Cycloaddition Of Azomethine Imines Research Articles

ChemInform Abstract: Copper(I) Acetate‐Catalyzed Cycloaddition Between Azomethine Imines and Propiolates under Additive‐Free Conditions.

AbstractA novel Cu(I)‐acetate catalyzed cycloaddition of azomethine imines (I) with activated terminal alkynes is described to give excellent yields of pyrazolo[1,2‐a]pyrazoles (III).

N-Heterocyclic Carbene-Catalyzed [3+4] Cycloaddition and Kinetic Resolution of Azomethine Imines

The first N-heterocyclic carbene (NHC)-catalyzed [3+4] cycloaddition of azomethine imines and enals is disclosed. Oxidative catalytic remote activation of enals affords 1,4-dipolarophile intermediates that react with 1,3-dipolar azomethine imines to generate dinitrogen-fused seven-membered heterocyclic products with high optical purities. Our approach also provides effective kinetic resolution of azomethine imines, in which the substrate chiral center that is remote from the NHC catalyst can be well resolved.

Desymmetrization of 1,4‐Pentadien‐3‐ol by the Asymmetric 1,3‐Dipolar Cycloaddition of Azomethine Imines

Desymmetrization of the divinyl carbinol 1,4-pentadien-3-ol was accomplished by the asymmetric 1,3-dipolar cycloaddition of azomethine imines based on a magnesium-mediated, multinucleating chiral reaction system utilizing diisopropyl (R,R)-tartrate as the chiral auxiliary. The corresponding optically active trans-pyrazolidines, each with three contiguous stereogenic centers, were obtained with excellent regio-, diastereo-, and enantioselectivity, with results as high as 99% ee. This reaction was shown to be applicable to both aryl- and alkyl-substituted azomethine imines. The use of a catalytic amount of diisopropyl (R,R)-tartrate was also effective when accompanied by the addition of MgBr2.

ChemInform Abstract: Development of a Tailor‐Made Bis(oxazolidine)pyridine—Metal Catalyst for the [3 + 2] Cycloaddition of Azomethine Imines with Propiolates.

AbstractA series of bis(oxazolidine)pyridine ligands is designed and applied in the title reaction.

Unexpected regioselectivities of [3 + 2] cycloaddition of azomethine imines to acrylonitrile and 4-nitrophenyl vinyl sulfone

The [3 + 2] cycloaddition of azomethine imines derived from 6-aryl-1,5-diazabicyclo[3.1.0]hexanes to acrylonitrile and 4-nitrophenyl vinyl sulfone proceeds with high diastereoselectivity, but with opposite regioselectivity, which has been clarified by quantum chemical calculations.

ChemInform Abstract: Catalyst‐Free and Stereoselective Synthesis of N,N‐Bicyclic Pyrazolidinone Derivatives.

AbstractThe 1,3‐dipolar cycloaddition of azomethine imines to nitroalkenes is investigated.

Ni-Catalyzed Enantioselective [3+3] Cycloaddition of Azomethine Imines

Ni-Catalyzed Enantioselective [3+3] Cycloaddition of Azomethine Imines

Nickel(II)‐Catalyzed Enantioselective 1,3‐Dipolar Cycloaddition of Azomethine Imines with Alkylidene Malonates

We demonstrated an asymmetric 1,3-dipolar cycloaddition of azomethine betaines with alkylidene malonates by using a chiral N,N'-dioxide-Ni(II) complex as a catalyst. Both aromatic- and aliphatic-substituted alkylidene malonates were found to be suitable for the reaction. A range of trans-pyrazolone derivatives was exclusively obtained with excellent yields (up to 99% yield) and good enantioselectivities (up to 97% ee) under mild reaction conditions. The reaction could be carried out on a gram scale with the good results being maintained. Control experiments were performed to elucidate the specific diastereoselectivity of the reaction. The formation of single trans isomers was dominated by secondary orbital interactions between the ester groups of the dipolarophile and the azomethine imine. On the basis of the experimental results and previous reports, a possible catalytic model was assumed.

