Phosphine‐Free Palladium‐Catalyzed Decarboxylative Coupling of Alkynylcarboxylic Acids with Aryl and Heteroaryl Halides

We herein report the design and development of a carboxyamido/carbene ligand and its Pd‐complex for the decarboxylative coupling of alkynylcarboxylic acids with aryl and heteroaryl halides to afford arylalkynes.     

One‐Pot Double Benzylation of 2‐Substituted Pyridines using Palladium‐Catalyzed Decarboxylative Coupling of sp2 and sp3 Carbons

An efficient and practical decarboxylative double benzylation method for various 2‐picolinic acids has been established by using a bimetallic catalytic system of palladium(II) chloride (PdCl₂) and silver(I) oxide (Ag₂O), which offered a variety of diarylmethane derivatives with moderate to good yields.

     

Iron‐Catalysed sp3–sp3 Cross‐Coupling Reactions of Unactivated Alkyl Halides with Alkyl Grignard Reagents

Iron‐catalysed sp³–sp³ Kumada coupling with primary and secondary alkyl halides (RX) and alkyl Grignard reagents has been achieved in low to good yields depending on the nature of the R group.     

Room Temperature Palladium‐Catalyzed Decarboxylative Acyl/Aroylation using [Fe(III)(EDTA)(η2‐O2)]3− as Oxidant at Biological pH

The purple‐coloured iron peroxo complex [Fe(III)EDTA(η²‐O₂)]³⁻ as a novel reagent system for Pd‐catalyzed decarboxylative ortho‐acylation of acetanilides with α‐oxocarboxylic acids at room temperature in aqueous media has been realized. This reaction provides an effective access to ortho‐acylacetanilides under mild conditions.     

Palladium‐Catalyzed Cross‐Coupling Reaction Using Arylgermanium Sesquioxide

Powdery reagents obtained by complete alkaline hydrolysis of arylgermanium trichlorides were found to undergo the palladium‐catalyzed cross‐coupling reaction with aryl bromides and iodides in good yields. The reaction is performed in an aqueous medium taking sodium hydroxide as an activator. Some base‐sensitive functionalities such as acetyl and trifluoromethyl groups survived the reaction.     

A General and Practical Palladium‐Catalyzed Direct α‐Arylation of Amides with Aryl Halides

An efficient system for the direct catalytic intermolecular α‐arylation of acetamide derivatives with aryl bromides and chlorides is presented. The palladium catalyst is supported by Kwong’s indole‐based phosphine ligand and provides monoarylated amides in up to 95% yield. Excellent chemoselectivities (>10:1) in the mono‐ and diarylation with aryl bromides were achieved by careful selection of bases, solvents, and stoichiometry. Under the coupling conditions, the weakly acidic α‐protons of amides (pK_a up to 35) were reversibly depotonated by lithium tert‐butoxide (LiO‐t‐Bu), sodium tert‐butoxide (NaO‐t‐Bu) or sodium bis(trimethylsilyl)amide [NaN(SiMe₃)₂].

     

Scope and Limitations of Palladium‐Catalyzed Cross‐Coupling Reactions with Organogold Compounds

Five different alkenylgold(I) phosphane complexes were prepared and then investigated in [1,1′‐bis(diphenylphosphino)ferrocene]palladium(II) dichloride‐catalyzed cross‐coupling reactions with different aryl halides, heterocyclic halides, an alkenyl halide, an alkynyl halide, allylic substrates, benzyl bromide and an acid chloride. With regard to the halides, the iodides were highly reactive, bromides or chlorides gave significantly reduced yields or failed, allylic acetates failed, too. The cross‐coupling partners contained a number of different functional groups, while free carboxylic acids did not deliver cross‐coupling products and o,o‐disubstituted arenes failed as well, a broad range of other functional groups like nitro groups, nitrile groups, ester groups, α,β‐unsaturated ester groups and lactones, aldehydes, alkoxy groups, pyridyl groups, thienyl groups, unprotected phenols and anilines, even aryl azides were tolerated. The structures of one alkenylgold(I) species and of four of the cross‐coupling products were proved by crystal structure analyses.     

Handy Protocols using Vinyl Nosylates in Suzuki–Miyaura Cross‐Coupling Reactions

Vinyl nosylates derived from 1,3‐dicarbonyl compounds could be engaged in Suzuki–Myaura cross coupling reactions with aryl‐, vinyl‐ and methylboronic acids or trifluoborate derivatives at room temperature in the presence of 2 mol% of [1,1′‐bis(diphenylphosphino)ferrocene]dichloropalladium(II) [PdCl₂(dppf)]. One‐pot procedures have been set up for practical and efficient nosylation–cross‐coupling reactions. Nosylate, as a cheap novel pseudo‐halide, gives very stable compounds and is very efficient in Suzuki–Myaura cross coupling reactions (21 examples, 44–99%).

