Tandem Coupling Reaction Research Articles

Pd(0)-Catalyzed Asymmetric Cyclization/Coupling Cascade of Alkyne-Tethered Unsaturated Carbonyls: Development and Mechanism Elucidation.

While the Pd(0)-catalyzed cyclization of alkyne-tethered unsaturated carbonyl substrates has been reported, the mechanism has not been well elucidated, and the potential asymmetric version remains to be developed. Here, we disclose that a chiral Pd(0) complex can efficiently promote the desymmetrizative cyclization of alkyne-tethered cyclohexadienones in CH3OH, and the resultant Pd(II) intermediates further undergo an array of tandem coupling reactions, including Suzuki, Sonogashira, and even chemoselective reduction by CH3OH in the absence of additional coupling partners. As a result, a broad spectrum of hydrobenzofuran derivatives, having a tetra- or trisubstituted exo-alkene motif, is constructed with moderate to outstanding enantioselectivity in an exclusive cis-difunctionalization pattern. In addition, this enantioselective protocol can be well expanded to linear alkyne-tethered unsaturated carbonyls, and a new desymmetrizative and asymmetric cyclization/coupling cascade of bis-alkyne-tethered enones is further realized efficiently, furnishing diversely structured frameworks with high stereoselectivity. Moreover, kinetic transformation for various racemic alkyne-tethered enones can be accomplished under similar catalytic conditions, and unusual kinetic reactions by chemoselectively undertaking Suzuki or Sonogashira coupling, or reduction by CH3OH, occur sequentially, finally yielding two types of chiral products, both with high enantioselectivity via either ligand- or substrate-based control. The experimental results demonstrate that the current Pd(0)-based strategy is superior to the classical Pd(II)-catalyzed carbopalladation/cyclization process of the identical substrates with regard to enantioselectivity and synthetic versatility. Moreover, density functional theory calculations are conducted to rationalize the Pd(0)-catalyzed oxidative cyclometalation pathway in the key cyclization step, which leads to the observed cis-difunctionalized products exclusively.

Al(OTf)3‐Catalyzed Tandem Coupling Reaction between N,N‐Disubstituted Aminomalonitriles and Substituted Arenes: a Synthesis of 1‐Cyano‐bisindolylmethane Analogues≠

AbstractA synthesis of 1‐cyano‐bisindolylmethane analogues via an Al(OTf)3‐catalyzed tandem coupling reaction between N,N‐disubstituted aminomalonitriles and substituted arenes has been developed. This method not only provides an alternative synthetic strategy for the synthesis of corresponding functional molecules, but also enriches the volume of bisarylmethanes library to facilitate related functional studies.magnified image

Direct Stereoconvergent Allylation of Chiral Alkylcopper Nucleophiles with Racemic Allylic Phosphates.

Copper-catalyzed stereoconvergent allylation of chiral sp3 -hybridized carbon nucleophiles with a racemic mixture of acyclic secondary allylic phosphates is reported. In the presence of a copper-catalyst complexed with chiral BenzP* ligand, tandem coupling reaction of vinyl arenes, bis(pinacolato)diboron, and racemic allylic phosphates provided β-chiral alkylboronates possessing (E)-alkenyl moiety through a direct stereoconvergent allylic coupling with concomitant generation of a C(sp3 )-stereogenic center. A range of vinyl (hetero)arenes and secondary allylic phosphates bearing 1°, 2°, 3° alkyl and phenyl α-substituents were suitable for the reaction, forming products with high enantioselectivities up to 95 % ee. Density functional theory calculations were conducted in detail to elucidate the origin of the observed regioselectivity of borylcupration and stereoconvergent (E)-olefin formation from racemic allylic phosphates.

Copper-catalyzed 1,1-alkynylalkylation of alkynes: access toward conjugated enynes

A copper-catalyzed 1,1-alkynylalkylation of alkynes with α-haloacetamides for the construction of conjugated enynes has been developed.

