Cycloaddition Reaction Of Azomethine Imines Research Articles

Organocatalyzed cycloaddition reactions of azomethine imines—A lookback

AbstractThe versatile and convergent nature of 1,3‐dipolar cycloaddition reactions has made them an indispensable tool in organic chemistry for synthesizing five‐membered heterocycles. Among the various dipoles, azomethine imines (AMI) constitute a versatile class, increasingly used to synthesize biologically relevant heterocycles. The organocatalytic cycloaddition reactions of azomethine imines are relatively unexplored compared to the corresponding transition metal‐catalyzed reactions. This review highlights the unique organocatalytic cycloaddition reactions of AMI with different dipolarophiles. The cycloaddition of azomethine imines catalyzed by organic bases such as prolinol, proline, alkaloids, 1,4‐diazabicyclo[2.2.2]octane, 1,8‐diazabicyclo[5.4.0]undec‐7‐ene (DBU), primary amines, tertiary amines, N‐heterocyclic carbene, and phosphine are discussed here. The mechanistic and electronic aspects, including broad functional group tolerance, catalyst loading, and reaction conditions, are evaluated. This review also demonstrates the scope and potential reactivity of azomethine imines in organocatalytic cycloadditions. We are positive that the reactions of azomethine imines discussed here will aid in discovering new and efficient reaction pathways in synthesizing biologically active and industrially relevant molecules.

CuI-Catalyzed [3+2] Cycloaddition of Hindered Vinylidenebisphosphonates (VBP) with Azomethine Imines for Highly Regioselective Access to Dinitrogen-Heterobicycle-Containing Bisphosphonates

A concise, atom-economic, and highly regioselective synthetic strategy for the construction of several dinitrogen-fused heterocycles bearing bisphosphonates by 1,3-dipolar cycloaddition reaction of azomethine imines with tetraethyl vinylidene-1,1-bisphosphonate in the presence of CuI in toluene media has been developed. The targeted compounds were obtained in good yields and with excellent regioselectivity. This method for the synthesis of gem-bisphosphonates (BPs) is particularly attractive due to features such as low cost, mild conditions, atom economy, high stereoselectivity, and potential biological activity of the product.

Chiral NHC-catalyzed 1,3-dipolar [3 + 2] cycloaddition of azomethine imines with α-chloroaldehydes for the synthesis of bicyclic pyrazolidinones.

A chiral N-heterocyclic carbene (NHC)-catalyzed 1,3-dipolar [3 + 2] cycloaddition reaction of 3-oxopyrazolidin-1-ium-2-ides and α-chloroaldehydes was developed for the synthesis of pyrazolo[1,2-a]pyrazole-1,7-diones in moderate to good yields (up to 76%) with good enantioselectivities (up to 98% ee) and diastereoselectivities (up to 8 : 1 dr).

Thermal 1,3-dipolar cycloaddition of azomethine imines with alkynes affording N,N-bicyclic pyrazolidinones under microwave irradiation

A metal and catalyst free 1,3-dipolar cycloaddition reaction of azomethine imines with internal alkynes has been developed. Various N,N-bicyclic pyrazolidinones could be prepared quickly under microwave irradiation in moderate to excellent yields (up to 96%). A wide range of azomethine imines and electron-deficient internal alkynes were applicable to this reaction. In addition, gram-scale reaction could be achieved and fully substituted pyrazole can be obtained by easy transformation of N,N-bicyclic pyrazolidinone. This environment friendly dipolar cycloaddition is remarkable for its simplicity in conditions and wide structural diversity.

ChemInform Abstract: DABCO‐Catalyzed [3 + 2] Cycloaddition Reactions of Azomethine Imines with N‐Aryl Maleimides: Facile Access to Dinitrogen‐Fused Heterocycles.

Abstract DABCO-catalyzed [3+2] cycloaddition of azomethine imines with maleimides has been developed. This method could efficiently furnish dinitrogen-fused tetracyclic heterocycles in high levels of regioselectivity and with good yields.

Thermal 1,3-dipolar cycloaddition reaction of azomethine imines with active esters.

An efficient method for the 1,3-dipolar cycloaddition of azomethine imines with active esters under thermal conditions has been described in good to high yields. This method offers a straightforward pathway to synthesize bioactive pyrazolidinones.

DABCO-catalyzed [3+2] cycloaddition reactions of azomethine imines with N-aryl maleimides: facile access to dinitrogen-fused heterocycles

DABCO-catalyzed [3+2] cycloaddition of azomethine imines with maleimides has been developed. This method could efficiently furnish dinitrogen-fused tetracyclic heterocycles in high levels of regioselectivity and with good yields.

Phosphine‐Catalyzed [3+2] Cycloaddition Reactions of Azomethine Imines with Electron‐Deficient Alkenes: A Facile Access to Dinitrogen‐Fused Heterocycles

An efficient method for the phosphine-catalyzed [3+2] cycloaddition reaction of azomethine imines with diphenylsulfonyl alkenes to give dinitrogen-fused bi- or tricyclic heterocyclic compounds in high yields has been described. Moreover, two phenylsulfonyl groups installed on the heterocyclic products could be conveniently removed or transformed to other functional groups, making the reaction more useful.