     

Catalytic Decarboxylative Cross‐Ketonisation of Aryl‐ and Alkylcarboxylic Acids using Magnetite Nanoparticles

In the presence of catalytic amounts of magnetite nanopowder, mixtures of aromatic and aliphatic carboxylic acids are converted selectively into the corresponding aryl alkyl ketones. As by‐products, only carbon dioxide and water are released. This catalytic cross‐ketonisation allows the regioselective acylation of aromatic systems and, thus, represents a sustainable alternative to Friedel–Crafts acylations.     

Mild and Functional Group Tolerant Method for Tandem Palladium‐Catalyzed Carbocyclization–Coupling of ε‐Acetylenic β‐Ketoesters with Aryl Bromides and Chlorides

We report a new protocol for the annulative difunctionalization of acetylenes via tandem carbocyclization–coupling of ε‐acetylenic β‐ketoesters with aryl and heteroaryl bromides and chlorides catalyzed by the palladium species derived from an air‐ and moisture‐stable palladacyclic precatalyst. In the tandem process, the palladium complex combines appropriate carbophilic Lewis acidity and redox activity to catalyze two mechanistically distinct reactions ‐ nucleophilic addition of the enolate to unactivated alkyne, followed by C C coupling. We found that a broad range of electronically varied aryl and heteroaryl bromides and chlorides underwent this reaction with various ε‐acetylenic β‐ketoesters, providing corresponding substituted vinylidenecyclopentanes in high yield with excellent functional group tolerance.

     

Rhodium‐Catalyzed Cross‐Coupling of Alkenyl Halides with Arylboron Compounds

The rhodium(I)‐catalyzed reaction between arylboronic esters and excess 1,2‐dichloroethene selectively afforded (2‐chlorovinyl)arenes. Double arylation yielding 1,2‐diarylethenes was observed when 1,2‐dibromoethene was reacted with 2.5 equivalents of arylboronic acid.

     

Palladium‐Catalyzed Desulfitative Cross‐Coupling Reaction of Sodium Arylsulfinates with H‐Phosphonate Diesters

A novel and convenient palladium‐catalyzed cross‐coupling reaction of H‐phosphonate diesters with sodium arylsulfinates was developed via desulfitation in the presence of silver carbonate and tetra‐butylammonium chloride. This method is highly efficient and provides a rapid access to a broad spectrum of arylphosphonate diesters in good to excellent yields.

     

A New Hybrid Phosphine Ligand for Palladium‐Catalyzed Amination of Aryl Halides

A new hybrid phosphine was designed. The phosphine combines two common structural characteristics found among the effective phosphine ligands reported recently, namely, three tert‐alkyl substituents binding to the phosphorus and an aryl group at an appropriate position. A hybrid phospine/palladium system is versatile and effective for the coupling reaction of various aryl halides with primary and secondary amines including carbazole.     

Synthesis of Dienes by Palladium‐Catalyzed Couplings of Tosylhydrazones with Aryl and Alkenyl Halides

Two different combinations of coupling partners can be employed for the synthesis of conjugated dienes by palladium‐catalyzed cross‐coupling with tosylhydrazones: α,β‐unsaturated ketone and aryl halide or alkenyl halide and non‐conjugated tosylhydrazone. Depending on the substrate, a vinylogous hydride elimination is responsible for the formation of the final dienes.     

A General Synthesis of α‐Trifluoromethylstyrenes through Palladium‐Catalyzed Cross‐Couplings with 1,1,1‐Trifluoroacetone Tosylhydrazone

1,1,1‐Trifluoroacetone tosylhydrazone is presented as a very convenient substrate for the palladium‐catalyzed cross‐coupling with aryl halides. Under the proper reaction conditions, 3,3,3‐trifluoromethylstyrenes – very valuable trifluoromethylated synthetic intermediates – are obtained with high yields. The reaction features a very wide scope, as the presence of most functional groups is tolerated. Moreover, the reaction has been extended to substituted trifluoromethylstyrenes by employing substituted tosylhydrazones derived from other trifluoromethyl ketones.

     

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.     

Palladium‐Catalyzed α‐Arylation of Methyl Sulfonamides with Aryl Chlorides

A palladium‐catalyzed α‐arylation of sulfonamides with aryl chlorides is presented. A Buchwald‐type pre‐catalyst formed with Kwong’s indole‐based ligand enabled this transformation to be compatible with a large variety of methyl sulfonamides and aryl chlorides in good to excellent yields. Importantly, under the optimized reaction conditions, only mono‐arylated products were observed. This method has been applied to the efficient synthesis of sumatriptan, which is used to treat migraines.

     

Cobalt‐Catalyzed Cross‐Coupling Reaction between Functionalized Primary and Secondary Alkyl Halides and Aliphatic Grignard Reagents

The coupling of primary and secondary unactivated alkyl bromides with alkyl‐Grignard reagents was performed in good yields under mild conditions by using a new catalytic system: consisting of cobalt chloride and tetramethylethylenediamine (CoCl₂⋅2 LiI, 4 TMEDA). The reaction is very chemoselective since ketone, ester and nitrile functions are tolerated.