Ring-Expansion of Ketones with [1.1.1]Propellane.

Here, we present an approach for the ring-expansion 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 g). It allows the rapid preparation of mono-, bis-, and tris-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.