Synthesis of MacMillan catalyst modified with ionic liquid as a recoverable catalyst for asymmetric Diels-Alder reaction

Article abstract of DOI:10.1039/c5ra09710j

MacMillan catalyst was modified with imidazolium ionic liquid by ester linkage and acts as recoverable and reusable catalyst for asymmetric Diels-Alder reactions. A Diels-Alder reaction between cyclopentadiene and crotonaldehyde was carried out using MacMillan catalyst modified with ionic liquid (5 mol%) using trifluoroacetic acid (5 mol%) as co-catalyst in acetonitrile-water (95 : 5) at room temperature, to give 94% conversion of Diels-Alder adduct with exo/endo (1 : 1.1) and 90% ee of endo product. The catalyst was recovered and reused up to 5 cycles with a slight decrease in ee and product conversion.

Full text of DOI:10.1039/c5ra09710j

View Article Online
View Journal
RSC Advances
This article can be cited before page numbers have been issued, to do this please use: M. M. S. Chauhan,
P. Kumar and S. Singh, RSC Adv., 2015, DOI: 10.1039/C5RA09710J.
This is an Accepted Manuscript, which has been through the
Royal Society of Chemistry peer review process and has been
accepted for publication.
Accepted Manuscripts are published online shortly after
acceptance, before technical editing, formatting and proof reading.
Using this free service, authors can make their results available
to the community, in citable form, before we publish the edited
article. This Accepted Manuscript will be replaced by the edited,
formatted and paginated article as soon as this is available.
You can find more information about Accepted Manuscripts in the
Information for Authors.
Please note that technical editing may introduce minor changes
to the text and/or graphics, which may alter content. The journal’s
standard Terms & Conditions and the Ethical guidelines still
apply. In no event shall the Royal Society of Chemistry be held
responsible for any errors or omissions in this Accepted Manuscript
or any consequences arising from the use of any information it
contains.
www.rsc.org/advances

Page 1 of 7
RSC Advances
View Article Online
DOI: 10.1039/C5RA09710J
RSC Advances
RSCPublishing
ARTICLE
Synthesis of MacMillan catalyst tailored with
ionic liquid as a recoverable catalyst for
asymmetric Diels-Alder reaction
Cite this: DOI: 10.1039/x0xx00000x
ManMohan Singh Chauhan, Pramod Kumar, Surendra Singh*
Received 00th January 2012,
Accepted 00th January 2012
MacMillan catalyst was tailored with imidazolium ionic liquid by ester linkage that acts as recoverable
and reusable catalyst for asymmetric Diels-Alder reaction. Diels-Alder reaction between
cyclopentadiene and crotonaldehyde was carried out using MacMillan catalyst modified with ionic liquid
(5 mol%) and trifluoroacetic acid (5 mol%) as co-catalyst in acetonitrile/water (95/5) at room
temperature, gave 94% conversion of Diels-Alder adduct with exo/endo (1:1.1) and 90% ee of endo
product. The catalyst was recovered and reused up to 5 cycles with slight decrease in ee and conversions
of product.
DOI: 10.1039/x0xx00000x
www.rsc.org/
developed a nanoporous heterogeneous chiral catalyst via acidꢀ
induced liquid crystal selfꢀassembly and subsequent
Introduction
photopolymersiation of monomer of imidazolidinone unit.28
Selkälä et al immobilized MacMillan catalyst on JandaJelTM
through amide bond using JandaJelꢀNH2 and NꢀFmocꢀprotected
(S)ꢀphenylalanine.29 Haraguchi et al used polymer supported
sulphonic acid for immobilization of MacMillan catalyst by
ionic interaction via ion exchange between sulfonated polymer
and quaternary ammonium salt.30 They also developed main
chain polymer by the reaction of chiral imidazolidinone dimer
with disulfonic acid.31 Mitsudone et al also supported
MacMillan catalyst on montmorillonite clay using cation
exchange method.32 Fluorous tag and tetraarylphosphonium
with Macmillan catalyst can act as a recoverable catalyst.33,34
Room temperature ionic liquids were also used for recovery of
MacMillan catalyst.35 Imidazolium based ionic liquids
connected with MacMillan catalyst through covalent bond and
supported on silica were also used for this reaction.36,37 In our
ongoing research project on the development of recoverable
catalyst, recently we have developed a α,αꢀdiphenylꢀ(L)ꢀ
prolinol modified with imidazolium ionic liquid as recoverable
catalyst for asymmetric reduction of ketones.39 Herein, we wish
to report the synthesis of MacMillan catalyst tailored with
imidazolium ionic liquid as a recoverable catalyst for the
enantioselective DielsꢀAlder reaction.
