Asymmetric Remote Aldol Cyclization Reaction to Synthesize Trifluoromethylated Heterospirocyclic Frameworks
José Trujillo-Sierra1, José Miguel Sansano1, Jorge Pardos2
1Departamento de Química Orgánica, Centro de Innovación en Química Avanzada (ORFEO-CINQA) and Institute of Organic Synthesis, Universidad de Alicante, Ctra. Alicante-San Vicente s/n, 03080 Alicante, Spain.
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.
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