This is the peer reviewed version of the following article: Catal. Sci. Technol., 2015, 5, 754, which has been published in final
form http://pubs.rsc.org/en/content/articlelanding/2015/cy/c4cy01344a#!divAbstract

Asymmetric Organocatalysts Supported on Vinyl Addition
Polynorbornenes for Work in Aqueous Media
Irina K. Sagamanova,a Sonia Sayalero,a Sheila Martínez-Arranz,b Ana C. Albéniz,*b Miquel A. Pericàs*a, c

In an effort to identify novel polymer architectures suitable for the covalent supporting of catalysts, L–proline derivatives have been
immobilized onto rationally designed vinyl addition polynorbornene (VA-PNB) resins through copper-catalyzed azide-alkyne
cycloaddition (CuAAC) reactions. The fully saturated VA-PNB resins have been found to be optimal catalyst supports, the resulting
proline-functionalized resins behaving as very active, easily recoverable and highly reusable organocatalysts for the asymmetric
direct aldol reaction of benzaldehydes with ketones in aqueous media. The results show that the combination of modular, VA-PNB
resins with proline derivatives and triazole linkers represents a promising strategy for the immobilization of organocatalytic species.

Introduction
As a result of increasing concerns on sustainable characteristics
of chemical processes, the use of polymer-supported catalysts
in synthetic chemistry has increased considerably in recent
years.1 The covalent immobilization of catalytic species, offer
important advantages.2 The catalytic activity of polymersupported species is importantly determined by the accessibility
of the catalytic sites to the reactants, and is modulated by mass
transfer limitations In this respect, different features of
polymeric supports, such as solubility/swellability profile,
degree of functionalization and the possible involvement of the
polymer backbone in the catalytic reaction need all to be
considered.3 The choice of polymeric support is therefore an
essential issue, since its structure and properties can
importantly influence the course of chemical reactions
mediated by catalysts immobilized on it. As a matter of fact, no
single polymer structure would be optimal for every
conceivable synthetic application.4 In spite of that, a vast
majority of the applications reported so far rely on the use of
polystyrenes as supports.1 Recently, we have developed a
straightforward route to functionalized, vinyl addition (VA)
polynorbornenes (PNB’s).5 In this approach, haloalkyl
substituted norbornenes, prepared by Diels-Alder reactions of
cyclopentadiene and terminal 1-haloalkenes, are copolymerized with norbornene in the presence of
[Ni(C6F5)2(SbPh3)2], and the intermediate ω-bromoalkyl
substituted VA-PNB's are finally converted into the functional
VA-PNB’s by nucleophilic substitution (Scheme 1).5

+

(CH2)n

[Ni]

x

Br

y
m

(CH2)n
+ Nu

x

Br
- Br

y
m

(CH2)n
Nu

	
  

Scheme 1. Synthesis of functionalized VA-PNB polymers
In sharp contrast with polynorbornenes prepared by ringopening metathesis polymerization (ROMP), VA-PNB’s do not
contain in their skeletons carbon-carbon double bonds. For this
reason, the possibility of uncontrolled side reactions triggered
by these skeletal functional groups that could occur on ROMPPNB’s is completely avoided in VA-PNB’s (Figure 1).

m

m

ROMP-PNB

VA-PNB

	
  

Figure 1. General structures of ROMP-PNB and VA-PNB
polymers.

In spite of this potential limitation, ROMP-PNB’s have been
used as supports for the immobilization of reagents and
catalysts.4 By the contrary, the chemically inert, fully saturated
VA-PNB resins have not been evaluated so far for these
applications.6 Our previous experience in the development of
polymer-supported, easily recyclable organocatalysts for
chemical
processes
with
improved
sustainability
characteristics7 led to the idea of anchoring suitably
functionalized proline derivatives onto VA-PNB’s with the
double goal of assessing the suitability of these versatile
polymers as inert supports for catalyst immobilization and of
developing new robust, efficient and recyclable organocatalysts
for asymmetric transformations. Herein we report the
successful achievement of these goals through the application
of the novel functional polymers 1-2 (Figure 2) as reusable
catalysts for the highly stereoselective direct asymmetric aldol
reaction in water.8 The reported strategy opens up new avenues
for supporting multiple-function catalytic systems onto fully
saturated VA-PNB supports.

	
  

support

(CH2)n
Br

x

m
ref. 5

O

H2C

spacer

(CH2)n

N

linker

N

CO2H

O

1

x

N

N

linker

[Ni(C6F5)2(SbPh3)2]

O

y
m

N

n = 1, 4
endo/exo = 85/15

y

support

x

ω-bromoalkylnorbornenes according to our previously reported
procedure.5 Two different lengths of the bromoalkyl chain (n =
1 and 4) were used to study the effect on catalytic behavior of
increased separations between the functional units and the
polymer chain. For each bromoalkyl chain length, two levels of
functionalization
were
studied.
Interestingly,
the
functionalization level can be adjusted by varying the relative
amounts of norbornene and ω-bromoalkylnorbornene used in
the copolymerization. When the one-carbon spacer was used,
the x/y ratio varied between 1.1 and 1.6. This corresponds in
both cases to rather heavily functionalized resins. With the long
spacer, in turn, the x/y composition ranged from 1.3 to 24.0,
thus covering a broad range in functionalization. The
composition of the copolymers (x/y ratio) was determined in all
cases by analysis of the bromine content in the polymer. From
the stereochemical point of view, the different ωbromoalkylnorbornenes used for the preparation of the
copolymers are mixtures of endo (major) and exo (minor)
stereoisomers in a ratio close to endo:exo = 85:15.

NH

catalytic site

2

N

HN

catalytic site

Copol

y
m

(CH2)n
CO2H

NB-NB

(CH2)n Br

3a, x/y = 1.1, n = 1
3b, x/y = 1.6, n = 1
3c, x/y = 1.3, n = 4
3d, x/y = 24.1, n = 4
CO2H

Br

5

	
  
NaN3

Figure 2. Schematic design of the polynorbornene-supported
prolines developed in this work.

Results and Discussion
Synthesis and characterization of the polynorbornenesupported catalysts
Previous studies on the covalent immobilization of proline
derivatives onto polystyrene (PS) resins through 1,2,3-triazole
linkers have shown that the triazole units appear to play an
active, synergistic role in catalytic processes mediated by these
species in aqueous solvents.8c
For similar immobilization approaches to be used in the present
instance, either alkyne- or azide-functionalized VA-PNB's
should be first prepared. This has been done as illustrated in
Scheme 2.
First, ω-bromoalkyl functionalized VA-PNBs (3a-d) were
prepared by Ni–catayzed copolymerization of norbornene and

Copol

DMF

NB-NB

(CH2)n N3

4a, x/y = 1.1, n = 1
4b, x/y = 1.6, n = 1
4c, x/y = 1.3, n = 4
4d, x/y = 24.1, n = 4

DBU
toluene, !

