Ring-opening metathesis polymerization-based recyclable magnetic acylation reagents

Article abstract of DOI:10.1002/cssc.201200453

An operationally simple method for the acylation of amines utilizing carbon-coated metal nanoparticles as recyclable supports is reported. Highly magnetic carbon-coated cobalt (Co/C) and iron (Fe/C) nanobeads were functionalized with a norbornene tag (Nb-tag) through a "click" reaction followed by surface activation employing Grubbs-II catalyst and subsequent grafting of acylated N-hydroxysuccinimide ROMPgels (ROMP= ring-opening metathesis polymerization). The high loading (up to 2.6 mmolg ^-1) hybrid material was applied in the acylation of various primary and secondary amines. The products were isolated in high yields (86-99%) and excellent purities (all >95% by NMR spectroscopy) after rapid magnetic decantation and simple evaporation of the solvents. The spent resins were successfully re-acylated by acid chlorides, anhydrides, and carboxylic acids and reused for up to five consecutive cycles without considerable loss of activity.

Full text of DOI:10.1002/cssc.201200453

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DOI: 10.1002/cssc.201200453
Ring-Opening Metathesis Polymerization-based Recyclable
Magnetic Acylation Reagents
Quirin M. Kainz,[a] Roland Linhardt,[a] Pradip K. Maity,[b] Paul R. Hanson,*[b] and Oliver Reiser*[a]
An operationally simple method for the acylation of amines
utilizing carbon-coated metal nanoparticles as recyclable sup-
ports is reported. Highly magnetic carbon-coated cobalt (Co/C)
and iron (Fe/C) nanobeads were functionalized with a norbor-
nene tag (Nb-tag) through a “click” reaction followed by sur-
face activation employing Grubbs-II catalyst and subsequent
grafting of acylated N-hydroxysuccinimide ROMPgels (ROMP=
ring-opening metathesis polymerization). The high loading (up
to 2.6 mmolgÀ1) hybrid material was applied in the acylation
of various primary and secondary amines. The products were
isolated in high yields (86–99%) and excellent purities (all
>95% by NMR spectroscopy) after rapid magnetic decantation
and simple evaporation of the solvents. The spent resins were
successfully re-acylated by acid chlorides, anhydrides, and car-
boxylic acids and reused for up to five consecutive cycles with-
out considerable loss of activity.
Introduction
Although polymer-supported reagents for organic synthesis
have been around for a while, they remain of current interest
especially in the field of combinatorial chemistry, with new
methods and new supports being continuously developed.[1]
The main reason for their popularity is the combination of
well-established solution-phase chemistry (along with sophisti-
cated analytical techniques) with ease of purification (mostly
filtration) and the possibility for automation. Among them,
a wide variety of acyl transfer resins have been developed, for
example, polymer-supported ortho-nitrophenol,[2] para-(hydrox-
yphenyl)sulfone,[3] a range of supported mixed anhydrides,[4]
and, more recently, tetrafluorophenol.[5] However, one of the
most commonly utilized resins for acylation reactions is sup-
ported N-hydroxybenzotriazole (HOBt).[6,7] Although its reactivi-
ty in acylations can be advantageous, it is hampered by poor
stability in DMF.[8]
demonstrated the immobilization of NHS on commercially
available Merrifield and ArgoPore-Cl resins.[12,13] We herein
report acyl derivatives of a NHS high capacity ROMPgel
(ROMP=ring-opening metathesis polymerization) grafted on
magnetic Co/C or Fe/C nanobeads as versatile and recyclable
active-ester equivalents for the acylation of various primary
and secondary amines.
Results and Discussion
Polymers and oligomers derived from ring-opening metathesis
polymerization (ROMP) of monomers containing the function-
ality of the desired reagent and a strained alkene have been
developed by the group of Barrett[14,15] and by Buchmeiser.[16]
More recently, Hanson and co-workers contributed to this field
with the development of new oligomeric reagents[17] as well as
scavengers.[18] The main advantages of these “designer” poly-
mers (termed as ROMPgels) over conventional polystyrene-
based polymers are the high mechanical stability, excellent
quality, and quantitative loading because of functionalization
performed usually on the monomer stage. Active esters of
a NHS ROMPgel were successfully utilized by Barrett et al. for
the synthesis of various amides, ureas, carbamates,[19] and oxa-
diazoles[20] in excellent yields and purities. Recently, Roberts[21]
reported the grafting of NHS ROMPgels on Wang resins to
combine the convenience of a bead format with the high load-
ing of the ROMPgels. Despite the good site accessibility, limita-
tions in the choice of acylating reagents occurred and per-
fluorinated solvents had to be employed to achieve adequate
yields.
Active esters derived from N-hydroxysuccinimide (NHS) are
considered to be more stable and were frequently applied to
the activation of amino acids, the introduction of carbamate
protecting groups, and as staining, radiolabeling, or crosslink-
ing agents in various biological systems.[9] Several polymer-
supported NHS analogues are known, for example, copoly-
(ethylene-N-hydroxymaleimide),[10] and copoly(styrene-N-hy-
droxymaleimide).[11] In addition, Adamczyk and co-workers
[a] Q. M. Kainz, R. Linhardt, Prof. Dr. O. Reiser
Institute for Organic Chemistry, University of Regensburg
Universitꢀtsstr. 31, 93053 Regensburg (Germany)
Fax: (+49)9419434121
E-mail: oliver.reiser@chemie.uni-regensburg.de
[b] Dr. P. K. Maity, Prof. Dr. P. R. Hanson
Department of Chemistry, University of Kansas
1251 Wescoe Hall Drive, Lawrence, KS, 66045 (USA)
Fax: (+1)7858645396
Magnetic nanoparticles as supports would even further facil-
itate the workup process by replacing the energy-intensive
pumping to draw solvent through a filter and the tedious re-
covery of the polymer by an operationally simple magnetic de-
cantation. Furthermore, the magnetic properties of the nano-
E-mail: phanson@ku.edu
Supporting Information for this article is available on the WWW under
http://dx.doi.org/10.1002/cssc.201200935.
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beads also allow application under continuous-flow conditions
by confining them within a magnetic field rather than in
a membrane reactor.[22] Recently, Stark et al. reported the syn-
thesis of carbon-coated cobalt (Co/C)[23] or iron (Fe/C)[24] nano-
particles on multigram scale (>30 ghÀ1) from inexpensive
metal carboxylates by performing reducing-flame spray pyroly-
sis. These metal nanoparticles combine excellent thermal and
chemical stabilities with high magnetization (up to
158 emugÀ1). The surface of the nanobeads is accessible by co-
valent and/or non-covalent functionalization,[25] which allows
for applications such as extraction of analytes or contaminants
from water,[26,27] purification of blood,[28] or as recyclable sup-
port for catalysts.[22,29,30]
Clearly, loadings of this magnitude, limited by the diazonium
functionalization step from 1 to 2, are not very attractive for
the direct immobilization of reagents because of the sheer
mass of support needed for considerable amounts of reactive
groups.
