N-(Morpholine-4-dithio)phthalimide: A Shelf-Stable, Bilateral Platform Molecule Enabling Access to Diverse Unsymmetrical Disulfides

Synthetic methods for unsymmetrical disulfides are greatly needed owing to their applications in drug discovery, linker chemistry, and materials sciences. In this study, a new shelf-stable and easy-to-prepare bilateral disulfurating platform molecule, N-(morpholine-4-dithio)phthalimide, has been developed for the divergent synthesis of unsymmetrical disulfides. The amino and imide leaving groups of this reagent can be orthogonally transformed. Under acidic conditions, the amino moiety undergoes selective protonation and thus can be displaced by various carbon nucleophiles, such as allyl trimethylsilanes, alkynyl silanes, and electron-rich arenes, leaving the phthalimide moiety untouched. Meanwhile, the phthalimide leaving group is amenable to substitution under basic or neutral conditions. The combination of these transformations provides rapid access to diverse unsymmetrical disulfides through two C-S bond-forming reactions.

Automated summary

This study developed a new shelf-stable and easy-to-prepare bilateral disulfurating platform molecule, N-(morpholine-4-dithio)phthalimide, for the synthesis of unsymmetrical disulfides. The amino and imide leaving groups of this reagent can be orthogonally transformed. Under acidic conditions, the amino moiety can be displaced by various carbon nucleophiles, while the phthalimide moiety remains untouched. Meanwhile, the phthalimide leaving group undergoes substitution under basic or neutral conditions. The combination of these transformations allows for rapid access to diverse unsymmetrical disulfides through two C-S bond-forming reactions.