Recent Advances in Thianthrenation/Phenoxathiination Enabled Site-Selective Functionalization of Arenes

Abstract

Site-selective functionalization of simple arenes remains a paramount challenge due to the similarity of multiple C–H bonds in the same molecule with similar steric environment and electronic properties. Recently, the site-selective thianthrenation/phenoxathiination of arenes has become an attractive solution to reach this challenging goal and it has been applied in the late-stage functionalization of various bioactive molecules. This short review aims to summarize recent advances in the site-selective C–H functionalization of arenes via aryl thianthrenium salts, as well as mechanistic insights in the remarkable site-selectivity obtained in thianthrenation step.1 Introduction2 Site-Selective Thianthrenation of Arenes and Mechanistic Insight3 Thianthrenation-Enabled Site-Selective Functionalization of Arenes3.1 Thianthrenation-Enabled C(sp 2)–C Bond Formation Reaction3.2 Thianthrenation-Enabled C(sp 2)–X Bond Formation Reaction4 Conclusion and Outlook

Synthesis of Polycyclic Hetero-Fused 7-Deazapurine Heterocycles and Nucleosides through C–H Dibenzothiophenation and Negishi Coupling

“…On the other hand, the other five-membered heterocycles 4o – 4y including furan and diverse azoles did not give any detectable sulfonium products. In all these cases, we also tried C–H thianthrenylation , that also did not provide the desired products. It seems that this C–H functionalization has a severe limitation for most five-membered heterocycles beyond thiophene.…”

“…To overcome the above-mentioned synthetic problems, we turned our attention to recently developed C–H functionalization of (hetero)­aromatics with sulfur heterocycles and further cross-coupling of the resulting sulfonium intermediates. , The Ritter group has reported seminal works on metal-free C–H thianthrenylation followed by Negishi coupling with aliphatic alkylorganozinc compounds or aromatic nucleophilic substitutions with diverse nucleophiles. Dibenzothiophene (DBT) and dibenzothiophene- S -oxide (DBTO) were also successfully used for C–H functionalization and further derivatizations.…”

Palladium-Catalyzed Carbonylative Synthesis of Diaryl Ketones from Arenes and Arylboronic Acids through C(sp2)–H Thianthrenation

“…Based on the above results and related literature, − a plausible reaction mechanism was proposed (Scheme ). Initially, the real active Pd(0) complex A was generated from the addition of the palladium precursor added.…”

“…Due to the pioneering achievements of Mukaiyama’s, Shine’s, and Ritter’s research groups and also many others, thianthrenium salts have recently attracted great attention from scientists. Thianthrenium salts as reactive precursors can be prepared directly from arenes in the presence of TTSO, and then various functionalization reactions can be carried out effectively and selectively (Scheme c).…”

Thianthrenation-Enabled Pyrrolidin-2-yl and Tetrahydrofuran-2-yl Methylation of (Hetero)Arenes

“…If these methods were applied to modify the complex bioactive molecules, the preparation of substrates would suffer from significant drawbacks such as multistep synthesis and regioselectivity issues. Electrophilic thianthrenation of arenes has attracted an enormous amount of attention since Ritter’s pioneering work in 2019 . The generated arylthianthrenium (aryl-TT) salt is prepared with an extremely high site selectivity via a C–H functionalization of arenes with thianthrene ( S )-oxides (TTSO).…”