New 1D chiral Zr-MOFs based on in situ imine linker formation as catalysts for asymmetric C–C coupling reactions

Article abstract of DOI:10.1016/j.jcat.2020.03.034

A novel chiral diimine Zr-MOF (DUT-136, DUT - Dresden University of Technology) is synthesized in a one-pot reaction from ZrCl₄, 4-formylbenzoic acid, and (R,R)-1,2-diphenylethylenediamine as an enantiopure core. Inspired by the versatile chemi

Full text of DOI:10.1016/j.jcat.2020.03.034

Journal Pre-proofs
New 1D chiral Zr-MOFs based on in situ imine linker formation as catalysts
for asymmetric C-C coupling reactions
Khoa D. Nguyen, Sebastian Ehrling, Irena Senkovska, Volodymyr Bon,
Stefan Kaskel
PII:
S0021-9517(20)30118-4
https://doi.org/10.1016/j.jcat.2020.03.034
YJCAT 13699
DOI:
Reference:
To appear in:
Journal of Catalysis
Received Date:
Revised Date:
Accepted Date:
20 January 2020
29 March 2020
30 March 2020
Please cite this article as: K.D. Nguyen, S. Ehrling, I. Senkovska, V. Bon, S. Kaskel, New 1D chiral Zr-MOFs
based on in situ imine linker formation as catalysts for asymmetric C-C coupling reactions, Journal of Catalysis
(
2020), doi: https://doi.org/10.1016/j.jcat.2020.03.034
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New 1D chiral Zr-MOFs based on
in situ imine linker formation as catalysts for
asymmetric C-C coupling reactions
a,b
a
a*
a
a*
Khoa D. Nguyen, Sebastian Ehrling, Irena Senkovska, Volodymyr Bon, and Stefan Kaskel
a
Department of Inorganic Chemistry, Technische Universität Dresden, Bergstraße 66, 01069 Dresden,
Germany.
b
Faculty of Chemical Engineering, HCMC University of Technology, VNU-HCM, 268 Ly Thuong
Kiet, District 10, Ho Chi Minh City, Viet Nam
KEYWORDS: Metal-organic framework, DUT-136, zirconium, in situ imine linker formation,
asymmetric C-C coupling

ABSTRACT
A novel chiral diimine Zr-MOF (DUT-136, DUT - Dresden University of Technology) is synthesized in
a one-pot reaction from ZrCl , 4-formylbenzoic acid, and (R,R)-1,2-diphenylethylenediamine as an
4
enantiopure core. Inspired by the versatile chemistry of the C=N bond, a variety of post-synthetic
derivatizations were performed. Oxidation, reduction, and metalation effectively generated the chiral
amide-, amine-, and Ni containing DUT-136 MOFs, respectively. The catalytic activity of these post-
synthetically modified materials was systemically evaluated in a wide range of asymmetric organic
transformations, including the Friedel Crafts alkylation, Michael addition, aldol reaction, and the Ni-
catalyzed C-C coupling.
2

INTRODUCTION
Schiff-base chemistry has emerged as a simple and useful tool in designing various types of porous
materials, including metal-organic frameworks (MOFs),[1-4] covalent organic frameworks (COFs),[5-7] and
porous organic polymers (POPs).[8, 9] These imine-based networks generally exhibit high stabilities in
most organic solvents, while their nitrogen atoms can coordinate to various transition metal ions, offering
ideal platforms for catalytic applications.[10, 11] In fact, metal complexes, based on dynamic imine
chemistry could be employed as effective catalysts for several organic reactions. More importantly, the
Shiff-base reactions also are an efficient and environmentally benign approach to generate
homochirality.[11] Recently, numerous reports dedicated to preparation of chiral porous materials based
on formations of chiral imine have been published.[12-15] These materials have not only been applied as
effective catalysts for asymmetric base-catalyzed reactions, but also offer vast possibilities for post-
synthetic transformations via chemical conversion of imine groups and metalation.[16-18] However, their
stability is still an intrinsic drawback, hindering practical applications. Therefore, the incorporation of
chiral imine containing ligands into Zr-based frameworks is a promising approach to obtain crystalline
porous materials, possessing high activities as well as outstanding stable structures.[11, 19] Assembling the
Zr -node and chiral imine ligands into a solid framework structure faces two major challenges: i)
6
formation of amorphous phases due to rapid nucleation and precipitation, and ii) decomposition of imine
groups in the acidic environment during Zr-MOFs synthesis. This issue was for the first time mentioned
by Zhou and co-workers, reporting formation of pure phase of PCN-160 in a synthesis containing mixture
of 4-[(E)-(4-carboxybenzylidene)amino]benzoic acid (CBAB) and azobenzene (4,4'-stilbenedicarboxylic
[2]
acid (AZDC)) linkers. This result could be rationalized assuming that the imine bonds in CBAB linkers
were broken up during Zr-MOF synthesis, which require either a high temperature (120 °C) or an excess
[2]
[20,
amount of acid modulators. A similar observation was reported by Jiang et al. and Cui et al. in 2018.
2
1]
Particularly, chiral Zr-MOFs based on salen ligands could only be obtained through a precious
3

modulated process, while the introduction of these chiral salen linkers could be only carried out by one-
or two-step ligand exchange.[20] In addition, the solubility of chiral diimine linkers is also a certain obstacle
to introduce them into metal-organic frameworks.[22] However, these hindrances could be overcome by
employing one-pot synthesis, in which formation of imine organic linkers and of MOF occur at the same
time, limiting the acidic influence of zirconium ion, and of monocarboxylic acid modulator, as well as
eliminating the low solubility problem. Actually, a series of Ti-MOFs based on imine linkages was
successfully synthesized via in situ generation of titanium clusters and imine ligands.[1, 3]
In the following, the synthesis of a new chiral Zr-MOF, DUT-136, via in situ formation of Zr-clusters
and chiral imine-organic building blocks is described, and its catalytic activity is evaluated in a wide range
of asymmetric C-C coupling reactions.
RESULTS AND DISSCUSION
Materials synthesis and characterization
In the first attempts to synthetize chiral imine Zr-MOF, we decided to utilize (R,R)-1,2-
diaminocyclohexane and 3-formyl-4-hydroxybenzoic acid as building blocks for in situ synthesis (Figure
1
b). Unfortunately, all efforts following this approach resulted in unknown amorphous phases, as
4
+
indicated by powder X-ray diffraction (PXRD). The presence of acidic reagents, such as Zr , HCl, and
modulators in MOF syntheses process are a serious hindrance to generate imine linkers.[21] To limit this
negative impact, a strategy using hydrophobic and bulky groups protecting the imine groups from acidic
reagents is proposed. In particular, the diimine ligand, built from 4-formylbenzoic acid and (R,R)-1,2-
diphenylethylenediamine was aimed, in which the phenyl groups are employed as imine protectors. This
strategy provided an efficient way to synthesize chiral Zr-MOF, DUT-136, via one-pot synthesis method
(Figure 1a).
4

