Total Synthesis of (−)-(α)-Kainic Acid via a Diastereoselective Intramolecular [3 + 2] Cycloaddition Reaction of an Aryl Cyclopropyl Ketone with an Alkyne

Abstract

An enantioselective synthesis of (-)-(α)-kainic acid in 15 steps with an overall yield of 24% is reported. The pyrrolidine kainoid precursor with the required C2/C3 trans stereochemistry was prepared with complete diastereoselectivity via an unprecedented SmI2-catalyzed intramolecular [3 + 2] cycloaddition reaction of an aryl cyclopropyl ketone and an alkyne. Double bond isomerization was then employed to set the remaining stereochemistry at the C4 position en route to (-)-(α)-kainic acid.