Chiral hybrid materials based on pyrrolidine building units to perform asymmetric Michael additions with high stereocontrol

Article abstract of DOI:10.1039/c8cy01650j

A new chiral mesoporous hybrid material was synthesized based on pyrrolidine units included in a siliceous framework, HybPyr, and integrated into the organic-inorganic structure, from a specific bis-silylated precursor. A fluoride sol-gel methodology under soft synthesis conditions and in the absence of sophisticated structural directing agents allowed the generation of a mesoporous architecture with a homogeneous distribution of active chiral moieties along the network. The hybrid material was studied by means of different characterization techniques (TGA, NMR and IR spectroscopy, chemical and elemental analyses, TEM, and textural measurements), verifying the stability and integrity of the asymmetric active sites in the solid. The hybrid material, HybPyr, is an excellent asymmetric heterogeneous and recyclable catalyst for enantioselective Michael addition of linear aldehydes to β-nitrostyrene derivatives with high stereocontrol of the reaction products.

Full text of DOI:10.1039/c8cy01650j

Catalysis
Science &
Technology
View Article Online
View Journal | View Issue
PAPER
Chiral hybrid materials based on pyrrolidine
building units to perform asymmetric Michael
additions with high stereocontrol†
Cite this: Catal. Sci. Technol., 2018,
8, 5835
Sebastián Llopis, Teresa García, Ángel Cantín,
Alexandra Velty,
*
*
Urbano Díaz
and Avelino Corma
A new chiral mesoporous hybrid material was synthesized based on pyrrolidine units included in a siliceous
framework, HybPyr, and integrated into the organic–inorganic structure, from a specific bis-silylated pre-
cursor. A fluoride sol–gel methodology under soft synthesis conditions and in the absence of sophisticated
structural directing agents allowed the generation of a mesoporous architecture with a homogeneous dis-
tribution of active chiral moieties along the network. The hybrid material was studied by means of different
characterization techniques (TGA, NMR and IR spectroscopy, chemical and elemental analyses, TEM, and
textural measurements), verifying the stability and integrity of the asymmetric active sites in the solid. The
hybrid material, HybPyr, is an excellent asymmetric heterogeneous and recyclable catalyst for enantio-
selective Michael addition of linear aldehydes to β-nitrostyrene derivatives with high stereocontrol of the
reaction products.
Received 9th August 2018,
Accepted 5th September 2018
DOI: 10.1039/c8cy01650j
rsc.li/catalysis
fication techniques to ensure their complete removal from
the final target molecules, especially in the case of pharma-
1. Introduction
Molecular chirality plays a key role in science and technology.
Enantioselective synthesis is a key process in the chemical in-
dustry, especially in the field of pharmaceuticals and agro-
chemicals, and the interest in implementing efficient and
economical routes to enantiomerically pure compounds is
constantly growing. Thus, the synthesis of optically active in-
termediates and products as pure enantiomers is a topic of
ever-increasing importance for academic research as well as
for pharmaceutical development1 and achieving heteroge-
neous asymmetric catalysis is the most challenging.
ceutical uses. Enzymes3 are versatile biocatalysts for a large
variety of reactions and exhibit, in biocatalytic transforma-
tions, excellent chemo-, regio-, and stereospecificity under
mild reaction conditions. Nevertheless, their main drawbacks
are long reaction times and low stability under process condi-
tions, which make their recovery and recycling difficult.
Recently, organocatalysts4 have undergone quick and fasci-
nating progress in a short period of time and offered new op-
portunities in asymmetric synthesis. Organocatalysis is defined
as the acceleration of chemical reactions with
a sub-
Until the last decade, the two main types of efficient asym-
metric catalysts were transition metal complexes and en-
zymes. Indeed, transition metals are considered key to the
development of enantioselective catalysts,2 since they are ac-
tive and enantioselective for a large variety of reactions. De-
spite their great benefit, there is still room for improvement
based on catalyst cost and toxicity that implies rigorous puri-
stoichiometric amount of an organic compound which does not
contain a metal atom. While they exhibit great potential, they
also present some limitations such as operation in organic sol-
vent, need of high loadings (10–30 mol%) to accomplish the
process in a reasonable reaction time, cost, low stability and dif-
ficult separation from reaction medium and recycling. For all,
the development of recyclable asymmetric catalysts constitutes
important research and, sometimes, industrial goals. Addition-
ally, for easy recovery of catalysts by simple filtration and their
possible recycling, the development of solid catalysts makes the
implementation of continuous flow processes possible.5 Unfor-
tunately, the number of solid chiral catalysts is small. Different
chiral heterogeneous systems have been described, and they are
generally based on the immobilization of homogeneous cata-
lytic species on a solid support.6 Nevertheless, ensuring the sta-
bility of the catalytic properties in the supported heterogeneous
system is a difficult task,7 and a loss of enantioselectivity is
Instituto de Tecnología Química, Universitat Politècnica de València-Consejo Supe-
rior de Investigaciones Científicas, Avenida de los Naranjos s/n, E-46022 Valencia,
Spain. E-mail: udiaz@itq.upv.es, acorma@itq.upv.es; Fax: +34963877809;
Tel: +34963877800
† Electronic supplementary information (ESI) available: Tables related to the ef-
fects of the solvent and additive addition on the enantioselective catalytic perfor-
mance of the HybPyr catalyst. NMR spectra of the bis-silylated precursor and
previous intermediates together with spectra of hybrid catalysts after successive
catalytic cycles. Racemic and chiral HPLC chromatograms for Michael adducts.
See DOI: 10.1039/c8cy01650j
This journal is © The Royal Society of Chemistry 2018
Catal. Sci. Technol., 2018, 8, 5835–5847 | 5835

