Stereoselective Formal Synthesis of (+)-Allokainic Acid <i>via</i> Thiol-Mediated Acyl Radical Cyclization

Abstract

Stereoselective formal synthesis of (+)-allokainic acid was accomplished starting from L-glutamate by using a thiol-mediated acyl radical cyclization as a key step. The cyclization of a formylalkenoate proceeded in a highly diastereoselective manner to give trans-4,5-disubstituted pyrrolidin-3-one without the production of the cis-isomer. The pyrrolidinone was then converted into the established synthetic intermediate of (+)-allokainic acid via the iron-catalyzed coupling reaction with an isopropenyl Grignard reagent.