Copol

NB-NB

CH2O

O

6b, x/y = 1.6

	
  
Scheme 2. Ready-to-click functional polymers employed in this
study.
The azido function was introduced on these copolymers by
nucleophilic substitution, by treatment with sodium azide in
DMF.5 In this manner, ω-azidoalkyl VA-PNB's 4a-d were
readily prepared. On the other hand, the intermediate
bromoalkyl VA-PNB's 3b (x/y = 1.6; n = 1) was treated with pethynylbenzoic acid (5) and DBU in toluene under reflux to

afford the alkynyl-functionalized resin 6b. While the
substitution of bromide by azide was essentially complete in the
preparation of 4a-d, the corresponding substitution by pethynylbenzoate leading to 6b left unreacted some 31% of the
bromomethyl groups present in 3b. In any case, this was not
problematic for the catalytic use of resins arising from 6b, since
these residual CH2Br groups turned out to be completely
unreactive. The incorporation of the functional unit in polymer
6b was monitored spectroscopically. Thus, characteristic IR
absorption bands for the ester and 4-ethynylphenyl groups
gained intensity as the reaction proceeded, while the C-Br
absorption at 638 cm-1 was almost absent at the end of the
process. Raman experiments also confirmed the presence of the
alkyne (2109 cm-1) and remaining Br (638 cm-1) in the polymer.
In addition, the 13C NMR spectrum of the polymer confirmed
the presence of 4- ethynylphenyl group.
For the preparation of the catalytic resins 1a-d, diastereo- and
enantiomerically pure (2S,4R)-N-Boc-4-propargyloxyproline
77b was used as the partner of resins 4a-d in copper-catalyzed
alkyne-azide cycloaddition (CuAAC) reactions (Scheme 3,
left).9 After deprotection with trifluoroacetic acid in
dichloromethane, the target prolines immobilized onto VAPNB supports 1a-d were obtained.
Catalyst 2, was readily prepared from copolymer 6b (Scheme 3,
right). First, the alkynyl functionalized polymer was
transformed into a fully protected form of the organocatalyst by
a CuAAC reaction with the diastereo- and enantiomerically
pure azido derivative 8.8c Then, deprotection with trifluroacetic
acid (TFA) in dichloromethane of N-Boc and t-butyl ester
groups led to the ready-to-act catalytic resin 2.
It is interesting to note that whereas VA-PNB 6b is a white
solid, soluble in common aprotic solvents of medium polarity,
copolymer 2 generated in the click reaction is completely
insoluble in the above mentioned media. This change of
properties is of particular interest in connection with the
recovery and reuse of the immobilized catalyst 2. A similar
behavior has already been noted in the preparation of ωazidoalkyl VA-PNB's from the corresponding ω-bromoalkyl
precursors.5 Besides the structural changes introduced by the
new substituent, a modification of the conformational behavior
of the rigid bicyclic units in the polymer backbone during the
cycloaddition plus deprotection process could also contribute to
this change in the solubility behavior.10
The incorporation of the functional proline derivatives onto the
copolymers via formation of a 1,2,3-triazole linker could be

easily followed by IR spectroscopy. For catalysts 1a-d,
characteristic IR absorption bands for the N-Boc and t-butyl
ester groups (ca. 1737, 1699; ca. 1392, 1365 cm-1) were present
after the click reaction, whereas the stretching band of the azido
group (ca. 2091 cm-1) had completely disappeared. The
presence of the free amino acid after the deprotection step was
also confirmed spectroscopically (1615-1631 cm-1). In the case
of catalyst 2, characteristic IR absorption bands for the t-butyl
groups (ca. 1392, 1365 cm-1) and the ester group in the pethynylbenzoate fragment (C=O, 1709 cm-1) were present after
the click reaction.
Table 1 summarizes the preparation of the copolymersupported organocatalysts 1a-d and 2: composition,
functionalization (f).11,12a yield12b and equilibrium swelling ratio
(SR).13 As a general trend, the overall yield for the click and
deprotection steps in the preparation of 1a-d was found to be in
the 83-95% range. Somewhat surprisingly, the more intensely
functionalized copolymers (1a and 1c) lead to the highest
incorporation of catalytic unit (Yield column). On the other
hand, the modification of the length in alkyl spacer connecting
the polymer backbone with the functional units (n= 1 or 4) had
little effect on the final functionalization yields (compare
entries 1-2 and 3-4). In any case, and as we will see later, 1b
presented optimal characteristics in catalysis.
The preparation of catalyst 2, where the complementary click
approach is used (alkyne on resin plus soluble azide) reveals as
slightly less efficient. As already discussed, the incorporation of
the p-ethynylbenzoate fragment to the bromomethyl substituted
VA-PNB 3b is not complete (ca. 69%). In addition, the click
reaction plus deprotection process required for the
incorporation of the catalytic units also suffers from somewhat
low efficiency, and the functionalization of the final resin
indicates overall yields of 49% (from 3b) or 75% (from 6b).
The occurrence of some solvolytic ester cleavage during the
final deprotection step could explain the decreased yield from
6b. Solvent uptake data using different solvents (water,
dimethyl sulfoxide and dichloromethane) indicate the swelling
ability of the copolymers. The equilibrium swelling ratio (SR)
measured for each solvent shows that copolymers 1 and 2
swelled better in dichloromethane than in water, while dimethyl
sulfoxide afforded an intermediate result. These data correlate
well with the experimental results in catalysis described in the
following section.

O

Copol NB-NB

(CH2)n N3

Copol

4a, x/y = 1.1, n = 1
4b, x/y = 1.6, n = 1
4c, x/y = 1.3, n = 4
4d, x/y = 24.1, n = 4

7

CH2O

6b, x/y = 1.6

N3

O

1)

NB-NB

CO2tBu

CO2tBu

1)
8

NBoc

NBoc

2.5 mol% CuI, DIPEA
THF, 80 oC, MW

2.5 mol% CuI, DIPEA
THF:DMF 1:1, 40 ºC
2) 2:1 TFA:CH2Cl2

2) 1:1 TFA:CH2Cl2

3) 2:98 Et3N:THF

3) 2:98 Et3N:THF
O

Copol NB-NB

Copol

(CH2)n
N

NB-NB

CH2O

N

2, x/y = 1.6

N

1a, x/y = 1.1, n = 1
1b, x/y = 1.6, n = 1
1c, x/y = 1.3, n = 4
1d, x/y = 24.1, n = 4

CO2H

O
NH

N
N

N

CO2H
NH

Scheme 3. Preparation of the VA-PNB immobilized catalysts 1a-d and 2.
Table 1. Characterization of polynorbornene-supported organocatalysts 1-2.
Entry

Cat.

x/ya

nb

f0 (mmol g-1)c,d

fmax (mmol g-1)e

f (mmol g-1)d

1
2
3
4
5

1a
1b
1c
1d
2

1.1
1.6
1.3
24.1
1.6

1
1
4
4
1

3.08
2.37
2.96
0.48
2.98g

2.02
1.69
1.97
0.44
1.79

1.80
1.47
1.88
0.37
0.87

Yield
(%)e
90
87
95
83
49

H2O
270
290
360
170
210

SR (%)f
DMSO
370
430
440
280
410

CH2Cl2
490
600
590
370
590

a

x/y = NB/NB(CH2)nX ratio in the starting copolymer. b Chain length of the alkyl spacer in the functional norbornene monomer (NB(CH2)nX). c
Functionalization of the starting copolymer (4a-d for 1a-d, and 3b for 2). d Calculated from the results of elemental analysis. See Ref. 11 e Calculated with the
formula given in Ref. 12. f Determined gravimetrically. See Ref. 13 and Supporting Information. g Determined by quantitative analysis of bromine in 3b. See
Ref. 11.