Development of a tailor-made bis(oxazolidine)pyridine–metal catalyst for the [3+2] cycloaddition of azomethine imines with propiolates

A series of bis(oxazolidine)pyridine ligands (the PyBodines) were newly designed and synthesized for the development of a highly efficient, tailor-made catalyst for the [3+2] cycloaddition of azomethine imines with propiolates. The PyBodine(l-Ala)-Cu(OAc)2 catalyst was selected on the basis of solid-phase catalysis/CD-HTS and exhibited high efficiency, producing the (R)-adducts with excellent enantioselectivity.

触媒的不斉［3＋2］環化付加反応：多置換ピロリジン化合物の新立体化学制御

Highly functionalized complex molecules are key tools for promoting biochemical research and developing pharmaceuticals, because the network of chiralities, positions of heteroatoms, and direction of lone-pairs in the molecules are strictly linked to their biological activities. Catalytic asymmetric synthesis is the basis and core technology to supply these complex compounds in a stereoselective manner. Here, the catalytic asymmetric [3+2]-cycloaddition of iminoesters and nitroalkenes has been intensively investigated for giving chiral pyrrolidine structures which are observed abundantly in natural products and pharmaceuticals. Although the endo- or exo-selective [3+2]-cycloaddition has been widely examined using chiral Cu-catalysts, there is no report on the catalytic asymmetric synthesis of exo’-adduct. We accomplished the first catalytic asymmetric exo’-selective [3+2]-cycloaddition of azomethine imines and nitroalkenes using imidazoline-aminophenol (IAP)-Ni(OAc)2 complex to give the exo’-adduct in up to 99% ee. The first catalytic asymmetric exo’-selective [3+2]-cycloaddition of methyleneindolinones with iminoesters was also achieved by the IAP-Ni(OAc)2 complex for the construction of a novel diastereomer of biologically important spiro[pyrrolidin-3,3’-oxindole]. Moreover, a novel C2-symmetric bis(imidazolidine)pyridine ligand (PyBidine) was easily synthesized in a single condensation of 2,6-pyridyl aldehyde and optically active (S,S)-diphenylethylene diamine. The newly developed PyBidine-Cu(OTf)2 complex enabled the highly endo-selective [3+2]-cycloaddition of iminoesters with nitroalkenes.

Gold catalyzed [3+2] cycloaddition of N-allenyl amides with azomethine imines

Gold(I) catalyzed [3+2] cycloaddition of azomethine imines with N-allenyl amides was developed to provide two types of pyrazolyl based bicyclic heterocycles. Both pyrazolidin-3-one derived and dihydroisoquinoline derived azomethine imines reacted smoothly with N-allenyl amides to give 6-methylene bipyrazolidin-1-ones and 1-methylene hexahydropyrazolo[5,1-a] isoquinolines in moderate to good yields.

ChemInform Abstract: Thermal [3 + 2] Cycloaddition Reaction of Azomethine Imines with Allenoates for Dinitrogen‐Fused Heterocycles.

AbstractFor the first time allenoate is applied as dipolarophile in thermal 1,3‐dipolar cycloaddition of azomethine imines.

Chiral Bis(Imidazolidine)Pyridine-Cu Complex-Catalyzed Enantioselective [3+2]-Cycloaddition of Azomethine Imines with Propiolates

[3+2] Cycloaddition of azomethine imines with electron-deficient terminal alkynes was smoothly catalyzed by a chiral bis(imidazolidine)pyridine-CuOAc complex to give bicyclic pyrazolo[1,2-a]pyrazolone derivatives with up to 74% ee.

Synthesis of Pyrazolidines (5-membered heterocyclic rings) through 1, 3- dipolar cycloadditions of azomethine imines

Dipolar cycloadditions of azomethine imines, formed in situ from aldehydes and hydrazines with electron deficient dipolarophiles produced pyrazolidines. Monosubstituted dipolarophiles afford principally 4substituted pyrazolidines.

