Presence Of Dipolarophiles Research Articles

Thermal rearrangement of 2,3-diaryl-1-phthalimidoaziridines

2,3-Diaryl-1-phthalimidoaziridines and 2,3-diaryl-1-phthalimidoaziridine-2-carbonitriles were found to readily undergo thermal rearrangement into imines via 1,2-migration of the phthalimido group and accompanying C–C bond cleavage. Isomerization proceeds regioselectively with preferable migration to the electron-deficient carbon atom. Interestingly, this reaction was found to predominate even in the presence of dipolarophiles.

Microwave-induced Pericyclic Reactions of Aza- and Diazafulvenium Methides

The pericyclic reactions of 4,5-dimethoxycarbonyl-substituted aza- and diazafulvenium methides generated under microwave-induced thermolysis conditions have been described. The 7,7-dimethyl-substituted derivatives undergo allowed suprafacial sigmatropic [1,8]-hydrogen shifts leading to the efficient synthesis of C-vinylpyrroles and Cvinylpyrazoles. These intermediates could not be trapped in [8Π+2Π] cycloaddition in the presence of dipolarophiles. Azaand diazafulvenium methides unsubstituted at C-1 and C-7 behave as 8Π 1,7-dipoles in the presence of dipolarophiles under microwave irradiation, leading to a range of pyrrolo and pyrazolo annulated heterocycles resulting from addition across positions 1 and 7. Aza- and diazafulvenium methide derivatives bearing only one methyl group at C-7 are intercepted in sigmatropic hydrogen shifts to give functionalized pyrroles and pyrazoles, respectively. In the presence of electron- deficient dipolarophiles, these 7-methyl-substituted derivatives act as 1,7-dipoles in [8Π+2Π] cycloadditions, however, competitive formation of the corresponding vinyl pyrroles and vinylpyrazoles is also observed.

ChemInform Abstract: Nitrolic Acids: Efficient Precursors of Nitrile Oxides under Neutral Conditions.

Abstract Nitrolic acids are prepared in good yields from primary nitroalkanes or primary alkyl bromides. Upon heating in THF, they afford the corresponding nitrile oxides under neutral conditions. In the presence of dipolarophiles, isoxazoles are obtained in yields up to 95%. For the less stable alkoxycarbonyl- and arylnitrolic acids the crude nitrolic acids can be directly engaged in the cycloaddition reaction.

Thermolysis of dimethyl cis- and trans-1 pthalimidoaziridine-2,3-dicarboxylates in the presence of dipolarophiles

Thermolysis of dimethyl esters of stereoisomeric phthalimidoaziridine-2,3-dicarboxylic acids in the presence of dimethyl fumarate, dimethyl maleate, and N-phenylmaleimide occurred stereo-specifically and stereoselectively led to the formation of derivatives of 1-phthalimidopyrrolidine, products of 1,3-dipolar additrion of intermediately arising azomethine ylides. In keeping with the rules of the conservation of orbital symmetry the thermal opening of the 2,3-disubstituted 1-phthalimidoaziridines into azomethine ylides occurred conrotatory. The relative positions of the substituents in the dipolarophiles is retained in the reaction products indicating the concerted addition mechanism.

Synthesis of 2‐C‐Branched Oligo(glyco–amino acid)s (OGAAs) by Ring Opening of 1,2‐Cyclopropanecarboxylated Sugar Donors

