Cyclopropenes and methylenecyclopropanes in 1,3-dipolar cycloaddition reactions

The review considers the main results of the cycloaddition reactions involving cyclopropenes and methylenecyclopropanes, the compounds bearing strained three-membered rings and, respectively, endo- and exocyclic double bonds. The main attention is focused on the reactions of these compounds with 1,3-dipoles (nitrones, azomethine imines, azomethine ylides, carbonyl ylides, etc.), which gave complex heterocyclic systems with high regio- and stereoselectivity.

     

Consistent theoretical description of 1,3-dipolar cycloaddition reactions

The cycloaddition reactions of 18 1,3-dipolar molecules to ethylene and acetylene have been reinvestigated by quantum chemical methods that are based on a second-order perturbation treatment of electron correlation. It is found that SCS-MP2 and the new perturbative B2-PLYP density functional provide accurate reaction barriers and outperform MP2 as well as standard density functionals such as B3-LYP. The new second-order based methods have the additional advantage that they perform better with increasing quality of the one-particle space, as is desired for a good quantum chemical method. The errors for the reaction enthalpies are in general larger than for the barriers when compared to CBS-QB3 literature values, which is related to strong changes in the electronic structures, but the deviations are again smaller than with MP2 or B3-LYP and are also more systematic. The results of a detailed basis set study suggest that properly polarized triple-zeta AO basis sets represent a good compromise between accuracy and computational speed. The combination of very inaccurate density functionals with small (double-zeta) basis sets, which yields good results for the initial part of the reactions due to error compensation, is not recommended.     

Chiral bis(2-oxazolinyl)xanthene (xabox)/transition-metal complexes catalyzed 1,3-dipolar cycloaddition reactions and Diels-Alder reactions

A series of chiral 4,5-bis(2-oxazolinyl)-(2,7-di-tert-butyl-9,9-dimethyl)-9H-xanthenes (xabox) and their transition-metal complexes were synthesized. The X-ray analysis of xabox-RhCl₃ complex shows a unique facial type structure. Xabox-Bn-Mn(II) and xabox-Bn-Mg(II) complexes were found to be efficient catalysts in nitrone 1,3-dipolar cycloaddition (1,3-D.C.) reaction resulting in good to excellent enantioselectivities ranging from 96:4 to >99:1of endo/exo ratio and 91-96% ee for the endo adduct. The correlation between enantiomeric excess of the ligand and the product in the nitrone 1,3-D.C. reaction shows a clear linear relationship, which suggests xabox-metal catalyst worked as a single molecular catalyst. In addition, xabox-i-Pr-Mn(II) complex was also found to be an active catalyst for Diels-Alder (D-A) reaction of acryloyloxazolidinone and cyclopentadiene affording the corresponding cycloadduct in quantitative yield along with 82% ee and 98:2 endo/exo ratio.     

Study on the 1,3-dipolar cycloaddition reaction of 4-ethoxy-1,1,1-trifluoro-3-buten-2-one with nitrile oxides

1,3-Dipolar cycloaddition (1,3-DC) reaction of 4-ethoxy-1,1,1-trifluoro-3-buten-2-one 1 with nitrile oxides was studied. It was found that besides its CC participating in the formation of isoxazole rings, trifluoromethyl activated CO also underwent 1,3-DC reaction with nitrile oxides to afford 1,4,2-dioxazole rings. Single crystal diffraction analysis also evidenced the diheterocyclic configuration.     

1,3-dipolar cycloaddition reactions of porphyrins with azomethine ylides

[reaction: see text] The behavior of porphyrins as dipolarophiles in 1,3-dipolar cycloadditions with azomethine ylides was studied. Depending on the nature of the substituent groups on the porphyrin macrocycles, the reaction can give monoadducts (chlorins) or bisadducts (isobacteriochlorins and bacteriochlorins). When a large excess of azomethine ylide is used, trisadducts can also be obtained. Mixed isobacteriochlorin derivatives were prepared from the reaction of azomethine ylides with the chlorin monoadducts previously obtained via Diels-Alder reactions.     

