Immobilization of oligostyrene-prolinol conjugates into polystyrene via electrospinning and applications of these fibers in catalysis

Article abstract of DOI:10.1055/s-2008-1067146

This paper reports the synthesis of prolinol-oligostytrene conjugates and their immobilization into a polystyrene matrix by using the electrospinning process. Via this approach fibers with a large surface area (fiber diameter of 1.2 μm) containing the pro

Full text of DOI:10.1055/s-2008-1067146

PAPER
2163
Immobilization of Oligostyrene-Prolinol Conjugates into Polystyrene via
Electrospinning and Applications of these Fibers in Catalysis
Electrospun
Poly
a
F
ib
r
ers with
e
Immobilize
n
d Oligostyrene-Pro
R
linol Conjugate
s
öben,a Michael Stasiak,b Birgit Janza,a Andreas Greiner,b Joachim H. Wendorff,*b Armido Studer*a
a
Institute of Organic Chemistry, Westfälische Wilhelms-Universität Münster, Corrensstrasse 40, 48149 Münster, Germany
Fax +49(251)8336523; E-mail: studer@uni-muenster.de
b
Department of Chemistry, Philipps-Universität Marburg, Hans-Meerwein-Strasse, 35032 Marburg, Germany
E-mail: wendorff@staff.uni-marburg.de
Received 31 March 2008
Dedicated to Prof. Reinhard W. Hoffmann on the occasion of his 75th birthday
plications of these fibrous systems in organocatalysis. The
advantage of this immobilization technique over other im-
mobilization methods (copolymerization) lies in the high
surface area of the polymer fibers obtained during electro-
Abstract: This paper reports the synthesis of prolinol-oligostytrene
conjugates and their immobilization into a polystyrene matrix by
using the electrospinning process. Via this approach fibers with a
large surface area (fiber diameter of 1.2 mm) containing the prolinol
conjugate are readily obtained. The fibers are shown to be catalyti- spinning. The high surface area may lead to a highly ac-
cally active in a test Michael reaction. The fibrous catalyst system
tive catalyst system.
can readily be removed from the reaction mixture and be reused.
The nitroxide-mediated controlled radical polymeri-
However, a decrease of the catalyst activity was noticed upon recy-
zation6 was chosen as polymerization technique for the
cling the fibrous catalyst systems.
preparation of well-defined oligostyrene-prolinol conju-
Key words: organocatalysis, polymer, stereoselective synthesis,
gates. The synthesis of the polymerization initiators is de-
picted in Scheme 1. Benzylic iodide 2 was readily
prepared in four steps starting from the dibromide 1 in
86% overall yield.5,7 Grignard addition of phenylmagne-
sium chloride to ester 3 (→ 4), etherification of the sec-
ondary alcohol with iodide 2, and silylation provided
initiator 5 in 45% overall yield. The methyl derivative 7
was prepared from ester 3 in 6 steps via ether 6 in accept-
able overall yield (27%).
synthetic methods
Organocatalysis has received great attention during the
last seven years.1 Different approaches for the immobili-
zation of organocatalysts have been reported.2 The sepa-
ration of the catalyst from the product is often a serious
problem. For economic reasons its recovery is highly de-
sirable, in particular, if expensive catalysts are used. In
pharmaceutical industry product contamination might be
a problem. Furthermore, on going from batch to continu-
ous reactions one faces the problem of keeping the cata-
lyst in the reaction vessel while the reaction components
are pumped through.
N
O
Br
a–d
We recently reported that the electrospinning process3 can
be used for the immobilization of homogeneous catalysts
into polymer nanofibers.4 Scandium triflate was readily
immobilized in polystyrene fibers during electrospinning
and the fibrous catalytic system obtained was shown to be
active in imino aldol and aza-Diels–Alder model reac-
tions. Moreover, we showed that catalysts covalently
bound to low-molecular weight polystyrene (Mn >4000
g/mol) can be immobilized into high molecular weight
polystyrene nanofibers by using the electrospinning pro-
cess.5 The oligostyrene catalyst conjugates were well dis-
persed in the polystyrene matrix. Leaching of the
oligostyrene-tagged catalysts out of the polystyrene ma-
trix was suppressed in DMSO. Herein we present the syn-
thesis of oligostyrene-prolinol conjugates, their
immobilization into high-molecular weight polystyrene
by using the electrospinning process, and finally first ap-
I
Br
1
2 (86%)
HO
O
O
HO
e
N
f, g
Ph
Ph
Ph
Ph
CO2Me
h,e,i,j
N
N
N
H
OSiMe3
OH
Boc
Boc
5 (55%)
3
4 (82%)
HO
O
O
N
f,k
Ph
Ph
Ph
Ph
N
N
H
OMe
OMe
Boc
7 (43%)
6 (63%)
Scheme 1 Reagents and conditions: a) TEMPO, Cu, Cu(OTf)2,
4,4¢-di(tert-butyl)bipyridine, benzene; b) n-BuLi, DMF, THF; c)
LiAlH4, THF; d) NaI, TMSCl, MeCN; e) PhMgCl, THF; f) NaH, 2,
THF; g) TMS-imidazole, CH2Cl2; h) TBDMSCl, imidazole, DMF; i)
MeI, NaH; j) HF·pyridine, THF; k) aq 4 N HCl, dioxane.