DielsꢀAlder reaction is an important tool for the synthesis of
enantiomerically enriched cyclohexene moiety and also for
carbonꢀcarbon bond formation reaction. It is a key step for the
synthesis of many natural products and pharmaceutical
compounds.1–4 Enantioselective DielsꢀAlder reaction was used
for the synthesis of (ꢀ)ꢀoseltamivir by Fukuyama and coꢀ
workers.5,6 The first enantioselective DielsꢀAlder reaction was
reported by MacMillan and coꢀworkers, involving an
organocatalyst, which proceeds by
a
LUMOꢀlowering
activation mechanism.7–9 Several organocatalysts employed for
the enantioselective DielsꢀAlder reaction are chiral diamines,10–
12 hydrazides,13–19 and diarylprolinol ether.20–21
Organocatalysts used in this reaction have some limitations like
required high catalyst loading, long reaction time and also these
catalysts are not easily separated from the reaction mixture
therefore difficult to recover and recycle. Several research
groups have made successful attempts to overcome these
problems by immobilizing or attaching the catalytic unit on a
recyclable supports. Tyrosineꢀderived imidazolidinꢀ4ꢀone was
immobilized on supports through covalent bond on modified
polyethylene glycol,22 poly(methylhydrosiloxane) (PHMS),23
siliceous and polymerꢀcoated mesocellular foam (MCF),24
mesoporous organosilica sphere,25 and chiral organosilica
polymer.26 Liang et al reported, use of internal functionalities of
the dendrimer to attach imidazolidinone as guests to the interior
of the dendrimer using olefin metathesis.27 Pecinovsky et al
This journal is © The Royal Society of Chemistry 2013
J. Name., 2013, 00, 1-3 | 1

RSC Advances
Page 2 of 7
View Article Online
ARTICLE
Journal Name
DOI: 10.1039/C5RA09710J
(10 mol%) and trifluoroacetic acid (10 mol%) as coꢀcatalyst
(Table 1). Acetonitrile as a solvent was found to be better than
other solvents (water and methanol), gave 74% conversion of
DielsꢀAlder adduct with exo/endo (1/1) and 75% ee of endo
product (12). In a methanol we have obtained 12% desired
product (11 and 12) and 88% of its dimethyl acetal was formed
as a byꢀproduct (Table 1, entry 5). Nonꢀpolar solvent like
dichloromethane also gave comparable ee of endo product, but
conversion of product was poor compared to acetonitrile (Table
N
N
O
N
O
CH3
CH3
X
N
O
O
H.HCl
N
X = Br (6)
= BF4 (7)
PF6 (8)
MacMillan Catalyst
N
H
=
Figure 1. MacMillan’s catalyst and modified MacMillan catalyst with ionic liquid
1, entry 6). We have also screened the IL
7 and 8 in acetonitrile,
Results and discussion
IL gave better ee of endo product (12) compared to other IL’s
8
(Table 1, entries 7, 8). The effect of water was studied for the
reaction and found that 5% water in acetonitrile improved the
ee and ratio of endo product (Table 1, entry 9). Catalyst loading
2 mol% was sufficient to convert product, but better ee (90%)
was obtained with 5 mol% (Table 1, entries 10 and 11). We
have also isolated the product by column chromatography in
84% isolated yield. We further increased the amounts of water
up to 10% in acetonitrile and ee was retained but conversion
dropped to 80% (Table 1, entry 12).
Preparation of modified McMillan catalyst tailored with
ionic liquid
MacMillan catalyst tailored with imidazolium cation and
bromide, tetrafluoroborate and hexafluorophosphate anion (6–
8
) shown in figure 1. Precursors 1–4 were synthesized
according to procedures reported by Kristense et al.38
Bromoester was synthesized by using a 5ꢀbromopentanoyl
chloride and compound in the presence of methanesulfonic
acid at rt, afforded in 70% yield. The bromoester was treated
with 1ꢀmethylimidazole at 100 C for 20 min, gave MacMillan
catalyst @ imidazolium bromide ( ) in 91% yield. The counter
anion bromide of ionic liquid ( ) was exchanged KBF4 and
5
4
5
̊
Table 1 Screening of different solvents and ionic liquids as a catalysts for
6
6
DielsꢀAlder reaction. a
KPF6 in acetone and water solvent, which afforded
tetrafluoroborate (BF4) and hexafluoroborate (PF6) anion
containing ionic liquids with 75% and 81% yields, respectively.
IL's 6-8 (10 mol%, TFA (10 mol%)
+
CHO
CHO
+
Solvent, r.t., 2h
CHO
12 (endo)
11 (exo)
9
10
O
CO2Me
COOH
NH2
OH
a
b
Ph
Ph
Ph
N
H
Cl
NH3
NH2
1
2
3
Conversio
ns (%)b
ee
(endo)d
Entry
Catalyst
Solvents
(exo/endo
c
)
c
Br
OH
O
O
O
O
1
2
4
5
6
7
8
6
6
6
6
6
7
8
Acetonitrile
THF
73
ꢀ
1.0/1.0
ꢀ
75
ꢀ
N
N
d
N
H
N
HCl
H
5
4
e
Water
44
12e
42
81
76
1.0/1.4
1.3/0.7
1.1/1.0
1.1/0.9
1.0/1.0
45
53
70
83
85
N
N
N
N
MeOH
Br
X
O
O
O
O
O
O
N
N
f,g
CH2Cl2
N
N
H
H
X = BF4 (7)
PF6 (8)
Acetonitrile
Acetonitrile
6
Scheme 1. (a) SOCl2, methanol, r.t., 28 h, 97% (b) Ethanolamine, r.t., 26 h, 84%
(c) Acetone, i-PrOH, p-TSA, reflux, 5 h, 81% (d) CH3SO3H, 5-bromovalleric acyl
chloride, 0-5 °C, 3.5 h, 70% (e) 1-Methylimidazole, 100 °C, 10 min, 91% (f) KBF4,
H2O/Acetone, r.t., overnight, 75% (g) KPF6, Acetone/H2O, r.t., overnight, 82%.
