Eco‐Friendly Solvents for Palladium‐Catalyzed Desulfitative CH Bond Arylation of Heteroarenes

Abstract

Herein, we report the Pd-catalyzed regioselective direct arylation of heteroarenes in which benzenesulfonyl chlorides are used as coupling partners through a desulfitative cross-coupling that can be performed in diethyl carbonate (DEC) or cyclopentyl methyl ether (CPME) as green and renewable solvents or even in neat conditions instead of dioxane or dimethylacetamide (DMA). Under these solvent conditions, the reaction proceeds with a wide range of heteroarenes. C2- or C5-arylated products were obtained with furan and pyrrole derivatives. Benzofuran was also arylated regioselectively at the C2-position, whereas the reaction proceeds selectively at the C3- or C4-positions if thiophenes and benzothiophenes are used. Moreover, in some cases, especially with 1-methylindole, solvent-free conditions afforded better regioselectivities and/or yields than the reaction performed in the presence of solvents.

Synthesis of symmetrical and unsymmetrical 1,3-diheteroarylbenzenes through palladium-catalyzed direct arylation of benzene-1,3-disulfonyl dichloride and 3-bromobenzenesulfonyl chlorides

“…We had previously demonstrated that the reaction could also be performed in green solvents such as diethyl carbonate (DEC) or cyclopentylmethyl ether (CPME) with comparable yields but with a lower reaction rates. 18 When the reaction was performed in DEC, the monoarylation product 1 was obtained in 95% selectivity with a full conversion of 2-n-butylfuran (Table 1, entry 2). A lower selectivity and reactivity was observed using CPME as solvent (87% of 1) (Table 1, entry 3).…”

New Arylating Agents in Pd-Catalyzed C–H Bond Functionalization of 5-Membered Ring Heteroarenes

“…as additive, which might prevent the decomposition of indoles (Scheme 17, bottom) [82]. It is important to note that the direct desulfitative arylation of indoles using benzenesulfonyl chlorides gives mixtures of C2-and C3-arylated indoles [72,74]. As seen in this section, sodium arylsulfinates were successfully used in C-H bond reactions.…”

“…In the same years, they disclosed that such desulfitative direct arylations of thiophenes, furans, and pyrroles could be performed in green solvents such as CPME or diethyl carbonate (DEC) and even in some case under free-solvent conditions in high yields using the same catalytic system, namely, 5 mol% PdCl 2 (CH 3 CN) 2 in the presence of 3 equiv. of lithium carbonate (Li 2 CO 3 ) as base at 140 C [74]. In 2015, Zhao and co-workers reported the direct C-3 arylation of indolizine derivatives with benzenesulfonyl chlorides as aryl sources (Scheme 14) [75].…”

Advance in C-H Arylation of Indoles

“…33). 该方法适用 [70] 、芳基硅氧烷(ArSi(OR) 3 ) [71] 、芳基磺酰氯 (ArSO 2 Cl) [72] 、芳基磺酰肼(ArSO 2 NHNH 2 ) [73] 均被用作芳 基化试剂, 在 Pd 催化下与吲哚的 C2 位发生偶联反应. 随后, 施章杰、李焕荣和徐立进等 [76] 在吲哚 N 原子 上引入嘧啶导向基团, 该嘧啶基团可以引导 Rh 催化剂 活化邻位的 C-H 键.…”