SYNTHESIS 2008, No. 14, pp 2163–2168
Advanced online publication: 18.06.2008
DOI: 10.1055/s-2008-1067146; Art ID: C00808SS
© Georg Thieme Verlag Stuttgart · New York
x
x.
x
x
.
2
0
0
8

2164
C. Röben et al.
PAPER
All polymerizations were performed in neat styrene the electrospun fiber. Importantly, PPX is known to be re-
(Scheme 2). To this end, the alkoxyamine 6 (or 7) was dis- sistant to most common solvents. The fibrous catalyst sys-
solved in styrene (100 equiv), the solution was degassed tem containing 9b with a PPX shell prepared via this route
in three freeze-thaw cycles, and the reaction mixture was (diameter of core fiber: 1.16 mm, PPX shell thickness:
sealed under argon and heated to 125 °C for 24 hours. The 0.19 mm) is designated herein as system C. As a test reac-
polymerization was stopped upon cooling to room tem- tion we investigated the 1,4-addition of dimethyl mal-
perature and the polymer was dissolved in dichloro- onate to cinnamaldehyde to give aldehyde 10
methane. The solution was poured into a Petri dish and the (Scheme 3).10
residual styrene monomer was removed in a vacuum dry-
ing cabinet at elevated temperature (60 °C for 12 h). The
conversion was determined gravimetrically (8: 67%; 9a:
64% and 9b: 58%); molecular weight and polydispersity
index (PDI) were determined by size exclusion chroma-
tography (SEC).
O
N
Figure 1 SEM images of catalyst system A (average diameter of the
fibers: 1.16 mm)
Ph
O
5 or 7
CHO
MeO2C
Ph
CO2Me
CHO
A, B or C
(5 mol%)
Ph
Ph
Ph
n
N
125 °C, 24 h
H
+
OR
EtOH, r.t.
MeO2C
CO2Me
10
8
(R = SiMe3, Mn = 7500 g/mol, PDI = 1.30)
9a (R = Me, Mn = 6700 g/mol, PDI = 1.16)
9b (R = Me, Mn = 5600 g/mol, PDI = 1.11)
Ph
Ph
OTMS
N
H
Scheme 2 Preparation of oligostyrene-prolinol conjugates 8, 9a,
and 9b
11
Scheme 3 Test reaction
For the electrospinning3 of the polystyrene fibers we ap-
plied a strong electric field in the order of 103 V/cm to the
droplet of the polymer solution emerging from a cylindri-
cal die. The electric charges accumulate on the surface of
the droplet and cause it to become deformed along the
field direction, even though the surface tension counter-
acts droplet evolution. In supercritical electric fields, the
field strength overcomes the surface tension and a fluid jet
emanates from the droplet tip. The jet is accelerated to-
wards the counter electrode. During this transport phase,
the jet is subjected to strong electrically-driven circular
bending motion, which causes a strong elongation and
thinning of the jet into a solvent evaporation until the solid
fiber is finally deposited on the counter electrode.
The Michael additions were conducted in EtOH (48 mM)
at room temperature for three days. The aldehyde was
added in a 2-fold excess. About 5 mol% of catalyst was
used in each run as calculated, based on the SEC data of
the polymer conjugates immobilized. The fibrous catalyst
system was fixed in a home made clamp and was readily
removed from the reaction mixture by simply removing
the clamp. After separation from the reaction mixture, the
fibrous catalyst system was thoroughly washed with
EtOH. In Figure 2, a picture of the reaction vessel is de-
picted. For some reactions the enantioselectivity was de-
termined by chiral HPLC after derivatization of 10
according to a literature procedure.10 Reactions were re-
peated 9 times (for A and C) and 6 times (for B), respec-
tively. Yields were determined based on isolated product
10. The results are presented in Figure 3.
To obtain the PS-fibers containing the oligostyrene-proli-
nol conjugates we performed electrospinning using N,N-
dimethylacetamide solutions containing high molecular
weight polystyrene (Mn = 150 000 to 300 000 g/mol; 18
weight%) and the oligostyrene 8, 9a, or 9b (9 weight%) to
give fibrous catalyst systems A (from 8) and B (from 9a,
see Experimental Section). We obtained fibers free of
beads with diameters around 1.2 mm (from 8 = 1.15 mm;
from 9a = 1.16 mm). SEM images of the fibrous catalyst
system A are presented as examples in Figure 1. To fur-
ther stabilize the fibers we decided to coat the fibers car-
rying the organocatalyst with a thin polymer film to obtain
core shell fibers via chemical vapor deposition (CVD)
starting from [2.2]paracyclophane as a precursor.8,9 To
this end, poly-p-xylylene (PPX) was deposited at 30 °C to
Pleasingly, the immobilized catalyst A turned out to be ac-
tive in the test reaction and 10 was isolated in 42% yield
with an enantiomer ratio of 96:4. It has often been ob-
served that catalyst immobilization leads to reduced activ-
ity. Therefore, we repeated the experiment under identical
conditions (48 mM) with the homogeneous catalyst 11.