Taking into account the close relationship between physical
surface properties of supported catalysts and its catalytic
performance, the surface morphology of the new polymers
was examined by SEM microscopy. Very interestingly, VAPNB supported catalysts 1a-c with high functionalization
level (x/y = 1.1-1.6) show a more porous surface than
catalyst 1d (Figure 3). Likewise, polymer 2 shows a porous
surface comparable to that of 1b (Figure 4).

200 µm

600 µm
100 µm

10 µm

1b

1a

500 µm

200 µm

1c

200 µm
90 µm

1d

	
  

Figure 3. SEM images of VA-PNB supported organocatalysts
1a-d.

recorded stereoselectivity continued to be only moderate
(entry13).
Table 2. Solvent effect on the aldol reaction of cyclohexanone
with p-nitrobenzaldehyde catalyzed by polymers 1a-b.a
CHO

O

OH

O

1a or 1b (10 mol%)
+
O2N

600 µm

2

90 µm

	
  

solvent, r.t.
O2N

10a

9a

11a

Entry

Cat.

Solvent

Time
(h)

Conv.b,c

anti:
synb

1

1a

DMSO

21

61

74:26

ee
antid
(%)
91

2

1a

H2O

21

74

71:29

73

3

1a

21

94

81:19

85

4

1a

16

100 (97)

89:11

90

5

1a

DMSO/
H2O
(50/50)
DMSO/
H2O
(83/17)
neat

21

10

77:23

76

6

1b

DMSO

21

82

76:24

92

7

1b

H2O

21

81

79:21

78

8

1b

21

96

86:14

93

9

1b

19

100 (98)

91:9

91

10

1b

21

100 (97)

92:8

93

11

1b

21

99 (90)

96:4

96

12

1b

DMSO/
H2O
(50/50)
DMSO/
H2O
(83/17)
DMSO/
H2O
(83/17)e
DMSO/
H2O
(83/17)f
neat

21

17

77:23

75

13

1b

neatg

6.5

94

78:22

76

Figure 4. SEM images of VA-PNB supported organocatalyst 2.
Asymmetric aldol reaction mediated by catalysts 1a-d.
For the optimization of reaction conditions, we centered our
attention on the use of benign reaction media (DMSO,
water, and their binary mixtures) and on work under neat
conditions with catalysts 1a and 1b. The reactions were
performed at room temperature with a 10 mol% catalyst
loading. The results of this study are summarized in Table 2.
A complete account of the performed solvent optimization
studies can be found in the Supporting Information.
With both catalysts, optimal performance regarding yield
(97-99%) and stereoselectivity (89:11 to 91:9 anti:syn ratio,
90-91% ee) was achieved in DMSO/water 83:17 mixtures
(entries 4 and 9). Reactions in pure DMSO (entries 1 and 6)
or in pure water (entries 2 and 7) led to decreased
conversions and enantioselectivities, as the use of higher
amounts of water also did (entries 3 and 8). This behavior
parallels that of organocatalytic aldol reactions mediated by
PS-proline immobilized through triazole linkers.8b Also in
that case, the use binary mixtures of polar aprotic solvents
and water had positive effects,14 importantly increasing both
reaction rate and enantioselectivity.7c,8
Likewise, the optimal solvent composition (DMSO/water
83:17) represents an optimal balance between ability for the
establishing of a hydrogen bond network and VA-PNB
swelling.8c The combination of 1b and this solvent mixture
(entry 9) exhibited a slightly better profile and, for this
reason, its use in combination with acidic additives (entries
10 and 11) was also studied. The best result (96:4 anti:syn
ratio, 96% ee, entry 11) was achieved with trifluoroacetic
acid (10 mol%), and attempts to further accelerate the
reaction at higher temperatures (see Supporting Information)
did not lead to any practical improvement.
When the reaction was performed under solvent free
conditions
very
low
conversion
and
moderate
stereoselectivity were observed (entries 5 and 12). However,
performing the reaction in a ball-mill,15 with the use of pnitrobenzaldehyde and cyclohexanone in essentially
stoichiometric amounts, resulted in significantly better
conversión after a notably short reaction time, although the

	
  

a

Reactions were performed with 1a or 1b (0.015 mmol), pnitrobenzaldehyde (9a, 0.15 mmol) and cyclohexanone (10a, 0.75 mmol)
in the indicated solvents (54 µL). b By 1H NMR on the reaction crude. c
The combined yield of isolated diastereomers is given in parentheses. d
By chiral HPLC. e p-Nitrobenzoic acid (0.022 mmol) was used as an
additive. f Trifluoroacetic acid (0.015 mmol) g Reaction performed in a
ball-mill: 9a (89 mg, 0.59 mmol), 10a (67 µL, 0.65 mmol), 1b (40 mg,
0.059 mmol) and 60 zirconium oxide balls, rotation speed of 250-400
rpm..

It became apparent from these optimization studies that the
best reaction conditions consisted in using 10 mol% of
catalyst in combination of 10 mol% of TFA as an additive, a

mixture DMSO:H2O (87:13) as solvent and performing the
reactions at room temperature. The transferability of these
conditions was next checked by performing the reaction of
9a with 10a under catalysis by 1a-d (Table 3). Catalysts 1a,
1b and 1c showed similar behavior in terms of conversion,
diastereo- and enantioselectivity (entries 1-3). Copolymer
1d, in turn, led to much lower conversion and decreased
stereoselectivity (entry 4). This provides clear indication that
the functionalization level of the catalytic polymers (1d is
much less functionalized than 1a-c) has a significant
influence on their performance. An examination of the effect
of the amount of catalyst 1b (entries 5-6) showed that
catalyst loading could be reduced to 5 mol%, but at the
expense of increased reaction times. Thus, after 42 h
conversion was only 73%, while diastereoselectivity and
enantioselectivity kept at the same level (entry 5).
Conversely, when 20 mol% of catalyst was used (entry 6), a
noticeable increase in reaction rate was observed, the
process being essentially complete in only 13 h.

