Aryl Source Research Articles

Transition‐Metal‐Free Synthesis of 1,2‐diphenyl‐1H‐benzo[d] Imidazole Derivatives from N‐phenylbenzimidamides and Cyclohexanones

AbstractA transition‐metal‐free strategy for the formation of 1,2‐diphenyl‐1H‐benzo[d] imidazoles from N‐phenylbenzimidamides and cyclohexanones is introduced. This is the first report on the direct synthesis of 1,2‐diphenyl‐1H‐benzo[d] imidazoles from cyclohexanones and N‐phenylbenzimidamides via iodine‐ promoted oxidative cyclization. Non‐aromatic cyclohexanones were smoothly dehydrogenated, and acted as an aryl source using oxygen as a green oxidant. The catalytic use of iodine makes this method quite simple, more economical and convenient. Under optimized conditions, various substituted 1,2‐diphenyl‐1H‐benzo[d] imidazoles were smoothly reacted, and the desired substituted imidazoles were generated with moderate to excellent yields.magnified image

Regiocontrolled palladium-catalyzed direct C2-arylations of Methoxalen using benzenesulfonyl chlorides and C2,C3-diarylations using aryl bromides as the aryl sources

Conditions for the regioselective palladium-catalyzed direct C2-arylation and C2,C3-diarylation of Methoxalen are described. The use of benzenesulfonyl chlorides as the coupling partner allowed control of the regioselectivity of the arylation in favor of the C2 carbon of Methoxalen. This method tolerates a variety of substituents on the benzenesulfonyl chloride derivative. Notably, 2-, 3-, and 4-bromobenzenesulfonyl chlorides and 4-iodobenzenesulfonyl chloride were coupled with Methoxalen without cleavage of the C-Br or C-I bonds. Conversely, the use of an excess amount of aryl bromides as the aryl source provides access to C2,C3-diarlyated Methoxalenes.

Palladium‐catalyzed regioselective C2‐arylation of 5‐aminoindole

AbstractPd(II)‐catalyzed C‐H arylations of 5‐aminoindole using iodobenzenes as aryl source was studied. Despite pivalamide directing group at 5‐position of the indole, the direct C2‐arylation of the indole observed in high yields and with high regioselectivity.

Desulfinative palladium‐catalyzed cross‐coupling of arylsulfonyl hydrazides with aryl bromides under air

A highly efficient and mild palladium‐catalyzed cross‐coupling of arylsulfonyl hydrazides and aryl bromides for the selective synthesis of unsymmetrical biaryls has been developed. This methodology has the advantages of easily accessible starting materials, functional group tolerance and a wide range of substrates, which provide rapid access to biaryls derivatives. In this protocol, abundant and stable aryl bromides serve as the aryl sources by coupling reaction of the aryl group generated from arylsulfonyl hydrazides via in situ release of nitrogen and sulfur dioxide. No external oxidants or acids are needed for this kind of transformation.

Pd/Cu-catalyzed facile approach to stilbenes: A novel diversity of TosMIC as an aryl source

Pd/Cu-catalyzed Heck type cross-coupling reaction of p-toluenesulfonylmethyl isocyanide (TosMIC) with various styrenes to access stilbenes in DMSO solvent under mild conditions is developed. This efficient and simple approach employs TosMIC as an aryl source for the first time and demonstrates the novel diversity of TosMIC.

Late stage Pd-catalyzed C-H bond functionalization: A powerful tool for the one step access to arylated Cyproheptadine and cyclobenzaprine derivatives

The reactivity of Cyproheptadine and Cyclobenzaprine in Pd-catalyzed arylation via C-H bond functionalizations was investigated. From Cyproheptadine using aryl bromides as aryl sources and 5 mol% of a palladium catalyst, the C10-arylated Cyproheptadine derivatives were regioselectively obtained. The highest yields were obtained with electron-rich aryl bromides, but the reaction tolerated useful functional groups on the aryl bromide such as dimethylamino, methoxy, hydroxyl, alkyl, aryl, fluoro, chloro and trifluoromethyl. Cyclobenzaprine was also reactive under the same reaction conditions. © 2019 Elsevier Science. All rights reserved.

Decarboxylative Arylation of Pyridine 1‐Oxides and Anilides with Benzoic Acid via Palladium‐Catalyzed C–H Functionalization

A novel method for the palladium‐catalyzed decarboxylative ortho C–H bond arylation of pyridine 1‐oxides and anilides with benzoic acids as aryl sources is described. The established methodology provides a direct approach for the synthesis of 2‐arylpyridine 1‐oxides and 2‐aryl anilides in good isolated yields.

