Cross-coupling Of Aryl Chlorides Research Articles

Sodium-iodide-promoted nickel-catalyzed C–N cross-coupling of aryl chlorides andN-nucleophiles under visible-light irradiation

Sodium iodide facilitates halogen exchange in single nickel photocatalysis, which is critical to achieve C–N couplings of aryl chlorides and diverse nitrogen nucleophiles under visible-light irradiation in the absence of an exogenous photocatalyst.

Cu/Mn-Catalyzed C–N Cross-Coupling Reaction of Aryl Chlorides and Amines Promoted by a Polyamidoamine Dendrimer

AbstractA bimetallic catalytic combination of Mn(OAc)2 and Cu(OAc)2 was found to be significantly effective for the Buchwald-type C–N cross-coupling of aryl chlorides and amines. The reaction was markedly affected by the presence of a poly(amidoamine) dendrimer as a promoter that also possesses the advantages of being stable, nontoxic, biocompatible, nonimmunogenic, and acting as a soluble support for the transition-metal complex. Although, manganese is cheap and environmentally benign, it has not been fully exploited, due to its low intrinsic catalytic activity. Here, the catalytic potential of manganese was drastically increased by the presence of another metal salt, Cu(OAc)2. In the bimetallic composition, Mn significantly influenced the activity and selectivity, and played a vital role in catalysis. We have developed a novel, green, and economical procedure for Buchwald-type C–N cross-coupling of aryl chlorides and amines. This coupling method works under aerobic and solvent-free conditions and gives excellent yields of value-added N-arylated or N-alkylated products.

Iron-Catalyzed Cross-Coupling Reactions of Alkyl Grignards with Aryl Chlorobenzenesulfonates.

Aryl sulfonate esters are versatile synthetic intermediates in organic chemistry as well as attractive architectures due to their bioactive properties. Herein, we report the synthesis of alkyl-substituted benzenesulfonate esters by iron-catalyzed C(sp2)–C(sp3) cross-coupling of Grignard reagents with aryl chlorides. The method operates using an environmentally benign and sustainable iron catalytic system, employing benign urea ligands. A broad range of chlorobenzenesulfonates as well as challenging alkyl organometallics containing β-hydrogens are compatible with these conditions, affording alkylated products in high to excellent yields. The study reveals that aryl sulfonate esters are the most reactive activating groups for iron-catalyzed alkylative C(sp2)–C(sp3) cross-coupling of aryl chlorides with Grignard reagents.

Low-Temperature Nickel-Catalyzed C-N Cross-Coupling via Kinetic Resolution Enabled by a Bulky and Flexible Chiral N-Heterocyclic Carbene Ligand.

The transition-metal-catalyzed C-N cross-coupling has revolutionized the construction of amines. Despite the innovations of multiple generations of ligands to modulate the reactivity of the metal center, ligands for the low-temperature enantioselective amination of aryl halides remain a coveted target of catalyst engineering. Designs that promote one elementary reaction often create bottlenecks at other steps. We here report an unprecedented low-temperature (as low as -50 °C), enantioselective Ni-catalyzed C-N cross-coupling of aryl chlorides with sterically hindered secondary amines via a kinetic resolution process (s factor up to >300). A bulky yet flexible chiral N-heterocyclic carbene (NHC) ligand is leveraged to drive both oxidative addition and reductive elimination with low barriers and control the enantioselectivity. Computational studies indicate that the rotations of multiple σ-bonds on the C2 -symmetric chiral ligand adapt to the changing needs of catalytic processes. We expect this design would be widely applicable to diverse transition states to achieve other challenging metal-catalyzed asymmetric cross-coupling reactions.

N-Butylpyrrolidone (NBP) as a non-toxic substitute for NMP in iron-catalyzed C(sp2)–C(sp3) cross-coupling of aryl chlorides

Although iron catalyzed cross-couplings show extraordinary promise in reducing the environmental impact of more toxic metals, one of the main challenges is the use of reprotoxic NMP (NMP = N-methylpyrrolidone) as the key ligand.

Cp*Co(iii) and Cu(OAc)2 bimetallic catalysis for Buchwald-type C–N cross coupling of aryl chlorides and amines under base, inert gas & solvent-free conditions

A strategy involving bimetallic catalysis which requires a combination of Cp*Co(CO)I2 and Cu(OAc)2 was used to perform Buchwald-type C–N coupling reactions of aryl chlorides with amines.