To obtain the desired products of good crystallinity, a series of various modulators in varying
concentrations was utilized in initial experiments. The reactions were carried out in DMF as solvent at
8
0 °C in the presence of CH COOH as modulator in the concentration range from 0 to 150 equivalents
3
(
based on ZrCl amount). However, the syntheses with less than 40 equiv. of CH COOH only produced
4
3
amorphous powders, while materials with highest crystallinity were obtained with 80 equiv. of
CH COOH. Higher amount of modulator does not lead to further crystallinity improvement (Figure S1a).
3
Figure 1. Combination of Zr-clusters and some chiral linkers to achieve chiral Zr-MOFs. Color scheme
of cluster: Zr (green); O (red); C (black).
Besides, the crystallinity was found to be affected also by the nature of modulator. Only poorly
crystalline phases were particularly formed in case of benzoic acid or formic acid as additives, while the
crystallization was not observed in the presence of CF COOH (Figure S1b). Although, the
3
monocarboxylic acids play a key role in improving the crystallinity of Zr-MOFs, an excess amount of
acids could promote the hydrolysis of imine to the corresponding precursors. This explains the formation
of the poorly crystalline products in the case of using either a strong acid such as CF COOH or high
3
concentrations of modulators. In addition, the fragility of such imine bonds in the acidic environment has
also been a major reason for forming non-crystalline powders when imine linkers are applied directly in
zirconium framework assembly.[2, 23] Therefore, the one-pot reaction of three components, including 1, 2-
diphenylethylenediamine, 4-formylbenzoic acid, and zirconium chloride (Figure 1a) has been found as
5

an advantageous approach to avoid these inherent drawbacks in the self-assembly synthesis of chiral Zr-
MOF containing diimine linkers
Activated SS-DUT-136
As-synthesized SS-DUT-136
Activated RR-DUT-136
As-synthesized RR-DUT-136
Theoretical pattern
5
10
15
20
25
30
2
  
Figure 2. PXRD patterns of as-synthesized and activated DUT-136 at room temperature (λ = 1.5405 Å).
Although, the resulting DUT-136 material is highly crystalline according to PXRD (Figure 2), the regular
spherical particles with approximately 500 nm in size were observed in the corresponding SEM images
(Figure S7a). The size of this particles is not sufficient for single crystal X-ray diffraction analysis.
Consequently, an attempt to increase the size of crystals was undertaken by varying temperature as well
as solvent in the presence of 80 equiv. of CH COOH with stoichiometric ratio of ZrCl ,4-formylbenzoic
3
4
acid, and 1,2-diphenylethylenediamine of 2:2:1. However, these conditions also lead to poorly crystalline
phases. In particular, amorphous powders with broadened peak profiles were found if conducting the
reaction at 60 °C in DMF, while further increase of temperature up to 100 °C or 120 °C produced only
particles, for which no reflections were detected in XRD pattern (Figure S2a). The change of solvent to
DEF or NMP also resulted in a slightly reduced crystallinity (Figure S2b).
6

Figure 3. Structure of DUT-136: a) Organic linker (4,4'-(((1,2-diphenylethane-1,2-
diyl)bis(azaneylylidene))bis(methaneylylidene))dibenzoate) formed in situ from 4-formylbenzoic acid
and (R,R)-1,2-diphenylethylenediamine; b) Zr O (OH) (CH OO) cluster; c) Interconnection of
6
4
4
3
12
Zr O (OH) Zr-clusters by organic linkers into chain (the pore is represented by yellow sphere with the
6
4
4
radius of 3 Å); d) View on the crystal structure along c direction. Color scheme: Zr (green); O (red); C
black); N (blue). H atoms are omitted for clarity.
(
Due to the microcrystalline nature of the resulting product, its structure was solved from PXRD data. In
the structure of DUT-136, the interconnection of the well-known hexanuclear cluster Zr O (OH) and
6
4
4
diimine building blocks results in a 6-connected one-dimensional chain (Figure 3c). Thus, each inorganic
SBU is connected to six diimine linkers, and each of these linkers is coordinated to two Zr-clusters. Six
acetate anions are additionally coordinated to the remaining coordination sites of the Zr-node. As a result,
7

the internal pore with diameters of about 6 Å is formed, restricted by zirconium cluster at vertices and the
diimine ligand as the edges of the pore.
The microporosity of crystalline material was confirmed by nitrogen physisorption at 77 K. The specific
2
3
BET surface area and total pore volume derived from the isotherm amount to 795 m /g and 0.35 cm /g,
respectively (in the case of R,R-configuration of linker) (Figure S4a). The pore size distribution
calculated by de quench solid density functional theory (QSDFT) for slit/cylindrical pore geometry is
shown in Figure S4b. The sharp peak at 3 Å appearing in the distribution, is close to the pore radius of
the cage obtained from crystallographic data. A similar isotherm was also recorded for a material
2
3
containing S,S-configuration of the linker, which showed 730 m /g and 0.32 cm /g for specific BET
surface area and total pore volume, respectively.
The thermal stability of the material was investigated by thermogravimetric analysis (TGA) and in situ
thermo-PXRD measurements (Figure S8). The PXRD patterns remained virtually unchanged up to
2
50 °C, after that the appearance of amorphous phase was observed following by the decomposition of
organic linker starting from 300 °C (Figure S8b). According to TGA, the decomposition of DUT-136 in
air proceed in two steps. The first weight loss of 8.57% at 200 °C corresponds to the residual DMF solvent
and acetate anions. The next weight decrease of 53.57% observed at 490 °C corresponds to the
decomposition of the organic building blocks. This oxidation reaction leads to ZrO as the final product
2
(
35.76%), which matches well with zirconium content found by ICP-OES measurement (27.34%).
Together with NMR results of digested samples, chemical formula
Zr O (L) (OH) (CH COO) ·2.3DMF (L = 4,4'-(((1,2-diphenylethane-1,2-diyl)bis(azaneylylidene))-
a
6
6
2.45
2
3
2.1
bis(methaneylylidene))dibenzoate) is proposed for “as made” material.
8

