Iron-Catalyzed Oxidative C−C Cross-Coupling Reaction of Tertiary Anilines with Hydroxyarenes by Using Air as Sole Oxidant

A mild procedure for the oxidative C−C cross-coupling of tertiary anilines with phenols is described which provides the products generally in high yields and with excellent selectivity. The reaction is catalyzed by the hexadecafluorinated iron–phthalocyanine complex FePcF₁₆ in the presence of substoichiometric amounts of methanesulfonic acid and ambient air as sole oxidant.     

Aerobic C−N Bond Formation through Enzymatic Nitroso-Ene-Type Reactions**

The biocatalytic oxidation of acylated hydroxylamines enables the direct and selective introduction of nitrogen functionalities by activation of allylic C−H bonds. Utilizing either laccases or an oxidase/peroxidase couple for the formal dehydrogenation of N-hydroxycarbamates and hydroxamic acids with air as the terminal oxidant, acylnitroso species are generated under particularly mild aqueous conditions. The reactive intermediates undergo C−N bond formation through an ene-type mechanism and provide high yields both in intramolecular and intermolecular enzymatic aminations. Investigations on different pathways of the two biocatalytic systems and labelling studies provide more insight into this unprecedented promiscuity of classical oxidoreductases as catalysts for nitroso-based transformations.     

Total Synthesis of Pyrolaside B: Phenol Trimerization through Sequenced Oxidative C−C and C−O Coupling

A facile method to oxidatively trimerize phenols using a catalytic aerobic copper system is described. The mechanism of this transformation was probed, yielding insight that enabled cross-coupling trimerizations. With this method, the natural product pyrolaside B was synthesized for the first time. The key strategy used for this novel synthesis is the facile one-step construction of a spiroketal trimer intermediate, which can be selectively reduced to give the natural product framework without recourse to stepwise Ullmann- and Suzuki-type couplings. As a result, pyrolaside B can be obtained expeditiously in five steps and 16 % overall yield. Three other analogues were synthesized, thus highlighting the utility of the method, which provides new accessibility to this area of chemical space. A novel xanthene was also synthesized through controlled Lewis acid promoted rearrangement of a spiroketal trimer.     

Stereoselective C−C Oxidative Coupling Reactions Photocatalyzed by Zwitterionic Ligand Capped CsPbBr3 Perovskite Quantum Dots

Semiconductor quantum dots (QDs) have attracted tremendous attention in the field of photocatalysis, owing to their superior optoelectronic properties for photocatalytic reactions, including high absorption coefficients and long photogenerated carrier lifetimes. Herein, by choosing 2-(3,4-dimethoxyphenyl)-3-oxobutanenitrile as a model substrate, we demonstrate that the stereoselective (>99 %) C−C oxidative coupling reaction can be realized with a high product yield (99 %) using zwitterionic ligand capped CsPbBr₃ perovskite QDs under visible light illumination. The reaction can be generalized to different starting materials with various substituents on the phenyl ring and varied functional moieties, producing stereoselective dl-isomers. A radical mediated reaction pathway has been proposed. Our study provides a new way of stereoselective C−C oxidative coupling via a photocatalytic means using specially designed perovskite QDs.     

Directing Group-Promoted Inert C−O Bond Activation Using Versatile Boronic Acid as a Coupling Agent

A simple Ni(cod)₂ and carbene mediated strategy facilitates the efficient catalytic cross-coupling of methoxyarenes with a variety of organoboron reagents. Directing groups facilitate the activation of inert C−O bonds in under-utilized aryl methyl ethers enabling their adaptation for C−C cross-coupling reactions as less toxic surrogates to the ubiquitous haloarenes. The method reported enables C−C cross-coupling with readily available and economical arylboronic acid reagents, which is unprecedented, and compares well with other organoboron reagents with similarly high reactivity. Extension to directing group assisted chemo-selective C−O bond cleavage, and further application towards the synthesis of novel bifunctionalized biaryls is reported. Key to the success of this protocol is the use of directing groups proximal to the reaction center to facilitate the activation of the inert C−OMe bond.     

