Induced chirality in a metal-organic framework by postsynthetic modification for highly selective asymmetric aldol reactions

Article abstract of DOI:10.1002/cctc.201402082

A straightforward synthetic route to chiral metal-organic frameworks is proposed that relies on an acid-base interaction between an acid linker and a chiral primary amino acid derived diamine organocatalyst. High ee values for the aldol condensation of linear ketones and aromatic aldehydes are reported with this heterogeneous catalyst. Three consecutive catalyst reuse experiments demonstrated that the majority of the activity was preserved, as was the enantioselectivity.

Full text of DOI:10.1002/cctc.201402082

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DOI: 10.1002/cctc.201402082
Induced Chirality in a Metal–Organic Framework by
Postsynthetic Modification for Highly Selective
Asymmetric Aldol Reactions
Anneleen L. W. Demuynck,[a] Maarten G. Goesten,[b] Enrique V. Ramos-Fernandez,[b]
Michiel Dusselier,[a] Jozef Vanderleyden,[c] Freek Kapteijn,[b] Jorge Gascon,*[b] and
Bert F. Sels*[a]
A straightforward synthetic route to chiral metal–organic
frameworks is proposed that relies on an acid–base interaction
between an acid linker and a chiral primary amino acid derived
diamine organocatalyst. High ee values for the aldol condensa-
tion of linear ketones and aromatic aldehydes are reported
with this heterogeneous catalyst. Three consecutive catalyst
reuse experiments demonstrated that the majority of the activ-
ity was preserved, as was the enantioselectivity.
that are usually large. On the other hand, the templated ap-
proach is limited by the stability of the organocatalyst.[6]
In this work, we present a straightforward postfunctionaliza-
tion based on the noncovalent immobilization of a phenylala-
nine-derived chiral ligand on a sulfated achiral MOF derivative
through acid–base pair interaction. The presence of the orga-
nocatalyst in the MOF structure was confirmed with N2 sorp-
tion measurements, FTIR spectroscopy, and thermal gravimetri-
cal analyses. The morphology and framework of the solid
chiral catalyst was characterized by SEM and X-ray diffraction,
respectively. Very high enantioselectivities were obtained in
the direct asymmetric aldol reactions of various linear ketones
with aromatic aldehydes. The presented postsynthetic modifi-
cation strategy is very practical, straightforward, and flexible
towards the synthesis of a variety of chiral MOF structures with
very high stability.
Postsynthetic modification[7] of a preassembled achiral MOF
offers the advantage that a single, stable parental framework
can be converted into an active chiral MOF by carefully select-
ing the suitable catalytic chiral units. In 2009, Banerjee et al. re-
ported the synthesis of a chiral MOF by the attachment of
l-proline-derived chiral ligands to the open metal coordination
sites of MIL-101(Cr).[8] These homochiral MOFs were successful-
ly used in direct asymmetric aldol reactions. However, despite
reasonable activities in aldol reactions of ketones and aromatic
aldehydes, the enantioselectivity of the resulting framework
was low relative to that of other systems.[9] Previously, we re-
ported the use of primary amino acid derived diamines with
long alkyl tails as organocatalysts for direct syn-selective aldol
reactions.[10] Such chiral amines have been demonstrated to be
well suited for simple noncovalent immobilization on sulfonat-
ed solid supports such as Nafion through electrostatic interac-
tion.[9e] In this approach, the acid acts as the anchor for the
amine, but its acid strength also plays a crucial role in modu-
lating the activity and stereoselectivity of the supported cata-
lyst.
