Halogen-Guided Reconstructive Transformation of Hydroxycoumarin to Coumaranone

Abstract

Halogenation-driven skeletal transformations play an important role in the biosynthesis of natural products, where halogenation can promote C–C bond cleavage under mild conditions. Drawing inspiration from these biosynthetic processes, the halogenative skeletal reconstruction of hydroxycoumarins is reported, which unexpectedly facilitates carbonyl deletion to yield valuable heterocyclic scaffolds. Notably, cleavage of both the C–C and C–O bonds occurs under the mildest nonenzymatic conditions reported to date (low reaction temperature and near-neutral reaction media), while also demonstrating broad substrate scope. This transformation converts readily accessible hydroxycoumarins into biologically relevant coumaranone scaffolds via a halogen-identity-dependent decarbonylative reconstruction. This work establishes halogenation-enabled carbonyl deletion as a useful strategy for skeletal transformation and provides an efficient approach to molecular scaffold editing relevant to medicinal chemistry.