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.