Improved Route To OCF₃ Building Blocks

A new synthetic strategy for introducing the trifluoromethoxy group into aliphatic organic molecules is a promising way to make pharmaceutical and agricultural chemicals, according to Karsten Koppe of Heinrich Heine University, in Düsseldorf, Germany. The OCF₃ group is strongly electron withdrawing and offers advantages such as increased lipophilicity over popular F or CF₃ substituents that are commonly used to improve drug efficacy. Although an industrial process using chlorine-fluorine exchange to prepare OCF₃-containing aromatic compounds exists, there are few examples of procedures to make aliphatic compounds bearing OCF₃ groups, and they are limited in scope, Koppe said. Koppe and coworkers, in collaboration with Nikolai V. Ignat’ev of Merck KGaA, in Darmstadt, Germany, devised a method that uses OCF₃ salts to introduce OCF₃ to aliphatic compounds bearing different functional groups. For example, the researchers prepared KOCF₃ by adding CF₃SO₂OCF₃ to KF in N,N-dimethylacetamide solvent. Adding organic halides or mesylates to KOCF₃ results in the trifluoromethoxy compounds, which can be derivatized to create epoxides, diols, aminoalcohols, and other intermediates, Koppe said, “giving us a whole factory of OCF₃ building blocks.”