A Concise, Stereocontrolled Thiazolium Ylide Approach to Kainic Acid

Article abstract of DOI:10.1021/jo00089a022

Racemic α-kainic acid (1) has been prepared from (1SR,2SR,5RS)-ethyl (N-(benzyloxycarbonyl)-3-aza-6-oxobicyclo<3.3.0>octane-2-carboxylate (11) in ca. 16percent overall yield via a concise six-step synthetic sequence.Compound 11 is prepared on a large scale in 50percent yield via the <3 + 2> cycloaddition of thiazolium ylide 9 and 2-cyclopentenone, which provides the requisite 2,3-trans, 3,4-cis stereochemical array about the trisubstituted pyrrolidine nucleus in 1.Chemoselective addition of the one-to-one adduct of MeLi and TiCl4 to the ketone functionality in 11 followed by dehydration, oxidative ring opening, and nonbasis methylenation of the stereochemically labile C4 acetate moiety with CH2I2-Zn-TiCl4 affords the fully protected penultimate intermediate 17 which is exhaustively hydrolyzed to provide 1.This represents a highly efficient and stereocontrolled preparation of (+/-)-α-kainic acid.