Synthsis of 4-Piperidones via Multicomponent Double Mannich Reaction Catalyzed by I2

A multicomponent double Mannich reaction of amines, aldehydes and ketones was efficiently catalyzed by molecular iodine, producing a series of 4-piperidones in a stereoselective way. A variety of amines, aldehydes and ketones were tolerated in this tandem process, including those with labile functinal groups. Further investigation of the reaction between alkyl-imines and ketones showed that imines from amines and ketones were formed in situ and isomerized to enamine in the presence of molecular iodine to accelerate the corresponding Mannich addition.