One-pot synthesis of functionalized piperid-4-ones: A four-component condensation

The one-pot synthesis of highly substituted piperid-4-ones has been achieved. Diketene is added to a tosyl imine in the presence of TiCl4 and MeOH, followed by 1 equiv of aldehyde to generate 2,6-disubstituted nonsymmetrical piperid-4-ones as a mixture of cis-/trans-diastereomers in good yields. This mixture of diastereomers can be converted to a single 2,6-cis-diastereomer by epimerization with K2O3.