C–N Cross-Couplings for Site-Selective Late-Stage Diversification via Aryl Sulfonium Salts

Abstract

We report diverse C–N cross-coupling reactions of aryl thianthrenium salts that are formed site-selectively by direct C–H functionalization. The scope of N-nucleophiles ranges from primary and secondary alkyl and aryl amines to various N-containing heterocycles, and the overall transformation is applicable to late-stage functionalization of complex, drug-like small molecules.

Synthesis, Structure, and Reactivity of 5‐(Aryl)dibenzothiophenium Triflates

“…It was hypothesized that the use of amonodentate neutral ligand, able to engage in strong s-donation to the S IV center of 2,m ight provide sufficient stabilization to allow the isolation of the corresponding adduct before side-reactions take place.H ence,o ne equivalent of DMAP was added to afreshly prepared suspension of 2 at À50 8 8C. This addition causes the slow formation of an orange/yellow solid (9), which was obtained in analytically pure form after washing with dry dichloromethane (Scheme 2a). X-ray diffraction analysis of the monocrystals obtained by cooling as aturated dichloromethane solution confirmed the formation of the expected Lewis adduct 9.I n the solid state, 9 adopts ad imeric structure in which the geometry around each dibenzothiophene S-atom can be defined as distorted octahedral.…”

“…Although the use of sulfonium moieties as linchpins in cross‐coupling chemistry, and as source of organic radicals, has been known for more than two decades, it has not been until very recently that the actual synthetic potential of these reagents has been broadly recognized. Variants of the Pd‐catalyzed Suzuki–Miyaura, Mizoroki–Heck, Sonogashira, Negishi, Stille, and related reactions, such as Buchwald–Hartwig aminations, are now available by employing aryl sulfonium salts as electrophilic partners. Moreover, either by direct reaction with nucleophiles or through photoredox catalyzed processes, the sulfonium moiety can be selectively exchanged with alkyl groups, halogens, or amines under mild reaction conditions .…”

Site‐Selective C−H Oxygenation via Aryl Sulfonium Salts

“…Previously, we have disclosed a site-selective C À H functionalization of arenes by thianthrenation, [4,16] but did not identify the utility of aryl thianthrenium salts for the field of CÀO bond formation. Herein, we report the development of a highly site-selective C À O bond forming process via aryl thianthrenium salts, in which oxygen-nucleophiles such as water, phenols, primary, and secondary alcohols are coupled with arenes including drug-like small molecules, such as flurbiprofen methyl ester (1) (Scheme 1 b).…”

Shining Light on C−S Bonds: Recent Advances in C−C Bond Formation Reactions via C−S Bond Cleavage under Photoredox Catalysis

“…Notably, this aza-FC reaction could tolerate N-nucleophiles such as indazole, with the formation of the corresponding CÀ N bond formation product 233 (Scheme 43b). This was also the first example of CÀ N bond formation [46][47][48][49] reaction involving CÀ S bond cleavage of thioether via photoredox catalysis.…”