Three‐Component Synthesis of Quinolines Based on Radical Cascade Visible‐Light Photoredox Catalysis

AbstractSynthesis of highly substituted quinolines has been developed based on three‐component radical cascade based on visible‐light photoredox catalysis. This tandem coupling reaction has been coordinated to proceed with high chemoselectivity based on the differential electronic properties of coupling partners. Subjection of electron‐rich β‐aminoacrylates with electron‐deficient halides and alkenes to the optimized conditions leads to the formation of quinolines in good yields after in situ oxidation of tetrahydroquinolines. Detailed mechanistic studies which reveal an unexpected reaction pathway is described.magnified image

Microwave-assisted synthesis of isoindolinones via Pd-mediated tandem coupling reactions

Abstract Palladium (Pd) coupling reactions have become an indispensable tool in modern synthetic organic chemistry. A simple procedure to obtain isoindolinones 7 bearing a quaternary C-atom, featuring a Pd-mediated tandem process, is presented. Readily available iodoamidoacrylate 3 and boronic acids 6 are used as the starting materials.

Surface-Triggered Tandem Coupling Reactions of Cyclic Azasilanes.

Cyclic azasilanes have been synthesized for the purpose of developing coupling agents appropriate for a variety of nanotechnologies including surface modification of nanoparticles, nanocrystals, mesoporous materials and substrates. N‐Methyl‐aza‐2,2,4‐trimethylsilacyclopentane is representative of this class of compounds. Preliminary data for the treatment of inorganic surfaces, including nanoparticles and oxidized silicon wafers, with cyclic azasilanes suggest high‐density monolayer deposition by a ring‐opening reaction. Cyclic azasilanes contain a cryptic amine functionality that can perform a subsequent tandem coupling reaction with functional molecules after the surface‐triggered ring‐opening reaction, allowing for a one‐pot self‐assembly route on nanostructures. Tandem coupling reactions are demonstrated via addition reactions of the cryptic amine with epoxy and acrylate systems.

A Green and Recyclable Copper and Ionic Liquid Catalytic System for the Construction of Poly‐heterocyclic Compounds via One‐pot Tandem Coupling Reaction

AbstractIn this contribution, we report the environmentally benign synthesis of various N‐containing heterocyclic compounds from two simple starting materials, 2‐aminobenzoic acid and/ or 2‐aminobenzamide and 4‐pentynoic acid using copper as a catalyst in ionic liquid media. This synthetic methodology affords products with good to excellent yield with several advantages such as less toxicity of catalyst, green solvent media and easy isolation of products. Both the catalyst and ionic liquid were successfully reused and recycled up to five times without any significant loss of activity.

Potassium carbonate-mediated tandem C–S and C–N coupling reaction for the synthesis of phenothiazines under transition-metal-free and ligand-free conditions

A potassium carbonate-mediated tandem coupling reaction for the synthesis of phenothiazines is described. This protocol affords an efficient approach for the construction of phenothiazine derivatives without the need for addition of transition-metal catalyst or ligand.

TEMPO Derivatives as Alternative Mild Oxidants in Carbon-Carbon Coupling Reactions

TEMPO-type oxidants are fundamentally associated with polymer chemistry, radical trapping processes, or the oxidation of alcohols to carbonyl compounds. However, in the past few years new exciting transformations using these kinds of oxidants in the area of C–C and C–heteroatom coupling have emerged. This review focuses on the application of TEMPO and its derivatives as mild reagents or catalysts in oxidative C–C coupling reactions. The review is divided into two main sections: i) the direct coupling of C–H bonds and ii) the use of organometallic reagents such as Grignard or boron species to generate the new C–C bond. In the last section, oxidative C–C/C–O tandem-coupling reactions, in which the TEMPO derivatives are incorporated in the final product, are also briefly described. 1 Introduction 2 Oxidative Couplings of C–X Bonds 2.1 C–C Bond Couplings of Grignard Reagents 2.2 C–C Bond Couplings of Boron Reagents 3 Oxidative Couplings of C–X with C–H Bonds 3.1 C–C Bond Couplings with Grignard Reagents 3.2 C–C Bond Couplings with Boron Reagents 3.3 Tandem C–C/C–O Coupling Reactions with Olefins 4 Oxidative Couplings of C–H Bonds 4.1 C(sp2)–H Bond Functionalizations 4.2 C(sp3)–H Bond Functionalizations 5 Conclusions

ChemInform Abstract: Palladium‐Catalyzed Tandem Coupling Reaction of Alkyne, Conjugated Diene, and Triethylborane.

ChemInform Abstract: Palladium‐Catalyzed Tandem Coupling Reaction of Alkyne, Conjugated Diene, and Triethylborane.