ROMP using Nb-tagged reagents is an effective method to
increase the loading and to control the properties of the poly-
mer shell around the nanobeads by varying the amount of cat-
alyst and monomer used. Thus, the acetylated NHS monomer
4 was synthesized from furan and maleic anhydride in three
steps following literature procedures.[21,35,36] Applying condi-
tions reported by Roberts[21] for ROMP of 4 at room tempera-
ture on modified Wang beads pre-activated with Grubbs-I cata-
lyst[37] led to no noticeable formation of ROMPgel on the Nb-
tagged Co/C nanobeads 3 (Table 1, entry 1), which was con-
firmed by elemental analysis. A control experiment at 608C re-
ROMPgels based on magnetic Co/C nano-supports have pre-
viously been reported by our group for the immobilization of
a highly active and recyclable palladium complex for Suzuki–
Miyaura cross-coupling reactions.[31] Furthermore, such nano-
particles were applied for the facile purification of intermolecu-
lar[32] as well as intramolecular[33] Mitsunobu reactions utilizing
norbornene-tagged (Nb-tagged) reagents and a surface-initiat-
ed sequestration protocol. It has been demonstrated that be-
cause of the explicitly high magnetic moment of the cobalt
nanobeads the overall magnetization of the resulting hybrid
material is significantly higher than that of polymer-coated
iron oxide nanoparticles with comparable metal content, thus
allowing rapid separation of the ROMPgel from reaction mix-
tures. The high loadings achieved using this approach make
the development of other supported reagents, which can be
recycled through rapid and simple magnetic decantation and
subsequent regeneration of the reactive groups, desirable.
Table 1. Screening of reaction conditions for the synthesis of 5 by ROM
polymerization on the magnetic beads.[a]
Entry
Particles
Catalyst
T
[8C]
Reaction
time [h]
Loading (N)[b]
[mmolgÀ1
]
1
2
3
4
5
Co/C-Nb (3)
Co/C-Nb (3)
Co/C-Nb (3)
Fe/C-Nb (3)
Co/C-N3 (2)
Grubbs-I
Grubbs-I
Grubbs-II
Grubbs-II
Grubbs-II
25
60
60
60
60
24
10
1
1
1
no gel[c]
no gel[c]
2.37
1.96
no gel[c]
[a] 50 Equiv. of monomer and 1.0 equiv. of catalyst with respect to the
norbornene units attached on the nanobeads. [b] Determined by nitro-
gen microanalysis. [c] Oligomers in solution.
Synthesis of magnetic ROMP-
gels for acylation reactions
To render the magnetic Co/C or
Fe/C nanoparticles 1 accessible
to the grafting of ROMPgels,
a covalent surface-functionaliza-
tion strategy introducing nor-
bornene groups was utilized. At
first, well-established diazonium
chemistry followed by hydroxyl
azide exchange to 2 via a Mitsu-
nobu reaction with hydrazoic
acid as nucleophile was carried
out (Scheme 1).[22,29] Subsequent-
ly, norbornene moieties were in-
troduced through a copper(I)-
catalyzed alkyne/azide cycloaddi-
tion (click reaction),[34] giving rise
to 3, which is a suitable precur-
sor for subsequent ROMP with
Nb-tagged catalysts or reagents.
Loadings of 0.10–0.15 mmol
norbornene groups per gram
nanoparticle were determined
by elemental microanalysis for 3. Scheme 1. Synthesis of the magnetic ROMPgel. DEAD=diethyl azodicarboxylate.
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vealed, that Grubbs-I catalyst is not suitable to conduct sur-
face-initiated ROMP on the magnetic nanobeads. However,
oligomers could be precipitated from the solution by addition
of MeOH. Grubbs-I catalyst was also not active in the surface-
initiated sequestration of Nb-tagged Mitsunobu reagents.[32,33]
In contrast, Grubbs-II catalyst[38] allowed the grafting of the
desired ROMPgels on the nanobeads: To initiate ROMP on the
surface of the nanobeads, Nb-tagged Co/C nanobeads 3 were
dispersed in degassed CH2Cl2 in a sealed vessel under nitrogen
atmosphere using a tempered (608C) ultrasonic bath. A solu-
tion of Grubbs-II catalyst (1.0 equiv. with respect to the loading
with norbornene groups of 3) was injected to generate an
active ruthenium carbene species on the surface of the nano-
beads by ring-opening metathesis with the immobilized nor-
bornene moieties. A NHS ROMPgel was grafted onto the nano-
beads by subsequent addition of a solution containing mono-
mer 4 (50 equiv.). Immediately, a voluminous black gel was
formed, which, after quenching with ethyl vinyl ether (EVE),
contracted. The lump was dried well under vacuum and
crushed for further use. Based on the gain in mass of magnetic
resin 5, more than 95% of monomer 4 was incorporated into
the hybrid material. Combustion analysis revealed 4.21% nitro-
gen, corresponding to a loading of 2.37 mmolgÀ1 (Table 1,
entry 3), thus increasing the loading from the initially azide-
tagged nanobeads 2 by a factor of more than 20. Images
taken by transmission electron microscopy (TEM) confirmed
the encapsulation of the Co/C-particles in a polymer matrix,
separating the previously densely packed nanoparticle clusters,
a characteristic owed to the highly magnetic remanence of the
metal nanobeads.[39]
Figure 1. IR-ATR spectra of functionalized nanobeads 2 and 3, the monomer
4, and the corresponding magnetic ROMPgels 5 and 9.
ROMPgel 5 (1822, 1788, and 1731 cmÀ1). A peak broadening,
typical for magnetic nanobeads functionalized with organic
molecules, was apparent at lower wavenumbers. For resin 9
bearing hydroxyl groups, the peak at 1822 cmÀ1 disappeared
completely indicating successful cleavage of the acetyl group
in 5.
To optimize the loading of magnetic ROMPgel 5, a series of
experiments was performed by varying the amount of mono-
mer 4 from 50 to 100 equivalents while keeping the amount
of nanobeads 3 and Grubbs-II catalyst constant (Table 2). The
particle yields and loadings increased up to 80 equivalents of
monomer 4; however, when using 100 equivalents of 4, a de-
crease in loading and yield was observed. Moreover, the gel
lump showed to be of inhomogeneous composition with
darker (more nanobeads) and lighter areas (more polymer)
caused by irregular polymerization, which was also confirmed
by inconsistent data obtained from multiple elemental analysis.
Hence, 80 equivalents of monomer 4 seemed to be optimal
with respect to the amount of ROMPgel produced, loading,
and sufficient homogeneity.
Alternatively, ROMPgels supported on Fe/C nanoparticles
were successfully synthesized, giving rise to high loading mag-
netic resins consisting of biologically well acceptable compo-
nents (Table 1, entry 4). The morphology and performance of
the Fe/C ROMPgel was identical with the Co/C analogue,
whereas variations in the overall loading arose from slightly
different loadings of norbornene moieties from batch to batch.
