This work was supported by a National Research Foundation of Korea (NRF) Basic Science Research Program NRF-2019R1A2C4070584 and the Science Research Center NRF-2016R1A5A1009405 funded by the Korea government (MSIP). S. Kim was supported by NRF Global Ph.D. Fellowship (NRF-2018H1A2A1062013).

1. Preparation of (S)-KUMOF-1 crystals in three sizes
NOTE: Each step follows the experimental section and supplementary information of previous reports2,24,27. Three different sizes of (S)-KUMOF-1 were prepared: large (S)-KUMOF-1-(L), medium (S)-KUMOF-1-(M), and small (S)-KUMOF-1-(S) with pa...

<ol>
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After the synthesis of (S)-KUMOF-1, crystals in some vials seem to be powdery and are not appropriate for use in catalysis. Therefore, proper crystals of (S)-KUMOF-1 need to be selected. The yield of (S)-KUMOF-1 is calculated using only those vials in which it was successfully synthesized. When withdrawn from the solvent, (S)-KUMOF-1 dismantles. Therefore, the crystals should always be kept wet. For this reason, weighi...

MOFs are considered a useful heterogeneous catalyst for chemical reactions. There are many different reported uses of MOFs for enantioselective catalysis1,2,3,4,5,6,7,8,9,10,11,12,13,14,15,16,17,18,19. Still, it has yet to be determined whether the reactions take place on the inner or outer surface of the MOFs. Recent studies have raised questions concerning the utilization of the available surface and reduced diffusion20,21,22,23. A more striking issue is that the chiral environment varies with the location of each cavity in the MOF crystal. This heterogeneity of the chiral environment implies that the stereoselectivity of the reaction product depends on the reaction site24. Thus, designing an efficient enantioselective catalyst requires identification of the location where the reaction would take place. To do so, it is necessary to ensure that the reaction occurs either only on the inner surface or only on the outer surface of the MOF while leaving the interior intact. The porous structure of MOFs and their large surface area containing chiral environment active sites can be exploited for enantioselective catalysis. For this reason, MOFs are excellent replacements of solid-supported heterogeneous catalysts25. The use of MOFs as heterogeneous catalysts needs to be reconsidered if the reaction does not occur inside them. The location of the reaction site is important, as well as the size of the cavity. In porous materials, the size of the cavity determines the substrate based on its size. There are some reports of MOF-based catalysts that overlook the cavity size issue25. Many MOF-based catalysts introduce bulky catalytic species (e.g., Ti(O-iPr)4) to the original framework structure3,8,13. There is a change in the cavity size when bulky catalytic species are adopted in the original framework structure. The reduced cavity size caused by the bulky catalytic species makes it impossible for the substrate to fully diffuse into the MOFs. Thus, discrimination of substrate size by the cavity size of the MOFs needs to be considered for these cases. The catalytic reactions by MOFs often make it difficult to support evidence of reactions taking place inside the MOF cavity. Some studies have shown that substrates larger than the MOF cavities are converted to the expected products with ease, which seems contradictory8,13. These results can be interpreted as a contact between the functional group of the substrate and catalytic site initiating the catalytic reaction. In this case, there is no need for the substrate to diffuse into the MOFs; the reaction occurs on the surface of the MOF crystals26 and the cavity size is not directly involved in the discrimination of the substrate based on its size.
To identify the reaction sites of MOFs, a known Lewis-acid promoted carbonyl-ene reaction was selected2. Using 3-methylgeranial and its congeners as substrates, four types of enantioselective carbonyl-ene reactions (Figure 1) were studied27. The reactions, which have been previously reported, were classified into two classes: a stoichiometric reaction using a Zn reagent and catalytic reactions using a Ti reagent27. The reaction of the smallest substrate requires a stoichiometric amount of Zn/KUMOF-1 (KUMOF = Korea University Metal-Organic Framework); it has been reported that this reaction takes place inside of the crystal27. Two kinds of MOFs were used in this method, Zn/KUMOF-1 for the stoichiometric reaction and Ti/KUMOF-1 for the catalytic reaction. Owing to the distinct reaction mechanisms of these two kinds of MOFs, a comparison between the reaction rate versus substrate size is possible2,28,29. The effect of particle size on the carbonyl-ene reaction with Zn/KUMOF-127 demonstrated that, as seen in the previous report, the chiral environment of the outer surface was different from the inner side of the MOF crystal24. This article demonstrates a method that determines the reaction sites by comparing the reactions of three kinds of substrates with two classes of catalysts and the effect of particle size as reported in the previous paper27.

