Palladium-catalyzed direct arylation of benzoxazoles with unactivated simple arenes

Abstract

Using CuBr(2) as an additive, the Pd-catalyzed intermolecular C-H-C-H cross-coupling between benzoxazoles and unactivated simple arenes has been developed. This protocol provides a straightforward approach for the biological activity of 2-arylbenzoxazole derivatives.

Deep eutectic solvent-catalyzed arylation of benzoxazoles with aromatic aldehydes

“…5,6 Among them, palladium-catalyzed cross-coupling is one of the most powerful and reliable tools to achieve arylsubstituted benzoxazoles through direct C-H activation and subsequent C-C bond formation. [7][8][9] However, this protocol still suffered from inherent drawbacks associated with the use of uncommon, toxic, and expensive agents such as aryltrimethylammonium triates, 7 aryl halides or triates, [10][11][12][13][14][15][16][17] aryl boronic acids, 18 sodium arylsulnates, 19 arylsulfonyl hydrazides, 20 and 3-phenylpropionic acid. 21 Additionally, the requirement of high-cost palladium catalysts and other expensive additives also prevents the palladium-catalyzed cross-coupling procedure from being employed in large-scale synthesis.…”

Direct C—H Bond Activation of Benzoxazole and Benzothiazole with Aryl Bromides Catalyzed by Palladium(II)‐N‐heterocyclic Carbene Complexes

“…Hence, the direct C-H bond arylation of such compounds is receiving growing attention in the context of organic synthesis. A variety of electrophilic reagents including aryl halides, [21][22][23][24] aryl organometallic reagents, [25] unactivated simple arenes, [26] and phenol derivatives such as triflates, [19,27,28] mesylates, [29] sulfamates [30] and acids [31] have been employed for the transformation. Similarly, arene sulfonyl chlorides [32] and arene diazonium salts [33] are inexpensive and readily available arylating reagents.…”

“…4-Bromobenzaldehyde gave the 2-aryl substituted benzoxazole and benzothiazole with 75%-95% and 71%-92% yields, respectively ( Table 3, entries 19-24). The electron-poor 4-bromoacetophenone was also a good substrate to afford the corresponding products 2-(4-acetylphenyl)benzoxazole and 2-(4-acetylphenyl)benzothiazole at between 78%-96% and 74%-93% yields, respectively ( Table 3, entries [25][26][27][28][29][30]. In general, the direct arylation of benzothiazole exhibited more good yields than the direct arylation of benzoxazole with a range of aryl bromides.…”

“…[19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] In previous works, similar substrates have been employed with higher catalyst loading (5%-20 mol%) and higher reaction time (5-48 h) has been chosen for the direct arylation of benzoazoles in presence of palladium catalysts. [21,22,[24][25][26][29][30][31][32] However, in the present work the catalyst loading was reduced to 1 mol%, and the reaction time was shortened to 4 h. Moreover, in the present study benzoxazole and benzothiazole can be efficiently and selectively arylated at the 2-position by palladium complexes bearing NHC ligands, and satisfactory results were obtained as compared to previously reported similar studies using aryl halides. [21,22,24] When compared with our previous work, in the present work, the reaction time was shortened to 4 h and higher yields were obtained, whereas in previous work, the reaction was carried out in presence of 1.5 mol% palladium(II)-NHC catalyst, in NMP as the solvent, K 3 PO 4 as the base, at 130 o C. Also, the reaction time was chosen as 48 h for arylation of benzoxazole and benzothiazole with aryl bromides.…”

Palladium‐Catalyzed Chemo‐ and Regioselective Oxidative Cross‐Dehydrogenative Coupling of Acetanilides with Benzothiazole

“…These reactions have been reported by using different aryl sources, including aryl halides [Scheme , Equation (1)], substituted benzoic acids [Equation (2)], arenesulfonyl chlorides [Equation (3)], sodium sulfonates, phenols and their derivatives such as mesylates and esters, arylboronic esters, aromatic aldehydes, aromatic amides [Equation (4)], arylsulfonyl hydrazides, arylboronic acids [Equation (5)], aryl thioethers, arylamines, substituted pyridines, aromatic amines, 2‐pyridones, N ‐sulfonyl ketimines, azobenzenes, N‐heteroarene‐substituted arenes, and o ‐methyl oximes . The direct arylation of azoles with simple arenes has also been reported . Among the reported reactions for arylation with simple arenes, troubles with regioselectivity are noticeable.…”