Oxacycles and benzoxepanes are privileged motifs present in a variety of natural products and functional molecules. However, their synthetic access is limited. Here, we demonstrate a rapid synthesis of unprecedented benzoxepanes from readily available starting materials in one step via a Passerini multicomponent reaction. The reaction proceeds smoothly under mild reaction conditions. We have obtained a single-crystal X-ray structure, revealing a butterfly conformation, combined with useful structural features. In addition, we have performed both a full interaction map on the X-ray structure and a profile analysis of a virtual library based on the proposed scaffold with a special focus on certain physicochemical parameters to demonstrate their potential usage in drug discovery.
Keywords: Dioxepinones; Multicomponent reactions (MCRs); Oxacycles; Passerini reaction; Rule of five (Ro5).
© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.