View Article Online
Paper
Catalysis Science & Technology
often observed during the immobilization process.8 For exam-
ple, an efficient polymer-supported organocatalyst synthesized
from chiral monomers for the Michael addition of ketones to
nitroolefins has been prepared by grafting a chiral pyrrolidine
nitroaldehydes which constitute key intermediates in organic
synthesis, since from nitro groups different functionalities
can be created through different organic transformations.23
monomer;9 metal surfaces were modified by anchoring chiral 2. Experimental
organic compounds10 and metal–organic frameworks (MOFs),
where a chiral tetracarboxylate ligand derived from 1,1′-bi-2-
2.1 General information
All reagents were purchased from commercial suppliers and
naphthol was incorporated, resulting in active asymmetric
Lewis acid catalysts after post-synthesis functionalization with
Ti(OiPr)4.11 Very few examples of organosilica hybrid materials
incorporating chiral siloxane precursors, such as 1,1′-
used without further purification. Solvents employed in the re-
actions were purified using a solvent purification system (SPS)
MBraun 800. Organic solutions were concentrated under re-
duced pressure on a Büchi rotary evaporator. The reactions were
monitored by GC-FID (Shimadzu, GC Plus ultra 2010) and GC-
binaphthalene,
(R,R)-
or
(S,S)-diamino-cyclohexane,12
cinchonidine derivatives,13 prolinamide14 or pyrrolidine-bridged
polyhedral oligomeric silsesquioxanes,15 were reported.
1
MS (Shimadzu, GCMS-QP2010 Ultra). H and 13C NMR spectra
were recorded on a Bruker 300 spectrometer and the chemical
shifts are reported in ppm relative to residual proton solvent
Regarding the catalytic topic, we will focus on the use of
organocatalysts in the field of asymmetric synthesis. The effi-
ciency and the scope of organocatalysis particularly amino-
catalysis have been broadly established since the rediscovery of
the proline-catalyzed intermolecular aldol reaction.16 What
makes proline different from other aminoacids is its higher ef-
fectiveness in aminocatalysis thanks to the pyrrolidine portion
which readily reacts with carbonyl compounds to form
iminium ions and enamines.17 Chiral secondary amines
showed to be effective catalysts for aldol condensation pro-
cesses by covalent activation of the carbonyl compounds either
1
signals. Data for the H NMR spectra are reported as follows:
chemical shift (δ, ppm), multiplicity (s = singlet, d = doublet, t =
triplet, q = quartet, m = multiplet, dd = double doublets), cou-
pling constant and integration. Data for 13C NMR spectra are
reported in terms of chemical shift (δ, ppm). High performance
liquid chromatography (HPLC) was performed with an Agilent
Technologies 1220 Infinity Series instrument using a Daicel
Chiralpak IC (4.6 × 250 mm). Optical rotations were measured
on a Jasco P-2000 polarimeter using the yellow line at 589 nm
and [α]20D. C, N, and H contents were determined with a Carlo
Erba 1106 elemental analyzer. Thermogravimetric and differen-
tial thermal analyses (TGA-DTA) were conducted in an air
stream with a Mettler Toledo TGA/SDTA 851E analyzer. Nitro-
gen adsorption isotherms were measured at 77 K with a Micro-
meritics ASAP 2010 volumetric adsorption analyzer. Before the
measurement, the sample was outgassed for 12 hours at 80 °C.
The BET specific surface area24 was calculated from the nitro-
gen adsorption data in the relative pressure range from 0.04 to
0.2. The total pore volume25 was obtained from the amount of
N2 adsorbed at a relative pressure of about 0.99. The external
surface area and micropore volume were estimated using the
t-plot method in the t range from 3.5 to 5. The pore diameter
and the pore size distribution were obtained using the Barrett–
Joyner–Halenda (BJH) method26 on the adsorption branch of
the isotherms. Solid state MAS-NMR spectra were recorded at
room temperature under magic angle spinning (MAS) using a
Bruker AV-400 spectrometer. IR spectra of the organic precur-
sors were recorded on KBr disks at room temperature.
via nucleophilic enamines or electrophilic iminium ions.18
A
wide variety of homogeneous enantioselective catalysts based
on pyrrolidine analogues and active to the asymmetric conju-
gate addition (ACA) have been reported such as pyrrolidine sul-
fonamide,19 diphenylprolinol silyl ether20 and trans-4-
hydroxyprolylamide.21 Other examples of supported polymer-
pyrrolidines have been prepared using analogs of Jørgensen
catalysts ((R)- and (S)-α,α-bisij3,5-bisIJtrifluoromethyl)phenyl]-2-
pyrrolidinemethanol trimethylsilyl ether) and prolyl-prolinol
catalysts.22 They have become of major significance for the
stereoselective formation of C–C bonds.
The aim of heterogenization of chiral organocatalysts lies
in industrial implementation, the possibility of reducing the
costs and facilitation of the recovery, reuse and/or regenera-
tion of the catalysts for several cycles. In this context, the de-
velopment of new asymmetric hybrid materials offers new op-
portunities with respect to the mechanical and chemical
stability of the materials under reaction process and regener-
ation conditions. Hybrid materials have been of large interest
for the scientific and industrial community because of their
potential commercial scope in their applications and because
of the challenges presented by their synthesis.
2.2 Preparation of disilane (PyrSil)
(2S,4R)-N-1IJBenzyl)-4-hydroxyproline-methylester (2).
In this work, we report the preparation of a chiral meso-
porous hybrid material, containing active pyrrolidine build-
ing fragments inserted and stabilized into the framework,
based on a methyl-(2S,4R)-4-hydroxypyrrolidine-2-carboxylate
bis-silylated derivative, for the enantioselective Michael addi-
tion of linear aldehydes to β-nitrostyrene derivatives with
high stereocontrol. The asymmetric Michael addition of car-
bonyl compounds to nitroalkenes is among the most useful
synthetic methods for the C–C bond formation and produces
5836 | Catal. Sci. Technol., 2018, 8, 5835–5847
This journal is © The Royal Society of Chemistry 2018

