Nickel‐Catalyzed Cross‐Electrophile Coupling with Organic Reductants in Non‐Amide Solvents

Cross‐electrophile coupling of aryl halides with alkyl halides has thus far been primarily conducted with stoichiometric metallic reductants in amide solvents. This report demonstrates that the use of tetrakis(dimethylamino)ethylene (TDAE) as an organic reductant enables the use of non‐amide solvents, such as acetonitrile or propylene oxide, for the coupling of benzyl chlorides and alkyl iodides with aryl halides. Furthermore, these conditions work for several electron‐poor heterocycles that are easily reduced by manganese. Finally, we demonstrate that TDAE addition can be used as a control element to ‘hold’ a reaction without diminishing yield or catalyst activity.     

Pd(0)‐Catalyzed Tandem One‐Pot Reaction of Biphenyl Ketones/Aldehydes to the Corresponding Di‐substituted Aryl Olefins

Synthesis of di‐substituted aryl olefins via a Pd(0)‐catalyzed cross‐coupling reaction of biphenyl ketones/aldehydes, tosylhydrazide, and aryl bromides (or benzyl halides) was developed. This methodology was achieved by one‐pot two‐step reactions involving the preparation of N ‐tosylhydrazones by reacting tosylhydrazide with biphenyl ketones/aldehydes, followed by coupling with aryl bromides (or benzyl halides) in the presence of Pd(PPh₃ )₄ and lithium t ‐butoxide to produce various di‐substituted aryl olefins in moderate to good yields.     

A general solid phase synthesis of 4-substituted quinolinones via Pd-catalyzed cross coupling

A general method for the solid phase synthesis of 4-hydroxy quinolinones and subsequent Pd-catalyzed cross coupling to afford 4-substituted quinolinones has been developed. Conversion of support-bound 4-hydroxy quinolinones to 4-tosyl quinolinones and subsequent treatment with alkyl, aryl, benzylzinc halides, or arylboronic acids in the presence of catalytic amount of Pd(PPh₃)₄ provides 4-alkyl, aryl, or benzyl quinolinones. This method allows for the introduction of alkyl, aryl, and benzyl groups at the 4-position of the quinolinone ring, and is ideal for parallel and combinatorial chemistry library synthesis.     

Multicomponent Reductive Cross‐Coupling of an Inorganic Sulfur Dioxide Surrogate: Straightforward Construction of Diversely Functionalized Sulfones

Conventionally, sulfones are prepared by oxidation of sulfides with strong oxidants. Now, a multicomponent reductive cross‐coupling involving an inorganic salt (sodium metabisulfite) for the straightforward construction of sulfones is disclosed. Both intramolecular and intermolecular reductive cross‐couplings were comprehensively explored, and diverse sulfones were accessible from the corresponding alkyl and aryl halides. Intramolecular cyclic sulfones were systematically obtained from five‐ to twelve‐membered rings. Naturally occurring aliphatic systems, such as steroids, saccharides, and amino acids, were highly compatible with the SO₂‐insertion reductive cross‐coupling. Four clinically applied drug molecules, which include multiple heteroatoms and functional groups with active hydrogens, were successfully prepared via a late‐stage SO₂ insertion. Mechanistic studies show that alkyl radicals and sulfonyl radicals were both involved as intermediates in this transformation.     

Direct vs Indirect Grafting of Alkyl and Aryl Halides

The direct and indirect electrochemical grafting of alkyl and aryl halides (RX, ArX) on carbon, metal and polymer surfaces is examined. Their electrochemical reduction occurs at highly negative potential in organic solvents and very often produces carbanions because the reduction potentials of RX and ArX are more negative than those of their corresponding radicals. Therefore, direct electrografting of alkyl and aryl radicals generated from RX and ArX is not easy to perform. This obstacle is overcome using aryl radicals derived from the 2,6-dimethylbenzenediazonium salt (2,6-DMBD), which do not react on the electrode surface due to their steric hindrance but react in solution by abstracting an iodine or bromine atom from RX (X=I, Br) or ArI to give alkyl or aryl radicals. As a consequence, alkyl and aryl radicals are generated at very low driving force by diverting the reactivity of aryl radicals derived from an aryl diazonium salt; they attack the electrode surface and form strongly attached organic layers. This strategy applies to the chemical modification of polymers (polyethylene, polymethylmethacrylate) by alkyl halides under heating.     

