Nickel-catalysed aromatic Finkelstein reaction of aryl and heteroaryl bromides

A fast and efficient nickel-catalysed iodination reaction of aryl and heteroaryl bromides has been developed. The transformation was found to be general for a wide range of substrates and was used for the synthesis of iodo-PK11195, an imaging agent of Alzheimer's disease and iniparib, a compound used in the treatment of breast cancer.     

Copper-catalyzed N-arylation of 2-arylindoles with aryl halides

10 mol% Cul combined with the DMEDA ligand can efficiently catalyze the N-arylation of 2-arylindoles with aryl iodides and aryl bromides in good to excellent yields. The aryl halides bearing electron-rich or electron-deficient functional groups can be well tolerated under this mild reaction conditions.     

Copper-catalyzed coupling of aryl halides and nitrite salts: a mild Ullmann-type synthesis of aromatic nitro compounds

Nitration of aromatic halides proceeded smoothly in the presence of catalytic amounts of Cu bronze and N,N′-dimethylethylenediamine. Sodium nitrite-18-crown-6, or tetra-n-butylammonium nitrite (n-Bu₄NNO₂) turned out to be efficient nitrating agents. The aromatic nitro compounds were synthesized under essentially neutral conditions.     

Copper-catalyzed decarboxylative cross-coupling of alkynyl carboxylic acids with aryl halides

The copper-catalyzed decarboxylative reactions of alkynyl carboxylic acids with aryl halides were performed under relatively mild reaction conditions. Benzofurans could be further prepared smoothly by a one-pot domino protocol on the basis of decarboxylative cross-coupling of 2-iodophenol.     

Copper-catalyzed reaction of alkyl halides with cyclopentadienylmagnesium reagent

Treatment of alkyl halides, including tertiary alkyl bromides, with cyclopentadienylmagnesium bromide in the presence of a catalytic amount of copper(II) triflate yielded the corresponding cyclopentadienylated products in high yields. The following hydrogenation of the products provided alkyl-substituted cyclopentanes.     

Copper-catalyzed synthesis of primary arylamines from aryl halides and 2,2,2-trifluoroacetamide

A catalytic method was developed to synthesize primary arylamines from the corresponding aryl bromides and iodides under mild conditions (yields = 80-99%). Crystalline 2,2,2-trifluoroacetamide was used as ammonia surrogate and CuI/N,N′-dimethyl ethylenediamine was used as catalyst to achieve the C-N cross-coupling.     

Copper-catalyzed synthesis of phenols from aryl halides and 4-methoxylbenzyl alcohol

A catalytic method was developed to synthesize substituted phenols from the corresponding aryl bromides and chlorides under mild conditions (yields = 34–92%). 4-Methoxylbenzyl alcohol was used as water surrogate and CuI/3,4,7,8-tetramethyl-1,10-phenanthroline was used as catalyst to achieve the C–O cross-coupling.     

Copper-catalyzed decarboxylative coupling of aryl halides with alkynyl carboxylic acids performed in water

Most alkynes are volatile liquids, which are relatively difficult to use and to transport. In contrast, alkynyl carboxylic acids offer a stable and attractive alternative for the alkynylation reactions. Here, we employed alkynyl carboxylic acids as reaction partners for the alkynylation of aryl halides. Copper-catalyzed decarboxylative coupling, including various challenging aryl bromides with phenylpropiolic acid, was performed in water without using co-solvents with good yields. Our approach provides a low-loading, low-cost, stable and environmentally friendly copper catalyst system for decarboxylative coupling.     

The selective reaction of aryl halides with KOH: synthesis of phenols, aromatic ethers, and benzofurans

The direct and selective synthesis of phenols from aryl/heteroaryl halides and KOH has been achieved through the use of highly active monophosphine-based catalysts derived from Pd(2)dba(3) and ligands L1 or L2 and the biphasic solvent system 1,4-dioxane/H(2)O. We have also demonstrated a one-pot method of phenol formation/alkylation for the preparation of alkyl aryl ethers from aryl halides. In many instances, this protocol overcomes limitations in existing Pd-catalyzed coupling reactions of aliphatic alcohols with aryl halides. Finally, we demonstrate that substituted benzofurans can be prepared efficiently via a Pd-catalyzed phenol formation/cyclization protocol starting from 2-chloroaryl alkynes.     

