Oxidative Coupling Of Phenols Research Articles

Advances in Exploring Mechanisms of Oxidative Phenolic Coupling Reactions

AbstractBiphenolic compounds serve as important scaffolds for the development of biologically active molecules. Among the methods for the synthesis of biarenols, oxidative coupling, which directly forms a C−C bond, has been extensively explored in various metal‐catalyzed (V, Cr, Co, Fe, Cu, etc.) reactions, electrochemical reactions, and photochemical reactions over the decades. While the exact mechanisms remain elusive in many cases, numerous mechanistic studies have provided valuable insights. This review focuses on the mechanistic details of the oxidative coupling of phenols or naphthols, involving at least one radical intermediate. Additionally, the factors governing chemoselectivity (homo‐ and cross‐coupling), regioselectivity (ortho‐, meta‐ and para−), and enantioselectivity (R and S configuration) are discussed, with a particular emphasis on intermediates and transition states, encompassing various oxidation sites for phenols and potential coupling sites.

Regioselective Oxidative Phenol Coupling by a Mushroom Unspecific Peroxygenase.

Bioactive dimeric (pre-)anthraquinones are ubiquitous in nature and are found in bacteria, fungi, insects, and plants. Their biosynthesis via oxidative phenol coupling (OPC) is catalyzed by cytochrome P450 enzymes, peroxidases, or laccases. While the biocatalysis of OPC in molds (Ascomycota) is well-known, the respective enzymes in mushroom-forming fungi (Basidiomycota) are unknown. Here, we report on the biosynthesis of the atropisomers phlegmacin A1 and B1 of the mushroom Cortinarius odorifer. The biosynthesis of these unsymmetrically 7,10'-homo-coupled dihydroanthracenones was heterologously reconstituted in the mold Aspergillus niger. Methylation of the parental monomer atrochrysone to its 6-O-methyl ether torosachrysone by the O-methyltransferase CoOMT1 precedes the regioselective homocoupling to phlegmacin, catalyzed by the enzyme CoUPO1 annotated as an "unspecific peroxygenase" (UPO). Our results reveal an unprecedented UPO reaction, thereby expanding the biocatalytic portfolio of oxidative phenol coupling beyond the commonly reported enzymes. The results show that Basidiomycota use peroxygenases to selectively couple aryls independently of and convergently to any other group of organisms, emphasizing the central role of OPC in natural processes.

Solvent-dependent reaction mechanisms in the electrooxidative coupling of phenols: insights by operando Raman spectroelectrochemistry.

The electrochemical oxidative phenol coupling reaction is a sustainable method for accessing biphenolic compounds. Using the dimerization of sesamol as a model reaction, insights into the reaction mechanism were gained via operando Raman spectroscopy. By varying the solvent and electrodes, different reaction mechanisms were identified and correlated with the respective product yields.

Regioselektive Oxidative Phenolkupplung durch eine Unspezifische Peroxygenase aus Ständerpilzen

Regioselektive Oxidative Phenolkupplung durch eine Unspezifische Peroxygenase aus Ständerpilzen

Synthesis of C2 symmetric hydroxylated biphenyls by microwave-assisted oxidative coupling of natural phenols

Phenolic compounds, abundant in various plants, exhibit a range of biological properties such as anti-inflammatory, antiseptic, and antioxidant activities. C2-symmetric biphenyl structures, present in many pharmacologically active substances, serve as fundamental backbones in many natural products, highlighting the significance of these compounds. This study introduces innovative microwave-assisted oxidative coupling methods for the synthesis of C2 hydroxylated biphenyls starting from thirteen natural phenols, focusing on eco-friendliness and efficiency. This approach aims to minimize environmental impact while emphasizing safety and sustainability by employing microwaves in environmentally sustainable solvents like water. The proposed mechanisms for the oxidative coupling of phenols include various possible reaction pathways, encompassing both homo and hetero radical-radical couplings.