To demonstrate that the ROMPgel was actually covalently
bound to the magnetic support and not just encapsulating the
nanobeads, a control experiment employing the azide-func-
tionalized nanobeads 2 instead of the Nb-tagged variant 3 was
performed. In this case no nanoparticle-supported ROMPgel 5
could be formed and nanoparticles 2 were recovered from the
solution, while oligomers remained in solution upon precipita-
tion with MeOH.
Determination of the loading and stability tests
The swelling properties of both resins were in line with liter-
ature reports for ROMPgels.[15,21] The resins exhibited a distinct
volume increase in THF, CH2Cl2, and CHCl3, whereas solvents
such as MeOH and Et2O did not induce such an effect. In DMF,
however, the formation of a gummy like mass was observed.
Spectroscopic data of the various beads was obtained by infra-
red spectroscopy using the attenuated total reflectance sam-
pling technique (IR-ATR). The azide-functionalized nanoparti-
cles 2 show a characteristic massive peak at 2100 cmÀ1, which
vanished after the click reaction yielded the Nb-tagged beads
3 (Figure 1). After ROMP, the characteristic carbonyl stretches
of monomer 4 were present in the spectrum of the magnetic
Although determination of the loading through nitrogen ele-
mental analysis is possible, for higher sample throughput
1
a H NMR assay was developed. An assay for the NMR titration
of ROMPgels as described by Roberts[21] was adjusted to fit the
needs of this project. Briefly, acylated ROMPgel 6 was treated
with an excess of benzylamine in a mixture of deuterated
chloroform and nondeuterated methanol (9:1). An internal
standard was added as accurate determination of the benzyla-
mine remaining in solution is not possible because the liberat-
ed N-hydroxyl resin 7 can capture amines from the solution
(Scheme 2).[40,41] We found the internal standard used by Rob-
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Acylation of various amines using magnetic ROMP-
gels
After detailed investigation of the synthesis, loading,
and stability of magnetic ROMPgels, the acylation of
amines and the recycling of the ROMPgel were exam-
ined (Scheme 3). In the first step, benzylamine as an
initial test substrate was stirred with a slight excess
of the acetylated Fe/C ROMPgel 5. After completion
of the acylation, ROMPgel was fully recovered by
using a magnet and benzylamide 8a was isolated by
simple decantation and evaporation of the solvents
(Figure 2).
Pure chloroform alone was not the ideal solvent
with respect to yield (82%) and product purity, but
addition of 10 vol% methanol gave rise to the benzy-
lamide in high yield (93%) and purity (>95% by
NMR). The solvent mixture was removed by simple
Scheme 2. Determination of the loading by using an NMR assay (50 mg test reactions).
erts, benzyl methyl ether, not to be ideal because of an overlap
with the product in some cases. Therefore, we used 4-methyla-
nisole instead. Owing to its magnetic properties, resin 7 had to
be removed from the solution by magnetic decantation before
1
acquiring the H NMR spectrum. To determine the loading, the
benzylic CH2 doublet of the resulting amide was compared
with that of the phenylic CH groups of the standard.[38] Load-
ings determined by this method closely matched the values
obtained by elemental analysis (Table 2).
Figure 2. Pictures of Fe/C ROMPgel 5: pristine (A), dispersed in CHCl3/MeOH
(9:1) by a magnetic stirrer (B), and after recovery by an external magnet (C).
To examine the long-time stability of the acetylated resin 5,
one batch was stored five months in the fridge and was then
1
analyzed again by elemental microanalysis and H NMR assay
(Table 3). NMR analysis revealed a decrease in loading of less
than one percent, whereas the data obtained from elemental
analysis indicated a slightly higher degree of decomposition
(4–7%).
distillation and reused for the next run. Also other, more sus-
tainable, solvents were tested. The yields are slightly lower
using EtOAc (89%) or THF (83%) while the product purity re-
mained excellent. However, the solvent range applicable for
this reaction is limited as sufficient swelling of the resin has to
be ensured during the reaction.
Table 2. Tuning of the hybrid material by variation of the amount of
monomer.[a]
In some cases the product solution was filtered over cotton
to remove traces of finely dispersed resin or degraded poly-
mer. An NMR comparison of the product before and after filtra-
tion showed slightly better line separation in the spectrum ac-
quired after filtration.[39] To quantify the effectiveness of the
magnetic decantation, we performed an additional experiment,
for which we determined the weight of the product before
and after filtration. Only 1 wt% was lost during filtration, which
is in line with the marginal weight gain of the filter. The mate-
rial collected by the filter corresponded to less than 0.3 wt%
of the initial resin, which underlines the effectiveness of the
magnetic decantation.[39]
Entry Monomer Yield
Loading [mmolgÀ1
[mg] calculated observed (N)[b] observed (NMR assay)
]
[equiv.]
1
2
3
4
50
60
80
147 2.31
163 2.50
201 2.79
196 2.99
2.16
2.23
2.46
2.09[c]
2.24
2.32
2.60
2.36
100
[a] For each reaction 70 mg of Co/C nanobeads and 1.0 equiv. of Grubbs-
II catalyst were used. [b] Determined by nitrogen analysis. [c] Inhomoge-
neous.
Table 3. Stability test of ROMPgel 5 by comparing the loading.
Keeping in mind our goal to develop a protocol that will
allow the use of different types of acyl transfer reagents, the
spent resin was stirred with an excess of benzylamine to
cleave the remaining acetyl groups. As free NÀOH resins are
capable of capturing amine from the solution,[40,41] a washing
step with acetic acid (15 vol%) in CH2Cl2 followed by THF was
conducted to regenerate 9.
Entry
Storage time
[month]
Loading [mmolgÀ1
N[b]
]
C[a]
NMR
1
2
0
5
2.30
2.15
2.34
2.24
2.28
2.26
[a] Determined by carbon analysis. [b] Determined by nitrogen analysis.
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Different acid chlorides readily
reacylated the Fe/C ROMPgel 9
following the procedure de-
scribed above. Three equivalents
of acid chloride were sufficient
to reach high loadings (>
2 mmolgÀ1), and the subsequent
acylation of different primary as
well as secondary amines yielded
the corresponding amides (8b–
d) in high purities and yields
with no detectable cross-con-
tamination (Table 5). Likewise,
anhydrides were able to reload
the free NÀOH resin 9 on addi-
tion of 4-(dimethylamino)pyri-
dine (DMAP) as a nucleophilic
catalyst with slightly decreased
Scheme 3. Acylation of amines using magnetic ROMPgels and subsequent recycling of the resin.
To investigate the recycling and reloading potential of the
magnetic ROMPgel, a series of reactions was performed. Co/C
ROMPgel 5 with an initial loading of 1.52 mmolgÀ1 was used
to synthesize N-benzylacetamide (8a) in 91% yield and excel-
lent purity by stirring for 5 h (Table 4). Remaining acyl groups
were cleaved and the resin washed with acid as described
efficiency when compared to acid chlorides (Table 5, entries 4
and 5). Notably, no racemization occurred using an enantio-
meric pure amine as substrate, demonstrating that the mag-
netic ROMPgels are very mild acylating agents applicable to
sensitive compounds.
