An efficient Cu(II)-bis(oxazoline)-based polymer immobilised ionic liquid phase catalyst for asymmetric carbon-carbon bond formation

Article abstract of DOI:10.1039/c3gc41378k

The asymmetric Diels-Alder reaction between N-acryloyloxazolidinone and cyclopentadiene and the Mukaiyama-aldol reaction between methylpyruvate and 1-phenyl-1-trimethylsilyloxyethene have been catalysed by heterogeneous copper(II)-bis(oxazoline)-based pol

Full text of DOI:10.1039/c3gc41378k

Green Chemistry
View Article Online
View Journal | View Issue
PAPER
An efficient Cu(II)-bis(oxazoline)-based polymer
immobilised ionic liquid phase catalyst for
asymmetric carbon–carbon bond formation†
Cite this: Green Chem., 2014, 16,
1470
Simon Doherty,*a Julian G. Knight,a Jack R. Ellison,a Peter Goodrich,b Leanne Hall,b
Christopher Hardacre,*b Mark J. Muldoon,b Soomin Park,b Ana Ribeiro,c
Carlos Alberto Nieto de Castro,c Maria José Lourençoc and Paul Daveyd
The asymmetric Diels–Alder reaction between N-acryloyloxazolidinone and cyclopentadiene and the
Mukaiyama-aldol reaction between methylpyruvate and 1-phenyl-1-trimethylsilyloxyethene have been
catalysed by heterogeneous copper(II)-bis(oxazoline)-based polymer immobilised ionic liquid phase
(PIILP) systems generated from a range of linear and cross linked ionic polymers. In both reactions
selectivity and ee were strongly influenced by the choice of polymer. A comparison of the performance
of a range of Cu(II)-bis(oxazoline)-PIILP catalyst systems against analogous supported ionic liquid phase
(SILP) heterogeneous catalysts as well as their homogeneous counterparts has been undertaken and their
relative merits evaluated.
Received 11th July 2013,
Accepted 9th December 2013
DOI: 10.1039/c3gc41378k
www.rsc.org/greenchem
Introduction
Over the past two decades ionic liquids (ILs) have been shown
to be extremely beneficial to a number of transition metal-cata-
lysed reactions including asymmetric catalysis.1 In this
respect, a range of chiral metal complexes of Pt, Zn, Cu and
Mg have been immobilised in ILs under homogeneous or het-
erogeneous (Supported Ionic Liquid Phase-SILP) conditions
and shown to be excellent catalysts for a host of important
asymmetric C–C bond forming reactions such as Diels–Alder
and Mukaiyama-aldol reactions, cyclopropanations and oxi-
dations, often with significant and marked enhancements in
rate and selectivity compared with the corresponding reaction
in conventional solvents.2 In the case of SILP catalysed Diels–
Alder reactions (Scheme 1), the presence of an IL film on the
silica oxide or carbon support proved crucial in maintaining
high conversions, good endo-selectivity and high levels of
Scheme 1 Asymmetric Diels–Alder reaction between N-acryloyloxazo-
lidinone and cyclopentadiene catalysed by 10 mol% Cu(II)-bis(oxazoline)
complexes.
enantioselectivity (ee).3 However, despite the success of SILP
catalysts some issues still limit the potential applications of
this concept including their low/poor mechanical stability,
leaching of IL into the solvent phase and the high cost of the IL.
Polymers with chirality incorporated into the backbone
have been widely studied as catalyst supports for a range of
asymmetric C–C bond forming reactions including Diels–Alder
cycloadditions, oxidations and hydrogenations.4–8 In contrast,
the concept of immobilising an ionic liquid in the form of a
cation-decorated polymer, e.g. in the form of a polyelectrolyte,
to combine the favourable properties of ionic liquids with the
advantages of heterogenisation as well as overcome leaching
and improve long term stability in asymmetric catalysis has
been far less studied.9,10 Selected examples include the use of
polymer-supported imidazolium based ILs in organocatalysed
nitroaldol reactions11 and enzyme-catalysed transesterifica-
tions.12 A Ru-BINAP complex immobilised on a polymer-
aNUCAT, School of Chemistry, Bedson Building, University of Newcastle upon Tyne,
Newcastle upon Tyne, NE1 7RU, UK. E-mail: simon.doherty@ncl.ac.uk;
Fax: +44 (0)191 222 6929; Tel: +44 (0)191 222 6537
bThe QUILL Research Centre, School of Chemistry and Chemical Engineering,
Queen’s University Belfast, Belfast BT9 5AG, UK. E-mail: c.hardacre@qub.ac.uk;
Fax: +44 (0)28 9097 4687; Tel: +44 (0)28 9097 4592
cDepartmento de Química e Bioquímica e Centro de Ciências Moleculares e Materiais
Faculdade de Ciências, Universidade de Lisboa, 1749-016 Lisboa, Portugal
dGivaudan, Schweiz AG, Überlandstrasse 138, CH-8600 Dübendorf, Switzerland
†Electronic supplementary information (ESI) available: 1H NMR, 13C NMR and
19F NMR spectra for the polymer precursors synthesised. TGA, SEM and FTIR
traces for the polymers used. HPLC traces of exo and endo-cycloadducts and
aldol adducts formed. See DOI: 10.1039/c3gc41378k
1470 | Green Chem., 2014, 16, 1470–1479
This journal is © The Royal Society of Chemistry 2014

View Article Online
Green Chemistry
Paper
Scheme 2 Asymmetric Mukaiyama-aldol reaction between methyl-
pyruvate and 1-phenyl-1-trimethylsilyloxyethene catalysed by 10 mol%
Cu(II)-bis(oxazoline) complex A.
Fig. 2 Pyrrolidinium monomers used to synthesise IPs 1–4.
9·NTf2 by metathesis with lithium bis{(trifluoromethyl)sulfo-
nyl}imide (Fig. 2). The corresponding cross-linker 10·NTf2
(Fig. 2) was prepared in an analogous manner by the reaction of 8
with 4-vinylbenzyl bromide followed by ion exchange of the
bromide with lithium bis{(trifluoromethyl)sulfonyl}imide;
both monomers were isolated in good yield as air-stable crys-
talline solids. Ionic polymers IP-1–4 were synthesised by the
AIBN-initiated radical co-polymerisation of 1-4-vinylbenzyl-
1-benzylpyrrolidinium
bis((trifluoromethyl)sulfonyl)imide
(9·NTf2) with styrene in methanol at 70 °C for 48 h; the cross-
linking was introduced by conducting the polymerisation with
the specified amount of divinylbenzene or 1,1-bis(4-vinylben-
zyl)pyrrolidinium bis((trifluoromethyl)sulfonyl)imide (10·NTf2)
and the degree of cross-linking varied by adjusting the amount
of added cross-linker. These in-house synthesised IPs were
compared with commercially available microporous gel-type
(IP-5) and macroreticular (IP-6) polymers which contain the tri-
methylammonium cation as well as the polystyrene (P-7) as a
non-ionic reference polymer.
Fig. 1 IPs 1–6 and polymer P-7 used in the immobilisation of Cu(II)-
bis(oxazoline) catalysts for the asymmetric Diels–Alder reaction. In
each case the degree of cross-linking (%DVB) and ionic loading
(mmol g−1) is shown.
