Inverse-Electron-Demand Diels–Alder Reactions for the Synthesis of Pyridazines on DNA

Abstract

The synthesis of pyridazines on DNA has been developed on the basis of inverse-electron-demand Diels-Alder (IEDDA) reactions of 1,2,4,5-tetrazines. The broad substrate scope is explored. Functionalized pyridazine products are selected for subsequent DNA-compatible Suzuki-Miyaura coupling, acylation, and S_NAr substitution reactions, demonstrating the feasibility and versatility of IEDDA reactions for DNA-encoded library synthesis.