Acetonitrile/ water
(95/5)
9
8
8
8
8
88
82
94
80
1.0/1.2
1.0/1.2
1.0/1.1
1.0/1.1
88
85f
Acetonitrile/ Water
(95/5)
10
11
12
Optimization of reaction conditions for Diel-Alder reaction
Ionic liquid supported MacMillan catalysts (6–8) were used
Acetonitrile/Water
(95/5)
90g,h
90g
for DielsꢀAlder reaction by choosing crotonaldehyde (
9) and
cyclopentadiene (10) as model substrates. Initially, we
Acetonitrile / Water
(90:10)
screened different solvents for DielsꢀAlder reaction using IL
6
2 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 2012

Page 3 of 7
Journal Name
RSC Advances
View Article Online
ARTICLE
DOI: 10.1039/C5RA09710J
aIL 6-8 (2ꢀ10 mol%) was dissolved in solvent (1 mL), trifluoroacetic acid (2ꢀ
10 mol%), crotonaldehyde (0.5 mmol, 42 ꢁL) and cyclopentadiene (0.5
mmol, 41 ꢁL) was added and stirred at room temperature. bConversion of
product was determined by Gas Chromatography. cExo/endo ratio was
determined by Gas Chromatography. dEe was determined by Gas
Chromatography using βꢀDex chiral column. e88% Dimethyl acetal of desired
product was formed as a byꢀproduct. fCatalyst 8 (2 mol%) was used. gCatalyst
cinamaldehyde derivatives (13a-d) using IL
8 (5 mol%) and
TFA (5 mol%) in acetonitrile/water (95/5) at room temperature
for 24 h. Cinnamaldehyde gave 92% yield of corresponding
DielsꢀAlder adduct with exo/endo (1.2:1) and ee for 14a/15a
(82/78) (Table 3, entry 1). Electron withdrawing group (nitro)
h
at
and ee of exo product (14a) was dropped (entry 2). Electron
donating group (methoxy) on ꢀposition of cinnamaldehyde
13d) found to be less reactive compared to cinnamaldehyde
and ꢀnitroꢀcinnamaldehyde (entry 3). ꢀChloroꢀ
pꢀposition on cinnamaldehyde (13b) gave comparable yield
8 (5 mol%) was used. 84% isolated yield was obtained after purification by
column chromatography.
p
Effect of different co-catalyst on Diels-Alder reaction
(
p
p
The effects of different acids as coꢀcatalysts were investigated
for the DielsꢀAlder reaction between crotonaldehyde and
cinnamaldehyde (13c) did not show significant difference in
reactivity and enantioselectivity compared to cinnamaldehyde
(entries 1 and 3).
cyclopentadiene using IL
8 as a catalyst (Table 2).
Trifluoroacetic acid (TFA) was found to be a better choice of
coꢀcatalyst in terms of conversion and ee of endo product
compared to the other coꢀcatalysts like HCl, H2SO4, acetic acid,
HClO4 and pꢀTSA. In case of HClO4 and acetic acid ratio of
endo product (12) was improved, but conversion and ee of endo
product (12) were poor compared to TFA.
Table 3 Comparisons of recoverable reported MacMillan
catalysts with IL 8 for enantioselective DielsꢀAlder reaction
between crotonaldehyde and cyclopentadiene.
Catalyst
Recoverable
MacMillan
Catalyst
loading
(mol%),
reaction
time (h)
ee
En
try
Yield (%)
(exo/endo)
(endo)
(%)
Ref.
