Asymmetric Remote Aldol Cyclization Reaction to Synthesize Trifluoromethylated Heterospirocyclic Frameworks

J Org Chem. 2024 Sep 20;89(18):13654-13660. doi: 10.1021/acs.joc.4c01839. Epub 2024 Sep 5.

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.