Copper-catalyzed synthesis of primary arylamines via cascade reactions of aryl halides with amidine hydrochlorides

We have developed an efficient method for the synthesis of primary arylamines from aryl halides using amidine hydrochlorides as the ammonia surrogates. The protocol uses 10 mol % CuI as the catalyst, 20 mol % L-proline as the ligand, Cs2CO3 as the base, and DMF as the solvent and proceeds the sequential coupling of aryl halides with amidine hydrochlorides and hydrolysis of intermediates to give the target products. This is a convenient, inexpensive, and practical approach to primary arylamines.     

A convenient synthesis of aromatic thiols from unactivated aryl halides

Aromatic thiols are obtained in good yields from unactivated aryl halides and excess MeSNa in HMPA.     

Copper-catalyzed C-N coupling reactions of aryl halides with α-amino acids under focused microwave irradiation

We have developed an efficient method for the preparation of enantiopure N-aryl-α-amino acids via copper-catalyzed N-arylation of α-amino acids and aryl halides under microwave irradiation. This protocol only needs less than 30 min to obtain the products, which are far superior to those obtained under conventional heating.     

Copper-catalyzed amination of aryl halides with nitrogen-containing heterocycle using hippuric acid as the new ligand

An efficient copper-catalyzed amination of nitrogen-containing heterocycles with various aryl halides has been developed. Commercially available and inexpensive hippuric acid is a novel ligand to afford the coupling products in moderate to excellent yields.     

Copper-catalyzed aerobic oxidation and cleavage/formation of C-S bond: a novel synthesis of aryl methyl sulfones from aryl halides and DMSO

With atmospheric oxygen as the oxidant, a novel copper(I)-catalyzed synthesis of aryl methyl sulfones from aryl halides and widely available DMSO is described. The procedure tolerates aryl halides with various functional groups (such as methoxy, acetyl, chloro, fluoro and nitro groups), which could afford aryl methyl sulfones in moderate to high yields. The copper-catalyzed aerobic oxidation and the cleavage/formation of C-S bond are the key steps for this transformation.     

DAB-Cy as an inexpensive and effective ligand for palladium-catalyzed homocoupling reaction of aryl halides

A novel catalytic system of PdCl₂(CH₃CN)₂ with N,N′-dicyclohexyl-1,4-diazabutadiene (DAB-Cy) ligand was successfully used in reductive coupling of aryl halides.     

Synthesis of primary aromatic amides by aminocarbonylation of aryl halides using formamide as an ammonia synthon

Primary aromatic amides were prepared by a palladium-catalyzed aminocarbonylation reaction of aryl halides in high yields (70-90%) using formamide as the amine source. The reactions require a palladium catalyst in combination with a nucleophilic Lewis base such as imidazole or 4-(dimethylamino)pyridine (DMAP). Aryl, heteroaryl, and vinyl bromides and chlorides were converted to the primary amides under mild conditions (5 bar, 120 degrees C) using 1 mol % of a palladium-phosphine complex. Best results were obtained in dioxane using triphenylphosphine as the ligand and DMAP as the base. For activated aryl bromides, a phosphine-to-palladium ratio of 2:1 was sufficient, but less reactive aryl bromides or aryl chlorides required ligand-to-palladium ratios up to 8:1 in order to stabilize the catalyst and achieve full conversion. The influence of catalyst, base, solvent, pressure, and temperature was studied in detail. The mechanism of the reaction could be clarified by isolating and identifying the reaction intermediates. In addition, methylamides and dimethylamides were prepared by the same method using N-methylformamide and N,N-dimethylformamide as the amine source.