Novel porphyrin-quinone architectures via 1,3-dipolar cycloaddition reactions

Porphyrinic pyridinium ylides react with 1,4-benzoquinone and 1,4-naphthoquinone to afford novel meso-substituted indolizine porphyrins.     

Trifluoromethyl-p-tolyldiazomethane in 1,3-dipolar cycloaddition reactions

Trifluoromethyl-p-tolyldiazomethane (I) forms [3+2]-cycloadducts with activated alkenes and alkynes. The products of these regiospecific reactions are substituted pyrazolines (II)–(VI) and pyrazoles (VIII)–(X). Reaction of (I) with fumarates, trifluoropyruvates and allyl chloride is accompanied by elimination of N₂ and formation of a 1,2-bis(trifluoromethyl)stilbene. The results obtained indicate that (I) enters only the HOMO-controlled 1,3-dipolar addition reactions.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 7, pp. 1589–1593, July, 1991.     

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.     

Preparation and stereoselectivity of 1,3-dipolar cycloaddition of C-glycosyl nitrones to N-arylmaleimides

Summary The cycloaddition of 3-hydroxyglycosyl-N-methylnitrone (1) to N-arylmaleimides gave thesyn isoxazolidines6, whereas 3-acetoxyglycosyl-N-methylnitrone (2) afforded theanti isoxazolidines8 and10. The formation of6 was rationalized by anexo attack, stereoelectronically preferred through the hydrogen bond between the pentose hydroxyl group and one of the carbonyl groups of N-arylmaleimide. The sterically preferredendo attack avoiding the repulsions between N-arylmaleimide and sugar moiety was proposed for addition of2. The structure and steric configuration of the products have been assigned on the basis of¹H- and¹³C-NMR spectroscopy, mainly by nuclear Overhauser effect difference spectroscopy. AM1 calculations of the nitrones and MM2 calculations of the adducts were performed.

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Darstellung und Stereoselektivität der 1,3-dipolaren Cycloaddition von C-Glycosyl-Nitronen an N-Arylmaleimiden

Zusammenfassung Die Cycloaddition von 3-Hydroxyglycosyl-N-methylnitron (1) an N-Arylmaleimide gab diesyn-Isoxazolidine6, mit 3-Acetoxyglycosyl-N-methylnitron (2) wurden hingegen dieanti-Isoxazolidine8 und10 erhalten. Die Bildung von6 wurde mit einemexo-Angriff erklärt, der stereoelektronisch wegen einer Wasserstoffbrückenbindung zwischen der Hydroxylgruppe der Pentose und einer Carbonylgruppe des N-Arylmaleimides bevorzugt wird. Für die Addition von2 wurde ein sterisch bevorzugterendo-Angriff vorgeschlagen, da dabei ungünstige Wechselwirkungen zwischen der N-Arylmaleimid- und der Zuckereinheit vermieden werden. Die Struktur und Stereochemie der Produkte wurde mittels¹H- und¹³C-NMR unter Verwendung von NOE-Differenzmessungen ermittelt. Es wurden auch AM1-Rechnungen für die Nitrone und MM2-Rechnungen für die Addukte durchgeführt.

     

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.

     

Synthesis of celecoxib via 1,3-dipolar cycloaddition

A regioselective 1,3-dipolar cycloaddition reaction between a nitrile imine and an enamine is described for the preparation of celecoxib. Nitrile imines are generated in situ from the corresponding hydrazonoyl benzenesulfonates.     

Synthesis of new beta-substituted meso-tetraphenylporphyrins via 1,3-dipolar cycloaddition reactions. 1

The azomethine ylide generated from the reaction of (beta-formyl-meso-tetraphenylporphyrinato)nickel(II) with N-methylglycine reacts with a range of dipolarophiles, yielding new beta-substituted-meso-tetraphenylporphyrins. The regio- and stereochemistry of the new compounds was established using one- and two-dimensional NMR techniques.     

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.     

Synthesis of novel dispiro-oxindoles via 1,3-dipolar cycloaddition reactions of azomethine ylides

The 1,3-dipolar cycloaddition of 1-allyl-5-haloisatin derivatives as dipolarophiles with the azomethine ylides generated in situ from N-allylisatin and l-proline to furnish novel dispiro-oxindoles has been investigated. The structures and relative stereochemistry of both types of cycloadducts were confirmed by single crystal X-ray diffraction, ¹H and ¹³C NMR spectroscopy and mass spectrometry.     

