The chemistry of molecules containing fluorine atoms has grown in interest and in consequence a great increase of the number of papers on synthetic strategies to introduce fluorine atoms in molecules has been observed during the last years. Fluor is known to improve the biological activity of drugs by enhancing properties such as the solubility, stability and lipophilicity of molecules. The OCF3 moiety in particular presents one of the highest lipophilicity values favouring  in vivo uptake and transport in biological systems.

orto OCF3 migration

Ngai and co-workers describe a useful procedure for the synthesis of ortho-trifluoromethoxylated anilines through a two-step sequence of O-trifluoromethylation of alkyl hydroxylamines followed by OCF3 migration. The methodology allows the formation o a wide range of ortho-OCF3 aniline derivatives with high regioselectivity and can be performed one-pot. One of the drawbacks is that the migration step requires higher temperatures than the initial trifluoromethylation making  almost unavoidable the removal of solvent and further re-dissolution to achieve the whole sequence.

Do you want to know more? You can find here the paper:

Katarzyna N. Hojczyk, Dr. Pengju Feng, Chengbo Zhan andProf. Ming-Yu Ngai. Trifluoromethoxylation of Arenes: Synthesis of ortho-Trifluoromethoxylated Aniline Derivatives by OCF3 Migration. Angew, Chem. Int. Ed. 2014, 53, 14559-14563.

Advertisements