Coupling Of Aryl Iodides Research Articles

Norbornene‐Mediated Palladium‐Catalysed Domino‐Type Catellani Reaction: an Efficient and Regiospecific Acylation/Suzuki Coupling of Aryl Iodides

The Catellani reaction is a domino reaction catalysed by palladium/norbornene. It can be used for the synthesis of a range of aromatic compounds in one step, and is of great interest in the synthesis of natural products and drugs. In this paper, we report a palladium/norbornene‐catalysed ortho‐acylation/ipso‐Suzuki coupling reaction of aryl iodides using acyl chlorides as acylating agents and arylboronic acids as quenching reagents. The reactions were carried out using readily available starting materials, and ortho‐aryl benzophenones were obtained in moderate to good yields. Compared with previous Catellani reactions, this reaction has a wider substrate scope, shorter reaction times, and higher yields of the target compounds.

Nuances in Fundamental Suzuki–Miyaura Cross-Couplings Employing [Pd(PPh3)4]: Poor Reactivity of Aryl Iodides at Lower Temperatures

We have explored fundamental Pd-catalyzed Csp2–Csp2 Suzuki–Miyaura cross-couplings of aryl iodides (Ar–I) employing “classical” Pd/PPh3 catalyst systems. Surprisingly, we observed particularly inefficient couplings of these ostensibly reactive electrophiles in a range of conventional solvent mixtures at lower temperatures (∼50 °C), which was in stark contrast to analogous reactions featuring the equivalent aryl bromides. This feature of well-established Pd/PPh3-mediated Suzuki–Miyaura reactions has received scant attention in the literature. Most significantly, our studies suggest that the inefficient coupling of aryl iodides at lower temperatures derives from the unexpectedly poor turnover of the key on-cycle intermediate trans-[Pd(PPh3)2(Ar)(I)] (or related PdII–I species) in the presence of PPh3.

DBU-Promoted Cu(OAc)•H2O-Catalysed Coupling Reactions of Aryl Iodides and Sodium Azide

An efficient and simple protocol for the synthesis of aryl azides by the coupling of aryl iodides with sodium azide, in good to excellent yields in DMSO at 95 °C under catalysis by Cu(OAc)2-H2O and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU), has been established. The optimised loadings of Cu(OAc)2-H2O and DBU were 10 mol% and 15 mol% respectively.

Sonogashira-type cross-coupling reactions catalyzed by copper complexes of pincer N-heterocyclic carbenes

Copper complexes of N-heterocyclic carbenes (NHC) have recently received great attention in catalysis, however, the application scope has been limited to neutral complexes bearing monodentate ligands. Herein, we report the synthesis and full characterization of a cationic Cu-pincer bis(NHC) complex with bulky tert-butyl wingtips that serves as catalyst for the coupling of aryl iodides and phenylacetylene, alongside its analogs with small alkyl substituents. Unlike other copper catalysts that require an inert atmosphere to prevent alkyne homocoupling, a competing side reaction to Sonogashira reaction, the Cu-pincer bis(NHC) complexes provide good to excellent cross-coupling yields in air. Interestingly, the reaction under argon affords substantially reduced cross-coupling, indicative of the oxygen involvement and its facilitating effect in the mechanism. In our controlled studies, the air-assisted cross-coupling reaction came to a complete stop when using a radical trap, suggesting the presence of a radical in the mechanism. Examining the reaction of Cu-pincer bis(NHC) complexes with oxygen via UV–vis spectroscopy reveals a dark green chromophore formation at −40 °C with strong absorbance (ε > 400 M−1cm−1) at 460 nm and 500 nm, likely due to a high-valent copper-oxygen adduct.

Meta-C-H arylation of fluoroarenes via traceless directing group relay strategy.

While several methods for the ortho selective arylation of fluoroarenes, meta-functionalisation has never been achieved. We report a new methodology, based on the traceless directing group relay concept, leading to the first meta-selective (hetero)arylation of fluoroarenes. In this strategy, CO2 is introduced as a transient directing group, to control a Pd-catalysed arylation meta to the fluoro functionality, prior to its release in a sequential, one-pot fashion. This method has shown compatibility with a number of functional groups and substitution patterns in both the fluoroarene core and aryl iodide coupling partners, and proceeds with complete meta-selectivity and mono vs. bis-arylation selectivity.

