Photochemical Generation and Cycloadditions of Strained Cycloalkynes

Strained cycloalkynes and their utilization have enabled prospective and tactical strategies for synthetic and medicinal chemistry, chemical biology, materials science, and allied fields. However, their full potential remains largely underexplored due to the limited availability of efficient sp³-rich cycloalkyne precursors with high synthetic efficiency and structural complexity. Herein, we describe an intuitive and modular photochemical approach to liberate cycloalkyne analogs from cyclic diacyl peroxides, without external reagents. This disclosed platform hinges on the leverage of cycloalkynes to realize two distinct classes of strain-promoted cycloadditions for the straightforward construction of diverse polycyclic scaffolds without the production of any side product except nitrogen and CO₂. Moreover, high functional group tolerance, biorelevant molecules compatibility, scalability, and late-stage functionalization of bioactive molecules demonstrate the synthetic utility of the presented methods. These features enrich synthetic strategies for assembling cycloalkenyl-containing polycyclic scaffolds with structural diversity, offering new opportunities for click chemistry and bioorthogonal reactions.