Post-synthetic derivatization
Utilization of the diimine linkers as organic struts in DUT-136 also offers various possibilities for
functionalization via chemical conversion of its imine groups. In fact, the post synthetic amidation and
amination of linker in DUT-136 could be carried out under mild conditions, giving DUT-136_amide and
DUT-136_amine, respectively.
Figure 4. NMR spectra and the corresponding linker in DUT-136_imine (black), DUT-136_amine (blue),
and DUT-136_amide (red).
The reaction to synthesize DUT-136_amine was performed in the presence of sodium borohydride as a
reducing reagent in methanol as solvent at room temperature. The successful reduction was confirmed by
Fourier transform infrared (FT-IR) spectroscopy (Figure 6). The spectrum of reduced material (DUT-
9

-1
1
36_amine) exhibits a broad signal at 3640 cm , which can be assigned to the free N-H stretching
vibrations. This conversion of imine linkers was quantified by NMR analysis of digested samples (Figure
and S14). In the NMR spectrum of DUT-136_amine, a new signal, attributed to the proton on carbon
4
at position 2 (Figure 4), appears at 5.4 ppm instead of signal at 5.2 ppm, characteristic for the parent
DUT-136 (Figure 4).
a)
(
(
R,R)-DUT-136_amine
R,R)-DUT-136_amide
(
R,R)-DUT-136_imine
20 25 30
5
10
15
2
  
b)
2
1
1
00
(
R,R)-DUT-136_imine
50
00
(
(
R,R)-DUT-136_amide
R,R)-DUT-136_amine
5
0
0
0
.0
0.2
0.4
0.6
0.8
1.0
p/p0
Figure 5. a) PXRD patterns ( λ = 1.5405 Å) and b) nitrogen physisorption isotherms at 77 K of DUT-
36_imine (black), DUT-136_ amine (blue) and DUT-136_amide (red).
1
1
0

By comparing the area of these proton peaks, the conversion of the material from imine to amine was
calculated to be approx. 92%. In addition, the transformation of –C=N to –C-NH groups was also recorded
1
3
in solid state C-NMR. A new peak, belonging to amine carbon, was observed at 190 ppm along with the
signal of imine carbon at 175 ppm, indicating the formation of amine linkages (Figure S15).For the
formation of DUT-136_amide, the oxidation reaction was performed using sodium chlorite as oxidizing
-1
reagent in dioxane as solvent, giving DUT-136_amide. The free N-H stretching at 3654 cm was also
observed in the FT-IR spectrum of oxidized material (Figure 6), however, only 70% conversion of imine
linkers was achieved after 24 hours of reaction, according to the NMR data (Figure 4 and S13).
DUT-136_imine
DUT-136_amide
DUT-136_amine
3
640 cm-1
654 cm-
1
3
N-H stretching
4
000 3500 3000 2500 2000 1500 1000 500
/ cm-
1

Figure 6. DFTIR spectra of DUT-136_imine and its derivatives.
The crystallinity of DUT-136_amide as well as of DUT-136_amine was confirmed by PXRD
measurements (Figure 5a), showing no substantial structural rearrangement of the material during the
course of chemical transformation. Although, the shape as well as the thermal stability of crystals still
maintained (Figure S7b-f; Figure S9 and S10), the nitrogen adsorption capacity at 77 K of oxidized and
1
1

2
2
3
2
reduced materials was significantly decreased from 795 m /g to 364 m /g (0.16 cm /g) and 198 m /g (0.11
3
cm /g), respectively (Figure 5b). Similar capacity drop was also found for CO at 25 °C. A moderate CO
2
2
3
uptake of 20.4 cm /g at 1 bar was found for DUT-136_imine, while this value decreased to 10.6 and 6.5
3
cm /g for the reduced and oxidized material, respectively (Figure S16).
Catalytic studies
To emphasize the catalytic activity of DUT-136 series, a wide range of organic transformations,
including acid-base and transition metal catalyzed C-C coupling reactions were investigated.
Friedel–Crafts alkylation reaction
As the first model reaction, the Friedel–Crafts alkylation between trans-β-nitrostyrene and indole (Figure
7
) was employed to assess the catalytic behavior of DUT-136.
Figure 7. Asymmetric Friedel–Crafts alkylation between trans-β-nitrostyrene and indole.
This reaction is not only an advantageous approach to obtain enantiopure aromatic derivatives with
perfect atom economy, but also allow to evaluate efficiency of acidic active sites of chiral catalytic
systems.[24] In fact, much effort in recent years has been devoted to the development of Brønsted and
Lewis acids with chiral environment to achieve improved performances in the Friedel–Crafts alkylation
of arenes with nitroalkenes.[24-26]
In this work, the effect of DUT-136 on reaction performance was studied in toluene with trans-β-
nitrostyrene/indole molar ratio of 1:1.5 at 50 °C.
A moderate conversion was achieved after 3 days of the reaction in the presence of 5 mol%, and 10 mol%
(based on Zr content) of DUT-136 catalyst, (33%, and 65%, respectively). The conversion increases to
1
2

8
8% using 15 mol% of catalyst (Table 1). DUT-136 with 6-connected Zr-clusters has higher activity than
DUT-67 (a typical 8-connected Zr-MOF) (Entry 1-Table 1),[27] which required 7 days to achieve a
comparable conversion (90%).
Table 1. Performance of various catalysts in the Friedel–Crafts alkylation.
Reaction
time (h)
Yield
(%)b
ee
(%)c
Entry
Catalyst a
1
2
3
4
DUT-67
168
72
90
88
81
85
0
0
0
0
RR-DUT-136_imine
RR_DUT-136_amine
RR_DUT-136_amide
72
72
a
Reaction conditions: 50 °C, 15 mol% catalyst based on zirconium content, 1.0 mmol trans-β-nitrostyrene, 1.5 mmol indole, 4 mL toluene; b Determined by
GC; c ee value determined by HPLC.
However, no enantioselectivity at all was found for all catalysts investigated. The absence of
enantioselective induction indicates the contribution of acidic Zr-clusters as active species.[28, 29] Despite
DUT-136 contains chiral diimine linkers, they are not sufficiently active (in comparison to Zr) to produce
enantiomeric excess of the product.
Aldol addition reaction
In an effort to demonstrate the function of enantiopure sites in DUT-136, its basic activity based on
diimine linkers was investigated via an acid-base catalyzed aldol addition of cyclohexanone and 4-
nitrobenzaldehyde in presence of benzoic acid as additive (Figure 8).[28]
Figure 8. Asymmetric aldol addition reaction of 4-nitrobenzaldehyde and cyclohexanone.
1
3

