Self-assembled organic-inorganic hybrid silica with ionic liquid framework: A novel support for the catalytic enantioselective Strecker reaction of imines using Yb(OTf)3-pybox catalyst

Article abstract of DOI:10.1039/c0cc01426e

Yb(OTf)₃-pybox is immobilized in a novel self-assembled ionic liquid hybrid silica and has been successfully applied as a catalyst for the asymmetric Strecker hydrocyanation of aldimines. This catalytic system can be reused for at least 6 times without any significant loss of activity and enantioselectivity.

Full text of DOI:10.1039/c0cc01426e

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Self-assembled organic–inorganic hybrid silica with ionic liquid
framework: a novel support for the catalytic enantioselective Strecker
reaction of imines using Yb(OTf)3–pybox catalystw
Babak Karimi,*a Aziz Maleki,a Dawood Elhamifar,a James H. Clarkb and Andrew J. Huntb
Received 16th May 2010, Accepted 2nd August 2010
DOI: 10.1039/c0cc01426e
Yb(OTf)3–pybox is immobilized in a novel self-assembled ionic
liquid hybrid silica and has been successfully applied as a catalyst
for the asymmetric Strecker hydrocyanation of aldimines. This
catalytic system can be reused for at least 6 times without any
significant loss of activity and enantioselectivity.
modification of the commercially available chiral ligands
(or catalysts) is necessary.7
Ionic liquids (ILs) have attracted significant attention over
the last decade, and their applications as green reaction media
have been widely explored.8 However, since ionic liquids are
very expensive and their environmental impact due to wasteful
preparation procedures or toxicity can be high, their wide-
spread practical applications are very limited, where the
properties of ILs offer particular value it is desirable to keep
the amount of ionic liquids required to a minimum and here
immobilization on solid supports is a viable option.9 Although,
these supported ionic liquid catalysis (SILC) systems signifi-
cantly reduce the amount of IL in a typical process, loading of
the chemically immobilized IL can mean very high solids
loading in the reaction and ILs commonly leach from the
support. Moreover, there is no precedent on the use of this
strategy in the catalytic asymmetric Strecker reaction of
imines. Very recently, we have explored a highly enantio-
selective Strecker hydrocyanation of a wide variety of aldimines
giving good to excellent yields and enantioselectivities using
homogeneous Yb(OTf)3–pybox complexes.10 Despite the signifi-
cant utility of this catalyst system in asymmetric Strecker
reaction, the catalysts could not be recycled.
The catalytic asymmetric Strecker reaction provides a straight-
forward and facile approach for the preparation of chiral
a-aminonitriles, which are important structural motifs for
construction of both natural and unnatural a-aminoacids.1
The development of efficient chiral catalysts continues
to be one of the most challenging aspects of this and a
number of either metal-based chiral Lewis acid catalysts2 or
organocatalysts3 have been introduced for the activation of
the carbon=nitrogen double bond of imines followed by the
enantioselective addition of cyanide ion sources. While signifi-
cant progress has been made, the majority of reported
catalysts are homogeneous where separation of the expen-
sive chiral catalysts from products and their reuse can be
problematic.4 This is an especially serious problem in the
pharmaceutical industry because the level of metallic impurities
in active pharmaceutical intermediates is closely regulated. In
this regard, immobilized catalysts offer advantages over non-
immobilized systems and in some instances heterogeneous
catalysts can lead to higher enantiomeric excess than their
homogeneous counterparts.5 However, despite the attractive-
ness of using immobilized enantioselective catalysts, to the
best of our knowledge, there are only two reports on the
application of supported chiral catalysts in the asymmetric
Strecker reaction through the pioneering work of Jacobsen
and Shibasaki.6 The main strategy in these is to immobilize
chiral catalysts through the formation of a covalent bond
between the solid support (polymeric or inorganic) and the
chiral catalyst. While this strategy is the most popular method
for the immobilization of chiral homogeneous catalysts, it
often needs an additional functionalization step of the chiral
ligands, which may increase the total catalyst preparation cost.
Therefore, in many applications it is more desirable to use
non-covalent immobilization strategies in which no further
Herein, we present the first use of a Self-Assembled organic–
inorganic hybrid silica with Ionic Liquid Phase (SAILP) as a
novel support for chiral Yb(OTf)3–pybox catalyst system in
which the catalyst remains active, and highly selective, over
extended periods in catalytic asymmetric Strecker reactions of
imines. We have found that not only SAILP hybrid silica is a
superb support for Yb(OTf)3–pybox, but also the resulting
immobilized material catalyzes the Strecker reaction in a hetero-
geneous pathway, without leaching of the catalyst into
solution under the described reaction condition. The self-
assembled ionic liquid phase (SAILP) was prepared by hydrolysis
and co-condensation of 1,3-bis(3-trimethoxysilylpropyl)-
imidazolium iodide (BTMSPI)11 under mild acidic conditions
(Scheme 1).
The resulting yellow solid was characterized by simul-
taneous thermal analysis and solid-state NMR. The uniform
a Department of Chemistry, Institute for Advanced Studies in Basic
Sciences (IASBS), Gava Zang, Zanjan 45137-6731, Iran.