Copper(II)-bis(oxazoline) complexes were selected for immo-
bilisation on the basis that they catalyse a host of asymmetric
C–C bond forming reactions and because they have been
studied on a variety of support materials which will enable the
relative merits of PIILP catalysis to be assessed. The bench-
mark Diels–Alder reaction between N-acryloyloxazolidinone
and cyclopentadiene catalysed by 10 mol% copper(II)-bis(oxa-
zoline) complexes was initially conducted in CH2Cl2, Et2O and
supported pyrrolidinium tetrafluoroborate has been applied to
the asymmetric hydrogenation of methylacetoacetate.13
Therein, high ee’s were obtained but the activity was lower
than in methanol under homogeneous conditions. Rhodium
and ruthenium complexes of phosphorylated BINAP have been
immobilised in polymer electrolytes and used to catalyse the
asymmetric hydroformylation of vinyl acetate and styrene14
and the asymmetric hydrogenation of dimethyl itaconate,14
respectively; the latter gave activities and selectivities that
matched those obtained under homogeneous conditions.
Having recently developed an efficient and recyclable per-
oxometalate-based polymer immobilised ionic liquid phase
oxidation catalyst using a cation-decorated ring opening
metathesis-derived polymer as support,15 we now report that
copper(II)-bis(oxazoline)-derived PIILP catalysts A and B either
rival or outperform their homogeneous or SILP counterparts
for the Diels–Alder (Scheme 1) and the Mukaiyama-aldol reac-
tion (Scheme 2). The ionic polymer structures tested (IP-1–6)
as well as polystyrene (P-7) used to support catalysts A and B
are shown in Fig. 1.
1-ethyl-3-methylimidazolium
bis{trifluoromethyl)sulfonyl}-
imide ([C2mim][NTf2]) under homogeneous, biphasic and SILP
conditions, full details of which are summarised in Table 1.
With the exception of Et2O, regardless of the choice of solvent
employed, catalyst A produced significantly higher ee’s and
endo selectivities than catalyst B. For both catalysts, under
homogeneous conditions, the presence of an IL either as an
additive (entries 4 and 5) or as a bulk solvent (entry 3) resulted
in higher conversions and ee’s compared with similar reac-
tions conducted in molecular solvents (entries 1 and 2).
With the aim of comparing the efficiency of polymer
immobilised ionic liquid supports against conventional SILP-
systems, catalysts A and B were also supported on SiO2 or
multi-walled carbon nanotubes (CNT) by wet impregnation
from dichloromethane using [C2mim][NTf2] as the ionic
liquid. Reactions were conducted in diethyl ether as the
solvent due to the low rates of reaction for the homogeneous
catalysts (entry 2) and the low solubility of [C2mim][NTf2] in
Results
1-(4-Vinylbenzyl)pyrrolidine 8 was prepared according to a lit- diethyl ether compared with dichloromethane, which should
erature procedure and reacted with benzylbromide in acetone reduce ionic liquid/catalyst leaching. A significant increase in
to afford 9·Br which was converted into the desired monomer both the ee and conversion was observed for reactions
This journal is © The Royal Society of Chemistry 2014
Green Chem., 2014, 16, 1470–1479 | 1471

View Article Online
Paper
Green Chemistry
Table 1 Comparison of the Diels–Alder reaction between N-acryloyloxazolidinone and cyclopentadiene catalysed by 10 mol% Cu(OTf)2/bis(oxazo-
line) complexes A and B in dichloromethane, diethyl ether and [C2mim][NTf2] under homogeneous conditions and on SiO2- and CNT-SILP under
heterogeneous conditions
Catalyst A
Catalyst B
Entry
Solvent/support
Time (min)
Conv.a,b (%)
endo eeb (%)
% endob
Conv.a,b (%)
endo eeb (%)
% endob
1
2
3
4
5
6
7
8
9
CH2Cl2
Et2O
IL
IL/Et2O
CH2Cl2/IL
SiO2
SiO2/IL
CNT
15
15
1
5
5
5
5
5
5
78
32
100
100
64
32
100
64
70(S)
14(S)
90(S)
91(S)
82(S)
16(S)
87(S)
66(S)
92(S)
88
87
89
89
96
88
85
87
87
44
38
100
100
100
76
100
44
100
16(R)
15(R)
19(R)
18(R)
16(R)
4(R)
8(R)
20(R)
3(R)
82
80
88
78
70
84
84
83
80
CNT/IL
100
a Conversion at 20 °C. b Determined by HPLC.
conducted using the SILP catalysts (entries 7 and 9) in com- of the less coordinating [NTf2]− anion compared with the [OTf]−
parison to the analogous heterogeneous reactions conducted anion in the original catalyst.17 Further studies are required to
in the absence of a [C2mim][NTf2] film (entries 6 and 8). In the fully understand the role of the anion and nature of the
case of the SiO2 support (entry 6) the very low conversion and support.
ee could be due to the role of the surface silanols which can
In order to further explore the effect of an ionic environ-
promote cyclopentadiene dimerisation and act as a non-chiral ment, catalysts A and B were supported on IPs 1–6 and non-
active catalyst.16 Moreover, both SiO2 and CNT supported ionic polymer P-7 using wet impregnation from dichloro-
systems based on catalyst A gave better conversions and mark- methane. The efficacy of the resulting PIILP catalysts for the
edly higher ee’s (entries 7 and 9) than that obtained for homo- asymmetric Diels–Alder reaction conducted between N-acryloyl-
geneous reactions using molecular solvents (entries 1 and 2). oxazolidinone and cyclopentadiene in diethyl ether was inves-
In all cases, the configuration of the Diels–Alder adduct was tigated and compared with the corresponding systems
identical to those obtained under homogenous conditions in modified with a thin film of IL; the results of which are sum-
both ionic liquid and molecular solvents. These results indi- marised in Table 2 and will be compared with the systems
cate that heterogenisation of a chiral catalyst in an ionic reported in Table 1. In agreement with previous studies per-
environment can lead to a marked improvement in perform- formed using these catalysts in ionic liquids3 the active PIILP
ance compared with the corresponding homogeneous and catalyst was formed after only 5 min by stirring a dichloro-
‘non-ionic’ heterogeneous systems; however, this enhancement methane solution of Cu(OTf)2 and bis(oxazoline) in the pres-
appears to be catalyst specific. Although support effects can ence of ionic polymer; for comparison much longer aging
influence the reaction the enhancement observed in the bulk times (>3 h) are generally required to achieve efficient and
IL and SILP systems could be, in part, due to the large excess reproducible catalysis in molecular solvents.1
Table 2 Comparison of asymmetric Diels–Alder reaction between N-acryloyloxazolidinone and cyclopentadiene using catalysts A and B immobi-
lised onto a range of polymer supports and polymer-IL supports
Catalyst A
Catalyst B
Entry
Polymer
Solvent
Conv.a,b (%)
endo eeb (%)
% endob
Conv.a,b (%)
endo eeb (%)
% endob
1
2
3
4
5
6
7
8
IP-1
IP-1
IP-2
IP-2
IP-3
IP-3
IP-4
IP-4
IP-5
IP-5
IP-6
IP-6
P-7
Et2O
IL/Et2O
Et2O
IL/Et2O
Et2O
IL/Et2O
Et2O
IL/Et2O
Et2O
IL/Et2O
Et2O
IL/Et2O
Et2O
IL/Et2O
86
100
80
65
69
77
100
60
27
98
47
91
0
90(S)
99(S)
48(S)
31(S)
28(S)
69(S)
99(S)
80(S)
7(S)
88
95
92
85
86
89
93
91
88
88
84
91
0
100
100
100
100
100
100
100
100
100
100
100
99
35(R)
27(R)
32(R)
26(R)
38(R)
15(R)
41(R)
31(R)
16(R)
18(R)
38(R)
18(R)
0
78
76
79
74
73
76
76
73
92
79
80
91
0
9
10
11
12
13
14
9(S)
44(S)
84(S)
0
0
100
P-7
74
84(S)
88
30(R)
73
a Conversion at 20 °C after 5 minutes. b Determined by HPLC.
