Scope of Ru(II)-catalyzed synthesis of pyridines from alkynes and nitriles

Pyridines can be efficiently synthesized by Ru(II)-catalyzed [2 + 2 + 2] cycloaddition of 1,6-diynes to alpha,omega-dinitriles or electron-deficient nitriles or by Ru(II)-catalyzed [2 + 2 + 2] cocyclization of electron-deficient alkynes and electron-deficient nitriles. The reactions with dinitriles seem likely to proceed via ruthenacyclopentadiene intermediates and the reactions with electron-poor nitriles via azaruthenacyclopentadienes. The reaction with asymmetric electron-deficient alkynes affords 2,3,6-trisubstituted pyridines in good yield.     

Nickel-catalyzed [4+2] cycloaddition for highly substituted arenes

Nickel(0) catalyzed [4+2] cycloaddition of electron-deficient dienes to alkynes and subsequent aromatization gave highly substituted arenes. This formal inverse electron-demand Diels-Alder cycloaddition is attributed to the formation of a seven-membered nickelacycle from a diene and an alkyne.     

Enantioselective rhodium-catalyzed [2+2+2] cycloaddition of alkenyl isocyanates and terminal alkynes: application to the total synthesis of (+)-lasubine II

The use of TADDOL-based phosphoramidite ligands on rhodium allows for the incorporation of terminal alkynes in the [2+2+2] cycloaddition with alkenyl isocyanates. Terminal aliphatic alkynes provide bicyclic lactams, while the use of aryl alkynes provides complementary access to vinylogous amides. Product selectivity seems to be governed by a combination of electronics and sterics, with smaller and/or more electron-deficient substituents favoring lactam formation. The use of homologous alkenyl isocyanates leads to an expedient asymmetric total synthesis of the alkaloid lasubine II.     

Photoreactions of bicyclic aziridines with alkenes and alkynes: a novel synthetic methodology for 8-azabicyclo[3.2.1]octane derivatives

The photochemical C-C bond cleavage of bicyclic aziridines 7 and subsequent [3 + 2] cycloaddition with electron-deficient alkenes and alkynes afforded the novel head-to-head adducts selectively and efficiently. The adducts contain the naturally occurring 8-azabicyclo[3.2.1]octane skeleton (e.g. tropane alkaloids). The aziridine 8 fused with a 6-membered ring also afforded the cycloadducts but in poor yields. The methylaziridine 9 reacted with an electron-deficient alkene, affording the head-to-tail adduct 23 in addition to head-to-head adducts 22a and 22b. The photoreactions of bicyclic aziridines with alkenes and alkynes indicate a similar behavior to that of aziridines with a linear chain.     

Direct [3+2]-cycloaddition of electron-deficient alkynes with CF3CHN2: Regioselective one-pot synthesis of 3-trifluoromethylpyrazoles

A direct and facile cycloaddition reaction of electron-deficient terminal alkynes with 2,2,2-trifluorodiazoethane under mild conditions to afford a series of 5-substituted 3-trifluoromethylpyrazoles in high yields is described. The potential application of this cycloaddition reaction was demonstrated via the efficient synthesis of a key intermediate of the antiviral drug AS-136A and a fluorinated analog of Tebufenpyrad.     

Unprecedented 1,4-stannatropy: effective generation of azomethine ylides as nitrile ylide equivalents from N-(stannylmethyl)thioamides

Generation and cycloaddition of less- or non-stabilized azomethine ylides, or nitrile ylide equivalents, via unprecedented 1,4-stannatropy of N-(tributylstannylmethyl)thioamides were achieved. The reactions with dipolarophiles, such as electron-deficient alkenes and alkynes, afforded corresponding pyrrolidine and pyrrole derivatives effectively.     

A highly efficient cycloaddition of vinylarenes with electron-deficient alkynes affording 1,2-disubstituted-3,4-dihydronaphthalenes catalysed by N,N-dimethylformamide dimethyl acetal

1,2-Disubstituted-3,4-dihydronaphthalenes could be conveniently synthesized with high yields by the cycloaddition reactions of easily available vinylarenes with electron-deficient alkynes such as dimethyl, or diethyl acetylenedicarboxylate, methyl phenylpropiolate in the presence of DMF.DMA (N,N-dimethylformamide dimethyl acetal) as organocatalyst.     

The Synthesis of 1,3-Dithiole Derivatives by Using Bun3P·CS2 Adduct

The red crystalline adducts formed between trialkylphosphines and carbon disulfide were confirmed to be l,3-dipolar structure by X-ray diffraction in 1961.^[1] Despite the apparent synthetic potential of the 1,3-dipolar structure, studies on its cycloaddition have only been restricted in electron-deficient alkynes as dipolarophiles.^[2-5] However, reactions with electron-rich alkynes have received little attention.     

Rearrangements of regioisomeric 4-isoxazolines: the novel formation of enaminoderivatives

Regioisomeric 4-isoxazolines are formed by 1,3-dipolar cycloaddition of C-benzoyl-N-phenylnitrone to electron-deficient alkynes. The 4- and 5-substituted cycloadducts react in different modes under the same conditions yielding enaminoderivatives, via a novel rearrangement process, and amines, aziridines and 1,3-oxazolines according to the substitution pattern.     

Photochemical cycloaddition reagents for rigidly attaching the 1, 4-dimethoxynaphthalene chromophore to scaffold alkenes

The norbornanecyclobutene epoxides 1a-1c containing a fused 1, 4-dimethoxynaphthalene chromophore have been reacted with cyclobutenes, cyclohexenes, norbornenes, 7-isopropylidenenorbornenes, 7-azanorbornenes, and other cyclic or electron-deficient alkenes at room temperature to form 1:1 adducts in stereoselective 1,3-dipolar cycloaddition reactions; alkynes can also participate in this reaction. The ability to form 2:1 adducts has also been demonstrated, thereby opening up opportunities for preparing functionalized products with large chromophore separations.     