As expected, a higher yield was achieved in this experi-
ment under similar conditions (84%, er = 97:3). Hence,
immobilization of the catalyst using our new approach
does slightly reduce its activity if compared with the result
obtained with the nonimmobilized homogenous catalyst.
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Electrospun Polystyrene Fibers with Immobilized Oligostyrene-Prolinol Conjugates
2165
silylation in A is probably not the reason for catalyst deac-
tivation. We thought that physically stabilizing the fibers
by coating PPX might lead to systems where catalytic ac-
tivity will not be reduced after recycling of the catalyst.
To this end, we tested fiber system C in the Michael addi-
tion. Due to the PPX layer, diffusion of substrates into the
fiber mat and products out of the fiber mat might be slow-
er and hence activity was expected to be reduced as com-
pared to system B. In fact, a lower yield was obtained for
runs 1 and 2 under similar conditions (13% and 12%, re-
spectively). Unfortunately, the PPX-coat could not sup-
press catalyst deactivation. Yields leveled at around 6%
for runs 6 to 10 (about 50% of initial activity).
The reason for the catalyst deactivation is not clearly un-
derstood. We assumed that the morphology of the fibers
might be changed during catalysis. The solvent might lead
to a change of the fiber structure as already noticed for
other solvents.5 Therefore, we reanalyzed catalyst system
B after run 7 by SEM. In Figure 4 the SEM images are
presented. It is obvious that small changes on the fiber mat
occurred during the reaction (compare the left panel of
Figure 1 with the left panel of Figure 4); fibers seem to be
cut (lower aspect ratios). However, the fibers themselves
(right hand side) seem not to be damaged. Therefore, we
believe that the small changes in the macrostructure of the
fibrous systems lead to a decrease of the catalyst activity
probably due to a change of the diffusion rates.
Figure 2 Reaction vessel containing the fibrous catalyst system A
Figure 3 Results of the Michael additions using catalysts A, B, and
C
Importantly, a similar selectivity was obtained in these
two experiments. Based on our previous results5 we ruled
out that catalyst leaching for conjugates bearing polysty-
rene tails larger than 4000 g/mol occurred during the pre-
washing process. Moreover, we did not identify any
Figure 4 SEM images of catalyst system B after 7 runs
catalyst conjugate 8 in the reaction mixture after removal In conclusion, we have shown that prolinol derivatives
of the fibrous system A. However, we cannot rule out that could be conjugated with low molecular weight oligosty-
some of the catalytically active prolinol moieties of the fi- rene. By using the nitroxide-mediated radical polymeriza-
bers were decomposed during electrospinning via elec- tion method the length of the oligostyrene tail could be
tron-transfer processes. Catalyst system A was recycled 9 adjusted. The oligostyrene-prolinol conjugates were
times. We found that the initial activity remained for the readily immobilized into a high molecular weight polysty-
rene matrix by co-electrospinning of the conjugate with
polystyrene. The fibers obtained were free of beads. All
fiber systems tested were catalytically active in the test
Michael addition. However, catalyst deactivation was ob-
served and activity decreased to 25–50% of the initial ac-
second run (42%, er = 96:4). However, the activity de-
creased in the third run and leveled at about 25% of the
initial activity in the following runs (see runs 5–10). We
assumed that desilylation might occur under the reaction
conditions since the fiber system stayed more than 30
days in EtOH at room temperature. The desilylation might tivity after 10 runs. We believe that the approach
be the reason for the decrease of activity. Therefore, cata- presented herein is promising and future experiments will
lyst system B, bearing a methyl ether instead of the rather be devoted to further stabilize the macrostructure of the
labile silyl ether was tested under the same conditions. catalytically active fibers.
Compared to system A, a lower yield and a slightly lower
selectivity (er = 91:9) were obtained for the first two runs
(1st run: 23%, 2nd run: 26%). As with fibrous catalyst A,
a decrease of activity was noticed in runs 3–7. Hence, de-
1H NMR (600 MHz, 300 MHz) and 13C NMR (150 MHz, 75 MHz)
spectra were recorded on a Bruker ARX 300 spectrometer or Varian
Associated Unity Plus 600 spectrometer. Chemical shifts (d) in ppm
Synthesis 2008, No. 14, 2163–2168 © Thieme Stuttgart · New York

