Electronic effects of ruthenium-catalyzed [3+2]-cycloaddition of alkynes and azides

A combined experimental and theoretical study of ruthenium-catalyzed azide-alkyne cycloaddition (RuAAC) reactions is presented and various electronic analyses were conducted to provide a basis in understanding the observed regioselectivity of the 1,2,3-triazole products. Computational studies using density functional theory (DFT) and atoms in molecules quantum theory (AIM) further yield fresh details on the electronic factors that determine the regioselectivity in the RuAAC. It is found that the formation of 1,2,3-triazole products is irreversible and from the Hammett study, the pathway involving a vinyl cationic intermediate is ruled out. The electronic effect favors the formation of 5-electron-donating-group substituted-1,2,3-trizoles.     

1-Protected 5-amido 1,2,3-triazoles via ruthenium-catalyzed [3+2] cycloaddition of azides and ynamides

Ynamides react with various azides in the ruthenium-catalyzed Huisgen [3+2] cycloaddition reaction. This ruthenium-catalyzed azide-ynamide cycloaddition reaction yields 1-protected 5-amido 1,2,3-triazoles.     

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.     

Synthesis of furanophane derivatives through [8+2]-cycloaddition of dienylisobenzofurans and alkynes

The coupling of various dienylisobenzofurans with dimethyl acetylenedicarboxylate (DMAD) has been examined. In most cases, this reaction proceeds via [8+2]-cycloaddition to afford furan-bridged decatetraene ring systems. The major competing reaction pathway is [4+2]-cycloaddition between DMAD and the isobenzofuran nucleus. Isobenzofuran intermediates were generated using either a chromium carbene-based method or an acid-catalyzed method.     

A density functional theory study of rhodium-catalyzed hetero-[5+2]-cycloaddition of cyclopropyl imine derivatives and alkynes

The intermolecular [5+2]-cycloaddition mechanism of cyclopropyl imines and alkynes catalyzed by [Rh(CO)2Cl]2 has been studied using density functional theory, comparing this multistep process with the two-step reaction in the absence of catalyst. Calculations show that a similar mechanism to that found for dihydroazepines could also lead to the formation of oxepines by replacing the imine nitrogen by oxygen. The results indicate that the formation of the oxepine can proceed with smaller barriers than those found for dihydroazepines. In fact, energy barriers are even smaller than those for other reactions employed for oxepine production, exhibiting values similar to those obtained for the reactions between acetilene and vinylcyclopropanes. Several substituted alkynes were tested for the reaction leading to no significant differences among them.     

Metal-free visible-light-promoted intermolecular [2+2]-cycloaddition of 3-ylideneoxindoles

The Rose Bengal sensitized intermolecular [2 + 2]-cycloaddition of 3-ylideneoxindoles for the synthesis of spirocyclic oxindoles was developed successfully under visible light irradiation conditions. The cycloaddition products were obtained in good yields (up to 93%) with excellent diastereoselectivity and regioselectivity by using a low loading of Rose Bengal (0.125 mol%) as a triplet sensitizer. This work demonstrates the potential benefits of Rose Bengal in visible light catalysis.     

Gold-catalyzed intramolecular [3 + 2]-cycloaddition of arenyne-yne functionalities

We report a new efficient intramolecular [3 + 2]-cycloaddition of unactivated arenyne (or enyne)-yne functionalities, catalyzed mainly by the AuPPh3SbF6 complex (2 mol %) under ambient conditions. The value of this cyclization is reflected by its applicability to a wide range of diyne substrates bearing various functional groups.     

A gold-catalyzed [4+3]-cycloaddition of functionalized dioxines

Treatment of 5-silyloxydioxins with 5 mol % AuCl₃/AgSbF₆ in the presence of cyclopentadiene or furan results in the rapid formation of [4+3]-cycloadducts at room temperature.     

Ruthenium-catalyzed regioselective [2 + 2 + 2] cyclotrimerization of trifluoromethyl group substituted internal alkynes

It found that the Ru(3)(CO)(12) coordinated with 2-(diphenylphosphino)benzonitrile (2-DPPBN) to effectively catalyze the [2 + 2 + 2] cyclotrimerization of the trifluoromethyl group substituted internal alkynes in high yields with up to >98% regioselectivity. Isolation of a ruthenacyclopentadiene was successful and confirmed that the complex is a reaction intermediate.     

Click chemistry in CuI-zeolites: the Huisgen [3 + 2]-cycloaddition

[reaction: see text] CuI-exchanged solids based on zeolite materials were investigated for the first time as catalysts in organic synthesis. The catalytic potential of these materials was evaluated in the Huisgen [3 + 2]-cycloaddition. Five CuI-exchanged zeolites were examined and CuI-USY proved to be a novel and efficient heterogeneous ligand-free catalyst for this "click chemistry"-type transformation.     

