Oxa-azabenzobenzocyclooctynes (O-ABCs): heterobiarylcyclooctynes bearing an endocyclic heteroatom

We report the synthesis of heterobiarylcyclooctynes bearing an endocyclic heteroatom, oxa-azabenzobenzocyclooctynes (O-ABCs). The integration of design strategies for accelerating strain-promoted azide-alkyne cycloadditions results in reactivity with organic azides that surpasses all cyclooctyne reagents reported to date. O-ABCs and related compounds provide insights into the effects of structural modifications on reactivity that can aid in the design of new reagents for click and bioorthogonal chemistry. We report the synthesis of heterobiarylcyclooctynes bearing an endocyclic heteroatom, oxa-azabenzobenzocyclooctynes (O-ABCs).