C−N Coupling Reactions on Graphene with Aromatic Macromolecules and the Spatial Conformation of Grafted Macromolecules

The fabrication of advanced graphene-based nanocomposites with high-performance polymers requires covalent modification of graphene with aromatic macromolecules. Herein, C−N coupling reactions between fluorinated graphene (FG) and aromatic polyamides containing the benzimidazole moiety are successfully achieved. The optimized conditions are presented based on the nucleophilic behavior of the C−N coupling reaction on graphene. Different from the C−N coupling reaction between two small aromatic molecules, the conformation of grafted aromatic polyamide after reaction changes from torsional to paralleled alignment on graphene with the molecular length increment. Non-covalent interactions between graphene and aromatic polyamides result in this conformational change owing to the extended π systems of graphene and aromatic polyamides, and the synergistic effect of covalent and non-covalent interactions is put forward. As a consequence, graphene dispersibility is greatly enhanced in the solution of aromatic polyamide.     

Transition Metal-Free Aromatic C−H,C−N,C−S and C−O Borylation

Aromatic organoboron compounds are highly valuable building blocks in organic chemistry. They were mainly synthesized through aromatic C−H and C−Het borylation, in which transition metal-catalysis dominate. In the past decade, with increasing attention to sustainable chemistry, numerous transition metal-free C−H and C−Het borylation transformations have been developed and emerged as efficient methods towards the synthesis of aromatic organoboron compounds. This account mainly focuses on recent advances in transition metal-free aromatic C−H, C−N, C−S, and C−O borylation transformations and provides insights to where further developments are required.     

Solid-State Radical C−H Trifluoromethylation Reactions Using Ball Milling and Piezoelectric Materials

The application of piezoelectricity for the generation of trifluoromethyl (CF₃) radicals is reported together with the development of a method for the mechanochemical C−H trifluoromethylation of aromatic compounds. As compared to conventional solution-based approaches, this mechanoredox C−H trifluoromethylation enables cleaner and more sustainable access to a wide range of trifluoromethylated N-heterocycles and peptides, which are important structural motifs in modern drug discovery. This study thus represents an important milestone for future applications of mechanoredox systems to medicinal and pharmaceutical science.     

Asymmetric Pd(II)-Catalyzed C−O,C−N,C−C Bond Formation Using Alkenes as Substrates: Insight into Recent Enantioselective Developments

This Review summarizes the advances in the catalytic enantioselective mono- and difunctionalization of alkenes, highlighting the fundamental role of ligands. Several types of asymmetric reactions have been developed involving different bonds formation, C−O, C−N and C−C, highlighting the urgency to go ahead in the search for new ligands and synthetic methodologies in order to improve the control over the reaction selectivity and activity and thus, to increase the applications in the synthesis of heterocyclic scaffolds and biologically active compounds. The Review is organized into paragraphs, which discuss the type of bond formed during the nucleopalladation, C−O, C−N, C−C bonds, and the type of reaction involved.     

Generation of FeIV=O and its Contribution to Fenton-Like Reactions on a Single-Atom Iron−N−C Catalyst

Generating Fe^IV=O on single-atom catalysts by Fenton-like reaction has been established for water treatment; however, the Fe^IV=O generation pathway and oxidation behavior remain obscure. Employing an Fe−N−C catalyst with a typical Fe−N₄ moiety to activate peroxymonosulfate (PMS), we demonstrate that generating Fe^IV=O is mediated by an Fe−N−C−PMS* complex—a well-recognized nonradical species for induction of electron-transfer oxidation—and we determined that adjacent Fe sites with a specific Fe₁−Fe₁ distance are required. After the Fe atoms with an Fe₁-Fe₁ distance <4 Å are PMS-saturated, Fe−N−C−PMS* formed on Fe sites with an Fe₁-Fe₁ distance of 4–5 Å can coordinate with the adjacent Fe^II−N₄, forming an inter-complex with enhanced charge transfer to produce Fe^IV=O. Fe^IV=O enables the Fenton-like system to efficiently oxidize various pollutants in a substrate-specific, pH-tolerant, and sustainable manner, where its prominent contribution manifests for pollutants with higher one-electron oxidation potential.     

Activation of N−O σ Bonds with Transition Metals: A Versatile Platform for Organic Synthesis and C−N Bonds Formation**

N−O σ bonds containing compounds are versatile substrates for organic synthesis under transition metal catalysis. Their ability to react through both polar (oxidative addition, formation of metallanitrene, nucleophilic substitution) and radical pathways (single electron transfer, homolytic bond scission) have triggered the development of various synthetic methodologies, particularly toward synthesizing nitrogen-containing compounds. In this review, we discuss the different modes of activation of N−O bonds in the presence of transition metal catalysts, emphasizing the experimental and computational mechanistic proofs in the literature to help to design new synthetic pathways toward the synthesis of C−N bonds.     

