Benzobthiophene 1,1-dioxide is a relatively underrepresented sulfone-embedded heterocycle with niche uses in material science (OLED emitters), pharmaceutical research (an electrophilic warhead in targeted covalent inhibitors), and as a structural unit in reversibly switchable diarylethene fluorophores. Benzobthiophene 1,1-dioxides are most commonly prepared by the oxidation of the corresponding benzothiophenes. Here, we propose an alternative approach based on Pd-catalyzed sulfinylation of ortho-carbonyl-substituted aryl triflates followed by S-alkylation and Knoevenagel condensation. This methodology allows for an expedient access to diversely substituted benzobthiophene 1,1-dioxides, including 6-dialkylamino “push-pull” type fluorophores possessing large (>140 nm) Stokes shifts. Fluorescent labels derived from this core structure are compatible with live-cell imaging using self-labeling protein tags (HaloTag, SNAP-tag, and CLIP-tag). Together with the established live-cell fluorescent labels and orthogonal self-labeling tags, they allow for simultaneous observation of up to three intracellular targets below the diffraction limit using fluorescence microscopy with three excitation lasers (485, 561, and 640 nm) and stimulated emission depletion (STED) at 775 nm.
Butkevich et al. (Mon,) studied this question.