Radical C(sp³)–S Coupling for the Synthesis of α-Amino Sulfides

Abstract

A unique transition-metal-free radical thiolation of 2-azaallyl anions has been developed. Easily accessible thiosulfonates and 2-azaallyls undergo the tandem process of single-electron transfer and radical–radical coupling to construct C(sp3)–S bonds. This robust protocol enables a mild and chemoselective coupling between 2-azaallyl anions and thiosulfonates to access α-amino sulfides in 50–92% yields (25 examples). The scalability of this protocol was demonstrated by telescopic gram-scale experiments. Mechanistic studies provide significant evidence for this radical thiolation reaction.

Single-Electron Reduction of “Push–Pull” C–C Single Bond and Decyanation Using Tertiary Amines as the Organic Electron Donor

“…Based on the control experiments and the literature precedents, − a single-electron reduction mechanism was proposed (Scheme ). Initially, the “push–pull” single bond was cleaved under the promotion of InCl 3 , and the iminium ion Int-1 was formed, releasing a nitromethyl anion.…”

“…Moreover, the reducibility of these metallic reductants typically cannot be modulated through structural modification. In contrast, organic electron donors (OEDs) are superior in tunability of structure, reducing ability, stability, solubility, and functional group tolerance. − Therefore, more recently, developing OEDs has attracted the attention of organic chemists. As one of the pioneers, Murphy and co-workers have synthesized a series of OEDs with the electron-rich tetraaminoethylene skeleton.…”

“…As one of the pioneers, Murphy and co-workers have synthesized a series of OEDs with the electron-rich tetraaminoethylene skeleton. Based on these OEDs with potent reduction abilities, a series of single-electron reductions mediated by radical species were developed, in which even the reductive coupling between aryl halides and arenes could be realized efficiently (Figure b). − However, the downsides lie in that these compounds are commercially unavailable; therefore, tedious synthetic steps as well as the relatively harsh reaction conditions are inevitable to obtain them, which confined their wide applications in organic synthesis. In view of this, it is highly desirable to develop cheaper and commercially available OEDs.…”

Recent Advances in Radical Coupling Strategies Enabled by 2‐Azaallyl Anions as Super‐Electron‐Donors

“…Subsequently, the same group has developed a transitionmetal-free radical thiolation of 2-azaallyl anions to access α-amino sulfides in 50-92% yields (25 examples) (Scheme 22). [52] 3.2 CÀ N and CÀ O Bonds Formation 2,5-Dihydro-1,2,4-oxadiazoles exist in many medicines and natural products and have attracted considerable interest. [53] They have been found to exhibit antiviral, anticancer, anti-inflammatory, anti-rhinovirus, and antiparasitic properties.…”

“…Subsequently, the same group has developed a transition‐metal‐free radical thiolation of 2‐azaallyl anions to access α‐amino sulfides in 50–92% yields (25 examples) (Scheme 22). [52] …”