Direct C‐3‐Arylations of 1H‐Indazoles

Abstract

The first example of intermolecular C–H arylation of substituted 1H‐indazoles is reported. Various 1‐substituted indazoles were used as starting materials, and (hetero)aryl bromides and iodides were investigated as coupling partners. Different reaction conditions were investigated. The best results were obtained using Pd(OAc)2 as catalyst, 1,10‐phenanthroline as ligand, K2CO3 as base, and DMA as solvent. The crucial role of the ligand on the C–H arylation of substituted 1H‐indazoles is highlighted.

“On Water” Palladium Catalyzed Direct Arylation of 1H-Indazole and 1H-7-Azaindazole

“…N -Benzylation of 1 H -pyrazolo[3,4- b ]pyridine [ 33 ]: 1 H -pyrazolo[3,4- b ]pyridine (1 g, 8.39 mmol, 1.00 equivalent) was dissolved in acetone (10 mL) at 0 °C in a 50 mL flask, along with KOH (1.41 g, 25.19 mmol, 3.00 equivalent). After few minutes of stirring, benzyl chloride (1.59 g, 12.59 mmol, 1.50 equivalent) was added dropwise.…”

“…N-Benzylation of 1H-pyrazolo[3,4-b]pyridine [33]: 1H-pyrazolo[3,4-b]pyridine (1 g, 8.39 mmol, 1.00 equivalent) was dissolved in acetone (10 mL) at 0 °C in a 50 mL flask, along with KOH (1.41 g,…”

“…N-Methylation of indazole [33]: the indazole (1 g, 1 equivalent) was dissolved in acetone (10 mL) at 0 • C in a 50 mL flask. KOH (3 equivalent) was added, and then CH 3 I (1.5 equivalent) was added dropwise.…”

“…Recently, different research groups have investigated the C3 direct arylation of indazole, including our own. In 2012, our group [ 33 ] in parallel with the Itami group [ 34 ] developed, for the first time, conditions to realize the direct arylation of 1 H -indazole series. The key of this success was the use of bidentate ligand (1,10-phenanthroline) with a high catalyst loading (10 to 20 mol%).…”

Direct Catalytic Functionalization of Indazole Derivatives

“…The desired C-3 arylated 1H-indazole (14 b) was obtained with good yield (Scheme 14). [80] The electron-withdrawing groups attaching to aryl iodide gave a higher percentage of yields than that of electron-donating groups. One of the most important advantages of this reaction was that heteroaryl bromides responded to the reaction and gave heteroarylated indazoles with good yields.…”