A general strategy for the synthesis of α-kainic acid has been developed, based on a [3 + 2] cycloaddition reaction between an azomethine ylide and an olefin to furnish the basic pyrrolidine skeleton.
In a first series of experiments, azomethine ylides were generated by a thermal decomposition of Δ2 -1,2,3-triazolines via aziridines and were trapped with dipolarophiles yielding pyrrolidine derivatives. The reaction failed with cyclopentenone and thermal decomposition did not take place with triazoline having an S-phenyl substituent. Attempts to prepare triazolines by an intramolecular 1,3-dipolar cycloaddition failed to yield the desired product.
In another series of experiments azomethine ylides were generated by a thermal isomerisation of imines derived from α-amino acid esters and were trapped with dipolarophiles yielding pyrrolidine derivatives. No thermal isomerisation was observed with thioformimidate derivatives of α-amino acid esters.
Azomethine ylides were generated by deprotonation of immonium salts derived from thioformimidate derivative of α-amino acid esters. They were trapped with dipolarophiles yielding pyrrolidine derivatives. No cycloadduct was obtained with cyclopentenone.
A strategy for generating azomethine ylides by desilylation of immonium cations derived from α-amino acid ester derivatives was developed. The basic precursor for the reaction could not be prepared.
Azomethine ylides were also generated by elimination of an S-phenyl group from sarcosine methyl ester derivative; trapping experiment with cyclopentenone failed to produce pyrrolidine derivative.
A strategy for generating azomethine ylides by a base promoted reaction from t-amine-N-oxide derivatives has been investigated.