View Article Online
Catalysis Science & Technology
Paper
The first step was the protection of the amine group of hy-
droxyproline compounds. Specifically, (2S,4R)-N-1IJbenzyl)-4-
hydroxyproline-methylester (2) was prepared by following an
adapted literature procedure for analogous pyrrolidines.27
Triethylamine (7.6 mL, 55.0 mmol) was added dropwise to a
formed suspension of methyl (2S,4R)-4-hydroxypyrrolidine-2-
carboxylate hydrochloride (5.0 g, 27.5 mmol) in 23 mL of dry
CH2Cl2, and the reaction mixture was continuously stirred.
Benzyl chloride (14.8 ml, 118.0 mmol) was added to the mix-
ture in one portion and the formed slurry was stirred at re-
flux overnight. After reaction, NaOH (solution 2 M) was
added until pH = 2. Then, the organic layer was separated
and the aqueous phase was extracted three times with
dichloromethane (15.0 mL). The combined organic layers
were washed with brine and, then, dried over anhydrous so-
dium sulfate and concentrated to give the crude product,
which was purified by silica gel column chromatography
(AcOEt/hexane 1/1 as eluent) to afford 2 as an orange yellow
liquid (6.1 g, 95%).
J = 12, 6 Hz 1H), 2.13 (m, 2H), 1.85 (m, 1H). 13C NMR (75
MHz, CDCl3) δ = 138.9, 128.6, 128.4, 127.2, 70.2, 63.3, 62.2,
60.9, 58.6, 37.5.
(3R,5S)-1-Benzyl-5-(8,8-diethoxy-3-oxo-2,9-dioxa-4-aza-8-
silaundecyl)pyrrolidin-3-ylIJ3-(triethoxysilyl)propyl)carbamate (4).
Compound 3 (7.7 g, 37.3 mmol) was added into a 250 mL
round-bottom flask and purged under a nitrogen flow. After
that, dry THF (62.0 mL) was added. Then, the solution was
stirred, and 3-(triethoxysilyl)propylisocyanate (18.4 g, 74.6
mmol) was added dropwise. The mixture was heated at reflux
until consumption of the product (∼2 days). After solvent re-
moval under vacuum, the product 4 was obtained in 99%
yield (26.1 g) as a yellow oil, without further purification.
1
[α]D19 = −59 (c = 1, CHCl3). H NMR (300 MHz, CDCl3) δ =
7.31 (m, 5H, Ar–H), 4.43 (m, 1H), 3.90 (d, J = 12 Hz, 1H), 3.66
(d, J = 12 Hz, 1H), 3.65 (s, 3H, OCH3), 3.32 (dd, J = 12, 2 Hz,
1H), 2.48 (d, J = 3 Hz, 1H), 2.44 (d, J = 3 Hz, 1H), 2.22 (m,
1H), 2.06 (m, 1H). 13C NMR (75 MHz, CDCl3) δ = 173.9, 138.1,
129.0, 128.3, 127.2, 70.3, 63.6, 61.1, 58.1, 51.7, 39.6.
1
[α]D22 = −26 (c = 1, CHCl3). H NMR (300 MHz, CDCl3) δ =
7.27 (m, 5H, Ar–H), 4.99 (m, 2H), 4.11 (m, 3H), 3.81 (m, 14H),
3.13 (m, 5H), 2.37 (m, 1H), 1.96 (m, 2H), 1.60 (m, 5H), 1.22
(t, J = 6 Hz, 18H, OCH2CH3), 0.62 (m, 4H, CH2SiO). 13C NMR
(75 MHz, CDCl3) δ = 156.4, 156.0, 138.8, 128.8, 128.2, 127.0,
72.7, 66.1, 61.2, 59.6, 58.9, 58.4, 43.4, 43.3, 42.9, 35.9, 23.3,
18.4, 18.3, 7.6.
(3R,5S)-1-Benzyl-5-(hydroxymethyl)pyrrolidin-3-ol (3).
(3R,5S)-5-(8,8-Diethoxy-3-oxo-2,9-dioxa-4-aza-8-silaundecyl)-
pyrrolidin-3-ylIJ3-(triethoxysilyl)propyl)carbamate, PyrSil, (5).
The second step was the reduction of the ester group of
compound 2. Then, (3R,5S)-1-benzyl-5-(hydroxymethyl)-
pyrrolidin-3-ol (3) was synthesized by modifying a reported
literature procedure.28 Specifically, a solution of pyrrolidine
derivative 2 (9.6 g, 40.8 mmol) in THF (20 ml) was added
dropwise to LiAlH4 suspension (2.3 g, 61.2 mmol) in THF
(60.0 ml) in a cold bath. When the addition was com-
pleted, the mixture was stirred for 30 min. Then, it was
heated at reflux for 8 h. The reaction mixture was stirred at
room temperature overnight and, using a cold bath, 30.0
mL of water were added, followed by filtration of the salts
and extraction with Et2O : AcOEt (1 : 1) (3 × 40.0 mL). The
combined organic layers were dried over anhydrous Na2SO4.
After solvent removal, product 3 was purified by flash chro-
matography on a silica gel, using a linear gradient of EtOH in
CHCl3. The product was obtained in 91% yield (7.7 g) as a
colorless liquid.
Finally, the amine group of the pyrrolidine backbone was
deprotected. For this, compound 4 (5.0 g, 7.1 mmol) was hy-
drogenated in methanol (15.0 mL) under a pressure of 30 bar
in an autoclave, using Pd/C-10% (0.4 g, 3.6 mmol) as a cata-
lyst. When the reaction was completed, the mixture was fil-
tered through Celite and the filtrate was evaporated. Product
5, PyrSil, was obtained in 96% yield (4.2 g) as a yellow oil.
1
[α]D23 = +12 (c = 1, CHCl3). H NMR (300 MHz, CDCl3) δ =
5.10 (m, 2H), 4.09 (m, 2H), 3.80 (q, J = 6 Hz, 12H, OCH2CH3),
3.14 (m, 6H), 2.12 (m, 1H), 1.60 (m, 5H), 1.67–1.53 (m, 4H (d,
d′)), 1.21 (t, J = 7 Hz, 18H, OCH2CH3), 1.00 (d, J = 6 Hz, 1H),
0.60 (m, 4H, CH2SiO). 13C NMR (75 MHz, CDCl3) δ = 156.5,
156.0, 67.0, 58.5, 58.4, 58.3, 56.2, 52.7, 50.7, 43.4, 43.0, 35.4,
23.6, 23.3, 18.4, 18.2, 14.6, 7.6, 7.2.
1
2.3 Synthesis of the chiral hybrid catalyst (HybPyr)
[α]D21 = −45 (c = 1, CHCl3). H NMR (300 MHz, CDCl3) δ =
7.30 (m, 5H, Ar–H), 4.34 (m, 1H), 4.00 (d, J = 12 Hz 1H), 3.69
(dd, J = 12, 3 Hz, 2H), 3.49 (d, J = 15 Hz, 1H), 3.42 (dd, J = 11,
3 Hz, 1H), 3.26 (dd, J = 12, 6 Hz, 1H), 3.09 (m, 1H), 2.39 (dd,
A non-ordered hybrid porous organic–inorganic material,
HybPyr, was obtained from a starting mixture of tetra-
methoxysilane (TMOS) as the silica precursor and an
This journal is © The Royal Society of Chemistry 2018
Catal. Sci. Technol., 2018, 8, 5835–5847 | 5837

View Article Online
Paper
Catalysis Science & Technology
appropriate amount of disilane PyrSil ((R′O)3Si–R–SiIJOR′)3), 5,
as bridged silsesquioxane (5% mol SiO2 with respect to total
mol of SiO2), in methanol. After dissolution of precursors, a
water solution of NH4F was added dropwise to the
organosilicon alkoxide solution under vigorous stirring. The
final reaction mixture has the following molar composition:
1SiO2 : 4MeOH : 4H2O : 0.00313 NH4F where the Si/NH4F and
TMOS/disilane ratios were adjusted to 479 and 4, respectively.
Hydrolysis and condensation of the silicon precursor were
carried out under vigorous stirring in a glass beaker at room
temperature. Stirring was continued until gelation occurred.
Then, the gel was aged for 24 h at 36 °C and, finally, dried at
150 °C for another 24 h. The solid obtained was a fine brown
powder that was exhaustively washed with ethanol and water
in consecutive steps to remove the disilane molecules not in-
corporated into the materials. Finally, the material was dried
at 60 °C overnight.
through condensation processes with isocyanate siloxane
molecules to produce silyl-derivatives (4), containing
pyrrolidine-urethane groups as organic bridges. The last
step was the deprotection step of pyrrolidine moieties, using
Pd/C as a catalyst under H2, to obtain the novel functional-
ized bis-silylated precursor (5), PyrSil, containing pyrrolidine
active units.
The non-ordered mesoporous organic–inorganic hybrid
material, HybPyr, was prepared in the presence of the previ-
ously obtained PyrSil monomer together with tetra-
methylorthosilicate (TMOS), as silicon precursors, through a
sol–gel synthesis process in methanolic fluoride medium
(Scheme 2). This synthesis methodology was based on con-
secutive hydrolysis and condensation steps at room tempera-
ture and neutral pH, with fluoride ions acting as mineralizing
agents. The formation of pentacoordinated organosilyl com-
plexes as activated intermediates allowed the rapid
gelification process, after a few seconds, by the covalent
bonding of siloxane terminal groups.
2.4 Catalytic tests
The aging period at 36 °C, followed by a drying process,
facilitated the generation of porous organosilicon structures
with pyrrolidine chiral moieties isolated into the porous
framework. There are few described examples in which this
type of chiral organocatalyst is stabilized in the architecture
of a robust siliceous material rather than adsorbed or
supported onto inorganic matrixes.14
The XRD pattern of the hybrid material HybPyr (not in-
cluded) did not show diffraction bands and confirmed the
formation of the structure without long-order spatial symme-
try, as could be expected for the materials obtained through
fluoride sol–gel processes in the absence of structural
directing agents. This low structuration level was not an ob-
stacle to including pyrrolidine chiral fragments in the net-
work, being ∼5 wt% as estimated from chemical analysis and
the associated C/N experimental molar ratio was 4.2, close to
the theoretical value for the organic bridge present in the
PyrSil monomer precursor (C/N = 4.3). This fact would imply
that the derived pyrrolidine building units were introduced
into the hybrid solid, maintaining their initial chemical
composition.
Asymmetric Michael additions: general procedure. The re-
action was performed in a 3 mL sealed vial under magnetic
stirring. Nitroalkene (0.1 mmol), 10 mol% 4-nitrophenol (0.01
mmol) and 20 mol% catalyst HybPyr (0.02 mmol) were added
to aldehyde solution (1.0 mmol) in dry DCM (1 mL). After
that, the resulting mixture was stirred at 15 °C for 20 h, and
the catalyst HybPyr was recovered by filtration and washed
several times with DCM and H2O. The solid catalyst was dried
in an oven at 100 °C overnight. The organic extracts were con-
centrated under reduced pressure. The Michael adducts were
obtained as evaporation residues and purified by silica gel col-
umn chromatography on TLC plates with hexane : EtOAc =
3 : 1 as the eluent phase. The spectroscopic data of all prod-
ucts obtained were in agreement with the published data.29
The reaction was monitored by GC analysis. The calcula-
tions of data for the yield, selectivity and conversion with re-
spect to the limiting reagent (nitrostyrene derivative) were de-
termined from GC analysis (GC-2010-Ultra, Shimadzu,
equipped with a FID). The characterization of the Michael ad-
ducts was performed by GC-MS and 1H and 13C NMR. The
enantiomeric excess (ee), diastereoisomeric ratio (dr) and
enantiomeric ratio (er) were determined by HPLC on the pu-
rified reaction mixture using
(Chiralpak IC column).
a chiral stationary phase
3. Results and discussion
3.1 Synthesis and characterization
A mesoporous chiral hybrid material (named HybPyr) was
prepared from a suitable bridged silsesquioxane monomer
precursor, which contained pyrrolidine-type active fragments
as chiral organic linkers, located between reactive siloxane
terminal groups (PyrSil). The preparation of this bis-
silylated precursor is summarized in Scheme 1. In detail,
hydroxypyrrolidine (1) was protected with Cl-Bnz, with ester
groups being consecutively reduced to hydroxyls (3) with
LiAlH4. Next, silylation of hydroxyl groups was performed
Scheme
1 Synthetic pathway to prepare the PyrSil monomer
precursor, containing pyrrolidine units between siloxane terminal
groups.
5838 | Catal. Sci. Technol., 2018, 8, 5835–5847
This journal is © The Royal Society of Chemistry 2018