1472 | Green Chem., 2014, 16, 1470–1479
This journal is © The Royal Society of Chemistry 2014

View Article Online
Green Chemistry
Paper
Reference systems generated by adsorbing catalysts A and B endo selectivity (entries 4 and 8). PIILP systems based on cata-
onto the non-ionic polymer (P-7) were completely inactive lyst B and IP’s 1–6 showed much smaller changes in ee but
when reactions were conducted in diethyl ether in the absence larger variations in endo/exo selectivity in the presence of an IL
of additional ionic liquid (entry 13), even after the catalyst was film in comparison to the changes observed with catalyst A
aged for 3 h. In contrast, significant conversions were obtained under comparable conditions. Moreover, in contrast to catalyst
for reactions performed with PIILP systems based on IP-1–6. In A, with the exception of IP-5, all of the IPs showed a decrease
general, higher ee’s were obtained with PIILP-systems gener- in ee upon the addition of an IL thin film. Despite this
ated by immobilisation of catalysts A and B onto the in-house decrease in ee, all of the PIILP catalyst-IL combinations gave
synthesised polymers IP-1–4 (entries 1–8) compared with those higher or equivalent ee’s compared with the same reactions
based on commercially available IP-5–6 (entries 9–12). More- conducted under homogeneous conditions in dichloro-
over, for both catalysts the most efficient PIILP systems were methane (Table 1).
those based on IP-4 with catalyst A giving cycloadduct endo-
While exceptionally high ee’s and endo/exo ratios have been
(2S) in 99% ee and catalyst B giving cycloadduct endo-(2R) in achieved using PIILP and PIILP/IL catalysts, the disparate and
41% ee at 100% conversion (entry 7). The former is the highest unpredictable variations in enantioselectivity and endo/exo
ee reported, to date, for a copper(II)-catalysed reaction of this selectivity as a function of the catalyst and ionic support or
substrate combination at room temperature under hetero- support-ionic liquid combination highlights the importance of
geneous or homogeneous conditions. In addition, the ee of developing a rational understanding of how catalyst–support
90% (S) obtained with PIILP catalyst based on IP-1 and catalyst interactions influence catalyst efficacy.
A (entry 1) also matched that obtained in neat ionic liquid and
Reasoning that a polymer immobilised ionic liquid phase
ionic liquid-diethyl ether (Table 1, entries 3–4). The significant support should effectively retain the catalyst, reusability exper-
difference between the reactions using the ionic and non-ionic iments were conducted on PIILP catalysts derived from A and
polymers is thought to be due to the reduced binding of the IP-1 and IP-6 as well as the corresponding catalysts immobi-
complex on the latter support. In this regard, leaching of up to lised onto SiO2, with and without a thin film of IL (Table 3).
50% of the copper into the diethyl ether phase for polymer P-7 Both PIILP catalysts recycled poorly with a significant decrease
together with a strong interaction of the cyclopentadiene with in ee and conversion upon successive recycles (entries 1–3
the polystyrene support were thought to be responsible for and 6–7).
catalyst inactivity.
ICP analysis of the diethyl ether used to extract the product
As supporting catalysts A and B in a thin IL film coated between recycles revealed that this procedure removed 4.2%
onto CNT and SiO2 supports was shown to have a beneficial and 8.0% of the copper from IP-1 and IP-6 respectively. Ligand
effect on reaction activity/selectivity (Table 1), the influence of leaching of 10.2% from IP-1 and 14.3% from IP-6 was also
combining [C2mim][NTf2] with polymers 1–7 was also studied. determined by HPLC. The addition of an IL film to both PIILP
Encouragingly, in some cases, the introduction of ionic liquid catalysts resulted in an increase in conversion and ee (entries
led to a marked increase in catalyst performance. The most 4–5 and 8–9) and a significant reduction in copper leaching to
significant increase in ee and conversion was obtained for 0.2% for systems based on both IP-1 and IP-6, respectively.
catalyst A immobilised on IP-6 which gave cycloadduct endo- Moreover, for the PIILP-IL systems the level of ligand leaching
(2S) in 84% ee and 91% conversion in the presence of ionic was below the limit of quantification by HPLC analysis.
liquid compared with 44% ee and 47% conversions in the However, these levels of copper/ligand leaching observed with
absence of [C2mim][NTf2] (entries 11–12). An enhancement in
ee was also achieved when a thin film of [C2mim][NTf2] was
added to PIILP systems based on catalyst A immobilised on
IP-1 and IP-3 (entries 1–2 and 5–6) with IP-3 giving the most
marked enhancement in ee from 28% to 69% (Δee = 41%);
however, there was little change in endo/exo-selectivity and con-
version. While the addition of ionic liquid to the catalyst immobi-
lised on P-7 also resulted in a marked improvement in conversion
(entry 14), it was not possible to quantify the enhancement in
ee as both catalysts are completely inactive in the absence of
ionic liquid (entry 13). In contrast, the increase in ee from
90% to 99% for the IP-1/catalyst A/[C2mim][NTf2] combination
was accompanied by an increase in endo/exo selectivity from
88% to 95%; the performance of this system matched that of
IP-4 in diethyl ether. Although IP-5 also showed a marked
increase in conversion in the presence of [C2mim][NTf2], there
was no significant change in ee which remained very poor,
(entry 10). Conversely, for IPs 2 and 4 the presence of a thin
Table 3 Recycle of the Diels–Alder reaction between N-acryloyloxazo-
lidinone and cyclopentadiene using catalyst A immobilised on IPs and
SiO2 with and without additional IL
Entry
Support
Run
Conv.a,b (%)
endo eeb (%)
% endob
1
2
3
4
5
6
7
8
1
2
3
1
2
1
2
1
2
1
2
1
2
3
86
68
30
100
98
47
90(S)
73(S)
7(S)
88
86
85
95
77
86
IP-1
IP-1/IL
IP-6
99(S)
74(S)
44(S)
No reaction
84(S)
88(S)
54(S)
43(S)
87(S)
84(S)
81(S)
IP-6/IL
SiO2
91
41
90
91
92
85
84
86
85
86
9
10
11
12
13
14
83
SiO2/IL
100
100
93
layer of ionic liquid led to a significant reduction in ee and a Conversion at 20 °C after 5 minutes. b Determined by HPLC.
