Ligand‐Free‐Palladium‐Catalyzed Direct 4‐Arylation of Isoxazoles Using Aryl Bromides

Abstract

Keywords: Atom-economy / Homogeneous catalysis / C-H activation / Heteroaryl halides / Isoxazole / Palladium 4-Arylisoxazoles can be easily prepared by a palladium-catalysed C-H bond activation/arylation of 3,5-disubstituted isoxazoles using aryl or heteroaryl bromides. Good yields were generally obtained by using 0.1-0.5 mol-% of the airstable PdCl 2 complex as the catalyst. A range of functional groups such as acetyl, formyl, ester, fluoro, nitro, trifluoro-

Cyclopentyl Methyl Ether: An Alternative Solvent for Palladium‐Catalyzed Direct Arylation of Heteroaromatics

“…3, isoxazole (25): [10] 4-Bromonitrobenzene (0.202 g, 1 mmol) and 3,5-dimethylisoxazole (0.192 g, 2 mmol) afforded 25 (0.135 g, 62 %).…”

“…benzonitrile (23): [10] 4-Bromobenzonitrile (0.182 g, 1 mmol) and 3,5-dimethylisoxazole (0.192 g, 2 mmol) afforded 23 (0.176 g, 89 %). benzaldehyde (24): [10] 4-Bromobenzaldehyde (0.187 g, 1 mmol) and 3,5-dimethylisoxazole (0.192 g, 2 mmol) afforded 24 (0.105 g, 52 %).…”

“…However, these reactions are currently performed, in most cases, by using relatively toxic solvents, such as DMF, DMAc, N-methylpyrrolidone (NMP), or dioxane. [3][4][5][6][7][8][9][10] Some palladium-catalyzed direct arylations of heteroaromatics have also been performed by using toluene, xylene or mesitylene. [3] Recently, a few solvents that can be considered as "greener", [11] according to Anastas principles, have been employed for direct arylations.…”

Environmentally Benign Arylations of 5‐Membered Ring Heteroarenes by Pd‐Catalyzed C−H Bonds Activations

“…Then, our group extended the low‐loading and phosphine‐free Pd‐catalyzed direct arylation to several heteroaromatics such as pyrroles, furans, thiophenes isoxazoles, benzofurans, imidazo[1,2‐ a ]pyridines, benzothiophenes, and indazoles, (Scheme ). It should be noted that with most heterocycles, a wide range of functional groups on the bromobenzene was tolerated.…”

Reactivity of 2,1‐Benzisoxazole in Palladium‐Catalyzed Direct Arylation with Aryl Bromides

“…[3] Since this initial report, the Pd-catalyzedd irect arylation [4] of isoxazole derivatives with aryl halides has proved to be av ery powerful methodf or the synthesis of aw ide variety of 4-arylated isoxazoles. [3,5] The major byproducts of theser eactions are ab ase associated with HX, instead of the metallic salts that are produced with more classical cross-coupling procedures.A lthough the 4-arylation of isoxazoles has been studied in detail, only one example of aP d-catalyzedd irect coupling of an aryl halide with ab enzisoxazole has been reported. [6] For this reaction, aq uite high catalyst loading was employed[ 5mol % PdCl 2 (MeCN) 2 with 10 mol %1 ,2-bis(diphenylphosphino)benzene (DPPBz);S cheme 1, top].M oreover,t he expensive base AgF (2 equiv.)…”