1,3-偶极环加成合成新型3a,6a-二氢-4,6-二氧代吡咯啉并[3,4-d]吡唑类衍生物

α-氯代-4-氧代-4H-1-苯并吡喃-3-甲醛芳腙与N-取代苯基-马来酰亚胺在三乙胺作用下通过1,3-偶极环加成合成了一系列含3-(4-氧代-4H-1-苯并吡喃-3-基)-3a,6a-二氢-4,6-二氧代吡咯啉并[3,4-d]吡唑类衍生物. 化合物结构经元素分析, IR, ¹H NMR及MS确证.     

[1,3,5]Triazino[1,2-a] azepines: A new ring system

The reaction of 2-pyrrolidino-1-aza-1-cycloheptene with aryl isocyanates leads, via 1,4-dipolar cycloaddition, to 1,3-diaryl-10a-pyrrolidinoperhydro[1,3,5]triazino[1,2-a]azepine-2,4-diones. The reaction provides a facile route to the novel [1,3,5]triazino[1,2-a]azepine ring system.     

A new synthesis of pyrimido[5,4-e]-as-triazine 4-oxides and their ring transformation to pyrrolo[3,2-d]pyrimidines

A new synthesis of certain pyrimido[5,4-e]-as-triazine 4-oxides and their ring transformation to pyrrolo-[3,2-d]pyrimidines by the 1,3-dipolar cycloaddition reaction is described. Thus, reaction of 6-hydrazino-1,3-dimethyluracil ( 1 ) with triethyl orthoformate gave 6-ethoxymethylenehydrazino-1,3-dimethyluracil ( 2 ). Treatment of 2 with arylamines gave 6-arylaminomethylenehydrazino-1,3-dimethyluracils ( 3a-e ). Nitrosative cyclization of 3a-e with sodium nitrite afforded 3-arylaminofervenulin 4-oxides ( 6a-e ). Reaction of 6a-e with acetylenic esters yielded 7-alkoxycarbonyl-6-arylamino-1,3-dimethylpyrrolo[3,2-d]pyrimidine-2,4(1H,3H-diones ( 15a-e and 16 ).     

A clean synthesis of oxazino[5,6-f]quinolinone and naphtho[1,2-e]oxazinone derivatives

A clean, simple, one-pot, and efficient synthesis of 1,2-dihydro-1-aryl[1,3]oxazino[5,6-f]quinolin-3-one and 1,2-dihydro-1-arylnaphtho[1,2-e]-[1,3]oxazine-3-one derivatives was accomplished in good yields via reaction between 6-quinolinol or 2-naphthol, aromatic aldehydes, and methyl carbamate in aqueous medium catalyzed by TEBA (triethylbenzylammonium chloride).     

Synthesis of pyridazino[3,4-b]quinoxalines and pyrazolo[3,4-b]-quinoxaline by 1,3-dipolar cycloaddition reaction

The pyridazino[3,4-b]quinoxalines 6a,b and pyrazolo[3,4-b]quinoxaline hydrochloride 9 were synthesized by the 1,3-dipolar cycloaddition reaction of 6-chloro-2-(1-methylhydrazino)quinoxaline 4-oxide 5 with dimethyl or diethyl acetylenedicarboxylate and 2-chloroacrylonitrile, respectively. The reaction mechanisms were postulated for the formation of 6a,b and 9 .     

Synthesis of the 5H-pyrrolo[2,1-a]isoindole ring with 1,3-dipolar cycloaddition reactions

The 1,3-dipolar cycloaddition reaction between mesoionic oxazolines, formed from either 1,3-dihydro-2-substituted-2H-isoindole-1-carboxylic acids or 1,3-dihydro-1-oxo-α-substituted-2H-isoindole-2-acetic acids, and dimethylacetylene dicarboxylate has led to the synthesis of several 5H-pyrrolo[2,1-a]isoindole derivatives 9a-d .     

