Intracellular Ruthenium-Promoted (2+2+2) Cycloadditions

Metal-mediated intracellular reactions are becoming invaluable tools in chemical and cell biology, and hold promise for strongly impacting the field of biomedicine. Most of the reactions reported so far involve either uncaging or redox processes. Demonstrated here for the first time is the viability of performing multicomponent alkyne cycloaromatizations inside live mammalian cells using ruthenium catalysts. Both fully intramolecular and intermolecular cycloadditions of diynes with alkynes are feasible, the latter providing an intracellular synthesis of appealing anthraquinones. The power of the approach is further demonstrated by generating anthraquinone AIEgens (AIE=aggregation induced emission) that otherwise do not go inside cells, and by modifying the intracellular distribution of the products by simply varying the type of ruthenium complex.