Solvent-free silica-promoted multicomponent condensation: synthesis of highly functionalized piperidines

Silica gel has been found to be an efficient and reusable medium for the synthesis of diastereospecific functionalized piperidines in good to high yields by a one-pot three-component condensation of aldehyde, amine and beta-ketoester under solvent-free conditions at room temperature. Using this environmentally benign, non-inflammable and non-toxic reaction medium, the non-chromatographic purification, reusability of the silica gel, and operational simplicity are the notable advantages of the present method. The procedure is applicable for large-scale synthesis of piperidines derivatives and represents a green synthetic protocol.