Synthesis of Oxazolyl‐Piperidines Bearing a Quaternary Stereocenter Through a Multicomponent Reaction Involving α‐Isocyanoacetates and Piperidones

The synthesis of 5‐alkyloxy‐oxazoles from α‐isocyanoacetates, aldehydes, and amines is well known, yet analogous reactions with ketones remain largely unexplored. Here, we investigate 3‐ and 4‐piperidones, selected for their biological relevance, in a multicomponent reaction with α‐(EWG‐phenyl)‐α‐isocyanoacetates and amines. This adapted multicomponent reaction (MCR) protocol provides an efficient, sustainable, and atom‐economic route to 4‐oxazolyl‐piperidines containing a quaternary stereocenter. The optimized conditions afford the desired heterocycles in good to excellent yields. Overall, this methodology expands the synthetic utility of isocyanoacetate‐based MCRs and delivers valuable scaffolds relevant to drug discovery.