Group 11 Metal Amide-Catalyzed Asymmetric Cycloaddition Reactions of Azomethine Imines with Terminal Alkynes

We developed a 1,3-dipolar cycloaddition reaction of azomethine imines with terminal alkynes catalyzed by group 11 metal amides to provide N,N-bicyclic pyrazolidinone derivatives. This reaction afforded the cycloadducts in a unique 5,7-disubstituted manner. Furthermore, we succeeded in applying this catalysis to asymmetric reactions, and the desired heterocycles were produced in high yields with exclusive regioselectivity and high enantioselectivity. Mechanistic studies elucidated a stepwise reaction pathway and critical features that determine the regioselectivity.

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.

Thermal [3+2] cycloaddition reaction of azomethine imines with allenoates for dinitrogen-fused heterocycles

The thermal [3+2] cycloaddition reactions of two classes of azomethine imines with allenoates have been investigated. The reactions are operationally simple and proceed smoothly under mild reaction conditions to provide a variety of dinitrogen-fused heterocycles in moderate to excellent yields.

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.

ChemInform Abstract: Recent Progress in a Chiral Multinucleating System Utilizing Tartaric Acid Esters

AbstractReview: 125 refs.

ChemInform Abstract: Asymmetric 1,3‐Dipolar Cycloaddition Reactions of Azomethine Imines with Acrolein Catalyzed by L‐Proline and Its Derivatives.

Abstract(S)‐Indoline‐2‐carboxylic acid as catalyst shows high exo‐selectivity, while with L‐proline exo‐products are favored due to isomerization of the exo‐ to the endo‐cycloadducts.

Recent progress in a chiral multinucleating system utilizing tartaric acid esters

In order to develop a practical method for the construction of chiral molecules, we have designed a novel chiral reaction system possessing multi-metal centers utilizing tartaric acid ester as a chiral auxiliary. Based on this concept, we have developed an asymmetric 1,3-dipolar cycloaddition reaction of azomethine imines, an asymmetric hetero Diels-Alder reaction of nitroso compounds, an asymmetric Diels-Alder reaction of o-quinodimethanes. Furthermore, an asymmetric nucleophilic addition of alkynylzinc reagents, prepared in situ from dialkylzinc and 1-alkynes, to nitrones was achieved with high level of stereocontrol. In the last case, the addition of methylzinc salt of a product-like racemic hydroxylamine was found to be effective for unprecedented enhancement of enantioselectivity.

Asymmetric 1,3-Dipolar Cycloaddition Reactions of Azomethine Imines with Acrolein Catalyzed by L-Proline and Its Derivatives

1,3-Dipolar cycloadditions between acrolein and various N,N'-cyclic azomethine imines in the presence of L-proline and its derivatives as organocatalysts were investigated. Reactions that were catalyzed by (S)-indline-2-carboxylic acid (30 mol%) in CHCl 3 /MeOH 97:3 (v/v) showed high exo-selectivities (exo/endo 91:9 ∼ 99:1) and enantioselectivities (75 ∼ 98% ee). In contrast, reactions catalyzed by L-proline (30 mol%) under similar conditions favored the endo-cycloadduct (83:27 ∼ 99:1) with modest to good enantioselectivities (31 ∼ 83% ee). Based on our studies, the diastereoselective mechanism of the L-proline-catalyzed reaction was found to involve the isomerization of the exo- to the endo-cycloadduct in the presence of L-proline.

Stereocontrolled Synthesis of Functionalized cis‐Cyclopentapyrazolidines by 1,3‐Dipolar Cycloaddition Reactions of Azomethine Imines.

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Stereocontrolled Synthesis of Functionalized cis-Cyclopentapyrazolidines by 1,3-Dipolar Cycloaddition Reactions of Azomethine Imines

The reaction of alkene-tethered alpha-ketocarboxylic acid derivatives with monosubstituted hydrazines allows highly substituted cis-cyclopentapyrazolidine ring systems to be constructed rapidly. Successful cyclocondensations are realized under thermal reaction conditions; in some cases, protic or Lewis acids accelerate these reactions. alpha-Methoxy-alpha,beta-unsaturated esters are suitable alkene components, as are alkenes having either electron-withdrawing or electron-donating substituents at the terminal alkene carbon. alpha-Ketoesters, alpha-ketoamides, and alpha-ketothioesters can be employed. Various hydrazines substituted with N-acyl, N-carboalkoxy, or N-carbamothioyl protecting groups are tolerated in these transformations. The rate of intramolecular cycloaddition is found to reflect not only the reactivity and equilibrium concentration of the azomethine imine intermediate, but, also in some cases, the rate at which hydrazone stereoisomers interconvert under the reaction conditions.

Synthesis of Novel Spiro‐[3H‐indole‐3,3′‐[1,2,4]triazolidine]‐2‐ones via Azomethine Imines.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of novel spiro-[3 H-indole-3,3′-[1,2,4]triazolidine]-2-ones via azomethine imines

Novel spiroindoles 5 are prepared easily via a one-pot, 1,3-dipolar cycloaddition reaction of azomethine imines with isatin imines under thermal conditions.