Solvent/Ligand-Controlled Switchable C3 or C7 C–H Arylations of 1-Methyl-4-nitro-1H-indazole

Abstract

A new solvent/ligand controlled switchable C–H arylation of 1-methyl-4-nitro-1H-indazole catalyzed by Pd(OAc)2 was achieved. A bidentate ligand in DMA promoted the activation at C7 position, while a phosphine ligand in H2O oriented the arylation at C3 position. The C3 and C7 arylation products were obtained in moderate to good yields and in high regioselectivity.

Palladium‐Catalyzed Site‐Selective C7 Oxidative Arylation of 4‐EWG‐1H‐Indazoles

“…Thus, CÀ H bond activation under concerted metalation-deprotonation (CMD) process is more suitable in this case. [34,35] Inspired by previous mechanistic studies [30][31][32] and pKa calculation, we propose a plausible CMD mechanism for this oxidative arylation in (Scheme 7). Thus, a CÀ H insertion of Pd(II) to the benzene in basic conditions, forms the intermediate 1.…”

“…It is very important to note that the oxidative arylation has allowed the introduction of heteroaryl by CÀ H/CÀ H activation at the C7 position in contrast to direct arylation conditions previously reported. [29,30] Then, the starting material 1' with benzyl as a protecting group at the N1 position was used instead of the starting material 1 bearing a methyl group. Under the same oxidative arylation conditions with benzene as coupling partner, the reaction has led to the expected product 2 j with lower yield (58 %) compared to the analog 2 a (69 %).…”

“…Products 2 a, 2 e, and 7 are well known, we found out their structure by a comparison between our spectral analysis and others that exist in the literature. [30,21] For the new products their data are collected in suporting information.…”

“…[29] Very recently, we have reported a regioselective C7-direct arylation of 4-nitro-1Hindazoles utilizing iodoaryls, as coupling partners (Scheme 1b). [30] Notably, in this case, the coupling reactions under optimized conditions were effective with iodoaryls as arylation agents, while no product was formed with iodo(hetero)aryls as coupling partners. Interestingly, Gao group has developed a palladium-catalyzed oxidative C3-arylation of 2H-indazole derivatives using a Pd(PPh 3 ) 4 /Cu(OAc) 2 system and heteroarenes.…”

Ligandless Palladium-Catalyzed Direct C-5 Arylation of Azoles Promoted by Benzoic Acid in Anisole

“…To overcome this relevant issue, research has almost always been oriented towards an optimization of the pre-catalyst/ligand system along with the search for the best inorganic base, while the potential effect of the solvent on the outcome of the coupling has been rarely discussed [ 84 , 85 , 86 , 87 ]. In fact, even in cases where a solvent screening has been reported, no comment has been added to justify the different outcome of the arylation.…”