New Benzo[ b ]xanthones from Diels-Alder Reactions of Chromone-3-carboxaldehydes with ortho -Benzoquinodimethanes

 New benzo[b]xanthone derivatives, having substituents in the A and D rings, were prepared from cycloaddition reactions of chromone-3-carboxaldehydes with ortho-benzoquinodimethanes, generated in situ from 1,3-dihydrobenzo[c]thiophene 2,2-dioxide, followed by oxidation of the obtained diastereomeric adducts. The structure of all compounds was fully established by 1D and 2D NMR, MS, and elemental analysis. The stereochemistry of the obtained diastereomeric cycloadducts was established by NOESY experiments.     

Synthesis of dispirooxindolecycloalka[d]pyrimidino[2,3-b]-thiazole pyrrolidine/thiapyrrolizidine ring systems

The synthesis of a new class of spirooxindolo pyrrolidines and spirooxindolo thiapyrrolizidines has been accomplished by a three component, one-pot 1,3-dipolar cycloaddition reaction. The cycloaddition was found to be highly regioselective.     

Substituent Effects on Fe+-Mediated [4+2] Cycloadditions in the Gas Phase

The Fe⁺-mediated [4+2] cycloaddition of dienes with alkynes has been examined by four-sector ion-beam and ion cyclotron resonance mass spectrometry. Prospects and limitations of this reaction were evaluated by investigating several Me-substituted ligands. Me Substitution at C(2) and C(3) of the diene, i.e., 2-methylbuta-1,3-diene, 2,3-dimethylbuta-1,3-diene, hardly disturbs the cycloaddition. Similarly, variation of the alkyne by use of propyne and but-2-yne does not affect the [4+2] cycloaddition step, but allows for H/D exchange processes prior to cyclization. In contrast, Me substituents in the terminal positions of the diene moiety (e.g., penta-1,3-diene, liexa-2,4-diene) induce side reactions, namely double-bond migration followed by [3+2] and [5+2] cycloadditions, up to almost complete suppression of the [4+2] cycloaddition for 2,4-dimethylhexa-2,4-diene. Similarly, alkynes with larger alkyl substituents (pent-1-yne, 3,3-dimethylbut-1-yne) suppress the [4 + 2] cycloaddition route. Stereochemical effects have been observed for the (E)- and (Z)-penta-1,3-diene ligands as well as for (E,E)- and (E,Z)-hexa-2,4-diene. A mechanistic explanation for the different behavior of the stereoisomers in the cyclization reaction is developed. Further, the regiochemical aspects operative in the systems ethoxyacetylene/pentadiene/Fe⁺ and ethoxyacetylcne/isoprene/Fe⁺ indicate that substituents avoid proximity.     

Synthesis of pyrrolo[3,4-b]pyrroles and perhydrothiazolo[3′,4′-2,3]pyrrolo[4,5-c]pyrroles

The 1,3-dipolar cycloaddition reactions of various N-tethered alkenyl aldehydes with some cyclic and acyclic amino acids have been studied. Some key sulfonamides having strategically positioned aldehyde and olefinic tether have been synthesized and effectively subjected to intramolecular azomethine ylide cycloaddition reaction resulting in a series of pyrrolo[3,4-b]pyrrole and its N-1-C-2 derivatives, and a series of novel heterotricyclic compounds, perhydrothiazolo[3′,4′-2,3]pyrrolo[4,5-c]pyrroles, in good yields. The intramolecular cycloaddition reaction was found to be highly stereoselective to form only cis-fused cycloadducts in all cases.     

A convenient synthesis of novel pyridazino[3,4-b]quinoxaline and pyrazolo[3,4-b]quinoxaline utilizing 1,3-dipolar cycloaddition reaction

The reaction of 2,6-dichloroquinoxaline 4-oxide 4 with methylhydrazine gave 6-chloro-2-(1-methylhydrazino)quinoxaline 4-oxide 5, whose reaction with dimethyl acetylenedicarboxylate or 2-chloroacrylonitrile resulted in the 1,3-dipolar cycloaddition reaction to afford 7-chloro-3,4-bismethoxycarbonyl-1-methyl-1,2-dihydropyridazino[3,4-b]quinoxaline 6 or 6-chloro-3-hydroxymethylene-1-methyl-2,3-dihydro-1H-pyrazolo[3,4-b] quinoxaline hydrochloride 7, respectively.     

