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.     

Substrate-controlled and site-selective [3+2] cycloadditions of N-heterocyclic carbene derived ambident dipoles

2-aryl thiocarbamoyl benzimidazolium and imidazolinium inner salts derived from benzimidazole and imidazoline carbenes are unique ambident C-C-S and C-C-N 1,3-dipolar systems, which undergo highly efficient and site-selective cycloaddition reactions with dimethyl acetylenedicarboxylate or dibenzoylacetylene to furnish spiro(imidazole-2,3'-thiophene) derivatives in excellent yields. When treated with ethyl propiolate, methyl acrylate or acrylonitrile, spiro(imidazole-2,3'-pyrrole) derivatives were formed in good yields. Theoretical studies revealed an asynchronous concerted mechanism for both the C-C-S and C-C-N 1,3-dipolar cycloaddition reactions. The site selectivity in the [3+2] cycloaddition reaction of ambident 1,3-dipoles was predictably regulated by both the electronic and steric effects of dipolarophiles.     

Studies on heteroaromaticity. XV . the 1,3-dipolar cycloaddition reaction of 5-nitro-2-furyldiazomethane

The 1,3-dipolar cycloaddition reaction of 5-nitro-2-furyldiazomethane ( 1 ) with acrylonitrile, acrylamide, methyl acrylate, diethyl fumarate, methyl methacrylate and methyl cinnamate afforded the corresponding 3-substituted pyrazolines. ( 2a-f ). Similarly the pyrazoles ( 3b-d ) were prepared by addition of 1 to acetylenic compounds such as diethyl acetylenedicarboxylate, methyl phenylpropiolate and cyanoacetylene. Reaction of 1 with fumaronitrile and ω-nitro-styrene gave also the corresponding pyrazoles ( 3a and 3e ) instead of the pyrazolines. 3-(5′-Nitro-2′-furyl)-4-phenyl-5-carbomethoxypyrazoline ( 2f ) was oxidized with lead tetraacetate to the corresponding pyrazole ( 3f ), which was different from 3c , an addition product of 1 with methyl phenylpropiolate. 3-(5′-Nitro-2′-furyl)-5-carbamidopyrazoline ( 2b ) was pyrolyzed to the corresponding cyclopropane derivative 4 in low yield.     

Stereoselective 1,3-dipolar cycloadditions of a chiral nitrone derived from erythrulose. An experimental and DFT theoretical study

We have investigated several 1,3-dipolar cycloadditions of a chiral nitrone prepared from L-erythrulose. While cycloadditions to carbon-carbon multiple bonds of dipolarophiles such as ethyl acrylate, ethyl propiolate, or dimethyl acetylenedicarboxylate were poorly stereoselective, reaction with acrylonitrile provided predominantly one diastereomeric adduct. Furthermore, the regioselectivity exhibited by the two structurally similar dipolarophiles ethyl acrylate and ethyl propiolate was found to be opposite. The molecular mechanisms of these cycloadditions have thus been investigated by means of density functional theory (DFT) methods with the B3LYP functional and the 6-31G and 6-31+G basis sets. A simplified achiral version of nitrone 1 as the dipole, and methyl propiolate or acrylonitrile as the dipolarophiles, were chosen as computational models. The cycloadditions have been shown to take place through one-step pathways in which the C-C and C-O sigma bonds are formed in a nonsynchronous way. For the reaction with methyl propiolate, DFT calculations predict the experimentally observed meta regioselectivity. For the reaction with acrylonitrile, however, the predicted regioselectivity has been found to depend on the computational level used. The calculations further indicate the exo approach to be energetically favored in the case of the latter dipolarophile, in agreement with experimental findings. The main reason for this is the steric repulsion between the nitrile function and one of the methyl groups on the nitrone that progressively develops in the alternative endo approach.     

Asymmetic organocatalytic 1,3-dipolar cycloaddition of azomethine ylide to methyl 2-(2-nitrophenyl)acrylate for the synthesis of diastereoisomers of spirotryprostatin A

The total synthesis of two diastereomers of spirotryprostatin A has been established starting with an asymmetric 1,3-dipolar cycloaddition of methyl 2-(2-nitrophenyl)acrylate with azomethine ylides catalyzed by a Br?nsted acid.     

1,3-Dipolar cycloaddition reactions of 4,6-diazaphenanthrene 6-phenacylide

Summary The 1,3-dipolar cycloaddition reactions of 4,6-diazaphenanthrene 6-phenacylide formed in situ from the appropriate quaternary bromide in basic medium were investigated; as dipolarophiles acrylonitrile, ethyl acrylate,n-butyl acrylate and diethyl maleate were used.

