STEREOSELECTIVE SYNTHESIS OF (+ -)-ALPHA-KAINIC ACID USING FREE-RADICAL KEY REACTIONS/

Thiol-mediated free radical isomerization of a deliberately substitute d but-3-enyl isocyanide 12a, and n-Bu(3)SnH/AIBN-mediated free radical cyclization of a deliberately substituted but-3-enyl isothiocyanate 2 2, afforded, respectively, the (ethylthio)pyproline 13a and the thiopy roglutamates 5 and 23. Reduction, protection, and deprotection of thes e heterocyclic compounds afforded proline derivatives 6 and 25 which c ontain all the structural elements of cr-kainic acid (1) except the C- 2 acetic acid moiety. These intermediates were stereospecifically conv ert-ed into (+/-)-alpha-kainic acid using a new method of temporary su lfur connection. Accordingly, CH(2)CO(9)Me is linked to the chiral iso propenyl anchor and then intramolecularly connected to the pyrrolidine ring and eventually disconnected from its anchor by a sequential redu ctive double elimination process in which the isopropenyl double bond is restored.