Solar‐Light‐Driven Photocatalytic Oxidative Coupling of Phenol Derivatives over Bismuth‐Based Porous Metal Halide Perovskites

AbstractThe selective oxidative coupling of phenol derivatives, involving carbon‐carbon (C−C) and carbon‐oxygen (C−O) bond formation, has emerged as a critical approach in the synthesis of natural products. However, achieving precise control over the selectivity in coupling reactions of unsubstituted phenols utilizing solar light as the driving force remains a big challenge. In this study, we report a series of porous Cs3Bi2X9 (X=Cl, Br, I) photocatalysts with tailored band gaps and compositions engineered for efficient solar‐light‐driven oxidative phenol coupling. Notably, p‐Cs3Bi2Br9 exhibited about 73 % selectivity for C−C coupling, displaying a high formation rate of 47.3 μmol gcat−1 h−1 under solar radiation. Furthermore, this approach enables control of the site‐selectivity for phenol derivatives on Cs3Bi2X9, enhancing C−C coupling. The distinctive porous structure and appropriate band‐edge positions of Cs3Bi2Br9 facilitated efficient charge separation, and surface interaction/activation of phenolic hydroxyl groups, resulting in the kinetically preferred formation of C−C over C−O bond. Mechanistic insights into the reaction pathway, supported by comprehensive control experiments, unveiled the crucial role of interfacial charge transfers and Lewis acid Bi sites in stabilizing phenolic intermediates, thereby directing the regioselectivity of diradical couplings and resulting in the formation of unsymmetrical biphenols.

Solar-Light-Driven Photocatalytic Oxidative Coupling of Phenol Derivatives over Bismuth-Based Porous Metal Halide Perovskites.

The selective oxidative coupling of phenol derivatives, involving carbon-carbon (C-C) and carbon-oxygen (C-O) bond formation, has emerged as a critical approach in the synthesis of natural products. However, achieving precise control over the selectivity in coupling reactions of unsubstituted phenols utilizing solar light as the driving force remains a big challenge. In this study, we report a series of porous Cs3Bi2X9 (X=Cl, Br, I) photocatalysts with tailored band gaps and compositions engineered for efficient solar-light-driven oxidative phenol coupling. Notably, p-Cs3Bi2Br9 exhibited about 73 % selectivity for C-C coupling, displaying a high formation rate of 47.3 μmol gcat -1 h-1 under solar radiation. Furthermore, this approach enables control of the site-selectivity for phenol derivatives on Cs3Bi2X9, enhancing C-C coupling. The distinctive porous structure and appropriate band-edge positions of Cs3Bi2Br9 facilitated efficient charge separation, and surface interaction/activation of phenolic hydroxyl groups, resulting in the kinetically preferred formation of C-C over C-O bond. Mechanistic insights into the reaction pathway, supported by comprehensive control experiments, unveiled the crucial role of interfacial charge transfers and Lewis acid Bi sites in stabilizing phenolic intermediates, thereby directing the regioselectivity of diradical couplings and resulting in the formation of unsymmetrical biphenols.

Racemic total synthesis of oxomaritidine by iodobenzene-catalyzed oxidative phenolic coupling under mild reaction conditions

A hypervalent iodine-catalyzed phenolic coupling reaction of norbelladine derivatives was examined with a catalytic amount of iodobenzene and meta-chloroperbenzoic acid as the terminal oxidant. The addition of acetic acid dramatically accelerated the reaction rate even at room temperature, and the cyclized products were successfully obtained under mild reaction conditions. The methods were applicable to the racemic total synthesis of oxomaritidine.

Recent advances in oxidative phenol coupling for the total synthesis of natural products.

Covering: 2008 to 2023This review will describe oxidative phenol coupling as applied in the total synthesis of natural products. This review covers catalytic and electrochemical methods with a brief comparison to stoichiometric and enzymatic systems assessing their practicality, atom economy, and other measures. Natural products forged by C-C and C-O oxidative phenol couplings as well as from alkenyl phenol couplings will be addressed. Additionally, exploration into catalytic oxidative coupling of phenols and other related species (carbazoles, indoles, aryl ethers, etc.) will be surveyed. Future directions of this particular area of research will also be assessed.

