Asymmetric Remote Aldol Cyclization Reaction to Synthesize Trifluoromethylated Heterospirocyclic Frameworks.

Abstract

The highly enantioselective organocatalytic synthesis of dihydropyran spirocyclic compounds bearing di- and trifluoromethyl groups by aldol cyclization reaction via trienamine using cyclic 2,5-dienones and different di- and trifluoromethylketones is described. Using a bifunctional aminothiourea catalyst, trifluoromethyl-functionalized dihydropyran spirocyclic products were obtained with good yields and enantioselectivities. Subsequent transformation with H₂ and Pd/C has allowed the synthesis of the tetrahydropyran structure with three stereocenters. The plausible reaction mechanism was investigated by computational methods.