Metal-Free Photoredox Four-Component Strategy to 1,3-Functionalized BCP Derivatives

Trifluoromethyl bicyclo[1.1.1]pentanes (BCPs) have attractedsignificantattention from the scientific community and pharmaceutical industriesdue to their advantageous physicochemical properties as arene bioisosteres.Initial photoredox perfluoroalkylation of [1.1.1]propellane triggersthe tandem reaction to the perfluoroalkyl BCP radical followed byGiese addition to an in situ generated electron-deficientalkene by Knoevenagel condensation in a four-component fashion toform 1,3-functionalized BCPs. This strategy provides easy access tovarious 1,3-functionalized perfluoroalkyl BCP derivatives with theadded advantage of nitrile group as a functional handle to diversifiedtransformations. This methodology offers scalability and late-stagederivatization of drug molecules with high chemoselectivity.

Automated summary

Trifluoromethyl bicyclo[1.1.1]pentanes (BCPs) have gained significant attention due to their advantageous physicochemical properties. A strategy of photoredox perfluoroalkylation and Giese addition was developed to synthesize 1,3-functionalized perfluoroalkyl BCP derivatives. This method offers easy access to a variety of derivatives and allows late-stage derivatization.