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

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.