Stereoselective Construction Of Fluorinated Indanone Derivatives Via A Triple Cascade Lewis Acid-Catalyzed Reaction

Cascade reaction is one of the important reaction in organic chemistry , it enable a rapid increase in molecular complexity from readily available starting compounds and construct several covalent bonds in one-pot, it is an efficient synthesis strategy of constructing complicated organic compounds economically and conveniently. So cascade reaction has attracted considerable attention in recent years.Indanone derivatives are useful compounds serving as building blocks for the synthesis of natural products, medicines and agrochemicals. Fluorine-containing indanone compounds may have appealed to many chemists because of its significant biologicalactivitives and great potential application values in drug. In this paper, a one-pot three component cascade reaction proceeds by way of a Lewis acid-catalyzed Knoevenagel condensation/Nazarov cyclization / electrophilic fluorination sequence to afford fluorinated 1-indanone derivatives in moderate to good yields with high diastereoselectivities.In this reaction, we examined comprehensive experimental factors, such as catalysts, loads of catalysts, solvents, temperatures and electronic fluorinating reagent . Good results were observed. The structures of the new products have been determined by IR, ¹⁹F NMR, ¹H NMR, ¹³C NMR, MS and element analysis. The major diastereomers for the cascade products methyl 1-(4-chlorophenyl)-2-fluoro-2,3- dihydro-3-oxo-1H-indene-2-carboxylate were recrystallized in pure form by using an ethyl acetate / petroleum mixture. The relative stereochemistry confirmed by X-ray crystallography indicates that subsequential fluorination occurs trans to the R group of Nazarov cyclization intermediate, and the cis attack was sterically restricted byβ-aromatic group of R.