Efficient route to 6-CF3-substituted nicotinic acid derivatives

A novel synthetic sequence for preparation of CF3-pyridines is presented. Reaction of α,β-unsaturated trifluoromethylketones with α-cyanoketones leads to α-hydroxydihydropyranes 1 containing CF3-group. α-Hydroxydihydropyranes can be easily transformed to α-hydroxytetrahydropyridines, 1,4-dihydropyridines and CF3-pyridines. All CF3-pyridine derivatives were obtained in good yields. This route can be applied for preparation of CF3-pyridines containing various substituents with further possible modification on cyano-group.

Graphical abstractA novel synthetic sequence for preparation of CF3-pyridines is presented. Reaction of α,β-unsaturated trifluoromethylketones with α-cyanoketones leads to α-hydroxydihydropyranes 1 containing CF3-group. α-Hydroxydihydropyranes can be easily transformed to α-hydroxytetrahydropyridines, 1,4-dihydropyridines and CF3-pyridines. All CF3-pyridine derivatives were obtained in good yields. This route can be applied for preparation of CF3-pyridines containing various substituents with further possible modification on cyano-group. Figure optionsDownload full-size imageDownload as PowerPoint slide