Para-Selective Borylation of Monosubstituted Benzenes Using a Transient Mediator

Abstract

Herein, we conceptualized a transient mediator approach that has the capability of <i>para</i>-selective C–H functionalization of monosubstituted aromatics. This approach is enabled by in situ generation of a versatile sulfonium salt via highly electrophilic phenoxathiine or thianthrene dication intermediate which can be readily generated from its sulfoxide with trifluoromethanesulfonic anhydride. Preliminary mechanistic study implied that the remarkable <i>para</i> selectivity might be related to the incredible electrophilicity of thianthrene dication intermediate. The versatility of this approach was demonstrated via <i>para</i>-borylation of various monosubstituted simple aromatics combining the sulfonium salt formation with further photocatalyzed transformation.

Pd‐Catalyzed Site‐Selective Borylation of Simple Arenes via Thianthrenation†

“…[ 11 ] As such, development of efficient site‐selective borylation of undirected arenes is desired. Inspired by our recently TTSO mediated para ‐arylation and alkenylation reaction of monosubstituted arenes with Pd catalyst, [ 10b ] we hypothesized that the TTSO‐mediated site‐selective borylation of simple arene could be realized with one synthetic operation via a thianthrenation/Pd‐catalyzed desulfurative borylation sequence. We are glad to find that the Pd‐catalyzed borylation reaction showed superior compatibility with the conditions used in the first sulfonium salts formation step.…”

“…[ 7‐9 ] Almost at the same timeline, we were developing a transient mediator approach for para ‐selective functionalization of monosubstituted simple arenes, and found thianthrene S ‐oxide (TTSO) and phenoxathiine 10‐oxide could serve as the most selective and efficient mediators via sulfide dication intermediates (Scheme 1a). [ 10a ] Ideally, this approach could provide a powerful alternative strategy providing a remarkable selectivity for a wide range of aromatics. However, this approach suffers from multiple manipulations requiring the isolation of sulfonium salts or removal of the solvent and acid in the first step.…”

High Site Selectivity in Electrophilic Aromatic Substitutions: Mechanism of C–H Thianthrenation

“… 32 A remarkably high site selectivity for C–H functionalization was obtained with a strong preference for the formation of the para isomer in greater than 200:1 selectivity for ethylbenzene. Not only do thianthrenation reactions have a broad scope but also the resulting aryl sulfonium salts ( Ar–TT + ) are versatile intermediates that enable diversification via transition-metal cross-coupling reactions and photoredox catalysis for C–C, 32 − 35 C–N, 36 C–O, 37 C–S, 38 C–F, 39 C–B, 32 , 40 and C–Ge 41 bond formation. In parallel, the groups of Procter and Alcarazo have reported the use of dibenzothiophene S -oxide ( DBTO ) to access the corresponding sulfonium salts ( Ar–DBT + ).…”

General and Practical Metal-Free Aziridination and Cyclopropanation of XH2 (X = N, C) with Alkenes by Thianthrenation

“…[29][30][31][32][33][34][35][36] Recently, Ritter and others developed the ipso-functionalization of aryl and alkenyl thianthrenium salts via metal-catalyzed cross-coupling and radical reactions (Scheme 1b, top). [37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52] In 2021, Wickens and our group independently reported the functionalization of alkenes by thianthrenation to formally transform allylic C-H bond to form C-C, C-O, and C-N bonds with C-, O-, and N-based nucleophiles (Scheme 1b, bottom). 53,54 Herein, a general and practical protocol for cyclopropanation and aziridination using free XH2 (X = C and N) with alkenes by thianthrenation was developed (Scheme 1c).…”