1,3-Dipolar cycloadditions of MeOPEG-bounded azides

1,3-Dipolar cycloadditions of MeOPEG-supported azide 2 with a variety of dipolarophiles have been studied. 1-MeOPEG-supported 1,2,3-triazoles 4 and 5, 1,2,3,4-tetrazoles 12 and aziridine 14 were obtained in nearly quantitative yields. The removal of the MeOPEG moiety from the 1,2,3-triazole nucleus was achieved by acidic cleavage of the cycloadduct mixtures 4 and 5 giving 4- and 5-substituted-1,2,3-triazoles 6 and 7.     

1,3-Dipolar cycloadditions with azomethine ylide species generated from aminocyclopropanes

Two types of bicyclic N-cyclopropyl glycine ester derivatives have been prepared and put under scrutiny as possible precursors of azomethine ylides. The results demonstrate that they can indeed participate in 1,3-dipolar cycloaddition reactions with dipolarophiles, as illustrated in the cases of phenyl vinyl sulfone, N-phenylmaleimide, diethyl fumarate and diethyl maleate. The relative configurations of the major diastereoisomers produced are consistent with the predicted generation of azomethine ylide species, reacting in concerted cycloaddition processes. This unprecedented way of generating such 1,3-dipoles provides access to functionalised pyrrolizidine and pyrrolidine derivatives, that would be difficult to make directly by more classic methods. It was also found that using phenyl vinyl sulfone or N-phenylmaleimide as the dipolarophile reactant, a domino nucleophilic conjugate addition/1,3-dipolar cycloaddition process may operate competitively.     

手性Lewis酸催化硝酮与烯烃的1,3-偶极环加成反应

综述了近年来利用手性Lewis酸催化剂对映选择催化硝酮与1,2-二取代烯烃的1,3-偶极环加成反应的研究进展.     

Light-Induced Tetrazole-Quinone 1,3-Dipolar Cycloadditions

Quinones were firstly used as dipolarophiles in a photoclick 1,3-cycloaddition with 2,5-diaryltetrazoles, as photoactivatable predipoles, providing a novel and efficient access to three types of pyrazole-fused quinones (indazoledione derivatives). Distinctive features of this protocol include the use of light as the unique reagent and readily available, stable, and easy to handle starting materials and good to excellent yields. Photophysical and electrochemical properties of the quinones and their potential application as photoredox catalysts are also detailed.     

1,3-Dipolar Cycloaddition of 5-Substituted-1-Methyl-3-Oxidopyridiniums

5-Methoxy- and 5-dimethylamino-1-methyl-3-oxidopyridiniums were shown to give the 1,3-dipolar cycloadducts widely with methyl acrylate, acrylonitrile, N-phenylmaleimide, styrene, phenylacetylene, cyclopentadiene, cyclopentene, diethyl azodicarboxylate and singlet oxygen.     

1,3-Dipolar cycloaddition route to novel isoxazole-type derivatives related to combretastatin A-4

A series of compounds related to combretastatin A-4, containing a five-membered heterocyclic ring interposed between the two phenyl groups have been prepared. Synthetic approach involves 1,3-dipolar cycloaddition of various 3,4,5-trimethoxyphenyl units with an in situ generated nitrile oxide from a suitable aldoxime using sodium hypochlorite. Depending on the nature of the dipolarophile, 3,5-diarylisoxazole derivatives were obtained along with the 3,4-regioisomeric isomers.     

A stereoselective method for the synthesis of enantiopure 3-substituted 4-hydroxyproline derivatives via 1,3-dipolar cycloadditions

The stereoselective 1,3-dipolar cycloaddition between (Z)-1,4-dichloro-2-butene and a menthone-derived nitrone led to the corresponding isoxazolidine. Regioselective azidation of a single chlorine atom followed by another Cu(I)-catalyzed azide–alkyne 1,3-dipolar cycloaddition (CuAAC) induced enantiopure 1,2,3-triazolyl-functionalized isoxazolidines. The subsequent acidic cleavage of the menthone chiral auxiliary and reductive cleavage of the isoxazolidine N–O bond triggered an intramolecular cyclization through the displacement of the second chlorine. This rapid and stereoselective synthetic strategy provided reliable access to a series of enantiopure 3-substituted 4-hydroxyproline derivatives.     