Nickel-Catalyzed Cross-Coupling of Aryl Chlorides with Organolithiums

Nickel-Catalyzed Cross-Coupling of Aryl Chlorides with Organolithiums

Iron-Catalyzed Cross Coupling of Aryl Chlorides with Alkyl Grignard Reagents: Synthetic Scope and FeII/FeIV Mechanism Supported by X-ray Absorption Spectroscopy and Density Functional Theory Calculations

Abstract A combination of iron(III) fluoride and 1,3-bis(2,6-diisopropylphenyl)imidazolin-2-ylidene (SIPr) catalyzes the high-yielding cross coupling of an electron-rich aryl chloride with an alkyl Grignard reagent, which cannot be attained using other iron catalysts. A variety of alkoxy- or amino-substituted aryl chlorides can be cross-coupled with various alkyl Grignard reagents regardless of the presence or absence of β-hydrogens in the alkyl group. A radical probe experiment using 1-(but-3-enyl)-2-chlorobenzene does not afford the corresponding cyclization product, therefore excluding the intermediacy of radical species. Solution-phase X-ray absorption spectroscopy (XAS) analysis, with the help of density functional theory (DFT) calculations, indicates the formation of a high-spin (S = 2) heteroleptic difluorido organoferrate(II), [MgX][FeIIF2(SIPr)(Me/alkyl)], in the reaction mixture. DFT calculations also support a feasible reaction pathway, including the formation of a difluorido organoferrate(II) intermediate which undergoes a novel Lewis acid-assisted oxidative addition to form a neutral organoiron(IV) intermediate, which leads to an FeII/FeIV catalytic cycle, where the fluorido ligand and the magnesium ion play key roles.

Palladium-Catalyzed Thiomethylation via a Three-Component Cross-Coupling Strategy.

In this report, the combination of masked inorganic sulfur and dimethyl carbonate was designed to achieve thiomethylated cross coupling of aryl chlorides. Remarkably, this powerful strategy realized thiomethylation of nucleosides bearing unprotected ribose, chloride-containing pharmaceuticals with late-stage coupling, and herbicides possessing multiple heteroatoms and steric hindrance. Moreover, this protocol is practically amenable to multigram-scale synthesis with a lower catalysis loading and a higher yield.

Highly active NHC–Pd(ii) complexes for cross coupling of aryl chlorides and arylboronic acids: an investigation of the effect of remote bulky groups

Highly active palladium(ii) complexes bearing remote bulky ligands for Suzuki–Miyaura coupling reactions under mild conditions are reported.

Acetylacetonato-based pincer-type nickel(ii) complexes: synthesis and catalysis in cross-couplings of aryl chlorides with aryl Grignard reagents.

In this work, three different types of acetylacetonato-based pincer-type nickel(ii) complexes (2) were prepared. Complex 2a possessed the tridentate ONN ligand, which was constructed by the condensation reaction of acetylacetone with N,N-diethylethylenediamine. Complex 2b contained the PPh2 donor group in contrast to the NEt2 group in 2a, i.e., an ONP ligand framework. Complex 2c was composed of the NNN ligand, which was prepared by the reaction of 4-((2,4,6-trimethylphenyl)amino)pent-3-en-2-one with N,N-diethylethylenediamine. In addition to X-ray diffraction analysis, these complexes were characterized spectroscopically. Their catalytic activity for a cross-coupling reaction of aryl halides with aryl Grignard reagents was also evaluated. Among these complexes, 2b acted as an effective catalyst for the cross-coupling reaction using aryl chlorides as electrophiles. The electronic properties of these Ni(ii) complexes were investigated by cyclic voltammetry and density functional theory calculations.

Photoinduced C-C Cross-Coupling of Aryl Chlorides and Inert Arenes

Here we report a facile, efficient, and catalyst-free method to realize C-C cross-coupling of aryl chlorides and inert arenes under UV light irradiation. The aryl radical upon homolytic cleavage of C-Cl bond initiated the nucleophilic substitution reaction with inert arenes to give biaryl products. This mild reaction mode can also be applied to other synthetic reactions, such as the construction of C-N bonds and trifluoromethylated compounds.

Mono- and Dinuclear Pincer Nickel Catalyzed Activation and Transformation of C–Cl, C–N, and C–O Bonds

Condensation of 2-NH2C6H4P(Et)Ph (2) with pyrrole-2-carboxaldehyde generated 2-(C4H4N-2′-CH═N)C6H4P(Et)Ph (3). Treatment of 3 with NaH and followed by (DME)NiX2 (X = Cl, Br) afforded mononuclear pincer nickel complexes [Ni{2-(C4H3N-2′-CH═N)C6H4P(Et)Ph}X] (4a, X = Cl; 4b, X = Br). Reaction of [2-NH2C6H4P(Ph)]2(CH2)n (5a, n = 3; 5b, n = 4) with pyrrole-2-carboxaldehyde or 5-tert-butyl-1H-pyrrole-2-carbaldehyde formed [2-(C4H4N-2′-CH═N)C6H4P(Ph)]2(CH2)n (6a, n = 3; 6b, n = 4) and [2-(5′-tBuC4H3N-2′-CH═N)C6H4P(Ph)]2(CH2)4 (6c). Respective treatment of 6a–c with NaH followed by (DME)NiX2 (X = Cl, Br) gave the dinuclear nickel complexes [Ni{2-(5′-RC4H2N-2′-CH═N)C6H4P(Ph)}X]2(CH2)n (7a, R = H, X = Cl, n = 3; 7b, R = H, X = Cl, n = 4; 7c, R = H, X = Br, n = 4; 7d, R = tBu, X = Cl, n = 4). Catalysis of the complexes for the activation and transformation of C–Cl, C–N, and C–O bonds was evaluated. Complex 7c exhibited excellent catalytic activity in the cross-coupling of aryl chlorides or aryltrimethylammonium iodides with arylzinc reagents as well as of aryl sulfamates with aryl Grignard reagents. The dinuclear nickel complexes 7b–d showed higher catalytic activity than the mononuclear complexes in each type of reaction.

