Metal‐Free Arylation of Benzothiophenes at C4 by Activation as their Benzothiophene S‐Oxides

Abstract

Benzothiophenes, activated by oxidation to the corresponding S‐oxides, undergo C−H/C−H‐type coupling with phenols to give C4 arylation products. While an electron‐withdrawing group at C3 of the benzothiophene is important, the process operates without a directing group and a metal catalyst, thus rendering it compatible with sensitive functionalities—e.g. halides and formyl groups. Quantum chemical calculations suggest a formal stepwise mechanism involving heterolytic cleavage of an aryloxysulfur species to give a π‐complex of the corresponding benzothiophene and a phenoxonium cation. Subsequent addition of the phenoxonium cation to the C4 position of the benzothiophene is favored over the addition to C3; Fukui functions predict that the major regioisomer is formed at the more electron‐rich position between C3 and C4. Varied selective manipulation of the benzothiophene products showcase the synthetic utility of the metal‐free arylation process.

Csp2–H functionalization of phenols: an effective access route to valuable materials via Csp2–C bond formation

“…219 Scheme 82 Metal-free arylation of phenols with variously functionalized benzothiophenes. 221 Scheme 83 Metal-free sulfoxide-mediated oxidative cross-coupling of phenols with various nucleophiles. 222 and subsequent 1,2-migration.…”

“…The synthetic utility of the metal-free, direct arylation process was underlined by the selective manipulation of the versatile benzothiophene products (Scheme 82). 221 The same research group reported a sulfoxide-mediated oxidative cross-coupling of phenols with various nucleophiles, including arenes, 1,3-diketones and other phenols. The metalfree protocol was mediated by a sulfoxide which allowed the selective ortho-arylation cross-coupling versus homo-coupling.…”

“…The synthetic utility of the metal-free, direct arylation process was underlined by the selective manipulation of the versatile benzothiophene products ( Scheme 82 ). 221 …”

Highly substituted benzo[b]furan synthesis through substituent migration

“…Recently, remarkable achievements in diverse transformations of sulfoxides through charge-accelerated [3,3]-sigmatropic rearrangement have enabled us to synthesize a wide variety of functionalized arenes owing to the intriguing reactivities of sulfonium intermediates. 3,4 A few examples of the [3,3]-sigmatropic rearrangement followed by migration of substituents realized the preparation of multisubstituted arenes in unusual manners. For instance, Maulide and coworkers developed a meta-selective rearrangement using o -substituted phenyl sulfoxides and ynamides catalyzed by Tf 2 NH through charge-accelerated [3,3]-sigmatropic rearrangement and subsequent alkyl migration (Fig.…”

Arylation of benzazoles at the 4 positions by activation of their 2-methylsulfinyl groups

“…1D). 11 The arylation takes place at the 4 position of the benzothiophene core and was calculated to proceed via a stepwise mechanism, i.e. , formal [5,5] rearrangement.…”