Hydrolytic and radical cyclization chemistries of imidate esters, and the photochemical rearrangement of 1-azabicyclo(2.2.2)octenones

The preparation of alkaloids is of continuing interest to the synthesis chemist. In this work, two new methods for the assembly of alkaloids from simpler compounds have been investigated. In the first, the radical cyclization of aryl radicals onto the nitrogen of an imidate ester is described. This cyclization yielded the 5-exo product only, unlike the similar radical cyclization of aldimines. This work was directed toward the synthesis of the mitomycins. In the second, the oxa-di-pi-methane rearrangements of heptyl and methyl 1-aza-5-oxobicyclo (2.2.2) oct-2-ene carboxylates are described. These rearrangements were directed toward the synthesis of heliotridine. Finally, the hydrolysis of imidates was used to effect the difficult transformation of primary amides to methyl esters, as illustrated by a synthesis of a precursor of the analgesic carfentanil.