Highly Stable Zr(IV)-Based Metal-Organic Frameworks with Chiral Phosphoric Acids for Catalytic Asymmetric Tandem Reactions

Article abstract of DOI:10.1021/jacs.9b02294

Heterogeneous Br?nsted acid catalysts featuring high porosity, crystallinity, and stability have been of great interest for both fundamental studies and practical applications, but synthetically, they still face a formidable challenge. Here, we illustrated a ligand design strategy for directly installing chiral phosphoric acid catalysts into highly stable Zr-MOFs by sterically protecting them from coordinating with metal ions. A pair of chiral porous Zr(IV)-MOFs with the framework formula [Zr₆O₄(OH)₈(H₂O)₄(L)₂] were prepared from enantiopure 4,4′,6,6′-tetra(benzoate) and -tetra(2-naphthoate) ligands of 1,1′-spirobiindane-7,7′-phosphoric acid. They share the same topological structure but differ in channel sizes, and both of them demonstrate excellent tolerance toward water, acid and base. Significantly enhanced Br?nsted acidity was observed for the phosphoric acids that are uniformly distributed within the frameworks in comparison with the nonimmobilized acids. This not only facilitates the catalysis of asymmetric two-component tandem acetalization, Friedel-Crafts, and iso-Pictet-Spengler reactions but also promotes the catalysis of asymmetric three-component tandem deacetalization-acetalization and Friedel-Crafts reactions benefiting from the synergy with exposed Lewis acidic Zr(IV) sites. The enantioselectivities are comparable or favorable compared to those obtained from the corresponding homogeneous systems. The features of high reactivity, selectivity, stability, and recyclability for Zr(IV)-MOFs make them hold promise as a new type of heterogeneous acid catalyst for the eco-friendly synthesis of fine chemicals.

Full text of DOI:10.1021/jacs.9b02294

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Article
Highly Stable Zr(IV)-Based Metal-Organic Frameworks with Chiral
Phosphoric Acids for Catalytic Asymmetric Tandem Reactions
Wei Gong, Xu Chen, Hong Jiang, Dandan Chu, Yong Cui, and Yan Liu
J. Am. Chem. Soc., Just Accepted Manuscript • DOI: 10.1021/jacs.9b02294 • Publication Date (Web): 15 Apr 2019
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Highly Stable Zr(IV)-Based Metal-Organic Frameworks with Chiral
Phosphoric Acids for Catalytic Asymmetric Tandem Reactions
Wei Gong,† Xu Chen,† Hong Jiang,† Dandan Chu,† Yong Cui, *,†, ‡, and Yan Liu*,†
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†School of Chemistry and Chemical Engineering and State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University,
Shanghai 200240, China
‡Collaborative Innovation Center of Chemical Science and Engineering, Tianjin 300072, China
Supporting Information
ABSTRACT: Heterogeneous Brønsted acid catalysts featuring high porosity, crystallinity and stability have been of great interest for
both fundamental studies and practical applications, but synthetically they still face a formidable challenge. Here we illustrated a ligand
design strategy for directly installing chiral phosphoric acid catalysts into highly stable Zr-MOFs by sterically protecting them from
coordinating with metal ions. A pair of chiral porous Zr(IV)-MOFs with the framework formula [Zr6O4(OH)8(H2O)4(L)2] were prepared
from enantiopure 4,4’,6,6’-tetra(benzoate) and -tetra(2-naphthoate) ligands of 1,1’-spirobiindane-7,7’-phosphoric acid. They share the
same topological structure but differ in channel sizes, and both of them demonstrate excellent tolerance towards water, acid and base.
Significantly enhanced Brønsted acidity was observed for the phosphoric acids that are uniformly distributed within the frameworks in
comparison with the non-immobilized acids. This not only facilitates the catalysis of asymmetric two-component tandem acetalization,
Friedel-Crafts and iso-Pictet-Spengler reactions, but also promotes the catalysis of asymmetric three-component tandem
deacetalization-acetalization and Friedel-Crafts reactions benefiting from the synergy with exposed Lewis acidic Zr(IV) sites. The
enantioselectivities are comparable or favorable compared to those obtained from the corresponding homogeneous systems. The features of
high reactivity, selectivity, stability and recyclability for Zr(IV)-MOFs make them hold promise as a new type of heterogeneous acid
catalyst for the eco-friendly synthesis of fine chemicals.