Kinetics, thermodynamics, and DFT studies of phenols oxidative coupling reactions with 4-amino-N, N-dimethylaniline

A spectrophotometric method has been established for the reaction kinetics of phenol oxidative coupling with 4-amino-N, N-dimethylaniline in the presence of potassium dichromate as an oxidant to form C14H14N2O, known as phenol blue. Optimum conditions for the reaction were investigated: maximum wavelength (λ max), linear range, molar absorptivity, and stability constant. The kinetic models were applied to the reaction, indicating that it is a first-order reaction. The activation energy (Ea) and Arrhenius constant (A) were calculated from the Arrhenius equation as 14.89 kJ·mol−1 and 3.75 × 105 s-1 respectively. Thermodynamic parameters were ΔH* 12.37 Kj·mol−1, ΔG* 5.47 kJ·mol−1 and ΔS* 22.77 J·mol−1·K−1 at 30oC.. Results indicate that the formation of the product phenol blue is non-spontaneous and endothermic in nature. Density function theory (DFT) has been done for the comparison between experimental and theoretical results using the common 6-311G(d,p) basis set. The results are in good agreement with each other, proving the reliability of the method. Finally, some preliminary test has been performed to check possibility of the product as dye.

Synthetic Studies of Hasubanan Alkaloids Based on Oxidative Phenolic Coupling and Intramolecular Aza-Michael Reaction

Synthetic Studies of Hasubanan Alkaloids Based on Oxidative Phenolic Coupling and Intramolecular Aza-Michael Reaction

Synthesis of Pentacyclic Core Structure ofAspidospermaAlkaloids by Sequential Ring Construction via Oxidative Phenolic Coupling

Synthesis of Pentacyclic Core Structure of<i>Aspidosperma</i>Alkaloids by Sequential Ring Construction via Oxidative Phenolic Coupling

Oxidative Coupling of Phenols and Alkenylphenols with TiO2 under Visible Light Irradiation

Key words titanium dioxide - oxidative coupling - visible light - phenols - alkenylphenols

Spectrophotometric Determination of Some Phenolic Compounds Via Oxidative Coupling Reaction Using 4-Aminoantipyrine

A spectrophotometric method has been developed for the determination of some phenolic compounds (Catechol, Resorcinol and Quinol). The method is based on oxidative coupling reaction of these compounds with 4-aminoantipyrine (4-AAP) in the presence of cupper sulphate as oxidizing agent in alkaine medium forming a brown colour. The products show maximum absorption at 404 nm, 474 nm and 392 nm for Catechol, Resorcinol and Quinol respectively. The molar absorptivities are 12133, 7695 and 16570 l/mol.cm for concentrations obeyed Beer’s law in the range 0.2 - 14, 0.04 - 18 and 0.2 - 4 μg.ml-1 for the above compounds respectively. The average recovery was ranged between 97.72% and 100.05% with relative standard deviation less than 3.4 for all the studied compounds, The 4-AAP products were formed in the ratio of 1:2 phenolic compound: 4-AAP With the exception of the complex catechol:4-amino antipyrine, it is in a 1:1 ratio. The stability constant of the products was 1.8369 × 104 (l.mol-1) , 2.82 × 1010 and 1.285 × 1010 (l2.mol-2) for Catechol, Resorcinol and Quinol products respectively indicating the good stability of these products, The effect of a number of interfering substances represented by primary and secondary aliphatic alcohols, aliphatic amines and other organic compounds was also studied. Finally, the results obtained indicate the selectivity of the method as there was no interference from the additives.

