Mild Palladium‐Catalyzed Regioselective Direct Arylation of Azoles Promoted by Tetrabutylammonium Acetate

Abstract

A mild, general, and convenient palladium-catalyzed direct arylation of the 5-position of azoles with aryl bromides, efficiently promoted by tetrabutylammonium acetate, is described. 1-Methylpyrazole, oxazole, and thiazole reacted at 70 degrees C in N,N-dimethylacetamide by using Pd(OAc)(2) as the catalyst precursor. Electron-poor and -rich functional groups, including the free hydroxy group, are well tolerated in the electrophilic partner. A variety of 5-aryl-1-methylimidazoles were also very efficiently obtained simply by raising the reaction temperature to 110 degrees C. This ligand-free protocol was successfully applied to the one-pot synthesis of two bioactive natural compounds, balsoxin and texaline, starting from oxazole by sequential direct arylation of the 5- and 2-positions

Conditions for palladium-catalyzed direct arylations of 4-bromo and 4-iodo N-substituted pyrazoles without C–Br or C–I bond cleavage

“…5 Again, the reaction was not regioselective and a mixture of C5,C4 arylated and diarylated products was obtained in a 78 : 16 : 6 ratio. 6 According to Gorelsky calculations, in the concerted metallation deprotonation (CMD) process, this regioselectivity issue can be explained by similar energies of activation of C4 and C5 protons (28.5 vs. 27.3). was employed (Fig.…”

Synthesis and Optical Properties of Imidazole‐Based Fluorophores having High Quantum Yields

“…A two-necked flask equipped with a magnetic stirrer and a reflux condenser was charged with the appropriate 5-aryl-1-methyl-1Himidazole 4 a-c [26] (0.75 mmol), 2-(4-bromophenyl)-1-methyl-1Hbenzo[d]imidazole 5 (323.0 mg, 1.13 mmol), Pd(OAc) 2 (8.4 mg, 0.04 mmol), and CuI (285.7 mg, 1.50 mmol). The apparatus was closed with a silicone septum, evacuated, and back-filled with argon.…”

“…In detail, 5-aryl-1-methyl-1H-imidazoles 4 a-c were prepared efficiently by a palladium-catalyzed direct C5ÀH arylation reaction, promoted by Bu 4 NOAc, involving 2 and aryl bromides 3 a-c as described recently by us. [26] The 5-arylimidazoles 4 a-c so obtained were then reacted with 2-(4-bromophenyl)-1-methyl-1Hbenzimidazole (5) according to our recent protocol for the palladium-and copper-promoted regioselective direct C2ÀH arylation reaction under base-and ligand-free conditions. [27] Intermediate 5 has been obtained by the condensation of 4-bromobenzaldehyde with N-methyl-1,2-benzenediamine and oxidation (see the Supporting Information).…”

Recent Developments in Pd-Catalyzed Direct Arylations of Heteroarenes with Aryl Halides

“…In 2013, a mild, general, and convenient phosphine-free direct arylation of 1-methylpyrazole, oxazole, and thiazole promoted by tetrabutylammonium acetate (Bu 4 NOAc) was developed by Bellina and co-workers [51]. Electron-poor and electron-rich aryl bromides were found to react at only 70 C in DMA, allowing the isolation of the corresponding 5-substituted azoles in good yields (Scheme 35).…”

“…This protocol, paired with the regioselective direct C2 arylation of azoles mediated by palladium and copper, was applied to the synthesis of the natural products balsoxin and texalin through a one-pot sequential C5-C2 double arylation [51] and, more recently, to the preparation of several imidazole analogues of resveratrol able to reduce the growth of human tumor cell lines [52]. The methods of palladium-catalyzed direct arylation of heteroarenes with (hetero) aryl halides displayed an exponential growth in less than 20 years.…”