Mild and Ligand‐Free Palladium‐Catalyzed Cross‐Couplings between Aryl Halides and Arylboronic Acids for the Synthesis of Biaryls and Heterocycle‐Containing Biaryls

Abstract

Ligand‐free palladium‐catalyzed Suzuki–Miyaura cross‐couplings between aryl halides and arylboronic acids performed at room temperature are presented. It was found that both solvent and base had a fundamental influence on the reaction, and the most effective system in terms of yield and rate was observed to be the combination of Pd(OAc)2 with MeONa and alcohols. In the presence of Pd(OAc)2 and MeONa, a variety of aryl halides reacted very rapidly with arylboronic acids in good to excellent yields at room temperature in EtOH as the solvent. Moreover, the Pd(OAc)2/MeONa catalytic system could also be applied in couplings between heteroaryl halides and arylboronic acids to provide satisfactory results in MeOH as the solvent after prolonged reaction times. It is noteworthy that the reactions were conducted under mild, aerobic, and ligand‐free conditions.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2007)

Ligand‐Free and Heterogeneous Palladium on Carbon‐Catalyzed Hetero‐Suzuki–Miyaura Cross‐Coupling

“…Pd/C-catalyzed hetero-Suzuki-Miyaura coupling between non-heteroaryl halides and heteroarylboronic acids. ) tion in the reactivity (Table 8, entries [1][2][3][4][5], and the use of Na 3 PO 4 ·12 H 2 O could be decreased to 1.0 equiv. (entries 6-10).…”

“…A few ligand-free SuzukiMiyaura coupling reactions of heterocycle-containing substrates catalyzed by a homogeneous palladium catalyst were recently reported. [4,5] Li and co-workers found that the Suzuki-Miyaura couplings between aryl halides and arylboronic acids worked when using the PdA C H T U N G T R E N N U N G (OAc) 2 /NaOMe catalytic system without any ligands and promoters at room temperature, but the protocol required the use of a strong base such as NaOMe, and the coupling between the heteroaryl halides and heteroarylboronic acids was not very efficient. [4] Bryce and co-workers succeeded in the syntheses of functionalized heteroarylpyridines by the Suzuki-Miyaura coupling reactions in the absence of any ligands and additives, but only particularly substituted boronic acids worked well for the smooth reaction.…”

“…[4,5] Li and co-workers found that the Suzuki-Miyaura couplings between aryl halides and arylboronic acids worked when using the PdA C H T U N G T R E N N U N G (OAc) 2 /NaOMe catalytic system without any ligands and promoters at room temperature, but the protocol required the use of a strong base such as NaOMe, and the coupling between the heteroaryl halides and heteroarylboronic acids was not very efficient. [4] Bryce and co-workers succeeded in the syntheses of functionalized heteroarylpyridines by the Suzuki-Miyaura coupling reactions in the absence of any ligands and additives, but only particularly substituted boronic acids worked well for the smooth reaction. [5] Furthermore, homogeneous catalysts were difficult to recover and reuse, and the residual Pd metal in the products could induce serious problems in the synthesis of bioactive and/or functional substrates.…”

A General and Highly Efficient Method for the Construction of Aryl‐Substituted N‐Heteroarenes

“…[9a-9d,9f, 12,14] It is noteworthy that the reaction between 2-bromopyridine and o-tolylboronic acid could be conducted in 94 % yield after 60 min (Table 2, entry 3), which is far more efficient than that carried out in an aqueous system.…”

Very Fast Suzuki–Miyaura Reaction Catalyzed by Pd(OAc)2 under Aerobic Conditions at Room Temperature in EGME/H2O

“…[22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41] Effective systems in terms of yield and rate are, for example, Pd(OAc) 2 / Na 2 CO 3 in acetone/H 2 O [37] and Pd(OAc) 2 /MeONa in alcohols. [38] However, the development of mild, rapid, lowcost, and aerobic ligandless-based procedures is still a topic of considerable interest in organic synthesis and industry.…”