Efficient synthesis of 1,3,5-trisubstituted benzenes via three Pd-mediated carbon-sulfur, carbon-nitrogen and carbon-carbon bond formation reactions

An efficient synthesis of 1,3,5-trisubstituted benzenes via a sequential Pd-mediated carbon-sulfur, carbon-nitrogen, and carbon-carbon bond formation reactions is reported. Selective amidation and sulfonamidation reactions are accomplished via Pd-catalyzed reactions between aryl chlorides and an acetamide or a methanesulfonamide.     

Tandem Photoredox Catalysis: Enabling Carbonylative Amidation of Aryl and Alkylhalides

We report a new visible-light-mediated carbonylative amidation of aryl, heteroaryl, and alkyl halides. A tandem catalytic cycle of [Ir(ppy)₂(dtb-bpy)]⁺ generates a potent iridium photoreductant through a second catalytic cycle in the presence of DIPEA, which productively engages aryl bromides, iodides, and even chlorides as well as primary, secondary, and tertiary alkyl iodides. The versatile in situ generated catalyst is compatible with aliphatic and aromatic amines, shows high functional-group tolerance, and enables the late-stage amidation of complex natural products.     

A general and efficient copper catalyst for the amidation of aryl halides

An experimentally simple and inexpensive catalyst system was developed for the amidation of aryl halides by using 0.2-10 mol % of CuI, 5-20 mol % of a 1,2-diamine ligand, and K(3)PO(4), K(2)CO(3), or Cs(2)CO(3) as base. Catalyst systems based on N,N'-dimethylethylenediamine or trans-N,N'-dimethyl-1,2-cyclohexanediamine were found to be the most active even though several other 1,2-diamine ligands could be used in the easiest cases. Aryl iodides, bromides, and in some cases even aryl chlorides can be efficiently amidated. A variety of functional groups are tolerated in the reaction, including many that are not compatible with Pd-catalyzed amidation or amination methodology.     

9-fluorenylphosphines for the Pd-catalyzed sonogashira, suzuki, and Buchwald-Hartwig coupling reactions in organic solvents and water

The lithiation/alkylation of fluorene leads to various 9-alkyl-fluorenes (alkyl=Me, Et, iPr, -Pr, -C18H25) in>95% yields, for which lithiation and reaction with R2PCl (R=Cy, iPr, tBu) generates 9-alkyl, 9-PR2-fluorenes which constitute electron-rich and bulky phosphine ligands. The in-situ-formed palladium-phosphine complexes ([Na2PdCl4], phosphonium salt, base, substrates) were tested in the Sonogashira, Suzuki, and Buchwald-Hartwig reactions of aryl chlorides and aryl bromides in organic solvents. The Sonogashira coupling of aryl chlorides at 100-120 degrees C leads to>90% yields with 1 mol% of Pd catalyst. The Suzuki coupling of aryl chlorides typically requires 0.05 mol% of Pd catalyst at 100 degrees C in dioxane for quantitative product formation. To carry out "green" cross-coupling reactions in water, 9-ethylfluorenyldicyclohexylphosphine was reacted in sulphuric acid to generate the respective 2-sulfonated phosphonium salt. The Suzuki coupling of activated aryl chlorides by using this water-soluble catalyst requires only 0.01 mol% of Pd catalyst, while a wide range of aryl chlorides can be quantitatively converted into the respective coupling products by using 0.1-0.5 mol% of catalyst in pure water at 100 degrees C. Difficult substrate combinations, such as naphthylboronic acid or 3-pyridylboronic acid and aryl chlorides are coupled at 100 degrees C by using 0.1-0.5 mol% of catalyst in pure water to obtain the respective N-heterocycles in quantitative yields. The copper-free aqueous Sonogashira coupling of aryl bromides generates the respective tolane derivatives in>95% yield.     

Rapid access to oxindoles by the combined use of an Ugi four-component reaction and a microwave-assisted intramolecular Buchwald-Hartwig amidation reaction

A two-step sequence involving an Ugi four-component reaction (Ugi-4CR) and a palladium-catalyzed intramolecular amidation of aryl iodide has been developed for rapid access to functionalized oxindole (1). Microwave heating was used to accelerate and to improve the efficiency of the intramolecular Buchwald-Hartwig reaction.     

