Palladium‐Catalyzed Direct Arylations of 1,2,3‐Triazoles with Aryl Chlorides using Conventional Heating

Generally applicable, palladium‐catalyzed direct arylations of 1,2,3‐triazoles with aryl chlorides were accomplished through conventional heating at reaction temperatures of 105–120 °C. Thereby, intra‐ and intermolecular C H bond functionalizations were achieved with a variety of differently substituted chlorides as electrophiles, bearing numerous valuable functional groups.     

Ligand‐Free and Heterogeneous Palladium on Carbon‐Catalyzed Hetero‐Suzuki–Miyaura Cross‐Coupling

A ligand‐free and heterogeneous palladium on carbon (Pd/C)‐catalyzed hetero‐Suzuki–Miyaura coupling reaction has been developed. The protocol enables the construction of both heterocyclic‐alicyclic and heterocyclic‐heterocyclic biaryl derivatives in good to excellent yields. Furthermore, Pd/C could be reused. The time‐course study clarified that palladium was leached into the reaction media as the reaction proceeded and then completely deposited on the carbon support.     

Mechanistic Studies on the Palladium‐Catalyzed Direct C‐5 Arylation of Imidazoles: The Fundamental Role of the Azole as a Ligand for Palladium

An in‐depth mechanistic study on the palladium‐catalyzed direct arylation of imidazoles at the C‐5 position is presented. The interactions of triphenylphosphine (PPh₃)‐ligated aryl‐Pd species with 1,2‐dimethyl‐1H‐imidazole (dmim) have been studied in detail. In contrast with previous suggestions, phosphine‐ligated organo‐Pd species are not active and the reaction proceeds through imidazole‐ligated organo‐Pd intermediates. The kinetics of the oxidative addition of aryl halides with dmim‐ligated Pd(0) species have been characterized in a Pd(dba)₂/dmim model system. A thorough study of the equilibria involving novel [ArPd(dmim)₂X] complexes (X=I, OAc) and the unexpected cationic [ArPd(dmim)₃]⁺ is also reported. The ability of these species to effect the C H arylation of dmim at room temperature in the presence of acetate is also demonstrated.

     

Iron‐Catalyzed Nitrogen‐Directed Coupling of Arene and Aryl Bromides Mediated by Metallic Magnesium

2‐Arylpyridines, 2‐alkenylpyridine, and aromatic imines can be coupled with aryl bromides in the presence of an iron catalyst, metallic magnesium, a diamine ligand and an organic dihalide oxidant at 0 °C. The use of a 1:1 mixture of tetrahydrofuran and 1,4‐dioxane is essential for this C H bond activation reaction. The reaction has wider scope of the substrate compared with the reaction using a separately prepared Grignard reagent, and proceeds with lower catalyst loading (2.5 mol%).     

Room Temperature Highly Enantioselective Nickel‐Catalyzed Hydrovinylation

At room temperature, nickel catalysts based on the new phosphoramidite (11bR)‐N‐[(S)‐1‐(naphthalen‐1‐yl)ethyl]‐N‐[(S)‐1‐(naphthalen‐2‐yl)ethyl]dinaphtho[2,1‐d:1′,2′‐f][1,3,2]dioxaphosphepin‐4‐amine provide excellent selectivities for 3‐arylbut‐1‐enes (93–99%) with high enantioselectivities (90–95% ee) and TOFs (up to 8300 h⁻¹) in the hydrovinylation of electron‐rich and electron‐poor vinylarenes. Within a few minutes, useful chiral building blocks and intermediates can be synthesized using this practical catalytic system.     

Copper‐Catalyzed Coupling of Indoles with Dimethylformamide as a Methylenating Reagent

By using N,N‐dimethylformamide (DMF) as a methylenating reagent, the copper‐catalyzed C H activation of indole was demonstrated as an efficient and facile protocol for synthesizing 3,3′‐diindolylmethane (DIM) and its derivatives. The results indicate that copper chloride was the best catalyst among the investigated transition metal salts, which affords an excellent regioselectivity and good yield when tert‐butyl hydroperoxide (TBHP) was used as an oxidant.

