Aryl Ketones Research Articles

Selective Oxyfunctionalization of Benzylic C-H with No Solvent.

The direct selective oxyfunctionalization of C-H into C═O represents a highly useful, yet challenging, synthetic methodology. Herein, a one-step oxyfunctionalization of benzylic C-H into aryl ketone, with no overoxidation of the -OH functional group, is reported through mechanochemistry. The substrate scope is also tolerant of a wide range of different functional groups, providing a particularly sustainable yet widely adaptable route for the synthesis of aryl ketones, which represent both a classic synthetic precursor and a useful strategy for lignin monomer valorization. A series of mechanistic and spectroscopic investigations were also conducted to shed light on the unique C-H over -OH selectivity, opening up new avenues for oxidation chemistry.

Unusual and Persistent Free Radical Intermediate Production from 2-Pyridyl Ketones via UV Irradiation: A Direct ESR Study.

Aryl ketones are often used as photosensitizers and photoinitiators. Free radical intermediates have been suggested, but not confirmed, to be generated after photoirradiation. Here we found, unexpectedly, that a persistent radical was produced from di-2-pyridyl ketone after UV irradiation, which was detected by the direct ESR method. Interestingly, the persistent radical was very sensitive to oxygen and the pH of the reaction medium. A similar persistent radical was also observed from phenyl-2-pyridyl ketone, but not from 3-benzoylpyridine, 4-benzoylpyridine, and benzophenone, suggesting that the presence of a carbonyl group connected to the ortho-position of the pyridine ring is critical for such radical production. By complementary applications of ESR, HPLC, and ESI-Q-TOF-MS, the possible chemical structures of the persistent radical and final product were identified, and the possible underlying reaction mechanism was proposed. This represents the first report on UV-induced persistent radical generation from 2-pyridyl ketones, which should be of great significance for future studies.

Photoreductive N-N Homocoupling Catalyzed by a Superphotoreductant.

Azines are valuable synthons or target molecules in organic synthesis. In this work, we report that CBZ6 could work as a photoreductive catalyst for the N-N homocoupling of oximes in high efficiency. This therefore enabled convenient access to a large variety of azines from the corresponding aryl and alkyl ketones, as well as aryl aldehydes in up to 99% yield. 2,4-Dinitrophenoxyl was used as the recyclable auxiliary and the CBZ6 photocatalyst could also be recycled. These together with the low catalyst loading (2 mol % of CBZ6), the short reaction time (4 h), and the nontoxic DMSO solvent make the current process a sustainable and practical alternative to the classic methods.

Visible-Light-Induced α-Arylation of Ketones with (Hetero)aryl Halides.

An enamine-mediated photoredox catalyzed C(sp2)-C(sp3) cross-coupling of dual radical precursors for the arylation of ketone is presented in this Letter. These reactions led to the formation of an enamine by using pyrrolidine to functionalize the C(sp3)-H bond in ketone substrates, which could be smoothly converted to α-arylated ketones with inert aryl bromides and even aryl chlorides in moderate to good yields under mild reaction conditions. The photocatalytically induced C(sp2)-C(sp3) cross-coupling between unactivated noncyclic ketones and aryl halides was achieved, and multiple carbonyl α-arylated backbones containing various natural products and drug molecules were successfully constructed.

Synthesis of Isotopically Labelled Alkyl Aryl Ketones by Nickel-Catalyzed Carbonylative Cross-Coupling

Synthesis of Isotopically Labelled Alkyl Aryl Ketones by Nickel-Catalyzed Carbonylative Cross-Coupling

Photooxidation of Toluene Derivatives under HAT and ROS Synergy.

