Carbonyl swapping converts cyclic ketones to saturated heterocycles

Saturated heterocycles are privileged scaffolds in bioactive molecules.1 Despite the availability of numerous de novo routes to various heterocyclic compounds, accessing diverse heterocycles from a unified, readily available carbocycle would offer a strategic alternative for constructing challenging heterocyclic structures from unconventional precursors.2 Here we report a modular approach that transforms a single cyclic ketone into various saturated heterocycles through formal carbonyl replacement with heteroatoms, via a scarcely explored bis(aroylperoxy) ketal intermediate. Through electronically guided peroxy cleavage, this intermediate enables double C–C bond scission of cyclic ketones, generating alkyl dichlorides as versatile handles for modular N/O/S/Se/Te incorporation using simple nucleophiles. This method exhibits broad substrate scope and functional-group tolerance, enabling both accelerated target synthesis and late-stage diversification of bioactive molecules. Its utility is also extended through “ring construction–carbonyl replacement” and “ring functionalization–carbonyl replacement” strategies, whereby cyclic ketones prepared via well-established methods are converted into challenging-to-access heterocycles for which analogous methods remain underdeveloped. By combining C–H oxidation with carbonyl replacement, a proof-of-concept formal “CH 2 -to-heteroatom” conversion is further demonstrated.