Although organocatalysis with amino acids and their deriva-
tives has proven very successful towards highly enantioselec-
tive condensation reactions, there is an urgent need to immo-
bilize these elegant and bioinspired chiral catalysis for easy
reuse. Many immobilization protocols that employ different or-
ganic and inorganic support materials have been discussed in
the literature, and most of them follow a covalent anchoring
strategy, sometimes with the prospect of using them in a flow
setup.[1] Metal–organic frameworks (MOFs)[2] are among the
most promising supporting materials: distinct from traditional
inorganic materials, MOFs can be synthesized from a large vari-
ety of building blocks. In spite of the large degree of unpre-
dictability in synthesis,[3] thousands of MOF structures have
been reported to date.[4] Different strategies have been em-
ployed to prepare homochiral MOFs, including chiral-template
and direct synthesis methods, either starting with enantiopure
ligands or through self-resolution from achiral or racemic mole-
cules.[5] The current methods for the synthesis of homochiral
MOFs have shown limited flexibility: on the one hand, if the
organocatalyst is used as a linker for MOF synthesis, catalysts
with limited stability are formed owing to linker dimensions
[a] Dr. A. L. W. Demuynck, Dr. M. Dusselier, Prof. B. F. Sels
Center for Surface Chemistry and Catalysis, KU Leuven
Kasteelpark Arenberg 23, B-3001 Heverlee (Belgium)
Fax: (+32)16321998
E-mail: bert.sels@biw.kuleuven.be
Building on the successful immobilization experiments with
the use of sulfonate-functionalized solid acids, herein we pres-
ent the first postmodification of a unique sulfated MIL-101(Cr),
denoted S-MIL-101(Cr), with chiral diamine organocatalysts
through acid–base interaction (Figure 1). As described recently,
treatment of preassembled MIL-101(Cr) with a stoichiometric
mixture of triflic anhydride and sulfuric acid results in an acidic
framework with Brønsted sulfoxy acid groups attached to 20%
of the aromatic terephthalate linkers.[11] This novel
[b] M. G. Goesten, E. V. Ramos-Fernandez, Prof. F. Kapteijn, Prof. J. Gascon
Chemical Engineering Department
Catalysis Engineering Section, Delft University of Technology
Julianalaan 136, 2628 BL Delft (The Netherlands)
E-mail: j.gascon@tudelft.nl
[c] Prof. J. Vanderleyden
Centre of Microbial and Plant Genetics, KU Leuven
Kasteelpark Arenberg 20, B-3001 Leuven (Belgium)
Supporting information for this article is available on the WWW under
http://dx.doi.org/10.1002/cctc.201402082.
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Figure 1. Schematic representation of the postsynthetic modification of a sul-
fated MIL-101(Cr) with a chiral primary amino acid derived diamine by acid–
base interaction.
S-MIL-101(Cr) has been employed as an acid catalyst in the
esterification of n-butanol with acetic acid.[11,12] By subsequent
noncovalent immobilization of a chiral diamine ligand [i.e.,
2-(S)-amino-3-phenylpropanoic acid dioctylamine] on the sul-
foxy acid groups of S-MIL-101(Cr), a MOF bearing chiral catalyt-
ic functionalities was created.
The presented postmodification strategy is straightforward
and versatile towards the synthesis of a variety of chiral MOF
structures. Although this communication particularly demon-
strates its use in catalyzing direct asymmetric aldol reactions of
ketones and aldehydes with very high enantiomeric excess (ee)
values, the range of potential catalytic applications is much
broader. Synthesis of the diamine/S-MIL-101(Cr) is simply per-
formed by dropwise addition of the diamine solution to a sus-
pension of S-MIL-101(Cr) in, for example, diethyl ether or an-
other polar volatile solvent of choice, followed by evaporation
of the solvent (for details see the Supporting Information).
Characterization of the diamine/S-MIL-101(Cr) was accom-
plished by using a range of standard techniques including N2
physisorption, XRD, thermogravimetric analysis (TGA), FTIR
spectroscopy, and SEM. The XRD pattern of the diamine/S-MIL-
101(Cr) material is similar to that of the MOF without the di-
amine (see Figure 2a), which indicates that the parental frame-
work structure after immobilization of the diamine ligand is re-
tained. The intensity of the diffraction peaks at approximately
2q<4 is considerably lower if the amine is adsorbed: the rela-
Figure 2. Physicochemical characterization of the chiral diamine modified
S-MIL-101(Cr) versus S-MIL-101(Cr): a) X-ray diffractogram with SEM images
given in the inset, b) FTIR spectra with zoom-in regions, and c) N2 physisorp-
tion.