We then set out to explore the applicability of 1b with
respect to the aldehyde reaction partners. As it can be seen in
Scheme 4, a wide range of aromatic aldehydes can
effectively participate in this reaction affording the anti aldol
products in very high yields and with both, high diastereoand enantioselectivity. As a general trend, reactions
performed in the absence of TFA additive required slightly
longer reaction times. Although higher yields were normally
achieved in the absence of TFA, stereoselectivity slightly
eroded in these experiments (11a,f-g,i-j), so that the
convenience or not of using this additive has to be evaluated
in each particular case.
These results show that VA-PNB supported proline 1b
works in close parallelism to other amphiphilic polymeric
proline derivatives that have proven to be efficient catalysts
for the asymmetric aldol reactions of ketones and
benzaldehydes in aqueous reaction conditions,7c,8b-c,17 and
even outperforms the first reported monomeric proline
derivative exhibiting aldolase-like behavior.18

Table 3. Benchmarking of VA-PNB supported catalysts 1a-d in
the aldol reaction of cyclohexanone with p-nitrobenzaldehyde.a
CHO

O

+
O2N

9a

OH

catalyst (10 mol%)
TFA (10 mol%)
DMSO/H2O (83:17)
O2N
r.t.

O

11a

10a

	
  

Entry

Time
(h)

Conv.
(%)b

Yield
(%)c

anti:
synb

ee anti
(%)d

1
2
3
4
5
6
a

Cat.
1a
1b
1c
1d
1be
1bf

23
23
23
23
42
13

95
96
93
43
73
95

88
90
80
38
64
91

96:4
96:4
96:4
89:11
96:4
96:4

96
96
96
85
96
96

Reactions were performed with resin 1 (0.015 mmol), 9a (0.15 mmol),
10a (0.75 mmol) in DMSO/water (83:17, 54 µL). b By 1H NMR on the
reaction crude. c Combined yield of isolated anti:syn diastereomers. d By
chiral HPLC. e 5 mol% catalyst used. f 20 mol% catalyst used.

O

CHO

OH

DMSO:H2O (87:13), r.t.

R

9a-j

OH

R

10a

O

O

1b (10 mol%)
TFA (10 mol%)

NO2

OH

O

OH

anti
11a-j

OH

O

O

O2N
O2N

NC

11a, 23 h, 90% yieldb
96:4 anti:sync, 96% eed

11b, 47 h, 94% yieldb
96:4 anti:sync, 96% eed

11c, 47 h, 93% yieldb
95:5 anti:sync, 97% eed

11d, 43 h, 88% yieldb
97:3 anti:sync, 96% eed

11a, 21 hf, 98% yieldb
91:1 anti:sync, 91% eed
OH

O

CF3

OH

O

OH

OH

O

O

MeO2C

F3C

yieldb

yieldb

yieldb

11f, 110 h, 65%
98:2 anti:sync, 96% eed

OH

11g, 93 h, 74%
95:5 anti:sync, 95% eed

11f, 110 hf, 98% yieldb
97:3 anti:sync, 91% eed

11e, 93 h, 87%
96:4 anti:sync, 97% eed

11h, 46 h, 81% yieldb
97:3 anti:sync, 96% eed

11g, 96 hf, 95% yieldb
90:10 anti:sync, 91% eed

OH

O

O

Br

11i, 88 h, 63% yielde
96:4 anti:sync, 91% eed

11j, 47 h, 79% yieldb
96:4 anti:sync, 96% eed

11i, 96 hf, 75% yieldb
90:10 anti:sync, 90% eed

11j, 65 hf, 98% yieldb
93:7 anti:sync, 93% eed

	
  

a

Reaction conditions: aldehyde (0.15 mmol), 10a (0.75 mmol), 1b (10.2 mg, 0.015 mmol), TFA (0.015 mmol) in DMSO:H2O (83:17, 54 µL) at room
temperature. b Combined yield of the isolated diastereomers. c By 1H NMR on the reaction crude. d By chiral HPLC of 11. e Isolated yield of anti isomer. f
Without TFA additive.

Scheme 4. Substrate scope of the aldol reaction catalyzed by 1b.a
Asymmetric aldol reaction mediated by catalyst 2.
Catalyst 2 was designed with the goal of increasing the
catalytic activity and stereoselectivity depicted by 1a-c. We
anticipated that the structural changes introduced in 2 would
modify the hydrophobic/hydrophilic balance in the
amphiphilic catalyst, leading to higher catalytic activity in
water and to higher levels of stereocontrol in this reaction
media.8,17
As a common characteristic, proline and pyrrolidine
derivatives able to catalyze aldol reactions in aqueous media
display well differentiated molecular regions with
hydrophobic and hydrophilic characters, as it is known for
type-I aldolases. In polymer-supported prolines, the
extended polymer backbone efficiently mimics the
hydrophobic pocket of the natural enzymes, while the
functional units need to provide the hydrophilic environment
where the reaction takes place. The same behavior could be

expected in case of copolymer 2 where, according to
precedents,8c the triazole unit could play the double role of
grafting the proline unit onto the polymer and allowing the
formation of a hydrogen bond network connecting the linker
with the amino and carboxy groups in the catalytic unit. In
addition, the p-phenylene spacer present in 2 could also
improve the catalyst activity and stereoselectivity because of
the increased separation between the hydrophilic,
catalytically active moiety and the hydrophobic polymer
backbone, as previously noted with polystyrene-supported
prolines.7c The study on the catalytic behavior of 2 in water
was initiated by using p-nitrobenzaldehyde (9a) and
cyclohexanone (10a) as model substrates in the aldol
addition (see Supporting Information for details). Pleasingly,
the reaction proceeded nicely in water, affording aldol 11a
in 22 h with excellent yield (90%) and stereoselectivity
(95:5 anti:syn ratio, 96% ee). Identical stereoselectivity was

recorded when the reaction was conducted in DMSO:H2O
(50:50) or DMF:H2O (50:50) mixtures. In these solvent
mixtures, a slightly improved yield (95%) was also recorded.
In practice, a (50:50) mixture of DMF and water was the
solvent of choice for these reactions. In this media, the
reactions catalyzed by 2 provided the aldol adducts 11a-l
with excellent yield and stereoselectivity, in shorter reaction
times than with catalyst 1b and without the need of added
acid (Scheme 5). It thus appears that the combination of the
polynorbornene skeleton, the p-phenylenecarboxylate spacer
and the triazole linker leads to a significant improvement of
the catalytic activity of the proline unit in aqueous media.
Reactions involving cyclopentanone (10b) and 4-pyranone

(10c) as pronucleophiles were remarkably fast, providing the
corresponding anti-aldol products 11k-l in very high yield
and good stereoselectivity.15b,17d,20 In general, products 11
were obtained in high purity after a simple filtration (to
recover 2), extraction with dichloromethane and
evaporation, no further purification being required. On the
negative side, when the use of 2 was attempted in the aldol
reactions of p-nitrobenzaldehyde (9a) with acyclic ketones
such as acetone and hydroxyacetone under the optimized
conditions in Scheme 5, very low conversions (< 5%) were
recorded after 48 h.

