DNA-Compatible Huisgen [3 + 2] Cycloaddition of In Situ Formed Nitrile Oxides with Alkenes or Alkynes to Synthesize Isoxazolines or Isoxazoles

DNA-encoded chemical library (DECL) technology is recognized as a robust screening platform for drug discovery. Developing new DNA-compatible reactions is crucial for expanding the chemical space of DECLs. Cyclization reactions, particularly those involving the formation of heterocycles, offer unique and efficient methods for accessing privileged scaffolds or lead-like small molecules. In this study, we introduce two new methods that utilize readily accessible aldehydes to create substituted isoxazolines and isoxazoles by the 1,3-dipolar cycloaddition reaction. These methods demonstrate high conversion efficiency and can be applied to a wide range of substrates. The reactions are DNA-compatible and do not cause significant DNA degradation.