Cycloadducts 4a Research Articles

Asymmetric Synthesis of Bicyclic Isoxazolines via Dearomative Cycloaddition of 4-Nitroisoxazoles with Zwitterionic π-Allyl Palladium Species.

Enantioselective dearomative cycloadditions of 4-nitroisoxazoles with vinylethylene carbonate (2) proceeded in the presence of Pd2(dba)3 and (S)-DTBM-SEGPHOS to give the corresponding bicyclic isoxazolines 3 and 4 in good to high yields with excellent enantioselectivities (≤99% ee). This synthetic approach could be applied to N-tosyl vinyl aziridine and 2-methylidenetrimethylene carbonate. Further transformations of the resulting cycloadducts 4a and 4i yielded not only its derivatives 10 and 11 but also the novel tetracyclic skeleton 12.

Isolation, characterization and semi-synthesis of natural products dimeric amide alkaloids

Isolation, characterization and semi-synthesis of natural products dimeric amide alkaloids

Functionalized polyhedral oligosilsesquioxane (POSS) based composites for bone tissue engineering: synthesis, computational and biological studies.

Functionalized polyhedral oligosilsesquioxanes (POSS) containing an isoxazolidine nucleus have been synthesized by microwave assisted 1,3-dipolar cycloaddition of N-methyl-C-alkoxycarbonyl nitrone 1 with POSS containing olefin moieties. The results of cycloaddition processes were rationalized by computational studies at the DFT level. The covalent conjugation of chitosan with the cycloadduct 3a leads to composite material CS-POSS 7 which was gelified using genipin as cross linking agent. The suitability of the system for bone tissue engineering purposes was evaluated by in vitro drug release studies using ketoprofen as a model drug and cytotoxicity assays performed on human fetal osteoblastic cells. The preliminary biological tests showed the lack of cytotoxicity of the hybrid material and suggest its potential role in bone tissue engineering applications.

Synthesis of New Spirooxindole‐Fused Isoxazoline/Triazole and Isoxazoline/Isoxazole Derivatives from Three‐Component 1,3‐Dipolar Cycloaddition

A series of diverse heterocycles containing spirooxindole, isoxazoline/triazole, and isoxazole rings has been synthesized via an efficient three‐component reaction of (E)‐2‐(1‐propargyl‐2‐oxoindoline‐3‐ylidene)acetophenones 1, arylnitrile oxides 2, and arylazides 3 using Cu(I) as catalyst. The regiochemistry and stereochemistry of cycloadducts 4a and 5a have been confirmed by X‐ray diffraction studies. The heterocycles were screened against Gram‐positive and Gram‐negative bacteria and fungi. Several compounds exhibit moderate to excellent activities comparable to those of established standard drugs.

ChemInform Abstract: Ruthenium‐Catalyzed Hydrohydroxyalkylation of Acrylates with Diols and α‐Hydroxycarbonyl Compounds to Form Spiro‐ and α‐Methylene‐γ‐butyrolactones.

Under the conditions of ruthenium(0)-catalyzed hydrohydroxyalkylation, vicinal diols 1a–1l and methyl acrylate 2a are converted to the corresponding lactones 3a–3l in good to excellent yield. The reactions of methyl acrylate 2a with hydrobenzoin 1f, benzoin didehydro-1f, and benzil tetradehydro-1f form the same lactone 3f product, demonstrating that this process may be deployed in a redox level-independent manner. A variety of substituted acrylic esters 2a–2h participate in spirolactone formation, as illustrated in the conversion of N-benzyl-3-hydroxyoxindole 1o to cycloadducts 4a–4h. Hydrohydroxyalkylation of hydroxyl-substituted methacrylate 2i with diols 1b, 1f, 1j, and 1l forms α-exo-methylene-γ-butyrolactones 5b, 5f, 5j, and 5l in moderate to good yield. A catalytic cycle involving 1,2-dicarbonyl–acrylate oxidative coupling to form oxaruthenacyclic intermediates is postulated. A catalytically competent mononuclear ruthenium(II) complex was characterized by single-crystal X-ray diffraction. The influe...

