Study On Methodology Of Double Mannich Reaction For Synthesis4-Piperidones Catalyzed By I₂

In this paper, we studied iodine catalyzed double-Mannich reaction andstereospecifically synthesized a series of4-piperidones in high yields, giving thefollowing results:1. The double Mannich reaction between inactivated ketones and aromatic iminesoccurred smoothly under iodine catalyzed conditions, producing the corresponding4-piperidones in high yields. Two pathways involving the balance between chelationeffects and hydrogen bonding were proposed to rationalize the formation of theproducts, which was supported by further investigation of the reaction between β-aminoketones and imines.2. A multicomponent double Mannich reaction of amines, aldehydes and ketones wasefficiently catalyzed by molecular iodine, producing a series of4-piperidones in astereoselective way. A variety of amines, aldehydes and ketones was tolerated in thistandem process, including those with labile functinal groups. Further investigation ofthe reaction between alkyl-imines and ketones showed that imines from amines andketones were formed in situ and enaminized in the presence of molecular iodine toaccelerate the corresponding Mannich addition.3. Cross double Mannich reaction and tandem cyclization were achieved under iodineinduced conditions, yielding a series of highly substituted4-piperidones. Among thepossible diastereomers, only one diastereomer was isolated, which could be ascribledto the chair-like transition state in six-membered ring, in which all of the hinderedgroups are located in the pseudoequatorial orientation, and the desired productsstructures was futher confirmed through the X-ray crystal diffraction.