This journal is © The Royal Society of Chemistry 2014
Green Chem., 2014, 16, 1470–1479 | 1473

View Article Online
Paper
Green Chemistry
PIILP catalysts in the presence or absence of an IL film do not compared with dichloromethane and diethyl ether was also
explain the significant drop in conversion and/or ee observed observed; however, this was offset by the formation of a minor
upon recycle. In addition, no significant change in the amount (∼10%) of by-product, identified by 1H NMR spec-
polymer structure as determined by infra-red spectroscopy was troscopy as 3-hydroxy-1,3-diphenyl-butan-1-one. Interestingly,
observed on recycle (see ESI† for data on IP-1 which showed this by-product was only generated during reactions conducted
the largest decrease in activity).
in ionic liquid and there was no evidence for its formation
The drop in catalyst activity upon recycle for PIILP systems during reactions catalysed by the PIILP, PIILP/IL or SILP
based on catalyst A is thought to be mainly attributed to the systems. This by-product results from a Mukaiyama-aldol reac-
build-up of cyclopentadiene dimer18 on the support surface, as tion between 1-phenyl-1-trimethylsiloxyethene and acetophe-
has been previously observed in other SILP catalysed Diels– none, the latter of which is generated via hydrolysis of the
Alder reactions.3 This proposal was supported by a reduction 1-phenyl-1-trimethylsiloxyethene substrate.2 In addition, both
in conversion from 86% to 32% and a drop in ee from 90% to SILP catalysts gave complete conversion in short reactions
19% upon addition of cyclopentadiene dimer (10 molar times with only a slight reduction in ee compared with the
equivalents with respect to substrate) to the ethereal layer of a homogenous reaction conducted in ionic liquid (entries 5–6).
freshly prepared PIILP system derived from IP-1 and catalyst A. In contrast to the SILP-based catalysts, in general, the ee’s and
While the PIILP and PIILP-IL catalysts performed poorly upon conversions obtained with the PIILP and PIILP/IL system were
recycle the SiO2-based SILP system maintained high conver- lower than found under homogeneous conditions. For the
sions and good ee’s upon recycle.3 This was thought to be PIILP and PIILP/IL catalysts derived from IP-2, ee’s of 86% and
associated with more efficient removal of the cyclopentadiene 90% were obtained, respectively, which are comparable with
dimer from the hydrophilic silica than from the surface of the those obtained under homogeneous IL or SILP conditions,
lipophilic IP. In this regard, studies are currently underway to albeit it with slightly lower conversions (entries 9 and 10). For
explore the effect on recycle efficiency of increasing the hydro- comparison, the reference system generated by supporting
philicity of the polymer by introducing PEG-derived co-mono- catalyst A on the non-ionic polymer P-7 were completely in-
mers or PEG-functionalised pyrrolidinium monomers.
active even in the presence of an IL film (entries 15–16). A high
Encouraged by the enhancement in performance obtained ee has previously been achieved for the Mukaiyama-aldol reac-
with selected PIILP catalysts, testing was extended to include a tion between ketene thioacetal and methyl pyruvate under het-
comparison of the Mukaiyama-aldol reaction (Scheme 2) cata- erogeneous conditions using an insoluble polymer-bound
lysed by 10 mol% copper(II)-bis(oxazoline) catalyst A under copper(II)-bis(oxazoline) catalyst; however, while the ee of 91%
homogeneous conditions in various solvents and under het- was comparable to that of the 93% obtained under homo-
erogeneous conditions with SILP and PIILP-based catalysts, geneous conditions the heterogeneous system was less active
full details of which are summarised in Table 4. Complete con- and required markedly longer reaction times to reach similar
version was achieved within 1 min at room temperature with conversions.19
catalyst A in the ionic liquid whereas only moderate conver-
sions were obtained after 15 min in dichloromethane and
diethyl ether (entries 1–3). A markedly higher ee in the ionic liquid
Discussion
For a microporous gel-type polymer, and to a lesser extent
macroporous polymers, a lack of swelling renders non-surface
Table 4 Mukaiyama-aldol reaction between 1-phenyltrimethoxysilane
and methylpyruvate using catalyst A under homogeneous, SILP and
catalytic sites less accessible.20 The negligible swelling for
some of these IPs in diethyl ether could result in poor catalyst
access and account for the poor conversions and low ee’s
obtained with catalyst A observed in the Diels–Alder reaction;
however, this explanation is not consistent with the complete
conversions observed with catalyst B under the same con-
ditions. In addition, it should be noted that the use of
dichloromethane and toluene as solvents to deliberately swell
the polymers during the Diels–Alder reaction resulted in com-
plete stripping of both catalysts A and B from PIILP systems
derived from IP-1, 4, 5 and 6. Therefore, although the effect of
solvent on the polymer structure and the reaction cannot be
ignored, the disparate variations in activity and ee are more
likely to be due to geometric constraints imposed by the
support on catalyst A containing the bulky (S,S)-t-Bu-Box, as
previously postulated. For example, it has been suggested that
the square planar geometry adopted by catalyst A is signifi-
cantly more sensitive to geometric changes upon interaction
PIILP conditions
Entry
System
Time (min)
Conv.a (%)
eeb (%) config
1
2
CH2Cl2
Et2O
15
15
1
5
5
5
5
5
5
5
5
5
5
5
5
5
43
32
100
100
100
100
49
47
63
56
56
69
36
55
0
82(S)
80(S)
89(S)
84(S)
86(S)
85(S)
24(S)
11(S)
86(S)
90(S)
13(S)
48(S)
40(S)
63(S)
—
3
4
5
6
IL
IL/Et2O
SiO2/IL
CNT/IL
IP-1
7
8
9
IP-1/IL
IP-2
10
11
12
13
14
15
16
IP-2/IL
IP-4
IP-4/IL
IP-6
IP-6/IL
P-7
P-7/IL
0
—
a Conversion at 20 °C determined by IH-NMR. b Determined by HPLC.
1474 | Green Chem., 2014, 16, 1470–1479
This journal is © The Royal Society of Chemistry 2014

View Article Online
Green Chemistry
Paper
with the support compared with the smaller and more flexible multiple active geometries could be responsible for the higher
(S,S)-Ph-Box in catalyst B.3,21 For catalyst A this leads to an conversions observed in comparison to catalyst A. Moreover,
equilibrium between the copper-bis(oxazoline) complex and these active catalysts can give cycloadducts with opposite con-
non-chiral catalytically active ligand free copper.22 By analogy, figurations which would result in a reduction in the product
the high degree of cross-linking in IP-3 and 6 could disrupt ee. Such a number of active catalyst geometries could also be
the square planar complex and, thereby, decreases the catalyst the origin of the large differences in endo selectivity which has
selectivity. For example, polymer supported copper-bis(oxazo- not been previously observed for similar reactions conducted
line) complexes derived from catalysts A and B have been pre- using SILP based silica and carbon supports.3
pared by grafting and their performance in the
As previously established, an ionic environment in SILP
cyclopropanation of styrene with diethyl azoacetate com- conditions is required for higher catalyst performance, there-
pared.23 The introduction of cross-linking into this system fore, it is also possible that the number and distribution of
resulted in a deterioration of trans/cis selectivity and a signifi- ionic sites in the polymer can influence the selectivity of
cant drop in ee compared with the corresponding reaction the reaction.27 In this study, the concentration of ions at the
conducted under homogeneous conditions. It was thought surface of the polymers is significantly higher than the
that the low catalytic activity was due to the support mor- loading of the Cu. For example, catalyst A/B loadings of
phology, which resulted in little interaction between the 0.1 mmol g−1 on the support are significantly lower than
Cu(OTf)2 and the covalently tethered bis(oxazoline) which was surface concentration of [NTf2]− present. For example, IP-5 has
buried in the cross-linked polymer. A significant drop in ee for an anion concentration of 0.99 mmol g−1. It may be expected
Nafion-polymer immobilised catalyst A compared with that that if the anion were the major determining factor with
obtained for the homogenous reaction was also attributed to respect to enantioselectivity, increasing anion concentration
steric interactions between the chiral ligand and the support would lead to high ee’s; however, the converse is observed with
which shifted the metal–ligand equilibrium in favour of the higher ee’s found for IP-1 and IP-4 which have [NTf2]− concen-
active non-chiral ligand free form. The corresponding Nafion- trations of 0.68 mmol g−1 and 0.76 mmol g−1, respectively,
polymer immobilised catalyst B experienced a much smaller compared with IP-5. This provides further evidence that it is
reduction in ee compared with the homogeneous reaction, the structure of the support and the support–IL–catalyst inter-
which may reflect a more favourable metal–ligand equilibrium actions that determine the catalyst activity/selectivity rather
due to the smaller size of the ligand. Therefore, the improve- than simply the concentration of ions present.