Table 2. Performance of various catalysts in the aldol reaction.
Amount
Catalyst a
RR-DUT-
Yield (%)b
syn/antic
ee (%)
c
Entry
(mol%)
1
2
3
4
5
6
5
32
37
41
43
55
48
-
0
0
0
5
9
7
1
36_imine
RR-DUT-
36_imine
RR-DUT-
36_imine
RR-DUT-
36_imine
RR-DUT-
10
15
20
20
20
-
1
-
1
73:23
77:23
78:22
1
1
36_amine
RR-DUT-
1
36_amide
a
Reaction conditions: 25 °C, 0.05 mmol benzoic acid, 0.25 mmol 4-nitrobenzaldehyde, 4 mmol cyclohexanone, 1 mL DMSO, reaction time 168h;
b
c
determined by GC; ee value for syn-isomers was determined by HPLC.
As expected from our recent investigation of RR-DUT-136_imine, a modest enantioselectivity of 5% ee
for syn-isomers (77:23 dr (syn:anti)) was observed in the reaction carried out in DMSO at 25 °C with 20
mol% catalyst (based on diimine linkers) in 7 days (Entry 4 - Table 2). Although there was a gradual rise
in aldolisation yield from 32% to 43% by increasing the catalyst amount from 5 mol% to 20 mol%,
respectively, further increase up to 30 mol% DUT-136 does not lead to further improvement. However,
the utilization of the post-synthetically functionalized DUT-136 provided a minor enhancement in
stereoselectivity. The reaction catalyzed by 20 mol% of oxidized material, DUT-136_amide, reaches up
to 48% yield and 7% ee for syn-isomers (Entry 6 - Table 2), while this enantiomeric excess for DUT-
1
36_amine, was 9% (syn-isomers) in line with 55% yield and 77:23 dr (syn:anti) (Entry 5 - Table 2 and
Figure S23). In addition, due to the steric effect of Zr-clusters,[28] DUT-136 and its derivatives showed a
unprecedentedly high syn-diastereoselectivity (syn over anti), which was rarely observed in previous
reports.[28, 30, 31]
1
4

Michael addition reaction
Since the achiral Zr-MOFs are not active in Michael addition reaction,[29] the performance of new
materials was investigated in addition reaction of trans-β-nitrostyrene and cyclohexanone (Figure 9).[29]
Figure 9. Asymmetric Michael addition of trans-β-nitostyrene and cyclohexanone.
The reaction involving chiral DUT-136_ imine catalysts in the mixture of isopropanol and methanol at 50
°
C proceeds slowly to only 12% yield and 5% ee for syn-isomers after 7 days. A minor improvement
(
17% yield and 17% ee) was achieved in the presence of trifluoroacetic acid (TFA) as additive (Entry 3
Table 3). This value could be further improved, if the post synthetically modified DUT-136 materials
-
were used as catalysts.
A yield of 27% and 23% ee were obtained with chiral RR-DUT-136_amide material, and 28% yield
and 31% ee in the case of DUT-136_amine (Entry 7-8 - Table 3 and Figure S24). As mentioned above,
although the acidic defect sites on Zr-cluster are not active in the Michael reaction, their presence can
have a negative effect on the performance of the nitrogen-containing functional groups.[29] Hence, the
application of acid additives not only enhances the formation rate of enamine intermediates, but also
improves the ability of DUT-136 and its derivatives to catalyze the Michael addition of trans-β-
nitrostyrene and cyclohexanone. Similarly, by transformation of DUT-136 into amide- as well as amine
derivatives, the basicity of the material is enhanced, which is reflected in clear improvement in enamine-
catalyzed reactions.
1
5

Table 3. Performance of various catalysts in the Michael reaction.
syn/
anti
c
Amount
Yield
(%)b
eec
(%)
Entry
Catalyst a
RR-DUT-
Additive
(mol%)
1
2
3
4
5
6
7
8
5
TFA
TFA
TFA
0
-
-
-
1
36_imine
RR-DUT-
36_imine
RR-DUT-
36_imine
RR-DUT-
36_imine
RR-DUT-
36_imine
RR-DUT-
36_imine
RR-DUT-
10
0
-
1
20
17
10
11
8
92:8
17
1
Formic
acid
Acetic
acid
Benzoic
acid
20
-
-
-
1
20
-
-
1
20
-
1
20
TFA
TFA
28
27
85:15
86:14
31
23
1
36_amine
RR-DUT-
20
1
36_amide
a
Reaction conditions: 50 °C, 0.05 mmol additives, 0.25 mmol trans-β-nitrostyrene, 5 mmol cyclohexanone, 4 mL isopropanol:methanol (1:1, v:v); b
Determined by GC; c ee value for syn-isomers determined by HPLC.
Ni(II)-catalyzed asymmetric Michael addition
The DUT-136_diimine offer many possibilities for post-synthetic metalation to afford organometallic
catalysts. In this context, the DUT-136 and its derivatives were also utilized as support to immobilize
nickel(II) catalytic sites. The materials were then applied as catalysts in a cross C-C coupling reaction of
diethyl malonate and trans-β-nitrostyrene (Figure 10).
Figure 10. Asymmetric Ni-catalyzed Michael reaction of trans--nitrostyrene and iethyl malonate.
1
6

