title: Stereoselective Synthesis of (+/-)-alpha-Kainic Acid Using Free Radical Key Reactions.
abstract: Thiol-mediated free radical isomerization of a deliberately substituted but-3-enyl isocyanide 12a, and n-Bu(3)SnH/AIBN-mediated free radical cyclization of a deliberately substituted but-3-enyl isothiocyanate 22, afforded, respectively, the (ethylthio)pyrroline 13a and the thiopyroglutamates 5 and 23. Reduction, protection, and deprotection of these heterocyclic compounds afforded proline derivatives 6 and 25 which contain all the structural elements of alpha-kainic acid (1) except the C-2 acetic acid moiety. These intermediates were stereospecifically converted into (+/-)-alpha-kainic acid using a new method of temporary sulfur connection. Accordingly, CH(2)CO(2)Me is linked to the chiral isopropenyl anchor and then intramolecularly connected to the pyrrolidine ring and eventually disconnected from its anchor by a sequential reductive double elimination process in which the isopropenyl double bond is restored.
authors.affiliation: Department of Organic Chemistry, The Weizmann Institute of Science, Rehovot 76100, Israel.
authors.forename: Mario D.
authors.initials: MD
authors.lastname: Bachi
authors.forename: Nira
authors.initials: N
authors.lastname: Bar-Ner
authors.forename: Artem
authors.initials: A
authors.lastname: Melman