Electrophile-Integrating Smiles Rearrangement Provides Previously Inaccessible C4′‑<i>O</i>‑Alkyl Heptamethine Cyanine Fluorophores

Abstract

New synthetic methods to rapidly access useful fluorophores are needed to advance modern molecular imaging techniques. A new variant of the classical Smiles rearrangement is reported that enables the efficient synthesis of previously inaccessible C4′-<i>O-</i>alkyl heptamethine cyanines. The key reaction involves <i>N</i>- to <i>O</i>- transposition with selective electrophile incorporation on nitrogen. A representative fluorophore exhibits excellent resistance to thiol nucleophiles, undergoes productive bioconjugation, and can be used in near-IR fluorescence imaging applications