The addition of malonates to electron deficient alkenes (conjugate addition reactions) is a well-known
tool to construct optically active 1,3-carbonyl compounds.[32] A series of significant breakthroughs,
reported by Evans and coworkers from 2005 to 2007, demonstrates the vital role of chiral Ni(II)
complexes based on diamine derivatives in asymmetric additions of 1,3-dicarbonyl compounds to
nitroalkenes.[32-34]
Post-synthetic Ni-metalation of DUT-136 and its derivatives was performed by immersing them in
methanol solution of Ni(OAc) at 25 °C. The resulting materials were washed several times with methanol
2
to remove unreacted chemicals before activation under vacuum at 100 °C for 24 h. The presence of metal
was confirmed by ICP-OES, indicating that the immobilization of Ni(II) significantly relied on the
nitrogen-containing functional groups in DUT-136. The highest Ni content was found in the DUT-
1
36_amide_Ni material with 2.1 wt%, while in case of DUT-136_imine_Ni and DUT-136_amine_Ni the
loadings of 1.4 wt% and 1.7 wt%, respectively, were reached. To verify the crystallinity of all resulting
samples, PXRD analysis was employed. It showed no significant changes in the structures after post
synthetic metalation (Figure S5).
The asymmetric cross C-C coupling reaction of trans--nitrostyrene and diethyl malonate was typically
carried out in toluene as solvent in the presence of 3 mol% catalyst (based on Ni) at 25 °C. It should be
noted that no traces of product were detected after 240 hours of reaction, if the parent DUT-136 materials,
as well as homogeneous Ni(OAc) catalysts were utilized (Entry 2, Table 4). If DUT-136_imine_Ni was
2
used, a yield of 36% was obtained (Entry 6, Table 4). The performance of Ni-catalyzed Michael addition
could be significantly improved (to 63%, and 67% yield), if DUT-136_amide_Ni, and DUT-
1
36_amine_Ni were applied (Entry 7 and 8, table 4). Moreover, a gradual increase in enantioselectivity
toward formation of R-isomer was observed. This value increases from 6% ee in the reactions catalyzed
by Ni-DUT-136_imine_Ni materials to 16%, and 12% ee in reaction catalyzed by DUT-136_amide_Ni,
and DUT-136_amine_Ni, respectively.
1
7

Table 4. Performance of various catalysts in the Ni-catalyzed Michael reaction.
Entry
1
Catalyst a
-
Solvent
Toluene
Reaction time (h)
240
Yield (%)b
0
ee c
0
2
3
4
5
6
7
8
9
Ni(OAc)
2
Toluene
Toluene
240
72
0
0
RR-amine core + Ni(OAc)
2
100
100
0
-34 (S-isomer)
SS-amine core + Ni(OAc)
2
Toluene
72
26 (R-isomer)
RR-DUT-136_imine
Toluene
240
240
240
240
240
240
240
240
240
240
240
240
240
240
240
0
6
RR-DUT-136_imine_Ni
RR-DUT-136_amine_Ni
RR-DUT-136_amide_Ni
SS-DUT-136_amide_Ni
RR-DUT-136_amide_Ni
RR-DUT-136_amide_Ni
RR-DUT-136_amide_Ni
RR-DUT-136_amide_Ni
RR-DUT-136_amide_Ni
RR-DUT-136_amide_Ni
RR-DUT-136_amide_Ni
RR-DUT-136_amide_Ni
RR-DUT-136_amide_Ni
RR-DUT-136_amide_Ni
Toluene
36
Toluene
67
12
16
18
18
6
Toluene
63
Toluene
61
1
1
1
1
1
1
1
1
1
1
0
1
2
3
4
5
6
7
8
9
Toluene
63
THF
48
1,4-dioxane
Methanol
59
8
100
100
100
65
4
Ethanol
5
Toluene/Ethanol (1%)
Toluene/Ethanol (5%)
Toluene/Ethanol (10%)
Toluene/Ethanol (15%)
Toluene/Ethanol (20%)
16
18
19
22
6
83
98
100
aReaction conditions: 25 °C, 3 mol% catalyst based Ni content, 0.25 mmol trans-β-nitrostyrene, 2.5 mmol diethyl malonate,
3
mL toluene; b determined by GC; c ee value was determined by HPLC.
More importantly, the utilization of DUT-136_amide_Ni causes a reversal in enantioselectivity in
comparison with the reaction catalyzed by respective homogeneous Ni-complex.
In the presence of an organometallic catalyst, obtained from (R,R)-1, 2-diphenylethylenediamine
and Ni(OAc) , the reaction proceeds to a complete conversion with 34% ee for S-enantiomer, while
2
the ee value toward generating R-product was observed to be 26% with the Ni-complex derived
from (S,S)-diamine core (Entry 3-4 - Table 4 and Figures S25 - S26). Although, RR-DUT-
1
36_amine_Ni was synthesized from (R,R)-1, 2-diphenylethylenediamine precursor, it promotes
the preferable formation of R-enantiomer as product. To confirm this observation, an additional
reaction using SS-DUT-136_amide_Ni as catalyst was investigated under optimized conditions.
Interestingly, the enantioselectivity was observed with 18% ee for R-isomer (Entry 9 - Table 4).
1
8

Recently, Kobayashi and co-workers also reported a novel chial heterogeneous system, obtained
by wet impregnation of chiral nickel–diamine complexes into MCM-41. These catalysts showed
excellent performances (90% yield and 90% ee) for asymmetric addition of dimethyl malonate and
trans--nitrostyrene, however, the inverse enantioselectivity was not observed in all
experiments.[35] A basic difference between chiral MCM-41 catalysts and RR-DUT-136 is the
[28]
presence of bulky Zr -clusters in framework, which could induce a reversed stereoselectivity.
6
Clearly, the steric effect of Zr -nodes on stereoselectivity in asymmetric reactions is complex, and
6
the issue still needs further investigations.
In the next step, the influence of various solvents was investigated to optimize the reaction
conditions. It was found that the product formation significantly relies on polarity of the reaction
medium. In particular, the conversion of trans--nitrostyrene proceeds slowly in polar aprotic
solvents, such as THF, 1,4-dioxane, only affording 48% and 59% yield with modest ee values of
6
% and 8%, respectively. A conversion up to 100% was observed if methanol or ethanol was
applied as solvent (Entry 11-14 - Table 4). Although the reaction yield could be significantly
improved in polar protic solvents, unexpected low enantioselectivity (ee values below 5%) was
detected by HPLC.
1
00
9
8
7
6
5
4
3
2
1
0
0
0
0
0
0
0
0
0
0
Kinetic curve
Leaching test
0
48
96
144
192
240
Time / h
Figure 11. The leaching test carried out at room temperature. Kinetic progress of the reaction with
catalyst (black cycles) and after filtration of catalyst after 72 h (red diamond).
1
9

By adjusting the content of ethanol and toluene in reaction mixture, the polarity was systematically
changed to evaluate the best conditions for catalysis. In fact, the yield of reaction gradually
increases from 65% to 98% as the ethanol content was changed from 1% to 15%, but also ee value
just increases up to 22% (Entry 18 - Table 4 and Figure S27). However, further increasing of
ethanol content leads to an abrupt decrease in enantioselectivity, though the conversion of reaction
still reaches excellent values.
Utilization of metalated materials as heterogeneous catalysts often leads to the leaching of metal
species into the liquid phase. In this context, the leaching test were performed, carrying out the
reaction under optimized conditions. The reaction progress was monitored by GC, and the DUT-
1
36_imine_Ni catalyst was removed by centrifugation after the first 72 h of reaction.
Approximately 42% yield was obtained after 72 h, and no further conversion of main product takes
place after the solid catalyst was removed (Figure 11). ICP-OES measurements indicates, that the
nickel content in the DUT-136 sample used in the reaction still maintained at 2.1 wt%, showing
high stability as well as activity of DUT-136_amide_Ni after 72h reaction time.
1
00
20
18
16
14
12
10
8
GC yield
ee value
9
8
7
6
5
4
3
2
1
0
0
0
0
0
0
0
0
0
0
6
4
2
0
1
2
3
4
5
Run
Figure 12. Catalyst recycling test.
2
0