Ruthenium-catalyzed formal [4 + 2] cycloaddition of alkynes with alkenes: formation of cyclohexenedicarboxylates via isomerization of alkynes and successive Diels-Alder reaction

Formal [4 + 2] cycloaddition of alkynes with electron-deficient alkenes, which affords 3,6-dialkyl-4-cyclohexene-1,2-dicarboxylates, was achieved using Ru(η⁶-1,3,5-cyclooctatriene)(η²-dimethyl fumarate)₂ as a catalyst. The reaction mechanism consists of two steps, isomerization of an alkyne to conjugated dienes and successive Diels-Alder reaction of the generated dienes with an electron-deficient alkene.     

Ligand-free copper(Ι)-catalyzed Sonogashira-type coupling of arylboronic acids with terminal alkynes

An efficient ligand-free CuI-catalyzed Sonogashira-type coupling reaction of arylboronic acids with terminal alkynes under air is described. The electron-deficient alkynes gave the desired cross-coupling products in good yields. Thus, it represents a simple and alternative method for the traditional Sonogashira reaction.     

Addition reactions of thiazol-5(4H)-ones—III : Cycloaddition reactions of mesoionic thiazol-5-ones

In contrast with the behaviour of mesoionic oxazol-5-ones, corresponding thiazol-5-ones give stable cycloadducts with electron-deficient alkenes. However, the thiazolones undergo cycloaddition-extrusion reactions with alkynes and with heterocumulenes, in many cases giving products identical with those from corresponding oxazolones. Examples of the influence of thiazolone substituents on the course of these cycloaddition reactions are provided by comparison of results of reactions of differently-substituted mesoionic thiazol-5-ones with phenyl isocyanate, phenyl isothiocyanate, or dimethyl furmarate.     

Activation of a CNXylyl ancillary ligand in the reaction of electron-deficient alkynes with a phosphido niobocene complex

The niobium phosphido complex [Nb(eta5-C5H4SiMe3)2-(CNXylyl)(PPh2)] (2) undergoes an unusual cycloaddition reaction with electron-deficient alkynes to give the novel five-membered heteroniobacycles [Nb(eta5-C5H4SiMe3)2(kappaC-C(=N(Xylyl))C(CO2Me)=C(R)PPh2-kappaP)] (R = H 3 and R = Me 4).     

[2+2]环加成反应机理的理论研究

[2+2]环加成反应是有机化学中非常重要的一类反应,其机理的研究一直是实验和理论工作者关注的课题之一。本文从理论的角度综述了三类[2+2]环加成反应的反应机理,即简单烯烃或炔烃参与的环加成反应、累积双键体系参与的环加成反应以及稀土钍化合物参与的环加成反应, 得出对于简单的烯烃或炔烃之间的环加成反应一般是按双自由基机理进行,而其他两类反应主要按协同或两性离子方式进行,并且从前线分子轨道作用理论角度分析了产生不同反应机理的原因。     

Highly satisfactory procedures for the Pd-catalyzed cross coupling of aryl electrophiles with in situ generated alkynylzinc derivatives

[reaction: see text] Two new and very efficient procedures (Procedures A and B) are reported for the Pd-catalyzed cross coupling of aryl electrophiles with terminal alkynes via their in situ conversion into alkynylzinc derivatives. Procedure A is particularly valuable in cases where electron-deficient alkynes are used, while Procedure B is operationally simple and very satisfactory in less demanding cases.     

BF3·Et2O promoted conjugate addition of ethanethiol to electron-deficient alkynes

An effective method for the synthesis of vinyl thioethers through the conjugate addition of ethanethiol to electron-deficient alkynes promoted by BF₃Et₂Ohas been developed.Electron-deficient internal alkynes react with ethanethiol in this system to yield mainly Z-isomer of vinyl thioether adducts,while electron-deficient terminal alkynes afford mainly E-isomer of vinyl thioether adducts.     

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.     

Phosphines catalyzed nucleophilic addition of azoles to allenes: synthesis of allylazoles and indolizines

Triphenylphosphine was used as nucleophilic catalyst for umpolung addition of azoles to electron-deficient allenes. This strategy offers a simple and efficient method for functional allylation of azoles under neutral conditions and affords heterocyclic substituted Michael olefins. Furthermore, this catalytic methodology has been extended to addition-cyclization reactions between electron-deficient allenes or alkynes and pyrrole-2-carboxaldehyde in the presence of catalytic amount of tributylphosphine. In such conditions, substituted indolizine-7-carboxylates are easily obtained.     

Chiral spiro-β-lactams from 6-diazopenicillanates

Chiral spiro-β-lactam derivatives have been prepared via stereoselective 1,3-dipolar cycloaddition of 6-diazopenicillanates. Using dipolarophiles such as acrylonitrile, acrylates or methyl vinyl ketone spiro-2-pyrazoline-β-lactams were obtained, whereas the cycloaddition with N-substituted-maleimides afforded spiro-1-pyrazoline-β-lactams. 6-Diazopenicillanates also reacted with electron-deficient alkynes to give the corresponding spiro-3H-pyrazole-β-lactam as single product. The observed stereoselectivity can be explained considering that the major product results from the addition to the less sterically hindered α-side of the β-lactam. Microwave-induced denitrogenation of spiro-1-pyrazoline-β-lactams allowed the stereoselective synthesis of novel spirocyclopropyl-β-lactams. The rationalization of the observed selectivity was supported by electronic structure calculations.