ChemInform Abstract: Catalytic Direct Cross‐Coupling of Organolithium Compounds with Aryl Chlorides.

AbstractDirect cross coupling of aryl chlorides with aryllithium reagents is achieved under mild conditions using the commercially available Pd2(dba)3/XPhos catalyst system or the air‐stable Pd‐PEPPSI‐IPent (PPI) catalyst.

Directional properties of fluorenylidene moieties in unsymmetrically substituted N-heterocyclic carbenes. Unexpected CH activation of a methylfluorenyl group with palladium. Use in palladium catalysed Suzuki-Miyaura cross coupling of aryl chlorides.

Benzimidazolium salts having their two nitrogen atoms substituted by different 9-alkylfluorenyl groups ( and , alkyl(1)/alkyl(2) = Me/Et, Me/Pr, Me/n-Bu, Me/i-Pr, Me/Bn, Me/CH2SMe have been synthesised in high yields in two or three steps from N,N'-bis(9H-fluoren-9-ylidene)benzene-1,2-diamine (). The imidazolium salts were converted readily into the corresponding PEPPSI-type palladium complexes (PEPPSI = pyridine-enhanced precatalyst preparation stabilisation and initiation), while reaction of the methylthioether-substituted salt with PdCl2/K2CO3/pyridine afforded the palladacycle resulting from metallation of the methyl group attached to the fluorenylidene moiety. NMR and X-ray diffraction studies revealed that the carbene ligands in behave as clamp-like ligands, the resulting metal confinement arising from a combination of the orientational properties of the fluorenylidene moieties that push the alkyl groups towards the metal centre and attractive anagostic interactions involving CH2(fluorenyl) groups. Complexes were assessed in Suzuki-Miyaura cross-coupling reactions. Like their symmetrical analogues they displayed high activity in the coupling of phenyl boronic acid with p-tolylchloride but their performance remained slightly inferior to that of the related, symmetrical Et/Et complex .

Mild and Rapid Pd‐Catalyzed Cross‐Coupling with Hydrazine in Continuous Flow: Application to the Synthesis of Functionalized Heterocycles

Minimizing risk: The synthesis of arylhydrazines through CN cross-coupling of aryl chlorides with hydrazine is described. Through the use of continuous flow, the hazards associated with the use of hydrazine in the presence of transition metals are decreased. In addition, multistep flow sequences have also been developed for the generation of functionalized heterocycles utilizing the arylhydrazine intermediates.

Phthalide: a direct building-block towards P,O and P,N hemilabile ligands. Application in the palladium-catalysed Suzuki–Miyaura cross-coupling of aryl chlorides

The direct synthesis of new hemilabile ligands from the economical, readily available lactone phthalide is described. Pd-complexes of one such ligand were found highly effective in general Suzuki-Miyaura cross-coupling reactions, including deactivated and hindered aryl chlorides.

ChemInform Abstract: NiCl2(PMe3)2‐Catalyzed Borylation of Aryl Chlorides.

AbstractThe reaction uses metal 2,2,2‐trifluoroethoxide as a unique base, generated in situ.

Abnormal N-heterocyclic carbene palladium complex: living catalyst for activation of aryl chlorides in Suzuki–Miyaura cross coupling

Palladium complexes bearing abnormal N-heterocyclic carbene were used as catalysts in Suzuki-Miyaura cross coupling of aryl chlorides at 25 °C. The catalyst remained active for 10 successive catalytic runs and can activate 4-chlorotoluene at 25 °C with 0.01 mol% catalyst loading resulting in a TON of 9500 within 6 h.

Corrigendum: Fe3O4@mesoporouspolyaniline: A Highly Efficient and Magnetically Separable Catalyst for Cross-Coupling of Aryl Chlorides and Phenols

A high surface, magnetic Fe 3 O 4 @mesoporouspolyaniline core-shell nanocomposite was synthesized from magnetic iron oxide (Fe 3 O 4 ) nanoparticles and mesoporouspolyaniline (mPANI). The novel porous magnetic Fe 3 O 4 was obtained by solvothermal method under sealed pressure reactor at high temperature to achieve high surface area. The mesoporouspolyaniline shell was synthesized by in situ surface polymerization onto porous magnetic Fe 3 O 4 in the presence of polyvinylpyrrolidone (PVP) and sodium dodecylbenzenesulfonate (SDBS), as a linker and structure-directing agent, through 'blackberry nanostructures' assembly. The material composition, stoichiometric ratio and reaction conditions play vital roles in the synthesis of these nanostructures as confirmed by variety of characterization techniques. The role of the mesoporouspolyaniline shell is to stabilize the porous magnetic Fe 3 O 4 nanoparticles, and provide direct access to the core Fe 3 O 4 nanoparticles. The catalytic activity of magnetic Fe 3 O 4 @mesoporousPANI nanocomposite was evaluated in the cross-coupling of aryl chlorides and phenols.