OH

O

CHO

O

2 (10 mol%)
X

R

DMF:H2O (50:50), r.t.

R

10a-c

9a-j

X= -CH2CH2-, -CH2-, -OCH2OH

O

NO2

OH

O

OH

X

anti
11a-l

OH

O

O

O2N
O2N

NC

11a, 22 h, 97% yieldb
96:4 anti:sync, 97% eed

OH

11b, 35 h, 69% yieldb
97:3 anti:sync, >99% eed

O

CF3

OH

11c, 26 h, 86% yieldb
97:3 anti:sync, 97% eed

OH

O

11d, 23 h, 97% yieldb
96:4 anti:sync, 97% eed

O

OH

O

MeOOC

F3C

yieldb

yieldb

11e, 26 h, 93%
95:5 anti:sync, 96% eed
OH

11f, 110 h, 55%
98:2 anti:sync, 94% eed
OH

O

11g, 82 h, 80%
93:7 anti:sync, 95% eed

O

Br

11i, 82 h, 76% yielde
95:5 anti:sync, 95% eed

yieldb

OH

OH

O

O2N

11j, 44 h, 99% yieldb
95:5 anti:sync, 97% eed

11h, 46 h, 95% yieldb
96:4 anti:sync, 96% eed

O2N

11k, 4 h, 93% yieldb
76:24 anti:sync, 90% eed

O

O
11l, 16 h, 92% yieldb
88:12 anti:sync, 69% eed

	
  

a

Reaction conditions: 9a-j (0.15 mmol), 10a-c (0.75 mmol), and 2 (17 mg, 0.015 mmol) in DMF:H2O (50:50, 54 µL) at room temperature. b Combined yield
of the isolated diastereomers after flash chromatography. c By 1H NMR on the reaction crude. d By chiral HPLC of 11. e Isolated yield of anti isomer.

Scheme 5. Substrate scope of the aldol reaction catalyzed by 2.a
Catalysts recycling and reuse.
To show the recyclability of polymers 1b and 2, two series
of experiments were planned where single samples of these
catalytic copolymers were repeatedly used at constant
reaction time to mediate the aldol addition of cyclohexanone
(10a) to p-nitrobenzaldehyde (9a) leading to 11a. The
results of these studies have been summarized in Figure 5.
The insoluble nature of the polymer allows for catalyst
recovery by performing a simple filtration. Thus, after each
run, the catalyst was readily recovered from the reaction

mixture, washed and reused in the next reaction cycle (see
Supporting Information).
Copolymer 1b was recycled seven times affording the aldol
product with constant stereoselectivity and with only
marginal decrease of catalytic activity in every cycle. IR
analysis of the catalyst after recycling did not show any
difference with the initial polymer. In an attempt to
understand the origin of the observed decrease in catalytic
activity, SEM studies were performed to monitor the change
of the catalyst surface morphology. Compared with fresh
catalyst 1b, a very similar surface morphology was observed
after the seventh run. This observation indicates that 1b does

not experience structural collapse with repeated use. On the
other hand, it was found that the %N determined by
elemental analysis decreased after recycling, which was
indicative that leaching of catalytic proline units from the
copolymer backbone takes place to some extent. Catalyst 2,
on the contrary, could be recycled and reused for at least
seven runs without any appreciable loss in yield or in
stereoselectivity. The polymer presented similar IR spectra
and the same surface morphology before and after recycling.
Furthermore, it was found that the %N determined by
elemental analysis remained unchanged after recycling (see
Supporting Information). It is thus clear that the presence of
the p-phenylenecarboxylate spacer has a notable and very
positive effect on the chemical stability of the
polynorbornene-supported organocatalyst.

complementary alkyne-azide click reactions. The versatility
of these species as organocatalysts has been also illustrated
by their application in asymmetric aldol additions of ketone
pronucleophiles to aromatic aldehydes in a variety of
reaction conditions. Polynorbornene-supported proline has
shown excellent performance in this particular aldol
transformation in an aqueous environment, and the
robustness of the new polymeric catalysts has been
demonstrated by the possibility of extending its use for up to
seven cycles in the aldol reaction of cyclohexanone and pnitrobenzaldehyde. These results show that VA-PNB's can
be considered as viable alternatives to well-established
polystyrene resins as supports for the immobilization of
catalysts. In addition, the absence of unsaturations in the
polymer backbone of VA-PNB's should make these
polymers transparent to UV light and therefore, could
greatly facilitate the use of catalysts supported on these
resins in photocatalytic processes. Further applications of
VA-PNB's as catalysts supports, dictated by the structural
characteristics of these copolymers, are now in progress in
our laboratories.

Experimental Section
Synthesis of catalysts 1a-d.

	
  

	
  
Figure 5. Catalyst recycling experiments in the aldol
addition of cyclohexanone (10a) to p-nitrobenzaldehyde (9a)
leading to 11a under optimized conditions with catalysts 1b
and 2. Black bars: yield (%); pale gray bars: dr; gray bars: ee
(%).

Conclusions
In summary, we have successfully developed a family of
modified prolines anchored onto VA-PNB's through two

1a: t-Butyl (2S,4R)-N-Boc-4-propargyloxyprolinate 7 (600
mg, 1.84 mmol), N,N-diisopropylethylamine (2.5 mL, 14.20
mmol) and copper(I) iodide (6.7 mg, 0.035 mmol) were
added to a suspension of copolymer 4a (Copol-NBNBCH2N3 x/y = 1.1:1, n = 1; 460 mg, f = 3.084 mmol g-1) in
a DMF:THF 1:1 mixture (9 mL) placed in a flask under N2.
The reaction mixture was shaken at 40 ºC for 24 h, the
reaction progress being monitored by FTIR. When the IR
band of the azido group had completely disappeared, the
polymer was collected by filtration, sequentially washed
with H2O (40 mL), THF (40 mL), THF-MeOH (40 mL),
MeOH (40 mL), THF (40 mL) and CH2Cl2 (50 mL) and
dried under reduced pressure at 40 ºC for 24 h. The
intermediate polynorbornene-supported t-butyl prolinate,
which was obtained as a white solid (892 mg, 97% yield)
[FTIR (ATR, neat): ν 2941, 2868, 1738 (C=O), 1699 (C=O),
1476, 1453, 1393 (t-butyl), 1393 (t-butyl), 1254, 1366 cm-1.
Elemental Analysis (%): Calcd.: N, 8.63. Found: N, 8.51; f =
1.52 mmol g-1], was directly submitted to the deprotection
process. To this end, the prolinate (870 mg) was swollen in
CH2Cl2 (10 mL), after 10 min TFA was added (20 mL) and
the mixture was shaken at room temperature. When the IR
bands of the t-butyl and carbonyl moieties in the protecting
groups had completely disappeared, the reaction mixture
was filtered off and the polymer was washed sequentially
with THF (with 2% of Et3N, 50 mL), H2O (50 mL), THF (50
mL), THF-MeOH 1:1 (50 mL), MeOH (50 mL), THF (50
mL) and CH2Cl2 (50 mL). The solid was dried under
reduced pressure at 40 ºC for 24 h (648 mg, 98% yield).
FTIR (ATR, neat): ν 3409 (COOH), 2942, 2866, 1622