Synthesis of spirooxindoles via asymmetric 1,3-dipolar cycloaddition

An efficient method was developed for the asymmetric synthesis of 2′-alkyl-4′aryl-1H-spiro[indole-3,3′-pyrrolidin]-2-ones, which are potential inhibitors of the p53-MDM2 interaction. Our X-ray crystallographic analysis revealed that this 1,3-dipolar cycloaddition proceeds with high stereoselectivity but differently from previously published results.     

Synthesis of novel tricyclic and tetracyclic sultone scaffolds via intramolecular 1,3-dipolar cycloaddition reactions

The initially prepared 2-formylphenyl-(E)-2-phenylethenesulfonates from the condensation of (E)-2-phenylethenesulfonyl chloride with 2-hydroxybenzaldehyde derivatives underwent intramolecular [3+2] cycloaddition with methyl or phenylhydroxylamine, sarcosine, and l-proline, affording the corresponding novel isoxazolidine, pyrrolidine and pyrrolizidine-annulated γ,δ-benzo-δ-sultones, respectively, in good yields. Unambiguous assignment of the molecular structures was carried out by single-crystal X-ray diffraction.     

Regioselective synthesis of 1,2,3-triazole derivatives via 1,3-dipolar cycloaddition reactions in water

Reaction of an arylacetylene with an azide in hot water gave 1,4-disubstituted 1,2,3-triazoles in high yields, while similar reaction between a terminal aliphatic alkyne and an azide (except m-nitroazidobenzene) afforded a mixture of regioisomers with the ratio of 1,4- to 1,5-isomers ranging from 3:1 to 28.6:1. Reactions of m-nitroazidobenzene with either arylalkynes or aliphatic alkynes formed only 1,4-disubstituted derivatives in excellent yields.     

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.     

2,5-Dimethoxy-2,5-dihydrofurans in 1,3-dipolar cycloaddition reactions

Itis shown that 2,5-dimethoxy-2,5-dihydrofurans enter into 1,3-dipolar cycloaddition with benzonitrile N-oxides and with diphenylnitrilimines to form derivatives of 1,3-dimethoxy-6-phenyl-1,3,3a,6a-tetrahydrofuro[3,4-d]isoxazole and 1,3-dimethoxy-4,6-diphenyl-1,3,3a,-6a-tetrahydrofuro[3,4-d]pyrazole, respectively.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 150–151, February, 1971.     

Synthesis of locked meso-beta-substituted chlorins via 1,3-dipolar cycloaddition

A novel approach toward "locked" chlorins with increased stability has been studied in detail. The chlorin skeleton is assembled in a convergent fashion from two fragments via a porphyrin forming reaction, followed by 1,3-dipolar cycloaddition of azomethine ylides, which are formed in situ. Central to the success of the process is the presence of two electron-withdrawing groups in vicinal positions at the perimeter of the porphyrin. As a result, the 1,3-dipolar cycloaddition took place regioselectively, on the bond activated by two electron-withdrawing groups. Moreover, the chlorins formed are locked and hence more stable because of the presence of two quaternary carbon atoms. Overall, in just six steps locked chlorins were constructed from easily available materials. The large array of functionalities tolerated in this approach validates it for a broad use in more advanced studies. The correlation between the results of the 1,3-dipolar cycloaddition and dipolarophile (porphyrin) LUMO energy was extensively studied. There was a definite correlation between the reaction time and the LUMO energy level, and a partial correlation between the reaction yield and the distribution of the LUMO. Additionally, various approaches toward crucial building blocks, namely 3,4-disubstituted-2,5-diformylpyrroles, were investigated.     

Solid-phase synthesis of 1,2,3-triazoles via 1,3-dipolar cycloaddition

The solid-phase synthesis of 1,2,3-triazoles via 1,3-dipolar cycloaddition of polymer-bound azides to various alkynes is reported. Polymer-bound azides were synthesized from polymer-bound halides and sodium azide and reacted with alkynes to produce polymer-bound 1,2,3-triazoles. Cleavage of the triazoles was performed with trifluoroacetic acid. A traceless synthesis of 1,2,3-triazoles was developed using 2-methoxy-substituted resin (polymer-bound 4-hydroxy-2-methoxybenzyl alcohol). In addition, a synthesis of 4-hydroxybenzyl-substituted 1,2,3-triazoles from the bromo-Wang resin (4-(bromomethyl)phenoxymethyl polystyrene) was achieved.     

Synthesis of coumarin-nucleoside conjugates via Huisgen 1,3-dipolar cycloaddition

An efficient synthesis of fluorescent coumarin-nucleoside conjugates via Cu(I) catalysed Huisgen 1,3-dipolar cycloaddition is described. Starting from azidonucleosides and coumarin derivatives, products are obtained in good yields. The fluorescent properties of the newly prepared coumarin-nucleoside conjugates are determined.