DFT study of 1,3-dipolar cycloaddition of azomethine imines with electron deficient dipolarophiles acrylonitrile, methylpropenoate, and dimethylmaleate

The 1,3-dipolar cycloaddition reactions of azomethine imines with some electron deficient dipolarophiles viz. acrylonitrile, methylpropenoate, and dimethylmaleate leading predominantly to 4-substituted pyrazolidines have been computationally studied which could be useful for the stereoselective synthesis of C-nucleosides. The mechanism of regioselectivity, chemoselectivity and diastereofacial selectivity were studied through the evaluation of activation parameters and philicity indices on the assumption of a concerted mechanism. The reactions were followed by performing transition state optimization, calculation of Intrinsic Reaction Coordinate and activation energies. The regioselectivity and reactivity were amply predicted by employing local and global electrophilicity and nucleophilicity indices. The reactions were considered to be nonpolar or at the most weakly polar on the basis of charge transfer calculated in the transition states. In the present cases, no facial selectivity could be observed due to energetic identity of the different enantiomeric transition states. A rationalization of the trends in regio- and chemoselectivity were also attempted in terms of chemical potential, hardness, global electrophilicity differences, local electrophilicity, local nucleophilicity, Pauling’s bond order and Wiberg bond indices in the transition state. Theoretical evaluation of rate constants for elementary reaction steps employing the transition state theory is very much useful for getting quantitative idea about the kinetic rates associated with those steps. Calculation of rate constants were performed with the Eyring’s TST rate equation and using total partition functions of the concerned species at different temperatures. The activation energy was recomputed for consistency from the slope of the plot of 1000/ T vs. −log ( k). All the computed results were derived from density functional calculations at the B3LYP/6-31G(d) level of theory. Considering the fact that the reactions are practically carried out in solutions, some calculations were performed in solvents of different polarity to examine its influence on the activation barrier or the reaction rate.

1,3-Dipolar Cycloaddition of Hydrazones with α-Oxo-ketenes: A Three-Component Stereoselective Entry to Pyrazolidinones and an Original Class of Spirooxindoles

Stereodefined monocyclic, spirobicyclic, and bis-spirotricyclic pyrazolidin-3-ones can be prepared efficiently by a three-component reaction involving a 1,3-dipolar cycloaddition of azomethine imines obtained from hydrazones with α-oxo-ketene dipolarophiles generated in situ. The reaction allows the creation of four covalent bonds and two contiguous chiral quaternary centers with excellent diastereoselectivity in a single catalyst/additive-free, highly atom-economical transformation. From a fundamental point of view, the reaction introduces α-oxo-ketenes as effective dipolarophiles in 1,3-dipolar cycloadditions.

Highly Regioselective [3 + 2] Annulation of Azomethine Imines with 1-Alkynyl Fischer Carbene Complexes to Functionalized N,N-Bicyclic Pyrazolidin-3-ones

The highly regioselective [3 + 2] cycloaddition of azomethine imines to 1-alkynyl Fischer carbene complexes has been successfully realized under mild conditions. Oxidative demetalation of the newly formed pyrazolo-pyrazolone carbene complexes with pyridine-N-oxide or ceric ammonium nitrate efficiently afforded pyrazolo-pyrazolone derivatives as well as cycloprop-2-enone and trisubstituted 1H-pyrazoles in some cases, providing a novel route to versatile functionalized N,N-bicyclic pyrazolidin-3-ones.

Stereoselective synthesis of polyoxygenated linear diaza-triquinanes via intramolecular 1,3-dipolar cycloaddition of sugar-derived hex-5-enals

An efficient and stereoselective synthesis of diaza-triquinanes, the skeleton structures of many natural products, has been accomplished by intramolecular 1,3-dipolar cycloaddition of azomethine imine generated from sugar-derived hex-5-enal and pyrazolidin-3-one.

Cascade cyclization, dipolar cycloaddition of azomethine imines for the synthesis of pyrazolidines

A tandem multi-step, one-pot reaction of aldehydes with hydrazines has been used for the preparation of tetrahydropyrazoles and dihydropyrazoles. The chemistry involves condensation then cyclization, followed by inter- or intramolecular dipolar cycloaddition of the resulting azomethine imine intermediates. The intramolecular cycloaddition gives fused tricyclic compounds as single diastereoisomers. The intermolecular cycloaddition was successful with a variety of activated alkene and alkyne dipolarophiles.

Asymmetric 1,3-Dipolar Cycloaddition of Azomethine Imines to Homoallylic Alcohols

Abstract The asymmetric 1,3-dipolar cycloaddition of azomethine imines to homoallylic alcohols was achieved by utilizing diisopropyl (R,R)-tartrate as a chiral auxiliary to give the corresponding optically active trans-pyrazolidines with excellent regio-, diastereo-, and enantioselectivities. The catalytic use of diisopropyl (R,R)-tartrate was also effective in the presence of MgBr2.