E-mail: karimi@iasbs.ac.ir; Fax: +98 241-4214949;
Tel: +98 241-4153225
b Green Chemistry Centre of Excellence, University of York, York,
YO10 5DD, UK
w Electronic supplementary information (ESI) available: Experimental
section, FT-IR, and 1H and 13C NMR spectra of the materials, HPLC
chromatograms of the products. See DOI: 10.1039/c0cc01426e
Scheme 1 Preparation of SAILP material.
c
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distribution of alkyl imidazolium group in the silica frame-
work of the material was confirmed by 29Si- and 13C-CP–MAS
NMR spectroscopy. The 29Si spectrum of SAILP displays
three signals at À49.1, À58.52 and À68.36 ppm corresponding,
respectively, to T1 [C–Si(OSi)(OH)2], T2 [C–Si(OSi)2(OH)],
and T3 [C–Si–(OSi)3] sites for Si species which are covalently
attached to carbon atoms (see ESIw, Fig. S1). In addition, the
absence of any resonance at À90 to À115 ppm which are
related to Qn sites of the silica framework clearly shows that
no carbon–silicon bond cleavage of the BTMSPI molecules
occurred in the synthesis conditions of SAILP.
The solid state 13C CP–MAS NMR spectrum of SAILP was
also determined to clarify the characteristic signals of the IL
bridging moieties (see ESIw, Fig. S2). This spectrum illustrates
carbon signals of ionic liquid moieties as follows: d (ppm) = 10.5
(SiCH2), 24.7 (CH2CH2CH2), 52.8 (CH2N), 123.6 (CHCH),
and 136.7 (NCHN). These data show that the ionic liquid
groups were indeed well incorporated intact into the material
network. Moreover, the absence of any other carbon signal
confirms that almost all of the Si–C bonds survived intact
under the synthesis conditions. Thermogravimetric analysis of
the SAILP composite was conducted from room temperature
to 900 1C (see ESIw, Fig. S3). A loss of 2–5 wt% below 120 1C
is due to the loss of residual methanol and water. This is
followed by a second large main weight loss of B39% between
350–450 1C due to decomposition of alkyl imidazolium
groups inside the SAILP framework. The amount of ionic
liquid incorporated into the framework of the materials was
estimated from the TGA to be B85% of the ionic liquid in the
initial gel. This was further confirmed by elemental analysis of
the material.
Table 1 Enantioselective Strecker reaction of N-benzylidenediphenyl-
methanamine catalyzed by Yb(OTf)3–pybox catalyst systema
Yield (ee)b,c
[%]
Run
Catalyst
T/oC
Time/h
1d
2
Yb(OTf)3–pybox@SAILP
Yb(OTf)3–pybox
À78
À78
À50
À50
À50
48
30
36
36
36
o5 (ND)
95 (97)
95 (80)
93 (53)
97 (39)
3d
4
Yb(OTf)3–pybox@SAILP
Yb(OTf)3–pybox
5
Yb(OTf)3–pybox/ILe
a
Yb(OTf)3 (10 mol%)/pybox (20 mol%), TMSCN (2 equiv.), MeOH
b
c
(2 equiv.). Yields refer to isolated products. Enantiomeric excesses
were determined by HPLC analysis on a CHIRALPAK AD column.
d
e
0.6 g of SAILP was used. BTMSPI was used as ionic liquid.
note that while the same reaction using homogeneous
Yb(OTf)3–pybox under identical reaction conditions went to
completion within 36 h, the enantiomeric excess of 3 was only
53% (Table 1, entry 4). In a separate experiment, the use of
1,3-bis(3-trimethoxysilylpropyl)imidazolium iodide (BTMSPI)
instead of the solid support was shown to give much worse results
further confirming the beneficial role of SAILP in obtaining
acceptable enantioselectivities (Table 1, entry 5). These results
clearly show the existence of a synergistic effect between the
SAILP and that of immobilized Yb(OTf)3–pybox catalyst system.
Under the optimized reaction conditions (Table 1, entry 3),
we then investigated the generality of our method with respect
to the aldimine structure (Table 2). A range of aromatic aldimines,
including substituted aromatic (entries 2–9, 12 and 13), hetero-
aromatic (entries 10 and 11), a,b-unsaturated (entry 14), and
aliphatic aldehyde-derived aldimines (entry15), were tested
in the asymmetric Strecker hydrocyanation using our new catalyst,
giving a-aminonitriles in good to excellent yields with modest to
high level of enantioselectivity. Remarkably, the imines derived
from pyridine-3-carbaldehyde and thiophene-2-carbaldehyde are
effective substrates, affording the respective products in 71% and
82% ee, respectively (Table 2, entries 10 and 11). However, when
more challenging a-unbranched aliphatic aldimines were used,
the enantioselectivities were not complete even under a modified
three-component procedure (Table 2, entries 15 and 16).
In the next stage, the ability of this self-assembled ionic
liquid to immobilize Yb(OTf)3–pybox catalyst and its use in
the Strecker reaction was examined (Scheme 2).