A benign initiating system for cationic polymerization of isobutyl vinyl ether: Silver salt/aryl(alkyl) halide/lewis base

Aryl(alkyl) halides and silver salts were studied as environmentally benign initiating systems for cationic polymerization of isobutyl vinyl ether (IBVE). The reactivity of the benzyl cations could be effectively controlled by using dimethyl sulfide (Me₂S) as an additive, which was shown to be an effective Lewis base (LB), and diethyl ether as a reaction solvent. Detailed study of various benzyl cations and the order of addition of the reagents revealed that the reaction was controlled by the electronic and steric features of aryl(alkyl) halides, LBs, and IBVE, and a plausible reaction mechanism was presented. © 2015 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2015 , 53, 2050–2058     

Reactivity of mixed organozinc and mixed organocopper reagents: 6. Nickel-catalyzed coupling of methylarylzincs with primary alkyl halides; an atom-economic aryl-alkyl coupling

A nickel-catalyzed process for the cross-coupling of mixed arylzincs and primary alkyl halides has been developed. The reaction of a methylarylzinc with a primary alkyl halide in THF in the presence of NiCl₂/PPh₃ takes place with selective aryl transfer at room temperature in moderate yields. This protocol provides an atom-economic alternative to aryl-primary alkyl coupling using diarylzincs.     

ESR studies on reactions of dicyclopentadienyl dicarbonyl titanium with organic halides

ESR method was used to elucidate the mechanism of the reactions of alkyl, allyl or benzyl halides with dicyclopentadienyldicarbonyl titanium. The paramagnetic [intermediates of the reactions were identified during the course of the reactions. The reaction mechanism based on ESR findings and the products analyses is postulated to operate on radical pathways. When alkyl halides were used to react with the organometallic compound 1, the intermediate found was [Cp₂Ti(CO)X] (C), and the main product was identified to be dicyclopentadienyl-acyl-halo titanium (3), an insertion of TiCO into R-X, i.e. [Cp₂Ti-C(0)R] X. When allyl or benzyl halides were used, the intermediate found was [Cp₂TiX] (B), and the main products were identified to be the dicyclopentadienyl titanium dihalides and the coupling products of allyl or benzyl groups.     

Syntheses of polycarbonate and polyurethane precursors utilizing CO2 over highly efficient, solid as-synthesized MCM-41 catalyst

As-synthesized MCM-41 was used as a reusable, heterogeneous catalyst for the eco-friendly synthesis of cyclic carbonate precursors of polycarbonates via a cycloaddition reaction of CO₂ with epoxides. This catalyst is also efficient for the synthesis of alkyl and aryl carbamate precursors of polyurethanes via the reaction of amines, CO₂ and alkyl halides. Both these reactions were carried out under mild conditions and without using any solvent or co-catalyst. CO₂ is utilized as a raw material replacement for toxic phosgene in the conventional synthesis of these chemicals.     

Palladium‐Catalyzed Heteroarylation and Concomitant ortho‐Alkylation of Aryl Iodides

Three‐component couplings were achieved from common aryl halides, alkyl halides, and heteroarenes under palladium and norbornene co‐catalysis. The reaction forges hindered aryl–heteroaryl bonds and introduces ortho‐alkyl groups to aryl rings. Various heterocycles such as oxazoles, thiazoles and thiophenes underwent efficient coupling. The heteroarenes were deprotonated in situ by bases without the assistance of palladium catalysts.     

Pd-catalyzed Negishi coupling of pyrazole triflates with alkyl zinc halides

A mild, functional group tolerant palladium-catalyzed Negishi coupling of pyrazole triflates and nonaflates with alkyl, benzyl, and aryl zinc halides has been developed. It allows quick access to 3-substituted pyrazole analogs at late stage via common synthetic intermediates.     

Expedient Iron‐Catalyzed Coupling of Alkyl,Benzyl and Allyl Halides with Arylboronic Esters

While attractive, the iron‐catalyzed coupling of arylboron reagents with alkyl halides typically requires expensive or synthetically challenging diphosphine ligands. Herein, we show that primary and secondary alkyl bromides and chlorides, as well as benzyl and allyl halides, can be coupled with arylboronic esters, activated with alkyllithium reagents, by using very simple iron‐based catalysts. The catalysts used were either adducts of inexpensive and widely available diphosphines or, in a large number of cases, simply [Fe(acac)₃] with no added co‐ ligands. In the former case, preliminary mechanistic studies highlight the likely involvement of iron(I)–phosphine intermediates.     

Direct Arylation/Alkylation/Magnesiation of Benzyl Alcohols in the Presence of Grignard Reagents via Ni-, Fe-, or Co-Catalyzed sp(3) C-O Bond Activation

Direct application of benzyl alcohols (or their magnesium salts) as electrophiles in various reactions with Grignard reagents has been developed via transition metal-catalyzed sp(3) C-O bond activation. Ni complex was found to be an efficient catalyst for the first direct cross coupling of benzyl alcohols with aryl/alkyl Grignard reagents, while Fe, Co, or Ni catalysts could promote the unprecedented conversion of benzyl alcohols to benzyl Grignard reagents in the presence of (n)hexylMgCl. These methods offer straightforward pathways to transform benzyl alcohols into a variety of functionalities.     