One-pot Pd/C catalysed 'domino' HALEX and Sonogashira reactions: a ligand- and Cu-free alternative

The advantages of combining heterogeneous catalysis and aryl chloride substrates for cross-coupling are introduced. A heterogeneous Pd/C catalyst is used for activating aryl bromides and electron withdrawing aryl chlorides via a one-pot 'domino' HALEX-Sonogashira reaction. No ligand or co-catalyst is required, and the cross-coupling products are obtained in moderate to good yields. The influence of the solvent, base, iodide source and catalyst is evaluated. The catalyst is reusable for at least six consecutive reaction cycles. A variation on this reaction using catalytic amounts of KI is also proposed.     

High turnover number and rapid, room-temperature amination of chloroarenes using saturated carbene ligands

[equation--see text] A catalytic system for the mild amination of aryl chlorides is described. This system consists of a Pd(0) precursor and a dihydroimidazoline carbene ligand, which is generated in situ from its protonated tetrafluoroborate salt (2). Using this catalyst, aryl and heteroaryl chlorides react with secondary amines and anilines within hours at room temperature. Turnover numbers as high as 5000 are obtained at elevated temperatures for reaction of morpholine with an unactivated aryl chloride.     

Pd-catalyzed amidation of aryl chlorides using monodentate biaryl phosphine ligands: a kinetic, computational, and synthetic investigation

We present results on the amidation of aryl halides and sulfonates utilizing a monodentate biaryl phosphine-Pd catalyst. Our results are in accord with a previous report that suggests that the formation of kappa(2)-amidate complexes is deleterious to the effectiveness of a catalyst for this transformation and that their formation can be prevented by the use of appropriate bidentate ligands. We now provide data that suggest that the use of certain monodentate ligands can also prevent the formation of the kappa(2)-amidate complexes and thereby generate more stable catalysts for the amination of aryl chlorides. Furthermore, computational studies shed light on the importance of the key feature(s) of the biaryl phosphines (a methyl group ortho to the phosphorus center) that enable the coupling to occur. The use of ligands that possess a methyl group ortho to the phosphorus center allows a variety of aryl and heteroaryl chlorides with various amides to be coupled in high yield.     

N-hydroxyimides as efficient ligands for the copper-catalyzed N-arylation of pyrrole, imidazole, and indole

An experimentally simple, efficient, and inexpensive catalyst system was developed for the N-arylation of pyrroles, indoles, and imidazole with aryl and heteroaryl iodides, bromides, and chlorides by applying CuI as catalyst, N-hydroxysuccinimide (L1), N-hydroxymaleimide (L2), or N-hydroxyphthalimide (L3) as ligand, CH3ONa as base, and DMSO as solvent. A variety of functional groups are tolerated in the reaction, including those that are not compatible with Pd-catalyzed amidation methodology.     

Suzuki cross-coupling reactions of aryl halides in phosphonium salt ionic liquid under mild conditions

The Suzuki cross-coupling of aryl boronic acids with aryl halides, including aryl chlorides, proceeds in the phosphonium salt ionic liquid tetradecyltrihexylphosphonium chloride under mild conditions.     

Microwave-assisted Pd(OH)2-catalyzed direct C−H arylation of free-(NH2) adenines with aryl halides

A direct C−H arylation of free-(NH₂) adenines using Pd(OH)₂/C (Pearlman’s catalyst) and stoichiometric amount of copper iodide under ligandless microwave activation is described. This new protocol proved to be highly effective to synthesize a variety of 8-aryladenine derivatives 3 without prior protection of the amino substituent. The arylation reaction takes place rapidly within few minutes and allows the coupling to proceed regioselectively at the 8-position with a wide range of aryl halides including aryl iodides, bromides and the less reactive aryl chlorides.     

Suzuki-Miyaura cross-coupling of aryl and alkyl halides using palladium/imidazolium salt protocols

A simple new protocol for the high yielding Suzuki-Miyaura cross-couplings of aryl chlorides with aryl boronic acids using a palladium/imidazolium salt catalytic system is presented. The first examples of a palladium/imidazolium salt protocol for sp³-sp³ Suzuki-Miyaura couplings of alkyl halides are also disclosed.     

