Palladium(II)-catalyzed olefin-coupling reactions of kainic acid: effects of substitution on the isopropenyl group on receptor binding

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Abstract
Two Pd-catalyzed C-C bond forming reactions were useful for the modification of a protected amino acid derivative containing a sterically hindered isopropenyl group. Arylation of the terminal methylene group of the dimethyl ester of N-(ethoxycarbonyl)kainic acid (3) was accomplished by treatment with an aromatic amine, Pd(II) acetate and tert-butyl nitrite. Substitution of the allylic methyl group of 3 was accomplished by conversion to the .pi.-(allyl)Pd complex which, on subsequent treatment with the carbanions of tert-butyl acetoacetate or phenylthioacetone, gave the alkylated products. Both the (Z) and (E)-3 nitrophenyl derivatives of kainic acid were active in the standard binding assay. Unexpectedly, the cis compound in the nitrophenyl series, which more closely resembles the extended conjugation found in domoic acid, was 20 times less potent than the trans derivative. The latter had 1/5 the receptor-binding affinity of kainic acid.