     

Synthesis of Well‐Defined Diphenylvinyl(cyclopropyl)phosphine‐Palladium Complexes for the Suzuki–Miyaura Reaction and Buchwald–Hartwig Amination

The well‐defined diphenylvinylphosphine‐palladium complex 1 and the diphenylcyclopropylphosphine‐palladium complex 2 were successfully synthesized. The crystal structures of these complexes were obtained by X‐ray crystallographic analysis. Both complexes were air‐ and moisture‐stable, and could be prepared on a gram scale. These palladium complexes catalyzed the Suzuki–Miyaura reaction of aryl bromides [turnover numbers (TON) up to 196,000] and aryl chlorides (TON up to 50,000). Furthermore, complex 2 catalyzed the Buchwald–Hartwig amination of aryl chlorides and aromatic/aliphatic amines with a low catalyst loading. These complexes showed different reactivities for the coupling of 2‐chloropyridine, and the origin of this difference is discussed.     

A Highly Active and General Catalyst for the Stille Coupling Reaction of Unreactive Aryl,Heteroaryl, and Vinyl Chlorides under Mild Conditions

A β‐diketiminatophosphane‐palladium complex was found to act as an efficient and general catalyst in the Stille coupling reaction of various aryl and heteroaryl chlorides with organostannanes. The results show that this catalytic system allows for the use of less reactive substrates such as deactivated or sterically hindered aryl chlorides. A catalyst loading of 0.5 mol% was sufficient to achieve excellent performance under relatively mild reaction conditions. Furthermore, the scope of catalyst was extended to the coupling of vinyl chlorides.     

One‐Pot Palladium‐Catalyzed Synthesis of Selectively Substituted Phenanthridines by Sequential Aryl‐Aryl and Heck Couplings,Aza‐Michael and Retro‐Mannich Reactions

A catalytic synthesis of selectively substituted phenanthridines is achieved through a reaction sequence involving palladium/norbornene‐catalyzed unsymmetrical aryl‐aryl and Heck couplings followed by aza‐Michael and retro‐Mannich reactions. In spite of the many steps involved the method is very simple and allows the formation of selectively substituted phenanthridines under mild conditions in a straightforward one‐pot reaction starting from readily available aryl iodides and bromides.     

An Electron‐Deficient Diene as Ligand for Palladium‐Catalyzed Cross‐Coupling Reactions: An Efficient Alkylation of Aryl Iodides by Primary and Secondary Alkylzinc Reagents

An electron‐deficient diene, L₁ , was found to be an effective ligand in facilitating palladium‐catalyzed Negishi couplings involving primary and secondary alkylzinc reagents. The reactions took place readily at 60 °C in THF with 5 mol% of a catalyst generated in situ from bis(acetonitrile)palladium dichloride [PdCl₂(MeCN)₂] and L₁ , and functional groups such as chloro, bromo, etc. attached to phenyl ring as well as β‐H atoms adjacent to the reaction site were well tolerated. The problematic isomerizations in secondary alkyzinc reagents involved in the reactions reported in the literature were also observed in our system when isopropylzinc chloride was employed alone as the nucleophile. However, the isomerization was significantly suppressed when i‐Pr₂Zn was utilized in the presence of L₁ .     

Cyanides‐Free Cyanation of Aryl Halides using Formamide

A novel method for cyanation of aryl halides using formamide as a non‐toxic cyanide source is reported. It is a single‐step, solvent‐free method wherein formamide itself acts as solvent as well as source of cyanide in the presence of phosphorus oxychloride and palladium acetate/xantphos catalyst. Aryl iodides as well as aryl bromides provided moderate to excellent yields of up to 93%.     

Palladium Supported on Cross‐Linked Imidazolium Network on Silica as Highly Sustainable Catalysts for the Suzuki Reaction under Flow Conditions

Highly cross‐linked imidazolium‐based materials, obtained by radical oligomerization of bis‐vinylimidazolium salts in the presence of 3‐mercaptopropyl‐modified silica gel, were used as supports for palladium catalysts. Thanks to the high imidazolium loading these materials were able to support a high amount of the metal (10 wt%). Such materials were characterized by several techniques (¹³C magic angle spinning nuclear magnetic resonance, the Brunauer–Emmett–Teller technique, X‐ray photoelectron spectroscopy, and transmission electron microscopy). The palladium catalysts displayed good activity allowing the synthesis of several biphenyl compounds in high yields working with only 0.1 mol% of palladium loading at 50 °C in ethanol/water under batch condition. Moreover, a flow apparatus, to optimize the efficiency of the isolation of the pure products and minimize waste (E‐factor), was investigated. For the first time the palladium catalyst and base (K₂CO₃) were placed in two separate columns allowing an easy recovery of the products with very low E‐factor values (<4). Waste production was reduced by over 99% compared to classic batch conditions. Because of the high Pd loading only 42 mg of catalysts were employed in the Suzuki reaction between 160 mmol of 4‐bromotoluene and 180 mmol of phenylboronic acid. No loss in activity was observed.     