ment in performance for the Diels–Alder reaction achieved by
addition of an IL thin film to PIILP systems derived from cata-
lyst A and IP-3 or IP-6 could be due to stabilization of the cata-
lyst and lower metal/ligand leaching. In this regard, catalyst
Conclusions
stabilisation is thought to occur by migration of the catalyst In summary, a number of Cu(II)-bis(oxazoline)-derived polymer
away from the polymer surface into the IL film which reduces supported ionic liquid phase systems have been prepared and
unfavourable catalyst–support interactions. Moreover, ILs are evaluated as catalysts for the asymmetric Diels–Alder and
known to swell polymers and this could also help to improve Mukaiyama-aldol reactions. For the Diels–Alder reaction, in
access to catalytic sites that were previously inaccessible.24 the majority of cases catalysts based on in-house synthesised
Similarly, catalyst access and poor catalyst stability could also IPs 1–4 were more active/selective than those prepared from
be responsible for the decreased conversions and ee’s observed commercial IPs 5–6 and, in some cases, gave higher endo selec-
for the Mukaiyama-aldol reaction catalysed by PIILP systems tivities and ee’s compared with the corresponding homo-
based on IP-4 and IP-6 in combination with catalyst A. An geneous reactions conducted in molecular solvents or IL or
increase in cross-linking has previously been associated with a under heterogeneous SILP conditions. For the Mukaiyama-
reduction in ee for the asymmetric Mukaiyama-aldol reaction aldol reaction, only catalyst A supported on the in-house syn-
using
a
polymer supported chiral Lewis acid catalyst.25 thesised IP-2 gave an ee that was comparable to those obtained
However, in the current study, the IP-2 derived PIILP system under homogeneous IL and SILP conditions. The contrasting
outperformed that based on IP-1 despite the former being conversions and ee’s for both reactions involving non-covalent
cross-linked while the latter was based on a linear polymer.
immobilisation of Cu-catalysts highlights the complex nature
For catalyst B smaller changes in the Diels–Alder cyclo- of these PIILP systems. The successful employment of IPs to
adduct ee were observed over the range of polymers studied. support copper-bis(oxazoline) catalysts suggests that tailoring
However, for all PIILP and PIILP-IL systems studied signifi- the ionic environment on a support may be sufficient to
cantly higher conversions were obtained than the corres- enhance catalyst stability and maximise catalyst efficiency.
ponding homogeneous reactions (Table 1) which highlights a Therefore, ionic solvation of these metal triflate complexes pre-
positive/synergistic influence of the catalyst–polymer–IL inter- viously encountered in a bulk IL or under SILP conditions is
action compared with the IL–catalyst interaction. It has been not paramount to maximise catalyst efficiency. To this end it
well-documented that for catalyst B the metal–ligand complex will be challenging but necessary to develop an understanding
exists as an equilibrium of several different geometries, all of of how the ionic microenvironment of the polymer influences
which are active catalysts,26 and thus the presence of such catalyst efficiency if this concept is to be fully realised and
This journal is © The Royal Society of Chemistry 2014
Green Chem., 2014, 16, 1470–1479 | 1475

View Article Online
Paper
Green Chemistry
applied to a wider range of substrate combinations and cataly- 10.6 Hz, 1H, HaCvCHbHc), 5.71 (d, J = 17.4 Hz, 1H,
tic processes. HaCvCHbHc), 5.16 (d, J = 10.5 Hz, 1H, HaCvCHbHc), 3.56 (s,
Although these PIILP systems showed excellent initial 2H, Ar–CH2–N), 2.46 (m, 4H, N–CH2), 1.73 (m, 4H, pyrrolidine
activity/selectivity, deleterious results were observed upon N–CH2–CH2). 13C{1H} NMR (100.52 MHz, CDCl3, δ): 139.03,
recycle which appeared to be due to the polymer interactions 136.55, 128.93, 125.97, 113.20, 60.33, 54.05, 23.34.
with the highly reactive cyclopentadiene and its dimer. In this
1-Benzyl-1-(4-vinylbenzyl)pyrrolidinium bromide (9·Br)
regard, it should be possible to develop a highly active and
recyclable catalytic system by tailoring the ionic polymer to A round bottom flask was charged with 8 (3.38 g, 18.0 mmol),
minimise these negative interactions.
benzyl bromide (4.2 cm3, 27.0 mmol) and acetonitrile
(20 cm3). The yellow solution was allowed to stir at room temp-
erature for 19 h after which time the reaction mixture was
added drop-wise to vigorously stirred diethyl ether
(ca. 500 cm3) to induce precipitation of the product. The resul-
tant yellow-white solid was isolated by filtration, washed with
diethyl ether and dried under high vacuum to give 9·Br as a
yellow-white powder in 82% yield (5.32 g). 1H NMR
(399.78 MHz, CDCl3, δ): 7.57 (m, 4H, Ar–H), 7.39 (m, 5H,
Ar–H), 6.66 (dd, J = 17.4, 10.6 Hz, 1H, HaCvCHbHc), 5.79 (d,
J = 17.4 Hz, 1H, HaCvCHbHc), 5.34 (d, J = 10.6 Hz, 1H,
HaCvCHbHc), 5.04 (s, 4H, Ar–CH2–N), 3.68 (m, 4H, N–CH2),
2.04 (m, 4H, pyrrolidine N–CH2–CH2); 13C{1H} NMR
(100.52 MHz, CDCl3, δ): 139.59, 135.48, 133.46, 133.22, 130.49,
129.15, 127.71, 126.92, 126.75, 116.12, 63.31, 57.64, 21.28;
Anal. Calcd for C20H24BrN: C, 67.04; H, 6.75; N, 3.91. Found:
C, 67.19; H, 7.11; N, 4.23; HRMS (ESI+): exact mass calcd for
C20H24N [M+] m/z 278.1909, found m/z 278.1904.
