Skeletal Editing of Ketones with [1.1.1]Propellane

Ketones are a common class of compounds in chemistry. Here, we present an approach for the skeletal editing of ketones, enabled by the rare electrophilic activation of [1.1.1]propellane. A broad spectrum of ketones was examined, showcasing excellent compatibility with various functional groups such as ester, amide, and amines. The novel reaction is practical and scalable (up to 56 grams). It allows the rapid preparation of mono-, bis-, and tri-spirocyclic scaffolds, which are highly valuable in organic synthesis and drug discovery. Mechanistic insights, supported by control experiments and density functional theory (DFT) calculations, provide a comprehensive understanding of the reaction mechanism.