Carbohydrates decorated with amino acids are becoming an important area of glyco-chemistry research. Possessing the architecture of a sugar and an amino acid in a single molecule, these glyco–amino acids (GAAs) are expected to exhibit the characteristics of both carbohydrates and amino acids, which are both biological polymer precursors. C-branched glyco–a-amino acid moieties are found in a ACHTUNGTRENNUNGvariety of nucleoside antibiotics, such as polyoxins, miharamycins, nikkomycin and amipuramycin. Very few methods are available in the literature for the synthesis of monosaccharide-derived C-branched GAA derivatives. Linking an a-amino acid at C-2 or C-4 through a C C bond has been found to be very difficult. For this reason, the biological importance of these GAAs is not yet fully understood. It has been shown that unnatural 2-C-acetonylsugars serve as metabolic substrates for cell surface engineering by mimicking 2-N-acetylsugars. Similarly, a 2-C-N-hydroxy ACHTUNGTRENNUNGacetamide mimic of GlcNAc was synthesised and shown to be an inhibitor of the biosynthesis of lipid A. Herein, we report the first stereoselective synthesis of 2-C-branched oligo(glyco– amino acid)s (OGAAs) by ring opening of 1,2-cyclopropanecarboxylated sugar donors. The high reactivity and regioselectivity of donor–acceptor cyclopropanes has been well documented in the literature. 1,2-cyclopropanecarboxylated sugars have been used as donor–acceptor cyclopropanes in the synthesis of 2-Cbranched monosaccharides through electrophilic C1–C7 ACHTUNGTRENNUNGcyclopropane ring opening or by transition-metal-catalysed glycosylation. Recently, a four-component Pavarov reaction and a transition-metal-mediated radical reaction were developed for the direct synthesis of 2-C-branched carbohydrate derivatives from glucals. These branched glycosides were further derivatised to bicyclic carbohydrate 1,2lactones. Glucal-derived donor–acceptor cyclopropanes have also been used as 1,3-dipoles under acidic conditions, which result in (3+2) cycloaddition reactions in presence of dipolarophiles. By using the ability of 1,2-cyclopropanecarboxylated sugars to undergo electrophilic ring opening assisted by the adjacent oxygen in presence of an electrophile, we herein present the N-iodosuccinimide (NIS)mediated ring opening of 1,2-cyclopropanecarboxylated glycosyl donors with carbohydrate O-nucleophilic glycosyl bond acceptors. To achieve this novel glycosylation reaction, we began by using 1,5-anhydro-2,6-dideoxy-1,2-C-(exo-carbomethoxymethylene)-3,4-di-O-benzyl-a-l-rhamnal 1 as the donor and 1,2-3,4-diisopropylidine-a-d-galactose 2 as the acceptor with NIS as the electrophile at 0 8C in acetonitrile. However, no expected disaccharide was observed under these reaction conditions, even with an excess of acceptor 2 (>3 equiv). Similar reaction conditions with dichloromethane as the

Efficient synthesis of isoxazoles and isoxazolines from aldoximes using Magtrieve ™ (CrO 2)

Treatment of aldoximes 1 with Magtrieve ™ (CrO 2) in presence of dipolarophile 3 or 4, furnished a variety of isoxazolines 5a–u and isoxazoles 6a–q as 1,3-dipolar cycloaddition (1,3-DC) products (38 examples; 63–90% isolated yields). In situ formation of a nitrile oxide intermediate was confirmed through isolation of the dimerization product furoxane 2a in absence of any dipolarophile. The methodology has been extended to intramolecular nitrile oxide cycloaddition (INOC) reactions to access highly useful chromane derivatives 7–8 (75–80% isolated yields). Magtrieve ™, as a new reagent for 1,3-DC reactions, has offered excellent substrate generality and at the same time demonstrated tolerance toward sensitive protecting groups and electron-rich functional groups.

Conversion of Oximes to Carbonyl Compounds by Triscetylpyridinium Tetrakis(oxodiperoxotungsto) Phosphate (PCWP)-mediated Oxidation with Hydrogen Peroxide

Aromatic and aliphatic oximes have been deoximated in chloroform-water to the corresponding aldehydes with dilute hydrogen peroxide and triscetylpyridinium tetrakis (oxodiperoxotungsto) phosphate as catalyst. The presence of dipolarophiles in the reaction mixtures allows a competitive reaction that converts oximes into isoxazole and isoxazoline derivatives via the intermediate formation of nitrile oxide species.

Thermolysis of furoxans annulated with five-membered carbocycles in the presence of dipolarophiles

The conditions for the thermolysis of furoxans annulated with differently strained five-membered carbocycles (cyclopentafuroxan 1, norbornenofuroxan 2, and acenaphthofuroxan 3) to bis(nitrile oxides) in the presence of various dipolarophiles (diethyl acetylenedicarboxylate, benzoylformonitrile, and ethoxycarbonylformonitrile) were optimized. It was found that the reactivities of the above furoxans as sources of bis(nitrile oxides) decrease in the order 2 > 1 > 3. Among the furoxans studied, only norbornenofuroxan 2 can be recommended as a possible cross-linking reagent for polymers. The formation of di-N-oxides of 3,4-bis(cyanopropyl)-, 3,4-bis(cyanocyclopentyl)-, and 3,4-bis(cyanonaphthyl)furoxans was detected. They resulted from intermolecular cyclodimerization of bis(nitrile oxides) initially formed in the thermolysis of furoxans 1–3.