(C=O), 1450, 1371, 1317, 1219, 1154 cm-1. Elemental
Analysis (%): Calcd.: N, 11.37; Found: N, 10.06; f = 1.80
mmol g-1. Catalysts 1b, 1c and 1d were synthesized in the
same way, starting from the corresponding azido-copolymer.
1b: The intermediate polynorbornene-supported t-butyl
prolinate (a white solid) was obtained from 7 (1.0 g, 3.08
mmol), N,N-diisopropylethylamine (4.2 mL, 23.70 mmol),
copper(I) iodide (10 mg, 0.059 mmol) and copolymer 4b
(Copol-NB-NBCH2N3 x/y = 1.6:1, n = 1; 1.0 g, f = 2.37
mmol g-1) in DMF:THF 1:1 (12 mL) after 22 h reaction in
95% yield (1.69 g). [FTIR (ATR, neat): ν 2943, 2867, 1737
(C=O), 1699 (C=O), 1476, 1453, 1392 (t-butyl), 1365 (tbutyl), 1255, 1217 cm-1. Elemental Analysis (%): Calcd.: N,
7.50. Found: N, 7.67; f = 1.37 mmol g-1]. Then final catalytic
polymer 1b (1.18 g, 99% yield) was obtained by shaking the
intermediate prolinate (1.50 g) in CH2Cl2 (15 mL) with TFA
(30 mL). FTIR (ATR, neat): ν 3430 (COOH), 2942, 2867,
1631 (C=O) cm-1. Elemental Analysis (%): Calcd.: N, 9.47.
Found: N, 8.26; f = 1.47 mmol g-1.
1c: The polynorbornene-supported t-butyl prolinate (a white
solid) was obtained from 7 (292 mg, 0.89 mmol), N,Ndiisopropylethylamine (1.2 mL, 6.90 mmol), copper(I)
iodide (3.3 mg, 0.017 mmol) and copolymer 4c (Copol-NBNBCH2N3 x/y = 1.3:1, n = 1; 233 mg, f = 2.96 mmol g-1) in
DMF:THF 1:1 (6 mL) after 23 h reaction in 98% yield (464
mg). [FTIR (ATR, neat): ν 2934, 2865, 1738 (C=O), 1698
(C=O), 1476, 1454, 1393 (t-butyl), 1365 (t-butyl), 1255,
1218 cm-1. Elemental Analysis (%): Calcd.: N, 8.46. Found:
N, 8.75; f = 1.56 mmol g-1]. Then final catalytic polymer 1c
(365 mg, 98% yield) was obtained by shaking the
intermediate prolinate (440 mg) in CH2Cl2 (4 mL) with TFA
(8 mL). FTIR (ATR, neat): ν 3416 (COOH), 2933, 2863,
1625 (C=O) cm-1. Elemental Analysis (%): Calcd.: N, 11.04.
Found: N, 10.56; f = 1.88 mmol g-1.
1d. The polynorbornene-supported t-butyl prolinate (a white
solid) was obtained from 7 (61 mg, 0.19 mmol), N,Ndiisopropylethylamine (250 mL, 1.43 mmol), copper(I)
iodide (1 mg, 5.74 mmol) and copolymer 4d (Copol-NBNB(CH2)4N3 x/y = 24.1:1, n = 4; 300 mg, f = 0.478 mmol g1
) in DMF:THF 1:1 (2 mL) after 24 h reaction in 92% yield
(320 mg). [FTIR (ATR, neat): ν 2940, 2865, 1743 (C=O),
1707 (C=O), 1451,1392 (t-butyl), 1366 (t-butyl), 1255, 1218
cm-1. Elemental Analysis (%): Calcd.: N, 2.31. Found: N,
1.91; f = 0.34 mmol g-1]. Then final catalytic polymer 1d
(280 mg, 98% yield) was obtained by shaking the
intermediate prolinate (300 mg) in CH2Cl2 (4 mL) with TFA
(8 mL). FTIR (ATR, neat): ν 2940, 2864, 1620 (C=O) cm-1.
Elemental Analysis (%): Calcd.: N, 2.48. Found: N, 2.09; f =
0.37 mmol g-1.
Synthesis of polymer 6b.
Bromoalkyl polynorbornene 3b (Copol-NB-NBCH2Br, x/y
= 1.6:1, 330 mg, f = 2.98 mmol g-1), toluene (21 mL), pethynylbenzoic acid (5, 393 mg, 2.69 mmol) and DBU (0.41
mL, 2.69 mmol) were mixed in a flask under N2, and the
mixture was heated under reflux for 22 h. The solvent was