<table border="1" fo:keep-together.within-page="1" fo:keep-with-next.within-page="always">
	<tbody>
		<tr>
			<td>Acetone</td>
			<td>Daejung</td>
			<td>1009-4110</td>
			<td></td>
		</tr>
		<tr>
			<td>Analytical Balance</td>
			<td>Sartorius</td>
			<td>CP224S</td>
			<td></td>
		</tr>
		<tr>
			<td>Copper(II) nitrate trihydrate</td>
			<td>Sigma Aldrich</td>
			<td>61194</td>
			<td></td>
		</tr>
		<tr>
			<td>Dichloromethane</td>
			<td>Daejung</td>
			<td>3030-4465</td>
			<td></td>
		</tr>
		<tr>
			<td>Dimethyl zinc</td>
			<td>Acros</td>
			<td>377241000</td>
			<td></td>
		</tr>
		<tr>
			<td>Ethyl acetate</td>
			<td>Daejung</td>
			<td>4016-4410</td>
			<td></td>
		</tr>
		<tr>
			<td>Filter paper</td>
			<td>Whatman</td>
			<td>WF1-0900</td>
			<td></td>
		</tr>
		<tr>
			<td>Methanol</td>
			<td>Daejung</td>
			<td>5558-4410</td>
			<td></td>
		</tr>
		<tr>
			<td>Microwave synthesizer</td>
			<td>CEM</td>
			<td></td>
			<td>Discover SP</td>
		</tr>
		<tr>
			<td>Microwave synthesizer 10 mL Vessel Accessory Kit</td>
			<td>CEM</td>
			<td>909050</td>
			<td></td>
		</tr>
		<tr>
			<td>N,N-Diethylformamide</td>
			<td>TCI</td>
			<td>D0506</td>
			<td></td>
		</tr>
		<tr>
			<td>N,N-Dimethylaniline</td>
			<td>TCI</td>
			<td>D0665</td>
			<td></td>
		</tr>
		<tr>
			<td>n-Hexane</td>
			<td>Daejung</td>
			<td>4081-4410</td>
			<td></td>
		</tr>
		<tr>
			<td>Normject All plastic syringe 5 mL luer tip 100/pk</td>
			<td>Normject</td>
			<td>A5</td>
			<td></td>
		</tr>
		<tr>
			<td>Pasteur Pipette 150 mm</td>
			<td>Hilgenberg</td>
			<td>HG.3150101</td>
			<td></td>
		</tr>
		<tr>
			<td>PTFE tape</td>
			<td>KDY</td>
			<td>TP-75</td>
			<td></td>
		</tr>
		<tr>
			<td>Rotary Evaporator</td>
			<td>Eyela</td>
			<td>243239</td>
			<td></td>
		</tr>
		<tr>
			<td>Shaker</td>
			<td>DAIHAN Scientific</td>
			<td>DH.WSO04010</td>
			<td></td>
		</tr>
		<tr>
			<td>Silica gel 60 (230-400 mesh)</td>
			<td>Merck</td>
			<td>109385</td>
			<td></td>
		</tr>
		<tr>
			<td>Synthetic Oven</td>
			<td>Eyela</td>
			<td>NDO-600ND</td>
			<td></td>
		</tr>
		<tr>
			<td>Titanium isopropoxide</td>
			<td>Sigma Aldrich</td>
			<td>87560</td>
			<td></td>
		</tr>
		<tr>
			<td>Vial (20 mL)</td>
			<td>SamooKurex</td>
			<td>SCV2660</td>
			<td></td>
		</tr>
		<tr>
			<td>Vial (5 mL)</td>
			<td>SamooKurex</td>
			<td>SCV1545</td>
			<td></td>
		</tr>
	</tbody>
</table>

development of heterogeneous enantioselective catalysts using chiral metal-organic frameworks (mofs)