2166
C. Röben et al.
PAPER
are referenced to the solvent residue peak as an internal standard
and are reported relative to TMS. To allocate the NMR signals H,H-
COSY and C,H-correlations (GHSQC, GHMBC) were recorded for
(2S,4R)-2-(methoxydiphenylmethyl)-4-{4-[1-(2,2,6,6-tetramethyl-
piperidin-1-yloxy)ethyl]benzyloxy}pyrrolidine-1-carboxylic acid
tert-butyl ester. These were also used to allocate the signals for all
analogue compounds diphenyl-((2S,4R)-4-{4-[1-(2,2,6,6-tetra-
methylpiperidin-1-yloxy)ethyl]benzyloxy}pyrrolidin-2-yl)methanol,
5 and 7. TLC was carried out on Merck silica gel 60 F254 plates; de-
tection by UV or dipping into a solution of KMnO4 (1.5 g),
NaHCO3 (5.0 g) and H2O (400 mL), or a solution of Ce(SO4)2⋅H2O
(10 g), phosphomolybdic acid hydrate (25 g), concd H2SO4
(60 mL), followed by heating. Flash chromatography (FC) was car-
ried out on Merck silica gel 60 (40–63 mm) at about 0.4 bar addi-
tional pressure. Solvents were purified and dried by standard
methods. Compounds sensitive to air and moisture were handled
under argon by means of modified Schlenk techniques.
(C), 70.9 (CH2), 63.8 (CH), 59.9 (C), 52.6 (CH2), 40.6 (CH2), 33.2
(CH2), 23.8 (CH3), 20.6 (CH3), 17.4 (CH2).
MS (ESI): m/z = 1085.7 [2 M + H]+, 543.3 [M + H]+.
HRMS (ESI): m/z calcd for C35H46N2O3 [M + H]+: 543.3581; found:
543.3585.
1-(1-{4-[(3R,5S)-5-(Diphenyltrimethylsilyloxymethyl)pyrroli-
din-3-yloxymethyl]phenyl}ethoxy)-2,2,6,6-tetramethylpiperi-
dine (5)
N-(Trimethylsilyl)imidazole (0.66 M in CH2Cl2, 4.5 mL, 3.0 mmol,
3.3 equiv) was added slowly to a solution of diphenyl-((2S,4R)-4-
{4-[1-(2,2,6,6-tetramethylpiperidin-1-yloxy)ethyl]benzyloxy}pyr-
rolidin-2-yl)methanol (500 mg, 0.921 mmol, 1.0 equiv) in CH2Cl2
(3 mL). The mixture was stirred overnight at r.t. The conversion
was monitored via TLC and N-(trimethylsilyl)imidazole (0.66 M in
CH2Cl2, 4.5 mL, 3.0 mmol, 3.3 equiv) was added for a second time.
The mixture was stirred at r.t. for 2 h and the reaction was quenched
by the addition of sat. aq NH4Cl (10 mL). The aqueous layer was ex-
tracted with CH2Cl2 (2 × 10 mL) and the combined organic layers
were dried (MgSO4). After concentration in vacuo, purification of
the residue by flash chromatography (acetone–CH2Cl2, 1:4) yielded
the desired silyl ether 5 (389 mg, 69%).
IR spectra were recorded on a Digilab FTS 4000 equipped with a
Specac MKII Golden Gate Single Reflection ATR System, or a
Bruker IFS-28. ESI-MS and HRMS were performed using a Bruker
MicroTof. Size exclusion chromatography (SEC) was carried out
with THF as eluent at a flow rate of 1.0 mL/min at r.t. on a system
consisting of a Merck Hitachi L-6200A Intelligent Pump, a set of
two Polymer Laboratories PLgel 5 mm MIXED-C columns (300 ×
7.5 mm, linear range of molecular weight: 200–2 000 000 g/mol),
and a Knauer Differential refractometer (l = 950 30 nm) detector.
Data were analyzed with PSS WinGPC compact V 7.20 software
based upon calibration curves built upon polystyrene standards
(Polymer Laboratories polystyrene medium MW calibration kit S-
M-10) with peak molecular weights ranging from 500–3000000
g/mol. HPLC was performed using a system consisting of a Hewlett
Packard Binary Pump and a Diacel Chiracel AD-H column. Data
were analyzed with Hewlett Packard Series 1100 Chem Station for
LC.
IR (neat): 3058, 2932, 1663, 1599, 1492, 1447, 1375, 1361, 1250,
1210, 1133, 1070, 1022, 936, 880, 839, 734, 701 cm–1.
1H NMR (300 MHz, CDCl3, 300 K): d = 7.52–7.48 (m, 2 Harom),
7.40–7.35 (m, 2 Harom), 7.31–7.21 (m, 10 H, C6H5), 4.80 (q,
J = 6.6 Hz, 1 H, CHCH3), 4.45–4.37 (m, 3 H, CHOR, CH2O), 3.85–
3.80 (m, 1 H, CHNH), 3.01 (dd, J = 2.7, 11.6 Hz, 1 H, CHaHbNH),
2.85 (dd, J = 5.0, 11.6 Hz, 1 H, CHaHbNH), 1.77–1.70 (m, 2 H,
CH2CHOR), 1.48 (d, J = 6.6 Hz, 3 H, CHCH3), 1.47–0.62 (m, 15 H,
3 × CH2, TEMPO, 3 × CH3, TEMPO), 0.71 (br s, 3 H, CH3,
TEMPO), –0.07 (s, 9 H, SiCH3).
