Chiral environment of catalytic sites in the chiral metal-organic frameworks

Article abstract of DOI:10.1039/c5dt01322d

Chiral metal-organic frameworks are considered a useful platform in heterogeneous catalysis for enantioselective chemical transformations. However, it has been observed that the enantioselectivity is sensitive to the site at which the reaction takes place

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Chiral Environment of Catalytic Sites in the Chiral
Metal-Organic Frameworks
Cite this: DOI: 10.1039/x0xx00000x
M. Lee, S. M. Shin, N. Jeong*, and Praveen K. Thallapally*
Received 00th January 2012,
Accepted 00th January 2012
DOI: 10.1039/x0xx00000x
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cavities. As shown in Figure 1, the chiral environment of the
reaction site on the surface is anisotropic, whereas that inside the
crystal is isotropic, much like a sphere enclosed by uniform
surroundings. The cavity inside more closely resembles the
Chiral metal-organic frameworks are considered a useful
platform in heterogeneous catalysis for enantioselective
chemical transformations. However, it has been observed that
the enantioselectivity is sensitive to the site at which the
reaction takes place, even in a single crystal, since the chiral
environment of the catalytic site varies according to its
location; e.g., that of the surface is anisotropic whereas that of
the interior is isotropic.
Impressive progress has been made in the development of
heterogeneous catalysts based on metal-organic frameworks
(MOFs), including chiral MOFs for the enantioselective reactions.1,2
Several reports on MOFs for catalysis has been reported by us2 and
others.3 However, it is still unclear to date the catalytic sites in these
materials (surface vs open metal sites in MOF). In order to design a
better enantioselective catalys, based on MOFs, it is necessary to
understand whether the catalytic reactions are taking place at the
surface of the crystals leaving the active sites inside the MOF
untouchedor the reactions taking place at the active sites inside the
MOF. If the reaction is taking place at the surface, the use of MOFs
as heterogeneous catalysts would be seriously undermined. As a
result it is difficult to highlight the true advantages of MOF-based
heterogeneous catalysts over conventional embedded catalysts on
solid supports.3
Scheme 1. Comparison of the enantioselectivity by a homogeneous
chiral catalyst and a MOF based heterogeneous chiral catalyst.
homogeneous system. Thus, it is expected that the optical purity of
the products would vary depending on the location at which the
reaction takes place. The obsereved optical purity of overall product
may be an average value of the ensemble of product fractions
originated from various locations. Prior to further studies, the
diffusion pattern of the substrate was exemplified using the two-
photon fluorescence microscopy (TPM) method we have developed.4
The (R)-KUMOF-1, obtained under the routine solvothermal
reaction conditions that we employed previously,2 and Zn/(R)-
KUMOF-1, prepared by addition of dimethylzinc to (R)-KUMOF-1
(Figure 2c). Both MOFswere incubated with a dye, pyrene-1-
carbaldehyde, 6 at room temperature. Penetration of the dye into the
MOF crystals was monitored by TPM at various time intervals. The
penetration of dye into (R)-KUMOF-1 was smooth. As the
incubation time lengthened, more dye gradually diffused into the
crystal until it was evenly saturated. On the other hand, the diffusion
pattern in the case of Zn/(R)-KUMOF-1 exhibited slightly different
features. The dye initially accumulated on the shallow layer due to a
strong interaction between the carbonyl group of 6 and biphenoxy-
zinc(II) of the framework. As a result, the channel would shrink and
further diffusion of more dye molecules could be substantially
hindered. However, the passageway, even with obstruction of the
channel by 6, would still be roomy enough to accommodate
The location of the reactive sites is an important aspect when
enantioselective reactions are mediated by a chiral MOF. In this
context, the chiral environments in MOFs are not necessarily
identical to those homogeneous counterparts, although the basic
skeleton and absolute configuration of the ligands in both cases is
essentially the same. Lin and co-workers presented an example to
illustrate this concept through a Friedel-Crafts reaction of indole, 1
with N-tosyl imine 2 to produce 3 (Scheme 1). The reaction with the
homogeneous catalyst 4 provided the product (S)-3 as the major
optical isomer, whereas the chiral MOF catalyst 5 yielded the
antipode, (R)-3, as the major isomer, despite both skeletons having
the same absolute configuration (Scheme 1).1h It implies that the
chiral environment of the cavities in the MOF must be different to
that the predicted based on the homogeneous catalyst.