Rhodium-Catalyzed C−H Methylation and Alkylation Reactions by Carbene-Transfer Reactions

In this combined computational and experimental study, the C−H functionalization of 2-phenyl pyridine with diazoalkanes was investigated. Initial evaluation by computational methods allowed the evaluation of different metal catalysts and diazoalkanes and their compatibility in this C−H functionalization reaction. With these findings, suitable reaction conditions for the C−H methylation reactions were quickly identified by using highly reactive TMS diazomethane and C−H alkylation reactions with donor/acceptor diazoalkanes, which is applied to a broad scope on alkylation reactions of 2-aryl pyridines with TMS diazomethane and donor/acceptor diazoalkane (51 examples, up to 98 % yield).     

Support-Free Pd3Co NCs as an Efficient Heterogeneous Nanocatalyst for New Organic Transformations of C−C Coupling Reactions

A support-free heterogeneous Pd₃Co nanostructured composite (NC), synthesized through a hydrothermal route, acted as an effective catalytic system in multivariate Heck-, Sonogashira-, and Suzuki-type coupling reactions of iodonium ylides. The XPS analysis of the bimetallic Pd₃Co NCs confirmed the elemental composition as 75 % palladium and 25 % cobalt. Furthermore, high-resolution (HR) TEM analysis confirmed the spherical morphology of the Pd₃Co bimetallic nanoparticles. The average diameter of the NCs is 14.8 nm. The coupling reaction proceeded through the generation of α-iodoenones with simultaneous migration of the phenyl group, thereby giving a scaffold with higher atom economy. The heterogeneous Pd₃Co NCs were recycled and reused without any significant change in catalytic ability for up to five reaction cycles. The high concentration of Pd and association of cobalt into the lattice of palladium appears to enhance its catalytic ability for the diverse coupling reactions in comparison with its monometallic counterparts as well as with bimetallic NCs with a comparatively lesser amount of Pd.     

Metal-Free Formal Oxidative C−C Coupling by In Situ Generation of an Enolonium Species

Much contemporary organic synthesis relies on transformations that are driven by the intrinsic, so-called “natural”, polarity of chemical bonds and reactive centers. The design of unconventionally polarized synthons is a highly desirable strategy, as it generally enables unprecedented retrosynthetic disconnections for the synthesis of complex substances. Whereas the umpolung of carbonyl centers is a well-known strategy, polarity reversal at the α-position of a carbonyl group is much rarer. Herein, we report the design of a novel electrophilic enolonium species and its application in efficient and chemoselective, metal-free oxidative C−C coupling.     

CuI-catalyzed Coupling Reactions of Aryl Iodides with Amides Using L-Proline and KF/Al2O3

An efficient experimentally simple and inexpensive catalyst system for the selective amidation of aryl iodides using 15 mol% of CuI as catalyst, 15 mol% of L-proline as ligand and KF/Al2O3 as a base in toluene is described.     

Divergent Coupling of Benzocyclobutenones with Indoles via C−H and C−C Activations

Highly selective divergent coupling reactions of benzocyclobutenones and indoles, in which the chemoselectivity is controlled by catalysts, are reported herein. The substrates undergo C2(indole)–C8(benzocyclobutenone) coupling to produce benzylated indoles and benzo[b]carbazoles in the Ni- and Ru-catalyzed reactions. A completely different selectivity pattern C2(indole)–C2(benzocyclobutenone) coupling to form arylated indoles is observed in the Rh-catalyzed reaction. Preliminary mechanistic studies suggest C−H and C−C activations in the reaction pathway. Synthetic utility of this protocol is demonstrated by the selective synthesis of three different types of carbazoles from the representative products.     

Directed C−H Activation and Tandem Cross-Coupling Reactions Using Palladium Nanocatalysts with Controlled Oxidation

Controlled oxidation of palladium nanoparticles provided high-valent Pd^IV oxo-clusters which efficiently promote directed C−H halogenation reactions. In addition, palladium nanoparticles can undergo changes in oxidation states to provide both high-valent Pd^IV and low-valent Pd⁰ species within one system, and thus a tandem reaction of C−H halogenation and cross-coupling (C−N, C−C, and C−S bond formation) was successfully established.