Tert-Butoxide-promoted Coupling of Aryl Iodides with Arenes Using Di-tert-butyl Hyponitrite as an Initiator

The coupling reaction of aryl iodides with arenes was found to proceed under mild conditions to give biaryls through a homolytic aromatic substitution mechanism, using potassium tert-butoxide and di-tert-butyl hyponitrite as a stoichiometric promoter and a radical initiator, respectively.

Carbonylative Sonogashira Coupling of Aryl Iodides with Terminal Alkynes Catalyzed by Palladium Nanoparticles

A convenient and efficient method for the synthesis of α,β‐alkynyl ketones from the three‐component coupling of aryl iodides, terminal alkynes, and carbon monoxide (carbonylative Sonogashira coupling reaction) is successfully developed. The carbonylative Sonogashira coupling reaction proceeded smoothly under mild conditions in the presence of palladium nanoparticles to produce the corresponding α,β‐alkynyl ketones in good to excellent yields.

Development of highly electron-deficient and less sterically-hindered phosphine ligands possessing 1,3,5-triazinyl groups

Highly electron-deficient and less sterically-hindered phosphine ligands with two or three 1,3,5-triazinyl groups on the phosphorus atoms have been synthesized and examined in transition metal-catalyzed reactions for the first time. Due to the lack of any hydrogens or substituents at ortho-positions of the 1,3,5-triazine towards the phosphorous atom, it is considered that the steric hindrance of the tris(triazinyl)phosphine ligand to a metal center is least among triarylphosphine ligands. In the Stille coupling of aryl iodides, these electron-poor phosphine ligands provided good product yields compared to hitherto well-known phosphine ligands.

Copper mediated coupling of 2-(piperazine)-pyrimidine iodides with aryl thiols using Cu(I)thiophene-2-carboxylate

A copper-mediated synthesis of diaryl sulfides utilizing Cu(I)-thiophene-2-carboxylate (CuTC) is described. We demonstrate the use of CuTC as a soluble, non-basic catalyst in the coupling of aryl iodides and aryl thiols in the synthesis of synthetically advanced diaryl sulfides. This method allows for the successful coupling of challenging substrates including ortho-substituted and heteroaryl iodides and thiols. Additionally, most of the aryl iodide substrates used here contain the privileged piperazine scaffold bound to a pyrimidine, pyridine, or phenyl ring and thus this method allows for the elaboration of complex piperazine scaffolds into molecules of biological interest. The method described here enables the incorporation of late-stage structural diversity into diaryl sulfides containing the piperazine ring, thus enhancing the number and nature of derivatives available for SAR investigation.

Straightforward and Recyclable System for Synthesis of Biaryl Ketones via Carbonylative Coupling Reactions of Aryl Halides with PhB(OH)2 and (EtO)3 PhSi

Solvent-dispersible magnetite (Fe3O4) chitosan-functionalized with methionine was effectively prepared to immobilize Pd(0) with a metal adsorption method. The catalyst was characterized by Transmission Electron Microscopy (TEM), Field emission scanning electron microscopy (FE-SEM), Powder X-ray Diffraction (XRD), Energy Dispersive X-ray spectroscopy (EDX), FT-IR spectra, thermogravimetric analyzer (TGA) and vibrating sample magnetometer (VSM). A variety of biaryl ketones were conveniently synthesized in good to high yields via carbonylative coupling of aryliodides with phenylboronic acid and PhSi(OEt)3 as phenylating reagents in the presence of Mo(CO)6 as a carbon monoxide reagent. Both electron-rich and electron-poor aryl iodides gave diaryl ketones in excellent yields and the catalytic system can be reused up to eight times.

Copper-Catalyzed Hydroarylation of Internal Alkynes: Highly Regio- and Diastereoselective Synthesis of 1,1-Diaryl, Trisubstituted Olefins

The copper-catalyzed hydroarylation of internal, unsymmeric alkynes is presented. Trisubstituted alkenes are obtained as single diastereomers in good to excellent yields and excellent regioselectivities. The scope of the reaction is presented with respect to alkyne and aryl iodide coupling partners. Initial mechanistic experiments indicate a hydrocupration event followed by a two-electron oxidative addition/reductive elimination pathway.