Total Synthesis of Fused Polycyclic Alkaloids Based on Oxidative Phenolic Couplings and Aza-Michael Reactions

AbstractAlkaloids with fused polycyclic frameworks are attractive targets for synthetic organic chemists because of their structural complexity and biological activities, and a variety of strategies for their synthesis have been developed. Herein, we describe our strategy of utilizing oxidative phenolic coupling and a regioselective intramolecular aza-Michael reaction to generate fused polycyclic structural frameworks, and its application for the total syntheses of (+)-gracilamine and various hasubanan alkaloids.1 Introduction2 Total Synthesis of (+)-Gracilamine3 Synthetic Studies on Monoterpene Indole Alkaloids4 Total Synthesis of Hasubanan Alkaloids5 Summary

Visible-Light-Induced Oxidative Coupling of Phenols and Alkenylphenols with a Recyclable, Solid Photocatalyst.

A photocatalytic method for phenol and alkenylphenol oxidative coupling is reported using an inexpensive heterogeneous titanium dioxide photocatalyst with air and visible light. During the coupling process, the Ti-substrate complex is activated under visible light through a ligand to metal charge transfer effect, and the diphenol adduct is proposed to form through a radical cation. The heterogeneous TiO2 catalyst remains stable throughout the reaction and can be easily removed and reused multiple times.

Thorectidiol A Isolated from the Marine Sponge Dactylospongia elegans Disrupts Interactions of the SARS-CoV-2 Spike Receptor Binding Domain with the Host ACE2 Receptor.

Thorectidiols isolated from the marine sponge Dactylospongia elegans (family Thorectidae, order Dictyoceratida) collected in Papua New Guinea are a family of symmetrical and unsymmetrical dimeric biphenyl meroterpenoid stereoisomers presumed to be products of oxidative phenol coupling of a co-occurring racemic monomer, thorectidol (3). One member of the family, thorectidiol A (1), has been isolated in its natural form, and its structure has been elucidated by analysis of NMR, MS, and ECD data. Acetylation of the sponge extract facilitated isolation of additional thorectidiol diacetate stereoisomers and the isolation of the racemic monomer thorectidol acetate (6). Racemic thorectidiol A (1) showed selective inhibition of the SARS-CoV-2 spike receptor binding domain (RBD) interaction with the host ACE2 receptor with an IC50 = 1.0 ± 0.7 μM.

Cu4Ti4-oxo clusters functionalized by in situ - generated 2,2'-biphenolate ligands from the oxidative coupling of phenols.

Herein, we report a twisted cubic Cu(I)4Ti(IV)4-oxo cluster stabilized by in situ - formed 2,2'-biphenolate ligands from the oxidative coupling of phenols. The 2,2'-biphenolate-functionalized Cu(I)4Ti(IV)4O4 cluster shows short Cu⋯C contacts and exhibits smaller HOMO-LUMO gaps than those of reported Ti(IV)4O4.

Edge-Decorated Polycyclic Aromatic Hydrocarbons by an Oxidative Coupling Approach.

Oxidative phenol coupling reduces reliance on halo/metalated substrates used in conventional redox neutral couplings. A new strategy for constructing polycyclic aromatic hydrocarbons (PAHs) that incorporates oxidative phenol coupling is outlined in a three-stage approach: oxidative fragment coupling, linking of the two resultant units, and oxidative cyclization. The protocol allows rapid assembly of both planar and helical systems with a high degree of edge functionalization. The incorporation of 12 alkoxy groups on systems with 12 rings gave rise to lower optical gaps compared to systems with a lesser degree of edge functionalization.

Catalytic Oxidative Coupling of Phenols and Related Compounds.

Phenols and their derivatives are the elementary building blocks for several classes of complex molecules that play essential roles in biological systems. Nature has devised methods to selectively couple phenolic compounds, and many efforts have been undertaken by chemists to mimic such coupling processes. A range of mechanisms can be involved and with well-studied catalysts, reaction outcomes in phenol-phenol oxidative coupling reactions can be predicted with a good level of fidelity. However, reactions with catalysts that have not been studied or that do not behave similarly to known catalysts can be hard to predict and control. This Perspective provides an overview of catalytic methods for the oxidative coupling of phenols, focusing on the last 10 years, and summarizes current challenges.