The overall goal of this synthetic procedure is to provide a rational way to make multi-metallic species with a pre-determined sequence of metal centers. This method can help answer key questions in organic chemistry field, such as building a unique, multi-nuclei heteromeric complex against the issues of phase separation and multiple structured outcomes. The main advantage of this technique is it's wide applicability for diverse chemical structures due to the simplicity of it's principle.
Demonstrating the procedure will be Purnandhu Bose, apostle from my laboratory. To begin this procedure, add 135 milligrams of TG sieber resin and distir bar to a 10-milliliter, two-neck flask bearing a drain at the bottom equipped with a glass filter and a two-way stopcock. Connect a three-way stopcock and a glass stopper to the joints of the flask.
Exchange the internal atmosphere with nitrogen by using a vacuum line. Then, swell the resin with one milliliter of dichloromethane. Add three millilimeters of dimethylformamide and one milliliter of piperidine to the resin.
Then, stir the mixture for 2.5 hours at room temperature. Following this, remove the solution by filtration through the drain. Wash the resin three times with three millimeters each of methanol and dichloromethane.
Then, wash the resin four times with three milliliters of dichloromethane. Combine all the solutions obtained in the previous step and dilute them with non-anhydrous acetonitrile to a volume of 50 milliliters. Transfer one millileter of the resultant solution into a quarts cuvette with an optical length of one centimeter, and dilute the sample with two millileters of acetonitrile.
Next, add dichloromethane, ruthenium monomer, HBTU, DMSO, and Hunig's base to the washed resin under a nitrogen atmosphere. Stir the mixture for 12 hours at room temperature. Following this, remove the solution by filtration through the drain.
Wash the resin three times with three milliliters of DMSO. Then, wash the resin three times with three milliliters each of methanol, and dichloromethane. After washing with additional dichloromethane, add five milliliters of dichloromethane, 0.28 grams of benzoic anhydride, and 0.1 milliliters of N-methylimidazole to the washed resin under a nitrogen atmosphere.
After stirring the mixture for two hours at room temperature, remove the solution by filtration through the drain. Wash the resin three times with three milliliters each of dichloromethane and methanol. Once the resin has been washed with additional dichloromethane, repeat the previous steps to quantify the mol number of loaded ruthenium monomer.
Now, add dichloromethane, Fmoc-protected glutamic acid ester, HBTU, DMSO, and Hunig's base to the washed resin under a nitrogen atmosphere. After repeating the washing and capping steps, transfer a small portion of the resin to a mixture containing 25 microliters of trifluoroacetic acid, 0.5 microliters of triethylsilane, and 47 microliters of 1, 2-dichloroethane. Sonic heat the mixture for 0.5 hours.
Repeat the previous steps on the residual resin in the flask to quantify the mol number of loaded Fmoc-protected glutamic acid ester monomer. After repeating the previous steps with platinum and rhodium monomers, add dichloromethane, TEGU acid, HBTU, dichloromethane, and Hunig's base to the washed resin under a nitrogen atmosphere. After stirring the mixture for 12 hours at room temperature, remove the solution by filtration through the drain.
Wash the resin two times with three milliliters of DMSO. Then, wash the resin three times with three milliliters each of methanol and dichloromethane. Once the resin has been washed with additional dichloromethane, wash it three times with four milliliters of diethyl ether.
After drying the resin under vacuum, swell it with one milliliter of dichloromethane. Add a mixture containing 0.1 milliliters of trifluoroacetic acid, 20 microliters of triethylsilane, and 1.9 milliliters of 1, 2-dichloroethane to the suspension. Stir the mixture for 12 hours at room temperature.
Following this, remove the solution by filtration through the drain, then add a new mixture of triflouroacetic acid, triethylsilane, and 1, 2-dichloroethane to the resin. Stir the mixture for one hour at room temperature, and then stop stirring. The molecular structures of the final target compound, precursors, and intermediates are shown here.
The multi tof mass spectra of the samples at selected procedural steps are shown here, demonstrating the ability of this analysis technique to trace the reactions and confirm the presence of target species. After watching this video, you should have a good understanding of how to make multi-metallic species with precisely designed metal centers.
