aza-Diels Alder Reaction Research Articles

Aza-Diels-Alder reaction between N-aryl-1-oxo-1H-isoindolium ions and tert-enamides: Steric effects on reaction outcome.

The synthesis of 5-substituted 6,6a-dihydroisoindolo[2,1-a]quinolin-11(5H)-ones via [4 + 2] imino-Diels–Alder cyclization from N-aryl-3-hydroxyisoindolinones and N-vinyl lactams under Lewis acid-catalysed anhydrous conditions is reported. Reactions of N-(2-substituted-aryl)-3-hydroxyisoindolinones with N-vinylpyrrolidone under identical conditions resulted in the formation of 2-(2-substitued-aryl)-3-(2-(2-oxopyrrolidin-1-yl)vinyl)isoindolin-1-one analogues indicating steric hinderance as the cause of deviation. The probable mechanism of the reaction based on the results from X-ray crystallography and molecular modelling is discussed.

ChemInform Abstract: Synthesis of Methyl Substituted [5,6]‐ and [7,8]‐Fused Pyridocoumarins via the Iodine‐Catalyzed Reaction of Aminocoumarins with n‐Butyl Vinyl Ether.

Abstract 2-Methyl substituted [5,6]- or [7,8]-fused pyridocoumarins are prepared from the Povarov-type, three-component reactions of 6- or 7-aminocoumarins with n -butyl vinyl ether, catalyzed by iodine in refluxing acetonitrile, through the aza-Diels–Alder reaction of the initially formed N -iminoaminocoumarins with a second equivalent of the vinyl ether.

The synthesis of polyarene-modified 5-phenyl-2,2’-bipyridines via the methodology and aza-Diels–Alder reaction

Nucleophilic substitution of hydrogen () in 6-phenyl-3-(2-pyridyl)-1,2,4-triazine under the action of lithium derivatives of polynuclear arenes followed by aza-Diels–Alder reaction with norbornadiene or morpholinocyclopentene gives the novel polyarenemodified photoluminescent 5-phenyl-2,2’-bipyridine ligands.

Organocatalytic Remote Activation in an Aza-Diels–Alder Reaction

Organocatalytic Remote Activation in an Aza-Diels–Alder Reaction

Three-component aza-Diels–Alder reactions using Yb(OTf)3 catalyst under conventional/ultrasonic techniques

The Yb(OTf)3 catalyzed formal aza-Diels–Alder (or Povarov) reaction of cyclopentadiene and 1,3-cyclohexadiene with in situ-generated N-arylimines under conventional/ultrasonic techniques is herein described. This kind of three-component Povarov reaction results in quinoline and phenanthridine derivatives, which are important biological compounds.

Catalyst- and solvent-free, pot, atom and step economic synthesis of tetrahydroquinazolines by an aza-Diels–Alder reaction strategy

2,4-Disubstituted tetrahydroquinazolines can be readily obtained via a four-component aza-Diels–Alder reaction inside a microwave reactor. The methodology developed is simple, catalyst- and solvent-free and can be tuned to get dihydroquinazoline derivatives.

Exploration of uracils: pot and step economic production of pyridine core containing templates by multicomponent aza-Diels–Alder reaction

Substituted pyrido[2,3-d]pyrimidines can be obtained with good yields via a multicomponent aza-Diels–Alder reaction from easily available starting materials. The diene behaviour of different uracil derivatives was also elaborately investigated to synthesize desired products.

Catalytic Asymmetric Aza-Diels–Alder Reactions: The Povarov Cycloaddition Reaction

The Povarov reaction provides a straightforward and modular entry to 1,2,3,4-tetrahydroquinolines (THQs). Despite its importance, it was only very recently that several highly efficient catalytic asymmetric protocols for this reaction have been developed, as summarized in this review which falls on the 50^th anniversary of Povarov’s pioneering disclosure. Furthermore, this review collects and critically discusses the interrupted versions of the reaction, often featuring intriguing and still unclear mechanicistic pathways. 1 Introduction 2 Catalytic Asymmetric Povarov Cycloaddition Reactions 2.1 Chiral Lewis Acid Catalysis 2.2 Chiral Brønsted Acid Catalysis 2.2.1 Chiral Phosphoric Acid Catalyzed Povarov Cycloaddition Reactions 2.2.2 Chiral Urea Catalyzed Povarov Cycloaddition Reactions 3 Catalytic Asymmetric Interrupted Povarov Reactions 3.1 Intermolecularly Interrupted Povarov Reactions 3.2 Intramolecularly Interrupted Povarov Reactions 3.2.1 Interrupted Povarov Reactions with Salicyaldehyde-Derived Imines 3.2.2 Interrupted Povarov Reactions with Glyoxylic Acid Derived Imines 4 Conclusion

One-Pot Synthesis of Nuevamine Aza-Analogues by Combined Use of an Oxidative Ugi Type Reaction and Aza-Diels–Alder Cycloaddition

A rapid and efficient one-pot synthesis of a series of four novel nuevamine aza-analogues is described based on the oxidative Ugi-type reaction and aza-Diels–Alder reaction as post-functionalization. A simple IBX-mediated oxidation of a secondary amine followed by isonitrile α-addition and finally an aza-Diels–Alder cycloaddition provides the desired compounds in excellent overall yields considering the short reaction time, atom economy, and the molecular complexity of the final products. This protocol presents a highly attractive procedure for the rapid generation of fused polyheterocycles.

Synthesis of Tetrahydropyridazine Amino Acid Derivatives by a Formal [4+2] Cycloaddition Reaction of 1,2-Diaza-1,3-dienes with Dehydroalanine Esters.

