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Numan and Brichacek developed a new method for the synthesis of chiral organophoshinates in 2021 with moderate yields and mediocre stereoselectivity. In their publication, they first generated isopropyl phenyl-H-phosphinate (i-Pr PhPHO) as a starting material by reaction of phenylphosphinic acid and liquid 2-propanol at high temperatures in a tightly sealed reaction vial. They reported yields of around 70-75%. However, when done in our lab, the yield was only 11% or less. Several attempts at improving yield centered around increases in temperature, but this ultimately made no changes in yield. Further research uncovered a different method for the synthesis of i-Pr PhPHO proposed by Afarinkia and Yu which utilizes alkyl chloroformates and phenylphosphinic acid. This new reaction yielded upwards of 90% product in our lab. It also takes far less time, requiring only 15 minutes to reflux compared to the 18 hours of the old method. The new method also has the benefit of being safer since it does not require heating a sealed-volume apparatus. We tested a new catalyst, HyperBTM, for its ability to create chiral organophosphinates using Numan’s protocol. Although very similar in structure to Numan’s catalyst (BTM), HyperBTM has an increased amount of steric bulk and slightly larger ring size that we envisioned would be more selective in the reaction. We found that the use of HyperBTM results in trace yields of the desired product. Enantiomeric excess was undetermined due to suspected degradation of the compound during HPLC through a chiral column. An alternative strategy is currently underway that combines BTM with various transition metals to form a cooperative bifunctional catalytic approach that we envision will have greater success.
Primary Advisor's Department
Stander Symposium, College of Arts and Sciences
"Exploration of Methods for the Synthetic Pathway of Chiral Organophosphonates" (2023). Stander Symposium Projects. 3205.
Presentation: 10:45 a.m.-12:00 p.m., Kennedy Union Ballroom