Radical Acylation of [1.1.1]Propellane with Aldehydes: Synthesis of Bicyclo[1.1.1]pentane Ketones

Bicyclo[1.1.1]pentanes (BCPs) are widely utilized in drug design as sp(3)-rich bioisosteres for tert-butyl, internal alkynes, and aryl groups. A general and mild method for radical acylation of [1.1.1]propellane with aldehydes has been developed. The protocol provides straightforward access to bicyclo[1.1.1]pentane ketones with a broad substrate scope. The synthetic utility of this methodology is demonstrated by the late-stage modification of bioactive molecules and the versatile transformation of bicyclo[1.1.1]pentane ketones, making it useful for drug discovery.

Automated summary

A general and mild method for radical acylation of [1.1.1]propellane with aldehydes has been developed, providing straightforward access to bicyclo[1.1.1]pentane ketones with a broad substrate scope. The synthetic utility of this methodology is demonstrated by the late-stage modification of bioactive molecules and the versatile transformation of bicyclo[1.1.1]pentane ketones, making it useful for drug discovery.