Table 2 Screening of different Coꢀcatalysts for DielsꢀAlder reaction
catalysed by IL 8.a
Immobilized on
JandaJelTM
Nanoporous
heterogeneous
Fluorous
organocatalyst
Montmorillonite
clay
1
2
3
4
10, 24
10, 24
91 (1/1.2)
71 (1/1.3)
80 (1/0.9)
85 (1/1.7)
91
90
92
89
29
28
33
32
IL 8 (5 mol%, Co-catalyst (5 mol%)
+
CHO
CHO
+
CH3CN/H2O (95/5), r.t., 2h
CHO
12 (endo)
11 (exo)
9
10
10, 40
0.1g, 48
Conversion b
Entry
Coꢀcatalyst
(exo/endo
c
Eed (%)
Polymer
(%)
5
6
7
8
supported via
ion exchange
Supported ionic
liquid catalyst
Tetraarylphosph
onium
10, 24
10, 22
10, 12
5, 2
99 (1/0.8)
61 (1/1)
83
83
92
90
30
36,37
34
)
1
2
3
HCl
H2SO4
CH3COOH
Trifluoroacetic
acid
30
26
11
1/1.1
1/1.1
1/1.4
76
40
70
4
94
1/1.1
90
95 (1/1.4)
94 (1/1.1)
Supported
5
6
7
HClO4
pꢀTSA
26
61
2
1/1.4
1/1.2
1/1.3
55
82
44
This
paper
ILꢀ8
ꢀ
aIL 8 (5 mol%) was dissolved in CH3CN/water (95/5, 1 mL), Coꢀcatalyst (5
mol%), Crotonaldehyde (0.5 mmol, 42 ꢁL) and cyclopentadiene (0.5 mmol,
41 ꢁL) was added and stirred at room temperature. bConversion was
determined by Gas Chromatography. cExo/endo ratio was determined by Gas
Chromatography. Ee was determined by Gas Chromatography using βꢀDex
chiral column
Table 4 Substrates scope for DielsꢀAlder reaction using IL 8.a
IL 8 (5 mol%, Co-catalyst (5 mol%)
R
R
+
CHO
CHO
d
+
CH3CN/H2O (95/5), r.t., 24h
CHO
R
13a; R = Ph
14a-d (exo)
15a-d (endo)
9
13b; R = 4-NO2-Ph
13c; R = 4-Cl-Ph
Comparisons of recoverable MacMillan catalysts
13d; R = 4-OMe-Ph
We have compared the results of IL 8 with other reported
recoverable MacMillan catalysts for enantioselective Dielsꢀ
Alder reaction between crotonaldehyde and cyclopentadiene.
(Table 3). Results show that IL 8 found to be better than other
reported catalysts in terms of less catalyst loading (5 mol%),
less reaction time and comparable ee of endo DielsꢀAlder
product (12).
Entry
Substrate
Yield
(%)c
92
84
87
eed (%)
(exo/endo)
82/78
75/76
80/82
75/nd
exo/endob
1.2:1
1.2:1
1.1:1
1.1:1
1
2
3
4
13a
13b
13c
13d
61
a IL 8 (5 mol%) was dissolved in CH3CN/water (95/5, 1 mL), trifluoroacetic
acid (5 mol%), Cinnamaldehyde or its derivatives (0.5 mmol) and
cyclopentadiene (0.5 mmol) was added and stirred at room temperature.
bCalculated by 1HꢀNMR. cIsolated yield after purification by column
chromatography. dEe was determined by HPLC using Chiralcel ODꢀH
column after reduction to alcohol.
Substrate scope for Diels-Alder reaction
After optimization of reaction conditions for the DielsꢀAlder
reaction, we wish to generalize the substrate scope. We carried
out the DielsꢀAlder reaction between cyclopentadiene and
This journal is © The Royal Society of Chemistry 2012
J. Name., 2012, 00, 1-3 | 3

RSC Advances
Page 4 of 7
View Article Online
ARTICLE
Journal Name
DOI: 10.1039/C5RA09710J
Recovery and reusability of the IL 8
silica gel 230ꢀ400 mesh. All the new synthesized compounds
1
were characterized by H, 13C NMR and HRMS and known
The recycling of MacMillan catalyst tailored with imidazolium
compounds were characterised by 1H and 13C NMR. The
experimental procedure for the known compounds were
followed according to literature reports and given in supporting
information (SI). The enantiomeric excess of DielsꢀAlder
products was determined on Shimadzu LCꢀ2010HT using ODꢀ
H and ADꢀH chiral columns and Shimadzu GCꢀ2010 plus using
βꢀdex chiral column. The optical rotation was taken using
Rudolph digipol polarimeter.
ionic liquid
DielsꢀAlder reaction between cyclopentadiene
crotonaldehyde (10) (Table 5). The IL was recovered and
reused up to 5 cycles with minor loss of conversions of Dielsꢀ
Alder adducts and 90–86 ee’s of endo product (12) but
8
was successfully achieved for the enantioselective
(9)
and
8
%
exo/endo ratios were retained. After the fresh catalytic cycle,
the reaction mixture was passed through a pad of anhydous
sodiumsulfate to remove the water from the reaction. The
solvent was removed under vacuum and hexane:diethyl ether (5
Synthetic procedures
mL, 1:1) was added, IL
8 was becaming a viscous liquid and
the product was in the solvent, which was decanted off. The 1Hꢀ 2-((5R)-5-benzyl-2,2-dimethyl-4-oxopyrrolidin-3-yl)ethyl-5-
NMR and 19FꢀNMR and HRMS data of recovered catalyst and bromopentanoate (5)
fresh catalyst in agreement (SI, Figure 4, 6). We have treated IL
In a 100 mL round bottom flask, anhydrous CH3SO3H (12 mL)
8
with 1 equivalent of trifluoroacetic acid in acetonitrile/water
was cooled in an ice/water bath and compound
4 (2.83 g, 10
(95/5), recorded the 1HꢀNMR and peak at 2.3 ppm of OCH2CO
of the ester linker indicate that ester is not hydrolising during
the reaction (SI, Figure 5).