As a class of fairly strong Brønsted acids, chiral phosphoric
INTRODUCTION
acids derived from axially chiral biaryls, especially BINOL
(1,1’-binaphthol)32 and SPINOL (1,1’-spirobiindane-7,7’-diol)33
To achieve high reactivity and selectivity, great efforts have
have been proved to be privileged catalysts enabling a broad range
of enantioselective reactions involving imines [e.g. Mannich,34
Friedel-Crafts (F-C),35 aza-Diels-Alder36 and Pictet-Spengler (P-S)
reactions37]. Compared with the BINOL backbone, the spirocyclic
SPINOL possess a geometrically different and more rigid and
narrow cavity and enable readily control of the steric and
electronic properties of the asymmetric environment of the
phosphoric acid catalyst.38 We envisaged that introduction of
steric bulky binding functional groups at the 6,6’-positions of the
SPINOL backbone may protect phosphoric acids from
coordinating to large metal clusters such as [Zr6O4(OH)8(H2O)4],
whereas the primary functional groups can be linked by
metal-connecting units to produce extended networks. Here we
reported the construction of two robust Zr(IV)-CMOFs with a
topological isostructure from the newly designed enantiopure
4,4’,6,6’-tetra(benzoate) and -tetra(2-naphthoate) ligands of
1,1’-spirobiindane-7,7’-phosphoric acid. The uncoordinated
phosphoric acids within the frameworks can catalyze asymmetric
two-component tandem acetalization, F-C and iso-P-S reactions
and can also work with the exposed Lewis acidic Zr(IV) sites to
promote asymmetric three-component tandem deacetalization
-acetalization and F-C reactions, with enantioselectivity
comparable to or surpassing the homogeneous analogs. It should
be noted that MOFs have been used in tandem reactions where
multiple continuous reactions are combined into one process, but
none of them are capable of promoting enantioselective tandem
reactions.39,40
been devoted to developing heterogeneous Brønsted acid catalysts
that are highly porous, crystalline and stable.1-5 Conventional
solid acids, however, generally lack structural uniformity and
possess diverse types of active sites, differing in both activity and
selectivity.6,7 One class of hybrid solids that can provide
exceptional structural uniformity and permanent porosity are
metal-organic frameworks (MOFs).8 Owing to the highly modular
nature and facile tunability, MOFs have shown promising
applications in diverse areas.9,10 Especially, the discovery of
MOFs constructed from high-valent metals such as Zr(IV) and
Cr(III) has dramatically increased MOF stability and
robustness,11-15 which make them an ideal platform for designing
single-site heterogeneous catalysts for important chemical
reactions such as asymmetric transformations.16-29 With few
exceptions,16-18 however, the reported chiral MOFs (CMOFs)
typically showed limited stability under acidic and alkaline
conditions.19-29 Moreover, the dominated majority of them are
Lewis acid-type catalysts derived from privileged chiral
ligands16-25 and only few are Brønsted acid species that displayed
only low to moderate enanioselectivities (6-84% ee).26-29 It is
difficult to prepare CMOFs with strong Brønsted acid sites (BASs)
from sulfonated or phosphonated organo- catalysts because they
tend to bind to metal ions and hence lose Brønsted acidity in MOF
synthesis.30,31 Therefore, the synthesis of highly stable CMOFs
with strong BASs remains a big challenge to be addressed. In this
work, we demonstrated that catalytically active chiral phosphoric
acids can be directly incorporated into robust and porous
Zr(IV)-MOFs by sterically protecting them from coordinating
with metal ions.
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O
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OH
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(S)-H4
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Zr6O4(OH)8(H2O)4(COO)8
O
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+
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HO
OH
O
O
O
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(S)-H4
OH
sjt-a topology
O
OH
HO
O
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Figure 1. (a) Construction of Spiro-1 and Spiro-2 from the Zr6 clusters linked by H4L to give the sjt-a topology. (b) The hexagonal bipyramid cages and (c)
the 3D porous structures in Spiro-1 (left) and Spiro-2 (right) viewed along the c-axis. The cavities are highlighted by yellow ellipsoids, and H atoms are
omitted for clarity.
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phosphoric acid functionalities that are beneficial for chiral guest
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RESULTS AND DISCUSSION
recognition and inclusion.
From the topological viewpoint, the Zr6 cluster and the SPINOL
ligand can be regarded as 8- and 4-connected nodes, respectively.
As a result, as shown in Figure 1a, the structures of Spiro-1 and
Spiro-2 can be simplified as (4,8)-connected net with the point
symbol of {410.616.82}{412.614.82}2{44.62}4{45.6}2, herein named
sjt (Shanghai Jiao Tong University) and now added to the
Reticular Chemistry Structure Resource (RCSR) database. By far,
a lot of (4,8)-connected MOFs have been reported and most of
them exhibit flu, scu, sqc or csq topology.15,42,44,45 Spiro-1 and
Spiro-2 represent the first two MOFs with sjt net topology. After
removing free solvent molecules, the total solvent-accessible
volumes of Spiro-1 and Spiro-2 are estimated to be 73.2% and
91.7%, respectively, as calculated using the PLATON routine.46
To our knowledge, the calculated void space of Spiro-2 are
among the highest values reported for Zr-MOFs and take over the
second place in about 70000 reported MOFs (The recorded
material is MOF-39947 with ca. 94% void space) (Table S12).
Circular dichroism (CD) spectra of Spiro-1 and Spiro-2 made
from S and R enantiomers of the corresponding ligand are mirror
images of each other, indicative of their enantiomeric nature
(Figure S4). The permanent porosity of Spiro-1 was demonstrated
by N2 adsorption measurements at 77 K. After desolvation of the
Synthesis and Characterization. Most of the reported Zr(IV)-
MOFs with tetratopic carboxylate ligands are based on rigid
platforms such as porphyrin,15 tetraphenylethylene,41 pyrene42 and
biphenyl.43 All these Zr-MOFs were found to display excellent
chemical stabilities and large surface areas. However, tetratopic
linkers with inherent chirality have not yet been explored for
construction of Zr-MOFs, although synthesis of highly stable
MOFs with rich chirality-related functions has been of great
concern. The newly designed linker H4L1 and H4L2 were prepared
from enantiopure (S)- or (R)-SPINOL in four steps in 58% and 47%
overall yields, respectively. Heating ZrCl4 and H4L1 or H4L2 in the
presence of formic acid as competing reagent in DMF afforded
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colorless
hexagonal
pyramid-shaped
crystals
of
[Zr6O4(OH)8(H2O)4(L1)2] (Spiro-1) or [Zr6O4(OH)8(H2O)4(L2)2]
(Spiro-2). They have been fully characterized by a variety
techniques including IR spectroscopy, microanalysis and
thermogravimetric analysis (TGA). The phase purity of them was
established by comparison of their observed and simulated powder
X-ray diffraction (PXRD) patterns.