View Article Online
Catalysis Science & Technology
Paper
Scheme 2 Synthesis procedure through a sol–gel process in fluoride medium to obtain the non-ordered mesoporous chiral hybrid material
(HybPyr), containing pyrrolidine units in the framework. In the bottom panel, intermediate reactive pentacoordinated siloxanes formed during the
synthesis process.
The organic content (∼18.7 wt%) was also determined by
thermogravimetric analysis (TGA) (see Fig. 1), which was
higher than that by elemental analysis due to the contribu-
tion of hydration water (∼8.4 wt%) and dehydroxylation wa-
ter (∼5.4 wt%), detected at temperatures lower than 100 °C
and higher than 500 °C, respectively, with the latter weight
loss being associated with the silanol condensation phenom-
enon. From the derivative curve (DTA), the main weight loss
assigned to the silyl pyrrolidine fragments (∼4.9 wt%) was
observed between 200 °C and 400 °C, with the hydrothermal
stability of the organic–inorganic porous chiral hybrid mate-
rial synthesized here being established in this temperature
range. It is remarkable that the organic content, regarded
only as pyrrolidine building units, was similar for both chem-
ical and thermogravimetric analyses, i.e. around 5 wt%.
atoms were detected between −60 and −80 ppm chemical
shifts assigned to Si–C species such as T1 (C–SiIJOH)2IJOSi)), T2
(C–SiIJOH)IJOSi)2) and T3 (C–SiIJOSi)3), together with Q-type sili-
con atoms of silicon tetrahedral units from the condensed
TMOS precursor. This result confirmed that the derivative
pyrrolidine units were integrated and stabilized into the
framework through effective hydrolysis and condensation be-
tween terminal siloxane groups. Additionally, the pure PyrSil
monomer precursor showed T-type silicon atoms centered in
the chemical shift range of −40–−50 ppm that was changed to
−60–−80 ppm when this organic fragment was incorporated
into the framework of the final non-ordered HybPyr solid,
The integrity of the derivative silyl-pyrrolidine building
units was confirmed by 13C NMR of the non-ordered meso-
porous HybPyr solid, which was able to identify all carbon
atoms present in the organic bridge, including those directly
bonded to silicon atoms (Fig. 2). This result showed that the
organic building units remained intact, as in the starting bis-
silylated PyrSil monomer precursor (see Fig. S1 in the ESI†).
The 13C NMR spectrum confirms that the organic frag-
ments preserved their integrity during the sol–gel synthesis
processes, and the 29Si MAS NMR spectra confirm that the or-
ganic building units not only remained intact but were also
incorporated covalently into the non-ordered porous network
bonded to inorganic silica units (Fig. 3). In fact, T-type silicon
Fig.
1 Thermogravimetric curve (TGA) and the corresponding
derivative (DTA) of the non-ordered mesoporous chiral hybrid material,
HybPyr.
This journal is © The Royal Society of Chemistry 2018
Catal. Sci. Technol., 2018, 8, 5835–5847 | 5839

View Article Online
Paper
Catalysis Science & Technology
Fig. 4 FTIR spectrum of non-ordered mesoporous hybrid material,
HybPyr.
Fig. 2 13C MAS NMR spectrum of the non-ordered mesoporous chiral
HybPyr material.
3260 cm−1) and bending (δ(–NH–): 1559 and 1643 cm−1) vibra-
tions of secondary amines introduced into the organic brid-
ges in the PyrSil monomer precursor, including those due to
cyclic aliphatic amines from pyrrolidine groups. The
stretching vibration band assigned to ureido-type fragments,
ν(–NH–CO–O–), was also located at 1703 cm−1. The –CH2–
units due to terminal propyl chains present in the building
units were detected through symmetric and asymmetric vi-
bration bands assigned to alkyl groups connected to amino
groups (ν(–N–CH2–): 2897 and 2958 cm−1; δ(–N–CH2–): 1383
and 1447 cm−1). Furthermore, a broad band due to the pres-
ence of water centered at 3467 cm−1 was clearly observed,
overlapping with the band attributed to surface silanol
groups (Si–OH), typical of inorganic silicates with structural
defects. However, the vibration band at 950 cm−1 was also as-
sociated with external silanol groups.
with this fact being another confirmation of the effective
integration of pyrrolidine moieties into the structure of the
hybrid material (see the inset in Fig. 3). Furthermore, the
integration of the T and Q signals in the 29Si BD/MAS NMR
spectrum allows estimation of the number of functionalized
silicon atoms present in the HybPyr material through the T/
(T + Q) integrated intensity ratio. The obtained result corrob-
orated that ∼5% of the silicon atoms are functionalized with
the derivative pyrrolidine units, with this value being similar
to both the amount of bis-silylated precursor used during the
synthesis process and the organic content estimated from the
chemical and thermogravimetric analyses.
Infrared spectroscopy results also corroborated the pres-
ence and integrity of the pyrrolidine derivative fragments in-
cluded in the framework of the organic–inorganic hybrid ma-
terial, HybPyr. The FTIR spectrum of the HybPyr solid shows
the bands associated with stretching (ν(–NH–): shoulder at
Additionally, in the infrared framework range, a character-
istic band located around 790 cm−1 assigned to the Si–C vi-
bration was observed, corroborating the covalent bonds
established between tetrahedral silicon units and bis-silylated
pyrrolidine moieties. In this range, typical vibration bands
(458 and 1080 cm−1) due to the presence of Si–O–Si groups,
Fig. 3 29Si MAS NMR spectra of the non-ordered mesoporous hybrid
material, HybPyr, and assignment of T- and Q-type silicon atoms: (a)
29Si BD/MAS NMR spectrum and (b) 29Si CP/MAS NMR spectrum. In the
inset: 29Si NMR spectrum of the pure bis-silylated precursor, PyrSil.
Fig. 5 N2 adsorption isotherms of the non-ordered mesoporous chiral
hybrid, HybPyr, and pure silica solids.
5840 | Catal. Sci. Technol., 2018, 8, 5835–5847
This journal is © The Royal Society of Chemistry 2018

