General chemoselective hindered amide coupling enabled by TCFH-catalytic Oxyma and transient imine protection

Abstract

We report a general chemoselective strategy for amide bond formation with poorly nucleophilic amines in the presence of reactive primary alcohols or amines as the competing nucleophiles. The selectivity for less reactive amines over competing alcohols was achieved using TCFH and catalytic Oxyma as a highly reactive, inexpensive, and safe reagent combination. By temporarily masking more reactive amines as imines through the use of electron-deficient aldehydes, the hindered amines could be similarly coupled with high efficiency and selectivity.