DNA‐Compatible Nitriles Hydrolysis for Late‐Stage Functionalization of DNA‐Encoded Libraries

Abstract Primary amides play a crucial role in organic and pharmaceutical synthesis. Herein, we present a rapid and convenient method for transforming diverse DNA‐conjugated nitriles into primary amides utilizing hydrogen peroxide and potassium carbonate. The substrate scope and DEL compatibility of this reaction were thoroughly investigated, revealing a wide range of substrates with moderate‐to‐excellent conversion. This on‐DNA transformation holds significant promise for constructing DNA‐encoded libraries (DELs) and enabling late‐stage functionalization to expand chemical diversity. Our approach not only highlights the versatility of the method but also underscores its potential for broad applications in organic and pharmaceutical synthesis.