3-Phenothiazinyl propiolates – Fluorescent electrophores by Sonogashira coupling of ethyl propiolate

Fluorescent ethyl 3-phenothiazinyl propiolates with reversible Nernstian oxidation potentials were efficiently synthesized by an improved Sonogashira coupling of aryl iodides and ethyl propiolate. The versatility of this modified alkynylation was illustrated by 13 ethyl 3-arylpropiolates in mostly excellent yields with a broad substrate scope. In addition to reversible one-electron oxidations, the title compounds reveal large Stokes shifts, high fluorescence quantum yields, and solvatochromic emission. The photophysical characteristics were corroborated and rationalized by DFT and TD-DFT calculations.

Carbonylations with CO2 as the CO Source and Reactivity Modifier.

A CO surrogate: In two recent studies, CO2 has not only been applied as a CO source in the hydroformylation of alkenes and the carbonylative Hiyama-Denmark coupling of aryl iodides, but more interestingly it also attenuates or improves the reactivity of the reactants.

A green approach for arylation of phenols using iron catalysis in water under aerobic conditions

The first efficient iron-catalyzed coupling of aryl iodides with phenols was developed exclusively with water as solvent. The reaction is performed with low cost and readily available FeCl3·6H2O and DMEDA catalytic system providing diaryl ethers in good to excellent yields. The effectiveness of this reaction was further revealed by compatibility with a wide range of functional groups. Moreover, the procedure is rendered simple as this transformation is carried out in the presence of air. Thus, the protocol represents a facile, economical and eco-friendly procedure to access diaryl ethers.

A polysalen based on polyacylamide stabilized palladium nanoparticle catalyst for efficient carbonylative Sonogashira reaction in aqueous media

Pd nanoparticles immobilized on polysalen based on polyacylamide was synthesized and used for carbonylative Sonogashira coupling of aryl iodides with terminal alkynes to produce α,β-alkynyl ketones in aqueous media.

Palladium-catalyzed Catellani-type couplings using methylating reagents for the synthesis of highly substituted ortho-methyl-arenes and heteroarenes

The incorporation of a methyl group into a small molecule can have a profound impact on its biological activity, pharmacokinetic profile, and physical properties. As part of an ongoing effort to develop novel methods for methylation of small molecule drug candidates, a three-component coupling of aryliodides, O-benzoylamines, and methylboronic acid that proceeds via a Catellani-type mechanism has been developed. The methodology allows for the ortho-amination/ipso-methylation of aryl- and heteroaryliodides with a wide variety of cyclic O-benzoylamines including pyrrolidines, piperidines, piperazines, morpholines, azepines, diazepines, and azocanes in a single step. A preliminary result for an ortho-methylation/ipso-olefination Catellani-type three component-coupling reaction is also described.

ChemInform Abstract: Palladium‐Catalyzed Carbonylative Coupling of Aryl Iodides with an Organocopper Reagent: A Straightforward Procedure for the Synthesis of Aryl Trifluoromethyl Ketones.

AbstractA carbonylation—trifluoromethylation of aryl iodides with a (trifluoromethyl)copper reagent (I) affords aryl trifluoromethyl ketones in good to excellent yields under mild conditions.

ChemInform Abstract: Palladium and Copper Catalyzed Sonogashira Decarboxylative Coupling of Aryl Iodides and Alkynyl Carboxylic Acids.

AbstractEfficient microwave promoted reaction conditions are developed for the decarboxylative Sonogashira coupling of propiolic acids with aryl iodides.

A Highly Efficient and Reusable Palladium(II)/Cationic 2,2'-Bipyridyl-Catalyzed Stille Coupling in Water.

A water-soluble PdCl2(NH3)2/cationic 2,2′-bipyridyl system was found to be a highly efficient catalyst for Stille coupling of aryl iodides and bromides with organostannanes. The coupling reaction was conducted at 110 °C in water, under aerobic conditions, in the presence of NaHCO3 as a base to afford corresponding Stille coupling products in good to high yields. When aryltributylstannanes were employed, the reactions proceeded smoothly under a very low catalyst loading (as little as 0.0001 mol %). After simple extraction, the residual aqueous phase could be reused in subsequent runs, making this Stille coupling economical. In the case of tetramethylstannane, however, a greater catalyst loading (1 mol %) and the use of tetraethylammonium iodide as a phase-transfer agent were required in order to obtain satisfactory yields.

Formation of polyaromatic compounds by coupling of aryl iodides with arylacetylenes in the presence of palladium-based ligand-free catalytic systems

Formation of polyaromatic compounds by coupling of aryl iodides with arylacetylenes in the presence of palladium-based ligand-free catalytic systems