aza-Diels Alder Reaction Research Articles

Indium(III) chloride/silica gel catalyzed synthesis of pyrazolo[3,4-b]pyrrolo[3,4-d]pyridines

A facile synthesis of pyrazolo[3,4-b]pyrrolo[3,4-d]pyridine was developed through an Aza-Diels–Alder reaction of pyrazoylimines with maleimides in the presence of 20% wt InCl3/silica gel in the sealed tube. Based on the metal catalyst scanning study, silica gel impregnated with indium trichloride was found to be the suitable catalyst to improve the Aza-Diels–Alder cycloaddition. In comparison with Brønsted–Lowery acetic acid condition, the Lewis acidic metal catalyst is more efficient for the Aza-Diels–Alder reaction.

Asymmetric Synthesis of Tetrahydropyridines via a Brønsted Acid Catalyzed Aza-Diels–Alder Reaction

The asymmetric synthesis of tetrahydropyridines employing a normal electron-demanding aza-Diels–Alder reaction has been developed. The [4+2] cycloaddition of ethyl glyoxylate imine with aryl-substituted 2-silyloxy-1,3-butadienes is catalyzed by 5 mol% of a BINOL-derived phosphoric acid and in general leads to good yields and ee values with good to excellent diastereoselectivities. The cycloadducts can be further converted into the corresponding piperidinones, which are important pipecolic acid derivatives.

Chiral Bimetallic Catalysts Derived from Chiral Metal Phosphates: Enantioselective Three-Component Asymmetric Aza-Diels-Alder Reactions of Cyclic Ketones.

A new type of chiral bimetallic catalyst is disclosed. These chiral bimetallic catalysts are easily formed through mixing a metal Lewis acid and a metal binaphthyl phosphate (MLA/M[P]3) in solution. (1)H and (31)P NMR spectroscopy, electron paramagnetic resonance (EPR) spectroscopy, matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry, and X-ray crystallographic analysis reveal a bimetallic structure of the Y(Yb)(III)/Y[P]3 complexes with bridging binaphthyl phosphate ligands. The Lewis acidity of these chiral bimetallic catalysts is readily tuned by changing either the metal Lewis acid or the chiral metal phosphate. Through cooperative metal Lewis acid-enamine catalysis, asymmetric three-component aza-Diels-Alder reactions of 5-, 6-, and 7-membered cyclic ketones, unsaturated ketoesters, and arylamines were successfully achieved to afford fused bicyclic dihydropyridines in high yields (up to 94%) with high enantioselectivity (up to 99% enantiomeric excess) and excellent chemoselectivity.

Synthesis and characterization of oxadisilole-fused phenanthridines and dioxatrisilole-fused phenanthridines from benzyne

An efficient protocol for the synthesis of oxadisilole-fused phenanthridines and dioxatrisilole-fused phenanthridines by aza Diels–Alder reactions and dehydrogenation aromatization reactions of benzyne with N-benzylideneanilines in good yields at room temperature. The photophysical, redox and thermal properties of oxadisilole-fused phenanthridines have been determined. The oxadisilole-fused phenanthridines show potential applications used as blue emitters for OLED due to their high fluorescence quantum yields and thermal stabilities.

ChemInform Abstract: 2‐Halogenoimidazolium Salt Catalyzed Aza‐Diels—Alder Reaction Through Halogen‐Bond Formation.

2-Halogenoimidazolium salts are found to catalyze aza-Diels–Alder reaction of aldimines with Danishefsky diene in an efficient manner. Comparative studies and titration experiments support the formation of halogen bonding between imines and catalysts.

Catalytic Asymmetric Formal Aza-Diels–Alder Reactions of α,β-Unsaturated Ketones and 3H-Indoles

Asymmetric formal aza-Diels–Alder reactions with α,β-unsaturated ketones and 3H-indoles with disubstituted groups on the C3 position catalyzed by primary amine-thiourea bifunctional catalyst have been developed. The reactions produced chiral hexahydropyrido-[1,2-a]-indole-2-ones in high yields with excellent diastereo- and enantioselectivities.

ChemInform Abstract: Endo‐Benzonorbornen‐2‐ol as an Efficient Non‐natural Chiral Auxiliary in the Asymmetric aza‐Diels—Alder Reactions Between Cyclopentadiene and (1‐Phenylethyl)iminoacetates.