Single-crystal X-ray diffraction reveals that Spiro-1 and
Spiro-2 crystallize in different space groups but with the same
structural topology. Spiro-1 crystallizes in the hexagonal chiral
space group of P6222 with three-fourths of the formula in the
asymmetric unit. There are two different types of eight-connected
Zr6O8 clusters with D4h or D2d symmetry in the framework (Figure
S1). Six Zr atoms are connected by four μ3-O and four μ3-OH
groups to generate Zr6(μ3-O)4(μ3-OH)4 cluster, with four -OH and
four H2O attached as terminal groups. Each Zr6 cluster is linked
by one bidentate carboxylate from a H4L1 ligand to give an
8-connected building unit. For the D4h cluster, an octahedral Zr6
cluster is capped by eight μ3-OH/O atoms, which form an ideal
octahedron (Figure S1). Similar D2d and D4h symmetric Zr6
building units were observed in PCN-22515 and NU-1000,42
o
acetone-exchanged sample by heating at 100 C under dynamic
vacuum overnight, Spiro-1 remained high crystallinity and exhibit
a type I sorption behavior, with a Brunauer–Emmett–Teller (BET)
surface area of 2002 m2 g-1. In contrast, the evacuated Spiro-2
almost lost crystallinity (Figure 2c) and exhibited moderate CO2
adsorption of 140.5 cm3 g-1 (27.8 wt%), but no N2 adsorption. It is
presumably due to the smaller kinetic diameter of CO2 (3.30 Å)
compared to N2 (3.64 Å), allowing its diffusion in the contracted
pore apertures. We also attempted to activate Spiro-2 through a
supercritical CO2 drying method to avoid capillary forces
collapsing the MOF, but still failed to keep its crystallinity. This
may be ascribed to the extremely high void space (91.7%) that
easily distorts in guest-free state. However, after soaking the
activated samples in fresh DMF, the crystallinity of Spiro-2 can
be fully restored (Figure 2c), suggesting that the material went
through a structural distortion that is recoverable via re-solvation.
This phenomenon is often observed in highly porous MOFs.17,47
Dye uptake experiments were then used to certify the structural
integrity of the CMOFs in solution. Spiro-1 and Spiro-2 can
adsorb 4.3 and 5.9 methyl orange (MO,  1.47 nm × 0.53 nm),
and 2.4 and 4.1 rhodamine 6G ( 1.43 nm × 1.61 nm) per formula
unit in MeOH, respectively (Table S4). In all cases, the inclusion
samples gave almost the same PXRD patterns as the pristine
sample (Figures 2a,c). The above results implied that the
structural integrity and open channels of the two MOFs are
maintained in solution.
Chemical Stability. As expected, both Spiro-1 and Spiro-2
showed excellent thermal stability. Thermogravimetric analysis
(TGA) showed that guest molecules within them could be
removed in the temperature ranging from 80 to 140 °C, and the
frameworks started to decompose at about 430 °C.
The chemical stability of their frameworks was examined by
PXRD and N2 sorption after treatment in boiling water, 0.01 M
NaOH (aq.) and concentrated HCl (aq.) at r.t. for one week, as
well as dye uptake measurements. As shown in Figure 2, PXRD
patterns of the two CMOFs after these treatments remained intact,
suggesting that no phase transition or framework collapse
happened. Moreover, in all cases, the Spiro-2 crystals still
displayed strong single-crystal diffractions with almost unchanged
unit cell parameter (Figure S7), further confirming the framework
stability. Both of the as-treated CMOFs remained permanent
porosity, as evidenced by BET measurements (Figures 2b,d). Dye
uptake measurements showed the samples of Spiro-1 and Spiro-2
respectively. The SPINOL ligand exhibits
a tetradentate
coordination fashion, binding to four Zr atoms of four Zr6 cluster
via four bidentate carboxylate groups. The bite angle of the
SPINOL skeleton in Spiro-1 is calculated to be 53.4°, which is a
little smaller than the angle of 57.3°of the ligand H4L1. As shown
in Figure 1b, the framework consists of a large hexagonal
bipyramid mesoporous cage with an inner cavity size of 2.3 × 3.3
× 3.9 nm3 (atom-to-atom distance), encapsulated by eight Zr6
clusters as the vertices and twelve L1 linkers as the faces that are
related by C3 symmetry. The cage cavities are periodically
decorated with the phosphoric acid groups of SPINOL backbones
that are accessible to guest molecules. The amphiphilic cage is
surrounded by ten adjacent cages with four of them sharing edges
and others sharing vertices (Figure S2), thus generating a 3D
porous structure with interconnected 1D open channels of 6.1 ×
3.2 Å2, 6.1 × 9.5 Å2 and 13.9× 13.9 Å2 along the a-, b- and c- axis,
respectively (Figure 1c).
Spiro-2 crystallizes in the trigonal chiral space group of P3221
with three-seconds of the formula in the asymmetric unit. It has a
similar 3D network to Spiro-1, despite their different space group.
In contrast to Spiro-1, Spiro-2 contains only one type of
8-connected Zr6 cluster with D2d symmetry, which may be
responsible for the lower symmetry of the whole framework. The
framework also possesses a hexagonal bipyramid cage with an
inner cavity size of about 2.5 × 4.1 × 4.9 nm3 (atom-to-atom
distance) (Figure 1b). When viewed along the a-, b- and c- axis ,
the porous structure exhibits interconnected 1D open channels of
10.3 × 6.5 Å2, 10.3 × 14.8 Å2 and 18.5 × 18.5 Å2, respectively
(Figure S3). To the best of our knowledge, Spiro-1 and Spiro-2
are the first two examples of zeolite-like MOFs containing chiral
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Figure 2. (a) PXRD patterns of Spiro-1 under different conditions. (b) N2 adsorption isotherms for Spiro-1 at 77 K. (c) PXRD patterns of Spiro-2 under
different conditions. (d) CO2 adsorption isotherms for Spiro-2 at 273 K, showing the framework stability upon treatment with boiling water, 0.01M NaOH
and concentrated HCl. (e) PXRD patterns of Spiro-1 after 10 recycle runs of catalytical reactions. (f) Recycle results for the Spiro-1 catalyzed
three-component F-C reaction using indole, p-bromobenzaldehyde and p-toluenesulfonamide as substrates.
after these treatments could adsorb 2.5/2.0/2.2 and 3.4/2.9/3.1
rhodamine 6G per formula unit (Table S4), respectively,
comparable to the untreated sample, indicative of the structural
integrity. The chemical stability of the present two CMOFs is
similar to that reported for similar Zr6-based MOFs, which makes
them attractive chiral porous candidates for heterogeneous
catalysis and adsorption.