The valorization of toluene offers a dual solution by addressing its environmental impact while also facilitating the synthesis of a diverse array of valuable fine chemicals and pharmaceutical intermediates, thus ensuring both ecological sustainability and economic viability. We report herein a synergistic approach that harmonizes hydrogen atom transfer (HAT) process with the generation of reactive oxygen species (ROS) under mild condition and low catalyst loading, which enables the efficient synthesis of a broad spectrum of esteemed benzoic acid derivatives and aryl ketones through the photocatalytic oxidation of toluene derivatives. Mechanistic elucidation reveals that the HAT reagent anthraquinone has both the capabilities to abstract hydrogen atoms and the ability to generate singlet oxygen 1O2 during energy transfer with triplet oxygen 3O2, and the combination of these two potencies significantly improves the catalytic efficiency of the reaction. This study not only introduces the amalgamation of HAT with ROS generation but also delineates a systematic approach for the selection of HAT reagents with energy transfer proficiency for ROS generation in catalytic oxidation reactions.

Ni(II)-catalyzed asymmetric alkenylation and arylation of aryl ketones with organoborons via 1,5-metalate shift

Chiral tertiary alcohols are an important structural motif, however, the general and efficient methodologies for their synthesis are less reported. Herein, we report a Ni(ІІ)-catalyzed asymmetric alkenylation and arylation of aryl ketones with organoborons under air via a 1,5-metalate shift strategy to obtain chiral tertiary allylic alcohols and diaryl alcohols. The reaction demonstrates good functional group tolerance and delivers chiral tertiary alcohols with good to excellent results. Furthermore, this method can be applied to the late-stage modification of drugs and the efficient synthesis of natural products. Notably, the reaction proceeds through an outer-sphere mechanism. The Ni(II) complex functions both as a Lewis acid to activate the ketone and create a chiral environment, and as coordination bridge linking the ketone and the organoboron-derived “ate” complex, facilitating the 1,5-metalate shift without forming a C-Ni bond. This approach contrasts with traditional transition metal-catalyzed nucleophilic addition reactions that involve carbon-metal bond formation.

Synthesis of β-(Hetero)aryl Ketones via Ligand-Enabled Nondirected C–H Alkylation

Synthesis of β<i>-</i>(Hetero)aryl Ketones via Ligand-Enabled Nondirected C–H Alkylation

Visible-light-induced palladium-catalyzed C-H acylation of Azobenzenes at room temperature

An efficient C-H acylation of azobenzenes has been achieved through the synergistic use of palladium catalysis and visible-light photoredox catalysis at room temperature. This metallaphotocatalytic system is effective for reaction systems composed of TBHP and benzaldehyde, as well as those involving oxygen and benzoyl formic acid. The strategy exhibits good tolerance to various sensitive functional groups, producing a series of azo-substituted aryl ketones in moderate to good yields. The method is cost-effective, highly efficient, and environmentally friendly, providing a basis for the future development of novel metallaphotocatalytic reactions.

Catalytic Generation of Benzyl Anions from Aryl Ketones Utilizing [1,2]-Phospha-Brook Rearrangement and Their Application to Synthesis of Tertiary Benzylic Alcohols.

A synthetic method of tertiary alcohols was developed based on the formal umpolung addition of aryl ketones with electrophiles utilizing the [1,2]-phospha-Brook rearrangement under Brønsted base catalysis. The addition reaction of α-hydroxyphosphonates, derived from alkyl aryl- and diaryl ketones, with electrophiles such as phenyl vinyl sulfone, afforded phosphates having a tertiary alkyl group, which were readily convertible to the corresponding tertiary benzylic alcohols. This operationally simple protocol provides efficient complementary access to tertiary alcohols that are difficult to synthesize by conventional methods.

N-heterocyclic carbene-catalyzed nucleophilic aromatic substitution reaction of polyfluoroarenes

Fluorinated asymmetric aryl ketones represent a pivotal class of organic synthesis intermediates, which have garnered widespread application in the realms of organic chemistry, materials science, and drug discovery. Herein, we report a pioneering nucleophilic aromatic substitution (S N Ar) reaction involving aryl aldehydes and polyfluoroarenes, elegantly catalyzed by N-heterocyclic carbene (NHC). This innovative strategy yields bis(hetero)aryl ketone products in yields ranging from moderate to exceptional (40–83%), all achieved under gentle conditions, devoid of both transition metals and directing groups. The versatility of this method is underscored by its compatibility with a broad spectrum of substrates, particularly exhibiting remarkable resilience toward alkoxy functional groups. Notably, we have successfully transformed an array of biologically active molecules, crafting a series of their corresponding derivatives with precision.