13C NMR (75 MHz, CDCl3, 300 K): d = 147.1 (C), 145.3 (C), 145.1
(C), 137.3 (C), 128.6 (CH), 127.9 (CH), 127.8 (CH), 127.7 (CH),
127.6 (CH), 127.1 (CH), 127.0 (CH), 126.7 (CH), 83.1 (C), 83.0
(CH), 79.4 (CH), 70.9 (CH2), 63.9 (CH), 59.9 (C), 53.1 (CH2), 40.6
(CH2), 34.5 (CH2), 23.8 (CH3), 20.5 (CH3), 17.4 (CH2), 2.41 (CH3).
Scanning Electron Microscopy (SEM) was performed with a
Hitachi S-4100 microscope using acceleration voltages between 5
and 10 kV.
Diphenyl-((2S,4R)-4-{4-[1-(2,2,6,6-tetramethylpiperidin-1-yl-
oxy)ethyl]benzyloxy}pyrrolidin-2-yl)methanol
MS (ESI): m/z = 615 [M + H]+.
HRMS (ESI): m/z calcd for C38H54N2O3Si [M + H]+: 615.3976;
NaH (60% in mineral oil, 109 mg, 2.72 mmol, 4.0 equiv) was added
slowly to a solution of 4 (250 mg, 0.677 mmol, 1.0 equiv) in THF
(10 mL) at r.t. and the mixture was then heated at reflux for 3 h. The
mixture was allowed to cool to r.t. and nitroxide 2 (273 mg,
0.681 mmol, 1.0 equiv) was added. The mixture was heated at re-
flux for 5 h, stirred overnight at r.t. and the reaction was quenched
by the addition of H2O (10 mL). The aqueous layer was extracted
with Et2O (3 × 10 mL) and the combined organic layers were dried
(MgSO4) After concentration in vacuo, purification of the residue
by flash chromatography (acetone–CH2Cl2, 1:4) yielded the title
compound (1.07 g, 79%).
found: 615.3984.
(2S,4R)-2-(Methoxydiphenylmethyl)-4-{4-[1-(2,2,6,6-tetra-
methylpiperidin-1-yloxy)ethyl]benzyloxy}pyrrolidine-1-car-
boxylic Acid tert-Butyl Ester
NaH (60% in mineral oil, 192 mg, 4.80 mmol, 4.0 equiv) was added
slowly to a solution of 6 (458 mg, 1.20 mmol, 1.0 equiv) in THF
(18 mL) at r.t. and the mixture was then heated at reflux for 2.5 h.
The mixture was allowed to cool to r.t. and then 2 (530 mg,
1.32 mmol, 1.1 equiv) was added. The mixture was heated at reflux
for 6 h, stirred overnight at r.t. and the reaction was quenched by the
addition of H2O (15 mL). The aqueous layer was extracted with
Et2O (3 × 15 mL) and the combined organic layers were dried
(MgSO4). After concentration in vacuo, purification of the residue
by flash chromatography [pentane–tert-butyl methyl ether
(TBME), 20:1 → 10:1] yielded the title compound (447 mg, 57%).
IR (neat): 3362, 3058, 2972, 2931, 1764, 1598, 1491, 1449, 1375,
1360, 1259, 1210, 1182, 1064, 1020, 821, 748, 701 cm–1.
1H NMR (300 MHz, CDCl3, 300 K): d = 7.52 (d, J = 7.3 Hz, 2
Harom), 7.39 (d, J = 7.3 Hz, 2 Harom), 7.26–7.06 (m, 10 H, C6H5), 4.71
(q, J = 6.6 Hz, 1 H, CHCH3), 4.54 (dd, J = 9.6, 6.8 Hz, 1 H,
CHOR), 4.35 (s, 2 H, CH2O), 4.01–3.92 (m, 1 H, CHNH), 3.07–
3.01 (m, 2 H, CH2NH), 1.80–1.70 (m, 1 H, CHaHbCHOR), 1.64–
1.58 (m, 1 H, CHaHbCHOR), 1.39 (d, J = 6.6 Hz, 3 H, CHCH3),
1.36–0.95 (m, 15 H, 3 × CH2, TEMPO, 3 × CH3, TEMPO), 0.61 (br
s, 3 H, CH3, TEMPO).
IR (neat): 2973, 2931, 1698, 1599, 1448, 1390, 1363, 1257, 1160,
1076, 1074, 936, 880, 822, 760, 704 cm–1.