mmol) was added in 20 min followed by the addition of 5ꢀ
bromopentanoyl chloride and the reaction mixture was stirred at
0ꢀ5 °C for 3.5 h. The clear solution was diluted with diethyl
ether and transferred to a separatory funnel and more diethyl
ether was added to give phase separation. The bottom yellow
layer of the product was allowed to drip directly into a mixture
of dichloromethane (60 mL) and aq. solution of K2CO3 (12.0 g
dissolved in 70 mL). After complete addition, the organic phase
was separated. The aq. phase was extracted with
dichloromethane (2 x 30 mL) and the combined solvent was
dried over anhydrous Na2SO4 and concentrated in vacuum. The
Table 5 Recycling performance of IL 8 for DielsꢀAlder reaction between
crotonaldehyde and cyclopentadiene. a
Entry
Cycle
Leaching
of
Conversionc
(%)
exo/endod
eee (%)
Endo
catalyst
(mg)b
0.12
0.10
0.00
0.01
0.02
0.02
1
2
3
4
5
6
0
1
2
3
4
5
94
90
88
87
81
81
1 : 1.1
1 : 1.1
1 : 1.1
1 : 1.1
1 : 1.1
1 : 1.1
90
89
88
88
88
87
product
5 was further purified by column chromatography
using a mixture of hexane/ethyl acetate (70:30) to afford yellow
25
α
1
D
liquid (2.86 g, 70%).
= ꢀ 36.6 (c 1.0, CHCl3); H NMR
aIL 8 (5 mol%, 14 mg) was dissolved in CH3CN/water (95/5, 1mL),
trifluoroacetic acid (5 mol%), crotonaldehyde (0.5 mmol, 42 ꢁL) and
cyclopentadiene (0.5 mmol, 41 ꢁL) was added and stirred at room
temperature for 24 h. bLeaching of the catalyst was determined by HPLC and
details are given in ESI. bConversion checked by Gas Chromatography.
cDiestereomaric ratio was calculated by Gas Chromatography. dEe was
determined by Gas Chromatography using βꢀDex chiral column.
(CDCl3, 400MHz) δ 7.25–7.15 (m, 5H), 4.13–4.07 (m, 2H),
3.74 (t, 1H,
6.59 Hz), 3.37–3.33 (m, 1H), 3.16–3.11 (m, 1H), 3.03 (d, 1H,
= 5.86 Hz), 2.24 (t, 2H,
J
= 5.49 Hz), 3.51–3.46 (m, 1H), 3.36 (t, 2H,
J
=
J
J
= 7.69 Hz), 1.86–1.79 (m, 2H), 1.74–
1.68 (m, 2H), 1.22 (s, 3H), 1.11 (s, 3H) ppm. 13C NMR (CDCl3,
100 MHz) δ 174.1, 173.2, 136.4, 129.3(2C), 128.3(2C), 126.5,
75.7, 61.1, 58.4, 38.9, 36.6, 33.8, 31.1, 28.5, 27.6, 26.2, 24.4
ppm.
Experimental
Materials and methods
(R)-3-(5-(2-(4-benzyl-2,2-dimethyl-5-oxoimidazolidin-1-
Cyclopentadiene was prepared from its dimer. Crotonaldehyde
was freshly disttiled and used. Proton and carbon nuclear
magnetic resonance spectra (1H and 13C NMR, respectively)
were recorded on 400 MHz (operating frequencies: H, 400.13
MHz; 13C, 100.61 MHz) JeolꢀFTꢀNMR spectrometer at ambient
yl)ethoxy)-5-oxopentyl)-1-methyl-1H-imidazol-3-ium bromide
(6)
Compound
5 (5 mmol, 2.04 g) and 1ꢀmethylimidazole (6 mmol,
1
0.492 g) were heated at 100° C for 10 min and cooled to room
temperature. The reaction mixture was washed with diethyl
ether to remove an excess of 1ꢀmethylimidazole. The residue
temperature. The chemical shifts (δ) for all compounds are
listed in parts per million downfield from tetramethylsilane
using the NMR solvent as an internal reference. The reference
values used for deuterated chloroform (CDCl3) and were 7.26
and 77.00 ppm for 1H and 13C NMR spectra, respectively.
HRMS analysis was carried out using Agilent G6530AA LC Qꢀ
TOF mass spectrometer. Thin layer chromatography was
carried out using Merck Kieselgel 60 F254 silica gel plates.
Column chromatography separations were performed using
was dried under reduced pressure to afford compound
6 (2.21 g,
25
α
D
90%) as a light yellow hygroscopic liquid.