The main advantage of heterogeneous catalyst is the possibility to reuse the catalyst several times.
Therefore, the catalyst recycling experiment was conducted. The catalyst was separated from
reaction mixture after every 240 h of reaction, washed, and activated at 100 °C for 8 hours and
then applied again. The catalyst shows stable performance, with the reaction yield of 62% and
1
8% ee for R-isomer after three cycles (Figure 12). However, a sudden drop was observed in the
4th run, as the reaction only produced 49% yield, while this value has decreased to 33% with 10%
ee in the next cycle (Figure 12). The nickel loading of the catalyst dropped to about 1.6 wt%,
according to ICP-OES analysis, although its high crystallinity remained (Figure S6). This shows
that the stability as well as activity of DUT-136_amide_Ni is maintained under these conditions
only for three cycles.
CONCLUSIONS
A new chiral metal-organic framework, DUT-136, was synthesized in a one-pot reaction,
promoting the in situ formation of the chiral diimin linker and the MOF simultaneously. As linker
precursors 4-formylbenzoic acid and (R,R)-1,2-diphenylethylenediamine (as an enantiopure core)
were applied. Although, the crystal size of DUT-136 obtained was insufficient for single crystal
X-ray analysis, its structure was solved and refined from the experimental PXRD data. In the
1
2+
structure, each hexanuclear Zr-cluster, [Zr O (OH) ]
is coordinated by six diimine linkers,
,
6
4
4
connecting the clusters into a one-dimensional chain. The material is porous after desolvation,
2
showing BET surface area of 795 m /g.
Post-synthetic derivatization effectively converts DUT-136_imine to amide-, and amine-
containing frameworks. The oxidized and reduced materials were obtained via amidation or
amination under mild conditions, which allowed preservation the original structure. The resulting
2
1

materials, DUT-136_imine, DUT-136_amine, and DUT-136_amide were applied in a series of
asymmetric catalytic reactions: Friedel–Crafts alkylation reaction, Aldol addition reaction,
Michael addition reaction and carbon-carbon cross coupling reaction.
The materials obtained post-synthetically, showed improved performance in asymmetric base-
catalyzed reactions. In the presence of the RR-DUT-136_amine as catalyst yields up to 55% and
9
% ee for syn-isomers in aldol reaction could be achieved. A 28% yield with 31% ee was obtained
in the Michael addition of trans-β-nitrostyrene and cyclohexanone.
No enantioselectivity was found for these chiral materials, if used in a typical acid-catalyzed
reaction, such as the Friedel Crafts alkylation, indicating the dominating role of Zr-clusters as
highly catalytically active species, overacting the activity of the chiral linker. Thus, enantiopure
active sites located at the nitrogen-containing functional groups provide a moderate
enantioselectivity for enamine-catalyzed reactions.
The immobilization of Ni(II) active sites through a simple post-synthetic metalation resulted in
catalysts highly active in asymmetric carbon-carbon cross coupling reactions of trans--
nitrostyrene and diethyl malonate. Especially, the Ni-containing chiral -DUT-136_amide material
shows excellent performance, affording high conversions (up to 100 %). However, the chiral
environment resulted again in modest enantiomeric excess values only. Interestingly, inversion of
enantioselectivities as compared to the reactions catalyzed by the corresponding homogenous Ni-
complex catalysts was observed. The materials could be easily reused at least three times without
any significant degradation in catalytic activity.
In overall, the poor performance of DUT-136 could originate from limited reaction space in the
pore due to the steric demand of phenyl groups on organic building block and new strategies to
increase the pore size are needed for the possible performance improvement.
2
2

EXPERIMENTAL SECTION
Materials and instrumentation
All reagents and starting materials were purchased from Sigma-Aldrich, and were used as received
without any further purification. Nitrogen physisorption measurements were carried out using a
BELSORP-max (MicrotacBEL, Japan) apparatus at 77 K up to 1 bar and high purity nitrogen gas
(99.999 %). The samples were heated in vacuum at 393 K for 24 h prior to adsorption experiments.
1
13
H and C NMR spectra were recorded on a Bruker DRX 500 P.
All room temperature solid-state NMR experiments were carried out on a Bruker AVANCE III
1
HD spectrometer operating at 14 T ( H frequency of 600.12 MHz), equipped with a Bruker 3.2
1
3
1
mm probe. C CP MAS NMR spectra were recorded with H excitation pulses of 2.5 μs, a contact
1
time of 2 ms, a repetition delay of 4 s, a MAS spinning rate of 14 kHz and up to 2000 scans. H
MAS NMR spectra were measured using single-pulse excitation of 2.5 MHz, a MAS spinning rate
of 22 kHz and up to 32 scans.
Scanning electron microscopy (SEM) images were recorded on a HITACHI SU 8020. The
zirconium content in the samples was determined by Inductively Coupled Plasma Mass
spectrometry (ICP-OES) using an Optima 7000 DV instrument. Gas chromatography (GC)
analyses were performed using a Shimadzu GC 17 A equipped with a flame ionization detector
(FID) and a BPX5 column (30 m length, 0.25 mm in inner diameter, and 0.25 mm film thickness).
The following temperature program for GC analysis was used: the samples were heated from 313
to 321 K with a heating rate of 4 K/min; then from 321 K to 373 K with 15 K/min and held at 373
K for 4 min; after that continuously heated from 373 to 543 K with 30 K/min and held at 543 K
for 5 min. Inlet and detector temperatures were set constant at 543 K. The n-dodecane was used as
2
3