Preparation of pyrazolo[5,1-c][1,4]benzoxazines by intramolecular [3+ + 2] cycloaddition reaction of hydrazonium chlorides with alkenes

Pyrazolo[5,1-c][1,4]benzoxazines were prepared by the reaction of 2-(allyloxy)phenylhydrazine with arylaldehydes in the presence of hydrochloric acid. The formation of the fused heterocycles can be explained by intramolecular 1,3-dipolar cycloaddition reaction of cationic dipole, i.e‥, hydrazonium chlorides.     

A convenient synthesis of 1,2,4-triazolo[4,3,2-o,p]-[1,3]diazocino[4,5-b]quinoxalines via a 1,3-dipolar cycloaddition reaction and a ring transformation

The reaction of 6-chloro-2-hydrazinoquinoxaline 4-oxide 5 with triethyl orthoformate gave 7-chloro-1,2,4-triazolo[4,3-a]quinoxaline 5-oxide 6. The reaction of compound 6 with phenyl isocyanate afforded 7-chloro-4-phenylamino-1,2,4-triazolo[4,3-a]quinoxaline 7 , while the reaction of compound 6 with phenyl isothiocyanate resulted in deoxygenation to provide 7-chloro-1,2,4-triazolo[4,3-a]quinoxaline 8. However, the reaction of compound 6 with allyl isothiocyanate effected the 1,3-dipolar cycloaddition reaction, but not deoxygenation, to furnish 9-chloro-4,5-dihydroisoxazolo[2,3-a][1,2,4]triazolo[3,4-c]quinoxalin-5-ylmethylisothiocyanate 9. Moreover, the reduction of compound 9 with iron/acetic acid resulted in ring transformation to give 11 -chloro-7-hydroxy-4-thioxo-4,5,6,7,8,9-hexahydro-1,2,4-triazolo[4,3,2- o,p][1,3]diazocino[4,5-b]quinoxaline 10 , whose acetylation afforded 5-acetyl-11-chloro-7-hydroxy-4-thioxo-4,5,6,7,8,9-hexahydro-1,2,4-triazolo[4,3,2-o,p][1,3]diazocino[4,5-b]quinoxaline 11.     

A new synthesis of 1,2,3,5‐tetrahydroimidazo[2,3‐b]‐[1,3]benzodiazocines

A new synthesis of 6‐carbomethoxy‐1,2,3,5‐tetrahydroirnidazo[2,3‐b][1,3]benzodiazocines 13 by the intramolecular cycloaddition reaction of methyl 2‐(1‐aziridinylmethyl)‐3‐(2‐ureidophenyl)propenoates 10 under Appel's dehydration conditions is described. The latter were readily obtained from 2‐nitrobenzalde‐hyde with methyl acrylate through the Baylis‐Hillman reaction.     

Synthesis of pyrrolo[1,3]diazepines by a dipolar cycloaddition—retro-Mannich domino reaction

Microwave irradiation facilitated the synthesis of 4-arylthio-3-oxazolin-5-ones from ethyl cyanoformate, thiophenol, and cyclic ketones. Subsequent decarboxylation and in situ [3+2] cycloaddition provided novel 2,3,4,5-tetrahydro-1H-pyrrolo[1,2-c][1,3]diazepine scaffolds after a spontaneous retro-Mannich domino reaction.     

6,6-Disubstituted furo[3,4-c]isoxazoles and 7,7-disubstituted pyrano-[3,4-c]isoxazoles from intramolecular cycloaddition reactions

The reaction of β-nitroenones with unsaturated alkoxides anions, followed by intramolecular 1,3-dipolar cycloaddition, afforded in good yields 6,6-disubstituted furo[3,4-c]isoxazoles and 7,7-disubstituted pyrano[3,4-c]isoxazoles.     

