aza-Diels Alder Reaction Research Articles

Cerium(III) immobilized on the functionalized halloysite as a highly efficient catalyst for aza-Diels–Alder reaction

Aza-Diels–Alder cycloaddition reaction is a critical synthetic method for the production of bioactive tetrahydroquinolines. To this aim, an imine obtained from the reaction of an aniline derivative and a carbonyl compound is cyclized with an alkene in the presence of a catalyst. In this research, some tetrahydroquinoline compounds are synthesized through aza-Diels–Alder reaction in the presence of a prepared Ce(III) immobilized on the functionalized halloysite (Ce/Hal-TCT-IDA) as a catalyst. Ce/Hal-TCT-IDA was prepared by incorporation of aminopropyl silane on the halloysite surface, followed by treatment with 2,4,6-trichloro-1,3,5-triazine (TCT) and iminodiacetic acid (IDA), and loading cerium nitrate. Then, it was characterized and analyzed by different analytical methods, indicating the amorphous agglomerated grains (20–60 nm), containing 0.00196 mmol g−1 Ce(III) ions. The catalytic activity and reusability of Ce/Hal-TCT-IDA were studied in this research.

Access to polysubstituted pyrimidine derivatives via the aza-Diels–Alder reaction of 1,2,3-triazine derivatives and amidines

The synthesis of highly substituted pyrimidine derivatives by the aza-Diels–Alder reaction of 1,2,3-triazines with amidine derivatives is described. This reaction provided direct access to a wide range of 6-aryl-2-substituted pyrimidine-4-carboxylates in good yields with good functional group compatibility. A broad substrate scope, and the operationally simple, metal-free, and neutral reaction conditions are the prominent features of this method.

I2-Promoted gem-Diarylethene Involved Aza-Diels–Alder Reaction and Wagner–Meerwein Rearrangement: Construction of 2,3,4-Trisubstituted Pyrimido[1,2-b]indazole Skeletons

A [3 + 1 + 2] cyclization-rearrangement reaction scheme was developed to synthesize pyrimido[1,2-b]indazoles from aryl methyl ketones, 3-aminoindazoles, and gem-diarylethenes. This metal-free process proceeds via a sequential aza-Diels-Alder reaction and Wagner-Meerwein rearrangement, and a possible reaction mechanism was demonstrated based on control experiments. This method exhibits good substrate compatibility and allows simple reaction conditions. Moreover, the products display significant aggregation-induced emission characteristics after simple modifications.

Transition-Metal-Free Dehydrogenation of Benzyl Alcohol for C-C and C-N Bond Formation for the Synthesis of Pyrazolo[3,4-b]pyridine and Pyrazoline Derivatives.

A series of cascade reactions that produce a range of functionalized aromatic heterocyclic compounds with pyrazole/pyrazoline cores have been developed. The method relies on a metal-free dehydrogenative process to produce in-situ benzaldehydes. The produced benzaldehyde was then allowed to react with some other substances, including acetophenone, pyrazole amine, and phenylhydrazine. The intermediate produced from these substrates underwent several chemical processes, including electrocyclization, the aza-Diels-Alder reaction, and the formation of intramolecular C-N bonds. These positive outcomes would open up the possibility of producing biologically active pyrazolo[3,4-b]pyridine and pyrazoline derivatives through a variety of possible reactions.

INTERACTION OF 2-AMINO-(4-ARYL)-SUBSTITUTED THIA- AND OXAZOLES WITH 5-CYANO-1,2,4-TRIAZINES

An interaction of 6-aryl-1,2,4-triazine-5-carbonitriles with 2‑amino-substituted thiazoles and oxazoles has been studied. The difference in the reactivity of these aminoheterocycles depending on the presence of an oxygen or sulfur atom in their composition has been demonstrated. Previously, the 4-aryl-3-hydroxy-2,2'-bipyridines were obtained as products of aza-Diels–Alder reaction between 6-aryl-3-(2-pyridyl)-1,2,4-triazine-5-carbonitriles and 2-amino-4-aryloxazoles. In the present work we have shown that the reaction of 6-aryl-1,2,4-triazine-5-carbonitriles with 2-aminothiazoles led to the products of ipso-substitution of cyano-group. The aza-Diels–Alder reaction of these compounds with 2,5-norbornadiene allowed to obtain (2,2'-bi)pyridines with the thiazol-2-amine moiety at alpha-position.

Synthesis And Characterization Of New 1,2,4- Triazine Based On 2,5-Dihydrazino-1,3,4- Thiadiazole

The chemistry of 1,2,4-triazine derivatives received a great deals of attention in recent year due to the use of such ring system as the core structure in many heterocyclic compound covering wide range of applications in many different field especially in industrial and biological fields. An efficient aza Diels-Alder reaction have been used in this presentation to prepare the hetero adducts represented by N2,N5-di(3,5,6-tri aryl-5,6-dihydro-1,2,4-triazine-4(3H)-yl)-1,3,4-thiadiazole-2,5-diamino( 9-20)from hetero dienes and hetero dienophile. However the preparation starting form 1,3,4-thiadiazole-2,5 dithaiole (1) which converted directly to the dihydrazino derivatives(2) which then afford under condensation reaction hetero dienophile represented by 2,5-bis Schiff bases of 1,3,4-thiadiazole(3-6) by its reaction with substituted benzaldehyde . The last compound were reacted through one-pot free solvent aza Diels-Alder reaction with appropriate hetero diene( hydrazine with substituted benzaldehyde in ratio 1:2) (7&8 ) to afford 1,2,5-triazine derivatives (9-20) using grinding and MWI techniques as a types of green chemistry approaches.