Titanium-Catalyzed Hydrohydrazination of Carbodiimides

Hydrazinediido complexes of the type [Cp*Ti(NxylN)(NNR2)(L)] (R = Ph, Me; Ar, fluorene, L = tBuNH2, Py; 3a–e) have been synthesized and used as catalysts for the hydrohydrazination of a series of carbodiimides, yielding aminoguanidines or fluoreneiminoguanidines. The highest yields were obtained for diarylhydrazines and fluorenone hydrazone at temperatures between 80 and 105 °C. Stoichiometric reactions of hydrazinediido complexes with iPrNCNiPr led to an equilibrium with the resulting [2 + 2] cycloadducts 4a–f, which were characterized by 1H, 13C, and 15N NMR spectroscopy as well as X-ray diffraction. The proposed mechanism, which is closely related to that previously established for the hydrohydrazination of alkynes and allenes, was found to be consistent with the results of a kinetic study. The dynamic structures of aminoguanidines and fluoreneiminoguanidines were characterized by NMR spectroscopy, and the minimum configurations were found to be stabilized by intramolecular hydrogen bonding.

Synthesis and characterization of 2-alkyl -5-{4-[(3-nitrophenyl-5-isoxazolyl)methoxy]phenyl}-2H-tetrazoles

Heteroaryl substituted analogs of antirhnoviral (A), was prepared by a convergent approach. 3-Nitrophenyl-5- bromooromethylisoxazoles 5a–b were synthesized by [3+2] cycloaddition of 3-(benzoyloxy)-propyne 2 to in situ generated arylnitrile oxides followed by deprotection of cycloadducts 3a–b and bromination of the resulting alcohols 4a–b. Coupling of 3- nitrophenyl-5-bromooromethylisoxazoles (5a–b) with 4-[5-(2-alkyl-2H-tetrazolyl)]phenols (6a–d) in N-methylpyrrolidinone under mild conditions afforded a new series of 2-alkyl-5-{4-[1-(3-nitrophenyl-5-isoxazolyl)methyloxy]phenylr}-2H-tetrazoles (7a–h) in high yields. The structures of the synthesized compounds were confirmed by their 1H NMR, Mass spectral, and Elemental Analysis data.

ChemInform Abstract: Utilization of Selenium-Directed (2 + 2) Cycloadditions: Concise Synthesis of (.+-.)-Fragranol.

The reaction of 2-(phenylseleno)prop-1ene 1 and methyl vinyl ketone 2 in the presence of EtAlCl2 gave the [2 + 2] cycloadducts 3a and 3b. A radical substitution of the adducts 3a and 3b with allytributyltin gave the allylated cyclobutane product, which was transformed into the cyclobutane natural product, (±)-fragranol. Stereoselective radical substitution using the ethylene glycol ketals of compounds 3a and 3b was also achieved.

ChemInform Abstract: Stereoselectivity of N-Benzyl-C-ethoxycarbonyl Nitrone Cycloaddition to (S)-5-Hydroxymethyl-2(5H)-furanone and Its Derivatives.

Abstract Stereoselectivity of the reaction of N-benzyl-C-ethoxycarbonyl nitrone (3) with (S)-5-hydroxymethyl-2(5H)-furanone (2a) and its 5-alkoxy substituted derivatives 2b-f was investigated. The reaction proceeds in a highly face-selective manner, the products 4–6 resulting from approach anti to the hydroxymethyl or alkoxymethyl group of the dipolarophile. The exo-stereoselectivity increases as the size of protective group attached to lactone (2b-f) increases. Endo-exo diastereoselectivity is affected significantly by the solvent. Microwave irradiation strongly accelerates the reaction with little effect on the diastereoselectivity to give the syn adduct 8a in addition to anti cycloadducts 4a–6a.

ChemInform Abstract: Chemistry of β-Functionalized α-Nitroso Ethylenes. Methyl β-Nitroso Acrylate as Heterodienophile in [4 + 2]-Cycloaddition to Cyclic Dienes.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

NMR and X-ray diffraction analysis of 3-thioamido-5-phosphono-1-cyclohexene derivatives: Conformational and stereochemical assignments

Reaction of N-(dienyl)-4-( R)-phenyloxazolidin-2-thione ( 1) with 1-diethoxyphosphoryl-1-buten-3-one ( 2a), methyl 3-(diethoxyphosphoryl)acrylate ( 2b) and 3-(diethoxyphosphoryl)acrylonitrile ( 2c) furnished the [4 + 2] cycloadducts 3a, 3b and 3c, respectively, as single stereoisomers, confirming the efficiency of the oxazolidin-2-thione chiral auxiliary in the facial discrimination of Diels–Alder reactions. The absolute configuration of the 3,4,5-trisubstituted cyclohexene derivatives ( 3a– c) was established by X-ray diffraction analysis. NMR studies confirmed the relative stereochemistries and showed two possible conformers in solution.

