Enantioselective total synthesis of (−)-α-kainic acid
a-Kainic acid and (-)-a-kainic acid ( 1) were synthesized. (-)-a-Kainic acid was obtained in 12% overall yield starting from tert-butyl isocyanoacetate. In the first step a chiral non-racemic oxazoline 19 was prepared. Oxazoline 19 was converted in three steps into the thioformimide 22 derived from a highly functionalized a-amino carboxylic acid. It was subjected to n-Bu3SnHlAIBN mediated free radical cyclization to enantiomerically pure pyrrolidine 25 which contain all the structural elements of (-)-a- kainic acid, except for the C-2 acetic acid moiety. This appendage was introduced by a new method of temporary sulfur connection. Accordingly, the 4-isopropenyl group was used as an anchor to which CH2C02Me was temporarily linked (26+13+ 14+15). It was then intramolecularly connected through a carbon-carbon bond to the pyrrolidine ring (15+ la), and eventually disconnected from its anchor by a sequential reductive double