Bioorthogonal Retro-Cope Elimination Reaction of <i>N</i>,<i>N</i>-Dialkylhydroxylamines and Strained Alkynes

Abstract

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.

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