Diaza-1,3-butadienes as Useful Intermediate in Heterocycles Synthesis.

Many heterocyclic compounds can be synthetized using diaza-1,3-butadienes (DADs) as key structural precursors. Isolated and in situ diaza-1,3-butadienes, produced from their respective precursors (typically imines and hydrazones) under a variety of conditions, can both react with a wide range of substrates in many kinds of reactions. Most of these reactions discussed here include nucleophilic additions, Michael-type reactions, cycloadditions, Diels–Alder, inverse electron demand Diels–Alder, and aza-Diels–Alder reactions. This review focuses on the reports during the last 10 years employing 1,2-diaza-, 1,3-diaza-, 2,3-diaza-, and 1,4-diaza-1,3-butadienes as intermediates to synthesize heterocycles such as indole, pyrazole, 1,2,3-triazole, imidazoline, pyrimidinone, pyrazoline, -lactam, and imidazolidine, among others. Fused heterocycles, such as quinazoline, isoquinoline, and dihydroquinoxaline derivatives, are also included in the review.

One-Pot Synthesis of Novel Functionalized Fused Pyridine Derivatives via Consecutive Pyrrolidine Ring-Closure/Ring-Opening/Formal Aza-Diels-Alder Reactions.

In this article, we report a highly regioselective method for the synthesis of new fused pyridine derivatives─2,3-disubstituted quinolines and 1,2-dihydro-3H-pyrazolo[3,4-b]pyridin-3-one derivatives. The method is based on the reaction of 1,1-diethoxybutane derivatives with aromatic and heterocyclic nucleophiles. The isolated compounds are similar to the products formed as a result of the Debner-Miller reaction. However, we have shown that the interaction of 1,1-diethoxybutane derivatives with (hetero)aromatic amines proceeds according to a mechanism different from that of the Doebner-Miller reaction. The proposed method is distinguished by the possibility of obtaining a wide range of substituted quinolines and 1,2-dihydro-3H-pyrazolo[3,4-b]pyridin-3-one derivatives in one step, the absence of the need to use expensive metal-containing catalysts, and a high product yield.

One-pot synthesis of cyclopentane-fused 5'-aryl-4-cycloalkylamino-2,2'-bipyridines via the aza-Diels–Alder/SNipso reactions

One-pot synthesis of cyclopentane-fused 5'-aryl-4- cycloalkylamino-2,2'-bipyridines based on the neat (200 °C) reaction of 3-(4-bromopyridin-2-yl)-1,2,4-triazines with enamines is reported. In the course of the transformation, consecutive aza-Diels–Alder reaction and nucleophilic substitution of bromine atom under the action of the liberating amine occur. The possibility of the solvent- and catalyst-free replacement of 4-positioned bromine atom in 2,2'-bipyridines by amino moieties was demonstrated.

Evaluation of the mechanism, regio-, and diastereoselectivity of aza-Diels–Alder reactions of 2H-azirine under a Lewis acid catalyst

Evaluation of the mechanism, regio-, and diastereoselectivity of aza-Diels–Alder reactions of 2H-azirine under a Lewis acid catalyst

Catalytic asymmetric inverse-electron-demand aza-Diels-Alder reaction of 1,3-diazadienes with 3-vinylindoles.

A facile chiral phosphoric-acid catalyzed asymmetric inverse-electron-demand aza-Diels-Alder reaction of 1,3-diazadienes with 3-vinylindoles was established. By using this mild and practical protocol, a broad range of benzothiazolopyrimidines with three contiguous stereogenic centers were prepared in good yields and excellent diastereo- and enantio-selectivities (43 examples, up to 83% yield, >99% ee and all >20 : 1 dr). A plausible concerted reaction pathway enabled by the dual hydrogen-bonding effect was proposed to account for the observed excellent enantioselectivity and specific trans-trans diastereoselectivity.

Enantioselective Inverse-Electron Demand Aza-Diels-Alder Reaction: ipso,α-Selectivity of Silyl Dienol Ethers.

A highly efficient enantioselective inverse-electron-demand aza-Diels–Alder reaction between aza-sulfonyl-1-aza-1,3-butadienes and silyl (di)enol ethers has been developed. The presented methodology allows the synthesis of benzofuran-fused 2-piperidinol derivatives with three contiguous stereocenters in a highly selective manner, as even the hemiaminal center is completely stereocontrolled. Density functional theory (DFT) calculations support that the hydrogen-bond donor-based bifunctional organocatalyst selectively triggers the reaction through the ipso,α-position of the dienophile, in contrast to the reactivity observed for dienolates in situ generated from β,γ-unsaturated derivatives. Moreover, the calculations have clarified the mechanism of the reaction and the ability of the hydrogen-bond donor core to hydrolyze selectively the E isomer of the dienol ether. Furthermore, to demonstrate the applicability of silyl enol ethers as nucleophiles in the asymmetric synthesis of interesting benzofuran-fused derivatives, the catalytic system has also been implemented for the highly efficient installation of an aromatic ring in the piperidine adducts.