1H NMR (600 MHz, CD2Cl2,, 253 K): d = 7.43–7.30 (m, 10 H,
C6H5), 7.25–7.20 (m, 2 Harom), 7.19–7.13 (m, 2 Harom), 5.17–5.13
(m, 1 H, CHOR), 4.69 (q, J = 6.6 Hz, 1 H, CHCH3), 4.31 (d,
J = 11.0 Hz, 1 H, CHaHbO), 4.25–4.19 (m, 1 H, CHaHbO), 3.77–
3.73 (m, 1 H, CHaHbNBoc), 3.51–3.47 (m, 1 H, CHaHbNBoc),
3.46–3.40 (m, 1 H, CHNBoc), 2.89 (s, 3 H, OCH3), 2.19–1.83 (m,
2 H, CH2CHOR), 1.50–1.42 (m, 4 H, 2 × CH2, TEMPO), 1.39 (d,
13C NMR (75 MHz, CDCl3, 300 K): d = 145.6 (C), 145.1 (C), 136.8
(C), 128.6 (CH), 128.2 (CH), 127.6 (CH), 127.0 (CH), 126.9 (CH),
126.7 (CH), 126.3 (CH), 125.3 (CH), 83.0 (CH), 79.3 (CH), 77.1
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Electrospun Polystyrene Fibers with Immobilized Oligostyrene-Prolinol Conjugates
2167
J = 6.6 Hz, 3 H, CHCH3), 1.37 (s, 9 H, t-C4H9), 1.23 (br s, 2 H,
CH2, TEMPO), 1.19 (br s, 3 H, CH3, TEMPO), 1.10 (br s, 3 H,
CH3, TEMPO), 0.94 (br s, 3 H, CH3, TEMPO), 0.57–0.53 (m, 3 H,
CH3, TEMPO).
13C NMR (150 MHz, CD2Cl2, 253 K): d = 156.0 (C), 145.4 (C),
140.2 (C), 140.0 (C), 136.5 (C)*, 128.0 (CH), 129.7 (CH), 127.8
(CH), 127.7 (CH), 127.4 (CH), 127.3 (CH), 126.7 (CH), 126.6
(CH), 87.2 (C), 83.0 (CH), 79.3 (C), 77.9 (CH), 71.0 (CH2), 59.5
(CH), 53.0 (CH3), 52.3 (CH2), 40.3 (CH2), 40.2 (CH2), 34.3 (CH2),
28.3 (CH3), 23.7 (CH3), 20.6 (CH3), 20.1 (CH3), 17.4 (CH2).
* Found in GHMBC-spectrum.
Oligostyrene-Prolinol Conjugate 9a
According to GP 1, NMP was conducted by using alkoxyamine 7
(71.0 mg, 0.128 mmol, 1.0 equiv) in styrene (1.50 mL, 13.1 mmol,
102 equiv) leading to oligostyrene-prolinol conjugate 9a (936 mg,
64%, Mn = 6700 g/mol, PDI = 1.16).
Oligostyrene-Prolinol Conjugate 9b
According to GP 1, NMP was conducted by using alkoxyamine 7
(51.0 mg, 91.7 mmol, 1.0 equiv) in styrene (1.05 mL, 9.14 mmol,
100 equiv) leading to oligostyrene-prolinol conjugate 9b (603 mg,
58%, Mn = 5600 g/mol, PDI = 1.11).
MS (ESI): m/z = 657 [M + H]+.
HRMS (ESI): m/z calcd for C41H56N2O5 [M + H]+: 657.4262; found:
Fibrous Catalyst Systems A, B, and C
Polystyrene (PS, 1.000 g, Mn = 150 000 to 300 000 g/mol) and the
oligostyrene conjugate (OS) 8, 9a or 9b (0.500 g) were dissolved in
dimethylacetamide (DMAc) (4.31 mL). The solution, stored within
a reservoir, was pumped through a metal capillary connected with a
voltage supply using a peristaltic pump. The circular orifice of the
capillary had a diameter of 0.45 mm. A circular shaped counter
electrode with a diameter of 18 cm was located below the reservoir,
so that a vertical arrangement of the electrodes resulted. Fibers were
collected on an aluminum foil. The distance between the tip of the
capillary and the counter electrode was typically of the order of 15
cm, the applied voltage was 20 kV. PPX deposition from the gas
phase was accomplished by evaporization of the starting material
[2.2]paracyclophane at 175 °C and 55 mbar and subsequent pyro-
lysis at 650 °C. The polymerization of the pyrolysis product 1,4-
quinodimethane on the fiber surface (r.t.) yielded homogeneously
coated fibers.
657.4270.
1-(1-{4-[(3R,5S)-5-(Methoxydiphenylmethyl)pyrrolidin-3-yl-
oxymethyl]phenyl}ethoxy)-2,2,6,6-tetramethylpiperidine (7)
(2S,4R)-2-(Methoxydiphenylmethyl)-4-{4-[1-(2,2,6,6-tetramethyl-
piperidin-1-yloxy)ethyl]benzyloxy}pyrrolidine-1-carboxylic acid
tert-butyl ester (340 mg, 0.518 mmol) was dissolved in a solution of
HCl in dioxane (4 M, 6 mL) at 0 °C. The mixture was stirred for 4 h
and was allowed to warm to r.t. Sat. aq NaHCO3 (10 mL) was then
added to adjust the pH to 7. The aqueous layer was extracted with
CH2Cl2 (3 × 10 mL) and dried (MgSO4). After concentration in vac-
uo, purification of the residue by flash chromatography (acetone–
CH2Cl2, 1:4) yielded the desired amine 7 (215 mg, 75%).
