Coupling of enamides with alkynes or arynes for synthesis of substituted pyridines and isoquinolines via amide activation

A novel and general procedure for Cu-catalyzed coupling of enamides with alkynes to synthesize substituted pyridines was developed. The chemistry was allowed to extend to the synthesis of substituted isoquinolines by coupling of enamides with arynes under transition-metal-free conditions.     

Synthesis of Isocoumarins through Three‐Component Couplings of Arynes,Terminal Alkynes,and Carbon Dioxide Catalyzed by an NHC–Copper Complex

A copper‐catalyzed multicomponent coupling reaction between in situ generated ortho‐arynes, terminal alkynes, and carbon dioxide was developed to access isocoumarins in moderate to good yields. The key to this CO₂‐incorporating reaction was the use of a versatile N‐heterocyclic carbene/copper complex that was able to catalyze multiple transformations within the three‐component reaction.     

Synthesis of Isocoumarins through Three‐Component Couplings of Arynes,Terminal Alkynes,and Carbon Dioxide Catalyzed by an NHC–Copper Complex

A copper‐catalyzed multicomponent coupling reaction between in situ generated ortho‐arynes, terminal alkynes, and carbon dioxide was developed to access isocoumarins in moderate to good yields. The key to this CO₂‐incorporating reaction was the use of a versatile N‐heterocyclic carbene/copper complex that was able to catalyze multiple transformations within the three‐component reaction.     

Chemo- and regioselective assembly of polysubstituted pyridines and isoquinolines from isocyanides, arynes, and terminal alkynes

We have disclosed a general and efficient synthetic strategy for polysubstituted pyridines and isoquinolines with high chemo- and regioselectivity. In this methodology, 1-alkynyl imines act as the key compound to undergo a sequential alkynyl imine-allenyl imine isomerization/aza-Diels-Alder reaction/aromatization. In the first place, 1-alkynyl imines were formed in situ by a highly selective multicomponent reaction of isocyanides, arynes, and terminal alkynes and reacted with another molecule of arynes or terminal alkynes to furnish target heterocyclic products in a highly efficient and atom-economic manner. On the other hand, we attempted to prepare 1-alkynyl imines by other approaches to undergo a similar reaction sequence to afford polysubstituted pyridines and isoquinolines with a wider range. Different from the first approach, the second approach utilized the preprepared 1-alkynyl imines to introduce the related different substitutents into the final products: arynes or terminal alkynes bearing substituents different from those of 1-alkynyl imines have been successfully applied for the synthesis a wide variety of pyridines and isoquinolines with diversity.     

Cyclotrimerization reactions of arynes and strained cycloalkynes

The use of arynes and related species as substrates in metal-catalyzed cycloaddition reactions leads to structurally interesting products. Palladium-catalyzed cyclotrimerization of arynes provides a new method for the synthesis of polycyclic aromatic hydrocarbons. For instance, the chemoselective formal [2 + 2 + 2] cocycloaddition of 2,3-triphenylynes with alkynes affords extended triphenylenes, which are good candidates to behave as liquid crystals. Cotrimerization of benzyne and electron-deficient alkenes selectively affords dihydrophenanthrenes or ortho-olefinated biaryls depending on the catalytic system employed. The use of 2,2'-bis(diphenylphosphino)-1,1'-binophythyl (BINAP)-based palladium(0) catalysts in the cocyclotrimerization of 7-methoxynaphthalyne and dimethyl acetylenedicarboxylate affords an enantiomerically enriched tetrasubstituted pentahelicene, the first example of a metal-catalyzed enantioselective reaction involving arynes. Strained cyclic alkynes can also participate in the palladium-catalyzed cyclotrimerization reactions, which again lead to structurally interesting products.     

Straightforward access to 2-iminoisoindolines via three-component coupling of arynes, isocyanides and imines

A three-component coupling reaction of arynes, isocyanides and N-tosylaldimines has been developed to offer modest to high yields of diverse 2-iminoisoindolines in one step. Intermediacy of arynes in the coupling has been verified by the reaction of unsymmetrical arynes.     

