β-CF3 Alkynones for Amine Conjugation under Aqueous Conditions.

We report an aqueous conjugate addition of primary and secondary amines to β-CF3 alkynones under mild conditions without added metal catalysts or activating reagents. This protocol affords stable, CF3-containing enaminone conjugates in phosphate buffer and is applicable to structurally diverse amine substrates. Its utility is demonstrated by the modification of drugs, amino acid esters, dipeptides, complex bioactive peptides, and proteins, as well as two-step fluorescent labeling of lysozyme confirmed by fluorescence SDS-PAGE analysis.