View Article Online
Catalysis Science & Technology
Paper
Table 1 Textural properties of the porous organic–inorganic hybrid, HybPyr, and pure silica materials
BET surface area
External surface
Micropore volume
Total pore volume
Mean pore
diameter (Å)
Sample
(m2 g−1
)
(m2 g−1
)
(cm3 g−1
)
(cm3 g−1
)
HybPyr
Pure silica
386
668
378
547
0.004
0.053
0.325
0.473
40
20–30
which were the main structural building units of the
organosilicon HybPyr framework, were detected (Fig. 4).
Thus, spectroscopic results (NMR and FTIR) evidenced unam-
biguously the integrity of the organic linker and its effective
covalent incorporation into the non-ordered porous hybrid
structure.
In this case, the large molecular dimensions of PyrSil
monomers inserted in the network of the hybrid solid would
favor the formation of mesopores with higher internal diame-
ters than in non-ordered pure silica materials without
inserted organic building units. This fact was also confirmed
from the TEM micrographs, where free mesoporous cavities
with a broad internal diameter distribution were observed for
the hybrid material containing pyrrolidine units in the frame-
work (Fig. 7).
The textural properties, specific surface area and free po-
rous volume of the organic–inorganic hybrid material,
HybPyr, were evaluated from nitrogen adsorption measure-
ments. Specifically, the adsorption isotherm was characteris-
tic of non-ordered porous materials with a marked slope shift
at a high relative pressure (P/P0 ∼0.3–0.4), indicating the
presence of a large pore diameter in the internal mesopores
present in the chiral hybrid architecture (Fig. 5), with a BET
surface area and total porous volume of ∼385 m2 g−1 and
∼0.325 cm3 g−1, respectively. The comparison of the textural
properties of the non-ordered mesoporous pure silica mate-
rial is shown in Table 1. It is observed that the presence of
pyrrolidine moieties in the framework promoted a reduction
of surface area, probably associated with the structural diffi-
culty to homogeneously assemble organic fragments without
partially collapsing internal porosity. However, the higher po-
rous contribution in the HybPyr material was due to the
formed mesopores, with the generated microporosity being
practically inappreciable.
3.2 Enantioselective catalysis
A study of enantioselective Michael addition between ali-
phatic aldehydes and nitrostyrene derivatives (see Scheme 3)
was performed to test the effectiveness and efficiency of the
synthesized chiral hybrid material, HybPyr. Amine-catalyzed
enantioselective Michael addition of aldehydes to nitro-
alkenes is an important C–C bond-forming transformation in
organic synthesis. Generally, the amine-catalyzed Michael ad-
dition of carbonyl compounds to nitroalkenes proceeds via
an enamine intermediate. The widely accepted mechanism
Indeed, the BJH pore size distribution of the non-ordered
chiral hybrid material, HybPyr, was characteristic of meso-
porous solids prepared through a fluoride sol–gel synthesis
route, exhibiting a broad distribution of pores in the meso-
porous range (from 17 Å to 300 Å), although with a higher
contribution of mesopores with diameters centered at 40 Å
(Fig. 6).
Fig. 6 Pore size distributions of the non-ordered mesoporous chiral
Fig. 7 TEM micrographs of the non-ordered mesoporous chiral mate-
hybrid, HybPyr, and pure silica solids calculated from the BJH method.
rial, HybPyr.
This journal is © The Royal Society of Chemistry 2018
Catal. Sci. Technol., 2018, 8, 5835–5847 | 5841

View Article Online
Paper
Catalysis Science & Technology
Scheme 3 Proposed mechanism of chiral amine-catalyzed Michael addition via E-enamine formation.
goes firstly via the formation of the enamine by condensation
of a chiral amine and a carbonyl compound. The following
enamine addition onto the nitroalkene substrate provides an
iminium intermediate. Then, the hydrolysis of the iminium
releases the Michael product with regeneration of the asym-
metric amine catalyst (Scheme 3). The catalytic cycle can be
limited by the last step associated with the amine catalyst re-
leased by hydrolysis and thus by its availability. Different
studies30 showed the effect of the addition of co-catalysts
such as weak acids or bases which boosted considerably the
rate of reaction by probably favoring the enamine forma-
tion31 and increasing the diastereoselectivity of the Michael
reaction, without changing the enantioselectivity.
termined by the catalyst structure, and according to steric
hindrance, the E-enamine was thermodynamically favored.
The chiral substituent on the catalyst not only controls the
geometry of the enamine but also influences the facial selec-
tivity of the Michael addition through steric shielding and/or
electronic interaction such as hydrogen bonding established
for different aminocatalysts as well as L-proline, tetrazole or
thiourea. In this case, hydrogen bonding can be established
between the nitro group and carbamate group (Scheme 4).
Furthermore, steric shielding could determine the facial se-
lectivity since the bulky substituent group on the catalyst
would force the attack from the opposite side. Likewise, for
the Michael addition mechanism, the less hindered SiSi tran-
sition state via an anti-enamine is usually favored for alde-
hydes while the ReRe transition state via a syn-enamine is
usually preferred for ketones. Both steric shielding and
electronic interaction are shown in Scheme 4.
When the chiral Michael addition was performed in the
presence of 20 mol% HybPyr catalyst at 30 °C and 0 °C, in
the presence of different solvents, the (2R,3S)-2-methyl-4-
nitro-3-phenylbutanal (1a) was the main isomer (syn)
(Table 2). Based on the enantioselective catalytic results a
proposed mechanism is outlined in Scheme 3. According to
both steric shielding and electronic interaction, the approach
of β-nitrostyrene from the less hindered Si-face of the
E-enamine was the most probable.
Herein, we initially studied the enantioselective catalytic
performance of the hybrid material HybPyr, containing
pyrrolidine-carbamate units in the framework, for the Mi-
chael addition of propanal to β-nitrostyrene. Mechanistic in-
sights32 showed that the geometry of enamine would be de-
Solvents with different polarities and properties (protonic)
as well as mixtures of them were used to maximize the
enantioselectivity of the reaction. In all cases, the selectivity
towards Michael adducts was >99%. When dichloromethane
(DCM), chloroform (CHCl3) or trifluorotoluene (CF3-toluene)
were used as solvents, the Michael product was obtained with
Scheme 4 Electronic interaction and steric shielding transition states
with a SiSi approach for propanaldehyde and β-nitrostyrene.
5842 | Catal. Sci. Technol., 2018, 8, 5835–5847
This journal is © The Royal Society of Chemistry 2018