Gold-catalyzed efficient tandem assembly of terminal alkynes and arynes: synthesis of alkynylated biphenyl derivatives

Gold catalysts have been found to catalyze the tandem assembly of arynes and terminal alkynes efficiently in the presence of CuI under mild reaction conditions to provide useful alkynylated biphenyl derivatives.     

Ene reaction of arynes with alkynes

Arynes, generated in situ from ortho-silylaryl triflates, undergo ene reaction with alkynes possessing propargylic hydrogen in the presence of KF/18-crown-6 in THF at room temperature to give substituted phenylallenes. Various terminal and internal alkynes as well as different arynes can be used to give the corresponding phenylallenes in good to moderate yields. The reaction of alkyne without propargylic hydrogen gave an acetylenic C-H addition product (a phenylalkyne) and a dehydro Diels-Alder product (a phenanthrene).     

Nucleophilic fluoroalkylation of alpha,beta-enones, arynes, and activated alkynes with fluorinated sulfones: probing the hard/soft nature of fluorinated carbanions

We have successfully accomplished the nucleophilic fluoroalkylation of alpha,beta-enones, arynes, and activated alkynes with fluorinated sulfones. It was found that for acylic alpha,beta-enones, although the reaction medium and the structure of the enones can all influence the regioselectivity of the nucleophilic alkylation reactions, the hard/soft nature of the carbanions played a major role. By using the 1,4- and 1,2-addition product ratio as a probe to determine the hard/soft nature of the above-mentioned four halogenated carbanions, the order of the softness of these carbanions can be given as follows: [(PhSO2)2CF(-)] (20) approximately = PhSO2CCl2(-) (32) > PhSO2CHF(-) (31) > PhSO2CF2(-) (30). In the case of fluoroalkylation of aryne (35 as the precursor) and alpha,beta-acetylenic ketones 46 with fluorobis(phenylsulfonyl)methane (21), fluorobis(phenylsulfonyl)methylated arenes 36 and beta-fluorobis(phenylsulfonyl)methylated alpha,beta-enones 47 were obtained as the corresponding products in good yields. During the reaction between 2-fluoro-2-(phenylsulfonyl)acetophenone (34) and arynes or activated alkynes 46, an intramolecular tandem reaction process leads to the formation of acyl-fluoroalkylated arenes 43 or alpha-acyl-beta-fluoroalkylated alpha,beta-enones 48. It turned out that the softness of a fluorine-bearing carbanion (such as 20 or 33 derived from 21 or 34) plays a crucial role for the success of the nucleophilic fluoroalkylation reactions with arynes and some activated alkynes (alpha,beta-acetylenic ketones).     

Three-component coupling using arynes and isocyanides: straightforward access to benzo-annulated nitrogen or oxygen heterocycles

A variety of aldehydes, ketones, benzoquinones, or sulfonylimines were found to couple with arynes and isocyanides, giving iminodihydroisobenzofuran or iminoisoindoline derivatives of structural diversity in a straightforward manner. Nucleophilic addition of isocyanides to arynes, a first step of the three-component coupling, was proved to be reversible by the reaction of an unsymmetrical aryne.     

Biaryl synthesis via palladium-catalyzed aryne multicomponent coupling

Aryl iodides have been introduced as electrophiles in the three-component Heck coupling of arynes. Following optimization studies to favor three- versus two-component coupling, the reaction proceeds in good yield to afford a variety of functionalized biaryls.     

Rapid Synthesis of Zwitterionic Phosphonium Benzoates by a Three‐Component Coupling Involving Phosphines,Arynes and CO2

A mild and easy to perform multicomponent coupling involving phosphines, arynes generated from 2‐(trimethylsilyl)aryl triflates, and CO₂ allowing the transition‐metal‐free synthesis of zwitterionic phosphonium benzoates has been developed. The reaction proceeds via the generation of 1 : 1 zwitterionic intermediates from phosphines and arynes followed by the interception with CO₂ to deliver the carboxylates in moderate to good yields instead of the anticipated benzooxaphosphol‐3(1H)‐ones.     

Direct access to anthranilic acid derivatives via CO2 incorporation reaction using arynes

CO2 was found to be directly convertible into anthranilic acid derivatives of great synthetic value through a three-component coupling using arynes and amines. Zwitterions arising from nucleophilic attack of amines to arynes serve as key intermediates in the coupling.     