evaporated and MeOH was added (30 mL). A solid
appeared, which was stirred for 30 min, filtered, washed
with MeOH (2 x 30 mL) and dried under reduced pressure at
40 ºC for 24 h. Compound 6b was obtained as a white solid
(375 mg) soluble in dichloromethane or THF, which
contained 73.3 mg of Br/g of copolymer, indicating that
substitution has proceeded to a 69% degree. 13C NMR (gelphase, 126 MHz, CDCl3): δ 166.3 (C=O), 132.2, 130.6,
129.6, 126.9, 83.0 (C=C), 80.2 (C=C), 56-52.8 (br), 52.250.2 (br), 47.9-45.9 (br), 43.7-41.6 (br), 40.2-38.6 (br), 36.834.4 (br), 32.2-31.0, 30.6-29.0 (br), 28.7-28.3 (br) ppm.
Raman: ν 2100 (C=C), 1720, 1600, 638 (C-Br) cm-1. FTIR
(ATR, neat): ν 3301 (=CH), 2942, 2866, 1719 (C=O), 1607,
1266 (C-O), 1173, 1094, 857, 768 cm-1.
Synthesis of catalyst 2.
(2S,4R)-N-Boc-4-azido-L-proline tert-butyl ester 8 (151 mg,
0.48 mmol), N,N-diisopropylethylamine (650 mL, 3.72
mmol) and copper(I) iodide (2 mg, 9.3 mmol) were added to
a solution of 4-ethynylphenyl-polynorbornene copolymer 6b
(220 mg) in THF (1.5 mL) placed in a flask under N2. The
reaction mixture was shaken at 40 ºC for 24 h, the reaction
progress being monitored by FTIR. When the IR band of the
alkynyl group had completely disappeared, the polymer was
collected by filtration, sequentially washed with H2O (20
mL), THF (20 mL), THF-MeOH (20 mL), MeOH (20 mL),
THF (20 mL) and CH2Cl2 (20 mL) and dried under reduced
pressure at 40 ºC for 24 h. The polynorbornene-supported
prolinate was obtained as an insoluble white solid (320 mg).
[FTIR (ATR, neat): ν 2942, 2867, 1709 (C=O), 1614 (C=O),
1392 (t-butyl), 1367 (t-butyl), 1266 (C-O) cm-1. Elemental
Analysis (%): Found: N, 5.05; f = 0.90 mmol g-1]. Then
polymer 2 (250 mg) was obtained by shaken the prolinate
(200 mg) in CH2Cl2 (1.5 mL) with TFA (1.5 mL). When the
IR bands of the t-butyl and carbonyl moieties in the
protecting groups had completely disappeared, the reaction
mixture was filtered off and the polymer was washed
sequentially with THF (with 2% of Et3N, 20 mL), H2O (20
mL), THF (20 mL), THF-MeOH 1:1 (20 mL), MeOH (20
mL), THF (20 mL) and CH2Cl2 (20 mL). The solid was
dried under reduced pressure at 40 ºC for 24 h. FTIR (ATR,
neat): ν 3431 (COOH), 2943, 2865, 1717 (C=O), 1615
(C=O), 1449, 1267 (C-O), 1177, 1100, 771 cm-1. Elemental
Analysis (%): Found.: N, 4.89; f = 0.87 mmol g-1.
General procedure for the asymmetric aldol reaction
catalyzed by polymers 1a-d.
Polynorbornene-supported proline 1 (0.015 mmol) was
swollen in 54 mL of a DMSO/H2O (87:13) mixture
containing TFA (0.015 mmol). The corresponding aldehyde
9a-j (0.15 mmol) and cyclohexanone (0.75 mmol) were
added and the reaction mixture was shaken at room
temperature. When the reaction is completed (see Table 3
and Scheme 4), dichloromethane (1 mL) was added and the
polymer was filtered off, washed with water (2 mL) and
dichloromethane (2 mL) and air-dried. The aqueous filtrate

was separated by decantation and extracted with
dichloromethane (3 x 10 mL). The combined organic phases
were washed with brine, dried (MgSO4) and concentrated
under reduced pressure.
Purification by flash column chromatography (ethyl
acetate/hexanes, 9:1 to 4:1) gave the aldol products 11aj as
mixtures of anti and syn diastereomers. Conversion and
diastereomeric ratio were determined by 1H NMR
spectroscopy on the crude samples after polymer removal.
The enantiomeric excess was determined by HPLC on a
chiral stationary phase after purification by flash column
chromatography on silicagel.

† Electronic Supplementary Information (ESI) available: Preparation
of compound 5, screening of additives and solvent and temperature
effects on the aldol reaction between 9a and 10a, recycling
experiments, spectroscopic and chromatographic data of the aldol
products, and characterization of the polymers are provided. See
DOI: 10.1039/b000000x/
1

Handbook of Green Chemistry & Technology, eds. J. Clark
and D. Mcquarrie, Blackwell Publ., London, 2002; (b) N.
E. Leadbeater and M. Marco, Chem. Rev. 2002, 102, 3217;
(c) C. A. McNamara, M. J. Dixon and M. Bradley, Chem.
Rev. 2002, 102, 3275; (d) Polymeric materials in organic

General procedure for the asymmetric aldol reaction
catalyzed by polymer 2.
Polynorbornene-supported proline 2 (0.015 mmol) was
swollen in a mixture of DMF/H2O (50:50, 54 µL). The
corresponding aldehyde 9a-j (0.15 mmol) and ketone 10a-c
(0.75 mmol) were added and the reaction mixture was stirred
at room temperature (see Scheme 5). After the indicated
time, dichloromethane (1 mL) was added and the polymer
was filtered off, washed with water (2 mL) and
dichloromethane (2 mL) and air-dried. The aqueous filtrate
was separated by decantation and extracted with
dichloromethane (3 x 10 mL). The combined organic phases
were washed with brine, dried (MgSO4) and concentrated
under reduced pressure. When required, purification by flash
column chromatography (ethyl acetate/hexanes, 9:1 to 4:1)
was performed to give the aldol products 11a-l as mixtures
of anti and syn diastereomers. Conversion and
diastereomeric ratio were determined by 1H NMR
spectroscopy on the crude samples after polymer removal.
The enantiomeric excess was determined by HPLC on a
chiral stationary phase after purification by flash column
chromatography on silicagel.

For reviews about polymer-supported catalysts, see: (a)

synthesis and catalysis, ed. M. R. Buchmeiser, WileyVCH, Weinheim, 2003; (e) M. Benaglia, A. Puglisi and F.
Cozzi, Chem. Rev. 2003, 103, 3401; (f) R. Haag and S.
Roller, Immobilized Catalysts in: Topics in Current
Chemistry, ed. A. Kirsching, Springer, Heidelberg, 2004;
(g)

Polymer-Supported

Reagents

and

Catalysts:

Increasingly Important Tools for Organic Synthesis, eds. P.
H. Toy and M. Shi, Tetrahedron 2005, 61, 12013; (h) B.
M. L. Dioos, I. F. J. Vankelecom and P. A. Jacobs, Adv.
Synth. Catal. 2006, 348, 1413; (i) S. Itsuno and N.
Haraguchi,

Heterogeneous

Enantioselective

Catalysis

Using Organic Polymeric Supports in Handbook of
Asymmetric Heterogeneous Catalysis, eds. K. Ding and Y.
Uozumi, Wiley-VCH, Weinheim, 2008; (j) Recoverable
and Recyclable Catalysts, ed. M. Benaglia, John Wiley &
Sons, Chichester, 2009; (k) K. E. Kristensen and T.
Hansen, Eur. J. Org. Chem. 2010, 3179.
2

C. Jimeno, S. Sayalero and M. A. Pericàs, Covalent
Heterogenization of Asymmetric Catalysts on Polymers and
Nanoparticles in Heterogenized Homogeneous Catalysts
for Fine Chemicals Production. Catalysis by Metal
Complexes, eds. P. Barbaro and F. Liguari, Springer,
Heidelberg, 2010, Vol. 33, chapter 4, pp. 123-170.

Acknowledgements

3

F. Cozzi, Adv. Synth. Catal. 2006, 348, 1367.

Financial support from Institute of Chemical Research of
Catalonia (ICIQ) Foundation, the Spanish MINECO (DGI,
grants CTQ2013-48406-P and CTQ2012-38594-C02-01),
DEC-Generalitat de Catalunya (Grant 2014SGR827) and the
Junta de Castilla y León (grant VA373A11-2) is gratefully
acknowledged. We also thank MINECO for support through
Severo Ochoa Excellence Accreditation 2014-2018 (SEV2013-0319). The authors thank Dr. Carles Lizandara for
valuable support in the characterization of polymers.