Experimental
Unless otherwise stated all reagents (ex Aldrich) were used as
received. Diethyl ether and dichloromethane were dried and
degassed prior to use. 1-Ethyl-3-methylimidazolium bis{(tri-
fluoromethyl)sulfonyl}imide, [C2mim][NTf2], was prepared in
house and after drying for 24 h at 60 °C under a high vacuum
whilst stirring, was found to contain <0.10 wt% water, deter-
mined by Karl-Fischer analysis, and <10 ppm halide, deter-
mined by suppressed ion chromatography.28
SI1320 silica support was obtained from GRACE Davison
and calcined at 400 °C prior to use. Carbon nanotubes were
obtained from Bayer Material Science. Commercial polymers
IRA-400 and IRA-900 were purchased from Aldrich as Cl− salts
and exchanged into the [NTf2]− form using LiNTf2 forming the
corresponding IPs 5 and 6. Polystyrene P-7 was used as
received.
All polymers were ground using a mortar and pestle and
particles of <250 μm were used for catalyst immobilisation. For
the Diels–Alder reaction the endo selectivity and conversions
were determined by HPLC and the ee’s based on the endo
isomer were calculated from the HPLC profile using a Chiralcel
OD-H column (hexane : propan-2-ol 90 : 10 flow rate 1 cm3
min−1 at 210 nm. The retention times of the endo enantiomers
were major (2S)-enantiomer tR ∼ 18 min and minor (2R)-enan-
tiomer tR ∼ 20 min.
1-Benzyl-1-(4-vinylbenzyl)pyrrolidinium bis{(trifluoromethyl)-
sulfonyl}imide (9·NTf2)
A
solution of lithium bis{(trifluoromethyl)sulfonyl}imide
(4.82 g, 16.8 mmol) in distilled water (30 cm3) was added drop-
wise to a rapidly stirred solution of 9·Br (3.00 g, 8.4 mmol) in
dichloromethane (30 cm3) and allowed to stir under ambient
conditions for 30 min. The organic layer was then extracted
and washed with distilled water (20 cm3) repeatedly, checking
the aqueous washings for bromide content with AgNO3. After
the third wash the aqueous extract did not become turbid
upon the addition of AgNO3, the organic layer was then dried
in vacuo to give the product as a yellow/white crystalline solid
in 92% yield (4.32 g). 1H NMR (399.78 MHz, CDCl3, δ): 7.57
(m, 4H, Ar–H), 7.39 (m, 5H, Ar–H), 6.66 (dd, J = 17.4, 10.6 Hz,
1H, HaCvCHbHc), 5.79 (d, J = 17.4 Hz, 1H, HaCvCHbHc), 5.34
(d, J = 10.6 Hz, 1H, HaCvCHbHc), 5.04 (s, 4H, Ar–CH2–N), 3.68
(m, 4H, N–CH2), 2.04 (m, 4H, pyrrolidine N–CH2–CH2); 13C{1H}
NMR (100.52 MHz, CDCl3, δ): 139.59, 135.48, 133.46, 133.22,
For the Mukaiyama-aldol reaction, conversions and selecti-
1
vity were determined by H-NMR. Enantioselectivity was calcu-
lated from the HPLC profile using a Chiralcel OD-H column
(hexane : propan-2-ol 96 : 4 flow rate 1 cm3 min−1 at 254 nm.
The retention times of the enantiomers were major (2S)-enan-
tiomer tR ∼ 23 min and minor (2R)-enantiomer tR ∼ 19 min.
1-(4-Vinylbenzyl)pyrrolidine (8)
An oven-dried Schlenk flask was charged with hexane (25 cm3) 130.49, 129.15, 127.71, 126.92, 126.75, 116.12, 63.31, 57.64,
and 4-vinylbenzyl chloride (4.6 cm3, 32.8 mmol) and cooled 21.28. 19F NMR (376.17 MHz, CDCl3, δ): −78.67 (s, NTf2); Anal.
using ice water. Pyrrolidine (5.4 cm3, 65.6 mmol) was added to Calcd for C22H24F6N2O4S2: C, 47.31; H, 4.33; N, 5.02. Found: C,
the cooled mixture over the course of 1 h causing an instant 47.49; H, 4.67; N, 5.33; HRMS (ESI+): exact mass calcd for
colour change of cloudy white to clear yellow. Following the C20H24BrN [M+] m/z 278.1909, found m/z 278.1904.
complete addition of pyrrolidine the reaction vessel was
1,1-Bis(4-vinylbenzyl)pyrrolidin-1-ium bromide (10·Br)
removed from the ice water and allowed to stir for 19 h at
room temperature after which time the mixture was filtered A round bottom flask was charged with 8 (0.66 g, 3.5 mmol),
and the solvent removed under reduced pressure to give the 4-vinylbenzyl bromide (0.82 g, 4.2 mmol) and acetonitrile
product as a yellow oil in 98% yield (6.02 g). 1H NMR (4 cm3), the mixture was then allowed to stir under ambient
(399.78 MHz, CDCl3, δ): 7.31 (m, 4H, Ar–H), 6.66 (dd, J = 17.4, conditions for 18 h. The product was precipitated by the drop
1476 | Green Chem., 2014, 16, 1470–1479
This journal is © The Royal Society of Chemistry 2014

View Article Online
Green Chemistry
Paper
wise addition of the reaction mixture into rapidly stirred by filtration, washed with diethyl ether and finally dried under
diethyl ether (ca. 100 cm3) and them isolated by filtration and high vacuum. Each of the polymers was isolated as an off
dried under high vacuum to give 10·Br as a yellow/white white crystalline solid.
powder in 74% yield (1.00 g). 1H NMR (399.78 MHz, CDCl3, δ):
7.55 (m, 4H, Ar–H), 7.42 (m, 4H, Ar–H), 6.67 (dd, J = 17.4,
General procedure for anion exchange for the commercial
resins
10.6 Hz, 2H, HaCvCHbHc), 5.81 (d, J = 17.4 Hz, 2H,
HaCvCHbHc), 5.34 (d, J = 10.6 Hz, 2H, HaCvCHbHc), 5.03 (s,
A solution of lithium bis{(trifluoromethyl)sulfonyl}imide
4H, Ar–CH2–N), 3.47 (m, 4H, CH2–N–CH2), 2.05 (m, 4H (1.00 g, 3.49 mmol) in distilled water (30 cm3) was added drop-
N–CH2–CH2); 13C{1H} NMR (100.52 MHz, CDCl3, δ): 139.6, wise to a rapidly stirred slurry of either IRA-400 or IRA-900
135.5, 133.5, 126.9, 126.8, 116.2, 63.1, 57.6, 21.3; Anal. Calcd (2.00 g) in distilled water (30 cm3) and allowed to stir under
for C22H26BrN: C, 68.75; H, 6.82; N, 3.64. Found: C, 69.08; H, ambient conditions for overnight. The aqueous layer was
7.11; N, 3.89; HRMS (ESI+): exact mass calcd for C22H26N [M+] removed and the resin was washed with distilled water
m/z 304.2065, found m/z 304.2054.
(20 cm3) for 1 h. This process was repeated a further two times
with fresh water. After the third wash the resin was dried
in vacuo at 60 °C for a minimum of 48 h or until no further
mass loss was recorded. The resultant ionic polymer was then
1,1-Bis(4-vinylbenzyl)pyrrolidin-1-ium bis((trifluoromethyl)-
sulfonyl)imide (10·NTf2)
A
solution of lithium bis{(trifluoromethyl)sulfonyl}imide used as a heterogeneous support for the Diels–Alder reaction.