Light-promoted AIBN-catalyzed oxidative cleavage of aryl olefins to aryl ketones

A convenient light-promoted 2,2-azobis(isobutyronitrile) (AIBN)-catalyzed synthesis of aryl ketone from aryl alkenes with molecular oxygen as the oxidant was developed. A series of aryl ketone were obtained in moderate to good yields. The new protocol features mild conditions and relatively broad substrate scope. The reaction was successfully applied for the synthesis of Fenofibrate in good yield. Based on previous documents and current experimental results, a plausible mechanism is proposed.

Nickel Catalyzed Carbonylative Cross Coupling for Direct Access to Isotopically Labeled Alkyl Aryl Ketones.

Here we present an effective nickel-catalyzed carbonylative cross-coupling for direct access to alkyl aryl ketones from readily accessible redox-activated tetrachlorophthalimide esters and aryl boronic acids. The methodology, which is run employing only 2.5 equivalents of CO and simple Ni(II) salts as the metal source, exhibits a broad substrate scope under mild conditions. Furthermore, this carbonylation chemistry provides an easy switch between isotopologues for stable (13CO) and radioactive (14CO) isotope labeling, allowing its adaptation to the late-stage isotope labeling of pharmaceutically relevant compounds. Based on DFT calculations as well as experimental evidence, a catalytic cycle is proposed involving a carbon-centered radical formed via nickel(I)-induced outer-sphere decarboxylative fragmentation of the redox-active ester.

Nickel Catalyzed Carbonylative Cross Coupling for Direct Access to Isotopically Labeled Alkyl Aryl Ketones

Nickel Catalyzed Carbonylative Cross Coupling for Direct Access to Isotopically Labeled Alkyl Aryl Ketones

Immobilization of cross-linked enzymes aggregates on hierarchical covalent organic frameworks: Highly stable chemoenzymatic nanoreactor for asymmetric synthesis of optically active halohydrins

Organometallic catalyst is extensively applied for the non-enzymatic regeneration of nicotinamide adenine dinucleotide (phosphate) cofactors, but suffering from the mutual inactivation with the enzymes in one pot. The spatially separated immobilization of organometallic catalyst and enzymes on suitable carriers not only can reduce their mutual inhabitation but also can enhance their reusability. Here in this work, we present a hierarchical porous COFs (HP-TpBpy) that incorporated with [(Cp*RhCl2]2 to generate the metalized COF, Rh-HP-TpBpy. The obtained Rh-HP-TpBpy exhibited superior performance in nicotinamide adenine dinucleotide (NADH) and nicotinamide adenine dinucleotide phosphate (NADPH) regeneration using formate as the hydride donor, significantly outperforming the natural formate dehydrogenases in cofactor preference toward NADP+. Subsequently, the Lactobacillus fermentum short-chain dehydrogenase/reductase 1 (LfSDR1) was then cross-linked into enzyme aggregates (CLEA) and immobilized on hierarchical Rh-HP-TpBpy, achieving the integrated chemoenzymatic catalyst, LfSDR1@Rh-HP-TpBpy, which can catalyze the chemoenzymatic reduction of halogenated aryl ketones and give the corresponding optically active halohydrins with high conversion and enantiomeric excess (ee) value up to 99 %. The LfSDR1@Rh-HP-TpBpy also exhibits largely enhanced stability compared with the free LfSDR1 and the CLEAs-LfSDR1, enabling its excellent reusability.

Homologation of Ketones: Direct Transformation of Alkyl Ketones to Aryl Ketones via Photoredox Catalyzed Deacylation-Aroylation Sequence.

Ketones, as essential functional group skeletons, have garnered significant interest due to their diverse transformations. Herein, we describe a versatile photoredox catalyzed deacylation-aroylation strategy that enables the direct transformation of alkyl ketones to aryl ketones. This process involves photoredox deacylation of dihydroquinazolinones derived from alkyl ketones to generate alkyl radicals, followed by subsequent NHC-catalyzed or NHC-mediated radical aroylation.