View Article Online
Catalysis Science & Technology
Paper
Table 2 Effect of the solvent on the enantioselective catalytic performance of the HybPyr catalyst
Entry
Solvent
T (°C)
t (h)
Yielda (%)
eeb (%)
drb
1
2
3
4
5
6
7
8
n-Hex
Tol
Et2O
DCM
CF3-Tol
CHCl3
THF
AcOEt
CH3CN
MeOH
30
30
30
30
30
30
30
30
30
30
30
30
30
30
30
30
0
24
24
24
12
16
20
24
72
24
8
24
20
24
16
24
16
69
160
135
21
21
44
99
97
95
96
97
97
95
95
91
99
99
81
93
97
92
100
83
41
94
82
99
69
56
64
60
72
72
70
68
60
66
64
58
60
66
66
66
72
74
74
70
70
72
58
64 : 36
70 : 30
67 : 33
83 : 17
78 : 22
74 : 26
74 : 26
68 : 32
74 : 26
77 : 23
69 : 31
76 : 24
86 : 14
76 : 24
85 : 15
79 : 21
88 : 12
89 : 11
86 : 16
81 : 19
86 : 14
86 : 14
9
10
11
12
13
14
15
16
17
18
19
20
21
22
EtOH
H2O
Tol : H2O (1 : 3)
Tol : THF (5 : 1)
DCM : H2O (1 : 3)
CHCl3 : IPrOH (9 : 1)
DCM
CHCl3
THF
iPrOH
MeOH
0
0
0
0
H2O
0
Reaction conditions: β-nitrostyrene (0.1 mmol), propanaldehyde (1 mmol), 1 mL of solvent and 20 mol% HybPyr catalyst. In all cases, the selec-
a
b
tivity towards Michael adducts was >99%. Yield and conversion were determined by GC. Determined by HPLC on the purified reaction mix-
ture, using a chiral stationary phase (Chiralpak IC column). Tol: toluene.
Table 3 Effect of the additive use on the enantioselective catalytic performance of the HybPyr catalyst
Entry
Additives
mol%
pKa
T °C
Time (h)
Conv.%a
ee%b
drb
1
2
3
4
5
6
7
8
—
—
—
—
—
—
15
10
5
—
—
—
3.41
4.2
30
15
0
12
21
69
30
9
64
64
48
4
7
8
12
5
9
5
7
9
6
9
24
96
97
83
93
63
28
25
86
98
98
94
92
99
93
99
98
98
97
95
94
72
76
74
74
70
74
72
76
76
78
78
78
74
76
68
76
76
76
76
74
83 : 17
86 : 14
88 : 12
81 : 19
86 : 16
91 : 09
91 : 09
87 : 13
84 : 16
89 : 11
88 : 12
88 : 12
82 : 18
89 : 11
63 : 37
82 : 18
82 : 18
89 : 11
88 : 12
70 : 30
NO2-PhCO2H
PhCO2H
PhCO2H
Acetic acid
NO2-PhOH
NO2-PhOH
NO2-PhOH
NO2-PhOH
NO2-PhOH
NMM
NMM
DMAP
PhOH
PhOH
K2CO3
K2CO3
K2CO3
0
30
−10
−10
0
4.2
5
4.75
7.15
7.15
7.15
7.15
7.15
7.61
7.61
9.6
9.95
9.95
10.33
10.33
10.33
20
20
20
10
5
20
20
20
20
20
10
5
9
30
15
15
15
30
15
30
30
15
15
15
0
10
11
12
13
14
15
16
17
18
19
20
20
Reaction conditions: β-nitrostyrene (0.1 mmol), propanaldehyde (1 mmol), 1 mL of DCM and 20 mol% HybPyr catalyst. In all cases, the selectiv-
a
b
ity towards Michael adducts was >99%. Yield and conversion were determined by GC. Determined by HPLC on the purified reaction mix-
ture, using a chiral stationary phase (Chiralpak IC column).
excellent yields (90–96%) and good enantiomeric excess (ee),
70–72% (Table 2, entries 4–6). However, when other solvents
were tested such as toluene, hexane (n-Hex), tetrahydrofuran
(THF), diethyl ether (Et2O), acetonitrile (CH3CN), ethyl ace-
tate (AcOEt), ethanol (EtOH), methanol (MeOH) or water, the
ee decreased while in all cases high Michael adducts yields
were achieved, up to 99%. Additionally, when the reaction
temperature was decreased to 0 °C, a slight increase of
enantiomeric excess and diastereoisomeric ratio (dr) was ob-
served (Table 2, entries 17, 18 and 21). Following the study
and according to these catalytic and enantioselective results,
dichloromethane was chosen as the more suitable solvent.
Furthermore, when the Michael addition was performed in
the presence of the homogenous pyrrolidine precursor
This journal is © The Royal Society of Chemistry 2018
Catal. Sci. Technol., 2018, 8, 5835–5847 | 5843

View Article Online
Paper
Catalysis Science & Technology
entries 10–12). At this stage, the evolution of ee% and the Mi-
chael adduct yield versus reaction time was examined (Fig. 8),
where ee% being observed remained constant independent
of the reaction progress. At this point, the heterogeneity of
the process was controlled filtering out the catalyst after 1 h
of reaction (conversion level: 30.6%) for the Michael addition
of propanal to β-nitrostyrene. Then, the process was contin-
ued for 4 h, and no change in the yield was registered, ensur-
ing that no active species migrated from the solid to the liq-
uid. Finally, the stability and recyclability of the
heterogeneous chiral catalyst were examined. The results
showed that the HybPyr catalyst could be reused perfectly for
four consecutive cycles without observing substantial activity
loss and providing good enantio- and diastereoselectivity
(Fig. 9), retaining the initial structuration of the hybrid cata-
lyst (see Fig. S2 and S3 in the ESI†).
When the hybrid material, HybPyr, was used to carry out the
Michael addition of isobutyraldehyde, a branched aldehyde,
onto β-nitrostyrene in DCM, a lower yield and enantiomeric ra-
tio were achieved. In order to improve the outcome of the reac-
tion, different solvents were examined. From Table S1,† we ob-
served that alcohols were the most adequate solvents,
especially methanol, since 96% yield of Michael adducts was
achieved (entry 14). Nevertheless, the enantiomeric ratio of the
reaction was moderate. When DMSO or DMF were used as the
solvent, a racemic mixture was obtained, probably because of
the competitive adsorption of reactants and high polar solvent
over the catalytic surface, limiting the optimal spatial organiza-
tion via non-covalent interactions between the substrates and
the chiral moieties through hydrogen bonds and van der Waals
interactions. Additionally, the reaction temperature was varied,
without substantial variation in the enantioselectivity (Table S1
(ESI†), entries 16 and 18). A similar trend was reported in the
literature, whereby the use of a 2,2′-bipyrrolidine organocatalyst
to perform asymmetric Michael addition showed that linear al-
dehydes provided higher reaction rates and selectivity than
branched aldehydes.33
Fig. 8 Evolution of ee% or Michael adduct yield versus time when the
Michael addition of propanaldehyde (1 mmol) to β-nitrostyrene (0,1
mmol) was performed in DCM (1 mL), at 15 °C, with 10 mol% nitro-
phenol and 20 mol% HybPyr catalyst. Selectivity towards Michael ad-
ducts was >99%.
Fig.
9 Catalytic performance of the HybPyr material for four
consecutive runs for the addition of propanal to β-nitrostyrene (β-
nitrostyrene (0,1 mmol), aldehyde (1 mmol), 10 mol% 4-nitrophenol,
1 mL of DCM and 20 mol% HybPyr), 8−10 h. Selectivity towards
Michael adducts was >99%.
On the other hand, when the Michael reaction was
performed with n-alkyl Michael donors such as butyraldehyde
and valeraldehyde, under the same reaction conditions, with
20 mol% catalyst at 15 °C in dichloromethane (1 mL), the hy-
brid material HybPyr exhibited good asymmetric catalytic
performance. Likewise, 88 and 95% Michael adduct yields
were achieved after 4 and 2 days of reaction with 77 and 76%
ee, respectively. These results confirmed the effect of steric
hindrance of branched versus linear aldehydes rather than an
inductive effect, since these latter higher reaction rate and
enantioselectivity were provided.
The beneficial addition of carboxylic acid (25 mol%)
allowed us to improve the Michael adduct yields, by reducing
the reaction time. The use of strong acids inhibited the reac-
tion (Table S2 (ESI†), entries 4, 9 and 12), while the use of
acids with moderate strength (pKa range: 4.2–4.75) increased
the reaction rate and gave higher adduct yields while the
stereoselectivity of the reaction was unaltered (Table S2
(ESI†), entries 5–8 and 11).
(PyrSil), 78% ee was provided after 6 h of reaction with 96%
Michael adduct yield. These results showed that the chiral
organo-disiloxane, containing pyrrolidine moieties, was suc-
cessfully incorporated into the hybrid material without loss
of its asymmetric catalytic properties.
The effect of the addition of acids or bases as additives or
co-catalysts with different strength values (pKa) to the reac-
tion medium was also examined. From Table 3, a clear trend
can be observed since the use of additives was advantageous
and allowed boosting the reaction rate and achieving higher
yields in shorter reaction times. The best results were pro-
vided with the addition of NMM (N-methylmorpholine), nitro-
phenol and K2CO3, the since reaction time was reduced up to
3 times at 30 °C. Moreover, a very slight increase of enantio-
selectivity, from 76% until 78%, and slight changes in
diastereoselectivity
were
observed,
especially
when
4-nitrophenol (NO2-PhOH) was used as the additive (Table 3,
5844 | Catal. Sci. Technol., 2018, 8, 5835–5847
This journal is © The Royal Society of Chemistry 2018