an internal standard to calculate reaction yields. Mass spectra were collected using a Shimadzu
GCMS-QP5000, and were compared with database of NIST library.
Enantiomeric excess was determined by HPLC (Elite LaChrom System from VWR/HITACHI
using a UV L2400 detector) using a Lux Amylose-1 chiral column (0.5 μm, 75/25 v/v).
The Fourier-transform infrared (FT-IR) spectra were obtained on a Vertex 70 instrument, with
samples dispersed on potassium bromide pellets. The measurements were carried out in 2 scans
−
1
with a resolution of 2 cm .
Powder X-ray diffraction (PXRD) patterns were collected on a STOE STADI P diffractometer
equipped with ω-2θ goniometer, Cu-Kα1 radiation (λ = 1.54056 Å) and MYTHEN® (DECTRIS)
detector. All routine measurements were performed at room temperature using spinning flatbed
sample holders in transmission geometry within range 2θ = 3 – 30° with increment of 0.015°.
PXRD patterns of the solvent free powder of DUT-136 was measured in the glass capillary (d =
0
.3 mm) at room temperature in range 2θ = 3 – 70°. Unit cell parameters and crystal symmetry
were determined by ab initio indexing of PXRD patterns in X-Cell program, implemented in
Materials Studio 5.0 program.[36] The unit cell parameters and PXRD profile were refined using
Pawley fit option of the Reflex module. Further the Zr O (OH) cluster was inserted in the random
6
4
4
position of the obtained unit cell containing symmetry elements of P3 space group. The structure
was solved by simulating annealing method, implemented in Materials Studio. The starting model
for the refinement was obtained using visualization module of Materials Studio by introducing of
the organic ligand to the model, obtained from solution. The composition of building blocks was
based on chemical formula of the material derived from elemental analysis, TGA and NMR data
(Figure S12 and S14). The model was optimized using geometry optimization tool with
implemented Universal Force Field (UFF). As a last step, the Rietveld refinement with energy
2
4

increment (1% UFF) was applied on the model. Because of low data / parameter ratio, rigid bodies
were defined. Zirconium and oxygen atoms in the cluster were refined as separate structural units
while phenyl rings and carboxylates moieties were defined as rigid units, which allowed to reduce
the overall motion group to 18 units with 94 allowed degrees of freedom. The final Into each unit
cell, one Zr6O8 cluster was combined with organic linkers and modulator molecules. Rietveld
refinement plot is shown in Figure S3.
-
Experimental data from Rietveld refinement of DUT-136: Zr O N C H , M = 2453.07 g mol
6
32
6
102 84
1,
trigonal P3 (No 143), a =19.7780 Å, c = 12.5744 Å, V = 4259.7 Å3, Z = 1, dcalc = 0.956 g cm-3,
zero point shift -0.00118, profile function Thompson-Cox-Hastings, U = 0.23279, W = -0.00227,
V = 0.02966, X = 0.48528, Y = 0.01153, asymmetry correction function Berar-Baldinozzi, P1 =
0
.29958, P2 = -2.21946, P3 = -0.88470, P4 = 4.38592, Final Rwp = 6.54 %, Rp = 4.74%.
Material synthesis
DUT-136: In a representative procedure, a mixture of ZrCl (0.92 g, 3.95 mmol) and 4-
4
formylbenzoic acid (0.54 g, 3.60 mmol, 0.91 equiv.) was dissolved in 100 mL of DMF and 15 mL
of CH COOH (262.5 mmol, 66.5 equiv.). A solution of (1R,2R)-1,2-diphenylethylenediamine or
3
(1S,2S)-1,2-diphenylethylenediamine (0.38 g, 1.80 mmol, 0.45 equiv.) in 50 mL of DMF was
added dropwise to the ZrCl solution. The resulting solution was then sonicated for 10 min before
4
distributing into 30 different vials (10 mL in volume). These vials were then heated at 80 °C for
1
68 hours. The solid product was consequently collected by decanting the mother liquor and
washed with DMF (3 × 100 mL). The DMF solvent was exchanged with acetone (5 × 100 mL) at
room temperature. The resulting product was then activated at 100 °C for 12 h under vacuum,
yielding white solid powders of DUT-136.
Yield: 0.91 g (71% based on (1R,2R)-1,2-diphenylethylenediamine).
2
5

Crystal data for DUT-136 (Zr C O N H ): M = 2453.07 g/mol, trigonal P3, a = 19.7780 Å,
6
102 32
6
84
c = 12.5744 Å, V = 4259.74 Å3.
Elemental analysis for Zr O (imine-L) .6(CH3COO) 6.8DMF: calcd: C 50.4%, H 4.72%, N
.
6
6
3
6
.15%; found: C 49.1%, H 4.83%, N 6.21%.
1H NMR spectrum after MOF digestion: (500 MHz, DMSO-d6/DCl): δ(ppm): 10.0 (s, 2H,
proton in aldehyde groups of 4-formylbenzoic acid), 7.99 (m, 8H, benzyl groups of 4-
formylbenzoic acid), 7.57 (m, 2H, benzyl groups of 1,2-diphenylethylenediamine), 5.21(s, 2H, CH
groups of 1,2-diphenylethylenediamine).
DUT-136_amine: 0.04 g of DUT-136 (0.013 mmol) was slowly stirred in 1.5 mL of methanol for
5
minutes at room temperature before NaBH (3 x 0.0025 g, 0.2 mmol, 15.3 equiv.) was added.
4
After 24 h, the liquid was removed, and the product was washed with 10 mL of water, 5 times with
5
mL of acetone, and desolvated at 100 °C for 12 h under vacuum.
Elemental analysis for Zr O (amine-L) (OH) ·0.14CH COO: calcd: C 48.6% H 4.05% N
6
6
3
5.86
3
3
.8%; found: C 47.2% H 3.98% N 3.75%.
1H NMR spectrum after MOF digestion: (500 MHz, DMSO-d6/DCl): δ(ppm): 8.22 (m, 4H,
benzyl group of 4-formylbenzoic acid), 7.76 (m, 4H, benzyl groups of 4-formylbenzoic acid), 7.98
m, 5H, benzyl group of 1,2-diphenylethylenediamine), 7.56 (m, 5H, benzyl groups of 1,2-
(
diphenylethylenediamine), 5.45 (s, 2H, CH groups of 1,2-diphenylethylenediamine).
DUT-136_amide: 0.04 g of DUT-136 (0.013 mmol) was dispersed in a mixture of 1,4-dioxane (1
mL) and 2-methyl-2-butene (0.62 mL, 5.9 mmol, 450 equiv). 100 µL of aqueous sodium chlorite
solution (3.3 M, 0.33 mmol, 25 equiv) and 35 µL of acetic acid (0.6 mmol, 47 equiv.) were added
slowly to the mixture without stirring. The reaction was carried out in dark for 24 h. The resulting
2
6