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1,3-Dipolare Cycloadditionsreaktionen von 4,6-Diazaphenanthren-6-phenacylid

Zusammenfassung Es wurden die 1,3-dipolaren Cycloadditionen von 4,6-Diazaphenanthren-6-phenacylid untersucht, welches in situ aus dem entsprechenden quaternären Bromid in Gegenwart von Alkali dargestellt wurde. Als Dipolarophile wurden Acrylnitril, Ethylacrylat,n-Buthylacrylat und Diethylmaleat eingesetzt.

     

Regio- and stereo-selective synthesis of multi-substituted 3-pyrrolines

A regio-and stereo-selective synthesis of multi-substituted 3-pyrrolines has been developed.The multi-substituted 3-pyrrolines were synthesized in good yields by 1,3-dipolar cycloaddition of methyl 2-(phenylselanyl)acrylate with azomethine ylides,followed by N-acylation and oxidation-elimination of phenylseleno group.     

Preparation of Multifunctional Stereodefined Dienes

A number of multifunctional 1,3-dienes with defined stereochemistry were prepared by using the products obtained in DABCO-catalyzed condensation reactions of α,β-unsaturated aldehydes with acrylonitrile or methyl acrylate, as substrates for nucleophilic substitution reactions.     

The regioselectivity in the reactions of N-aryl-C-ethoxycarbonylnitrilimines with acrylic acid derivatives

The cycloaddition of a series of C-ethoxycarbonyl-N-arylnitrilimines 5a-f to acrylic acid derivatives namely acrylamide, acrylonitrile and ethyl acrylate has been studied. Under thermal conditions 1,3-dipolar cycloadditions proceed with complete regioselectivity to give 5-R substituted 2-pyrazolines 8–10 in high yield. The structures of the cycloadducts 8–10 were confirmed by ¹³C nmr, ¹H nmr and ir spectra. The regioselectivity is interpreted in terms of HOMO(nitrilimine)-LUMO(dipolarophile) interaction.     

1,3-Dipolar cycloaddition reactions of benzo[h]naphthyridinium N-phenacylides

The 1,3-dipolar cycloaddition reactions of 1,5- and 1,6-benzo[h]naphthyridinium N-phenacylides, formedin situ from the appropriate quaternary bromides in basic medium, with acrylonitrile, ethyl acrylate and dimethyl acetylenedicarboxylate were investigated.

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1,3-Dipolare Cycloadditionsreaktionen von Benzo[h]naphthyridinium-N-phenacyliden

Zusammenfassung Es wurden die 1,3-dipolaren Cycloadditionsreaktionen von 1,5- und 1,6-Benzo[h]naphthyridinium-N-phenacyliden untersucht, diein situ aus den entsprechenden quaternären Bromiden in Gegenwart von Alkali dargestellt wurden. Als Dipolarophile wurden Acrylnitril, Ethylacrylat und Acetylendicarbonsäuredimethylester eingesetzt.

     

7,8,9,10-Tetrahydropyrrolo[2,1-a]isoquinolines in the search for new indolizine derivatives

7,8,9,10-Tetrahydropyrrolo[2,1-a]isoquinolines were obtained by 1,3-dipolar cycloaddition reactions of their corresponding N-ylides with olefinic (acrylonitrile) and symmetrical or non-symmetrical acetylenic dipolarophiles (methyl/ethyl propiolate, dimethyl acetylenedicarboxylate). Also, stable 5,6,7,8-tetrahydroisoquinolinium dicyanomethylide was isolated and characterized by X-ray diffraction analysis.     

Copolymerization and homopolymerization reactions in systems containing electron-donor monomer,electron-acceptor monomer,and lewis acid

Investigations of the copolymerization of acrylonitrile, methacrylonitrile, methyl acrylate, methyl methacrylate, acrylic acid, acryloyl chloride, methyl vinyl ketone, and acrolein with styrene, and of acrylonitrile with acenaphthylene and 1,3-cyclopentadiene in the presence of Lewis acids as catalysts have been carried out. It was found that the free-radical alternating copolymerization and ionic copolymerization or homopolymerization reactions can proceed in these systems. The yield of the competitive free-radical and ionic reactions was related to the type of monomers and strength of the Lewis acid. The mechanism of the catalytic effect of Lewis acids in the reactions studied is discussed.     

Multifunktionellebis-(trifluormethyl)-substituierte Synthesezwischenstufen aus 4,4-Bis-(trifluormethyl)-1-oxa-3-azabuta-1,3-dienen viaBaylis-Hillman Reaktion

Summary TheBaylis-Hillman reaction of 4,4-bis-(trifluoromethyl)-1-oxa-3-azabuta-1,3-dienes with acrolein, methyl vinyl ketone, ethyl vinyl ketone, acrylonitrile, ethyl acrylate, andn-butyl acrylate provides useful multifunctional partial fluorinated building blocks in one step.