View Article Online
Catalysis Science & Technology
Paper
Table 4 Scope of asymmetric and catalytic performance of the HybPyr catalyst
Substrate R1 = Ph
R2 = Me
R1 = 4-BrPh
R1 = 4-MePh
R1 = 2-CF3Ph
R1 = 4-MeOPh
6a:
6d:
6b:
6c:
6e:
yield = 94% (8 h)
yield = 94% (56 h)
yield = 98% (8 h)
yield = 99% (14 h)
yield = 95% (24 h)
dr = 89 : 11/ee = 78%
dr = 89 : 11/ee = 78%
dr = 90 : 10/ee = 80%
dr = 88 : 12/ee = 76%
dr = 89 : 11/ee = 78%
syn/anti = 88 : 12
syn/anti = 89 : 11
syn/anti = 88 : 12
syn/anti = 89 : 11
syn/anti = 87 : 13
R2 = Et
7a:
7d:
7b:
7c:
7e:
yield = 99% (10 h)
yield = 94% (45 h)
yield = 100% (10 h)
yield = 99% (14 h)
yield = 99% (45 h)
dr = 91 : 9/ee = 82%
dr = 91 : 9/ee = 82%
dr = 90 : 10/ee = 80%
dr = 91 : 9/ee = 80%
dr = 89 : 11/ee = 78%
syn/anti = 92 : 8
syn/anti = 89 : 11
syn/anti = 89 : 11
syn/anti = 92 : 8
syn/anti = 87 : 13
R2 = Pr
8a:
8d:
8b:
8c:
8e:
yield = 97% (12 h)
yield = 98% (40 h)
yield = 97% (7 h)
yield = 94% (15 h)
yield = 93% (29 h)
dr = 90 : 10/ee = 80%
dr = 91 : 9/ee = 82%
dr = 91 : 9/ee = 82%
dr = 91 : 9/ee = 82%
dr = 88 : 12/ee = 76%
syn/anti = 87 : 13
syn/anti = 95 : 5
syn/anti = 91 : 9
syn/anti = 92 : 8
syn/anti = 87 : 13
Reaction conditions: β-nitrostyrene (0.1 mmol), propanaldehyde (1 mmol)), 10 mol% 4-nitrophenol, 1 mL of DCM and 20 mol% HybPyr cata-
lyst. In all cases, the selectivity towards Michael adducts was >99%.
Generalizing the scope of the reaction, the addition of dif-
ferent linear aldehydes to β-nitrostyrene with several aro-
matic substituent groups was examined. The presence of
electron donating (Me, OMe) or withdrawing (Br, CF3) groups
was analyzed, in order to evaluate the performance of the hy-
brid material HybPyr as an asymmetric heterogeneous cata-
lyst. The Michael addition was then performed with 20 mol%
catalyst, at 15 °C, in dichloromethane. As we expected, when
withdrawing groups were present in the para position, an in-
crease of reaction rate (shorter reaction time) was observed
(Table 4, 6b, 7b and 8b). Meanwhile, when a donating group
in the para position or withdrawing group in the meta posi-
tion was present, a decrease of reactivity was noticed (Table 4
, 6d, 7d, 8d, 6c, 7c, 8c, 6e, 7e and 8e). In all cases, high Mi-
diastereoselectivity and enantioselectivity were also high, up
to 90% and 75%, respectively, indicating that changes of the
electronic properties of the nitroaromatic compound did not
affect the stereocontrol and the course of reaction. In conclu-
sion, the high potential of the pyrrolidine-carbamate-type hy-
brid catalyst (HybPyr) for addition of linear aldehydes to
β-nitrostyrene derivatives with high enantioselectivity was
confirmed.
Definitively, this study shows the successful incorporation
and stabilization of pyrrolidine carbamate disilane into the
mesoporous siliceous framework together with the high po-
tential of the hybrid material, HybPyr, as an effective and effi-
cient asymmetric catalyst to perform the Michael addition of
linear aldehydes onto nitro aromatic compounds, overcoming
traditional problems of chiral organocatalytic moieties
chael
adduct
yields
were
achieved,
and
the
This journal is © The Royal Society of Chemistry 2018
Catal. Sci. Technol., 2018, 8, 5835–5847 | 5845

