Palladium-catalyzed regioselective C–H bond arylations at the C3 position of ortho-substituted fluorobenzenes

Abstract

. Palladium-catalyzed regioselective C-H bond arylations at the C3 position of ortho-substituted fluorobenzenes. Organic and Biomolecular Chemistry, Royal Society of Chemistry, 2017, 15 (35) The influence of an ortho-substituent on fluorobenzene derivatives for palladium-catalyzed C-H bond arylation has been explored. In the presence of 2-bromo, 2-chloro and 2-methoxy substituents, the reaction proceeds nicely using a diphosphine-palladium catalyst and potassium acetate/dimethylacetamide (PivOK/DMA) as catalytic system. In all cases, a regioselective arylation at the the other ortho-position to the fluorine atom (C3) was observed. A variety of electronwithdrawing substituents on the aryl bromide coupling partner, such as formyl, nitro, nitrile, and also heteroaryl bromides was tolerated. Moreover, tri(hetero)aryl derivatives containing a fluorobenzene as central unit have been prepared from 2-bromofluorobenzene through palladium-catalyzed-successive C-H bond (hetero)arylations.

Application of Palladium-Catalyzed C(sp2)–H Bond Arylation to the Synthesis of Polycyclic (Hetero)Aromatics

“…However, this methodology could not be transferred to the synthesis of [7]helicenes. In line with CMD mechanism, the authors observed that when the 2′-aryl group of the binaphthyl triflate contains a meta-fluoro substituent, arylation at the more acidic ortho-CH bond adjacent to the fluorine was favored; [70][71][72][73] whereas, when a meta-CF3 group was present, the regioselectivity was driven by steric factors (Scheme 60 During their investigations on the preparation of tetrabenzo [7]circulene via Pd-catalyzed intramolecular C-H bond arylation (Scheme 62), 99 Miao and co-workers also applied their strategy to the synthesis of thiophene-annulated [7]-circulenes by replacing 2bromophenylboronic acid with 3-bromothiophene-2-boronic acid pinacol ester (Scheme 72). 99 The reaction was operated in a two-pots procedure without the isolation of the intermediate generated by a two-fold Suzuki coupling.…”

“…However, the reaction seemed to be sensitive to steric factors. Interestingly, from difluorinated substrates a strong fluorine effect [70][71][72][73] was observed resulting in a high regioselectivity control at the ortho position Moreover, this reaction had been employed for the preparation of more π-extended systems using chlorobenzene derivatives bearing two naphthalene rings. The synthesis of sulfuranalogs PAHs using a benzothiophene-substituted derivative or a chlorothiophene derivative was also reported.…”

Recent Developments in Palladium-Catalysed Non-Directed C–H Bond Activation in Arenes

“…Scheme 7 Effect of substituents on the arylation of fluoroarenes as reported by Doucet and co-workers [16][17][18]…”

“…As a continuation of this work, in 2017, the same research group explored the effect of the ortho-substituent on the reactivity of fluorobenzenes using 2 mol% of PdCl(C 3 H 5 )(dppb) and 2 equivalents of KOAc in DMA (Scheme 7, c). 18 The presence of bromo, chloro and methoxy groups at the ortho-position of the fluorobenzene increased the reactivity at the C-3 position, while nitro, nitrile, formyl, acetyl and amino groups inhibited the arylation reaction. On the other coupling partner, the presence of electron-withdrawing groups at para-position on the aryl bromide resulted in formation of the desired products, unlike in the cases with electron-donating groups.…”

Halo-substituted benzenesulfonyls and benzenesulfinates: convenient sources of arenes in metal-catalyzed C–C bond formation reactions for the straightforward access to halo-substituted arenes

“…However, we demonstrated that an iodo-substituent at the indolyl C3-position act as temporary blocking group allowing the formation of halo-substituted 2-arylindoles 44 through direct desulfitative C2-arylation, followed by in situ deiodination (Scheme 24, b). 46 On the contrary, from 3-bromoindole derivatives, the 2-aryl-3bromoindoles 45 and 46 were obtained without debromination (Scheme 24, c). 47 The reaction was conducted under oxygen atmosphere using Pd(OAc) 2 catalyst and 1.2 equiv.…”