A Bioorthogonal Ligation of Cyclopropenones Mediated by Triarylphosphines

Bioorthogonal chemistries have been widely used to probe biopolymers in living systems. To date, though, only a handful of broadly useful transformations have been identified because of the stringent requirements placed on the reactants. Here we report a novel bioorthogonal ligation between cyclopropenones and functionalized phosphines. These components are stable in physiological buffers and react rapidly with one another to form covalent adducts. The cyclopropenone ligation is also distinct from other bioorthogonal chemistries in that it makes use of readily accessible, commercially available reagents and proceeds via a nucleophilic reaction pathway. On the basis of these features, the cyclopropenone ligation is poised to join the ranks of chemistries with utility in living systems.