However, in some cases acid chlorides or anhydrides are nei-
ther readily available nor easily synthesized and their high re-
activity might cause stability problems, for example, racemiza-
tion.[42] Therefore, acylation of the magnetic Fe/C ROMPgel 9
by coupling with aryl and alkyl carboxylic acids was investigat-
ed (Table 5, entries 7–10). Initially, 1-ethyl-3-(3-dimethylamino-
propyl)carbodiimide (EDC; free-base form) was applied as cou-
pling reagent in a mixture of DMF and CH2Cl2 (1:1) leading to
a moderate loading (0.74 mmolgÀ1), which corresponded to
47% functionalization with acyl groups taking into account the
distinct mass increase; subsequently, the corresponding amide
8 h was formed in high yields and purities. Other coupling re-
agent and base combinations, such as 2-(1H-benzotriazole-1-
yl)-1,1,3,3-tetramethylaminium tetrafluoroborate/ethyldiisopro-
pylamine (TBTU/DIPEA) or diisopropylcarbodiimide/DMAP (DIC/
DMAP), showed slightly improved loadings when using the
same acid, with the best result (0.89 mmolgÀ1, 56% functional-
ization) achieved by the most reactive reagent (TBTU; Table 5,
entry 8). In all cases three equivalents of acid and three equiva-
lents of coupling reagent were used. The high purities of the
product amides underline the successful removal of the spent
coupling reagents from the resin in the washing steps, which
is sometimes not trivial when using extraction to purify the re-
action mixture. Moreover, entries 7 and 8 (Table 5) demonstrate
the reproducibility of the acylation when using the same
amine.
Table 4. Consecutive synthesis of N-benzylacetamide (8a) and subse-
quent regeneration of the magnetic Co/C acylation reagent.
Entry Run Yield (iso- Purity[a] Loading after
lated) [%] [%]
recycling[a] [mmolgÀ1] initial loading[b] [%]
Regeneration of
1
2
3
4
5
1
2
3
4
5
91
98
99
98
91
>95
1.39
1.49
1.24
1.32
1.41
91
98
82
87
93
>95
>95
>95
>95
[a] Determined by NMR. [b] Initial loading: 1.52 mmolgÀ1
.
above. Effective re-acylation (91%, 1.39 mmolgÀ1) of the resin
was achieved by stirring with acetyl chloride (3 equiv.) in the
presence of an excess of triethylamine. The high product yields
(91–99%) and the ability for reloading (82–98%) were main-
tained for five consecutive cycles (Table 4). Despite the numer-
ous washing steps, 76% of the initial amount of nanobeads
was recovered after five runs, but with a slightly lower loading
of 1.41 mmolgÀ1. Images acquired by using a TEM revealed no
substantial differences between freshly prepared and reisolated
(after five cycles) ROMPgel 5.[39]
Having successfully demonstrated the reacyclation of mag-
netic NHS resin 9 using the same acid chloride for five consec-
utive cycles, we next examined whether it is possible to arm
the resin with various acid chlorides, anhydrides, or carboxylic
acids (Scheme 3). Especially, the potential emergence of prod-
uct mixtures within the amides 8 after consecutive reacylation
of resin 9 with different acylating agents was of particular in-
terest, as such cross-contamination would clearly restrict the
versatility and reusability of the resin.
Although the loadings obtained with carboxylic acids
cannot compete with the excellent loadings obtained using
acid chlorides, they are comparable with other acyl transfer
resins.[7,12,13] Reasons might be the reduced reactivity of activat-
ed esters compared to acid chlorides and the steric demand of
the coupling reagents. The loadings might be significantly im-
proved when using more equivalents of acid and coupling re-
agent or double couplings.[21] However, one has to decide for
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coated iron or cobalt nanoparti-
cles. Whereas Grubbs-I catalyst
failed to initiate the polymeri-
zation on the nanoparticle sur-
face, Grubbs-II catalyst efficiently
catalyzed the formation of mag-
netic ROMPgels, which were rap-
idly recovered from reaction
mixtures by magnetic decanta-
tion. Further experiments re-
vealed an optimal amount of
80 equivalents of monomer,
leading to a high loading (up to
2.6 mmolgÀ1) hybrid material
that was stable for more than
five months. Furthermore, IR
spectra, TEM pictures, and an
NMR-assay were applied to thor-
oughly characterize the ROMP-
gels.
Table 5. Reloading of ROMPgel 9 by acid chlorides, anhydrides, and acids and subsequent synthesis of amides
(8b–j) recycling the resin after each run.
Entry
Cycle
Acylating agent
Additives for
coupling
Loading[a]
[mmolgÀ1
Product amide[b]
Yield
[%]
]
1
1
Et3N
Et3N
2.26
2.27
96
94
2
3
2
3
Et3N
2.18
1.80
86
91
4
4
DMAP, Et3N
Synthesis of various amides in
excellent yields and purities fol-
lowed by subsequent regenera-
tion of the magnetic acyl trans-
fer resin was achieved for at
least five consecutive cycles. The
resin was efficiently recovered
by magnetic decantation after
each step, dispensing the need
of tedious and energy-intensive
filtration or even chromatogra-
phy. No cross-contamination was
detected when using different
acylation reagents or amines,
suggesting the magnetic resins
to be reliable and readily recycla-
ble acyl transfer reagents.
Although acid chlorides and an-
hydrides readily reacylated the
resin, couplings with carboxylic
acids only generated moderate
loadings regardless of the cou-
pling reagent or reaction condi-
tions. Further studies, which are
currently conducted in our labo-
ratories, include the improve-
ment of these loadings, the use
of more sophisticated substrates,
and the use of ROMPgels as sup-
5
6
5
1
DMAP, Et3N
1.36
2.14
95
95
Et3N
7
8
2
3
EDC
0.74
0.89
90
88
TBTU, DIPEA
9
4
5
DIC, DMAP
0.80
0.67
87
97
10
TBTU, DIPEA
[a] Determined by NMR assay. [b] Purity >95% in all cases based on NMR. [b] Product 8b–j. [c] Acylation on
monomer stage.
each application, if slightly increased loadings compensate for
the need for higher amounts of high molecular weight cou-
pling reagents and potentially laborious acids.
port for fluorescent labels. Also, the upscaling to multi-gram
experiments is planned, for which the advantages of the mag-
netic resins should even be more apparent.
Conclusions
We have demonstrated the successful synthesis of acylated
magnetic ROMPgels starting from readily synthesized carbon
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General procedure for the acylation of amines using mag-
netic ROMPgels
Experimental Section
Materials and methods
An excess (1.3 equiv. acyl groups) of magnetic ROMPgel 7 was
stirred with amine (1.0 equiv) in 5 mL of a CHCl3/MeOH (9:1) mix-
ture at RT for 2–16 h (TLC monitoring). The nanoparticles were re-
covered by using a magnet, the solution decanted, and the nano-
beads washed three times with a CHCl3/MeOH (9:1; 5 mL) mixture.