1,3-Dipolar cycloaddition of diazoalkanes onto dimethyl 1-(formylamino)ethylenephosphonate: a new route to 1-aminocyclopropanephosphonic acids and 3-phosphorylated pyrazoles

Diazoalkanes regiospecifically react with dimethyl 1-(formylamino)ethylenephosphonate (1a) to afford 5-substituted dimethyl 3-(formylamino)-4,5-dihydro-3H-pyrazol-3-phosphonates 2 in high yields. Their thermal decomposition followed by hydrolysis provides a straightforward access to 2-substituted 1-aminocyclopropanephosphonic acids 4. Aromatization of 2 under acidic conditions leads to 3-phosphorylated pyrazoles 5.     

The 1,3-Dipolar Cycloadditions of 3-Arylsydnone-4-Carbonitrile Oxides with Alkenes

3-Arylsydnone-4-carbonitrile oxides may undergo 1,3-dipolar cycloadditions with alkenes to produce the corresponding 3-aryl-4-(5-substituted-isoxazolin-3-yl)sydnones. The direct reaction of 3-arylsydone-4-carbohydroximic acid chlorides with alkenes may also give the same products, and with higher yield.     

微波促进的葡萄糖烯与硝酮的1,3-偶极环加成反应

在微波辐射下, 葡萄糖烯(1)与硝酮2环加成反应的效率大大提到, 在乙二醇二甲醚溶液中, 200 ℃封管反应2 min, 环加成反应产物的收率可高达96%, 而且反应的立体选择性无明显变化. 利用环加成产物可进一步合成各种含官能团的碳糖苷衍生物, 找到了一种合成碳糖苷衍生物中间体的简便有效方法.     

Direct construction of novel dispiro heterocycles through 1,3-dipolar cycloaddition of azomethine ylides

The 1,3-dipolar cycloaddition of 2-oxo-(2H)-acenaphthylen-1-ylidene-malononitrile and 2-fluoren-9-ylidene-malononitrile as dipolarophiles have been investigated for the first time with the azomethine ylides generated in situ from N-substituted isatin and sarcosine to furnish novel dispiro heterocycles. The structure and relative stereochemistry of both types of cycloadducts were confirmed by single crystal X-ray diffraction, as well as with the help of ¹H, ¹³C, and HMBC spectroscopic methods.     

Origins of the Reactivity in 1,3-Dipolar Cycloadditions of Acyl Isocyanide Ylides

1,3-Dipolar cycloadditions are the preferred method to generate five-membered heterocyclic rings. Surprisingly, cycloadditions based on acyl-isocyanide ylides have remained underexplored by the chemical community. Acyl-isocyanide ylides readily react with dipolarophiles, such as substituted alkenes, to yield Δ¹-pyrroline derivatives. As an explanation for the observed reactivity of this reaction is lacking, extensive density functional theory calculations were performed to scrutinize the mechanistic features of the transformation. Herein we explain the experimental outcome of the reaction using a variety of reactivity theories and predict opposed regioselectivity for electron-poor and electron-rich dipolarophiles. With the insights obtained, we hope to incentivize the design of new cycloaddition reactions based on the acyl-isocyanide ylides motif.     

1,3-Dipolar cycloaddition of azomethine ylides generated from aziridines in supercritical carbon dioxide

The 1,3-dipolar cycloaddition of azomethine ylides with DMAD in supercritical carbon dioxide is reported. The photolysis reaction conditions were optimized with a suitable adjustment of pressure, temperature, irradiation time and co-solvent concentration leading to a more efficient reaction than in neat acetonitrile. Similar results were observed using thermal reaction conditions. Supercritical carbon dioxide with a minute co-solvent addition is shown to be a very efficient medium for promoting this type of cycloadditions.     

