The preparation and reactions of protected glyphosate imidate, thioimidate, and thiono esters from N-[diphenoxyphosphinylmethyl]glycinonitrile: Comparative reactivities of activated carboxylate versus phosphonate esters

Abstract

The highly efficient syntheses of novel protected glyphosate imidate, thioimidate, and thiono ester derivatives are described starting from N-[diphenoxyphosphinylmethyl]glycinonitrile 3b. The scope, utility and limitations in using each of these activated carboxylate functionalities for further transformations to new “masked” heterocyclic derivatives are defined. While the solution stability of the imidate and thioimidate series limited the synthetic application of these species, the corresponding thiono ester derivatives were valuable synthetic intermediates, providing a short, efficient route to the first glyphosate derivatives containing 1,3,4-oxadiazole and 1,2,4-triazole ring systems in place of the carboxylate group. These thiono esters thus undergo selective nucleophilic addition at this activated carboxylate center, while retaining the reactive diphenyl phosphonate moiety.