Unexpected formation of highly functionalized dihydropyrans via addition-cyclization reactions between dimethyl oxoglutaconate and α,β-unsaturated hydrazones

The condensation between dienophiles and α,β-unsaturated hydrazone azadienes was previously reported to afford piperidines. During an attempt to adapt this reaction to the preparation of piperidine-based conformationally restricted analogs of glutamate, it was discovered that the electrophile, dimethyl oxoglutaconate (DOG) led to highly substituted dihydropyrans in 20–50% yield. The unexpected pyran product likely results from an initial 1,4-addition of the hydrazone to the oxoglutaconate followed by intramolecular cyclization of the resultant enolate oxygen to the α,β-unsaturated iminium ion. Further manipulations afford substituted tetrahydropyran 6-methamino-2,4-dicarboxylic acids.