Strain-Promoted Azide–Alkyne Cycloadditions of Benzocyclononynes

Preliminary studies related to the design and development of new cycloalkyne reagents for metal-free click coupling are reported. Cyclononynes are more stable than cyclooctynes, and the robust benzocyclononyne platform offers spontaneous reactivity toward azides at rates competitive with other azidophiles that have been employed for metal-free click coupling. Benzocyclononynes (e.g., 1) provide valuable insight into the design of new cycloalkynes for strain-promoted azide–alkyne cycloaddition (SPAAC) couplings for applications in which side reactions and decomposition of the reagent must be kept to a minimum.