IR (neat): 3056, 2973, 2932, 1492, 1447, 1375, 1360, 1258, 1210,
1183, 1132, 1075, 936, 882, 822, 757, 702 cm–1.
1H NMR (300 MHz, CDCl3, 300 K): d = 7.39–7.33 (m, 4 Harom),
7.26–7.14 (m, 10 H, C6H5), 4.70 (q, J = 6.6 Hz, 1 H, CHCH3), 3.49
(dd, J = 7.6, 7.6 Hz 1 H, CHOR), 4.32 (s, 2 H, CH2O), 3.58 (m, 1 H,
CHNH), 3.01 (s, 3 H, OCH3), 2.81 (dd, J = 1.2, 11.9 Hz, 1 H,
CHaHbNH), 2.39 (dd, J = 4.6, 11.9 Hz, 1 H, CHaHbNH), 2.24 (s, 1
H, NH), 1.95 (dd, J = 7.6, 13.8 Hz 1 H, CHaHbCHOR), 1.67 (m, 1
H, CHaHbCHOR), 1.38 (d, J = 6.6 Hz, 3 H, CHCH3), 1.37–0.94 (m,
15 H, 3 × CH2, TEMPO, 3 × CH3, TEMPO), 0.60 (br s, 3 H,
CH3, TEMPO).
13C NMR (75 MHz, CDCl3, 300 K): d = 145.4 (C), 143.0 (C), 141.7
(C), 137.0 (C), 129.4 (CH), 129.2 (CH), 127.9 (CH), 127.6 (CH),
127.6 (CH), 127.5 (CH), 127.3 (CH), 126.8 (CH), 85.1 (C), 83.0
(CH), 79.6 (CH), 71.0 (CH2), 61.2 (C), 59.9 (CH), 52.6 (CH2), 51.7
(CH3), 40.6 (CH2), 34.5 (CH2), 23.8 (CH3), 20.5 (CH3), 17.4 (CH2).
Application of the Fibrous Catalyst Systems A, B, and C;
General Procedure (GP 2)
The fibrous catalyst system (5 mol%) was dipped into a solution of
dimethyl malonate (1.0 equiv) and cinnamaldehyde (2.0 equiv) in
EtOH (see Figure 2). The mixture was stirred at r.t. for 3 d. The re-
action was stopped by simply removing the fiber mat, which was
immersed in EtOH (3 × 7–12 mL) for 30 min to completely extract
the product. After concentration in vacuo, purification of the residue
by flash chromatography (pentane–TBME, 4:1 → 1:1) yielded the
desired aldehyde. The recycled catalyst system was reused under
identical reaction conditions.
Application of the Fibrous Catalyst System A
According to GP 2, the activity of catalyst system A [385 mg
(125 mg OS 8, 260 mg PS), 16.7 mmol of the catalytic active spe-
cies, 5 mol%] was tested in a Michael reaction of dimethyl
malonate (38.4 mL, 334 mmol, 1.0 equiv) with cinnamaldehyde
(84.1 mL, 668 mmol, 2.0 equiv) in EtOH (7.0 mL). The reaction
was repeated 9 times (Figure 3). Enantiomeric ratio (er) was deter-
mined by chiral HPLC after derivatization according to reference 10
(i-PrOH–cyclohexane, 1.5:98.5, flow rate 0.8 mL/min, major enan-
tiomer tR = 23.5 min, minor enantiomer tR = 23.5 min).
MS (ESI): m/z = 1114 [2 M + H]+, 557 [M + H]+.
HRMS (ESI): m/z calcd for C41H56N2O5 [M + H]+: 557.3738; found:
557.3738.
Nitroxide-Mediated Polymerization (NMP) with 5 or 7; General
Procedure (GP 1)
The alkoxyamine (1.0 equiv) was dissolved in styrene (100–
102 equiv) and the solution was degassed in three freeze-thaw cy-
cles. The mixture was sealed under argon and heated to 125 °C for
24 h. The polymerization was stopped by cooling to r.t. and the
polymer was dissolved in CH2Cl2 (2 mL). The solution was poured
into a Petri dish and the residual styrene monomer was removed in
a vacuum drying cabinet at 60 °C for 12 h. The conversion was de-
termined gravimetrically, molecular weight and polydispersity in-
dex (PDI) were determined by size exclusion chromatography
(SEC).
Application of the Fibrous Catalyst System B
According to GP 2, the activity of catalyst system A [1.06 g
(354 mg OS 8, 707 mg PS), 52.8 mmol of the catalytic active spe-
cies, 5 mol%] was tested in a Michael reaction of dimethyl mal-
onate (122 mL, 1.06 mmol, 1.0 equiv) with cinnamaldehyde
(267 mL, 2.12 mmol, 2.0 equiv) in EtOH (22 mL). The reaction
was repeated 6 times.
