Intramolecular Cyclization of Grignard or Blaise Intermediates for the Synthesis of a Chiral Piperidine-2,4-dione Derived from (R)-(‒)-Phenylglycinol

In this work, we describe the synthesis of chiral (R)-(‒)-piperidine-2,4-dione derived from (R)-(‒)-phenylglycinol, a valuable building block for the diastereoselective synthesis of piperidine alkaloids. The key step involves intramolecular cyclization: when the electrophile is an ester, the reaction proceeds via the formation of a Grignard intermediate, whereas when the electrophile is a nitrile, the cyclization follows a Blaise-type mechanism.