The combined solutions were filtered over cotton, the solvents
were distilled for reuse in the next cycle, and the crude product
was dried under high vacuum.
The recovered particles were subsequently stirred in a solution of
CH2Cl2/MeOH/benzylamine (8:1:1; ꢀ1 mL per 100 mg resin) over-
night. After decantation of the solution, the particles were washed
with 15% AcOH/CH2Cl2 (3x), THF (3x), and Et2O (1x). 1 mL of sol-
vent per 100 mg resin was used in each washing step, and the par-
ticles were suspended by stirring for 15 min. The particles were
dried under vacuum for 5 h.
The carbon-coated cobalt nanomagnets (Co/C, 20.5 m2 gÀ1, mean
particle sizeꢀ25 nm) were purchased from Turbobeads Llc, Swit-
zerland. Prior to use, they were washed five times for 24 h in a con-
centrated HCl (Merck, puriss.)/deionized water (Millipore) mixture
(1:1). Acid residuals were removed by washing with Millipore water
(5ꢁ), and the particles were dried at 508C in a vacuum oven.[27]
Azide- (2)[22,29] and norbornene- (3)[31] functionalized nanobeads
were synthesized according to literature procedures. Acetylated
monomer 4 was prepared in three steps following literature-
known syntheses.[21,35,36] All other commercially available com-
pounds were used as received. 1H NMR (300 MHz) and 13C NMR
(75.5 MHz) spectra were recorded by using a Bruker AC300 spec-
trometer with CHCl3 (7.26 ppm) as a standard. Magnetic nanobeads
were dispersed using an ultrasound bath (Sonorex RK 255 H-R,
Bandelin) and recovered with the aid of a neodymium-based
magnet (side length 12 mm). They were characterized by using
a IR-ATR spectrometer equipped with a Specac Golden Gate Dia-
mond Single Reflection ATR-System and elemental microanalysis
(LECO CHN-900).
N-Benzylacetamide (8a): According to the general procedure Fe/C
ROMPgel 5 (508 mg, 0.71 mmol, 1.39 mmolgÀ1) loaded with acetyl
groups was used to acetylate benzylamine (59 mL, 543 mmol) while
stirring for 5 h. Crude N-benzylacetamide 8a (79.9 mg, 536 mmol,
99%) was obtained as a pale brown solid and the resin recycled
for the next run.
1H NMR (300 MHz, CDCl3): d=7.39–7.18 (m, 5H), 6.11 (bs, 1H), 4.39
(d, J=5.6 Hz, 2H), 1.98 ppm (s, 3H); 13C NMR (75 MHz, CDCl3): d=
170.2, 138.3, 128.8, 127.9, 127.6, 43.8, 23.3 ppm; MS (ESI-MS): m/z
(%)=150.1 (50) [M+–H], calc. 149.1.
Synthesis of magnetic ROMPgel (5)
In a typical experiment, Nb-tagged, carbon-coated iron nanoparti-
cles (400 mg, 0.12 mmolgÀ1) were dispersed in dry CH2Cl2 (5 mL)
by sonication for 15 min in a sealed reaction vessel under nitrogen
atmosphere. A solution of Grubbs-II catalyst (40.8 mg, 48 mmol,
1.0 equiv. with respect to the loading with Nb) in dry CH2Cl2 (3 mL)
was injected and the dispersion subjected to sonication for 30 min
with the ultrasonic bath tempered to 608C. Next, a solution of the
acetylated N-hydroxysuccinimide monomer 4 (672 mg, 2.88 mmol,
60 equiv.) in dry CH2Cl2 (10 mL) was added and the sonication con-
tinued for 1 h at 608C. The pressure in the reaction vessel was re-
leased from time to time to allow formation of ROMPgel 5 after
a few minutes. The magnetic gel was separated by an external
magnet and washed with CH2Cl2 (3ꢁ5 mL). To quench the reaction,
a CH2Cl2/EVE (1:1; 5 mL) mixture was added followed by sonication
at ambient temperature for 20 min. The gel lump was washed with
CH2Cl2 (3ꢁ5 mL), dried under vacuum, and crushed to yield NHS-
functionalized magnetic ROMPgel.
1-[3,4-Dihydroisoquinolin-2(1H)-yl]ethanone
(8b):
1H NMR
(300 MHz, CDCl3, mixture of rotamers): d=7.24–7.04 (m, 9H, rmaj
+
rmin), 4.73 (s, 3H, rmaj), 4.61 (s, 2H, rmin), 3.82 (t, J=6.0 Hz, 2H, rmin),
3.67 (t, J=5.9 Hz, 3H, rmaj), 2.90 (t, J=5.9 Hz, 3H, rmaj), 2.85 (t, J=
5.9 Hz, 2H, rmin), 2.18 (s, 3H, rmin), 2.17 ppm (s, 4H, rmaj); 13C NMR
(75 MHz, CDCl3, mixture of rotamers): d=169.5, 169.4, 135.1, 134.1,
133.6, 132.6, 129.0, 128.3, 126.9, 126.7, 126.6(4), 126.5(6), 126.4,
126.1, 48.1, 44.1, 44.0, 39.5, 29.5, 28.6, 22.0, 21.7 ppm; MS (ESI-MS):
m/z (%)=351.0 (100) [2M+–H], calc. 51.2.
4-{[2-(1H-Indol-3-yl)ethyl]amino}-4-oxobutanoate (8c): 1H NMR
(300 MHz, CDCl3): d=8.22 (s, 1H), 7.60 (d, J=7.8 Hz, 1H), 7.37 (d,
J=8.0 Hz, 1H), 7.20 (t, J=7.3 Hz, 1H), 7.12 (t, J=7.3 Hz, 1H), 7.04
(d, J=1.6 Hz, 1H), 5.73 (s, 1H), 4.11 (q, J=7.1 Hz, 2H), 3.59 (dd, J=
12.8 Hz, 6.5, 2H), 2.96 (t, J=6.7 Hz, 2H), 2.64 (t, J=6.8 Hz, 2H), 2.40
(t, J=6.8 Hz, 2H), 1.23 ppm (t, J=7.1 Hz, 3H); 13C NMR (75 MHz,
CDCl3): d=173.2, 171.5, 136.5, 127.5, 122.2(8), 122.2(6), 119.6, 118.8,
113.0, 111.4, 60.8, 39.9, 31.2, 29.7, 25.4, 14.3 ppm; MS (ESI-MS): m/z
(%)=288.9 (50) [M+–H], calc. 288.2.
Incorporation of monomer: >95%; IR: n˜ =1822, 1788, 1731, 1368,
1200, 1154, 1059, 1002, 967, 914, 809, 729 cmÀ1; elemental micro-
analysis: 35.77% C; 2.58% H, 3.84% N.
