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 work, a new, shelf-stable, and easy-to-prepare bilateral disulfurating platform molecule, N-(morpholine-4-dithio)phthalimide, has been developed for the synthesis of divergent 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 allyltrimethylsilanes, alkynylsilanes, 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 divergent unsymmetrical disulfides via two C–S bond formation.

Asanuma, H.; Kanemoto, K.; Watanabe, T.; Fukuzawa, S. Angew. Chem. Int. Ed. 2023, e202219156.