Fluoral Hydrate: A Perspective Substrate for the Castagnoli–Cushman Reaction

The reactivity of
azomethines based on trifluoroacetaldehyde hydrate
in the Castagnoli–Cushman reaction (CCR) was researched. The
impact of the nature of anhydrides explored on the reaction route
was determined. The preparative procedures for the synthesis of N-substituted
(3R*,4R*)-1-oxo-3-(trifluoromethyl)-1,2,3,4-tetrahydroisoquinoline-4-carboxylic
and (1R*,2R*)-4-oxo-2-(trifluoromethyl)-2,3,4,5-tetrahydro-1H-benzo­[d]­azepine-1-carboxylic acids in
gram scales were elaborated. It was shown that the trifluoromethyl
group remarkably decreased the reactivity of azomethines in CCR. The
mechanism for the formation of different products depending on the
anhydride’s nature was proposed.