= ꢀ 16.3 (c 1.2,
1
MeOH); H NMR (CDCl3, 400MHz) δ 10.13 (s, 1H), 7.52 (s,
1H), 7.45 (s, 1H), 7.24–7.13 (m, 5H), 4.32 (t, 2H, = 7.63 Hz),
4.01 (s, 3H), 4.05–4.01 (m, 2H), 3.7–3.64 (m, 1H), 3.49–3.36
(m, 1H), 3.15–3.12 (m, 1H), 3.00–2.95 (m, 2H), 2.29 (t, 2H,
J
J
=
8.01 Hz), 1.94–1.89 (m, 2H), 1.61–1.57 (m, 2H), 1.20 (s, 3H),
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 2012

Page 5 of 7
Journal Name
RSC Advances
View Article Online
ARTICLE
DOI: 10.1039/C5RA09710J
1.11 (s, 3H) ppm. 13C NMR (CDCl3, 100 MHz) δ 174.5, 172.5, IL
8
(5 mol%, 14 mg) was taken in acetonitrile/water (95/5) (1
137.1, 136.7, 129.3 (2C), 128.4 (2C), 126.7, 123.3, 122.1, 75.9, mL) and TFA (5 mol%) was added and stirred for 5 min, then
61.6, 58.6, 49.4 38.9, 36.9, 36.5, 32.7, 29.2, 27.8, 26.3, 20.9 α,βꢀunsaturated aldehyde (0.5 mmol) was added and reaction
+
ppm. HRMS (ESI) calcd for C23H33N4O3 [M]+: 413.2547; mixture was stirred for 10 min at rt. Finally, cyclopentadiene
found 413.2531.
(R)-3-(5-(2-(4-benzyl-2,2-dimethyl-5-oxoimidazolidin-1-
yl)ethoxy)-5-oxopentyl)-1-methyl-1H-imidazol-3-ium
tetrafluoroborate (7
The ionic liquid
(0.5 mmol) was added and reaction was stirred at rt for
specified time. Conversion was monitored by GC in case of
crotonaldehyde and rest was checked by TLC using
Hexane/EtOAc (80/20). The solvent was evaporated by
)
6
(1 mmol, 0.491 g) was dissolved in a mixture rotavapor and products were purified by column
of water/acetone (1:1, 10 mL) and potassium tetrafluoroborate chromatography.
(1.2 mmol, 0.152 g) was added and stirred at room temperature
Procedure for recycling of catalyst
for overnight. After reaction, acetone was removed and the
aqueous layer was extracted with CH2Cl2 (10 mL x 3). The After the fresh catalytic cycle of the reaction, the solvent was
combined organic layer was washed with water (5 mL x 3), passed through a pad of anhydrous sodiumsulfate to remove the
dried with anhydrous Na2SO4, filtered and concentrated under water from the reaction. Solvent of the reaction mixture was
25
α
D
vacuum to give ionic liquid
7
(0.373 g, 75%).
= ꢀ 14.9 (c removed under vaccum and hexane:diethyl ether (5 mL, 1:1)
was precipited out as viscous liquid and the
= 6.87 product was in the solvent which was decanted off. The residue
= 6.10 Hz), IL was dissolved in acetonitrile/water (95/5) and TFA (5
3.51–3.40 (m, 1H), 3.18–3.14 (m, 1H), 3.06–2.93 (m, 2H), 2.29 mol%) was added and resulting mixture was stirred at rt for 10
1
1.0, CH2Cl2); H NMR (CDCl3, 400MHz) δ 8.91 (s, 1H), 7.38 was added, IL
(s, 1H), 7.33 (s, 1H), 7.25–7.15 (m, 5H), 4.17 (t, 2H,
Hz), 4.12–4.04 (m, 2H), 3.88 (s, 3H), 3.72 (t, 1H,
8
J
J
8
(t, 2H,
J = 6.87 Hz), 1.90–1.85 (m, 2H), 1.60–1.56 (m, 2H), min then crotonaldehyde (2.0 mmol) and cyclopentadiene (2.0
1.22 (s, 3H), 1.14 (s, 3H) ppm. 13C NMR (CDCl3, 100 MHz) δ mmol) was added. The reaction was monitored on GC. Solvent
174.5, 172.6, 136.8, 136.4, 129.3(2C), 128.5(2C), 126.7, 123.5, was evaporated by rotavapor. Similar procedure was also
122.2, 76.0, 61.7, 58.7, 49.3, 38.9, 37.0, 36.1, 32.7, 29.0, 27.8, followed for next catalytic run.
26.3, 20.9 ppm. 19F NMR (CDCl3, 304 MHz) δ ꢀ150.9 (s).
HRMS (ESI) calcd for C23H33N4O3 [M]+: 413.2547; found
+
Conclusions
413.2564.
