Fluoral hydrate: A perspective substrate for the Castagnoli-Cushman reaction

Abstract

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.