Enamine -oxides: Design, Synthesis, and Function in Bioorthogonal Reactions.

Enamine -oxides act as a chemical linchpin bridging two bioorthogonal associative and dissociative reactions. This article describes the design of enamine -oxides; their synthesis through the retro-Cope elimination reaction; the use of solvent, hyperconjugation, strain, and rehybridization effects to achieve bioorthogonal reactivity; and their rapid reductive cleavage with diboron reagents. The coordinated assembly and disassembly of the enamine -oxide motif constitutes a powerful chemical operation that enables the attachment and detachment of small molecules from biomacromolecules in a biological setting.