Late-stage N-functionalization of diazo NH-heterocycles via alkylation by Mitsunobu reaction or with alkyl halides

Abstract

a-Diazo carbonyl compounds are widely used as reagents of vast synthetic potential, capable delivering biologically relevant compounds and diverse molecular scaffolds. Herein we present methods for selective N-alkylation of various diazo NH-heterocycles while maintaining the diazo function for further modifications. a-Diazo homophthalimide, diazo arylidene succinimides, diazo barbituric and thiobarbituric acids, and a-diazo pyrazolones were readily alkylated with alkyl halides or alcohols under Mitsunobu reaction conditions. This is the first time that the Mitsunobu reaction has been applied for the functionalization of diazo carbonyl compounds. The method expands the scope of substituents that can be introduced into the diazo molecule, including such challenging moieties as adamantyl, cholesteryl and menthyl.