Highly enantioselective 1,3-dipolar cycloaddition reactions of 2-benzopyrylium-4-olate catalyzed by chiral Lewis acids

We have found that significant levels of enantioselectivity are obtained in the 1,3-dipolar cycloadditions of 2-benzopyrylium-4-olate using chiral 2,6-bis(oxazolinyl)pyridine (Pybox)-rare earth metal triflate complexes as chiral Lewis acid catalysts. The reactions with benzyloxyacetaldehyde derivatives catalyzed by Sc(III)-Pybox-i-Pr (10 mol %) proceeded to give endo-adducts selectively with high enantioselectivity (up to 93% ee). The reaction with benzyl pyruvate under similar conditions gave an exo-adduct selectively with 87% ee. In the reaction with 3-acryloyl-2-oxazolidinone, Yb(III)-Pybox-Ph was found to be effective in providing an exo-adduct with extremely high enantioselectivity (98% ee).     

1,3-dipolar cycloaddition of nitrile oxides with 2-phenyl-4-ethoxymethylene-5(4H)-oxazolone

2-Phenyl-4-ethoxymethylene-5(4H)-oxazolone 1 reacts regioselectively with nitrile oxides to give cycloadducts 3 . Reactions of the cycloadducts 3 with nucleophiles lead to 4-aminoisoxazole derivatives.     

Efficient synthesis of isoxazolidine-substituted bisphosphonates by 1,3-dipolar cycloaddition reactions

Several bisphosphonates bearing a substituted isoxazolidine ring have been synthesized in good yield by direct 1,3-dipolar cyclization reaction, under microwaves catalysis, in the absence of solvent. The method allows the simultaneous incorporation, on the geminal position of the bisphosphonate framework, of a basic nitrogen and of an oxygen atom, as third hook. Hydrophobicity-hydrophilicity of BPs is discussed with the help of distribution coefficients.     

Regioselective synthesis of novel spiroindane-1,3-diones through 1,3-dipolar cycloaddition reactions

A facile synthesis of novel spiroindane-1,3-diones has been achieved via 1,3-dipolar cycloaddition of an azomethine ylide, generated in situ from ninhydrin and 1,2,3,4-tetrahydroisoquinoline, with the conjugated double bond of chalcone derivatives. The regiochemistry and structures of the cycloadducts were determined with spectroscopic data and by X-ray crystal structure analysis.     

Gold(I)-catalyzed diastereo- and enantioselective 1,3-dipolar cycloaddition and Mannich reactions of azlactones

Azlactones participate in stereoselective reactions with electron-deficient alkenes and N-sulfonyl aldimines to give products of 1,3-dipolar cycloaddition and Mannich addition reactions, respectively. Both of these reactions proceed with good to excellent diastereo- and enantioselectivity using a single class of gold catalysts, namely C(2)-symmetric bis(phosphinegold(I) carboxylate) complexes. The development of the azlactone Mannich reaction to provide fully protected anti-α,β-diamino acid derivatives is described. 1,3-Dipolar cycloaddition reactions of several acyclic 1,2-disubstituted alkenes and the chemistry of the resultant cycloadducts are examined to probe the stereochemical course of this reaction. Reaction kinetics and tandem mass spectrometry studies of both the cycloaddition and Mannich reactions are reported. These studies support a mechanism in which the gold complexes catalyze addition reactions through nucleophile activation rather than the more typical activation of the electrophilic reaction component.     

Tricyclic-isoxazolidine analogues via intramolecular 1,3-dipolar cycloaddition reactions of nitrones

The tricyclic-isoxazolidine analogues tetrahydrothiochromenoisoxazoles, hexahydroisoxazolequinolines and tetrahydroisoxazolepyranopyridines were prepared by an intramolecular 1,3-dipolar cycloaddition reaction of a nitrone with an alkene. For N-alkylated hexahydroisoxazolequinolines, reduction of the reaction time from two days to 40 min was achieved using microwave heating. The cyclization to form tetrahydroisoxazolepyranopyridines only proceeded when the alkene was substituted with an electron withdrawing group.     