Iron (III) Trichloride-Catalyzed One-Pot Three-Component Coupling of Indoles and Sodium Nitrite: A Convenient Synthesis of 2,3’-Bi(3H-indol)-3-one oximes

A simple, convenient and efficient three-component coupling (TCC) reaction toward a variety of (E)-2,3'-bi(3H-indol)-3-one oxime derivatives has been developed. This transformation proceeds via an iron (III)-catalyzed tandem coupling reaction between indoles and sodium nitrite. This methodology provides an alternative approach for easy access of (E)-2,3'-bi(3H-indol)-3-one oximes in good to excellent yields at room temperature.

Interest of designed cyclodextrin-tools in gene delivery

Cyclodextrins (CyDs) currently displays even today the image of a natural macrocyclic compound largely dominant in the formation of inclusion complexes with small hydrophobic molecules. During the past 10 years, advances in this field allowed to achieve more and more sophisticated CyDs derivatives opening a simple access in scale-up quantities to original and better CyD-based gene delivery systems. In addition, possibility to combine covalent and supramolecular approaches offers new venues for the design of tailor-made CyD-based nanovehicles to improve their transfection ability and gene transfer in cells. In this account, we describe our recent progress in the construction of a novel CyD-based G0 (generation number) core dendrimer, scalable to CyD oligomers by a strategy using protonable guanidine tethers and whose concept can be generalized for the assembly of CyD pre-coated dendrimers. The synthetic strategy based on an original Staudinger-Aza-Wittig tandem coupling reaction. We present an outline of the different analytical strategies to characterize CyD-ODN (cyclodextrin-oligodeoxynucleotide) complexes. Among them, Capillary electrophoresis (CE) was used to perfectly characterize our CyD-siRNA and CyD-DNA complexes and shown to be a very attractive method with advantages of low sample consumption, rapid analysis speed, and high efficiency that make this technology a major tool for association constant measurement. Finally, we present the different biological methods that can be used, in vitro, to study gene delivery, and more precisely ones we have performed to evaluate the capability of our original model bis-guanidinium-tetrakis-β-cyclodextrin dendrimeric tetrapod, to deliver efficiently DNA or siRNA in eukaryotic cells.

Access to C(sp3)–C(sp2) and C(sp2)–C(sp2) Bond Formation via Sequential Intermolecular Carbopalladation of Multiple Carbon–Carbon Bonds

A synthetic strategy of 4-benzyl-substituted 1,3-butadiene derivatives through Pd-catalyzed three-component coupling reaction of benzyl chlorides, alkynes, and monosubstituted alkenes is described. This tandem coupling reaction forms a C(sp(3))-C(sp(2)) bond and a C(sp(2))-C(sp(2)) bond sequentially in a single-step operation.

Tandem coupling reactions of benzynes and 1,3-diones: a novel synthesis of 2,2-diphenyl-1,3-diones

A novel, general, and mild method is described to prepare 2,2-diphenyl-1,3-diones with benzyne using CuBr and trichloroacetic acid as the catalyst.

Synthesis of 2‐Vinylic Indoles and Derivatives via a Pd‐Catalyzed Tandem Coupling Reaction.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

Synthesis of 2-Vinylic Indoles and Derivatives via a Pd-Catalyzed Tandem Coupling Reaction

A novel one-step synthesis of valuable 2-vinylic indoles and their tricycle derivatives is described. This reaction, which utilizes a gem-dibromovinyl unit as a readily available starting material, occurs via an efficient Pd-catalyzed tandem Buchwald-Hartwig/Heck reaction.

Palladium(II)‐Catalyzed Coupling of Allenoic Acids and α,β‐Unsaturated Carbonyl Compounds Through Tandem Intramolecular Oxypalladation and Conjugate Addition Reactions.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Palladium(II)-catalyzed coupling of allenoic acids and α,β-unsaturated carbonyl compounds through tandem intramolecular oxypalladation and conjugate addition reactions

A regioselective divalent palladium-catalyzed tandem coupling reaction of allenoic acids with α,β-unsaturated carbonyl compounds was developed. The reaction involves intramolecular oxypalladation of an allene, followed by insertion of the α,β-unsaturated carbonyl compound and protonolysis of the CPd bond to regenerate the Pd(II) species in the presence of excess halide ions. Functionalized lactones, tetrahydropyranones and dihydropyranones can be synthesized with high regioselectivity in one step.