(1.12 g, 3.9 mmol) in distilled water (5 cm3) was added drop
wise to a rapidly stirred solution of 10·Br (0.5 g, 1.3 mmol) in
dichloromethane (5 cm3) and allowed to stir under ambient
conditions for 30 min. The organic layer was then extracted
and washed with distilled water (10 cm3) repeatedly, checking
General procedure for the homogeneous Lewis acid catalyzed
Diels–Alder and Mukaiyama-aldol reactions in molecular
solvents
A
flame dried Schlenk flask was charged with ligand
the aqueous washings for bromide content with AgNO3. After (0.011 mmol), Cu(OTf)2 (0.010 mmol, 10 mol%) and dichloro-
the third wash the aqueous extract did not become turbid methane (5 cm3) and the resulting solution stirred at room
upon the addition of AgNO3, the organic layer was then dried temperature for 3 h to afford a clear green solution. Thereafter,
in vacuo to give the product as a off-white crystalline solid in N-acryloyloxazolidinone (0.0143 g, 0.1 mmol) was added
1
92% yield (0.69 g). H NMR (399.78 MHz, CDCl3, δ): 7.51 (m, followed by freshly distilled cyclopentadiene (50 µL). For the
4H, Ar–H), 7.43 (m, 4H, Ar–H), 6.65 (dd, J = 17.4, 10.6 Hz, 2H, Mukaiyama-aldol reaction, methyl pyruvate (0.0102 g,
HaCvCHbHc), 5.79 (d, J = 17.4 Hz, 2H, HaCvCHbHc), 5.35 (d, 0.1 mmol) followed by (0.0243 g, 0.12 mmol) of 1-phenyl-1-tri-
J = 10.6 Hz, 2H, HaCvCHbHc), 5.04 (s, 4H, Ar–CH2–N), 3.49 methylsiloxyethene. The reaction mixture was stirred at the
(m, 4H, CH2–N–CH2), 2.07 (m, 4H N–CH2–CH2). 13C{1H} NMR desired temperature for the specified amount of time and then
(100.52 MHz, CDCl3, δ): 139.5, 135.4, 133.6, 126.8, 126.7, diluted with 5 cm3 of 1 : 1 ethyl acetate–hexane.
116.4, 63.2, 57.7, 21.5. 19F NMR (376.17 MHz, CDCl3, δ):
Following concentration of the Diels–Alder reaction
−78.73 (s, NTf2); Anal. Calcd for C22H26F6N2O4S2: C, 49.31; H, mixture, the crude adduct was dissolved in 5 cm3 of diethyl
4.48; N, 4.79. Found: C, 49.77; H, 4.67; N, 5.09; HRMS (ESI+): ether and filtered through a small plug of silica gel to afford
exact mass calcd for C22H26N [M+] m/z 304.2065, found m/z unpurified product and analysed directly.
304.2054.
Following concentration of the Mukaiyama-aldol reaction
mixture, the residual oil was redissolved in THF (5 cm3) and
the corresponding silyl-adduct was hydrolysed by stirring for
1 h using 2 M HCl (10 cm3). The THF was removed under
vacuum and the keto-alcohol was extracted from the aqueous
by washing with Et2O (3 × 5 cm3). The crude product was ana-
General procedure for radical initiated polymerisations of
1-benzyl-1-(4-vinylbenzyl)pyrrolidinium bis{(trifluoromethyl)-
sulfonyl}imide with styrene and cross-linker: synthesis of
IP-1–4
In typical procedure, an oven-dried Schlenk flask was charged lysed directly.
with the 1-benzyl-1-(4-vinylbenzyl)pyrrolidinium monomer
For reactions conducted in diethyl ether, the catalyst was
9·NTf2 (5.2 mmol), styrene (10.3 mmol) and the specified activated in dichloromethane which was then removed under
amounts of azobisisobutyronitrile and corresponding cross- vacuum followed by addition of diethyl ether (5 cm3) and
linker. After dilution with dry methanol (50 mL) the resulting stirred for 30 min after which the substrates were added. The
reaction mixture was degassed with 5 freeze/thaw cycles using reaction was worked up as previously described to afford the
liquid nitrogen. Upon warming to room temperature the reac- unpurified products which were analysed directly.
tion mixture was heated to 75 °C and allowed to stir for 48 h.
General procedure for the homogeneous Lewis acid catalyzed
Diels–Alder and Mukaiyama-aldol reaction in 1-ethyl-3-
methylimidazolium bis{(trifluoromethyl)sulfonyl}imide
([C2mim][NTf2])
In the case of insoluble polymers such as IP-2, IP-3 and IP-4
the solvent was decanted and the resulting precipitate washed
with hexane and diethyl ether before drying under high
vacuum, whereas the reaction mixture containing soluble IP-1
was added drop-wise to rapidly stirred diethyl ether to induce
A flame dried Schlenk flask was charged with ligand
precipitation of the product which was subsequently isolated (0.011 mmol) and Cu(OTf)2 (0.010 mmol, 10 mol%). To this
This journal is © The Royal Society of Chemistry 2014
Green Chem., 2014, 16, 1470–1479 | 1477

View Article Online
Paper
Green Chemistry
was added dichloromethane (5 cm3) and [C2mim][NTf2] by pipette and the heterogeneous catalyst was further extracted
(3.00 g, 2 cm3) and the resulting solution stirred at room temp- with diethyl ether (2 × 5 cm3). After extraction fresh diethyl
erature for 5 min. The dichloromethane was then removed ether (5 cm3) was added to the heterogeneous catalyst and the
under high vacuum for one hour leaving the active catalyst dis- resultant slurry was charged with further portions of Diels–
solved in the ionic liquid. Thereafter, the Diels–Alder or Alder substrates. ICP analysis of a portion of the supernatant
Mukaiyama-aldol substrates were added. The resulting mixture phase between recycles was conducted using a using a Perkin
was stirred at room temperature for the specified amount of Elmer Optima 4300DV ICP-OES (Inductively Coupled Plasma
time after which the ionic liquid was extracted with diethyl Optical Emission Spectrometer).
ether (3 × 5 cm3) in air. Both the Diels–Alder and Mukaiyama-
aldol reaction was worked up as previously described to afford
the unpurified products which were analysed directly.
Notes and references
General procedure for the liquid–liquid biphasic Lewis acid
catalyzed Diels–Alder and Mukaiyama-aldol reactions in
[C2mim][NTf2]/diethyl ether
1 D. Evans, S. Miller and T. Lectka, J. Am. Chem. Soc., 1993,
115, 6460–6461; D. Evans, M. Kozlowski and J. Tedrow,
A
flame dried Schlenk flask was charged with ligand
Tetrahedron Lett., 1996, 37, 7481–7484.
(0.011 mmol) and metal(II) triflate (0.010 mmol, 10 mol%). To
this was added dichloromethane (5 cm3) and [C2mim][NTf2]
(0.15 g, 0.23 cm3) and the resulting solution stirred at room
temperature for 5 min. Dichloromethane was then removed
under high vacuum for one hour leaving the active catalyst dis-
solved in the ionic liquid. Thereafter, diethyl ether (5 cm3) was
added followed by the Diels–Alder or Mukaiyama-aldol substrates.
The resulting mixture was stirred at the desired temperature for
the specified amount of time after which the diethyl ether was
removed and the remaining ionic liquid was extracted with
diethyl ether (2 × 5 cm3) in air. The Diels–Alder or Mukaiyama-
aldol products were worked up as previously described to afford
the unpurified products which were analysed directly.