Brønsted acidity. The Brønsted acidity of a solid catalyst is of
great importance for catalytic applications. So, we tested the
Brønsted acidity of the two Zr-CMOFs as well as the related
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SPA
(3.3 ≤ H0 ≤ 4.0)
Thio-SPA
(-2.4 ≤ H0 ≤ -0.2)
Dithio-SPA
(-3.2 ≤ H0 ≤ -3.0)
Spiro-1
(-3.0 ≤ H0 ≤ -2.4)
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Me4L1
(2.8 ≤ H0 ≤ 3.3)
Me4L2
(2.8 ≤ H0 ≤ 3.3)
Spiro-2
(-2.4 ≤ H0 ≤ -0.2)
Figure 3. Hammett acidity of some SPINOL-based phosphoric acids, thio- and dithiophosphoric acids and Spiro-1 and Spiro-2.
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organic phosphoric acid and their derivatives by the Hammett
indicator method.48 As shown in Figure 3, the homogeneous
catalysts Me4L1 and Me4L2 displayed higher acidity (2.8 ≤ H0 ≤
3.3) than the unsubstituented SPINOL phosphoric acid (3.3 ≤ H0 ≤
4.0) because of installing electron-withdrawing carboxylate
groups on the SPINOL backbone.49 After incorporation into
MOFs, continue enhancement of the acidity of the SPINOL
phosphoric acid was observed (-3.0 ≤ H0 ≤ -2.4 and -2.4 ≤ H0 ≤
-0.2 for Spiro-1 and Spiro-2, respectively), which even surpass
that of the SPINOL thiophosphoric acid (-2.4 ≤ H0 ≤ -0.2).
Moreover, Spiro-1 showed a color change even in a benzene
solution of 4-nitrodiphenylamine, indicating H0 ≤ -2.40 (Table
S13), a value approach to the strong SPINOL dithiophosphoric
acid (-3.2 ≤ H0 ≤ -3.0). Besides, the dehydrated Spiro-1 showed a
similar Brønsted acidity (-3.0 ≤ H0 ≤ -2.4) to the pristine sample,
indicating that the water molecules binding to the Zr6 clusters
have no obvious effects on the acidity of the immobilized
organocatalysts. The enhanced acidity may be attributed to
coordination of carboxylate groups of the linkers to metal ions that
withdraws electrons from the SPINOL skeleton, and the isolation
of phosphoric acids that prevents the formation of intermolecular
hydrogen bonding and promotes proton transfer.50 Further study is
greatly needed to understand the origin of the Brønsted acidity
enhancement of CMOFs.
Heterogeneous Catalysis. As mentioned above, chiral phosphoric
acids have been found to be excellent asymmetric Brønsted acid
catalysts for many meaningful organic transformations.32-37,51-54
Meanwhile, the Zr-oxo clusters are shown to be potential
catalytically active Lewis acid sites for a number of organic
transformations.12 The large crystalline pore sizes within the two
robust CMOFs should provide efficient access to uniformly
distributed phosphoric acid sites and Zr6 cluster and facilitate the
transport of reactants and products, which may give rise to high
activity and enantioselectivity in different catalytic reactions. This
prompted us to evaluate their heterogeneous catalytic behaviors in
several different organic transformations.
We first investigated the asymmetric acetalization reaction by
the condensation/amine addition cascade sequence, which is one
of the most efficient methods for the synthesis of optically active
2,3-dihydroquinazolinones that show extensive important
pharmacological activities.55 After screening various reaction
conditions including catalyst loading, reaction time and
temperature (Table S5), we found that, at 1.4 mol% loading,
Spiro-1 could catalyze the condensation/amine addition of
2-aminobenzamide and 4-bromobenzaldehyde to give the product
2,3-dihydroquinazolinone in 99% yield and 96% ee in CHCl3 at
60 °C after 18 h. Moreover, the electronic nature or positions of
the substituent on the aldehyde have limited effects on the
catalytic results, and, in all cases, the 2,3-dihydroquinazolinones
were obtained in 90-99% yields and 92-99% ee (Table 1, entries
1-8). The chiral nature of the product is dominated by the
handedness of the catalyst, as evidenced by that reaction catalyzed
by (R)-Spiro-1 gave the R enantiomer over the S enantiomer
(Table 1, entry 2). Spiro-2 was also effectively in catalyzing the
condensation/amine addition of 2-aminobenzamide and aromatic
aldehydes, providing almost quantitative yields and 80-90% ee in
10 h. Kinetic study suggested that Spiro-2 presented higher active
than Spiro-1 (Figure S13). The large pores in Spiro-2 are thus
favorable for substrate and product diffusion, but are unfavorable
for high enantiodiscrimination, leading to decreased ee values.
Interestingly, in the CMOF catalyst system, we even can detect
the imine intermediate during the reaction process, as indicated by
1H NMR (Figure S14), whereas no imine signal was detected in
the homogeneous system. This was probably attributed to the
confined cavities in the structure, which may slow down the
reaction rate by stabilizing the intermediates via supramolecular
interactions.
Considering that the coordinated water molecules of Zr6
clusters can be removed through a thermal activation process,
which lead to the exposure of Zr(IV) sites as Lewis acids, we
designed a deacetalization/acetalization tandem reaction utilizing
both Lewis acid and Brønsted acid sites of the CMOFs. Acetals
are highly valuable in organic synthesis because they are capable
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of acting as protecting groups for reactive aldehydes, which are
directly converted to 2,3-dihydroquinazo- linones in 88-95%
yields with 86-97% ee. Besides, cyclic acetals could also undergo
the desired transformation to afford the targeted
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one of the most important classes of organic molecules widely
used in industry. The open Lewis acidic Zr(IV) and/or phosphoric
acid sites in the CMOF promoted the deacetalization of dimethyl
or cyclic acetals to aldehydes, which were subsequently converted
to optically active 2,3-dihydroquinazolinones catalyzed by chiral
phosphoric acids. As shown in Table 2 a broad scope of
arylaldehyde dimethyl acetals with different substituents can be
2,3-dihydroquinazolinones with satisfactory yields (85-96%) and
excellent enantioselectivity (83-95%). The yields and ee values
compared well with those obtained from the above
two-component reaction systems. In addition, under identical
conditions, Spiro-2 catalyzed the tandem reactions of dimethyl or
cyclic acetals, producing comparable yields (92-98% or 88-96%)
but decreased stereoselectivities (77-84% ee or 78-84% ee) in
relative to Spiro-1.