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tive intensity of reflections [022], [113], and [222] is also
clearly affected. We attribute this intensity change to the suc-
cessful encapsulation of the amine unit in both the middle and
the large cavities, which is in line with results presented earlier
by Fꢁrey et al. after impregnation of heteropoly acids in MIL-
101(Cr)[13] and by Canioni et al. after encapsulation of other
HPAs in MIL-100(Fe).[14]
Table 1. Aldol reactions of linear ketones and aromatic aldehydes cata-
lyzed by diamine/S-MIL-101(Cr).[a]
Entry R1, R2, R3
Solid acid
Time Yield[b] dr[b]
ee[c]
[h]
[%]
syn/anti [%]
Similar crystal morphologies measured by SEM before and
after treatment with the diamine ligand confirm the stability of
the crystals and the absence of additional phases resulting
from nonabsorbed diamine (Figure 2a, see also Figure S3 in
the Supporting Information). The IR spectrum of the diamine/
S-MIL-101(Cr) shows additional bands at 2942, 2925, and
2854 cmÀ1, which represent the alkyl chains of the diamine,
and at 3282 cmÀ1, which corresponds to one of the NÀH
stretching bands (compare Figure 2b with Figure S4c).
In the fingerprint region, a small band appears at 700 cmÀ1
that represents one of the CÀH out-of-plane bending modes
of the diamine benzyl group. The bands at 1621 and
1506 cmÀ1 in Figure 2b corresponding to the C=C modes of
the aromatic rings in S-MIL-101(Cr) are maintained after func-
tionalization with the diamine. Further, the bands at 1276 and
1170 cmÀ1 along with the characteristic shoulder at 1430 cmÀ1,
which are attributed to O=S=O symmetric and asymmetric
stretching modes, can still be observed after postmodification,
as can the band at 1100 cmÀ1 corresponding to the interplane
skeletal vibration of the sulfoxy acid substituted benzene
ring.[11] The SÀO stretching band at 1030 cmÀ1 is slightly
changed, which is indicative of the interaction of the sulfonic
acid hydrogen atom with the tertiary amine nitrogen atom of
the chiral ligand.
1
2
3[d]
4[e]
5
H, CH3, 4-CF3
S-MIL-101
S-MIL-101
S-MIL-101
S-MIL-101
MIL-101
20
44
20
20
20
53
83
52
89
18
38
91
95
87
49
82
78
73
70
97
94
93
90
5:2
2:1
2:1
3:2
7:2
5:2
5:2
4:1
3:1
3:1
–
2:1
11:1
4:1
5:1
5:1
5:1
5:1
96
93
93
89
96
98
90
78
97
94
62
61
95
87
95
93
94
92
H, CH3, 4-CF3
H, CH3, 4-CF3
H, CH3, 4-CF3
H, CH3, 4-CF3
H, CH3, 4-CF3
H, CH3, 2-NO2
H, CH3, 4-NO2
H, CH3, 2-Cl
CH3, CH3, 4-CF3
H, H, 4-CF3
H, CH2CH3, 4-CF3 S-MIL-101
H, OH, 2-NO2
H, OH, 4-NO2
H, OH, 4-CF3
H, OH, 4-CF3
H, OH, 4-CF3
H, OH, 4-CF3
6[f]
7
8
9
10
11
12[g]
13
14
15
16[h]
17[h]
18[h]
NafionSAC-13 20
S-MIL-101
S-MIL-101
S-MIL-101
S-MIL-101
S-MIL-101
20
20
20
90
20
40
40
40
20
24
26
30
S-MIL-101
S-MIL-101
S-MIL-101
S-MIL-101
S-MIL-101
S-MIL-101
[a] All reactions were performed under neat conditions in ketone with al-
dehyde (0.125m), diamine (15 mol%), and solid acid (15 mol%) at room
temperature, unless indicated otherwise. [b] Determined by GC (chiral sta-
tionary phase) or 1H NMR spectroscopy. [c] The ee of the major syn
isomer, as determined by GC or HPLC on a chiral stationary phase.
[d] With 0.25m aldehyde. [e] Reaction at 458C. [f] See Ref. [10]. [g] Regio-
isomeric ratio branched/linear=2:5. [h] Entries 16–18: three consecutive
reuses of the catalyst used in entry 15.
As could be expected, diamine/S-MIL-101(Cr) contains
a larger carbon fraction than the parent MOF, as determined
by TGA analysis and in agreement with the amount of added
binding complex (see Figure S5 and calculations). TGA analysis
also suggests the presence of diamine in the pores of S-MIL-
101(Cr), as without the diamine more water was released from
the pores relative to that released by diamine-functionalized S-
MIL-101(Cr). The N2 physisorption data in Figure 2c clearly
show a reduced micropore volume owing to diamine grafting.