Copper nanoparticles supported on polyaniline‐functionalized multiwall carbon nanotubes: An efficient and recyclable catalyst for synthesis of unsymmetric sulfides using potassium ethyl xanthogenate in water

A new and powerful polyaniline‐functionalized carbon nanotube‐supported copper(II) nanoparticle catalyst was successfully prepared and evaluated as a heterogeneous catalyst for the one‐pot synthesis of unsymmetric thioethers by coupling of aryl, alkyl and benzyl halides using potassium ethyl xanthogenate as source of sulfur in water. All of these reactions gave the desired products in good to excellent yields. The catalyst is available, air‐stable and can be reused several times without significant loss in its catalytic activity.     

Hiyama cross‐coupling reaction catalyzed by a palladium salt of 1‐benzyl‐4‐aza‐1‐azoniabicyclo[2.2.2]octane chloride under microwave irradiation

An efficient catalytic system using 1‐benzyl‐4‐aza‐1‐azoniabicyclo[2.2.2]octane chloride ((BeDABCO)₂Pd₂Cl₆) was developed for the Hiyama cross‐coupling reaction of various aryl halides with triethoxy(phenyl)silane. The substituted biaryls were produced in excellent yields in short reaction times using a catalytic amount of this catalyst in NMP at 100 °C. Copyright © 2014 John Wiley & Sons, Ltd.     

Single‐Electron‐Transfer‐Induced Coupling of Arylzinc Reagents with Aryl and Alkenyl Halides

Arylzinc reagents, prepared from aryl halides/zinc powder or aryl Grignard reagents/zinc chloride, were found to undergo coupling with aryl and alkenyl halides without the aid of transition‐metal catalysis to give biaryls and styrene derivatives, respectively. In this context, we have already reported the corresponding reaction using aryl Grignard reagents instead of arylzinc reagents. Compared with the Grignard cross‐coupling, the present reaction features high functional‐group tolerance, whereby electrophilic groups such as alkoxycarbonyl and cyano groups are compatible as substituents on both the arylzinc reagents and the aryl halides. Aryl halides receive a single electron and thereby become activated as the corresponding anion radicals, which react with arylzinc reagents, thus leading to the cross‐coupling products.     

Nickel‐Catalyzed Umpolung Arylation of Ambiphilic α‐Bromoalkyl Boronic Esters

A nickel‐catalyzed reductive arylation of ambiphilic α‐bromoalkyl boronic esters with aryl halides is described. This platform provides an unrecognized opportunity to promote the catalytic umpolung reactivity of ambiphilic reagents with aryl halides, thus unlocking a new cross‐coupling strategy that complements existing methods for the preparation of densely functionalized alkyl‐substituted organometallic reagents from simple and readily accessible precursors.     

Multicomponent Reductive Cross-Coupling of an Inorganic Sulfur Dioxide Surrogate: Straightforward Construction of Diversely Functionalized Sulfones

Conventionally, sulfones are prepared by oxidation of sulfides with strong oxidants. Now, a multicomponent reductive cross-coupling involving an inorganic salt (sodium metabisulfite) for the straightforward construction of sulfones is disclosed. Both intramolecular and intermolecular reductive cross-couplings were comprehensively explored, and diverse sulfones were accessible from the corresponding alkyl and aryl halides. Intramolecular cyclic sulfones were systematically obtained from five- to twelve-membered rings. Naturally occurring aliphatic systems, such as steroids, saccharides, and amino acids, were highly compatible with the SO₂-insertion reductive cross-coupling. Four clinically applied drug molecules, which include multiple heteroatoms and functional groups with active hydrogens, were successfully prepared via a late-stage SO₂ insertion. Mechanistic studies show that alkyl radicals and sulfonyl radicals were both involved as intermediates in this transformation.     

Cobalt‐Catalyzed Intermolecular C(sp2)O Cross‐Coupling

Cobalt(II)‐catalyzed C(sp²)?O cross‐coupling between aryl/heteroaryl alcohols and vinyl/aryl halides in the presence of Cu^I has been achieved under ligand‐free conditions. In this reaction, copper plays a significant role in transmetalation rather than being directly involved in the C?O coupling. This unique Co/Cu‐dual catalyst system provides an easy access to a library of aryl–vinyl, heteroaryl–styryl, aryl–aryl, and heteroaryl–heteroaryl ethers in the absence of any ligand or additive.     

Ni‐Catalyzed Cross‐Coupling Reaction: The Direct Synthesis of Symmetrical Disulfanes from Aryl and Primary Alkyl Halides

A novel Ni‐catalyzed cross‐coupling reaction is introduced for the direct synthesis of diaryldisulfanes and dialkyldisulfanes from aryl halides and primary alkyl halides at normal atmospheric conditions, respectively. This one‐pot and domino protocol utilizes only 10 mol% of NiCl₂ as a catalyst and morpholin‐4‐ium morpholine‐4‐carbo‐dithioate as a new, stable, solid, and odorless sulfurating reagent in the presence of ethylene glycol as a cosolvent and bidentate ligand in dimethyl formamide (DMF) at 130°C with good to excellent yields and relatively short time reaction.