Substrate size discrimination by the pore size and homogeneity of the chiral environment at the reaction sites are important issues in the validation of the reaction site in metal-organic framework (MOF)&#8211;based catalysts in an enantioselective catalytic reaction system. Therefore, a method of validating the reaction site of MOF-based catalysts is necessary to investigate this issue. Substrate size discrimination by pore size was accomplished by comparing the substrate size versus the reaction rate in two different types of carbonyl-ene reactions with two kinds of MOFs. The MOF catalysts were used to compare the performance of the two reaction types (Zn-mediated stoichiometric and Ti-catalyzed carbonyl-ene reactions) in two different media. Using the proposed method, it was observed that the entire MOF crystal participated in the reaction, and the interior of the crystal pore played an important role in exerting chiral control when the reaction was stoichiometric. Homogeneity of the chiral environment of MOF catalysts was established by the size control method for a particle used in the Zn-mediated stoichiometric reaction system. The protocol proposed for the catalytic reaction revealed that the reaction mainly occurred on the catalyst surface regardless of the substrate size, which reveals the actual reaction sites in MOF-based heterogeneous catalysts. This method for reaction site validation of MOF catalysts suggests various considerations for developing heterogeneous enantioselective MOF catalysts.

The enantioselective carbonyl-ene reaction using the Zn reagent is stoichiometric because of the difference in the binding affinities of the alkoxy and carbonyl groups to the metal (Figure 2). For this reason, the substrates were converted into the products at the reaction site and remained there. The desired products were obtained by dismantling the crystals, as detailed in section 4 of the protocol. The results of the heterogeneous enantioselective carbonyl-ene reaction of substrates by Zn...

Watch this Scientific Journal Video about Development of Heterogeneous Enantioselective Catalysts using Chiral Metal-Organic Frameworks MOFs at JoVE.com

Development of Heterogeneous Enantioselective Catalysts using Chiral Metal-Organic Frameworks MOFs

Here, we present a protocol for active site validation of metal-organic framework catalysts by comparing stoichiometric and catalytic carbonyl-ene reactions to find out whether a reaction takes place on the inner or outer surface of metal-organic frameworks.

Development of Heterogeneous Enantioselective Catalysts using Chiral Metal-Organic Frameworks (MOFs)

Substrate size discrimination by the pore size and homogeneity of the chiral environment at the reaction sites are important issues in the validation of ...

