Synthesis Of Aryl Ketones Research Articles

Visible‐Light‐Mediated Synthesis of Aryl Ketones and Aldehydes from N‐(acyloxy)phthalimides Esters

AbstractA visible‐light‐mediated decarboxylative oxidation of benzylic redox active esters is described. A diverse array of aromatic ketones or aldehydes could be achieved (15 examples) from secondary or primary aliphatic carboxylic acids. A mechanism involving resonance transformation in the presence of Cs2CO3 is proposed.

Quinazoline-Assisted Acylation with Aldehydes through Pd(II)-Catalyzed C(sp2)–H Activation

An efficient quinazoline-assisted ortho-aroylation of 4-phenylquinazolines with aromatic aldehydes has been developed using Pd(OAc)2 as the catalyst in presence of tert-butyl hydroperoxide (TBHP). This work provides an efficient strategy to synthesis of arylketones, giving yields of up to 90%. Meanwhile, the reaction system exhibits good functional group tolerance and a wide substrate scope. Radical trapping and control experiments suggest that the aroylation reaction involves a benzoyl radical pathway.

Palladium-Catalyzed Synthesis of Aryl Ketones from Carboxylic Acids and Arylboronic Acids Using 2-Chloroimidazolium Chloride as a Coupling Reagent

AbstractCarboxylic acids are an abundant and structurally diverse class of commercially available materials, which are commonly used as stable reagents in organic synthesis. The Suzuki–Miyaura coupling reaction directly using carboxylic acid as a substrate has been rarely reported. Here, we report an efficient coupling reaction of carboxylic acids with arylboronic acids in toluene in the presence of IPrCl-Cl, Pd(OAc)2, PPh3, and K3PO4·7H2O at 90 °C to give the corresponding aryl ketones.

Recyclable palladium-catalyzed Suzuki coupling of aromatic triazine esters: A practical one-pot synthesis of aryl ketones from aromatic acids

An efficient heterogeneous palladium-catalyzed Suzuki coupling of aromatic triazine esters with arylboronic acids has been developed. The reaction proceeds smoothly in toluene at 110 °C using 2 mol% of MCM-41-bound bidentate phosphine palladium complex [MCM-41-2P-Pd(OAc)2] as catalyst and provides a novel and practical method for the synthesis of aryl ketones starting from readily available aromatic acids in a one-pot procedure with moderate to excellent yields. The MCM-41-2P-Pd(OAc)2 catalyst can be reused at least seven times without any apparent decrease in its catalytic activity.

Electrochemical Catalytic Hydrocarbonylation of Arylacetylenes

AbstractAn efficient and environmentally‐friendly synthesis of aryl ketones through the electrochemical catalytic hydrocarbonylation of arylacetylene is demonstrated. The reaction conditions are mild without transition metal catalysts, extra oxidants, or strong acids involved. By using Selectfluor as the additive, this electrochemical transformation exhibits good functional‐group tolerance. The aryl ketone product is obtained with up to 90% isolated yield in the mixed electrolytes of acetonitrile and water. This method may open a new window for the green synthesis of aryl ketones from arylacetylenes.

Cobalt-catalyzed synthesis of aryl ketones and aldehydes from redox-active esters.

A cobalt-catalyzed decarboxylative oxidation of benzylic redox-active esters is described. This protocol efficiently converts secondary or primary aliphatic carboxylic acids into aromatic ketones or aldehydes. A wide range of substrates selectively reacted in good to excellent yields with broad functional group tolerance. Notably, various biologically active molecules could also work well, which indicated the synthetic application of such a methodology.

Photo-induced oxidative cleavage of C-C double bonds for the synthesis of biaryl methanone via CeCl3 catalysis.

A Ce-catalyzed strategy is developed to produce biaryl methanones via photooxidative cleavage of C-C double bonds at room temperature. This reaction is performed under air and demonstrates high activity as well as functional group tolerance. A synergistic Ce/ROH catalytic mechanism is also proposed based on the experimental observations. This protocol should be the first successful Ce-catalyzed photooxidation reaction of olefins with air as the oxidant, which would provide inspiration for the development of novel Ce-catalyzed photochemical synthesis processes.

Water Phase, Room Temperature, Ligand‐Free Suzuki–Miyaura Cross‐Coupling: A Green Gateway to Aryl Ketones by C–N Bond Cleavage

We report herein a green strategy for synthesis of aryl ketones from twisted amides by using Pd(OAc)2 as catalysts. This method shows high functional group tolerance to offer a variety of ketones in good yields under mild conditions (up to 94 %). Notably, this methodology demonstrates the first water phase, room temperature, ligand‐free Suzuki–Miyaura coupling through C–N bond cleavage, which is environmentally friendly and might facilitate the development of amide based green chemistry.