Prof. Dr. Rolf Huisgen zum 75. Geburtstag gewidmet     

A theoretical investigation of the regio- and stereoselectivities of the 1,3-dipolar cycloaddition of C-diethoxyphosphoryl-N-methylnitrone with substituted alkenes

A theoretical study of the regio- and stereoselectivities of the 1,3-dipolar cycloaddition of C-diethoxyphosphoryl-N-methylnitrone with substituted alkenes (allyl alcohol and methyl acrylate) is carried out using DFT at the B3LYP/6-31G(d,p) level of theory. The FMO analysis and DFT-based reactivity indices confirmed the experimental ortho regioisomeric pathway. Potential energy surface analysis shows that these 1,3-dipolar cycloaddition reactions favor the formation of the ortho-trans cycloadduct in both cases. The obtained results are in agreement with experimental data.     

Addition of diazocyclopropane generatedin situ to acrylic acid derivatives and transformations of resulting functionally substituted spiro(pyrazolinecyclopropanes)

The reaction of diazocyclopropane generatedin situ with acrylonitrile or methyl acrylate to give 1∶1, 1∶2, and 2∶1 cycloadducts was carried out. The products resulting from 1,3-dipolar cycloaddition and subsequent isomeriation,viz., 3-cyano- and 3-methoxycarbonylspiro(2-pyrazoline-5,1′-cyclopropanes), isolated in the first step in ∼70% yield, react in an alkaline solution with the above acrylates or diazocyclopropane as C(3)-nucleophiles to give the corresponding 3-(2′-cyanoethyl)-, 3-(2′-methoxycarbonylethyl)-, or 3-(cyclopropylazo)-1-pyrazolines. The thermal deazotization of these pyrazolines to spiropentane derivatives was investigated. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 532–539, March, 1997.     

1,3-Dipolar cycloaddition approach to pyrrolidine analogues of C-nucleosides related to pseudouridine

Pyrrolidine analogues of C-nucleosides related to pseudouridine have been synthesized by 1,3-dipolar cycloaddition reactions of uracil-5 and 2,4-dimethoxypyrimidine-5 nitrones with allyl alcohol and methyl acrylate, and subsequent reductive cleavage of the isoxazolidine cycloadducts. The dimethoxy derivatives have been easily deprotected to the corresponding uracils bearing the pyrrolidine ring instead of a sugar moiety. The regio and stereoselectivity of the reactions are discussed.     

Fluorinated ketones in the Baylis-Hillman reaction

Hexafluoroacetone, bromopentafluoroacetone, 1,3-dichloro-1,1,3,3-tetrafluoroacetone, and trifluoropyruvic acid methyl ester react with ethyl acrylate, acrylonitrile, acrolein, and methyl vinyl ketone in the presence of 1,4-diazabicyclo[2,2,2]octane with the formation of -alkylation products.A. N. Nesmeyanov Institute of Heteroorganic Compounds, Russian Academy of Sciences, 117813 Moscow. Translated fromIzvestiya Akademii Nauk, Seriya Khimicheskaya, No. 12, pp. 2763–2767, December, 1992.     

Formation of lactones in the heck reaction

The Heck reaction of methyl 2-bromobenzoate with methyl acrylate gave a mixture of alkene 1 and lactone 9 . Acrylonitrile and methyl 2-bromobenzoate gave lactone 10 . Ethyl 2-bromobenzoate and methyl acrylate or acrylonitrile gave the alkenes 2 and 4 respectively.     

Concise synthesis of zanamivir and its C4-thiocarbamido derivatives utilizing a [3+2]-cycloadduct derived from d-glucono-δ-lactone

A concise synthesis of zanamivir (GG167, 1) has been accomplished utilizing the adduct of a highly diastereoselective 1,3-dipolar cycloaddition between methyl acrylate and the nitrone derived from d-glucono-δ-lactone. Azide-free introduction of C4 nitrogen functionality and one-pot selective O-acetylation followed by straightforward generation of dihydropyran moiety are two advantages in this synthesis. Using the established methodology and common intermediate, two representative C4-thiocarbamido derivatives of zanamivir were also synthesized.     

A Simple and Efficient Method for the Synthesis of Novel Pyrazolyl Isoxazoline Derivatives Using Hypervalent Iodine (III) Reagent

A series of novel pyrazolyl isoxazolines were synthesized by 1,3‐dipolar cycloaddition of pyrazolyl nitrile oxide with various activated alkene, such as acrylonitrile, methyl acrylate, and vinyl acetate, in the presence of iodobenzene diacetate in methanol containing a catalytic amount of TFA at room temperature (13 compounds upto 92% yield were isolated).