Abstract: Bioorthogonal chemistries have provided methods to investigate biomolecules in their native environments with minimal effects on cellular processes. Efforts to develop new bioorthogonal reactions have equipped researchers with powerful tools to probe complex biological systems. Despite the advancement of these tools, they remain limited in scope. Most bioorthogonal reactions comprise cycloadditions, and many of the key reagents cannot be used simultaneously due to cross reactivity issues. To address these limitations, I have developed new phosphine-based bioorthogonal chemistries with cyclopropenones (CpOs) and methods to deploy the two motifs in biological settings. This talk will focus on chemical activation of CpOs with bioorthogonal phosphines as a general proximity labeling platform.