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 “CH2-to-heteroatom” conversion is further demonstrated.
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