Furthermore, chiral environments of the catalytic sites even in a
single MOF crystal, would vary depending on the location of the
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additional incoming dyes. Thus, the dye is eventually uniformly more products would be obtained from the isotropic environment
distributed inside, but a heavy localization of 6 on the boundary was and would contribute to the optical purity of the overall product
detected. Thus, it is reasonable to assume that the aldehyde (Table 1). The products obtained from the reaction quenched after 1
substrates diffuse into the crystals in the same manner.
h, at which most of the unreacted starting materials remained in the
solution, afforded 8 in 11% yield, but its optical purity was
approximately zero. From the second reaction vessel, quenched after
2 h, 8 was obtained in 30 % yield with a marginal, but significant,
stereoselectivity (10 % ee). The third reaction, quenched after 3.5 h,
provided 8 in 62 % yield with a further improved optical purity of
24 % ee. Finally, the reaction mixture was allowed to react to
completion over 12 h. The chemical yield and optical purity of the
overall product was improved to 92 % and 50 % ee, respectively.
Scheme 2. Carbonyl-ene reaction mediated by Zn/(R)-KUMOF-1
Table 1. Optical purity dependency on the degree of reaction progress
entry
t (h)
1
2
3.5
12
yield (%)a
Ee (%)b
1
2
3
4
11
30
62
92
0
10
24
50
a. Reaction condition; All the reactions were carried out at 0°C in
dichloromethane using 3 equivalent Zn/(R)-KUMOF-1. b. Absolute
configuration of the major isomer is (S(C1), R(C2)).
Table 2. Optical purity dependency on the substrate amount
entry
Eq of 7
0.033
0.067
0.33
t (h)
12
12
yield (%)
Ee (%)
0
17
50
With this information in hand, it was envisioned that, if a
stoichiometric reaction in which the product remained at the location
where it was formed is employed, it may be possible to correlate the
contribution of the product at each location to the optical purity of
the overall product. In this regard, a stoichiometric enantioselective
carbonyl-ene reaction of 7, promoted by Zn/(R)-KUMOF-1, was
chosen (Scheme 2, See ESI).2,5 This benchmark stoichiometric
reaction would allow us to identify the origin of each product
because, after the reaction, the product, 9 or 10, would remain in the
position at which the reaction had taken place(Scheme 2). First, four
identical reactions were set up; each was charged with 7 (15 mg,
0.089 mmol) and Zn/(R)-KUMOF-1 (102 mg, 0.27 mmol, 3 equiv
1
2
3
91
90
89
12
a. Reaction condition; All the reactions were carried out at 0°C in
dichloromethane. b. Absolute configuration of the major isomer is (S(C1), R(C2)).
It is noteworthy that the optical purity of the overall product
linearly increased with increasing reaction time and that the absolute
configuration of the major product is (S(C1), R(C2)), which remained
the same. These points can be accounted for as follows: the optical
purity of the overall product improved significantly with the
increasing ratio of product obtained from the internal cavities, which
are likely to act as homogeneous catalysts due to their chiral
environment. Nonetheless, a general conclusion cannot be made on
which location provides the better chiral environment, although in
this case isotropic chiral bias provides the better chiral environment.
A set of reactions with different amounts of substrate was performed
(see ESI).7 Each reaction vessel was charged with the same amount
of active sites to the substrate)† in CH2Cl2 (0.1 mL) and the reaction
was then performed with mild shaking to allow the catalyst crystals
to remain intact. The reactions were quenched after different time
intervals by filtration of the crystals from the reaction mixture. Then
the crystals were dismantled by treatment with aqueous acidic
solution (6 N HCl) and the resultant products were harvested as
described previously.2,5,6
With a shorter reaction time the optical purity of the product would
be expected to primarily reflect the anisotropic chiral environment,
since most substrates were trapped only in the cavities on the
shallow layer of the crystals. As the reaction time is extended, more
substrate could penetrate deeper to find free reaction sites. Thus,
of the MOF-based catalyst,† and with 0.033, 0.067, and 0.33 equiv
of substrate, respectively. All the reactions were allowed to proceed
to completion and the crystals were then treated as usual (Table 2).
The optical purity of the overall product dramatically improved as
the amount of substrate increased to afford 0, 17, and 50% ee with
0.033, 0.067, and 0.33 equiv of 7, respectively. Once again, as the
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amount of substrate increased, the share of product obtained from Since it is important that the shape of the catalyst crystals remains
the interior increased.
unaffected during the reaction, the reactions were carried out by mild
shaking and then the shape of the crystals were re-examined before
and after the reaction. As shown in Figure 3c, the cubic shape of the
crystals persisted even after prolonged shaking, albeit not perfect.