2 P. Goodrich, C. Hardacre, C. Paun, V. I. Parvulescu and
I. Podolean, Adv. Synth. Catal., 2008, 350, 2473–2476;
S. Doherty, P. Goodrich, C. Hardacre, C. Paun and
V. I. Parvulescu, Adv. Synth. Catal., 2008, 350, 295–302;
S. Doherty, P. Goodrich, C. Hardacre, H.-K. Luo,
D. W. Rooney, K. R. Seddon and P. Styring, Green Chem.,
2004, 6, 63–67; L. Lou, K. Yu, F. Ding, W. Zhan, X. Peng
and S. Liu, Tetrahedron Lett., 2006, 47, 6513–6516;
M. R. Castillo, L. Fousse, J. M. Fraile, J. I. García and
J. A. Mayoral, Chem.–Eur. J., 2007, 13, 287–291.
3 P. Goodrich, C. Hardacre, C. Paun, A. Ribeiro, S. Kennedy,
M. J. V. Lourenco, H. Manyar, C. A. Nieto de Castro,
M. Besnea and V. I. Parvulescu, Adv. Synth. Catal., 2011,
353, 995–1004.
4 C. A. McNamara, M. J. Dixon and M. Bradley, Chem. Rev.,
2002, 102, 3275–3279; N. E. Leadbeater and M. Marco,
Chem. Rev., 2002, 102, 3217–3273.
General procedure for the heterogeneous Lewis acid catalyzed
Diels–Alder and Mukaiyama-aldol reactions in diethylether/
support
A
flame dried Schlenk flask was charged with ligand
5 A. Puglisi, M. Benaglia and V. Chiroli, Green Chem., 2013,
15, 1790–1813.
6 B. M. L. Dios, D. E. De Vos, I. V. F. J. Vankelecom and
P. A. Jacobs, Adv. Synth. Catal., 2006, 348, 1413–1446;
S. Itsuno, K. Watanabe, T. Koizumi and K. Ito, React.
Polym., 1995, 24, 219–227.
7 Polymeric Chiral Catalyst Design and Chiral Polymer Syn-
thesis, ed. S. Itsuno, John Wiley and Sons, 2011.
8 H. Bae, J. Han, S. Jung, M. Cheong, H. Kim and J. Lee,
Appl. Catal., A, 2007, 331, 34–38.
(0.011 mmol), metal(II) triflate (0.010 mmol, 10 mol%) and
dichloromethane (5 cm3) and the resulting solution stirred at
room temperature for 5 min. To the resulting green solution
was added silica, carbon or IP support (0.1 g) and for catalysts
using a supported ionic liquid film, 0.1 cm3 of ionic liquid was
also added. (For the non-ionic polystyrene polymer 7, the
resulting metal triflate–ligand solution was stirred for 3 h
before the addition of the polymer support.) After stirring for
5 min, the dichloromethane was removed under vacuum for
one hour to afford a free flowing powder after which the flask
9 P. Barbaro and F. Liguori, Chem. Rev., 2009, 109, 515–529.
was charged with diethyl ether (5 cm3) followed by the 10 J. M. Fraile, J. I. García and J. A. Mayoral, Chem. Rev., 2009,
addition of the Diels–Alder or Mukaiyama-aldol substrates.
The reaction mixture was stirred at room temperature for the 11 M. I. Burguete, H. Erythropel, E. García-Verdugo, S. V. Luis
specified amount of time after which the silica was extracted and V. Sans, Green Chem., 2008, 10, 401–407.
with diethyl ether (3 × 5 cm3) in air. The reaction was worked 12 P. Lozano, E. García-Verdugo, R. Piamtongkam, N. Karbass,
109, 360–417.
up as previously described to afford the unpurified products
which were analysed directly.
T. De Diego, M. I. Burguete, S. V. Luis and J. L. Iborra, Adv.
Synth. Catal., 2007, 349, 1077–1084; P. Lozano, E. García-
Verdugo, N. Karbass, K. Montague, T. De Diego,
M. I. Burguete and S. V. Luis, Green Chem., 2010, 12, 1803–
1810.
Procedure for recycle of the heterogeneously catalysed
reactions
The catalyst/ether slurry solution was left to settle in order to 13 A. Wolfson, J. F. J. Vankelecom and P. A. Jacobs, Tetra-
separate the phases after which the ethereal layer was removed
hedron Lett., 2003, 44, 1195–1198.
1478 | Green Chem., 2014, 16, 1470–1479
This journal is © The Royal Society of Chemistry 2014

View Article Online
Green Chemistry
Paper
14 A. Köckritz, S. Bischoff, V. Morawsky, U. Prüße and 22 J. M. Fraile, J. I. García, C. I. Herrerías, J. A. Mayoral,
K.-D. Vorlop, J. Mol. Catal. A: Chem., 2002, 180, 231–243. S. Gmough and M. Vaultier, Green Chem., 2004, 6, 93–98.
15 S. Doherty, J. G. Knight, J. R. Ellison, D. Weekes, 23 M. J. Fernandez, J. M. Fraile, J. I. García, J. A. Mayoral,
R. W. Harrington, C. Hardacre and H. Manyar, Green
Chem., 2012, 14, 925–929.
16 D. Rechavi, B. Albela, L. Bonneviot and M. Lemaire, Tetra-
hedron, 2005, 61, 6976–6981.
M. I. Burguete, E. García-Verdugo, S. V. Luis and
M. A. Harmer, Top. Catal., 2000, 13, 303–309; J. M. Fraile,
J. I. García, C. I. Herrerías, J. A. Mayoral and M. A. Harmer,
J. Catal., 2004, 221, 532–540.
17 J. M. Fraile, J. I. García, C. I. Herrerías, J. A. Mayoral, 24 P. Izák, Š. Hovorka, T. Bartovsky, L. Bartovská and
D. Carrié and M. Vaultier, Tetrahedron: Asymmetry, 2001,
12, 1891–1894.
18 Y. Wan, P. McMorn, F. E. Hancock and G. J. Hutchings,
Catal. Lett., 2003, 91, 145–148.
19 S. Orlandi, A. Mandoli, D. Pini and P. Salvadori, Angew.
Chem., Int. Ed., 2001, 40, 2519–2521.
20 B. Corain, M. Zecca and K. Jeřábek, J. Mol. Catal. A: Chem.,
2001, 177, 3–20.
J. G. Crespo, J. Membr. Sci., 2007, 296, 131–138.
25 S. Itsuno, S. Arima and N. Haraguchi, Tetrahedron, 2005,
61, 12074–12080.
26 G. Desimoni, G. Faita, A. G. Invernizzi and P. Righetti,
Tetrahedron, 1997, 53, 7671–7688.
27 M. I. Burguete, E. García-Verdugo, I. Garcia-Villar, F. Gelat,
P. Licence, S. V. Luis and V. Sans, J. Catal., 2010, 269, 150–
160.
21 H. Wang, J. Liu, P. Liu, Q. Yang, J. Xiao and C. Li, 28 C. Villigrán, M. Deetlefs, W. R. Pitner and C. Hardacre,
Chin. J. Catal., 2006, 27, 946–948.
Anal. Chem., 2004, 76, 2118–2123.
This journal is © The Royal Society of Chemistry 2014
Green Chem., 2014, 16, 1470–1479 | 1479