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

Abstract

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.

New Approach to Perthiyl Radicals for the Synthesis of Unsymmetric Disulfides

“…Notably, we found that heterocycle substituents, such as N-protected pyrrolidines, N-protected piperazine, thiophene, were well-tolerated on the alkyl bromides (17)(18)(19). Additionally, substrates containing unsaturated propargyl and allyl derivatives underwent the conversionsmoothly, providing the desired products (20,21). Next, secondary alkyl bromides were tested in the reaction.…”

“…Traditional methods to prepare disul des primarily rely on the disul de exchange or the couplings of two sulfur-containing compounds. Contemporary strategies for disul de synthesis often employ disulfurating reagent (RSS-LG) to forge C-SS bonds, with persul de cations (RSS + ) or persul de anions (RSS -) serving as crucial intermediates [9][10][11][12][13][14][15][16][17][18][19][20][21] (Fig. 1B).…”