Organocatalytic Domino Michael-Heterocyclization Reaction of Unsaturated Aldehydes and Cyano Ketones. Synthesis of Enantioenriched 4,5,6-Trisubstituted 3,4-Dihydropyranones

Abstract

α,β-Unsaturated aldehydes with aliphatic, electron-poor aromatic, or electron-withdrawing substituents at the β position easily react with different ketones leading to enantioenriched hemiacetals, which were further oxidized to give 4,5,6-trisubstituted-3,4-dihydropyranones in good yields and with excellent enantioselectivities. The behavior of the ketones is dependent on the α substituent of the carbonyl group, and a fine-tuning of the pKa values is necessary to obtain good results.