Application of the Fibrous Catalyst System C
According to GP 2, the activity of catalyst system C [928 mg
(308 mg OS 8, 620 mg PS), 1.16 mm PPX, 55.0 mmol of the cata-
lytic active species, 5 mol%] was tested in a Michael reaction of
dimethyl malonate (127 mL, 1.10 mmol, 1.0 equiv) with cinnamal-
Oligostyrene-Prolinol Conjugate 8
According to GP 1, NMP was conducted by using alkoxyamine 5
(41.0 mg, 66.8 mmol, 1.0 equiv) in styrene (0.780 mL, 6.80 mmol,
102 equiv) leading to oligostyrene-prolinol conjugate 8 (543 mg,
67%, Mn = 7500 g/mol, PDI = 1.30).
Synthesis 2008, No. 14, 2163–2168 © Thieme Stuttgart · New York

2168
C. Röben et al.
PAPER
Easwar, S.; Trombini, C. Adv. Synth. Catal. 2007, 349,
2061. (j) Zhou, L.; Wang, L. Chem. Lett. 2007, 628.
(k) Siyutkin, D. E.; Kucherenko, A. S.; Struchkova, M. I.;
Zlotin, S. G. Tetrahedron Lett. 2008, 49, 1212.
dehyde (277 mL, 2.20 mmol, 2.0 equiv) in EtOH (11 mL). The re-
action was repeated 9 times.
Acknowledgment
(3) Reviews: (a) Greiner, A.; Wendorff, J. H. Angew. Chem. Int.
Ed. 2007, 46, 5670; Angew. Chem. 2007, 119, 5770. (b) Li,
D.; Xia, Y. Adv. Mater. 2004, 16, 1151. (c) Huang, Z. M.;
Zhang, Y. Z.; Kotaki, M.; Ramakrishna, S. Compos. Sci.
Technol. 2003, 63, 2223.
We gratefully acknowledge the financial support by the Deutsche
Forschungsgemeinschaft within the program Organokatalyse (SPP
1179).
(4) Stasiak, M.; Studer, A.; Greiner, A.; Wendorff, J. H. Chem.
Eur. J. 2007, 13, 6150.
References
(5) Stasiak, M.; Röben, C.; Rosenberger, N.; Schleth, F.; Studer,
A.; Greiner, A.; Wendorff, J. H. Polymer 2007, 48, 5208.
(6) Reviews: (a) Hawker, C. J.; Bosman, A. W.; Harth, E. Chem.
Rev. 2001, 101, 3661. (b) Studer, A. Chem. Soc. Rev. 2004,
33, 267. (c) Studer, A.; Schulte, T. Chem. Rec. 2005, 5, 27.
(7) Molawi, K.; Studer, A. Chem. Commun. 2007, 5173.
(8) Bognitzki, M.; Hou, H.; Ishaque, M.; Frese, T.; Hellwig, M.;
Schwarte, C.; Schaper, A.; Wendorff, J. H.; Greiner, A. Adv.
Mater. 2000, 12, 637.
(1) For recent reviews on organocatalysis, see the special issue:
Chem. Rev. 2007, 107, issue 12.
(2) Some recent papers: (a) Miyabe, H.; Tuchida, S.; Yamauchi,
M.; Takemoto, Y. Synthesis 2006, 3295. (b) Doyaguez, E.
G.; Calderón, F.; Sánchez, F.; Fernández-Mayoralas, A.
J. Org. Chem. 2007, 72, 9353. (c) Chouhan, G.; Wang, D.;
Alper, H. Chem. Commun. 2007, 4809. (d) Gruttadauria,
M.; Giacalone, F.; Marculescu, A. M.; Meo, P. L.; Riela, S.;
Noto, R. Eur. J. Org. Chem. 2007, 4688. (e) Font, D.;
Bastero, A.; Sayalero, S.; Jimeno, C.; Pericàs, M. A. Org.
Lett. 2007, 9, 1943. (f) Alza, E.; Cambeiro, X. C.; Jimeno,
C.; Pericàs, M. A. Org. Lett. 2007, 9, 3717. (g) Mason, B.
P.; Bogdan, A. R.; Goswami, A.; McQuade, D. T. Org. Lett.
2007, 9, 3449. (h) Luo, S.; Li, J.; Xu, H.; Zhang, L.; Cheng,
J.-P. Org. Lett. 2007, 9, 3675. (i) Lombardo, M.; Pasi, F.;
(9) Hou, H.; Jun, Z.; Reuning, A.; Schaper, A.; Wendorff, J. H.;
Greiner, A. Macromolecules 2002, 35, 2429.
(10) Brandau, S.; Landa, A.; Franzén, J.; Marigo, M.; Jørgensen,
K. A. Angew. Chem. Int. Ed. 2006, 45, 4305; Angew. Chem.
2006, 118, 4411.
Synthesis 2008, No. 14, 2163–2168 © Thieme Stuttgart · New York