Chemo- and Regioselective 1,3-Dipolar Cycloaddition of 2-Diazopropane over 1,4-Benzoquinone: Synthesis of New Pyrazoloquinones

Abstract

1,3-Dipolar cycloaddition reaction of 2-diazopropane 1 with 1,4-benzoquinone 2 carried out at ?20 °C led to a minor mono-cycloadduct 4 and mixture of bis-cycloadducts 6 and 7. The same addition realized with 3H-pyrazole 7 at ?60 °C for 2 h yields a mixture of compounds 8 and 9 and results in O-alkylation. The reaction of 3H-pyrazoles 4 and 7 with dimethylsulfoxide and oxalyl chloride under Swern conditions led to pyrazolenines 11 and 12.     

Three-Component Synthesis and 1,3-Dipolar Cycloaddition of Highly Functionalized Pyrans with Nitrile Oxides: Easy Access to 1,2,4-Oxadiazoles

Three-component reaction of 1-[(4-chlorophenyl)sulfanyl]acetone, malononitrile, and substituted aromatic aldehydes in the presence of sodium ethoxide under simple mixing at ambient temperature for 5–8 min afforded highly functionalized 4H-pyrans in good to excellent yields. 1,3-Dipolar cycloaddition of nitrile oxides over the nitrile functionality of the 4H-pyrans furnished 1,2,4-oxadiazoles in moderate yields.

Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for full experimental and spectral details.     

A facile regioselective 1,3-dipolar cycloaddition protocol for the synthesis of new class of quinolinyl dispiro heterocycles

The 1,3-dipolar cycloaddition reaction of azomethine ylides generated in situ from isatin and secondary amino acids with quinolinyl dipolarophiles in refluxing methanol afforded new class of quinolinyl dispiro heterocycles with multi hetero core units. The regio and stereochemistry of the product was unambiguously assigned by ¹H, ¹³C, 2D NMR techniques and single crystal X-ray analysis. The structures of the compounds are stabilized through the presence of intermolecular hydrogen bonding and intramolecular non-covalent interactions.     

Novel 1,3-dipolar cycloadditions of fulvenes and hydrazonyl chlorides: a facile synthesis of the cyclopenta[d]pyridazines

A simple and convenient route for one-pot synthesis of cyclopenta[d]pyridazine through 1,3-dipolar cycloaddition of fulvenes and hydrazonyl chlorides is described. The reaction of fulvenes with hydrazonyl chlorides in the presence of silver carbonate smoothly afforded a series of cyclopenta[d]pyridazines.     

1,3-Dipolar addition of nitrones to symmetrically substituted allenes: for the determination of absolute configuration of chiral allenes by NMR spectroscopy

5-Methyl-5-phenylpyrroline N-oxide was proved to be a useful 1,3-dipole for determining the absolute configuration of chiral allenes by means of NMR spectroscopy.     

1,3-Dipolar cycloaddition for selective synthesis of functionalized spiro[indoline-3,3'-pyrrolizines]

The 1,3-dipolar cycloaddition reaction of dimethyl hex-2-en-4-ynedioate with azomethine ylides derived from reaction of L-proline with various isatins in methanol selectively resulted in the formation of functionalized spiro[indoline-3,3'-pyrrolizine]acrylates as main products and spiro[indoline-3,3'-pyrrolizine]propiolates as minor products.This result indicated that the electron-deficient alkyne has higher reactivity than that of electron-deficient alkene in 1,3-dipolar cycloaddition reaction.     

1,3-Dipolar Cycloaddition of Nitrones with 5-Methylenehydantoins: Synthesis and Transformation of New Spirohydantoin Derivatives

1,3-Dipolar cycloaddition of various acyclic nitrones with 5-methylenehydantoin derivatives afforded new chiral spiroadducts in good yields. All the spirohydantoins were obtained through a regio- and stereospecific pathway, and the spirocarbon atom was linked to the isoxazolidine oxygen atom. A representative example of the reduction of the spirohydantoin 8 with Zn/AcOH led to the substituted 1,3-aminoalcohol hydantoin 20.