N-(2,2-Dimethoxyethyl)-4-nitrobenzamide
(8d):
1H NMR
(300 MHz, CDCl3): d=8.32–7.26 (m, 2H), 7.96–7.91 (m, 2H), 6.44 (bs,
1H), 4.50 (t, J=5.0 Hz, 1H), 3.63 (t, J=5.4 Hz, 2H), 3.44 ppm (s, 6H);
13C NMR (75 MHz, CDCl3): d=165.7, 149.8, 140.0, 128.3, 124.0,
102.6, 54.9, 41.8 ppm; MS (ESI-MS): m/z (%)=255.1 (100) [M+–H],
calc. 255.1.
1H NMR assay for the determination of the loading
(R)-N-(1-Phenylethyl)isobutyramide (8e): [a]D = +1188 (1.0 g per
100 mL in CHCl3, 218C); ee>99%, determined by HPLC analysis
using a Chiralpak AS-H column eluting with a 95:5 heptane/2-
A stock solution was prepared by introducing benzyl amine
(1.64 mL, 15 mmol), p-methylanisole (378 mL, 3 mmol), and metha-
nol (2.5 mL, nondeuterated) into a 25 mL volumetric flask and fill-
ing up with CDCl3. To the Co/C-ROMPgel or Fe/C-ROMPgel 6
(50 mg) in a capped vial, stock solution (1.00 mL) was added and
the ROMPgel suspended by magnetic agitation utilizing the intrin-
sic magnetic properties of the material. After agitation for 5 h at
RT, the magnetic beads were separated by using an external
magnet and the solution was filtered over cotton. NMR spectra
were acquired, and the integration of the benzylic CH2 doublet of
the product (typically 4.3–4.5 ppm) was compared with that of the
phenylic CH groups of the standard (typically 6.75 ppm).
1
propanol mixture; H NMR (300 MHz, CDCl3): d=7.39–7.27 (m, 5H),
5.65 (bs, 1H), 5.23–5.04 (m, 1H), 2.43–2.24 (m, 1H), 1.49 (d, J=
6.8 Hz, 3H), 1.15 ppm (t, J=6.7 Hz, 6H); 13C NMR (75 MHz, CDCl3):
d=176.1, 143.5, 128.8, 127.4, 126.3, 48.5, 35.8, 21.8, 19.7 ppm; MS
(ESI-MS): m/z (%)=192.2 (100) [M+–H], calc. 192.1.
N-(3-Azidopropyl)-2,2,5-trimethyl-1,3-dioxane-5-carboxamide
(8f): 1H NMR (300 MHz, CDCl3): d=7.22 (bs, 1H), 3.90 (d, J=
12.4 Hz, 2H), 3.77 (d, J=12.4 Hz, 2H), 3.46–3.35 (m, 4H), 1.84 (p, J=
6.7 Hz, 2H), 1.48 (s, 3H), 1.43 (s, 3H), 1.00 ppm (s, 3H); 13C NMR
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(75 MHz, CDCl3): d=175.3, 98.7, 68.4, 67.3, 49.3, 40.3, 37.0, 29.2,
28.9, 18.3, 17.9 ppm; IR (ATR): n˜ =3375, 2989, 2937, 2872, 2095,
1650, 1537, 1454, 1375, 1265, 1201, 1082, 828, 637 cmÀ1; MS (ESI-
MS): m/z (%)=257.1605 (100) [M+–H], calc. 257.1608.
program CPTUSA-2006-4560 for funding this research. We thank
Turbobeads Llc for generously providing the magnetic nanobeads
and Dr. Alexander Schꢀtz for his support during this project.
N-(Furan-2-ylmethyl)acetamide (8g): 1H NMR (300 MHz, CDCl3):
d=7.35 (d, J=1.1 Hz, 1H), 6.32 (dd, J=3.0 Hz, 1.9, 1H), 6.22 (d, J=
3.0 Hz, 1H), 5.87 (bs, 1H), 4.42 (d, J=5.4 Hz, 2H), 2.00 ppm (s, 3H);
13C NMR (75 MHz, CDCl3): d=170.0, 151.3, 142.3, 110.6, 107.6, 36.7,
23.6 ppm; MS (ESI-MS): m/z (%)=157.1 (100) [M+–NH4], calc. 157.1.
(4-Iodophenyl)(morpholino)methanone (8h): 1H NMR (300 MHz,
CDCl3): d=7.77 (d, J=8.3 Hz, 2H), 7.15 (d, J=8.3 Hz, 2H), 3.94–
3.31 ppm (m, J=72.7 Hz, 8H); 13C NMR (75 MHz, CDCl3): d=169.6,
137.9, 134.8, 129.0, 96.3, 67.0 ppm; MS (ESI-MS): m/z (%)=317.0
(30) [M+–H], calc. 317.0.
Keywords: acylation · metathesis · magnetic nanobeads ·
polymerization · supported catalyst
[1] a) R. J. Booth, J. C. Hodges, Acc. Chem. Res. 1999, 32, 18–26; b) A.
Kirschning, H. Monenschein, R. Wittenberg, Angew. Chem. 2001, 113,
670–701; Angew. Chem. Int. Ed. 2001, 40, 650–679; c) Microwave-Assist-
ed Combinatorial Chemistry (Ed.: A. Loupy), Wiley-VCH, Weinheim, 2002;
d) R. E. Dolle, J. Comb. Chem. 2005, 7, 739–798.
[2] a) M. Fridkin, A. Patchornik, E. Katchalski, J. Am. Chem. Soc. 1965, 87,
4646–4648; b) M. Fridkin, A. Patchornik, E. Katchalski, J. Am. Chem. Soc.
1966, 88, 3164–3165; c) M. Fridkin, A. Patchornik, E. Katchalski, J. Am.
Chem. Soc. 1968, 90, 2953–2957; d) G. T. Panse, D. A. Laufer, Tetrahedron
Lett. 1970, 11, 4181–4184; e) J. W. Lee, Y. Q. Louie, D. P. Walsh, Y.-T.
Chang, J. Comb. Chem. 2003, 5, 330–335.
[3] a) T. Wieland, C. Birr, Angew. Chem. 1966, 78, 303; Angew. Chem. Int. Ed.
1966, 5, 310; b) E. Flanigan, G. R. Marshall, Tetrahedron Lett. 1970, 27,
2403–2406; c) D. L. Marshall, I. E. Liener, J. Org. Chem. 1970, 35, 867–
868.
[4] a) T. L. Ang, H. J. Harwood, J. Macromol. Sci. 1973, A7, 1079–1083;
b) M. B. Shambhu, G. A. Digenis, Tetrahedron Lett. 1973, 14, 1627–1629;
c) S. Porto, J. Durꢂn, J. M. Seco, E. QuiÇoꢂ, R. Riguera, Org. Lett. 2003, 5,
2979–2982.