In conclusion, we have developed an efficient method for the
enantioselective DielsꢀAlder reaction catalyzed by recoverable
MacMillan catalyst tailored with imidazolium ionic liquid at
(R)-3-(5-(2-(4-benzyl-2,2-dimethyl-5-oxoimidazolidin-1-
yl)ethoxy)-5-oxopentyl)-1-methyl-1H-imidazol-3-ium
hexafluorophosphate (8)
room temperature. IL
8 (5 mol%) acts as catalyst in presence
coꢀcatalyst trifluoroacetic acid (5 mol%) for the DielsꢀAlder
reaction between cyclopentadiene and crotonaldehyde, gave
94% conversion of product with exo/endo (1/1.1) and 90% ee
of endo product which is comparable to MacMillan catalyst and
better than other reported reusable catalysts. Ionic liquid
The ionic liquid
of water/acetone
6
(3 mmol, 1.47 g) was dissolved in a mixture
(1:1, 30 mL) and potassium
hexafluorophosphate (3.6 mmol, 0.66 g) was added and stirred
at room temperature for overnight. After reaction, acetone was
removed and the aqueous layer was extracted with CH2Cl2 (30
mL x 3), the combined organic layer was washed with water
(15 mL x 3), dried over anhydrous Na2SO4, filtered and
supported MacMillan catalyst
8 can be recovered and reused up
to 5 cycles with minor decrease in conversions DielsꢀAlder but
ee’s was in range of 90–87%.
concentrated under vacuum to give ionic liquid
8 (1.35 g, 81%).
25
α
= ꢀ 19.7 (c 1.0, CH2Cl2); 1H NMR (CDCl3, 400MHz) δ 8.52
(s, 1H), 7.31–7.16 (m, 7H), 4.14–4.05 (m, 4H), 3.84 (s, 3H),
3.74–3.67 (m, 1H), 3.42–3.53 (m, 1H), 3.19–3.16 (m, 1H),
D
Acknowledgements
SS acknowledges the financial assistance from Science and
Engineering Research Board (SERB), Department of Science
and technology (DST), India, under scheme Fast Track Young
Scientist (SB/FT/CSꢀ020/2012) and University Science
Instrumentation Center (USIC), University of Delhi, India for
analytical data. Authors are thankful to DUꢀDST mass facility
at USIC. MSC is thankful to University Grant Commission
(UGC), New Delhi for providing SRF.
3.07–3.03 (m, 1H), 2.98–2.93 (m, 1H), 2.29 (t, 2H,
J = 6.48,
Hz), 1.91–1.85 (m, 2H), 1.62–1.55 (m, 2H), 1.23 (s, 3H), 1.15
(s, 3H) ppm. 13C NMR (CDCl3, 100 MHz) 174.6, 172.7, 136.9,
136.0, 129.4 (2C), 128.5 (2C), 126.8, 123.5, 122.1, 76.1, 61.7,
58.7, 49.4, 39.0, 37.0, 36.1, 32.7, 28.9, 27.8, 26.3, 20.9 ppm.
19F NMR (CDCl3, 304 MHz) δ ꢀ71.9 (d,
J
= 563.74 Hz). 31P
= 758.75 Hz).
NMR (CDCl3, 162 MHz) δ ꢀ144.0 (septet,
J
+
Notes and references
HRMS (ESI) calcd for C23H33N4O3 [M]+: 413.2547; found
413.2530.
a Department of Chemistry, University of Delhi, Delhi, Indiaꢀ110007.
†
Electronic Supplementary Information (ESI) available: [details of any
General procedure of enantioselective Diels-Alder reduction
supplementary information available should be included here]. See
DOI: 10.1039/b000000x/
This journal is © The Royal Society of Chemistry 2012
J. Name., 2012, 00, 1-3 | 5

RSC Advances
Page 6 of 7
View Article Online
ARTICLE
Journal Name
DOI: 10.1039/C5RA09710J
28. C. S. Pecinovsky, G. D. Nicodemus, D. L. Gin, Chem. Mater.
,
1. D. A. Evans, J. S. Johnson, in Comprehensive Asymmetric
17, 2005, 4891.
Catalysis, ed. E. N. Jacobsen, A. Pfaltz and H. Yamamoto,
29. S. A. Selkala, J. Tois, P. M. Pihko, A. M. P. Koskinen, Adv.
Synth. Catal., 344, 2002, 941.
Springer, New York, 1999, vol. 3, p. 1177
2. Y. Hayashi, in Cycloaddition Reaction in Organic Synthesis
,
30. N. Haraguchi, Y. Takemura, S. Itsuno, Tetrahedron Letters,
ed. S. Kobayashi and K. A. Jorgensen, WileyꢀVCH,
Weinheim, 2002, ch. 1.
51, 2010, 1205.
31. N. Haraguchi, H. Kiyono, Y. Takemura, S. Itsuno, Chem.
Commun., 48, 2012, 4011.
3. E. J. Corey, Angew. Chem., Int. Ed., 41, 2002, 1650.
4. K. C. Nicolaou, S. A. Snyder, T. Montagnon, G.
Vassilikogiannakis, Angew. Chem., Int. Ed., 41, 2002, 1668.
5. N. Satoh, T. Akiba, S. Yokoshima, T. Fukuyama, Angew.
Chem., 119, 2007, 5836.