Chemoselective Synthesis of Aryl Ketones from Amides and Grignard Reagents via C(O)–N Bond Cleavage under Catalyst-Free Conditions

Conversion of a wide range of N-Boc amides to aryl ketones was achieved with Grignard reagents via chemoselective C(O)-N bond cleavage. The reactions proceeded under catalyst-free conditions with different aryl, alkyl, and alkynyl Grignard reagents. α-Ketoamide was successfully converted to aryl diketones, while α,β-unsaturated amide underwent 1,4-addition followed by C(O)-N bond cleavage to provide diaryl propiophenones. N-Boc amides displayed higher reactivity than Weinreb amides with Grignard reagents. A broad substrate scope, excellent yields, and quick conversion are important features of this methodology.

Structure and Catalytic Mechanism of a Bacterial Friedel-Crafts Acylase.

C−C bond‐forming reactions are key transformations for setting up the carbon frameworks of organic compounds. In this context, Friedel–Crafts acylation is commonly used for the synthesis of aryl ketones, which are common motifs in many fine chemicals and natural products. A bacterial multicomponent acyltransferase from Pseudomonas protegens (PpATase) catalyzes such Friedel–Crafts C‐acylation of phenolic substrates in aqueous solution, reaching up to >99 % conversion without the need for CoA‐activated reagents. We determined X‐ray crystal structures of the native and ligand‐bound complexes. This multimeric enzyme consists of three subunits: PhlA, PhlB, and PhlC, arranged in a Phl(A2C2)2B4 composition. The structure of a reaction intermediate obtained from crystals soaked with the natural substrate 1‐(2,4,6‐trihydroxyphenyl)ethanone together with site‐directed mutagenesis studies revealed that only residues from the PhlC subunits are involved in the acyl transfer reaction, with Cys88 very likely playing a significant role during catalysis. These structural and mechanistic insights form the basis of further enzyme engineering efforts directed towards enhancing the substrate scope of this enzyme.

Mn/Cu catalyzed addition of arylboronic acid to nitriles: Direct synthesis of arylketones

A direct and efficient synthesis of arylketones via arylboronic acid addition to nitriles in presence of inexpensive Mn/Cu catalytic system is reported. The use of non-precious Mn and Cu salts has been found to be highly advantageous both in terms of accessibility as well as cost effectiveness. A series of arylboronic acids as well as nitriles were used to synthesize a variety of symmetrical and unsymmetrical arylketones. Based on the literature studies, the reaction mechanism is anticipated to go through an aryl radical intermediate which reacted with the copper activated nitrile to give the desired arylketones after the hydrolysis of the imine intermediate.

Integrating Metal-Catalyzed C-H and C-O Functionalization To Achieve Sterically Controlled Regioselectivity in Arene Acylation.

One major goal of organometallic chemists is the direct functionalization of the bonds most recurrent in organic molecules: C-H, C-C, C-O, and C-N. An even grander challenge is C-C bond formation when both precursors are of this category. Parallel to this is the synthetic goal of achieving reaction selectivity that contrasts with conventional methods. Electrophilic aromatic substitution (EAS) via Friedel-Crafts acylation is the most renowned method for the synthesis of aryl ketones, a common structural motif of many pharmaceuticals, agrochemicals, fragrances, dyes, and other commodity chemicals. However, an EAS synthetic strategy is only effective if the desired site for acylation is in accordance with the electronic-controlled regioselectivity of the reaction. Herein we report steric-controlled regioselective arene acylation with salicylate esters via iridium catalysis to access distinctly substituted benzophenones. Experimental and computational data indicate a unique reaction mechanism that integrates C-O activation and C-H activation with a single iridium catalyst without an exogenous oxidant or base. We disclose an extensive exploration of the synthetic scope of both the arene and the ester components, culminating in the concise synthesis of the potent anticancer agent hydroxyphenstatin.

Highly efficient synthesis of aryl ketones by PEPPSI-palladium catalyzed acylative Suzuki coupling of amides with diarylborinic acids

An improved acylative cross-coupling of various N-methyl-N-tosyl amides with diarylborinic acids for synthesis of aryl ketones is developed. In most cases, aryl ketones could be obtained in excellent yields by using 1 mol% 2,6-diisopropylphenylimidazolylidene and 3-chloropyridine co-supported palladium chloride as catalyst in the presence of 3 equiv. K2CO3 as base in refluxing THF. The readily prepared and cost-effective substrates, N-methyl-N-tosylamides and diarylborinic acids, and the commercially available catalyst system promise a practical and efficient access to aryl ketones.

Pd(II)-Catalyzed Denitrogenative and Desulfinative Addition of Arylsulfonyl Hydrazides with Nitriles.