Conformational preferences of methacrolein in Diels-Alder and 1,3-dipolar cycloaddition reactions

A B3LYP/6-31G* study has been carried out for the reactions of methacrolein with cyclopentadiene, parent nitrone, 1-pyrroline-1-oxide, and (Z)-C,N-diphenylnitrone, in which the coordination of a Lewis acid (borane) and the solvent polarity (dichloromethane) have been taken into account. Calculated activation parameters, regioselectivities (for 1,3-dipolar cycloaddition reactions), and endo/exo stereoselectivities show good agreement with available experimental data. Gas-phase calculations show a varied behavior of the s-cis/s-trans TS stability for noncatalyzed reactions (from the systematic s-cis preference for the cyclopentadiene reaction to the systematic s-trans predilection encountered in the diphenylnitrone cycloaddition). BH3 coordination leads to a preferential stabilization of s-trans TSs in the reactions of cyclopentadiene (exo approach) and diphenylnitrone but a larger stabilization of s-cis structures in the processes involving the parent nitrone or 1-pyrroline-1-oxide. Additionally, a rather systematic preferential stabilization of s-trans structures is induced by solvent polarity in most reactions. As a consequence, an s-trans preference is predicted in solution for both thermal and catalyzed types of reactions in most approaches. Such a conclusion is consistent with some experimental results suggesting a preference for a particular conformation of the methacrolein-Lewis acid complexes.     

分子内1,3-偶极环加成反应的研究II: 呋喃偶极体系的热及光化学反应

合成并研究了呋喃1,3-偶极C-2-呋喃-N-烯基硝酮(1)的热和光化学反应.1的热化学环加成反应具有区域选择性.生成氧氮杂二环辛烷类化合物.日光灯照明下加热还可得到双键迁移产物.1在波长>302nm下的光化反应产物是氧氮杂环丙烷,而在λ>270nm下除了还有重排产物N-戊烯基-2-呋喃甲酰胺,氧氮杂环丙烷不稳定,加热下通过1发生分子内环加成反应.     

Optically active nitrile oxides: synthesis and 1,3-dipolar cycloaddition reactions

Baker’s yeast-promoted reduction of the CC bond in 2-aryl-1-nitropropenes gave the corresponding optically active (R)-2-aryl-1-nitropropanes of high enantiomeric purity (ee >90%). They were next converted with the aid of the Mukaiyama and Hoshino method into the optically active nitrile oxides, which were made to react in situ with ethyl propiolate, methylvinyl ketone and (R)-1-phenyl-2-(phenylsulfonyl)ethyl acrylate to yield the appropriate, enantiomerically enriched, isoxazoles or 4,5-dihydroisoxazoles as diastereomeric mixtures, respectively.     

The face selectivity of 1,3-dipolar cycloaddition reactions of 4-butyloxycarbonyl-3,4,5,6-tetrahydropyridine 1-oxide

A study of the stereo- and face selectivity of the cycloaddition reactions of a series of mono- and disubstituted alkenes with 4-butyloxycarbonyl-3,4,5,6-tetrahydropyridine 1-oxide has been carried out. Rate constants for the cycloaddition of the nitrone to methyl acrylate, styrene, and methyl methacrylate have been determined at various temperatures by ¹H NMR spectroscopy. The activation parameters indicate the concerted nature of the reaction. The 4-substituted nitrone is found to be more reactive than its unsubstituted counterpart 3,4,5,6-tetrahydropyridine 1-oxide. The addition reactions have displayed a very high degree of face selectivity (9:1), and those reactions in micellar media are found to be very efficient. Conformational analysis and peracid-induced ring opening of a cycloadduct has been carried out to give second-generation cyclic nitrones.     

Synthesis of heterocycles by 1,3-dipolar cycloaddition reactions with the participation of nitroalkenes (review)

The advances in the synthesis of five-membered nitrogen-containing heterocycles by reactions involving 1,3-dipolar cycloaddition of conjugated and unconjugated nitroalkenes to various 1,3-dipoles (diazo compounds, azides, nitrile N-oxides, etc.) are systematized.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 435–452, April, 1990.     

Discovery of long-wavelength photoactivatable diaryltetrazoles for bioorthogonal 1,3-dipolar cycloaddition reactions

Several long-wavelength (365 nm) photoactivatable diaryltetrazoles were discovered by screening a series of substituted diaryltetrazoles and subsequently showed excellent reactivity in the photoactivated 1,3-dipolar cycloaddition reactions toward electron-deficient and conjugated alkenes in organic solvents as well as an alkene-containing protein in the aqueous buffer.