Exo-2-azabicyclo[2.2.1]hept-5-enes were obtained by cycloaddition reactions between cyclopentadiene and protonated (S)- and (R)-1-phenylethylimines of (1R,endo)-benzonorbornen-2-yl glyoxylate. The non-natural (1R,endo)-benzonorbornen-2-ol proved to be an efficient chiral auxiliary in these asymmetric aza-Diels–Alder reactions, which afforded only exo-cycloadducts with 1S : 1R diastereomeric ratios of 15 : 85 for (S)-(1-phenylethyl)imine and 93 : 7 for (R)-(1-phenylethyl)imine. The obtained diastereoisomers were effortlessly and efficiently isolated using a chromatographic column. The absolute configuration of all the formed adducts was unequivocally assigned through NMR, specific optical rotation and X-ray data.

Heteropoly acid-catalyzed three-component aza-Diels–Alder reaction in a continuous micro-flow system

The first direct aza-Diels–Alder reaction catalyzed using phosphotungstic acid combined with a water absorption device in a micro-flow system was reported.

The catalytic asymmetric synthesis of tetrahydropyridazines via inverse electron-demand aza-Diels-Alder reaction of enol ethers with azoalkenes.

A highly efficient Cu(II)-catalyzed enantioselective inverse-electron-demand aza-Diels-Alder reaction of in situ formed azoalkenes with enol ethers is reported. This methodology provides a facile entry to biologically important and enantioenriched tetrahydropyridazine derivatives in generally good yield (up to 95% yield) with good to excellent enantioselectivity (up to 94% ee).

Simple descriptors for assessing the outcome of aza-Diels–Alder reactions

Taft’s constants are important descriptors for predicting the outcome of aza-Diels–Alder reactions, correctly reproducing the results from DFT calculations.

Structural diversity in coordination polymers with a semirigid Lewis acidity ligand: structures and properties

Reaction of semirigid Lewis acidity ligand 1-carboxymethylpyridinium-4-carboxylate (L) with various salts affords five new coordination networks: two 2D layered coordination polymers [Ag2(L)(NO3)]·H2O (2) and [Pb(L)(NO3)] (3), and three 3D metal–organic frameworks [Cu4(L)4(OH)2Cl2]·11.55H2O (1), [Pb3(L)4Br2(H2O)2] (4) and [Pr(L)2(H2O)2(NO3)] (5). Complex 1 features a planar tetranuclear [Cu4(μ3-OH)2]6− cluster as a 6-connected node, connecting with eight L ligands to generate a tilted α-Po type structure. Compared with 1, 2 possesses a unique 2D double-layered structure with 1D channels, which is composed of (4,4) topological networks pillared by nitrate anions. Complexes 3 and 4 are both made up of 1D chains. 3 is composed of homo-chiral 21 helices, which provides a chiral 2D polymeric network, whereas 4 consists of two types of infinite 1D chains linked in a cross-like fashion, which displays a 3D plywood-like structure. Complex 5 consists of 4-connected metal nodes, which exhibits a 3-fold interpenetrating 3D diamondoid framework. The results suggest that the semirigid L ligand adopting different coordination modes plays important roles in determining the final structures of complexes 1–5. Moreover, complexes 3 and 5 with an acentric space group show modest powder second-harmonic-generation (SHG) efficiency at room temperature. Based on the Lewis acidity of the pyridinium unit of ligand L, complexes 1–5 were also used as catalysts for aza-Diels–Alder reaction.

Ceric Ammonium Nitrate (CAN)–Catalyzed, Efficient, One-Pot, Three-Component, aza-Diels–Alder Reactions for a Facile Synthesis of Tetrahydropyranoquinoline Derivatives

A simple, efficient, and cost-effective method for the synthesis of tetrahydropyranoquinoline derivatives by a one-pot condensation of aromatic aldehyde, aromatic amine, and 3,4-dihydro-2H-pyran respectively in the presence of ceric ammonium nitrate (CAN) has been described.

Synthesis of cyclic analogues of hexamethylenebis(3-pyridine)amide (HMBPA) in a one-pot process

A series of cyclic analogues of hexamethylenebis(3-pyridine)amide was prepared based upon a Ugi-3CR and aza-Diels–Alder reaction as a post-functionalization in a one-pot process. A simple condensation of commercially available diamine and aldehydes followed by isonitrile α-addition provides the oxazole intermediates, finally an aza-Diels–Alder cycloaddition and ring-opening using maleic anhydride provides the desired compounds in modest overall yields in approximately 40min using microwaves as the heat source and scandium(III) triflate as a catalyst.