A Pd(II)-catalyzed denitrogenative and desulfinative addition of arylsulfonyl hydrazides with nitriles has been successfully achieved under mild conditions. This transformation is a new method for the addition reaction to nitriles with arylsulfonyl hydrazides as arylating agent, thus providing an alternative synthesis of aryl ketones. The reported addition reaction is tolerant to many common functional groups, and works well in the presence of electron-donating and electron-withdrawing substituents. Notably, the reported denitrogenative and desulfinative addition was also appropriate for alkyl nitriles, making this newly developed transformation attractive.

Nickel-Catalyzed Addition of Arylboronic Acids to Alkyl Nitriles for Synthesis of Aryl Ketones in Fluorinated Solvent

A mild and efficient nickel-catalyzed addition of arylboronic acids to alkyl nitriles in a fluorinated solvent for the synthesis of various aryl ketones is described. A broad range of arylboronic acids and alkyl nitriles were investigated, and the desired products were obtained with good to excellent yields under the optimized conditions. This method provides an opportunity for the synthesis of aryl ketones from alkyl nitriles, especially acetonitrile, with a non-noble metal catalyst in one pot.

Two efficient pathways for the synthesis of aryl ketones catalyzed by phosphorus-free palladium catalysts

Allylic alcohols, 1-buten-3-ol, 1-penten-3-ol and 1-octen-3-ol, reacted with aryl iodides (iodotoluene, 4-iodotoluene, 4-iodophenol and 4-iodanisole) under Heck reaction conditions to form corresponding saturated aryl ketones in one step. The same products were obtained in a two-step tandem reaction consisted of the Heck coupling of allylic alcohols with aryl iodides, followed by hydrogenation. Reactions were catalyzed by phosphorus-free palladium precursors modified with the menthol-substituted imidazolium chlorides. Formation of crystalline palladium nanoparticles, of the diameter up to 65nm, in the reaction mixture was evidenced by TEM.

Biocatalytic Friedel–Crafts Acylation and Fries Reaction

AbstractThe Friedel–Crafts acylation is commonly used for the synthesis of aryl ketones, and a biocatalytic version, which may benefit from the chemo‐ and regioselectivity of enzymes, has not yet been introduced. Described here is a bacterial acyltransferase which can catalyze Friedel–Crafts C‐acylation of phenolic substrates in buffer without the need of CoA‐activated reagents. Conversions reach up to >99 %, and various C‐ or O‐acyl donors, such as DAPG or isopropenyl acetate, are accepted by this enzyme. Furthermore the enzyme enables a Fries rearrangement‐like reaction of resorcinol derivatives. These findings open an avenue for the development of alternative and selective C−C bond formation methods.

Biocatalytic Friedel-Crafts Acylation and Fries Reaction.

The Friedel–Crafts acylation is commonly used for the synthesis of aryl ketones, and a biocatalytic version, which may benefit from the chemo‐ and regioselectivity of enzymes, has not yet been introduced. Described here is a bacterial acyltransferase which can catalyze Friedel–Crafts C‐acylation of phenolic substrates in buffer without the need of CoA‐activated reagents. Conversions reach up to >99 %, and various C‐ or O‐acyl donors, such as DAPG or isopropenyl acetate, are accepted by this enzyme. Furthermore the enzyme enables a Fries rearrangement‐like reaction of resorcinol derivatives. These findings open an avenue for the development of alternative and selective C−C bond formation methods.

Palladium-Catalyzed Denitrogenative Synthesis of Aryl Ketones from Arylhydrazines and Nitriles Using O2 as Sole Oxidant.

An efficient and simple palladium-catalyzed approach for the synthesis of aryl ketones from low-cost nitriles and arylhydrazines using molecular oxygen (O2) as sole oxidant via C-N bond cleavage is reported. Various aryl ketones were synthesized in moderate to good yields under mild conditions. A possible mechanism involving the PdII/Pd0 catalytic cycle process is depicted, and a cationic palladium intermediate was detected by ESI-MS.

Palladium Catalyzed Carbonylative Coupling for Synthesis of Arylketones and Arylesters Using Chloroform as the Carbon Monoxide Source

We describe a modular, palladium catalyzed synthesis of aryl(hetero)aryl benzophenones and aryl benzoates from aryl(hetero)aryl halides using CHCl3 as the carbonyl source in the presence of KOH. The reaction occurs in tandem through an initial carbonylation to generate an aroyl halide, which undergoes coupling with arylboronic acids, bornonates, and phenols. Direct carbonylative coupling of indoles at the third position has also been accomplished under slightly modified reaction conditions by in situ activation of the C-H bond. Notably, CHCl3 is a convenient and safe alternation of CO gas, provides milder reaction conditions with high functional group tolerance, and gives the products in moderate to good yields.