Table 1. Enantioselective Tandem Two-Component
Condensation and Cyclization of 2-aminobenzamide with
Aldehydesa
9
Table 2. Enantioselective Tandem Three-Component
Deacetalization-Acetalization of 2-aminobenzamide with
Arylaldehydes Dimethyl Acetala
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
O
O
NH
CHO
1.4 mol% Cat.
NH2
R
+
N
CHCl3/60 oC/18 h
MgSO4
NH2
R
H
O
O
O
NH
1.4 mol% Cat.
CHCl3/60 oC/24 h
MgSO4
NH2
O
R
+
N
entry
cat.
yield (%)b
96
ee (%)c
95
NH2
R
R
H
1
(S)-Spiro-1
4-H
99 (99)d
94
96 (96)d
97
entry
cat.
yield (%)b
ee (%)c
2
4-Br
4-Me
4-F
R
3
1
(S)-Spiro-1
95 (79)d
93
92 (90)d
94
4-H
4
99
95
2
4-Br
4-Me
4-F
4-NO2
5
99
92
3
90
94
3-NO2
6
4
88
91
90
99
5
89
86
3-Cl
4-NO2
3-NO2
3-Cl
2-NO2
G1
7
92
92
6
90
97
2-NO2
8
92
98
7
90
87
G1
G2
G3
9
73
91
8
89
93
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
28
77
9
70
90
< 8%
99
n.d.
70
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
21
75
G2
e
(S)-Me4L1
4-H
n.r.
96
n.r.
32
G3
99
76
e
4-Br
4-Me
G1
ZrOCl2/(S)-Me4L1
4-H
71
99
95
32
4-Br
4-Me
G1
69
99
94
42
52
93
26
99
G2
G3
88
24
G2
n.d.
90
99
85
n.d.
75
G3
(S)-Spiro-2f
99
4-H
84
4-H
(S)-Me4L1
(S)-Spiro-2f
NU-1000g
99
87
4-Br
4-Me
4-F
83
75
4-Br
4-Me
4-H
99
80
80
72
99
85
98
84
99
83
4-NO2
4-Br
4-Me
4-H
95
84
96
87
3-NO2
92
77
86 (67)i
98
86 (26)i
88
BINOL-PO2Hg
SPINOL-PO2Hh
4-H
n.r.
n.r.
aFor reaction details see experimental section in SI. The MOF was activated
overnight at 220°C under vacuum to remove coordinated water molecules. 1.4
mol% catalyst is the ratio of the MOF formula derived mole amount and the
mole amount of 2-aminobenzamide. cDetermined by HPLC. The absolute
configurations of the products were assigned as S by comparing their HPLC
profiles with those reported in literature.56 dThe data in parentheses are
4-Br
CHO
CHO
CHO
O
O
O
O
e
catalyzed by the non-activated Spiro-1. Catalyzed by 2.8 mol% (S)-Me4L1
and 8.4 mol% ZrOCl2. fReaction time: 15 h. g Catalyzed by 1.4 mol% NU-1000
(activated).
G1
G2
G3
aFor reaction details see experimental section in SI. 1.4 mol% catalyst is the
ratio of the MOF formula derived mole amount and the mole amount of
2-aminobenzamide. bIsolated yield. cDetermined by HPLC. The absolute
configurations of the products were assigned as S by comparing their HPLC
profiles with those reported in literature.56 dData in brackets are catalyzed by
(R)-Spiro-1. eCatalyzed by 2.8 mol% (S)-Me4L1. fReaction time: 10 h.
gCatalyzed by 10 mol% 3,3’-bis(9-anthracenyl)-BINOL-PO2H.56. hCatalyzed by
10 mol% 6,6’-bis(9-anthracenyl)-SPINOL-PO2H.57 iCatalyzed by 10 mol%
To assess the contribution of the frameworks to the
enantioselective catalysis, the activities of related molecular and
solid catalysts were examined. When the salt ZrOCl2 and the
activated MOF NU-100042 composing of identical Zr6 clusters to
Spiro-1 was respectively used as catalysts for catalyzing the
acetalization and deacetalization-acetalization reactions under
identical conditions, no target products were detected by 1H NMR
even after 48 h, suggesting that the Zr6 clusters in the CMOF were
not the active sites for the acetalization transformation. However,
3,3’-bis[4-(9-anthracenyl)-2,6-bis(isopropyl)phenyl]-BINOL-PO2H.58
related catalyst structures and reaction conditions are given in Table S11.
The
6
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Journal of the American Chemical Society
the deacetalization of aldehyde dimethyl acetals and cyclic acetals
catalytic cycles, both the PXRD pattern and BET surface area
1
2
3
4
5
6
7
8
to aldehydes proceeded smoothly in the presence of ZrOCl2 or the
activated NU-1000, implying that aldehyde formation was
catalyzed by the open Lewis acidic Zr(IV) sites in Spiro-1.
Controlled experiments were also performed for the homogeneous
catalyst Me4L1 and a mixture of Me4L1 and ZrOCl2 under
identical conditions. Both systems were efficient in catalyzing the
acetalization and deacetalization-acetalization reactions, but gave
the targeted products with much lower enantioselectivties than
Spiro-1 (Table 1, entries 12-14, Table 2, entries 12-14 and 18-20).
