Synthesis of CF3-substituted 1,2,3,4-tetrahydroisoquinolines and 1,2,3,6-tetrahydropyridines

A three-step method for the preparation of CF3-substituted 1,2,3,4-tetrahydroisoquino-lines and 1,2,3,6-tetrahydropyridines has been suggested. The first step includes alkylation of isoquinoline or 4-methylpyridine at the nitrogen atom with the formation of salts, which are involved into the reaction with Grignard reagent or lithium triethylborohydride to give enamines. The enamines undergo nucleophilic trifluoromethylation upon the action of Me3SiCF3 under acidic conditions.