4

J. Lu and P. H. Toy, Chem. Rev. 2009, 109, 815.

5

(a) S. Martínez-Arranz, A. C. Albéniz and P. Espinet,
Macromolecules 2010, 43, 7482; (b) A. C. Albéniz, S.
Martínez-Arranz and P. Espinet, ES2364781A1.

6

addition polynorbornes in the Stille reaction see: (a) S.
Martínez-Arranz, N. Carrera, A. C. Albéniz, P. Espinet and
A. Vidal-Moya, Adv. Synth. Catal. 2012, 354, 3551; (b) I.
Meana, A. C. Albéniz and P. Espinet, Adv. Synth. Catal.
2010, 352, 2887; (c) N. Carrera, E. Gutierrez, R.

Notes and references
a

mapericas@iciq.es
b

IU CINQUIMA/Química Inorgánica, Universidad de Valladolid,

47071 Valladolid, Spain. E-mail: albeniz@qi.uva.es
c

Benavente, M. M. Villavieja, A. C. Albéniz and P. Espinet,

Institute of Chemical Research of Catalonia (ICIQ), Av. Països

Catalans 16, 43007 Tarragona, Spain. Fax: (+34)977920244; E-mail:

Departament de Química Orgànica, Universitat de Barcelona, 08028

Barcelona, Spain.

For examples of the use of tin reagents supported on vinyl

Chem. Eur. J. 2008, 14, 10141.
7

For recent examples see: (a) E. Alza, S. Sayalero, X. C.
Cambeiro, R. Martín-Rapún, P. O. Miranda and M. A.
Pericàs, Synlett 2011, 464; (b) X. C. Cambeiro, R. MartínRapún, P. O. Miranda, S. Sayalero, E. Alza, P. Llanes and
M. A. Pericàs, Beilstein J. Org. Chem. 2011, 7, 1486; (c) C.
Ayats, A. H. Henseler and M. A. Pericàs, ChemSusChem
2012, 5, 320; (d) X. Fan, S. Sayalero and M. A. Pericàs,

Adv. Synth. Catal. 2012, 354, 2971; (e) P. Kasaplar, C.

Tao, Catal. Lett. 2008, 120, 281. For cross-linked supports,

3498; (f) R. Martín-Rapún, S. Sayalero and M. A. Pericàs,

see: (c) F. Giacalone, M. Gruttadauria, A. M. Marculescu

Green Chem. 2013, 15, 3295; (g) X. Fan, C. Rodríguez-

and R. Noto, Tetrahedron Lett. 2007, 48, 255; (d) M.

Escrich, S. Sayalero and M. A Pericàs, Chem. Eur. J. 2013,

Gruttadauria, F. Giacalone, A. M. Marculescu, P. Lo Meo,

19, 10814; (h) L. Osorio-Planes, C. Rodríguez-Escrich and

S. Riela and R. Noto, Eur. J. Org. Chem. 2007, 4688. For

M. A. Pericàs, Chem. Eur. J. 2014, 20, 2397.

acrylic polymers, see: (e) T. E. Kristensen, K. Vestli, K. A.

(a) Modern Aldol Reactions, ed. R. Mahrwald, Wiley-

Fredriksen, F. K. Hansen and T. Hansen, Org. Lett. 2009,

VCH, Weinheim, 2004. For selected examples see: (b) D.

8

18, 2649. (b) Y.-X. Liu, Y.-N. Sun, H.-H. Tan and J.-C.

Rodríguez-Escrich and M. A. Pericàs, Org. Lett. 2013, 15,

11, 2968; (f) T. E. Kristensen, K. Vestli, M. G. Jakobsen, F.

Font, C. Jimeno and M. A. Pericàs, Org. Lett. 2006, 8,
4653; (c) D. Font, S. Sayalero, C. Jimeno and M. A.

K. Hansen and T. Hansen, J. Org. Chem. 2010, 75, 1620.
18

Pericàs, Org. Lett. 2008, 10, 337.
9

Y. Hayashi, T. Sumiya, J. Takahashi, H. Gotoh, T.
Urushima and M. Shoji, Angew. Chem. Int. Ed. 2006, 45,

(a) Centenary Lecture - 1,3-Dipolar Cycloadditions, R.
Huisgen, Proc. Chem. Soc. London 1961, 357; (b) R.

958.
19

(a) M. Gruttadauria, F. Giacalone and R. Noto, Adv. Synth.

Huisgen, 1,3-Dipolar Cycloaddition Chemistry, ed. A.

Catal. 2009, 351, 33; (b) J. Paradowska, M. Stodulski and

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10

Raj and V. K. Singh, Chem. Commun. 2009, 44, 6687.

P. P. Chu, W.-J. Huang, F.-C. Chang and S. Y. Fan,
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11

from the results of elemental analysis with the formulae:
For nitrogen containing functional resins: f (mmol g-1) =
0.714(%N)/nN, (%N) representing the weight percentage of
determined

by

elemental

analysis

and

nN

representing the number of nitrogen atoms in the functional
unit; For bromine containing functional resins: f (mmol g-1)
=

0.125(%Br)/nBr,

(%Br)

representing

the

weight

percentage of bromine determined by elemental analysis
and nBr representing the number of bromine atoms in the
functional unit.
12

(a) The maximal functionalization (fmax) of a given resin
can be calculated from the functionalization of a precursor
resin (f0) by means of the following formula: fmax (mmol g1

) = f0/(1 + f0(ΔMW/1000), where ΔMW represents the

variation in molecular mass of the functional unit along the
considered transformation(s); (b) Yield in reactions
involving functional resins is not related to mass recovery,
which is generally complete, but rather to the ratio between
actual functionalization (f) and maximal functionalization
(fmax) for the resin undergoing the considered process: yield
(%) = 100(f/fmax).
13

The equilibrium swelling ratio (SR) in each solvent was
determined gravimetrically with the formula: Swelling
Ratio (SR, %) = 100(Ws-Wdry)/Wdry, where Ws is the weight
of swollen samples after the certain time and Wdry is the
weight of dried samples.

14

P. M. Pinko, K. M. Laurikainen, A. Usano, A. I. Nyberg
and J. A. Kaavi, Tetrahedron 2006, 62, 317.

15

For the role of concentration effect in solvent-free aldol
reactions, see: (a) B. Rodríguez, T. Rantanen and C. Bolm,
Angew. Chem. Int. Ed. 2006, 45, 6924; (b) B. Rodríguez,
A. Bruckmann and C. Bolm, Chem. Eur. J. 2007,13, 4710.

16

J. Rudolph, N. Hermanns and C. Bolm, J. Org. Chem.
2004, 69, 3997.

17

K. Sakthivel, W. Notz, T. Bui and C. F. Barbas, III, J. Am.
Chem. Soc. 2001, 123, 5260.

The functionalization of a given resin can be calculated

nitrogen

20

For linear supports, see: (a) Y.-X. Liu, Y.-N. Sun, H.-H.
Tan, W. Liu and J.-C. Tao, Tetrahedron: Asymmetry 2007,