Site-Selective C–H alkylation of Complex Arenes by a Two-Step Aryl Thianthrenation-Reductive Alkylation Sequence

Abstract

Herein, we present an undirected para-selective two-step C−H alkylation of complex arenes useful for late-stage functionalization. The combination of a site-selective C−H thianthrenation with palladium-catalyzed reductive electrophile crosscoupling grants access to a diverse range of synthetically useful alkylated arenes which cannot be accessed otherwise with comparable selectivity, diversity, and practicality. The robustness of this transformation is further demonstrated by thianthrenium-based reductive coupling of two complex fragments.

Vinyl Thianthrenium Tetrafluoroborate: A Practical and Versatile Vinylating Reagent Made from Ethylene

“…We conceived 1 as a suitable coupling partner that could overcome the above-mentioned challenges and enable fast oxidative addition in view of its electropositive character ( E red = −1.13 V vs SCE). Moreover, in line with what has been observed in palladium-catalyzed reactions of aryl thianthrenium salts, 58 − 63 cleavage of the C vinyl –S bond selectively over the two C aryl –S bonds may be explained by irreversible oxidative addition into the vinyl bond but reversible oxidative addition into the aryl bond 64 , 65 of the annulated structure of the thianthrene core (see Supporting Information for a discussion). To demonstrate the performance of 1 in cross-coupling reactions, we developed a Suzuki-type vinylation of aryl boronic acids ( Table 2 A).…”

18F-Fluorination: Challenge and Opportunity for Organic Chemists

“…Over the past couple of years, our group has introduced a highly regioselective arene C–H functionalization to access aryl thianthrenium salts; the thianthrene substituent serves as a versatile linchpin for further manipulation, − including C–F bond formation . The most practical reaction with promise for fluorine-18 translation was obtained when we switched from the thianthrene scaffold to the dibenzothiophene scaffold .…”

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

“…In 2021, the Ritter group demonstrated a C( sp 2 )–C( sp 3 ) reductive cross-coupling between aryl thianthrenium salts 10 and readily available alkyl iodides by employing a Pd catalyst in the presence of the reductant (Zn) (Scheme 17 ). 25 A variety of alkyl motifs containing different functional groups were regioselectively introduced to the arene. Moreover, two complex building blocks were also cross-linked via this process.…”