Asymmetric Synthesis of Fused Tetrahydroquinolines via Intra­molecular Aza-Diels–Alder Reaction of ortho-Quinone Methide Imines

AbstractAza-Diels–Alder reactions are straightforward processes for the construction of N-heterocycles, featuring inherent atom-economy and stereospecificity. Intramolecular strategies allow the formation of bicyclic core structures with up to three stereocenters within a single step. Herein, this concept is combined with the chemistry of chiral Brønsted acid bound ortho-quinone methide imines to generate a range of interesting fused tetrahydroquinolines in a diastereo- and enantioselective­ manner.

Synthesis of Pyridazine Derivatives via Aza-Diels-Alder Reactions of 1,2,3-Triazine Derivatives and 1-Propynylamines.

A highly regioselective method was developed for the preparation of pyridazine derivatives via the aza-Diels-Alder reaction of 1,2,3-triazines with 1-propynylamines under neutral conditions. This methodology allowed direct access to a wide range of 6-aryl-pyridazin-3-amines in high yields with good functional group compatibility. Key features of this strategy included a broad substrate scope and simple, metal-free, and neutral reaction conditions.

Novel Pentafluorophenyl- and Alkoxyphenyl-Appended 2,2′-Bipyridine Push–Pull Fluorophores: A Convenient Synthesis and Photophysical Studies

AbstractA convenient method for the synthesis of new highly in non-polar solvents soluble photoactive pentafluorophenyl-substituted and extended alkoxyphenyl-substituted 2,2′-bipyridines is reported. The synthetic strategy for the preparation of such ligands involves a sequence of several structural transformations, such as O-alkylation, nucleophilic substitution of hydrogen (SN H) in 1,2,4-triazine precursors via the ‘addition–elimination’ scheme, and the subsequent conversion of the obtained 1,2,4-triazines into 2,2′-bipyridines by means of the aza-Diels–Alder reaction. The photophysical properties of the synthesized novel pentafluoroaryl-substituted 2,2′-bipyridines were comprehensively studied. The obtained photophysical data indicate the competitive advantages of the herein reported pentafluoroarylated push–pull fluorophores, bearing extended aliphatic moieties, over their analogues containing benzoxy or phenolic fragments in terms of improvement in quantum yield and well-pronounced positive solvatochromism confirmed by the mathematical analysis according to the Lippert–Mataga equation.

Diastereoselective synthesis of highly substituted tetrahydroquinolines using benzoylacetonitrile via aza Diels–Alder reaction

Diastereoselective aza-Diels–Alder reaction between in situ generated 2-aminophenyl-substituted enones and α-cyano-α,β-unsaturated aromatic ketone has been developed. In the presence of TEA as a catalyst prepared highly substituted tetrahydroquinolines with an all-carbon quaternary center in an in situ fashion. Both tetrahydroquinoline isomers (exo and endo) with excellent diastereoselectivity and high yields were synthesized in very mild conditions.

The Aza Diels‐Alder Reaction on Brominated Conjugated Dienes

AbstractThe use of electron‐deficient dienes as substrates in the aza Diels‐Alder reaction (ADA) has been studied scarcely. However, the ADA process offers a wide range of applications in organic synthesis. In this communication, the reaction between different brominated conjugated dienes and 4‐phenyl‐1,2,4‐triazoline‐3,5‐dione (PTAD), one of the most vigorous dienophiles, is reported. We have synthesized tricyclic compounds from acyclic substrates in only two steps, considering variables such as ring size and steric hindrance and substantially improved the results obtained with other dienophiles.

Diastereoselective synthesis of functionalized tetrahydropyridazines containing indole scaffolds via an inverse-electron-demand aza-Diels–Alder reaction

A base-promoted and catalyst-free unprecedented inverse-electron-demand aza-Diels–Alder reaction between the in situ generated azoalkenes and 3-vinylindoles has been developed to afford tetrahydropyridazines containing indole scaffolds.

Molecular diversity of TEMPO-mediated cycloaddition of ketohydrazones and 3-phenacylideneoxindoles

This reaction selectively proceeded via aza-Diels–Alder reaction, [3+2] cycloaddition and ring-opening of oxindole to give diverse spirooxindoles and polysubstituted pyrazoles.

Rapid metal free construction of 3-positioned 2-pyridyl substituent in indoles

New access to substituted 2-(indol-3-yl)pyridines involves two stage protocol, namely, a reaction of deoxygenative nucleophilic substitution of hydrogen in 1,2,4-triazine-4-oxides under the action of indoles followed by aza-Diels–Alder reaction of thus obtained 5-indolyl-1,2,4-triazines with 2,5-norbornadiene in a pressure vessel. The reactions sequence provides good yields and is suitable for wide scope of substituted 1,2,4-triazines.