Monofluoro-substituted azomethine ylides in fluorocarbene reactions with imines. Synthesis and transformations of monofluoroaziridines

N-Arylmethylene and N-benzhydrylideneamines react with fluorocarbene yielding fluoro-substituted azomethine ylides that undergo 1,3-π-cyclization into aziridines. Generation of fluoroylides in the presence of dipolarophiles (dimethyl maleate or dimethyl acetylenedicarboxylate) led to the reaction of 1,3-dipolar cycloaddition resulting in substituted 2-pyrrolines or pyrroles. 2-Fluoroaziridines, products of N-alkyl-N-benzhydrylideneamines 1,3-π-cyclization, in the presence of acid catalysts suffer isomerization into α-fluoroimines and 1,3-disubstituted indoles.

1,4‐Diazabicyclo[2.2.2]octane (DABCO) as an Efficient Reagent for the Synthesis of Isoxazole Derivatives from Primary Nitro Compounds and Dipolarophiles: The Role of the Base

AbstractThe dehydration of primary nitro compounds can be performed by bases in the presence of dipolarophiles. The reactivity of several tertiary amines or azaheteroaromatic compounds containing one or two basic centres is shown to be related to the ability of the protonated base to establish H‐bonded ion pairs with the adduct that is formed from the nitronate and the dipolarophile in chloroform. Among the organic bases examined, caged tertiary diamine 1,4‐diazabicyclo[2.2.2]octane (DABCO) gave the best results. The reaction is applicable to activated nitro compounds and to phenylnitromethane and affords isoxazoline derivatives in higher yields compared with those of other methods. The reaction, however, is not compatible with nitroalkanes. The proposed mechanism of the reaction is based on the collapse of the H‐bonded ion pair. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

Synthesis, structure and reactivity of 5-pyranosyl-1,3,4-oxathiazol-2-ones

5-(1,2,3,4-Tetra- O-acetyl-α- d-xylopyranos-5 S- C-yl)-1,3,4-oxathiazol-2-one ( 8) has been prepared from glucuronamide in two steps and 73% overall yield by conversion to the tetra- O-acetyl derivative 7 followed by reaction with chlorocarbonylsulfenyl chloride. 5-(2,3,4-Tri- O-acetyl-β- d-xylopyranosyl)-1,3,4-oxathiazol-2-one ( 12) was synthesised from d-xylose by a four-step sequence involving conversion to the xylopyranosylnitromethane derivative 9, reaction with PCl 3 to afford nitrile 10, hydrolysis to amide 11, and finally treatment with ClCOSCl. d-Glucose-derived analogue 13 was prepared similarly. The structure of oxathiazolone 8 was established by X-ray crystallography. Thermolysis of the oxathiazolones 8 and 12 at 130–160 °C resulted in decarboxylation and desulfuration to yield the corresponding nitriles. Attempts to trap the putative nitrile sulfide intermediates by repeating the thermolysis in the presence of dipolarophiles, such as ethyl cyanoformate, afforded only traces of the 1,3-dipolar cycloadducts; however, under microwave irradiation oxathiazolone 8 and ethyl cyanoformate afforded ethyl 3-(1,2,3,4-tetra- O-acetyl-α- d-xylopyranos-5 S- C-yl)-1,2,4-thiadiazole-5-carboxylate 22 in good yield.

Isoxazoline derivatives from activated primary nitrocompounds and tertiary diamines

Activated nitrocompounds, in the presence of dipolarophiles and a tertiary diamine (e.g., DABCO), undergo dehydration to afford directly isoxazoline derivatives, formal cycloadducts of nitrile oxides; this mild procedure is very efficient for the synthesis of the reported isoxazolines.