powder was then washed with water (2 times, 5 mL) acetone (5 imes,10 mL) and desolvated at
1
00 °C for 12 h under vacuum, producing white solid of DUT-136_amide.
Elemental analysis for Zr O (amide-L) (OH) ·0.14CH COO: calcd: C 47.8%, H 3.45%, N
6
6
3
5.86
3
3
.7%; found: C 47.2%, H 4.01%, N 3.63%.
1H NMR spectrum after MOF digestion: (500 MHz, DMSO-d6/DCl): δ(ppm): 8.12 (m, 8H,
benzyl groups of 4-formylbenzoic acid), 7.95(m, 10H, benzyl groups of 1,2-
diphenylethylenediamine), 5.40 (s, 2H, CH groups of 1,2-diphenylethylenediamine).
DUT-136_ Ni: 0.05 g of DUT-136 or its derivatives were dispersed in 5 mL of ethanol containing
0
.21 g of Ni(OAc) ·4H O. for 24 hours at room temperature. The resulting solid samples were
2 2
collected by centrifuging, washed with ethanol (5 times,10 mL) and desolvated at 100 °C for 12 h
under vacuum. The nickel contents were further confirmed by ICP-OES analysis.
Catalytic studies
Asymmetric Friedel Craft alkylation
In a typical experiment, a mixture of a trans-β-nitrostyrene (0.0375 g, 0.25 mmol), indole (0.0585
g, 0.5 mmol) and n-hexadecane (0.05 mL) as an internal standard were placed into a 10 mL Schlenk
tube containing toluene (4 mL) and the catalyst. The reaction was performed at 50 °C for 7 days.
The conversion was monitored by sampling periodically the reaction mixture. The organic
constituents were then diluted with ethyl acetate (1mL), dried over anhydrous Na SO , and
2
4
analyzed by GC and HPLC.
GC temperature programme used: Initial heating from 40 to 48 °C with a heating rate of 4
oC/min; then from 48 °C to 100 °C with 15 °C/min and held at 100 °C for 4 min; after that
o
continuously heated from 100 to 270 °C with 30 C/min and held at 270 °C for 10 min. Inlet and
2
7

detector temperatures were set constant at 270 °C. The n-hexadecane was used as an internal
standard to calculate reaction conversion. The retention time of the product was 20.27 min.
Enantiomeric excess was analyzed by HPLC Elite LaChrom System with a UV L2400 detector
and a Lux Amylose-1 chiral column. The mobile phase was a mixture of hexane and isopropanol
(85:15, v:v) with flow rate of 0.5 mL/min. The product was detected by UV detector operated at

= 250 nm. The retention times of two enantiomers were 25.161 and 27.510 min, respectively.
Asymmetric Aldol addition reaction
In a typical experiment, a mixture of 4-nitrobenzaldehyde (0.0375 g, 0.25 mmol) and n-dodecane
(
0.05 mL, 0.22 mmol) was placed into a 10-mL Schlenk tube containing 1.00 mL of dimethyl
sulfoxide (DMSO) and catalysts. After that, 20 equiv of cyclohexanone (0.50 mL, 5 mmol) and
.2 equiv of benzoic acid were added. The resulting mixture was stirred at 298 K for 7 days. The
pure product, 2-(hydroxy(4-nitrophenyl)methyl)cyclohexan-1-one as an orange solid, was isolated
in 95% yield) by column chromatography (silica gel, ethyl acetate/isohexane = 1:3). This product
0
(
was used as standard compound to record a calibration curve for the determination of the yield by
GC.
For kinetic studies, reaction progress was monitored by GC/MS as followed: Aliquots (0.02 mL)
were removed from the reaction mixture, diluted with ethyl acetate (1.00 mL), and dried over
o
Na SO . The resulting samples were heated from 40 to 48 °C with a heating rate of 4 C/min; then
2
4
from 48 °C to 100 °C with 15 °C/min and held at 100 °C for 4 min; after that continuously heated
from 100 to 270 °C with 30 °C/min and held at 270 °C for 5 min. Inlet and detector temperatures
were set constant at 270 °C. The yield was identified by comparing the area of product peak (t =
1
7.398 min) with the area of n-dodecane peak (t = 10.555 min).
2
8

In the recycling test, the catalyst was separated by centrifugation, washed intensively with
o
ethanol to remove any undesired compounds, and dried in vacuum at 120 C for 24 h, and reused
for a new catalytic run. To ensure the heterogeneity of the catalyst, the solid catalyst was removed
after 72 h of the reaction. The remaining reaction solution was stirred for further 5 h. Reaction
progress was monitored by GC as previously described.
Enantiomeric excess of 2-(hydroxy(4-nitrophenyl)methyl)cyclohexan-1-one in product mixture
was determined by HPLC (Elite LaChrom System from VWR/HITACHI using a UV L2400
detector) using a Lux Amylose-1 chiral column (0.5 μm, 75/25 (v/v) hexane/isopropanol, 0.5
mL/min,  = 225 nm), retention times: t((S)-2-((S)-hydroxy(4-nitrophenyl)methyl)cyclohexan-1-one) = 19.0432 min
(major),
t((R)-2-((R)-hydroxy(4-nitrophenyl)methyl)cyclohexan-1-one)
=
17.223 min, t((S)-2-((R)-hydroxy(4-
=
28.113 min, and t((R)-2-((S)-hydroxy(4-nitrophenyl)methyl)cyclohexan-1-one) = 21.103
nitrophenyl)methyl)cyclohexan-1-one)
min.
Asymmetric Michael addition reaction
In a standard preparation, trans-β-nitrostyrene (0.0375 g, 0.25 mmol), n-hexadecane as internal
standard (0.05 mL, 0.17 mmol), and catalysts (15 mol%) were placed into a 10-mL Schlenk tube
containing 3 mL of a solvent mixture of isopropanol and ethanol (1:1 v:v). 20 equiv of
cyclohexanone (0.50 mL, 5 mmol) was added to the reaction Schlenk tube. The resulting mixture
o
was consequently stirred for 3 min before heating up to 50 C. Reaction progress was monitored
by GC as followed: Aliquots (0.20 mL) were removed from the reaction mixture, diluted with
isopropanol (1.00 mL), and dried over Na SO . The samples were analysed by GC and HPLC.
2
4
For the recycling test, the catalyst was collected by centrifugation, washed intensively with DMF
o
and ethanol to remove any undesired compounds, activated in vacuum at 120 C for 24 h, and
reused for a new catalytic run. To ensure the heterogeneity of the catalyst, the MOF catalyst was
2
9