Rearrangements of the Diels−Alder Cycloadducts Obtained from Acetylenic Sulfones and 1,3-Diphenylisobenzofuran

1,3-Diphenylisobenzofuran afforded Diels-Alder cycloadducts 4a,b with n-butyl- and phenyl-substituted acetylenic sulfones 3a,b, respectively. The products underwent various types of rearrangements under pyrolytic, acid-catalyzed, and photochemical conditions. In the presence of acid, or upon heating in xylenes, they afforded the ketones 5a,b. In addition, the dehydration product 7a was produced from the pyrolysis of 4a, and the unexpected transposed ketone 6b was generated under acid-catalyzed or pyrolytic conditions from 4b via a postulated epoxide intermediate. The photolysis of 4a afforded ketone 5a as the sole isolated product, whereas 5b afforded oxepin 8b and indenyl phenyl ketone 9b. The formation of the latter two products can be rationalized by a series of pericyclic reactions. These include an intramolecular [2+2] cycloaddition, followed by a 1,3-dipolar cycloreversion, for the transformation of 4b to 8b and a series of electrocyclic and [1,3]sigmatropic reactions to convert 8b into 9b.

Diels–Alder Reactions of 2′‐Hydroxychalcones with ortho‐Benzoquino‐dimethane: A New Synthesis of 3‐Aryl‐2‐naphthyl 2‐Hydroxyphenyl Ketones

AbstractDiels–Alder reactions of the 2′‐hydroxychalcones 1a–e with ortho‐benzoquinodimethane (3) yielded the 3‐aryl‐1,2,3,4‐tetrahydro‐2‐naphthyl 2‐hydroxyphenyl ketones 4a–e in good yields. The dehydrogenation of the cycloadducts 4a–e to 3‐aryl‐2‐naphthyl 2‐hydroxyphenyl ketones 5a–e was studied. Good results were obtained when DDQ was used as oxidant and microwave irradiation as energy source. Several benzoxanthone derivatives were also obtained as minor products. Structures of all new compounds were established by extensive NMR studies. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

The high-pressure [4+2]cycloaddition of 1-methoxybuta-1,3-diene to the glycolaldehyde-derived heterodienophiles, catalyzed by chiral metallosalen complexes

A high-pressure (ca. 10 kbar) reaction of 1-methoxybuta-1,3-diene 1 with variously O-protected glycolaldehydes 2, catalyzed by the chiral (salen)Cr(III)Cl 4a– d and 5 or (salen)Co(II) 6a– f and 7 complexes, has been studied. The best results were obtained for tert-butyldimethylsilyloxyacetaldehyde 2a. The reaction afforded, in good yield (up to 90%) and with very good diastereoselectivity (up to 92%) and enantioselectivity (up to 93% ee), the [4+2]cycloadducts 3a, which are compounds of significant synthetic interest. The stereochemical model of the cycloaddition reaction is discussed.

Synthesis and Structural Elucidation of Novel Spiropyrazolines Precursors to Spiro-gem-dimethylcyclopropanes

1,3-dipolar cycloaddition reaction of 2-diazopropane (DAP) 1 with 2-arylidene-1-tetralone 2a–b led exclusively to spiro-Δ1-pyrazolines 3a–b. When 4-methyl-2-arylidene-1-tetralones 2c–d was used as starting dipolarophile a mixture of diastereiosomeric cycloadducts 4a–b and 5a–b was obtained. The photochemical nitrogen-extrusion studied for spiropyrazolines 3a–b and 4a–b led stereospecifically to spiro-gem-dimethylcyclopropanes. In all cases, the reaction regiochemistry and stereochemistry was discussed on the basis of 2D-NMR experiments.

First Cobalt(I)-Catalyzed [6 + 2] Cycloadditions of Cycloheptatriene with Alkynes

[reaction: see text] The CoI2(dppe)/Zn/ZnI2 system effectively catalyzes the [6 + 2] cycloaddition of cycloheptatriene with terminal alkynes to afford 7-alkyl-bicyclo[4.2.1]nona-2,4,7-trienes in fair to excellent yields. The catalyst proved to be tolerant toward functional groups such as ketone, sulfone, ester, ketal, ether, alcohol, imide, and nitrile. The enantioselective cycloaddition of CHT and phenylacetylene with BINOL phosphoramidite ligand 4 afforded the cycloadduct 3a (R = Ph) in 91% yield and 74% ee.

