When I was working with one of the leading agrochemicals company, I was using 4-chlorobenzotriflouride as starting material for my two projects (trifluralin and a pyrazole derivative with diflouromethyl substituted phnyl). I know how difficult is to introduce the triflouromethyl group (use of anhydrous HF to convert CCl3 to CF3) and that is why we got the starting material imported.
Now, MIT chemists have designed a new way to attach a trifluoromethyl group to certain compounds, which they believe could allow pharmaceutical companies to create and test new drugs much faster and potentially reduce the cost of drug discovery.
MIT Chemistry Professor Stephen Buchwald, who led the research team, says achieving the synthesis has been a long-standing challenge for chemists. "Some people said it couldn't be done, so that's a good reason to try," says Buchwald, the Camille Dreyfus Professor of Chemistry at MIT.
With the new reaction, the CF3 group can be added at a much later stage of the overall drug synthesis. The reaction can also be used with a broad range of starting materials, giving drug developers much more flexibility in designing new compounds. Though many groups are trying, the major challenge has been finding a suitable catalyst to transfer the CF3 entity from another source to the carbon ring.
During the reaction, a CF3 group is transferred from a silicon carrier to the palladium, displacing a chlorine atom. Subsequently, the aryl-CF3 unit is released and the catalytic cycle begins anew. The researchers tried the synthesis with a variety of aryl compounds and achieved yields ranging from 70 to 94 percent of the trifluoromethylated products.
Researchers conclude that, in its current state the process is too expensive for manufacturing use. For drug discovery, however, it may lower overall costs because it streamlines the entire synthesis process.
"For discovery chemistry, the price of the metal is much less important," says Kinzel....
Ref : http://www.sciencemag.org/cgi/content/abstract/328/5986/1679