3+2]-CYCLOADDITION REACTIONS OF THIOISATIN WITH L-PROLINE AND (R)-(−)-THIAPROLINE

The [3+2]-cycloaddition reactions of cyclic secondary α-amino acids viz L-proline and (R)-(−)-thiaproline with 5-methylthioisatin via azomethine ylide in the presence of dipolarophiles afford azabicyclooctane derivatives in moderate-to-good yields. The cycloadducts have been characterized by elemental analysis and spectral techniques viz IR, 1H NMR, 13C NMR, MASS. In addition, stereochemical aspects of the cycloaddition have been ascertained by MOPAC-6 calculations using AM1 hamiltonians.

Straightforward Access to New Cage‐Functionalized Sulfur Heterocycles.

Reaction of pentacyclo[5.4.0.02,6.0 3 , 1 0 .0 5 . 8 ]undecane-8-thione (7) with diazomethane (9a) and 2-diazopropane (9b) afforded the 1,3,4-thiadiazolines 12a and 12c, which subsequently were used as precursors of reactive thiocarbonyl ylides 13a,b, respectively. Diphenyldiazomethane reacted rapidly with 7 to yield thiirane 14c as the final product. When decomposition of 12a or 12c was carried out in the presence of dipolarophiles, such as TCNE, DMAD or N-methylmaleinimide, new cage-functionalized heterocvcles were obtained.

1,3‐Dipolar Cycloaddition of Azomethine Ylides Generated from Ketimines and Difluorocarbene to Symmetrically Substituted Olefins.

AbstractFor Abstract see ChemInform Abstract in Full Text.

An Easy and Efficient Method for the Synthesis of Hydroximoyl Chloride from Nitro Olefin and Silyl Enol Ether.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Straightforward Access to New Cage-Functionalized Sulfur Heterocycles

Reaction of pentacyclo[5.4.0.02,6.0 3 , 1 0 .0 5 . 8 ]undecane-8-thione (7) with diazomethane (9a) and 2-diazopropane (9b) afforded the 1,3,4-thiadiazolines 12a and 12c, which subsequently were used as precursors of reactive thiocarbonyl ylides 13a,b, respectively. Diphenyldiazomethane reacted rapidly with 7 to yield thiirane 14c as the final product. When decomposition of 12a or 12c was carried out in the presence of dipolarophiles, such as TCNE, DMAD or N-methylmaleinimide, new cage-functionalized heterocvcles were obtained.

An easy and efficient method for the synthesis of hydroximoyl chloride from nitro olefin and silyl enol ether

Abstract Reactions of nitro olefin 1 with silyl enol ether 2 in the presence of TiCl 4 in CH 2 Cl 2 at 0°C gave high yields of hydroximoyl chloride 3 . When the hydroximoyl chloride 3 was treated with Et 3 N in the presence of dipolarophile, the corresponding 2-isoxazolines were obtained.

1,3-Dipolar Cycloaddition of Azomethine Ylides Generated from Ketimines and Difluorocarbene to Symmetrically Substituted Olefins

Iminiodifluoromethanides generated from difluorocarbene and benzophenone or fluorenone imines enter into reaction of 1,3-cycloaddition with electron-deficient alkenes to furnish pyrrolidone derivatives. The generation of iminiodifluoromethanides from alkyl N-benzhydrylidene glycinates in the presence of dipolarophiles is liable to complication by a concurrent proton shift in the initial imine giving NH-azomethine ylide also capable of 1,3-dipolar cycloaddition resulting in a side product of pyrrolidone series. The use of active lead instead of lead powder as reductant for dibromodifluoromethane in generation of difluorocarbene permits suppressing formation of the side products in these reactions.

Generation and cycloaddition reactions of pyranose-1-carbonitrile oxides

Stannate(II) reduction of the β- d-glucopyranosylnitromethane derivative 4 affords aldoxime 5 , which provides access to the nitrile oxide 7 , either on treatment with aq. hypochlorite, or via conversion to the hydroximoyl chloride 11 followed by base-mediated dehydrohalogenation. d-Galactose-, d-mannose- and d-xylose-derived nitrile oxides are generated similarly. The nitrile oxides either dimerise to 3,4-dipyranosyl-1,2,5-oxadiazole N-oxides or are trapped as cycloadducts in the presence of dipolarophiles.