Annulation Reactions of Ortho-Chloromethyl Aryl Cuprates

Formation of o-chloromethyl aryl cuprates via halogen-metal exchange of 2-iodobenzyl chlorides with n-butyllithium provides a cuprate that may be added to unhindered enones and ammonium salt 5 giving intermediates suitable for subsequent annulation reactions.     

Rapid and Efficient Copper‐Catalyzed Finkelstein Reaction of (Hetero)Aromatics under Continuous‐Flow Conditions

A general, rapid, and efficient method for the copper‐catalyzed Finkelstein reaction of (hetero)aromatics has been developed using continuous flow to generate a variety of aryl iodides. The described method can tolerate a broad spectrum of functional groups, including N‐H and O‐H groups. Additionally, in lieu of isolation, the aryl iodide solutions were used in two distinct multistep continuous‐flow processes (amidation and Mg–I exchange/nucleophilic addition) to demonstrate the flexibility of this method.     

Fe‐Catalyzed Cross‐Coupling Reaction of Vinylic Ethers with Aryl Grignard Reagents

Iron‐catalyzed cross‐coupling reaction of vinylic ethers with aryl Grignard reagents is described. The reaction proceeded at room temperature with catalytic amounts of an iron salt without the aid of costly ligands and additives. In this catalytic system, vinylic C?O bonds were preferentially cleaved over aromatic C?O bonds of aryl ethers or aryl sulfonates.     

A copper-free Sonogashira reaction using a Pd/MgLa mixed oxide

A new Pd/MgLa mixed oxide is found to be an efficient catalyst for the Sonogashira reaction of aryl iodides, bromides and even activated chlorides in the absence of a copper salt.     

Palladium‐catalysed reductive carbonylation of aryl halides with iron pentacarbonyl for synthesis of aromatic aldehydes and deuterated aldehydes

The first use of iron pentacarbonyl is described for the novel and efficient conversion of aryl iodides, bromides and chlorides into their corresponding aryl aldehydes and/or aryl deuterated aldehydes. The reaction is catalysed with Pd(0) in aqueous N,N‐dimethylformamide at atmospheric pressure. In this protocol, neither gaseous hydrogen nor any reducing agent is required for the formation of the carbonylated product. The reaction can be performed without a P(III) ligand for aryl iodides; however, employing a P(III) ligand is necessary to perform the reaction with aryl bromides and chlorides. Copyright © 2015 John Wiley & Sons, Ltd.     

A versatile catalyst for Heck reactions of aryl chlorides and aryl bromides under mild conditions.

In the presence of Cy2NMe, Pd/P(t-Bu)3 serves as an exceptionally mild and versatile catalyst for Heck reactions of aryl chlorides and bromides. A sterically and electronically diverse array of aryl bromides, as well as activated aryl chlorides, couple with a range of mono- and disubstituted olefins at room temperature, furnishing the arylated product with high E/Z stereoselection. The corresponding reactions of a broad spectrum of electron-neutral and electron-rich aryl chlorides proceed at elevated temperature, also with high selectivity. In terms of scope and mildness, Pd/P(t-Bu)3/Cy2NMe represents an advance over previously reported catalysts for these Heck coupling processes.     

Catechol violet as new, efficient, and versatile ligand for Cu(I)-catalyzed C-S coupling reactions

Combination of CuI and Catechol violet (CuI-CV) was employed as catalyst for the first time in the C-S coupling reaction of a wide variety of aromatic halides, such as aryl iodides, bromo pyridines, activated aryl chlorides, and vinyl iodide with thiols to afford the corresponding thioethers in good to excellent yields. Broad range of functional group tolerance present in both the coupling partners has been observed in this reaction protocol.     

Benzimidazolin‐2‐ylidene–palladium‐catalysed coupling reactions of aryl halides

The in situ prepared three‐component system Pd(OAc)₂–1,3‐dialkylbenzimidazolium chlorides ( 2a – f ) and Cs₂CO₃ catalyses, quantitatively, the Suzuki cross‐coupling of deactivated aryl chlorides and Heck coupling reactions of aryl bromide and iodide substrates. The 1,3‐dialkylbenzimidazolium salts ( 2a – f ) were characterized by conventional spectroscopic methods and elemental analysis. Copyright © 2005 John Wiley & Sons, Ltd.