Synthesis of Highly Functionalized Piperidines via One-Pot, Five-Component Reactions in the Presence of Acetic Acid Solvent

A simple and efficient method was developed for one-pot, five-component synthesis of highly functionalized piperidines from reactions of β-keto esters, aromatic aldehydes, and various amines catalyzed in acetic acid medium. The reaction proceeded smoothly to generate the corresponding product in good yield. We have found that the use of acetic acid as reaction medium has a remarkable beneficial effect on the reaction, allowing it to be performed without the need to incorporate a catalyst, which is the case in other similary reported methodologies. In all cases, the substituted piperidine precipitates out of solution.