Endo-benzonorbornen-2-ol as an efficient non-natural chiral auxiliary in the asymmetric aza-Diels–Alder reactions between cyclopentadiene and (1-phenylethyl)iminoacetates

Exo-2-azabicyclo[2.2.1]hept-5-enes were obtained by cycloaddition reactions between cyclopentadiene and protonated (S)- and (R)-1-phenylethylimines of (1R,endo)-benzonorbornen-2-yl glyoxylate. The non-natural (1R,endo)-benzonorbornen-2-ol proved to be an efficient chiral auxiliary in these asymmetric aza-Diels–Alder reactions, which afforded only exo-cycloadducts with 1S : 1R diastereomeric ratios of 15 : 85 for (S)-(1-phenylethyl)imine and 93 : 7 for (R)-(1-phenylethyl)imine. The obtained diastereoisomers were effortlessly and efficiently isolated using a chromatographic column. The absolute configuration of all the formed adducts was unequivocally assigned through NMR, specific optical rotation and X-ray data.

ChemInform Abstract: Catalytic Asymmetric Synthesis of [2,3]‐Fused Indoline Heterocycles Through Inverse‐Electron‐Demand Aza‐Diels—Alder Reaction of Indoles with Azoalkenes.

An unprecedented catalytic asymmetric inverse-electron-demand aza-Diels–Alder reaction of indoles with in situ formed azoalkenes is reported. A diverse set of [2,3]-fused indoline heterocycles were achieved in generally good yields (up to 97 %) with high regioselectivity and diastereoselectivity (>20:1 d.r.), and with excellent enantioselectivity (up to 99 % ee).

(Benzo[h])Quinolinyl-Substituted Monoazatriphenylenes: Synthesis and Photophysical Properties

We propose a method for the synthesis of quinolinyl- and benzo[h]quinolinylmonoazatriphenylenes through 1,2,4-triazine intermediates with subsequent transformations in aza-Diels–Alder reaction. The photophysical properties of these new compounds were examined, and the effects due to additional fused aromatic rings were explored.

The Extension of Conjugated System in Pyridyl-Substituted Monoazatriphenylenes for the Tuning of Photophysical Properties

We propose a method for the synthesis of diaryl-substituted pyridylmonoazatriphenylenes by the heterocyclization reaction of dihalosubstituted phenanthrenequinones with pyridine-2-carboxylic acid amidrazone, followed by aza-Diels–Alder reaction and Suzuki cross coupling. The obtained compounds showed more promising photophysical properties, compared to non-arylated analogs.

Synthesis of pyrazolo[3,4-b]pyrrolo[3,4-d]pyridine derivatives via Aza-Diels–Alder reaction: evaluation of torsion effect of pyrazoylimines

A modified method for the synthesis of pyrazolo[3,4-b]pyrrolo[3,4-d]pyridine was developed through an Aza-Diels–Alder reaction of pyrazoylimines with maleimides in the sealed tube. Based on the control experiment, the yields for the Aza-Diels–Alder reaction seemed proportional to the suitable torsion conformation of pyrazoylimine, which was modulated by N,N-disubstituted amidinyl moiety. The versatile sealed tube technique was also proved to promote the higher isolated yields in the Aza-Diels–Alder reaction.

β,γ-Regioselective inverse-electron-demand aza-Diels-Alder reactions with α,β-unsaturated aldehydes via dienamine catalysis.

A stereoselective inverse-electron-demand aza-Diels-Alder cycloaddition process of cyclic 1-aza-1,3-butadienes and α,β-unsaturated aldehydes has been developed via dienamine catalysis. This reaction exhibits excellent β,γ-regioselectivity for enal substrates with substantial structural diversity and broad functionalities, readily producing highly enantioenriched fused piperidine derivatives and enabling efficient sequential construction of complex polycyclic frameworks.

THE EXTENSION OF CONJUGATED SYSTEM IN PYRIDYL-SUBSTITUTED MONOAZATRIPHENYLENES FOR THE TUNING OF PHOTOPHYSICAL PROPERTIES

We propose a method for the synthesis of diaryl-substituted pyridylmonoazatriphenylenes by the heterocyclization reaction of dihalosubstituted phenanthrenequinones with pyridine-2-carboxylic acid amidrazone, followed by aza-Diels–Alder reaction and Suzuki cross coupling. The obtained compounds showed more promising photophysical properties, compared to non-arylated analogs. How to Cite Kopchuk, D. S.; Khasanov, A. F.; Kovalev, I. S.; Zyryanov, G. V.; Kim, G. A.; Nikonov, I. L.; Rusinov, V. L.; Chupakhin, O. N. Chem. Heterocycl. Compd. 2014 , 50 , 871. [ Khim. Geterotsikl. Soedin. 2014 , 943.] For this article in the English edition see DOI 10.1007/s10593-014-1541-0