N-Cyclohexyl-4-iodobenzamide (8i): m.p. 171–1738C; IR (ATR): n˜ =
3296, 2934, 2853, 1715, 1623, 1585, 1537, 1477, 1445, 1330, 1151,
;
1006, 890, 837, 713, 677 cmÀ1 1H NMR (300 MHz, CDCl3): d=7.77
(d, J=8.4 Hz, 2H), 7.47 (d, J=8.3 Hz, 2H), 5.88 (bs, 1H), 4.03–3.88
(m, 1H), 2.08–1.96 (m, 2H), 1.82–1.52 (m, 4H), 1.53–1.33 (m, 2H),
1.32–1.18 ppm (m, 2H); 13C NMR (75 MHz, CDCl3): d=165.9, 137.8,
134.6, 128.6, 98.2, 49.0, 33.3, 25.7, 25.0 ppm; MS (ESI-MS): m/z
(%)=330.0351 (100) [M+–H], calc. 330.0349.
tert-Butyl (4-oxo-4-(prop-2-yn-1-ylamino)butyl)carbamate (8j):
1H NMR (300 MHz, CDCl3): 6.45 (bs, 1H), 4.73 (bs, 1H), 4.05 (dd, J=
4.8 Hz, 2.4, 2H), 3.17 (t, J=6.4 Hz, 2H), 2.34–2.15 (m, 3H), 1.90–1.73
(m, 2H), 1.44 ppm (s, 9H); 13C NMR (75 MHz, CDCl3): d=172.5,
156.7, 79.8, 79.6, 39.7, 33.5, 29.3, 28.5, 26.6 ppm; MS (ESI-MS): m/z
(%)=241.1 (100) [M+–H], calc. 241.2.
[5] a) J. M. Salvino, B. Gerard, H. F. Ye, B. Sauvagnat, R. E. Dolle, J. Comb.
Chem. 2003, 5, 260–266; b) J. M. Salvino, N. V. Kumar, E. Orton, J. Airey,
T. Kiesow, K. Crawford, R. Mathew, P. Krolikowski, M. Drew, D. Engers, D.
Krolikowski, T. Herpin, M. Gardyan, G. McGeehan, R. Labaudiniere, J.
Comb. Chem. 2000, 2, 691–697.
[6] a) R. Kalir, A. Warshawsky, M. Fridkin, A. Patchornik, Eur. J. Biochem.
1975, 59, 55–61; b) M. Mokotoff, A. Patchornik, Int. J. Pept. Protein Res.
1983, 21, 145–154.
General method for the reacylation of magnetic ROMPgels
using acid chlorides or anhydrides
[7] O. W. Gooding, L. Vo, S. Bhattacharyya, J. W. Labadie, J. Comb. Chem.
2002, 4, 576–583.
Magnetic ROMPgel resin bearing free N-hydroxyl groups (9) was
dispersed in CH2Cl2 by stirring for 15 min. After cooling to 08C,
Et3N (4.0 equiv.) and acid chloride or anhydride (3.0 equiv., drop-
wise/in portions) were added. In the case of anhydrides, 0.1 equiv.
of DMAP were added as catalyst. The slurry was stirred for 30 min
at 08C, and the stirring continued for 16 h at RT. Thereafter, the
magnetic ROMPgel was collected by using a magnet, and the solu-
tion decanted. The particles were subsequently washed with THF
(3ꢁ5 mL), CH2Cl2 (3ꢁ5 mL), and Et2O (1ꢁ5 mL). After drying under
high vacuum, the loading was determined by an NMR assay.
[8] I. E. Pop, B. P. Dꢃprez, A. L. Tartar, J. Org. Chem. 1997, 62, 2594–2603.
[9] a) J. V. Staros, Biochemistry 1982, 21, 3950–3955; b) G. T. Hermanson,
Bioconjugate Techniques, 2nd ed., Academic Press, San Diego, 1996.
[10] a) D. A. Laufer, T. M. Chapman, D. I. Marlborough, V. M. Vaidya, E. R.
Blout, J. Am. Chem. Soc. 1968, 90, 2696–2698; b) M. Fridkin, A. Patchor-
nik, E. Katchalski, Biochemistry 1972, 11, 466–471.
[11] a) M. Akiyama, M. Narita, M. Okawara, J. Polym. Sci., Part A: Polym.
Chem. 1969, 7, 1299–1306; b) M. Akiyama, Y. Yanagisawa, M. Okawara,
J. Polym. Sci., Part A: Polym. Chem. 1969, 7, 1905–1912; c) M. Akiyama,
K. Shimizu, M. Narita, Tetrahedron Lett. 1976, 1015–1016.
[12] M. Adamczyk, J. R. Fishpaugh, P. G. Mattingly, Tetrahedron Lett. 1999, 40,
463–466.
General method for the reacylation of magnetic ROMPgels
using acids
[13] M. Adamczyk, J. R. Fishpaugh, P. G. Mattingly, Bioorg. Med. Chem. Lett.
1999, 9, 217–220.
[14] A. G. M. Barrett, B. T. Hopkins, J. Kçbberling, Chem. Rev. 2002, 102,
3301–3324.
[15] A. G. Barrett, B. Bibal, B. T. Hopkins, J. Kçbberling, A. C. Love, L. Tedeschi,
Tetrahedron 2005, 61, 12033–12041.
[16] a) M. R. Buchmeiser, Chem. Rev. 2000, 100, 1565–1604; b) M. R. Buchme-
iser, Bioorg. Med. Chem. Lett. 2002, 12, 1837–1840.
[17] a) A. M. Harned, W. Sherill, D. L. Flynn, P. R. Hanson, Tetrahedron 2005,
61, 12093–12099; b) A. M. Harned, H. S. He, P. H. Toy, D. L. Flynn, P. R.
Hanson, J. Am. Chem. Soc. 2005, 127, 52–53; c) T. R. Long, P. K. Maity,
T. B. Samarakoon, P. R. Hanson, Org. Lett. 2010, 12, 2904–2907.
[18] a) J. D. Moore, A. M. Harned, J. Henle, D. L. Flynn, P. R. Hanson, Org. Lett.
2002, 4, 1847–1849; b) J. D. Moore, R. H. Herpel, J. R. Lichtsinn, D. L.
Flynn, P. R. Hanson, Org. Lett. 2003, 5, 105–107; c) A. Rolfe, D. A. Probst,
K. A. Volp, I. Omar, D. L. Flynn, P. R. Hanson, J. Org. Chem. 2008, 73,
8785–8790.
Resin 9 was predispersed in a DMF/CH2Cl2 mixture (1:1) and cooled
to 08C. Acid (3.0 equiv.), TBTU (3.0 equiv.), and DIPEA (3.0 equiv.)
were stirred together in 3 mL DMF/CH2Cl2 at 08C for 15 min before
dropwise addition to the resin. The resulting slurry was stirred for
1 h at 08C and overnight at RT before the ROMPgel was recovered
by using a magnet. The particles were subsequently washed with
THF (3ꢁ5 mL), CH2Cl2 (3ꢁ5 mL), and Et2O (1ꢁ5 mL). After drying
under high vacuum, the loading was again determined by using
an NMR assay.
Acknowledgements
[19] A. G. M. Barrett, S. M. Cramp, R. S. Roberts, F. J. Zecri, Org. Lett. 2000, 2,
261–264.
