N-(N-Morpholindithio)phthalimide: A Shelf-Stable, Bilateral Platform Molecule for Accessing Diverse Unsymmetrical Disulfides

A new, shelf-stable, and odorless bilateral disulfurating platform molecule, N-(N-morpholindithio)phthalimide, was developed. This reagent can be easily prepared in high yields on a gram scale in a single step from the readily available N,N'-dithiobis(phthalimide). The two leaving groups bound to sulfur were selectively transformed: the morpholino and phthalimide groups were transformed in the presence and absence of H+, respectively. The platform molecule enabled the facile replacement of the morpholino moiety with various substituents, such as allyl (Csp3), aryl (Csp2), and alkynyl (Csp) groups, affording the products in high yields. The wide substrate scope of these transformations and the transformability of the resulting dithiophthalimide moiety provided rapid access to divergent multi-functionalized unsymmetrical disulfides. These results demonstrate the utility of this method for structural expansion in drug discovery and efficient conjugation in linker chemistry.