Our idea for the reaction site validation of MOF-based catalyst gives reliable data about whether a reaction takes place on the inner or outer surface of MOFs. These methods can be used to evaluate reaction sites, which can be crucial in the design of MOF-based catalyst. Research studies of developing MOF-based catalyst may use these methods to achieve an objective perspective for catalyst characterization.Visual demonstration of these methods is essential as the techniques are difficult to run through text instruction alone. Demonstrating the procedure will be Jeehwan Han, a grad student from my research team. For small size KUMOF-1 synthesis, dissolve 0.2 milligrams of copper(II)nitrate, 0.24 milligrams of dicarboxylic acid ligand in four milliliters of DEF in methanol.Cap the reaction cell with a PTFE cap and place the cell in a microwave reactor at 65 degree Celsius, 100 pounds per square inch and 50 Watts for 20 minutes. At the end of the reaction, whisk gently with a small spatula to float the obtained blue cubic crystals and decant the crystals onto filter paper. And wash the crystals three times with three milliliters of hot DEF per wash followed by three washes with three milliliters of anhydrous DCM per wash before transferring the crystals into fresh anhydrous DCM for storage.For medium size KUMOF-1 synthesis, dissolve 7.2 milligrams of copper nitrate in 1.5 milliliters of methanol and nine milligrams of dicarboxylic acid ligand in 1.5 milliliters of DEF. Combine the two solutions in a four milliliter vial and cover the vial with PTFE tape. Puncture the tape with a needle and place the four milliliter vial into a 20 milliliter vial.Add one milliliter of DMA into the space between the small and large vials. Cap the large vial tightly for a 24 hour incubation in a 65 degree Celsius oven. Next day, whisk the formula liter vial solution gently with a small spatula to float the resulting blue cubic crystals and decant the crystals onto a piece of filter paper.Wash three crystals three times with three milliliter of fresh hot DEF and methanol as demonstrated before storing the crystals in three milliliters of fresh DCM. For zinc/KUMOF-1 crystal preparation, add 680 microliters of dimethyl zinc to 180 milligrams of suspension of KUMOF-1 in two milliliters of DCM at minus 78 degree Celsius. Shake the mixture at this temperature at 180 rotations per minute for three hours.At the end of the incubation decant the supernatant and wash the resulting product with three milliliters of cold DCM several times for the complete removal of any unreacted dimethyl zinc. And follow the KUMOF-1 crystal preparation protocol as demonstrated to obtain small, medium, and large sized zinc/KUMOF-1 crystals. To synthesize titanium/KUMOF-1 crystals add 59 microliters of titanium isopropoxide to a 24 milligrams suspension of KUMOF-1 in two milliliters of DCM.Shake the mixture for five hours at 180 rotations per minute at room temperature. At the end of the incubation, decant the supernatant, wash the resulting product with three milliliters of cold DCM several times for the complete removal of any residual titanium isopropoxide. And follow the KUMOF-1 crystal preparation protocol as demonstrated to obtain small, medium, and large sized titanium/KUMOF-1 crystals.For a heterogeneous stoichiometric carbonyl-ene reaction by zinc/KUMOF-1, add the substrate solution in 100 microliters of DCM to a 102 milligram suspension of zinc/KUMOF-1 in two milliliters of DCM at minus 78 degree Celsius. Place the reaction mixture in a cryogenic cooling bath for three and half hours with shaking. At the end of the incubation, quench the reaction with three milliliters of an aqueous 6 Normal hydrochloric acid solution and filter the resultant mixture through a diatomaceous silica pad.For heterogeneous catalytic carbonyl-ene reaction by titanium/KUMOF-1, add the substrate solution in 100 microliters of DCM to a 12 milligrams suspension of titanium/KUMOF-1, in two milliliters of DCM at zero degree Celsius. Shake the solution for 36 hours at this temperature at 180 rotations per minute. At the end of the incubation collect the supernatant and wash the resultant crystals three times with three milliliters of fresh DCM per wash.The enantioselective carbonyl-ene reaction using the zinc reagent is stoichiometric because of the difference in the binding affinities of the alkoxy carbonyl groups to the metal. Results of the heterogeneous enantioselective carbonyl-ene reaction of substrates by zinc/KUMOF-1 showed that the smallest substrate could diffuse inside the crystal and convert to the product in a high-yield proving that all of the reaction sites of the metal organic frameworks were available. The yield and the enantiomeric excess decreased as the substrate size increased suggesting that the larger substrates could not access the reaction sites inside the metal organic framework crystal.Largest substrate did not undergo the reaction in this system possibly because the reaction channel was blocked by the corresponding reaction products. If the size of the substrate is too large, the surface reaction site makes the first contact and directly blocks the entrance of the channel, which makes it impossible for other substrates to penetrate. When the size of the substrate is sufficiently small compared to the size of the void, additional substrates can penetrate the crystal.Unlike the zinc mediated system, the titanium catalyzed system provides more information about the events occurring at the catalytic reaction sites with no discrimination by substrate size. Indeed, most reactions occur on or beneath the surface and the products were immediately removed to the solution. Carefully following the steps of carbonyl-ene reaction procedures as demonstrated, it's important for obtaining reliable experimental results.Two-photon microscopy measurements will provide additional data for the actual reaction site of various kinds of MOF-based catalyst. As a verification procedure for the reaction site of the MOF catalyst is necessary. Our method can be used as a means for double checking the results.

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JoVE Journal

Chemistry

7.1K vistas.  Korea University. Nuestra idea para la validación del sitio de reacción del catalizador basado en MOF proporciona datos fiables sobre si una reacción tiene lugar en la superficie interna o externa de los MOF. Estos métodos se pueden utilizar para evaluar sitios de reacción, que pueden ser cruciales en el diseño de catalizador basado en MOF. Los estudios de investigación sobre el desarrollo de catalizadores basados en MOF pueden utilizar estos métodos para lograr una perspectiva objetiva para la caracte...