Transition-metal free C(sp2)-C(sp2) bond formation: arylation of 4-aminocoumarins using arynes as an aryl source.

A mild, efficient and transition-metal free synthetic strategy has been developed for the α-arylation of 4-aminocoumarins. This synthetic strategy proceeds via C(sp2)-C(sp2) bond formation between 4-aminocoumarins and aryne precursors in a single step by simple treatment with a fluoride source in the absence of a metal-catalyst. Moreover, this methodology affords good yields of 4-amino-3-arylcoumarin derivatives bearing halide functionality.

Nickel-catalyzed decarbonylation of N-acylated N-heteroarenes.

Nickel-catalyzed decarbonylation of N-acylated N-heteroarenes is developed. This method can be used to produce a variety of N-aryl heteroarenes, including pyrroles, indoles, carbazoles and phenoxazines, using benzoic acid derivatives as arylating reagents. Arylnickelamide intermediates that are relevant to the catalytic reaction were characterized by X-ray crystallography. When N-acylated benzimidazoles are used as substrates, decarbonylation accompanied 1,2-migration to form 2-arylated benzimidazoles.

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

AbstractThe palladium‐catalyzed functionalization of 5‐membered ring heteroaromatics, through a C−H bonds activation, for access to arylated heteroaromatics represent a very attractive alternative to more classical cross‐coupling reactions, as it saves steps and reduces the amount of wastes. Despite these advantages, these transformations initially suffered from major limitations in terms of sustainable chemistry concerning the reaction media, the nature of the catalyst, the catalyst loading, the aryl source or the regioselectivity control. Tremendous improvements allowing more sustainable reaction conditions using greener solvents, new aryl sources or employing easily removable catalysts and lower catalyst loadings have been described during the last decades. This review summarizes some of the most important contributions made in these directions.

Palladium-Catalyzed Ring-Forming Alkene Aminoaroylation of Unsaturated Hydrazones and Sulfonamides.

The first example of a Pd(OAc)2-catalyzed ring-forming alkene aminoaroylation of unsaturated hydrazones and sulfonamides is described. This protocol features the use of diaryliodonium salts as both oxidants and aryl sources, thus enabling mild reaction conditions, good chemoselectivity, a broad substrate scope, and high functional group tolerance. A wide range of synthetically and biologically important functionalized dihydropyrazoles and isoxazolidines have been obtained in good yields.

Palladium-catalyzed redox cascade for direct β-arylation of ketones

Herein we report a full article about the detailed design and development of two palladium-catalyzed redox cascade methods that enable direct β-arylation of ketones. Palladium-catalyzed ketone dehydrogenation, aryl-X bond activation and conjugate addition were merged into a redox-neutral catalytic cycle. Non-metal-based aryl electrophiles were used as both the oxidant and the aryl source. The β-arylation with aryl iodides was achieved site-selectively with Pd(TFA)2/P(i-Pr)3 as the precatalyst and AgTFA as the iodide scavenger. Both cyclic and linear ketones can react to give β-aryl ketones with excellent functional group tolerance. The β-arylation with diaryliodonium salts was realized without stoichiometric heavy metal additives, and proved to be redox-neutral. A wider substrate scope regarding aryl groups and ketones was obtained for the arylation with diaryliodonium salts, and the possible involvement of palladium nanoparticles as the active catalyst was examined and discussed.

Iodination and O‐Arylation of 2‐Arylquinolin‐4(1H)‐one with PhI(OAc)2 Under Metal‐free Conditions

AbstractIodination and O‐arylation of 2‐arylquinolin‐4(1H)‐one with PIDA under mild conditions have been developed, in which PIDA play a dual role as an iodine source and an aryl source. This protocol provides a facile access to 3‐iodo‐4‐phenoxy‐2‐arylquinolines with tolerance of a broad range of functional groups. Furthermore, This method is employed for concise synthesis of topoisomerases catalytic inhibitor analogue.

Decarbonylative C-P Bond Formation Using Aromatic Esters and Organophosphorus Compounds.

Ni-catalyzed C-P bond formation was achieved using aromatic esters as unconventional aryl sources. The key to success was the use of a thiophene-based diphosphine ligand (dcypt). Several aromatic esters including heteroaromatics can be coupled with phosphine oxides and phosphates, providing aryl phosphorus compounds. The synthetic utility of the method was demonstrated by application of the present protocol to the sequential coupling reactions.