Mechanism, regioselectivity, and the kinetics of phosphine-catalyzed [3+2] cycloaddition reactions of allenoates and electron-deficient alkenes

With the aid of computations and experiments, the detailed mechanism of the phosphine-catalyzed [3+2] cycloaddition reactions of allenoates and electron-deficient alkenes has been investigated. It was found that this reaction includes four consecutive processes: 1) In situ generation of a 1,3-dipole from allenoate and phosphine, 2) stepwise [3+2] cycloaddition, 3) a water-catalyzed [1,2]-hydrogen shift, and 4) elimination of the phosphine catalyst. In situ generation of the 1,3-dipole is key to all nucleophilic phosphine-catalyzed reactions. Through a kinetic study we have shown that the generation of the 1,3-dipole is the rate-determining step of the phosphine-catalyzed [3+2] cycloaddition reaction of allenoates and electron-deficient alkenes. DFT calculations and FMO analysis revealed that an electron-withdrawing group is required in the allene to ensure the generation of the 1,3-dipole kinetically and thermodynamically. Atoms-in-molecules (AIM) theory was used to analyze the stability of the 1,3-dipole. The regioselectivity of the [3+2] cycloaddition can be rationalized very well by FMO and AIM theories. Isotopic labeling experiments combined with DFT calculations showed that the commonly accepted intramolecular [1,2]-proton shift should be corrected to a water-catalyzed [1,2]-proton shift. Additional isotopic labeling experiments of the hetero-[3+2] cycloaddition of allenoates and electron-deficient imines further support this finding. This investigation has also been extended to the study of the phosphine-catalyzed [3+2] cycloaddition reaction of alkynoates as the three-carbon synthon, which showed that the generation of the 1,3-dipole in this reaction also occurs by a water-catalyzed process.     

Asymmetric Brønsted Base Catalyzed and Directed [3+2] Cycloaddition of 2‐Acyl Cycloheptatrienes with Azomethine Ylides

Conjugated cyclic trienes have the potential for different types of cycloaddition reactions. In the present work, we will, in a novel asymmetric cycloaddition reaction, demonstrate that the organocatalytic reaction of 2‐acyl cycloheptatrienes with azomethine ylides proceeds as a [3+2] cycloaddition, which is in contrast to the Lewis acid‐catalyzed reaction, in which a [3+6] cycloaddition takes place. In the presence of a chiral organosuperbase, 2‐acyl cycloheptatrienes react in a highly enantioselective manner in the [3+2] cycloaddition with azomethine ylides, providing the 1,3‐dipolar cycloaddition product in high yields and up to 99 % ee. It is also shown that the diene formed by the reaction can undergo stereoselective dihydroxylation, bromination, and cycloaddition reactions. Finally, based on experimental observations, some mechanistic considerations are discussed.     

Aktivierte Chinone: regiospezifische Synthesen von substituierten Dibenzo [b,d]pyran-6-onen und Benzo [b]naphtho [d]pyran-6-onen

Activated Quinones: Regiospecific Syntheses of Substituted Dibenzo [b, d]pyran-6-ones and Benzo[b]naphtho [d]pyran-6-ones The reaction of 2-methoxycarbonyl-1, 4-benzoquinone (1) with substituted phenols leads in an acid-catalyzed, regiospecific way to substituted dibenzo [b, d]-pyran-6-ones (compounds 3 and 6 ). The cycloaddition of 1,3-butadiene to the latter yields compounds 7. Tautomerisation of 7 and oxidation gives the benzo[b]-naphtho[d]pyran-6-ones 8 and 10 , respectively.     

Synthesis of Naphtho[2,1-b]pyrano Pyrrolothiazole Derivatives through 1,3-Cycloaddition Reaction

Facile synthesis of a series of naphtho[2,1,b]pyrano pyrrolo thiazoles was accomplished in good yields in a one-pot reaction through intramolecular 1,3-dipolar cycloaddition of cyclic azomethine ylides with Baylis–Hillman adducts as dipolarophiles. The protocol is applicable to a wide variety of photochromic and biologically active napthopyrano products. The regio- and stereochemical outcome of the cycloaddition reaction was ascertained by x-ray crystallographic study of one of the cycloadducts.