One-pot amidation of esters by exploiting iridium-nitrene intermediacy

Abstract

In this study, we developed the new practical approach of Ir-catalyzed one-pot amidation of esters to access to α-amido ester compounds, significant structural scaffolds in pharmaceutical agents and natural products. We developed an α-amidation reaction of silyl ketene acetals using N-tosyloxycarbamate as a nitrene precursor by harnessing the electrophilic reactivity of putative oxycarbonylnitrenoid mediated by Cp*(LX)Ir(III) catalyst. This one-pot procedure exploits in situ prepared silyl ketene acetal from abundant esters for subsequent α-amidation, without separate purification via distillation. The present amidation takes place selectively at the α-C–H bonds to both aryl and alkyl substituted esters. Also, DFT studies revealed that the chelation of the counter cation facilitates the N–O bond cleavage of the nitrene precursor, providing facile generation of key Ir-nitrenoid intermediate.