Additionally, the non-activated Spiro-1 gave lower yield than the
activated sample (79% vs 95%) in catalyzing the
deacetalization-acetalization reaction (Table 2, entry 1). Taken
together, the above findings indicate that chiral phosphoric acids
that together with the Zr6 clusters and SPINOL rings generate a
chiral microenvironment in the MOF, which should be responsible
for the observed high catalytic activity and eantioselectivity by
concentrating reactants and creating additional steric and
electronic effects around the Lewis acid and Brønsted acid sites.
(1849 m2 g−1) of Spiro-1 remained almost the same as those of the
pristine sample (Figures 2b and 2e), indicating the robustness of
the framework. Third, removal of Spiro-1 by hot filtration of the
reaction mixture after 4 h completely shut down the reaction,
suggesting that the supernatant is inactive in promoting the
reaction. Inductively coupled plasma mass spectrometric
(ICP-MS) analysis of the product solution showed almost no loss
of Zr ions (< 0.002%) from the structure per cycle. Final, to probe
the role of the pore in catalysis, three sterically demanding
substrates were subjected to the acetalization and
deacetalization-acetalization reactions. As shown in Tables 1 and
2, the yield gradually decreases when the size of the aldehyde
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
substrate
increase.
For
the
largest
substrate
of
3,5-bis[3,5-di(tert-butyl)benzyloxy] benzaldehyde (14 × 21 Å2),
only < 8% conversion of the targeted product was detected after
72 h for both of the two reactions,
Table 4. Enantioselective Tandem Three-Component
Friedel-Crafts Reaction of Indole with Aldehydes and
p-Toluenesulfonamidea
Table 3. Enantioselective Two-Component Friedel-Crafts
Reaction of Indole with N-Sulfonyl Aldiminesa
NH2
TsHN
TsHN
O S O
CHO
NTs
R
R
1.4 mol% Cat.
DCE/80 oC/48 h
1.4 mol% Cat.
R
+
+
R
+
N
DCE/40 oC/24 h
N
N
N
H
H
H
H
yield (%)b
ee (%)c
yield (%)b
ee (%)c
entry
cat.
R
entry
cat.
R
87
96
95
96
96
95
96
96
99
98
84
n.r.
33
31
25
46
45
n.d.
96
93
97
n.r.
n.r.
1
(S)-Spiro-1
4-H
98
99
92
98
91
99
94
92
81
26
n.r.
88
91
85
86
67
44
97
95
95
71
98
99
1
(S)-Spiro-1
4-H
2
4-Br
4-Me
4-F
86
99.9
96
2
4-Br
4-Me
4-F
3
90
3
4
83
99.9
95
4
4-NO2
5
89
5
4-NO2
4-CF3
2-Cl
1-naphthyl
G1
4-CF3
2-Cl
6
87
6
99.9
98
7
92
7
1-naphthyl
8
95
8
99
G1
G2
G3
9
80
9
99
10
11
12
13
14
15
16
17
18
19
20
21
22
20
10
11
12
13
14
15
16
17
18
19
20
21
22
86
G2
n.r.
19
n.r.
96
G3
d
ZrOCl2/(S)-Me4L1
d
4-H
4-Br
4-Me
G1
(S)-Me4L1
4-H
25
90
4-Br
4-Me
G1
26
95
29
98
G2
G3
18
75
G2
< 5%
89
n.d.
99
G3
(S)-Spiro-2e
4-H
(S)-Spiro-2e
4-H
92
4-Br
4-Me
4-H
4-Br
4-Me
4-Br
4-H
97
92
93
NU-1000f
n.r.
n.r.
BINOL-PO2Hf
82
g
(S)-Me4L1
4-H
SPINOL-PO2Hg
98
aFor reaction details see experimental section in SI. The MOF was activated
overnight at 220°C under vacuum to remove coordinated water molecules. 1.4
mol% catalyst is the ratio of the MOF formula derived mole amount and the
mole amount of aldehyde. bIsolated yield. cDetermined by HPLC. The absolute
configurations of the products were assigned as S by comparing their HPLC
profiles with those reported in literature.35 dCatalyzed by 2.8 mol% (S)-Me4L1
and 8.4 mol% ZrOCl2. eReaction time: 40 h. fCatalyzed by 1.4 mol% NU-1000
(activated). gCatalyzed by 2.8 mol% (S)-Me4L1.
aFor reaction details see experimental section in SI. 1.4 mol% catalyst is the
ratio of the MOF formula derived mole amount and the mole amount of imine.
bIsolated yield. cDetermined by HPLC. The absolute configurations of the
products were assigned as S by comparing their HPLC profiles with those
e
reported in literature.35 dCatalyzed by 2.8 mol% (S)-Me4L1. Reaction time: 14
h. Catalyzed by 10 mol% 3,3’-bis(1-naphthyl)-BINOL-PO2H.35 gCatalyzed by
f
2
mol% of 6,6’-bis(2-naphthyl)-SPINOL-PO2H.59 The related catalyst
structures and reaction conditions are given in Table S11.
which was much lower than ~99% yield obtained with Me4L1.
This extremely low conversion is presumably because the large
substrate cannot access the catalytic Brønsted acid sites in the
cavity of the MOF through the windows (13.9 × 13.9 Å2) due to
its large diameter (14 × 21 Å2), indicating that catalysis occurs
mainly at the active sites within the inner pores. Several tests also
confirmed that Spiro-1 was a heterogeneous and recyclable
7
Several experiments were performed to demonstrate the
heterogeneity and recyclability of the MOF catalyst. First, upon
completion of the acetalization of 2-aminobenzamide and
4-bromobenzaldehyde, Spiro-1 could be recovered by simple
filtration and reused at least 10 times without any obvious loss of
the activity and enantioselectivity (Figure S9). Second, after 10
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Journal of the American Chemical Society
Page 8 of 12
catalyst in catalyzing two and three-component F-C alkylation and
efficiency and enantioselectivity (Figures S10 and 2f), and the
1
2
3
4
5
6
7
8
iso-P-S reactions (Figures 2f, S10 and S11).
recovered catalyst retained crystallinity and remained structurally
intact, as revealed by PXRD and BET surface area measurements
(Figures 2b and 2e). Moreover, as shown in Tables 3 (entries 9-11)
and 4 (entries 9-11), both reactions catalyzed by Spiro-1 greatly
depend on the substrate size: as the size of the aldehyde increases,
the yield steadily decreases (80, 20 and 0%). In each case, the
yield for the largest aldehyde is much lower than that produced by
Me4L1, indicating that the reaction was associated with the
substrate being bound in the pore.