Together with the IR spectroscopy data, these results indicate
the successful attachment of the chiral diamine ligand in the
porous MOF structure.
port (Table 1, entry 5). Despite high stereoselectivity, the activi-
ty of the organocatalyst was significantly reduced compared to
the reaction with the sulfated MOF, which yielded only 18% of
the aldol product after a reaction time of 20 h. Note that the
latter experiment was similar to aldol reactions performed with
the homochiral postmodified MIL-101(Cr) as described by
Banerjee et al., though with a primary amino acid derivative in-
stead of a proline-based ligand as the chiral unit.[8] Interesting-
ly, the activity of the diamine catalyst is clearly higher with the
sulfated MOF than with the previously investigated commercial
sulfonated silica-polymer Nafion SAC-13 as support (Table 1,
entry 6),[9e] with 53 versus 38% yield after a reaction time of
20 h, than with the sulfonated carbon and homemade resins,[9e]
though the reason is not yet clear.
The catalytic performance of the diamine immobilized on S-
MIL-101(Cr) was evaluated in asymmetric aldol reactions of var-
ious linear ketones and aromatic aldehydes. First, the support-
ed diamine was applied in the model reaction with 2-butanone
and the reaction conditions were optimized. As shown in
Table 1, fairly high activity and very high enantioselectivity for
the syn product were obtained in the model reaction with
15 mol% diamine/S-MIL-101(Cr) under neat conditions (Table 1,
entries 1 and 2). Neither increasing the aldehyde concentration
(Table 1, entry 3) nor raising the temperature (Table 1, entry 4)
had a beneficial influence on either the activity or the stereose-
lectivity of the diamine/S-MIL-101(Cr) catalyst. Next, the model
reaction was catalyzed by the diamine in the presence of the
original, non-sulfated MIL-101(Cr) framework as the acid sup-
Ultimately, the scope of the diamine/S-MIL-101(Cr) catalyst
was extended to other substrates (Table 1, entries 7–15). With
2-butanone, 3-pentanone, and hydroxyacetone as ketone
donors, good activities and fair to outstanding stereoselectivi-
ties were achieved. For instance, in the reaction of hydroxyace-
tone and 4-trifluoromethylbenzaldehyde a very high yield and
enantiomeric excess of 95% for the syn product were observed
(Table 1, entry 15). With acetone and 2-pentanone (Table 1, en-
tries 11 and 12), the catalytic performance of diamine/S-MIL-
101(Cr) was somewhat limited, inherent to the homogeneous
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complex, but this was also observed with previous heteroge-
neous catalysts such as Nafion as a solid acid.[9e,10]
Keywords: aldol
heterogeneous catalysis
organocatalysis
reaction
·
asymmetric catalysis
·
·
·
metal–organic frameworks
To exclude significant leaching of the chiral ligand during
1
catalytic reactions, the H NMR spectra of the filtered reaction
solutions and the diamine catalyst were compared region by
region. In Figure S6, the regions from 3.2 to 2.0 ppm of the
1H NMR spectra of the diamine and the reactions mixtures with
different ketones are displayed. The absence of characteristic
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1
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after reaction and reused in three consecutive reactions under
identical conditions (i.e., Table 1, entries 16–18). A slight deacti-
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achieve yields >90%. However, the majority of the activity
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In summary, we presented a new strategy for the synthesis
of MOFs bearing chiral functionalities by postsynthetic modifi-
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l-phenylalanine-derived diamine was immobilized on a sulfated
MIL-101(Cr) framework through acid–base pair electrostatic in-
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excellent enantioselectivities in direct asymmetric aldol reac-
tions of linear ketones and aromatic aldehydes. We believe
that this synthesis method is an elegant and practical method
to obtain MOFs with chiral properties, as synthetic efforts for
the parent MOF are limited. The modular and combinatorial
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catalytic properties of some MOF materials paves the way to
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We are grateful to the Instituut voor Innovatie door Wetenschap
en Technologie (IWT) for a Ph.D. fellowship to A.D. M.D. acknowl-
edges FWO Vlaanderen for financial support as a postdoctoral re-
searcher. Interuniversity Attraction Poles (IAP) as well as EU-Marie
Curie Actions and the Dutch National Science Foundation (NWO-
CW VENI) are thanked for financial support.
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Received: February 27, 2014
Published online on July 14, 2014
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