Asymmetric catalysis using the supported chiral catalyst 1
(equivalent to 10 mol% of Yb(OTf)3–pybox) was investigated
in the reaction of N-benzylidenediphenylmethanamine 2 with
trimethylsilyl cyanide (TMSCN) under our previously reported
condition at À78 1C (Table 1, entry 1).10 Although high yields
and enantioselectivity were obtained under homogeneous
conditions (Table 1, entry 2), using the heterogeneous chiral
catalyst 1 gave disappointing results (Table 1, entry 1). In light
of the above observation, and based on the assumption that
the aldimine 2 is less prone to reaction at À78 1C, we examined
the Strecker reaction of 2 at higher temperatures. We found
that by increasing the reaction temperature to À50 1C, the
Strecker reaction started and proceeded smoothly at this
temperature using 1 as catalyst, and the desired a-aminonitrile
3 was isolated in an excellent yield of 95% after 36 h with high
enantioselectivity of 80% (Table 1, entry 3). It is important to
We attribute the low enantioselectivities in the case of
aliphatic aldimines to isomerization of the imine to the corres-
ponding enamine and also to a-racemization of the corres-
ponding a-aminonitriles under the reaction conditions. However,
considering the significant difficulty of this type of reaction, we
believe that the enantioselectivities are still in a synthetically useful
range. To further clarify the advantages of our heterogeneous
chiral ytterbium catalyst, Table 2 also summarizes both the
catalytic activity and enantioselectivity of our previous homo-
geneous system10 for the same reaction conditions at À50 1C
(entries 17–24). These results clearly confirm that ee values were
consistently higher when using 1 rather than its homogeneous
analogue under the described reaction conditions (temperature
range À60 1C to À40 1C).
We have also found that our catalyst demonstrated excellent
reusability; after the first use of the catalyst 1 in the asymmetric
Scheme 2 Preparation of heterogeneous chiral catalyst 1 and its
application in the asymmetric Strecker reaction.
c
6948 Chem. Commun., 2010, 46, 6947–6949
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Table 2 Enantioselective Strecker reaction of aldimines catalyzed by
Yb(OTf)3–pybox@SAILP catalyst systema
Notes and references
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Yield (ee)b,c
[%]
Run
R
Time/h
T/1C
1
2
3
4
5
6
7
8
Ph
36
48
72
72
72
72
72
72
72
72
96
72
48
72
48
48
36
72
72
72
48
72
72
48
À50
À60
À50
À50
À40
À40
À40
À40
À60
À50
À50
À50
À50
À50
À50
À50
À50
À40
À40
À50
À60
À50
À50
À50
95 (80)
94 (79)
93 (71)
86 (77)
81 (86)
71 (53)
88 (71)
58 (71)
92 (74)
95 (71)
55 (82)
89 (60)
81 (72)
97 (90)
91 (44)
85 (45)
95 (53)
95 (46)
97 (70)
96 (50)
98 (62)
98 (62)
72 (56)
95 (34)
2-Me–C6H4
3-Me–C6H4
4-Me–C6H4
2-Br–C6H4
3-Br–C6H4
4-Br–C6H4
2-Cl–C6H4
2-Naphthyl
3-Pyridyl
9
10
11
12
13
14
15d
16d
17e
18e
19e
20e
21e
22e
23e
24d,e
2-Thenyl
3-TBDMSO–ph
2,4-Me2–C6H3
Ph–CHQCH
Ph–CH2CH2
CH3(CH2)5
Ph
2-Cl–C6H4
2-Br–C6H4
4-Me–C6H4
2-Me–C6H4
Ph–CHQCH
3-Pyridyl
Ph–CH2CH2
a
Yb(OTf)3 (10 mol%)/pybox (20 mol%), SAILP (0.6 g), TMSCN
b
(2 equiv.), MeOH (2 equiv.) unless otherwise stated. Yields refer to
c
isolated products. Enantiomeric excesses were determined by HPLC
d
analysis on a CHIRALPAK AD column. Reaction was performed
e
under one pot conditions. Yb(OTf)3 (10 mol%)/pybox (20 mol%),
TMSCN (2 equiv.), MeOH (2 equiv.) under homogeneous conditions.
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catalyst was washed with n-hexane and the recovered catalyst
was successfully used in 6 subsequent reaction runs and exhibited
remarkably consistent enantioselectivities (Fig. 1). To rule out
the contribution of homogeneous catalysis, the asymmetric
Strecker reaction of 2 was attempted using the residue from
the n-hexane extraction. No appreciable amount of enantio-
selectivity was observed even after prolonged reaction time
(72 h) at À50 1C. This result clearly confirms that the reaction
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The authors acknowledge the IASBS Research Council and Iran
National Science Foundation (INSF) for support of this work.
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Fig. 1 Reusability of the Yb(OTf)3–pybox@SAILP catalyst in the
enantioselective Strecker reaction of N-benzylidenediphenylmethanamine.
12 For further discussion about the nature of catalyst see ESIw.
c
This journal is The Royal Society of Chemistry 2010
Chem. Commun., 2010, 46, 6947–6949 6949