Palladium/Phosphite or Phosphate Catalyzed Oxidative Coupling of Arylboronic Acids with Alkynes to Produce 1,4‐Diaryl‐1,3‐butadienes

The intermolecular oxidative coupling of arylboronic acids with internal alkynes efficiently proceeds in a 2:2 manner in the presence of palladium acetate, a triaryl phosphite or phosphate, and silver carbonate as catalyst, ligand, and oxidant, respectively, to produce the corresponding 1,4‐diaryl‐1,3‐butadiene derivatives.     

Sulfonic Acid‐Catalyzed Autoxidative Carbon‐Carbon Coupling Reaction under Elevated Partial Pressure of Oxygen

An aerobic organocatalytic oxidative C C bond formation reaction of benzylic C H bonds with various C‐nucleophiles is described. The coupling reaction proceeds by simply stirring the substrates under elevated partial pressure of oxygen in the presence of a sulfonic acid catalyst at room temperature. Elevation of the pressure enables the reaction of a broad scope of nucleophile substrates otherwise showing poor reactivity at ambient pressure. The benzylic C H bonds of xanthene, acridanes, isochromane and related heterocycles could be functionalized with nucleophiles including ketones, 1,3‐dicarbonyl compounds and aldehydes. Electron‐rich arenes could be utilized as nucleophiles at elevated temperatures. The reactions are believed to proceed via autoxidation of the benzylic C H bonds to the hydroperoxides and subsequent nucleophilic substitution catalyzed by sulfonic acids.     

Synthesis of 1,4‐Diarylbuta‐1,3‐dienes through Palladium‐ Catalyzed Decarboxylative Coupling of Unsaturated Carboxylic Acids

It has been found that readily available hydroxylated cinnamic acids such as ferulic acid undergo palladium‐catalyzed decarboxylative coupling with aryl iodides and internal alkynes in a 1:1:1 manner to produce 1,4‐diarylbuta‐1,3‐dienes. The butadiene synthesis has also been achieved through the coupling of aryl halides with dienoic acids. Some of the products exhibit solid‐state fluorescence.     

Nickel‐Catalyzed Suzuki–Miyaura Coupling of a Tertiary Iodocyclopropane with Wide Boronic Acid Substrate Scope: Coupling Reaction Outcome Depends on Radical Species Stability

We describe a nickel‐catalyzed Suzuki–Miyaura arylation of a tertiary iodocyclopropane with arylboronic acids; this is an efficient and convergent strategy for providing various enantioenriched arylcyclopropanes with a quaternary stereogenic center. This is the first metal‐catalyzed coupling between a tertiary alkyl electrophile and a wide range of aromatics, including heteroaromatics. We found that the outcome of the Ni‐catalyzed coupling with halides as electrophiles was dependent on the stability of the radical species formed during the reaction. The use of tert‐butyl alcohol (t‐BuOH) as the reaction solvent was very effective, because of its stability under the radical‐generating reaction conditions.

     

The Actual Active Species of Sulfur‐Modified Gold‐Supported Palladium as a Highly Effective Palladium Reservoir in the Suzuki–Miyaura Coupling

The actual active species of the recently developed sulfur‐modified, gold‐supported palladium material, S ‐modified A u‐supported Pd (SAPd), with one of the lowest Pd‐releasing levels and high recyclability in the Suzuki–Miyaura coupling, was investigated. Also, SAPd was found to work repeatedly as an excellent Pd reservoir for liquid‐phase combinatorial synthesis.     

Iron‐Catalyzed Ligand‐Free Carbon‐Selenium (or Tellurium) Coupling of Arylboronic Acids with Diselenides and Ditellurides

Carbon‐selenium and carbon‐tellurium cross‐couplings of arylboronic acids with diselenides and ditellurides have been catalyzed by iron(0), iron(II) chloride or iron(III) chloride without any ligand and additive in the air. The method yields the corresponding unsymmetrical diorgano monoselenides and monotellurides in good to excellent yields, displays a broad substrate scope, and is simple, convenient, effective, economical and environmentally friendly.