View Article Online
Paper
Catalysis Science & Technology
embedded into organic polymers in which the porous con-
finement effect is not possible and random distribution of
chiral active sites is also observed.34
6 R. A. Sheldon and van H. Bekkum, Fine Chemicals through
Heterogeneous
Catalysis,
Wiley-VCH Verlag GmbH,
Weinheim, 2001.
7 H. F. Rase, Handbook of Commercial Catalysts: Heterogeneous
Catalysts, CRC Press, New York, 2000.
8 K. Hallman and C. Moberg, Tetrahedron: Asymmetry,
2001, 12, 1475; R. J. Clarke and I. J. Shannon, Chem.
Commun., 2001, 1936; F. Bigi, L. Moroni, R. Maggi and G.
Sartori, Chem. Commun., 2002, 716.
9 E. Alza, X. C. Cambeiro, C. Jimeno and M. A. Pericas, Org.
Lett., 2007, 9, 3717.
10 T. Mallat, E. Orglmeister and A. Baiker, Chem. Rev.,
2007, 107, 4863; V. Humblot, S. Haq, C. Muryn, W. A. Hofer
and R. Raval, J. Am. Chem. Soc., 2002, 124, 503.
11 L. Ma, J. M. Falkowski, C. Abney and W. Lin, Nat. Chem.,
2010, 2, 838.
12 J. Moreau, L. Vellutini, M. Man and C. Bied, J. Am. Chem.
Soc., 2001, 123, 1509; Q. Yang, D. Han, H. Yang and C. Li,
Chem. – Asian J., 2008, 3, 1214.
13 A. Corma, S. Iborra, I. Rodríguez, M. Iglesias and F. Sánchez,
Catal. Lett., 2002, 82, 237.
14 A. Monge-Marcet, R. Pleixats, X. Cattoën, M. Wong Chi Man,
D. A. Alonso and C. Nájera, New J. Chem., 2011, 35, 2766.
15 T. Luanphaisarnnont, S. Hanprasit, V. Somjit and V.
Ervithayasuporn, Catal. Lett., 2018, 148, 779.
4. Conclusions
In summary, we have synthesized an innovative chiral meso-
porous hybrid material, HybPyr, based on a bis-silylated chi-
ral derivative of pyrrolidine, using a fluoride sol–gel route in
the absence of structural directing agents and under soft syn-
thesis conditions. The effective incorporation and stabiliza-
tion of these organic units were confirmed by different char-
acterization techniques (elemental analysis, TGA, NMR, FTIR,
and TEM). The chiral material was successfully used as an
asymmetric catalyst to perform the Michael addition between
a wide range of linear aldehydes to nitroalkenes offering di-
rect access to highly functionalized products through a rapid
and atom-economical way and, at the same time, with excel-
lent yields as well as high enantioselectivity. The hybrid cata-
lyst was stable, easily separable and can be reused several
times. We believe that the solid chiral hybrid catalyst pre-
pared in this work may provide new synthetic possibilities for
multicomponent transformations, with the consequent prep-
aration of chiral and more sophisticated demanded products
and commodities.
16 B. List, R. A. Lerner and C. F. Barbas, J. Am. Chem. Soc.,
2000, 122, 2395.
17 P. W. Hickmott, Tetrahedron, 1982, 38, 1975.
18 G. Lelais and D. W. C. MacMillan, Aldrichimica Acta,
2006, 39, 79; B. List, Chem. Commun., 2006, 819; C. Palomo
and A. Mielgo, Angew. Chem., Int. Ed., 2006, 45, 7876.
19 W. Wang, J. Wang and H. Li, Angew. Chem., 2005, 117, 1393;
W. Wang, J. Wang and H. Li, Angew. Chem., Int. Ed.,
2005, 44, 1369.
20 Y. Hayashi, H. Gotoh, T. Hayashi and M. Shoji, Angew.
Chem., 2005, 117, 4284; Y. Hayashi, H. Gotoh, T. Hayashi
and M. Shoji, Angew. Chem., Int. Ed., 2005, 44, 4212.
21 C. Palomo, S. Vera, A. Mielgo and E. Gomez-Bengoa, Angew.
Chem., 2006, 118, 6130; C. Palomo, S. Vera, A. Mielgo and E.
Gomez-Bengoa, Angew. Chem., Int. Ed., 2006, 45, 5984.
22 I. Atodiresei, C. Vila and M. Rueping, ACS Catal., 2015, 5,
6241; F. Giacalone, M. Gruttadauria, P. Agrigento, V.
Campisciano and R. Noto, Catal. Commun., 2011, 16, 75.
23 A. Berkessel and H. Gröger, Asymmetric Organocatalysis:
From Biomemetic Concepts to Applications in Asymmetric
Synthesis, Wiley-VCH, Weinheim, 2005; B. J. Berner, L.
Tedeschi and D. Enders, Eur. J. Org. Chem., 2002, 12, 1877.
24 S. J. Gregg and K. S. W. Sing, Adsorption, Surface Area and
Porosity, Academic Press, 2nd edn, 1982.
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
The authors are grateful for financial support from the Span-
ish Government by MAT2014-52085-C2-1-P, MAT2017-82288-
C2-1-P and Severo Ochoa Excellence Program SEV-2016-0683.
S. Ll. thanks predoctoral fellowships from MINECO for eco-
nomical support (BES-2015-072627). The authors thank the
MULTY2HYCAT (EU-Horizon 2020 funded project under grant
agreement no. 720783). The European Union is also acknowl-
edged by ERC-AdG-2014-671093-SynCatMatch.
References
1 R. E. Gawley and J. Aub, Principles of Asymmetric Synthesis,
Elsevier, 2012.
2 K. C. Hultzsch, Adv. Synth. Catal., 2005, 347, 367; R. Giri,
B. F. Shi, K. M. Engle, N. Maugel and J. Q. Yu, Chem. Soc.
Rev., 2009, 38, 3242.
3 T. D. Machajewski and C. H. Wong, Angew. Chem., Int. Ed.,
2000, 39, 1352; K. Drauz and H. Waldmann, Enzyme
Catalysis in Organic Synthesis, WCH, Weinheim, 1995.
4 P. I. Dalko and L. Moisan, Angew. Chem., Int. Ed., 2004, 43,
5138; K. N. Houk and B. List, Acc. Chem. Res., 2004, 37, 487;
W. Notz, F. Tanaka and C. F. Barbas, Acc. Chem. Res.,
2004, 37, 580.
25 K. S. W. Sing, D. H. Everett, R. A. W. Haul, L. Moscou, R. A.
Pierotti, J. Rouquerol and T. Siemieniewska, Pure Appl.
Chem., 1985, 57, 603.
26 E. P. Barrett, L. G. Joyner and P. P. Halenda, J. Am. Chem.
Soc., 1951, 73, 373.
5 V. Chiroli, M. Benaglia, A. Puglisi, R. Porta, R. P. Jumdeb
and A. Mandoli, Green Chem., 2014, 16, 2798.
27 D. Gray, C. Concellón and T. Gallagher, J. Org. Chem.,
2004, 69, 4849; A. Orliac, J. Routier, F. Burgat Charvillon,
5846 | Catal. Sci. Technol., 2018, 8, 5835–5847
This journal is © The Royal Society of Chemistry 2018

View Article Online
Catalysis Science & Technology
Paper
W. H. B. Sauer, A. Bombrun, S. S. Kulkarni, D. Gómez Pardo
and J. Cossy, Chem. – Eur. J., 2014, 20, 3813.
Rodríguez-Escrich, I. G. Molnár, S. Sayalero, R. Gilmour and
M. A. Pericàs, ACS Catal., 2015, 5, 6241.
28 S. Kovačková, M. Dračínský and D. Rejman, Tetrahedron,
2011, 67, 1485; C. Heindl, H. Hübner and P. Gmeiner,
Tetrahedron: Asymmetry, 2003, 14, 3153.
30 K. Patora-Komisarskaa, M. Benohouda, H. Ishikawaa, D.
Seebach and Y. Hayashi, Helv. Chim. Acta, 2011, 94,
719.
29 J. M. Betancort and C. F. Barbas, Org. Lett., 2001, 3, 3737; A.
Alexakis and O. Andrey, Org. Lett., 2002, 4, 3611; O. Andrey,
A. Alexakis, A. Tomassini and G. Bernardinelli, Adv. Synth.
Catal., 2004, 346, 1147; W. Wang, J. Wang and H. Li, Angew.
Chem., 2005, 117, 1393; W. Wang, J. Wang and H. Li, Angew.
Chem., Int. Ed., 2005, 44, 1369; M. T. Barros and A. M. Faísca
Phillips, Eur. J. Org. Chem., 2007, 1, 178; D. Lu, Y. Gong and
W. Wang, Adv. Synth. Catal., 2010, 352, 644; W. H. Wang, T.
Abe, X. B. Wang, K. Kodama, T. Hirose and G. Y. Zhang,
Tetrahedron: Asymmetry, 2010, 21, 2925; I. Sagamanova, C.
31 T. Rantanen, I. Shiffers and L. Zani, Angew. Chem., Int. Ed.,
2005, 44, 1758.
32 S. Sulzer-Mossé and A. Alexakis, Chem. Commun., 2007, 3123.
33 A. Alexakis and O. Andrey, Org. Lett., 2002, 4, 3611.
34 P. Li, L. Wang, M. Wang and Y. Zhang, Eur. J. Org. Chem.,
2008, 7, 1157; L. Androvic, P. Drabina, M. Svodova and M.
Sedlak, Tetrahedron: Asymmetry, 2015, 27, 782; E. M. Omar,
K. Dhungana, A. D. Headley and M. B. A. Rahman, Lett. Org.
Chem., 2011, 8, 170; B. Ni, Q. Zhang, K. Dhungana and A. D.
Headley, Org. Lett., 2009, 11, 1037.
This journal is © The Royal Society of Chemistry 2018
Catal. Sci. Technol., 2018, 8, 5835–5847 | 5847