Synthesis of isochromenones and oxepines via Pd-catalyzed cascade cyclization of alkynes and benzynes involving C-H activation

A new method for the synthesis of various isochromen-6-ones and phenanthro[1,10-bc]oxepines via a palladium-catalyzed cascade carbocyclization of 2-iodobenzyl-3-phenylpropiolates and 1-iodo-2-(2-(phenylethynyl)benzyloxy)benzenes with arynes is described. The reactions involve interesting biscarbocyclization of alkynes and benzynes and C-H bond activation.     

Palladium-catalyzed arylation of enynes and electron-deficient alkynes using diaryliodonium salts

A new single-pot procedure for the synthesis of aryl alkynes is described. Palladium catalyzes the coupling reaction of diaryliodonium compounds with enynes and electron-deficient alkynes to give aryl alkynes in good yields.     

Sonogashira Coupling Reaction with Palladium Powder,Potassium Fluoride in Aqueous Media

Abstract

A Sonogashira coupling reaction of aromatic iodides and bromides with terminal alkynes in the presence of palladium powder, potassium fluoride, cuprous iodide, and triphenylphosphine in aqueous media was developed. The reaction generates the corresponding coupling products aryl alkynes in good to excellent yields.     

Sonogashira Coupling Reaction with Palladium Powder and Potassium Fluoride in Methanol

A Sonogashira coupling reaction of aromatic halides with terminal alkynes in the presence of palladium powder,potassium fluoride,cuprous iodide and triphenylphosphine in methanol,giving the corresponding coupling products aryl alkynes in good to excellent yiekls,was investigated.     

Three characteristic reactions of alkynes with metal compounds in organic synthesis

Alkynes have two sets of mutually orthogonal π‐bonds that are different from the π‐bonds of alkenes. These π‐bonds are able to bond with transition metal compounds. Alkynes easily bond with the various kinds of compounds having a π‐bond such as carbon monoxide, alkenes, other alkynes and nitriles in the presence of the transition metal compounds. The most representative reaction of alkynes is called the Pauson–Khand reaction. The Pauson–Khand reactions include the cyclization of alkynes with alkenes and carbon monoxide in the presence of cobalt carbonyls. Similar Pauson–Khand reactions also proceed in the presence of other transition metal compounds. These reactions are the first type of characteristic reaction of alkynes. Other various kinds of cyclizations with alkynes also proceed in the presence of the transition metal compounds. These reactions are the second type of characteristic reaction of alkynes. These include cyclooligomerizations and cycloadditions. The cyclooligomerizations include mainly cyclotrimerizations and cyclotetramerizations, and the cycloadditions are [2 + 2], [2 + 2 + 1], [2 + 2 + 2], [3 + 2], [4 + 2], etc., type cycloadditions. Alkynes are fairly reactive because of the high s character of their σ‐bonds. Therefore, simple coupling reactions with alkynes also proceed besides the cyclizations. The coupling reactions are the third type of characteristic reactions of alkynes in the presence of, mainly, the transition metal compounds. These reactions include carbonylations, dioxycarbonylations, Sonogashira reactions, coupling reactions with aldehydes, ketones, alkynes, alkenes and allyl compounds. Copyright © 2008 John Wiley & Sons, Ltd.     

Rh(I)-catalyzed coupling cyclization of N-aryl trifluoroacetimidoyl chlorides with alkynes: one-pot synthesis of fluorinated quinolines

[reaction: see text]. Rh(I) complexes were found to catalyze the coupling cyclization of N-aryl trifluoroacetimidoyl chlorides with alkynes to afford 2-trifluoromethylated quinolines in good yields. Various alkynes were applied to this cyclization coupling with regioselectivity.     

Synthesis of naphthalenes through three-component coupling of alkynes, Fischer carbene complexes, and benzaldehyde hydrazones via isoindole intermediates

The synthesis of naphthalene derivatives through three-component coupling of 2-alkynylbenzaldehyde hydrazones with carbene complexes and electron-deficient alkynes has been examined. The reaction involves formation of an isoindole derivative, followed by intramolecular Diels-Alder reaction, followed by nitrene extrusion. The reaction was highly regioselective using unsymmetrical alkynes.