O
NH
n
Cat. BSH
CH2Cl2, 40 °C
N
O
O
+
N
8
R
10, R = OCH3, n = 0; yield = 95%, ee = 68%
11, R = H, n = 1; yield = 97%, ee = 50%
12, R = H, n = 2; yield = 90%, ee = 89%
Scheme 3 The enantioselective aza Michael addition of aromatic and aliphatic amines by using the catalyst (BSH)
effect of the catalyst (BSH) in aza Michael addition of other
aromatic and aliphatic amines were also investigated. All
amines gave the desired products in high yields and excellent
enantioselectivity (Scheme 3).
heterogeneous catalyst. The catalyst was easily synthesized
by the reaction of (S)-BINOL and SiCl4. The synthesized
catalyst offers some advantages such as clean reaction,
low loading of catalyst, short reaction time, high yields
and excellent diastereo- and enantioselectivity of products,
which make it as a useful and attractive catalyst in the
asymmetric synthesis. Further studies of applicability of
the catalyst for synthesis of chiral organic compounds are
currently in progress.
4 Conclusions
The catalytic asymmetric Diels–Alder cycloaddition and
aza Michael addition have been achieved by using a hybrid
inorganic–organic silica as a reusable and inexpensive
1 3

Facile Synthesis of a New Chiral BINOL–Silica Hybrid Catalyst for Asymmetric Diels–Alder and…
17. Shylesh S, Thiel WR (2011) ChemCatChem 3:278–287
Compliance with Ethical Standards
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37:1118–1126
Conflict of interest No potential conflict of interest was reported by
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AffiWlieainthioeimns
Hamid Saeidian1 · Hossein Paghandeh1 · Zahra Parvin2 · Zohreh Mirjafary3 · Mohammad Ghaffarzadeh2
2
* Hamid Saeidian
Chemistry and Chemical Engineering Research Center
of Iran, PO Box 14335-186, Tehran, Iran
Saeidian1980@gmail.com
3
Department of Chemistry, Tehran Science and Research
Branch, Islamic Azad University, Tehran, Iran
1
Department of Science, Payame Noor University (PNU), PO
Box 19395-4697, Tehran, Iran
1 3