32. T. Mitsudome, K. Nose, T. Mizugaki, K. Jitsukawa, K.
Kaneda, Tetrahedron Lett., 49, 2008, 5464.
33. Q. Chu, W. Zhang, D. P. Curran, Tetrahedron Lett., 47, 2006,
9287.
6. N. Satoh, T. Akiba, S. Yokoshima, T. Fukuyama, Tetrahedron
,
34. Z. Lin, Z. Chen, G. Yang, C. Lu Catalysis Communications,
65, 2009, 3239.
35, 2013, 1.
7. K. A. Ahrendt, C. J. Borths, D. W. C. MacMillan, J. Am.
Chem. Soc., 122, 2000, 4243.
35. J. K. Park, P. Sreekanth, B. M. Kim, Adv. Synth. Catal., 346,
2004, 49.
8. B. Northrup, D. W. C. MacMillan, J. Am. Chem. Soc., 124,
2002, 2458.
36. ZꢀL. Shen, HꢀL. Cheong, YꢀC. Lai, WꢀY. Loo, TꢀP. Loh,
Green. Chem., 2012, 14, 2626. (b) Z. L. Shen, K. K. K. Goh,
C. H. A. Wong, W. Y. Loo, Y. S. Yang, J. Lu and T. P.
Loh, Chem. Commun., 2012, 48, 5856
9. R. M. Wilson, W. S. Jen, D. W. C. MacMillan, J. Am. Chem.
Soc., 127, 2005, 11616.
10. T. Kano, Y. Tanaka, K. Maruoka, Org. Lett., 8, 2006, 2687.
11. K. H. Kim, S. Lee, DꢀW. Lee, DꢀH. Ko, DꢀC. Ha Tetrahedron
Lett., 46, 2005, 5991.
37. H. Hagiwara, T. Kuroda, T. Hoshi, T. Suzuki, Adv. Synth.
Catal., 352, 2010, 909.
38. T. O. Kristense, K. Vestli, M. G. Jakobsen, F. K. Hansen, T.
Hansen, J. Org. Chem., 75, 2010, 1620.
12. C. Biaggi, S. Rossi, S. Proto, R. Annunziata, M. Benaglia,
Tetrahedron Lett., 48, 2007, 8521.
39. M. S. Chauhan, S. Singh, J. Mol. Catal. A. Chem., 398, 2015,
184.
13. M. Lemay, WꢀW. Ogilvie Org. Lett., 7, 2005, 4141.
14. Y. Langlois, A. Petit, P. Rémy, MꢀC. Scherrmann, C.
Kouklovsky, Tetrahedron Lett., 49, 2008, 5576.
15. M. Lemay, W. W. Ogilvie, J. Org. Chem., 71, 2006, 4663.
16. M. Lemay, L. Aumand, W.W. Ogilvie Adv. Synth. Catal., 349,
2007, 441.
17. H. He, BꢀJ. Pei, HꢀH. Chou, T. Tian, WꢀH Chan, A. W. M.
Lee, Org. Lett., 10, 2008, 2421.
18. Q. Li, WꢀY, Wong, WꢀH. Chan, A. W. M. Lee Adv. Synth.
Catal., 352, 2010, 2142.
19. E. Gould, T. Lebi, A. M. Z. Slawin, M. Reid, T. Davies, A. D.
Smith Org. Biomol. Chem., 11, 2013, 7877.
20. H. Gotoh, Y. Hayashi, Org. Lett., 9, 2007, 2859.
21. Y. Hayashi, S. Samanta, H. Gotoh, H. Ishikawa, Angew. Chem.
Int. Ed., 47, 2008, 6634.
22. (a) M. Benaglia, G. Celentano, M. Cinquini, A. Puglisi, F.
Cozzi, Adv. Synth. Catal., 344, 2002, 149; (b) A. Puglisi, M.
Benaglia, M. Cinquini, F. Cozzi, G. Celentano, Eur. J. Org.,
2004, 567.
23. S. Guizzetti, M. Benaglia, J. S. Siegel, Chem. Commun., 48,
2012, 3188.
24. Y. Zhang, L. Zhao, S. S. Lee, J. Y. Ying, Adv. Synth. Catal.
,
348, 2006, 2027.
25. J. Y. Shi, C. A. Wang, Z. J. Li, Q. Wang, Y. Wang, W. Wang,
Chem. Eur. J., 17, 2011, 6206.
26. C. A. Wang, Y. Zhang, J. Y. Shi, W. Wang Chem. Asian J., 8,
2013, 1110.
27. C. O. Liang, J. M. J. Fréchet, Macromolecules, 38, 2005, 6276.
6 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 2012

Page 7 of 7
RSC Advances
View Article Online
DOI: 10.1039/C5RA09710J
Graphical Abstract
Synthesis of MacMillan catalyst tailored with ionic liquids as a recoverable catalyst
for asymmetric Diels-Alder reaction
ManMohan Singh Chauhan, Pramod Kumar and Surendra Singh*