Bioorthogonal Retro-Cope Elimination Reaction of N,N-Dialkylhydroxylamines and Strained Alkynes.

A bioorthogonal reaction between N,N-dialkylhydroxylamines and cyclooctynes is described. This reaction features a highly regioselective transformation between small, easily functionalizable reaction components with second-order rate constants reaching 84 M-1 s-1. The reaction is orthogonal to the inverse-electron demand Diels-Alder reactions between tetrazine and strained alkenes, and its components exhibit exquisite stability and chemoselectivity in cell lysate. This retro-Cope elimination reaction introduces a new member to the bioorthogonal reaction compendium outside the prolific class of cycloaddition reactions.