Spiro-1 was also highly efficient in promoting the asymmetric
Friedel-Crafts (F-C) alkylation of indole with N-sulfonyl aryl
aldimines, which can provide direct access to enantiopure indole
scaffolds that are common structural motifs found in a number of
pharmaceuticals and natural products.35 Specially, the reaction of
N-sulfonyl aldimine and indole in the presence of 1.4 mol%
Spiro-1 gave the desired product in 98% isolated yield and 99%
ee in DCE at 40 °C after 24 h. A range of substituted aryl
aldimines were tested under the optimal conditions to expand the
reaction scope, and all of them afforded the targeted
3-indolylmethanamine derivatives in 91-99% yields with 95-99.9%
ee. Controlled experiments showed that the homogeneous control
Me4L1 (2.8 mol% loading) gave lower reactivity and
enantioselectivity than the solid catalyst, illustrating the
superiority of the MOF catalyst. Spiro-2 catalyzed the F-C
reactions in nearly quantitive yields with up to 99% ee, as shown
in Table 3 (entries 18-20), indicating pore sizes of the the
framework have limited effects on the F-C reactions.
9
We have also demonstrated that the two CMOFs were capable
of catalyzing more asymmetric organic transformations. For
example, they were effective Brønsted acid catalysts in catalyzing
the iso-Pictet-Spengler (P-S) reactions of o-aminobenzylindole
with various trifluoromethyl ketones, which can give access to
biologically important N-containing heterocyclic compounds
bearing cyclic quaternary stereocenters with a -CF3 moiety.59 In
the presence of 2.2 mol% of Spiro-1 or Spiro-2, the reaction
between o-aminobenzylindole and phenyl trifluoromethyl ketone
proceeded smoothly to give the desired cyclization product in
87-98% isolated yields and 89-96% ee in CHCl3 at 60°C after
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
57
58
59
60
To take advantage of the Lewis acidity of Zr(IV) sites in the
CMOF catalyst, we performed the one-pot three-component
Table 5. Enantioselective Two-Component iso-Pictet-Spengler
tandem
reaction
by
using
indole,
aldehydes
and
Reaction of o-amino-benzylindole with Trifluoromethylated
p-toluenesulfonamide as the substrates. To our delight, the CMOF
could serve as a heterogeneous catalyst for condensation of
aromatic aldehydes and p-toluenesulfonamide followed by
enantioselective F-C alkylation of indole with N-sulfonyl
aldimines to afford the targeted 3-indolylmethanamine derivatives
(Table 4). The open Zr(IV) sites capable of promoting the
condensation of aldehyde and p-toluenesulfonamide to N-sulfonyl
aldimines was suggested by that both ZrOCl2 and the activated
NU-1000 were active in catalyzing the condensation reaction (~50%
conversion). After optimizing the reaction conditions, the one-pot
tandem reactions using 1.4 mol% loading of Spiro-1 as the
catalyst was performed in DCE at 80 oC for 48 h. Aromatic
Ketonesa
R
CF3
NH
O
H2N
2.2 mol% Cat.
CF3
+
R
CHCl3/60 oC/36 h
N
N
H
H
MgSO4
entry
cat.
yield (%)b
ee (%)c
R
94
94
87
91
90
89
96
96
96
90
90
90
82
92
95
90
93
1
(S)-Spiro-1
4-H
2
4-F
3
4-Me
4-CF3
4-Cl
4-Br
3-F
4
98
92
92
98
88
90
81
97
95
90
92
aldehydes
with
both
electron-donating
and
5
electron-withdrawingsubstituents proceeded smoothly to afford
the targeted tandem products in 83-95% yields and 95-99% ee,
which are comparable to those obtained from the above
non-tandem reactions. It also should be noted that Spiro-2
promoted the three component tandem reactions to give
comparable yields and enantioselectivities to Spiro-1, indicating
the framework pore sizes have limited confinement effects on the
tested F-C reactions.
6
7
d
8
S
( )-Me L
4 1
4-H
9
4-F
10
11
12
13
14
4-Me
4-H
(S)-Spiro-2e
4-Br
4-Me
4-CF3
Under otherwise identical conditions, when only Me4L1,
ZrOCl2 or the activated NU-1000 alone was used as a catalyst to
catalyze the three-component F-C reaction, no targeted product
was observed at all. Moreover, when water was added to the
reaction catalyzed by the activated Spiro-1, almost no targeted
product was detected. When the mixture of Me4L1 and ZrOCl2
was used to catalyze the three-component F-C reactions, in all
cases the main products were identified as bis(indolyl)methanes
(BIMs) and the F-C products were obtained in 19-26% yields and
25-33% ee (Table 4, entries 12-14), which were much lower than
those obtained with Spiro-1. This may be ascribed to the
coordination of Zr(IV) ions with Me4L1 to form metal phosphates,
as indicated by 31P NMR spectra (Figure S12), which significantly
decreases Lewis acidity of Zr(IV) ions and Brønsted acidity of
phosphoric acids and shows a decreased ability to catalyze the
asymmetric F-C reactions,. Again, these results suggested that the
well-defined chiral cavities formed by two different catalytic acid
centers in the CMOF to implement the two- and three-component
tandem F-C reactions with high efficiency and enantioselectivity.
