The construction of DNA-encoded chemical libraries (DECLs) crucially relies on the availability of chemical reactions, which are DNA-compatible and which exhibit high conversion rates for a large number of diverse substrates. In this work, we present our optimization and validation procedures for three copper and palladium-catalyzed reactions (Suzuki cross-coupling, Sonogashira cross-coupling and copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC)), which have been successfully used by our group for the construction of large encoded libraries.