Environmentally Benign Arylations of 5‐Membered Ring Heteroarenes by Pd‐Catalyzed C−H Bonds Activations

Abstract

The palladium‐catalyzed functionalization of 5‐membered ring heteroaromatics, through a C−H bonds activation, for access to arylated heteroaromatics represent a very attractive alternative to more classical cross‐coupling reactions, as it saves steps and reduces the amount of wastes. Despite these advantages, these transformations initially suffered from major limitations in terms of sustainable chemistry concerning the reaction media, the nature of the catalyst, the catalyst loading, the aryl source or the regioselectivity control. Tremendous improvements allowing more sustainable reaction conditions using greener solvents, new aryl sources or employing easily removable catalysts and lower catalyst loadings have been described during the last decades. This review summarizes some of the most important contributions made in these directions.

Nickel-catalyzed and Li-mediated regiospecific C–H arylation of benzothiophenes

“…11,12 Among heterobiaryls, benzothiophenes are widely used as API 13,14 and optoelectronics building blocks. [15][16][17][18] In contrast to 30 years of literature on Pd [19][20][21][22][23][24] or Ir-catalyzed reactions, 25,26 the direct C-H arylation of benzothiophene using earth-abundant metal systems remains scarcely studied. For example, Daugulis and co-workers reported the C-H phenylation of benzothiophene catalyzed by the combination of 10 mol% CuI/phenanthroline and lithium 3-ethyl-3-pentanolate in N,N'dimethylpropyleneurea.…”

A Convoluted Polyvinylpyridine‐Palladium Catalyst for Suzuki‐Miyaura Coupling and C−H Arylation

“…Since 1 exhibited high catalytic activity and reusability when used for the Suzuki-Miyaura coupling, CÀ H arylation of various thiophene and furan derivatives, benzene, and anisole using polyvinylpyridine-palladium 1 was investigated. While there are many reports on homogeneous catalysis of this reaction, [5][6][7]38] the 4 e 5 c 6 k 90 11 [c] 4 e 5 d 4-Ph 6 l 75 12 [d] 4 a-Br 4-MeO, Br 5 a 6 a 94 13 [d] 4 b-Br 4-Me, Br 5 a 6 b 99 14 [d] 4…”

“…The use of both CÀ H arylations and Suzuki-Miyaura couplings to prepare (hetero)aromatic biaryl compounds is important not only for fundamental catalytic chemistry but also for the production of functional materials and pharmaceutical compounds. [1][2][3] In recent years, many homogeneous catalysts for these reactions have been reported that utilize precious transition metals such as palladium, [4][5][6][7] rhodium, [8] ruthenium, [9] copper, [10] and iridium. [11] Converting such systems from homogeneous to heterogeneous catalysis is desirable because it would allow these precious transition metal species to be readily recovered and reused.…”

Regioselective Pd-catalyzed direct C1- and C2-arylations of lilolidine for the access to 5,6-dihydropyrrolo[3,2,1-ij]quinoline derivatives

“…The late stage C–H bond functionalization of molecules represents a powerful method for the easy screening of the biological properties of compounds containing a bioactive unit. Since the seminal work by Ohta et al on the Pd-catalyzed C–H bond functionalization of heteroarenes such as thiophenes, furans, pyrroles and indoles [14–15], this methodology has been widely applied for the preparation of new aryl-substituted heteroarenes [16–21]. Several results dealing with the C–H bond functionalization of indoles have been reported allowing to prepare either α- [22–31] or β-arylated [32–37] indoles, depending on the reaction conditions.…”