All three forms of crystal promoted the reaction with unremarkable
activity and the difference in reaction rate was not noticeable either;
the reactions were complete in 12 h to provide 8 in 90% yield by
Zn/(R)-KUMOF-1(1), 88% yield by (2), and 90 % by (3),
respectively (Table 3). However, as expected, the optical purity of
the product dramatically increased as the crystal size increased, 70%
ee by (1), 50 %ee by (2), and 0 %ee by (3). In other words, as more
of the reaction takes place internally, where the chiral bias is
isotropic or pseudoisotropic, the optical purity of the overall product
improved considerably.
Although the chiral metal-organic frameworks are considered as a
useful platform of heterogeneous catalyst for the enantioselective
chemical transformation, it seems to be overlooked that the chiral
MOF is merely an ensemble of cavities bearing diverse chiral
environments. Since the chiral environment of cavities is not
uniform and varies according to their location; e.g. that of surface is
anisotropic whereas that of the inside isotropic, the exact location of
the reaction would be critical to the overall optical purity of the
product. The previous catalytic reactions exhibiting high
enantioselectivity might happen to be the very special where even
the cavities on surface have sufficient chiral bias to discriminate
efficiently. In general, the reaction must be manipulated to limit the
reaction sites only on the uniform chiral environment to obtain the
consistent result. However, this task can hardly be done.
Table 3. The carbonyl-ene reaction of 7 with MOF-based reagents
bearing various crystal size.
This work was supported by a National Research Foundation of
Korea (NRF) grant (2011-0016303 and 2009-0053318) funded by
the Korea government (MSIP). Experiments at PAL (beamline 2D)
were supported in part by MEST and POSTECH.
8
t (h)
12
12
yielda (%)
ee (%)
70
50
Zn/(R)-KUMOF-1(1)
Zn/(R)-KUMOF-1(2)
Zn/(R)-KUMOF-1(3)
92
89
91
Notes and references
12
0
a Department of Chemistry, Korea University, Seoul, 136-701, Korea.
E-Mail: njeong@korea.ac.kr; bPacific Northwest National Laboratory,
Richland, WA 99352. USA; E-mail: Praveen.thallapally@pnnl.gov
a.Reaction condition; All the reactions were carried out at 0°C in
dichloromethane using 3 equivalent of Zn/(R)-KUMOF-1. b. Absolute
configuration of the major isomer is (S(C1), R(C2)).
Subsequently, we attempted to examine the influence of the crystal
size. Since the ratio of surface area to total volume is inversely
proportional to the crystal size, the contribution of the product
obtained from the surface to the overall optical purity would become
more substantial as the crystal size decreased. If the reaction was
catalytic and progressed primarily on the surface, it is expected that
the increasing surface area would increase the reaction rate – i.e. a
higher reaction rate would be observed as the surface area increased
by reducing the crystal size. In addition, the products obtained from
the anisotropic environment would be dominant and would
determine the optical purity of overall product.
Electronic Supplementary Information (ESI) available: Materials and
methods and experimental details. See DOI: 10.1039/c000000x/
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Three batches of crystals according to the crystal size were prepared
(see supporting information). (R)-KUMOF-1 crystals used in the
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1(2) by filtration through glass filter (50 µm) (Fig. S1). Meantime,
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identical, except the size (Figure S2 - S4 ), by XRD, SEM, TGA etc.
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6. Details are described in the reference 2. As the reaction progressed and
even after complete disappearance of
the solution; eventually, neither nor
indicated that the product was entrapped somehow in Zn/(
KUMOF , and therefore, could be released from the crystals only
after catalyst crystals were dismantled by a treatment with an aqueous
HCl (6 ) solution. It was suggested that was bound to the Zn ion
7
, product
were detected on TLC. This
)-
8 did not appear in
7
8
8
S
-1
8
N
8
centers in the MOF even after the chemical transformation was
completed, lingering there and thus blocking another catalytic cycle,
since the product
8
has alcohol group, and their coordinating ability
,. This
to zinc ion is presumably much stronger than the carbonyl of
7
explains the need for more than a stoichiometric amount of the
catalyst for completing the transformation with reasonable
enantioselectivity to determine the stereoselectivity depending on the
locatrion of reaction sites.
7. Z. Ni and R. I. Masel., J. Am. Chem. Soc., 2006, 128, 12394–12395.
4 | J. Name., 2012, 00, 1-3
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