Synthesis of Piperidones by MCR

Significance

Based on a previous synthesis of piperidines by using the Diels-Alder reaction of 3-trialkylsilyloxy-2-azadienes with electron-poor olefins (L. Ghosez and co-workers Tetrahedron Lett. 1991, 32, 1401), a new four-component ­reaction (aldehyde, an equivalent of ammonia, acyl chloride, dienophile) has been developed for the synthesis of polysubstituted piperidones. By this process, the synthesis of the intermediate diene and its cycloaddition reaction occur in one pot, avoiding the problem of instability of the azadiene as observed in the previous work. When the acyl chloride is linked to the dienophile, piperidones fused to a five- or six-membered ring are obtained in the one-pot process. The stereo-chemistry of those piperidone products was confirmed by NMR spectroscopy as well as X-ray diffraction analysis studies.