Site-Selective Late-Stage C–H Functionalization via Thianthrenium Salts

Abstract

The high abundance of C–H bonds in organic molecules makes C–H functionalization a powerful approach to quickly increase the complexity of an organic molecule. However, the high abundance of C–H bonds also provides a challenge to C–H functionalization reactions: selectivity. While most C–H functionalization reactions produce mixtures of different products for most substrates, we have developed a highly selective method for aromatic C–H functionalization via sulfonium salts. The reaction does not require a certain directing group to be selective. The introduced functional group is a sulfonium group, which participates in various follow-up reactions such as palladium-catalyzed cross-coupling reactions and photoredox catalysis. Here we discuss our pathway to develop the reaction as well as its scope and utility.1 Introduction2 Site-Selective Synthesis of Sulfonium Salts3 Sulfonium Salts in Palladium-Catalyzed Cross-Coupling4 Sulfonium Salts in Photoredox Catalysis5 Sulfur(IV) Reductive Elimination6 Cine Substitution7 Conclusion

Synthesis of I(III)/S(VI) reagents and their reactivity in photochemical cycloaddition reactions with unsaturated bonds

“…7, product 5i was reduced to cyclic ketone 15 using Raney-Nickel in refluxing isopropanol. Protonation of sulfoxonium ylide 5i with HOTf gave the corresponding sulfoxonium salt (16) in 90% yield and with a 1:1.5 dr ratio. The in situ generated sulfoxonium salt was converted into sulfide 17 in high dr using a Brønsted acid.…”

“…In contrast, sulfoxonium, a class of S (VI) compounds with a S = O double bond and three attached carbons remain underexplored. Compared to its S (IV) analogs, sulfonium salts [12][13][14][15][16] , sulfoxonium compounds exhibit higher nucleofugality, increased stability, and decreased basicity. Among them, sulfoxonium ylides have been explored as a diazo-free carbene precursor in synthesis [17][18][19][20][21] .…”

Studies on the Synthesis of Perfluoroaryl Sulfides and their Application in Desulfurative Nickel-Catalyzed Reductive Cross-Coupling

“…The concept of C−S bond activation has also been exploited for the functionalization of C−H /C−X bonds (X = halide). Organosulfur reagents like thianthrene sulfoxide, [60][61][62][63] dibenzothiophene S-oxide, [64][65] xanthate [66][67] , thiocarbamate, [68][69] and tetrafluoropyridinyl disulfide [48][49][50][51][52] can be added to arenes or organohalides to obtain sulfonium salts or sulfides, which contain a weak C−S bond that can be easily replaced in a reductive C−S bond cleavage step. Despite the success of the above methods, which are all based on C−S bond activation, one still lacks a generally applicable tool for the efficient conversion of mercapto groups into other functionalities.…”

Regiospecific Alkene Aminofunctionalization via an Electrogenerated Dielectrophile

“…Recent advances have revealed diverse and unique electrophilic reactivity from C­(sp 2 ) and C­(sp 3 ) thianthrenium salts. − Among these efforts, our group has introduced an oxidative alkene aziridination strategy that relies on the generation of dicationic adducts derived from electrolysis of an alkene and thianthrene. In all reported studies regarding the reactivity of these dielectrophiles, both carbon–sulfur bonds were displaced either through substitution or elimination pathways. , Indeed, nothing is known about selective manipulation of just one of the electrophilic sites of these adducts.…”