Palladium(0)-catalyzed, copper(I)-mediated coupling of boronic acids with cyclic thioamides. selective carbon-carbon bond formation for the functionalization of heterocycles

The palladium-catalyzed cross-coupling of cyclic thioamides with arylboronic acids in the presence of stoichiometric amounts of a copper(I) cofactor is described. The desulfitative carbon-carbon cross-coupling protocol is performed under neutral conditions and can be applied to a range of heterocyclic structures with embedded thioamide fragments. Successful carbon-carbon cross-coupling is independent of the ring size, aromaticity/nonaromaticity, the presence of additional heteroatoms, or other functional groups in the starting thioamide structure. Employing controlled microwave irradiation at 100 degrees C, most cross-couplings can be completed within 2 h and proceed in high yields. An advantage of using thioamides as starting materials is the fact that the system can be tuned to an alternative carbon-sulfur cross-coupling pathway by changing to stoichiometric copper(II) under oxidative conditions. Both types of thioamide cross-couplings are orthogonal to the traditional base-catalyzed Suzuki-Miyaura cross-coupling of aryl halides with boronic acids.     

Pd-catalyzed, Cu(I)-mediated cross-couplings of bisarylthiocyclobutenediones with boronic acids and organostannanes

Bisarylthiocyclobutenedione 7 reacted smoothly with a variety of both organostannanes and (hetero)arylboronic acids in the presence of a catalytic amount of Pd and a stoichiometric amount of CuTC to produce symmetrical disubstituted cyclobutenediones in yields that range from 37 to 94% (18 examples).     

Cu(I)-mediated reductive amination of boronic acids with nitroso aromatics

[reaction: see text] A mild method for the reductive amination of aryl boronic acids with nitroso aromatic compounds is reported. This C-N bond formation is mediated by a stoichiometric amount of CuCl as both a catalyst and a reducing agent. Alternatively, 10% Cu(I)-3-methylsalicylate (CuMeSal) catalyzes the same reaction in the presence of either ascorbic acid or hydroquinone as the terminal reducing agent. Diarylamines bearing a variety of functional groups can be obtained in good yields.     

Palladium-catalyzed carbonylative coupling of benzyl chlorides with aryl boronic acids in aqueous media

A novel chemoselective protocol for the carbonylative Suzuki coupling of benzyl chlorides with aryl boronic acids at low pressure of carbon monoxide has been developed. Applying a commercially available palladium acetate/PCy₃ catalyst system in the presence of potassium phosphate as the base and water as the solvent the coupling reactions proceeded smoothly. To demonstrate the general applicability 12 different α-arylated acetophenones have been synthesized in moderate to good yields (41-78%) under mild conditions.     

Palladium-catalyzed copper(I)-mediated cross-coupling of arylboronic acids and 2(1H)-pyrazinones facilitated by microwave irradiation with simultaneous cooling

The application of a palladium-catalyzed Cu(I)-mediated Liebeskind-Srogl protocol for the decoration of the 2(1H)-pyrazinone scaffold resulted in significantly improved yields and rates when performed under microwave irradiation with simultaneous cooling.     

Palladium-catalyzed benzylation of N-Boc indole boronic acids

The direct benzylation of indole 2-boronic acid can be efficiently achieved using trans-PdBr(N-Succ)(PPh₃)₂, alleviating the need for strong bases or toxic organotin reagents. Under these reaction conditions substituted indole-2-boronic acids and substituted benzyl bromides are cross-coupled to afford aryl(indolo)methanes in good yield.     

Palladium-catalyzed reaction of boronic acids with chiral and racemic alpha-bromo sulfoxides

Palladium-catalyzed cross-coupling reactions of racemic alpha-bromo sulfoxides with boronic acids are carried out in either aqueous or nonaqueous medium with formation of a new C sp(3)-C sp(2) bond. The arylation of chiral alpha-bromo sulfoxides occurs without racemization. The cross-coupling reaction is general and gives high yields with arylboronic acids substituted with either donor or acceptor groups but gives poor results with heteroarylboronic acids. The best yields are obtained using degassed solvents and CsF instead of aqueous base. The use of aqueous base and the presence of oxygen favor the homocoupling side reaction.     

Palladium-catalyzed coupling reaction of amino acids (esters) with aryl bromides and chlorides

The bulky and electron-rich MOP type ligands and Pd(dba)₂ combinations showed high efficiency for the coupling reactions of amino acids and inactive aryl halides to give N-aryl amino acids. Under the catalytic conditions, not only α-amino acids, but also β-, γ-, and δ-amino acids have been coupled with aryl chlorides in moderate to high yields; in the case of optically pure β-amino acids as substrates, the optical purities of the coupling products retained.     