1,3‐Dipolar Cycloaddition of exo‐Methylenesugars with Nitrone: Approach to New Amino‐C‐ketosyl Disaccharides.

AbstractFor Abstract see ChemInform Abstract in Full Text.

1,3-Dipolar cycloaddition of exo-methylenesugars with nitrone: approach to new amino-C-ketosyl disaccharides

Stereoselective 1,3-dipolar cycloadditions of exo-methylenesugars 1a–c to a sugar nitrone 2 were carried out with refluxing a toluene solution and afforded the corresponding cycloadducts, ketosyl spiro-isoxazolidine disaccharides 3a and 4a–c. Followed by reductive cleavage of the N–O bond of the isoxazolidine ring with the treatment of Zn–AcOH–Ac2O or with catalytic hydrogenation (Pd(OH)2/C), the cycloadduct 3a could be readily converted into a novel amino-C-disaccharide possessing a ketose form, providing an access to a novel amino-C-ketosyl disaccharides.

Silicon−Carbon Unsaturated Compounds. 67. Photolysis of cis- and trans-1,2-Dimethyl-1,2-diphenyl-1,2-disilacyclopentane

The photolysis of cis- and trans-1,2-dimethyl-1,2-diphenyl-1,2-disilacyclopentane (la,b) was carried out in the presence of isobutene, acetone, and tert-butyl alcohol. Irradiation of la with a low-pressure mercury lamp inthe presence of isobutene in hexane proceeded stereospecifically to give a cis ene-type adduct (2a) and a cis [2 + 2] cycloadduct (3a) in 34% and 8% yields, respectively. Similar irradiation of la with acetone afforded a cis-ene-type adduct (4a) with high stereospecificity and 1-[hydroxymethylphenylsilyl]-3-(methylphenylsilyl)propane (5) in 28% and 15% yields. The photolysis of 1b with isobutene gave a trans [2 + 2] cycloadduct (3b) and the cis ene-type adduct 2a in 20% and 6% yields, respectively. With acetone, 1b afforded compound 5 as the major product. The photolysis of la in the presence of tert-butyl alcohol produced a mixture of cis- and trans-2,3-benzo-1-tert-butoxy-1,4-dimethyl-4-phenyl-1,4-disilacyclohept-2-ene (6a,b) in a 4:1 ratio in 30% combined yield, in addition to a 14% yield of 1-[tert-butoxymethylphenylsilyl]-3-(methylphenylsilyl)propane (7). Similar photolysis of 1b with tert-butyl alcohol gave again a mixture of 6a and 6b in 22% yield, in a 1:4 ratio, along with 7 in 15% yield. The thermolysis of 3a and 3b proceeded stereospecifically to give the respective ene-type products 2a and 2b in quantitative yields. Computational analyses for the formation of the rearranged silenes have also been reported.

Benzoannulation of Quinones by a Cycloaddition‐Fragmentation Approach. A Simple Synthesis of Methoxycarbonyl‐Substituted Polyacenoquinones

AbstractThe cycloadducts 2A‐5A obtained from the Diels‐Alder cycloadditions of 1,2,3,4‐tetrachloro‐4,5‐dimethoxycyclopentadiene (1) with p‐benzoquinone (2), 1,4‐naphthoquinone (3), 1,4‐anthraquinone (4), and 2,3‐dicyano‐1,4‐benzoquinone (5) were subjected to the reaction with triethylamine in dichloromethane at room temperature. Cycloadducts 2A and 5A enolized to give the corresponding hydroquinones 2B and 5B, which were oxidized with DDQ to afford naphthoquinone ester 2D and anthraquinone ester 5D, respectively. In the cases of cycloadducts 3A and 4A, the enolization occurred concurrently with oxidation and fragmentation to produce directly the polyacenoquinone esters 3D and 4D, respectively. Under the same reaction condition, the unsymmetrical cycloadduct 6A derived from naphthoquinone ester 2D and 1 yielded isomeric polyacenoquinone esters 6Da and 6Db in a ratio of about 8:1.