Halo-substituted benzenesulfonyls and benzenesulfinates: convenient sources of arenes in metal-catalyzed C-C bond formation reactions for the straightforward access to halo-substituted arenes.

Palladium-catalyzed reactions using aryl halides as one of the coupling partners represent a very popular method for generating carbon-carbon bonds. However, such couplings suffer from important limitations. As most palladium catalysts are very effective for the cleavage of C-halo bonds (Halo = Cl, Br or I), in many cases, the presence of several halide functional groups on arenes is not tolerated. Since two decades, and especially during the last few years, a new class of coupling partners, benzenesulfonyl and benzenesulfinate derivatives, has emerged as a powerful alternative to aryl halides for the Pd-catalyzed C-C bond formation, as the reactions performed with these substrates generally tolerate C-halo bonds. With these substrates, after a metal-catalyzed desulfitative coupling, a variety of halo-substituted arenes such as biaryls, styrenes, phenylacetylenes, acetophenones, benzonitriles… has been synthesized with high chemoselectivities. The use of these aryl sources allowed the synthesis of molecules containing several halo-substituents including iodo-substituents in only a few steps and provides very simple access to a very wide variety of halo-substituted arenes useful to materials chemists and also to biochemists. In this review, we will summarize the scope of the use of halo-substituted benzenesulfonyls and benzenesulfinates as coupling partners in metal-catalyzed C-C bond formation.

Transition-Metal-Free C-S Bond Formation: Synthesis of Polysubstituted Diaryl Sulfides and α-Thioarylcarbonyl Compounds.

A transition-metal-free protocol for the construction of C-S bonds has been developed. Acetylacetone acts as a new and green aryl source for the synthesis of polysubstituted diarylsulfides bearing a free hydroxy group and a ketone group, which provides a new access to a series of flavonoids containing a thioaryl group. In addition, a series of α-thioarylcarbonyl compounds are obtained in good to excellent yields.

Copper-Catalyzed Azidative Multifunctionalization of Alkynes.

A facile and efficient copper-catalyzed azidative multifunctionalization of alkynes has been developed by using N-fluorobenzenesulfonimide (NFSI) as both nitrogen source and aryl source and trimethylsilyl azide (TMSN3) as azido source. This transformation proceeds under mild conditions, providing a series of α-azido-α-aryl imine in good yields by a single operation starting from a wide range of alkynes. The prepared α-azido-α-aryl imines could be easily converted into 1,5-piperizine-fused 1,2,3-triazoles and azido enamines.

Base-assisted, copper-catalyzed N-arylation of (benz)imidazoles and amines with diarylborinic acids

N-Arylation of (benz)imidazoles and amines with diarylborinic acids as cost-effective aryl source has been efficiently effected via Cu(OAc)2-catalyzed Chan-Lam coupling in assistance of tetramethylethylenediamine (TMEDA) in methanol and pyridine (Py) in dichloromethane, respectively, in air at room temperature. The diarylborinic acids could be well accommodated by the Chan-Lam coupling oxidative conditions containing a proper combination of bases and solvents. The steric hindrance appeared to affect the copper-catalyzed N-arylation using the high-order arylboron reagent more significantly than the electronic factors, especially for low reactive anilines and aliphatic amines.

Modular Synthesis of Carbazole-Based Conjugated Molecules through a One-Pot Annulation/Dehydrogenation Sequence.

An efficient one-pot indole-to-carbazole strategy with cyclohexanones as the aryl source is described. This cascade carbazole formation is enabled by the NH4I-catalyzed annulation of indoles, cyclohexanones, and alkenes and subsequent dehydrogenative aromatization. The present work provides a modular synthesis of arylcarbazoles, benzocarbazoles, and naphthocarbazoles with excellent regioselectivity and broad functional group tolerance. More than 40 benzo-fused carbazoles were synthesized, and the UV-vis absorption and photoluminescent spectra of some products were measured to study their photophysical properties.

Facile and Metal-Free Synthesis of Phenols from Benzaldoxime and Diaryliodonium Salts

A metal-free, base-promoted facile synthesis of phenol derivatives utilising diaryliodonium salts as the aryl source and benzaldoxime as the hydroxide surrogate has been developed. The reaction is fast and shows good substrate compatibility, giving the corresponding products in good to excellent yields. A gram-scale synthesis of phenols utilising this protocol has also been achieved.