SPINOL-PO2Hf
aFor eaction details see experimental section in SI. 2.2 mol% catalyst is the
ratio of the MOF formula derived mole amount and the mole amount of indole.
bIsolated yield. cDetermined by HPLC. The absolute configurations of the
products were assigned as S by comparing their HPLC profiles with those
reported in literature.60 d Catalyzed by 4.4 mol% (S)-Me4L1. eReaction time: 20
f
h. Catalyzed by 5 mol% 6,6’-bis(3,5-trifluoromethyl)-SPINOL-PO2H.60 The
related catalyst structures and reaction conditions are given in Table S11.
36 h. The ee values are comparable to those obtained with the
homogeneous counterpart (Table 5, entries 8-10). Spiro-1 was
also proven to be heterogeneous and recyclable catalyst for the
iso-P-S reactions (Figure S11 and Figures 2b,e). Besides, the
CMOFs can also serve as Brønsted acid catalysts for the catalytic
arylation of indole61 (Table S8) and oxidative dearomatization of
naphthol (Table S9).62 Further research on using our CMOF
catalysts with different acid active centers for related tandem
catalysis is in progress.
To allow their recyclable uses, intensive efforts have been
focused on immobilizing chiral phosphoric acids on amorphous
solid supports such as linear and dendrimer-like polymers and
Several tests also proved the heterogeneous nature of Spiro-1 in
the two- and three-component F-C reactions. The CMOF catalyst
can also be readily recycled and reused with negligible loss of
8
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Journal of the American Chemical Society
porous organic polymers, but the reported catalyst systems
generally suffer from the disadvantages of low catalyst loading,
uneven catalytic sites and typically unsatisfactory
financially supported by the National Science Foundation of
1
2
3
4
5
6
7
8
China (Grants 21522104, 21620102001, 21875136, and
91856204), the National Key Basic Research Program of China
(2016YFA 0203400), Key Project of Basic Research of Shanghai
(17JC1403100 and 18JC1413200) and Shanghai Rising-Star
Programe (19QA1404300).
enantioselectivity.63-66 In particular, a pair of Brønsted acidic
MOFs have been constructed from enantiopure BINOL
phosphoric acid-derived ligands and Cu2(carboxylate)4 building
units and used as catalyst to catalyze F-C alkylation of indole with
aldimines, but with much lower activity (20-45% yields) and
enantioselectivity (6-44% ee) than Spiro-1.29 Notably, there are
no chiral heterogeneous phosphoric acids catalysts having been
reported for enantioselectively catalyzing acetalization and
iso-P-S reactions. The 6,6’-bis-9-anthracenyl-spinol phosphoric
acid and 6,6’-bis-(3,5-trifluoromethylphenyl)-spinol phosphoric
acid were shown to afford the best stereoselectivities for the
acetalization reactions of 2-aminobenzamide and aldehydes and
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(14) Férey, G.; Mellot-Draznieks, C.; Serre, C.; Millange, F.;
iso-P-S
reactions
of
o-amino-benzylindole
with
trifluoromethylated ketones with 80-98% ee and 87-96% ee,
respectively, which are comparable to the results of the Spiro-1
catalyst. So, high enantioselectivities are salient features of our
Brønsted acidic CMOF-based protocol, which are among the
highest ee values having been reported for homogeneous
enantiopure phosphoric acid catalysts.35,57,60
CONCLUSIONS
We have designed a strategy for direct installation of the chiral
phosphoric acid sites in Zr(IV)-MOFs by protecting them from
coordinating to metal clusters via the incorporation of bulky
functional groups at the 6,6’-positions of the enantiopure SPINOL
backbone. The CMOFs with the same topological structure
displayed excellent chemical stability in acidic, neutral and
alkaline aqueous solutions. Incorporation of the chiral phosphoric
acid catalysts into porous frameworks led to significant
enhancement of their Brønsted acidity. The CMOFs exhibited
high reactivity, enantioselectivity and recyclability in
heterogeneous Brønsted acid-catalyzed two-component tandem
transformations such as acetalization, F-C and iso-P-S reactions
and Lewis and Brønsted acid-catalyzed three-component tandem
transformations such as deacetalization-acetalization and F-C
reactions. This work thus provides a new strategy for preparing
heterogeneous Brønsted acid catalysts combining high catalytic
reactivity, steroselectivity and durability and would facilitate the
rational design of novel porous multifunctional materials for
heterogeneous catalysis, molecular adsorption and separation.
ASSOCIATED CONTENT
Supporting Information.
Experimental procedures and characterization data. This material
is available free of charge via the Internet at http://pubs.acs.org.
AUTHOR INFORMATION
Dutour, J.; Surblé, S.; Margiolaki, I.
A
Chromium
Terephthalate-Based Solid with Unusually Large Pore Volumes
and Surface Area. Science 2005, 309, 2040–2042.
(15) Jiang, H. L.; Feng, D. W.; Wang, K. C.; Gu, Z. Y.; Wei, Z.
W.; Chen, Y. P.; Zhou, H. C. An Exceptionally Stable,
Corresponding Author
*yongcui@sjtu.edu.cn
*liuy@sjtu.edu.cn
Porphyrinic
Zr
Metal-Organic
Framework
Exhibiting
ORCID
pH-Dependent Fluorescence. J. Am. Chem. Soc. 2013, 135,
13934–13938.
Wei Gong: 0000-0002-1458-054X
Yong Cui: 0000-0003-1977-0470
Yan Liu: 0000-0002-7560-519X
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Park, S. M.; Seo, G.; Kim, K. Postsynthetic Modification Switches
an Achiral Framework to Catalytically Active Homochiral
Metal-Organic Porous Materials. J. Am. Chem. Soc. 2009, 131,
7524–7525.
Notes
The authors declare no competing financial interest.
(17) Falkowski, J. M.; Sawano, T.; Zhang, T.; Tsun, G.; Chen, Y.;
Lockard, J. V.; Lin, W. B. Privileged Phosphine-Based
ACKNOWLEDGMENTS
We acknowledge many helpful discussions with Professor Qilin
Zhou and Jianhua Xie (Nankai University, China). This work was
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