Stereoselective synthesis of (+/-)-alpha-kainic acid using free radical key reactions

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)pyproline 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 cr-kainic acid (1) except the C-2 acetic acid moiety. These intermediates were stereospecifically convert-ed into (+/-)-alpha-kainic acid using a new method of temporary sulfur connection. Accordingly, CH(2)CO(9)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.