A highly efficient formal inverse electron demand aza Diels–Alder reaction of 1,2-diaza-1,3-dienes (DDs) is accomplished using dehydroalanine esters (DhAs) as electron-rich dienophiles. Both diastereoisomers of unprecedented ,-disubstituted cyclic tetrahydropyridazine amino acids were obtained in excellent yields, in refluxing acetonitrile without activation. Keywords: Cycloaddition reaction, dehydroalanine esters, 1, 2-Diaza-1, 3-dienes, N, N-disubstituted quaternary center, nitrogen heterocycles, tetrahydropyridazine amino acids.

Synthesis of methyl substituted [5,6]- and [7,8]-fused pyridocoumarins via the iodine-catalyzed reaction of aminocoumarins with n-butyl vinyl ether

2-Methyl substituted [5,6]- or [7,8]-fused pyridocoumarins are prepared from the Povarov-type, three-component reactions of 6- or 7-aminocoumarins with n-butyl vinyl ether, catalyzed by iodine in refluxing acetonitrile, through the aza-Diels–Alder reaction of the initially formed N-iminoaminocoumarins with a second equivalent of the vinyl ether.

Total Syntheses of (±)‐Spiroquinazoline, (−)‐Alantryphenone, (+)‐Lapatin A, and (−)‐Quinadoline B

Quick access: The aza-Diels–Alder reaction of unprecedented aminal-embodied olefins with azadienes provides quick access to indoline-containing spiroquinazoline alkaloids. This approach was utilized in the total syntheses of the title compounds (see figure).

Unexpected reduction of the nitro group in (3-nitrophenyl)-1,2,4-triazines during their aza-Diels–Alder reaction with 1-morpholinocyclopentene

Unexpected reduction of the nitro group to the amino one during aza-Diels–Alder reaction between (3-nitrophenyl)-1,2,4-triazines and 1-morpholinocyclopentene (neat, 200°C, argon) occurred to furnish 4-(3-aminophenyl)-6,7-dihydro-5H-cyclopenta[c]pyridines.

Preparation of Pyridyl-substituted Monoazatriphenylenes

An efficient method for the preparation of cycloalkene-anellated derivatives of monoazatriphenylenes based on an aza-Diels—Alder reaction of triazine (III) with 1-morpholinocycloalkenes is presented.

Two new approaches towards the synthesis of annomontine using Pictet–Spengler and aza-Diels–Alder reactions

Two new routes were established for the synthesis of biologically active natural product annomontine utilizing Pictet–Spengler and aza-Diels–Alder reactions as key steps.

ChemInform Abstract: Catalytic Enantioselective [4 + 2]‐Cycloaddition: A Strategy to Access Aza‐Hexacycles

AbstractReview: 55 refs.

A rational protocol for the synthesis of 1-(2-pyridyl)isoquinolines

Aza-Diels–Alder reaction between 3-(2-pyridyl)-1,2,4-triazines and 1-morpholinocyclohexene followed by aromatization of the cyclohexene moiety affords 1-(2-pyridyl)isoquinolines. Crystal structures of two tetrahydroisoquinolines were confirmed by X-ray diffraction analysis.

The origin of stereoselectivity in cycloaddition reactions promoted by stereoisomers of 8-phenylmenthyl glyoxylate oxime

A structural study of three synthesized stereoisomeric oximes, (−)-8-phenylmenthyl glyoxylate oxime (8-PMGO), (+)-8-phenylneomenthyl glyoxylate oxime (8-PnMGO), and (−)-8-phenylisoneomenthyl glyoxylate oxime (8-PinMGO), was performed by means of variable temperature 1H NMR spectroscopy, X-ray crystallography, and ab initio calculations. It was found that in 8-PMGO a conformation where the phenyl and oxime moieties are stacked is significantly favored, whereas in the other stereoisomers this preference was not so evident. The conformational differences found between the isomers were used to rationalize the outcome of the reaction (simultaneous 1,3-cycloaddition and aza-Diels–Alder reaction) between the referred oximes and cyclopentadiene, in which the stereoselectivity was evaluated and found to be nicely reproduced by a simple conformational analysis. The global results indicate that the stereoselectivity of the studied oximes, a bit higher for 8-PMGO, originates from their particular conformational distribution, in which the phenyl∙oxime aromatic interaction plays a decisive role.

ChemInform Abstract: Microwave‐Assisted Efficient Synthesis of Spiroquinoline Derivatives via a Catalyst‐ and Solvent‐Free Aza‐Diels—Alder Reaction.

Abstract A microwave-assisted, one-pot three-component aza-Diels–Alder reaction strategy has been developed for the synthesis of some complex spiroquinoline derivatives from 1-aminonaphthalene, aromatic aldehyde, and 5-benzylidene-1,3-dimethyl pyrimidine-2,4,6-trione under catalyst- and solvent-free conditions.

Aza-Diels–Alder addition of cyclopentadiene to propynyliminoglyoxylates

The aza-Diels–Alder reaction of cyclopentadiene with protonated propynylimine of methyl (Me) and tert-butyl (t-Bu) carboxylate was studied, using density functional theory (DFT) at the X3LYP/6-31G (d) level, in order to elucidate the role of the ester group of the dienophile. Four independent reaction pathways were found for each diene/dienophile pair, all of them proceeding through a concerted, highly asynchronous, mechanism. Both systems exhibit a clear tendency for the formation of exo adducts and show the same overall behavior, despite steric hindrances. The exo cycloadducts are always favored relative to the endo analogs, both by kinetic and thermodynamic reasons. Gas-phase results showed that the exo/endo rate would be mostly controlled by the relative thermodynamic stability of the final products. However, the application of the polarizable continuum model (PCM) preferentially lowered the activation enthalpy of the reaction exo channels, stressing the importance of the kinetic over the thermodynamic aspects of the proposed mechanism. This resulted in a reaction model that satisfies the experimental evidence.