Diboron-Mediated Reduction and in situ Generated Cu(I) for DEL-Compatible Synthesis of Dihydroquinazolinones

DNA-encoded library (DEL) technology has become an essential approach for accelerating hit discovery in drug development, yet its success is closely tied to the availability of robust and DNA-compatible reactions. Here we report a diboron-mediated strategy that leverages in situ generated Cu(I) to enable the efficient on-DNA construction of dihydroquinazolinones, a privileged heterocyclic scaffold with broad pharmacological relevance. This transformation proceeds via selective nitro group reduction followed by intramolecular cyclization with aldehydes or ketones under mild, aqueous-compatible conditions. The method tolerates diverse building blocks, delivering high conversions across a panel of substrates. By providing a reliable and atom-economical route to dihydroquinazolinones directly on DNA, this study expands the accessible chemical space of DELs and enriches the toolbox of DNA-compatible heterocycle syntheses.