Regioselective Annulation of 3(5)‐Aminopyrazole with Aryl Ketones or Aryl Alkynes Using N,N‐Dimethylethanolamine as a Single/Triple Carbon Synthon

AbstractAn efficient and regioselective cyclization for construction of pyrazolo[3,4‐b]pyridines and methylene‐bridged bis(pyrazolo[1,5‐a]pyrimidines) has been established. It involves a [3+2+1] annulation of 3(5)‐aminopyrazole, N,N‐dimethylethanolamine (DMEA), with 1,2‐insertion of aryl methyl ketones or 2,1‐insertion of aryl alkynes. DMEA is oxidized through C(sp3)‐H activation to provide a single or triple carbon source.

Enantioselective Synthesis of Tertiary Alcohols by a Nickel-Catalyzed Reductive Arylation of Ketones

Enantioselective Synthesis of Tertiary Alcohols by a Nickel-Catalyzed Reductive Arylation of Ketones

Modifying Proton Relay into Bioinspired Dye‐Based Coordination Polymer for Photocatalytic Proton‐Coupled Electron Transfer

AbstractProton‐coupled electron transfer (PCET) imparts an energetic advantage over single electron transfer in activating inert substances. Natural PCET enzyme catalysis generally requires tripartite preorganization of proton relay, substrate‐bound active center, and redox mediator, making the processes efficient and precluding side reactions. Inspired by this, a heterogeneous photocatalytic PCET system was established to achieve higher PCET driving forces by modifying proton relays into anthraquinone‐based anionic coordination polymers. The proximally separated proton relays and photoredox‐mediating anthraquinone moiety allowed pre‐assembly of inert substrate between them, merging proton and electron into unsaturated bonds by photoreductive PCET, which enhanced reaction kinetics compared with the counter catalyst without proton relay. This photocatalytic PCET method was applied to a broad‐scoped reduction of aryl ketones, unsaturated carbonyls, and aromatic compounds. The distinctive regioselectivities for the reduction of isoquinoline derivatives were found to occur on the carbon‐ring sides. PCET‐generated radical intermediate of quinoline could be trapped by alkene for proton relay‐assisted Minisci addition, forming the pharmaceutical aza‐acenaphthene scaffold within one step. When using heteroatom(X)−H/C−H compounds as proton‐electron donors, this protocol could activate these inert bonds through photooxidative PCET to afford radicals and trap them by electron‐deficient unsaturated compounds, furnishing the direct X−H/C−H functionalization.

Modifying Proton Relay into Bioinspired Dye-Based Coordination Polymer for Photocatalytic Proton-Coupled Electron Transfer.

Proton-coupled electron transfer (PCET) imparts an energetic advantage over single electron transfer in activating inert substances. Natural PCET enzyme catalysis generally requires tripartite preorganization of proton relay, substrate-bound active center, and redox mediator, making the processes efficient and precluding side reactions. Inspired by this, a heterogeneous photocatalytic PCET system was established to achieve higher PCET driving forces by modifying proton relays into anthraquinone-based anionic coordination polymers. The proximally separated proton relays and photoredox-mediating anthraquinone moiety allowed pre-assembly of inert substrate between them, merging proton and electron into unsaturated bonds by photoreductive PCET, which enhanced reaction kinetics compared with the counter catalyst without proton relay. This photocatalytic PCET method was applied to a broad-scoped reduction of aryl ketones, unsaturated carbonyls, and aromatic compounds. The distinctive regioselectivities for the reduction of isoquinoline derivatives were found to occur on the carbon-ring sides. PCET-generated radical intermediate of quinoline could be trapped by alkene for proton relay-assisted Minisci addition, forming the pharmaceutical aza-acenaphthene scaffold within one step. When using heteroatom(X)-H/C-H compounds as proton-electron donors, this protocol could activate these inert bonds through photooxidative PCET to afford radicals and trap them by electron-deficient unsaturated compounds, furnishing the direct X-H/C-H functionalization.