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.