(NHC)Copper(I)-catalyzed [3+2] cycloaddition of azides and mono- or disubstituted alkynes

A versatile and highly efficient catalyst for the Huisgen cycloaddition reaction has been developed. Previously isolated or in situ generated azides yielded 1,2,3-triazoles with differently substituted alkynes in the presence of a [(NHC)CuBr] complex (NHC = N-heterocyclic carbene). Extremely high reaction rates and excellent yields were obtained in all cases. This catalytic system fulfils the requirements of "click chemistry" with its mild and convenient conditions, notably in water or solvent free reactions and simple isolation with no purification step. Furthermore, for the first time, an internal alkyne was successfully used in this copper-catalyzed cycloaddition reaction. DFT calculations on this particular system allowed for the proposition of a new mechanistic pathway for disubstituted alkynes.     

Phosphorus compounds with unusual coordination - 201. 1,2,3,4- triazaphospholes by [3+2]-cycloaddition of azides to a stable phosphaalkyne

The azides 2a-i undergo regiospecific [3+2]-cycloaddition with the phospha-alkyne 1 to form the l,2,3,4-triazaphospholes 3a-i; in the case of the reaction with 2J, an additional silyl shift occurs resulting in the formation of 4j. The latter product can by hydrolyzed to 6 which has also been prepared independently from 1 and hydrazoic acid(7). Flash vacuum pyrolyses of the 1,2,3,4-triazaphospholes 3c and 3e produce mixtures of the isomers 13a,b and 14a,b, respectively, from which the 1,2-azaphospholes 14 can be isolated as the major reaction products.     

Intermolecular [3 + 3]-cycloadditions of azides with the Nazarov intermediate

Tetrasubstituted 1,4-dien-3-ones undergo Nazarov cyclization at low temperature, followed by reaction with organic azides via an apparent [3 + 3]-cycloaddition to give bridged bicyclic triazenes. These products do not appear to be intermediates in the previously described Schmidt-type process to furnish dihydropyridones. The reaction typically occurs with high diastereoselectivity.     

Synthesis of substituted imidazolines via [3+2]-cycloaddition of aziridines with nitriles

An efficient synthesis of 2,4-disubstituted 1H-imidazolines from aziridines and nitriles in the presence of BF₃-Et₂O or triethyloxonium tetrafluoroborate has been described. The reaction proceeds via a [3+2]-cycloaddition reaction. Most of the nitriles successfully underwent cycloaddition reactions with aziridines even at room temperature in a very short time.     

NbCl3-catalyzed three-component [2 + 2 + 2] cycloaddition reaction of terminal alkynes, internal alkynes, and alkenes to 1,3,4,5-tetrasubstituted 1,3-cyclohexadienes

Three-component [2 + 2 + 2] cycloaddition of terminal alkynes, internal alkynes, and terminal alkenes is achieved using an NbCl(3)(DME) catalyst, leading to 1,3,4,5-substituted 1,3-cyclohexadienes in excellent yields with high chemo- and regioselectivity.     

Nickel-catalyzed intermolecular [3 + 2 + 2] cocyclization of ethyl cyclopropylideneacetate and alkynes

The [3 + 2 + 2] cocyclization of ethyl cyclopropylideneacetate (1a) and terminal alkynes (2) proceeded smoothly in the presence of 10 mol % "Ni(PPh3)2", which was prepared in situ from Ni(cod)2 and PPh3. The high reactivity of 1a, which was induced by the introduction of an electron-withdrawing group, is very important for the progress of this reaction. The cycloheptadiene derivatives were synthesized in highly selective manner in good yields.     

A rigid GABA analog from a [4+3]-cycloaddition

A rigid GABA analog has been prepared from the adduct obtained from the [4+3]-cycloaddition of pentachloroacetone and a 2-substituted furan.     

On the [4+2]-cycloaddition reaction of levoglucosenone with piperylene

The Diets-Alder reaction of levoglucosenone with piperylene catalyzed by ZnCl₂ proceeds regio- and stereoselectively to give thesin-cis-adduct3; the thermal reaction yields an epimeric mixture of compound3 withsin-trans-adduct4 in the ratio of 4 : 1.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 10, pp. 2584–2585, October, 1996.     

Highly regioselective construction of spirocycles via phosphine-catalyzed [3 + 2]-cycloaddition

A direct entry to spirocycles with low to moderate regioselectivity was achieved by triphenylphosphine-catalyzed [3 + 2]-cycloaddition of active exo-methylenecycles (1) and ethyl 2,3-butadienoate (2). The regioselectivity of the reaction was greatly improved by using the bulky tert-butyl ester of the 2,3-butadienoate (5). The regioselectivity of the reaction was further enhanced by using the tert-butyl 2-butynoate as the substrate. This protocol provided an efficient entry to the skeleton of spirocarbocycles, especially spiro[4.n]alkanes.