The overall goal of this procedure is to demonstrate that aerated olefins are smoothly formed by the cross coupling of aero bromides with olefins under mild reaction conditions in the presence of catalytic amounts of di chloro bis one one prime, one double prime phosphine Tri tri papine palladium. This is accomplished by first preparing the amino phosphine based ligand one one prime, one double prime phosphine tri tri papine, and a one step synthesis with cheap and commercially available starting materials. The second step involves formation of the active pre catalyst one by coordination of two equivalents of the amino phosphine on the palladium center by mixing chloro one five cyclo dyne palladium with a slight excess of the amino phosphine.
Next, the cross coupling reaction between styrene and four promo benzene is carried out by a simple one pot reaction containing the substrates base, solvent stabilizer and catalyst. The final step is to purify the formed coupling product by column chromatography and to analyze and fully characterize the pure compound. Ultimately the novel highly active amino phosphine based palladium catalyst one is used to couple arrow bromides with oleic substrates using am meki he reaction under much milder reaction conditions than typically required.
This uniformly applicable reaction allows shortened synthetic access to new organic molecules containing vinyl benzene units in very high yields, which are found in pharmaceutically active compounds. The main advantage of this catalyst over existing systems is that this catalyst is simple and rapidly prepared from very cheap and commercial available starting materials in one step and combines high stability, universal applicability, and excellent functional group tolerance with high reactivity on the mild conditions. First, add 150 milliliters of dry di ethyl ether and five milliliters of phosphorus tri chloride to an oven dried 500 milliliter round bottom flask.
After placing a stir bar in the flask, attach a 250 milliliter dropping funnel and cover it with a septum. Then cool down the solution to zero degrees Celsius by placing the flask in an ice bath mix 42.5 milliliters of papine with 100 milliliters of dathyl ether and transfer this solution to the dropping funnel. Next, slowly add the solution via the dropping funnel into the stirring phosphorus tri chloride solution.
After complete addition, remove the ice bath and warm the reaction mixture to room temperature. In order to ensure full conversion, stir the solution for an additional 30 minutes. Following this, filter the reaction mixture over a glass frit and collect the filtrate in a 500 milliliter round bottom flask in order to increase the yield of the amino phosphine.
Wash the filter cake with an additional 100 milliliters of dry dathyl ether. Evaporate the filtrate on a rotary evaporator to obtain the pure ligand in greater than 80%yield as an off-white oil, which solidifies with time. Check the product purity by proton decoupled phosphorus and MR spectroscopy.
For the catalyst synthesis, add 100 milligrams of diora, one five cyclo dyne palladium to a clean oven dried 50 milliliter round bottom flask containing five milliliters of dry tetra hydro furin. Add a stir bar, cover the flask with a septum and stir the suspension. Next, add 248 milligrams of the amino phosphine to a clean dry vial containing 10 milliliters of dry THF.
After transferring the solution to a syringe added to the tetra hydro furan suspension of di Chloro one five cyclo dyne palladium. In order to remove the insoluble solids, pass the reaction mixture quickly through an oven dried glass frit and collect the filtrate in a 25 milliliter round bottom flask, remove the volatiles under reduced pressure. When finished, wash the palladium complex three times with five milliliters of pentane.
Following this, remove the pentane dry the yellow powder under reduced pressure to quantitatively obtain analytically pure to chloro bis. One one prime, one double prime phosphine tri trippi paridine palladium. Check the purity of the palladium complex by proton decoupled phosphorus.
MR spectroscopy. At this point, add 37.15 milligrams of chloro bis one one prime, one double prime phosphine tri tri paridine palladium to an oven dried 50 milliliter schlink flask. After covering the flask with a septum, evacuate it and backfill with nitrogen gas.
Add 10 milliliters of dry and degas tetra hydro furan via syringe to the flask, add 322.4 milligrams of tetra butyl ammonium bromide, and 2.77 grams of potassium carbonate to a clean oven dried 50 milliliter round bottomed sch flank flask. Using a syringe add 20 milliliters of end methyl to perone to the flask. After adding a stir bar and covering the flask with a septum, evacuate and backfill the flask with nitrogen gas.
Next, add 1.75 milliliters of one bromo, four phenoxy benzene via syringe to the flask. Attach a reflux condenser to the flask by applying a stream of nitrogen. Then connect the reflux condenser to an oil bubbler and set a slight over pressure of nitrogen gas.
Heat the reaction solution to 100 degrees Celsius and stir the solution for five minutes at this temperature. Following this, add one milliliter of the catalyst solution to the reaction mixture via syringe and stir it vigorously for three hours. Check the product formation by GCMS.
Once the reaction is complete, remove the schlink flask from the oil bath and quench the reaction mixture With 50 milliliters of one molar hydrochloric acid, transfer the cooled reaction mixture to a 500 milliliter separation funnel and add 50 milliliters of ethyl acetate. Separate the HEC product by extraction After repeating the extraction two more times. Combine all organic phases in an erlenmeyer flask.
Add magnesium sulfate to the flask to soak up any last amount of water present in the solution. Next, filter the combined organic layers over a paper filter into a round bottom flask. Wash the filter cake with an additional 50 milliliters of ethyl acetate.
Then concentrate the solution on a rotary evaporator to obtain the crude coupling product. Separate the he product via column chromatography using a five to one mixture of hexane and ethyl ether as the eent. After evaporating the solvent on a rotary evaporator, check the product purity by proton and proton decoupled carbon.
And MR spectroscopy shown here is a selection of recently prepared cross coupling products that demonstrates the scope of this protocol. The coupling products are cleanly formed and typically obtained in excellent yields within reasonable reaction times. The e isomer of the aerated olefins is often exclusively formed Accordingly.
Chloro BIS one one prime, one double prime Phosphine Tri. Tri Perine Palladium is a cheap, easily accessible and green catalyst. Although stable, it is a highly reactive HEC catalyst with high functional group tolerance, which efficiently and reliably operates at low catalyst loadings with an easily adaptable and robust reaction protocol.
Best results were achieved with NN dimethylformamide when electronically activated or nonactivated aero bromides were used to give compounds a two a five, a six, a seven a 13, a 17, A 18 B one, and H four N methyl two. Parone, however, was found to be the solvent of choice when electronically deactivated and hysterically hindered or heterocyclic. Arol bromides were coupled with ine.
Examples include the preparation of compounds, a nine, a 12, a 14 C, 3D, 3D four E two, E three F two, F four, G three, G four, H five, and H six. After watching this video, you should have a good understanding of how to apply this uniformly applicable reaction protocol. To perform a typical catalytic reaction in a HEC type manner is frac aminos based, palladium catalyst.