[20] A. G. Barrett, R. S. Roberts, F. J. Zꢃcri, S. M. Cramp, Comb. Chem. High
Throughput Screen. 2000, 3, 131–138.
We gratefully acknowledge the International Doktorandenkolleg
NANOCAT (Elitenetzwerk Bayern), the Deutsche Forschungsge-
meinschaft DFG (Re 948/8-1, ‘‘GLOBUCAT’’) and the EU-Atlantis
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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&
ÞÞ
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www.chemsuschem.org
[21] R. S. Roberts, J. Comb. Chem. 2005, 7, 21–32.
[22] A. Schꢄtz, R. N. Grass, Q. Kainz, W. J. Stark, O. Reiser, Chem. Mater. 2010,
22, 305–310.
[23] R. N. Grass, E. K. Athanassiou, W. J. Stark, Angew. Chem. 2007, 119,
4996–4999; Angew. Chem. Int. Ed. 2007, 46, 4909–4912.
[24] I. K. Herrmann, R. N. Grass, D. Mazunin, W. J. Stark, Chem. Mater. 2009,
21, 3275–3281.
[25] Q. M. Kainz, A. Schꢄtz, A. Zçpfl, W. J. Stark, O. Reiser, Chem. Mater. 2011,
23, 3606–3613.
[26] a) F. M. Koehler, M. Rossier, M. Waelle, E. K. Athanassiou, L. K. Limbach,
R. N. Grass, D. Gꢅnther, W. J. Stark, Chem. Commun. 2009, 4862–4864;
b) M. Rossier, F. M. Koehler, E. K. Athanassiou, R. N. Grass, M. Waelle, K.
Birbaum, D. Gꢅnther, W. J. Stark, Ind. Eng. Chem. Res. 2010, 49, 9355–
9362; c) Q. M. Kainz, A. Spꢄth, S. Weiss, T. D. Michl, A. Schꢄtz, W. J. Stark,
B. Kçnig, O. Reiser, ChemistryOpen 2012, 1, 125–129.
[27] M. Rossier, F. M. Koehler, E. K. Athanassiou, R. N. Grass, B. Aeschlimann,
D. Gꢅnther, W. J. Stark, J. Mater. Chem. 2009, 19, 8239–8243.
[28] I. K. Herrmann, M. Urner, F. M. Koehler, M. Hasler, B. Roth-Z’Graggen,
R. N. Grass, U. Ziegler, B. Beck-Schimmer, W. J. Stark, Small 2010, 6,
1388–1392.
[33] P. K. Maity, Q. M. Kainz, S. Faisal, A. Rolfe, T. B. Samarakoon, F. Z. Basha,
O. Reiser, P. R. Hanson, Chem. Commun. 2011, 47, 12524–12526.
[34] a) V. V. Rostovtsev, L. G. Green, V. V. Fokin, K. B. Sharpless, Angew. Chem.
2002, 114, 2708–2711; Angew. Chem. Int. Ed. 2002, 41, 2596–2599;
b) C. W. Tornøe, M. Meldal in American Peptide Symposium (Eds.: M.
Lebl, R. A. Houghten), American Peptide Society, Kluwer Academic Pub-
lishers, San Diego, 2001; c) C. W. Tornøe, C. Christensen, M. Meldal, J.
Org. Chem. 2002, 67, 3057–3064.
[35] W. H. Heath, F. Palmieri, J. R. Adams, B. K. Long, J. Chute, T. W. Hol-
combe, S. Zieren, M. J. Truitt, J. L. White, C. G. Willson, Macromolecules
2008, 41, 719–726.
[36] N. A. O’Connor, A. J. Berro, J. R. Lancaster, X. Gu, S. Jockusch, T. Nagai, T.
Ogata, S. Lee, P. Zimmerman, C. G. Willson, N. J. Turro, Chem. Mater.
2008, 20, 7374–7376.
[37] (PCy3)2(Cl)2Ru=CHPh; a) P. Schwab, M. B. France, J. W. Ziller, R. H.
Grubbs, Angew. Chem. 1995, 107, 2179–2181; Angew. Chem. Int. Ed.
1995, 33–34, 2039–2041; b) P. Schwab, R. H. Grubbs, J. W. Ziller, J. Am.
Chem. Soc. 1996, 118, 100–110.
[38] (IMesH2)(PCy3)(Cl)2Ru=CHPh; M. Scholl, S. Ding, C. W. Lee, R. H. Grubbs,
Org. Lett. 1999, 1, 953–956.
[29] A. Schꢄtz, R. N. Grass, W. J. Stark, O. Reiser, Chem. Eur. J. 2008, 14, 8262–
8266.
[30] a) A. Schꢄtz, O. Reiser, W. J. Stark, Chem. Eur. J. 2010, 16, 8950–8967;
b) S. Wittmann, A. Schꢄtz, R. N. Grass, W. J. Stark, O. Reiser, Angew.
Chem. 2010, 122, 1911–1914; Angew. Chem., Int. Ed. 2010, 49, 1867–
1870.
[39] See the Supporting Information.
[40] C. Somlai, G. Szꢆkꢂn, L. Balꢂspiri, Synthesis 1992, 285–287.
[41] C. Somlai, G. Szꢆkꢂn, B. Penke, Synthesis 1995, 683–686.
[42] a) S. Han, K. Young-Ahn, Tetrahedron 2004, 60, 2447–2467; b) L. A. Car-
pino, M. Beyermann, H. Wenschuh, M. Bienert, Acc. Chem. Res. 1996, 29,
268–274.
[31] A. Schꢄtz, T. R. Long, R. N. Grass, W. J. Stark, P. R. Hanson, O. Reiser, Adv.
Funct. Mater. 2010, 20, 4323–4328.
Received: June 29, 2012
[32] P. K. Maity, A. Rolfe, T. B. Samarakoon, S. Faisal, R. D. Kurtz, T. R. Long, A.
¨
Revised: October 10, 2012
Published online on && &&, 0000
Schatz, D. L. Flynn, R. N. Grass, W. J. Stark, O. Reiser, P. R. Hanson, Org.
Lett. 2011, 13, 8–10.
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemSusChem 0000, 00, 1 – 10
&
9
&
ÞÞ
These are not the final page numbers!

FULL PAPERS
Q. M. Kainz, R. Linhardt, P. K. Maity,
P. R. Hanson,* O. Reiser*
&& – &&
Ring-Opening Metathesis
Polymerization-based Recyclable
Magnetic Acylation Reagents
Do it magnetic: Amines are acylated
utilizing N-hydroxysuccinimide ROMP-
gels (ROMP=ring-opening metathesis
polymerization) grafted onto highly
magnetic nanobeads. The products are
isolated by operationally simple mag-
netic decantation in excellent yields and
purities, and the ROMPgel is recycled
more than five times without loss of
activity.
ꢀ 2013 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
ChemSusChem 0000, 00, 1 – 10
&10
&
ÞÞ
These are not the final page numbers!