A mild,nonbasic synthesis of thioethers. The copper-catalyzed coupling of boronic acids with N-thio(alkyl,aryl, heteroaryl)imides

[reaction: see text] A new synthesis of thioethers is described. The reaction of boronic acids with aryl, heteroaryl, and alkyl N-thioimides in the presence of catalytic quantities of a Cu(I) carboxylate affords good to excellent yields of thioethers. This reaction takes place in the absence of a base under mild conditions (THF, 45-50 degrees C, 2.5-12 h) and represents an interesting complement to known methods for thioether synthesis.     

Copper (II)-mediated arylation with aryl boronic acids for the N-derivatization of pyrazole libraries

A N-derivatized 3-dimethylaminopropyloxypyrazole library was prepared using solution-phase parallel synthesis. The library was designed using physicochemical constraints designed to remove non-membrane-permeable molecules. Cupric acetate-mediated N-arylation with aryl boronic acids proceeded regioselectively to form the N-2-substituted derivatives. The presence of the 3-dimethylaminopropyloxy group was found to completely control the regioselectivity of the arylation. Presence of a dimethylaminoethyloxy or dimethylaminobutyloxy group gave a lesser degree of regioselectivity. The scope of the method as applied to library synthesis is discussed.     

Copper-promoted Chan-Lam coupling between enaminones and aryl boronic acids

A novel copper-promoted N-arylation of enaminones with aromatic boronic acids has been developed, which provides an efficient way to synthesize N-aryl enaminones with a broad substrate scope and excellent functional group compatibility. The N-aryl enaminones could be converted into a series of highly valuable building blocks and bioactive compounds. Notably, in comparison with traditional methods, this alternative approach provides accesses to N-aryl enaminones bearing multiple aromatic rings.     

Palladium-catalyzed coupling of pyrazole triflates with arylboronic acids

[reaction: see text] A general protocol for the palladium-mediated Suzuki coupling reaction of pyrazole triflates and aryl boronic acids has been developed. The use of additional dppf ligand was determined to increase product yields allowing for the use of a broad range of reaction substrates.     

Regiochemistry of copper(I)-mediated cyclization reactions of halo-dienamides

Reaction of 2-substituted dienamides with catalytic amounts of copper halide/tripyridylamine (TPA) furnishes either 5-exo or 6-endo products with the outcome dependent upon the radical initiating unit. Reaction of 3-substituted dienamides produces beta-lactams via a 4-exo cyclization with termination of the reaction occurring via either halogen atom transfer, trapping with oxygen, elimination, or radical-radical coupling depending upon the diene.     

Palladium-catalyzed decarboxylative coupling of quinolinone-3-carboxylic acids and related heterocyclic carboxylic acids with (hetero)aryl halides

An efficient and practical decarboxylative cross-coupling reaction of quinolin-4(1H)-one 3-carboxylic acids with (hetero)aryl halides has been established. Under a bimetallic system of PdBr(2) and silver carbonate, the protocol proved to be general, and a variety of 3-(hetero)aryl 4-quinolinones and related heterocycles, such as 3-aryl-1,8-naphthyridin-4(1H)-ones, 3-arylcoumarins, 3-arylquinolin-2(1H)-ones, and 2-arylchromones, can be prepared in good to excellent yields.     

Palladium-catalyzed decarboxylative coupling of isatoic anhydrides with arylboronic acids

The decarboxylative coupling of isatoic anhydrides with arylboronic acids was realized for the first time in the presence of Pd(2)(dba)(3) and DPEphos, achieving aryl o-aminobenzoates with yields ranging from moderate to good. The efficiency of this procedure was demonstrated by good compatibility with fluoro, chloro, bromo, nitro, cyano, trifluoromethyl, formacyl, acetyl, thienyl, and naphthyl groups. Preliminary mechanistic experiments using deuterium labeling showed that the oxygen atom was derived from dioxygen.     

Indium/Cu(II)-mediated one-pot synthesis of unsymmetrical diaryl amines from aryl boronic acids and azides

Aryl azides react smoothly with aryl boronic acids in the presence of indium metal in methanol to furnish a variety of unsymmetrical diaryl amines in good yields. This is the first report on the synthesis of diaryl amines from the cross coupling of aryl azides with aryl boronic acids via N-arylation.     

A recyclable nanosize aminoarenethiolato copper(I) catalyst for C-C coupling reactions

An aminoarenethiolato copper(I) catalyst was attached to a carbosilane dendritic wedge, which had been prepared via a novel convergent synthetic method. Compared with the unsupported complex, this novel dendritic copper(I) catalyst is more robust towards hydrolysis and oxidation and has increased solubility in common organic solvents. The catalytic activity of the dendritic copper catalyst was tested in the 1,4-addition of Et₂Zn to 2-cyclohexenone. In both polar (Et₂O) and apolar (hexane) solvents excellent activity was observed. The fact that the catalytic copper site remains attached to the nanosize dendritic aminoarenethiolate ligand allows separation of this catalyst by means of nanofiltration.