Synthesis of spiroannulated dihydroisobenzofuranylated monosaccharides

An efficient synthesis of spiroannulated dihydroisobenzofurans is achieved using easily accessible carbohydrate-derived furanyl propargyl ethers via an AuCl₃ promoted intramolecular Diels-Alder (IMDA) reaction. The scope of the spiroannulation protocol was demonstrated using a diverse range of pentofuranosyl, hexofuransoyl and hexopyranosyl derived substrates in order to synthesize spiroannulated dihydroisobenzofurans. The reaction is high yielding, moisture tolerant, fast and uses only a catalytic amount of AuCl₃.     

Formation of halogenated cyclopent-2-enone derivatives by interrupted Nazarov cyclizations

Allenyl vinyl ketones were exposed to titanium and indium halides in order to carry out Nazarov cyclizations. Whereas TiI₄ and InX₃ (X = Cl, Br, and I) led to cyclopentenones in which a halogen was trapped highly regioselectively, the reactions mediated by TiBr₄ gave mixtures of brominated isomers. When the allenyl vinyl ketones were treated first with Br₂ and then with TiBr₄, doubly brominated cyclopentenones resulted, and treatment with I₂ followed by TFA gave cyclopentenones bearing both hydroxyl and iodo groups.     

Synthesis and characterization of terbium doped TiO2 nanoparticles and their use as recyclable and reusable heterogeneous catalyst for efficient and environmentally sustainable synthesis of spiroannulated indolo[3,2-c]quinolines- mimetic scaffolds of isocryptolepine

An efficient and environmentally sustainable domino protocol has been presented for the synthesis of structurally diverse spiroannulated indolo[3,2-c]quinolines involving three component sequential reaction of phenylhydrazine, o-aminoacetophenone and cyclic ketones using nanostructured terbium doped TiO₂ as recyclable and reusable heterogeneous catalyst. The nanostructured catalyst was synthesized successfully and characterized by X-ray Diffraction (XRD), transmission electron microscopy (TEM), EDX and Fourier transform infra-red spectroscopy (FTIR). The substitution of Ti⁺⁴ with Tb⁺³ and the formation of Ti-O-Tb bonds as a result of doping of Terbium with TiO₂ NPs increases the catalytic efficiency and facilitates the reaction to provide the products in excellent yields. The present protocol with special features; operational simplicity, atom-economy, mild reaction conditions, environmental sustainability and high synthetic efficiency with recyclability and reusability of catalyst has been reported for the first time to synthesize spiroannulated indoloquinolines and expecting to provide the library of promising new leads in drug discovery research.     

Novel chemical modifications at the 4-position of chromones. Synthesis and reactivity of 4H-chromene-4-spiro-5′-isoxazolines and related compounds

Reactions of chromones with dilithiooximes proceed via nucleophilic 1,2-addition to give, on acidification, 4H-chromene-4-spiro-5′-isoxazoline derivatives in high yields. On treatment with concentrated H₂SO₄ the isoxazoline ring of this novel spiroannulated heterocyclic system opens to give α,β-unsaturated oximes, which undergo nitrosation, bromination, and the Beckmann rearrangement to the corresponding spiroisoxazolines and α,β-unsaturated amides, respectively. The latter can be obtained directly by the Beckmann rearrangement of 4H-chromene-4-spiro-5′-isoxazolines.     

Crystallographic report: Bis(3‐methyl‐2‐cyclopenten‐1‐one)dichloro‐oxovanadium(IV)

The crystal structure of the oxovanadium(IV) complex (CH₃C₅H₅O)₂VOCl₂ was determined. The molecule has trigonal bipyramidal geometry, with oxygen atoms of cyclopentenones in axial positions and oxygen and two chlorine atoms in equatorial positions. Copyright © 2005 John Wiley & Sons, Ltd.     

One‐Pot Transformation of Simple Furans into 4‐Hydroxy‐2‐cyclopentenones in Water

A highly efficient one‐pot transformation of readily accessible furans into 4‐hydroxy‐2‐cyclopentenones in H₂O, using singlet oxygen as oxidant, has been developed.     

Synthetic studies related to pentalenolactones; Part II: Cyclopentanation with 2-chloromethyl-allyl phenylsulfone.

The title sulfone was cyclocondensed with cyclopentenones under palladium catalysis in a biphasic system (1N KOH-TEBA/CH₂Cl₂) to give methylene-bicyclo [3,3,0]octanones in 39-43% yield.     

Intermolecular Pauson–Khand reactions of N-substituted maleimides

Co₂(CO)₈-mediated intermolecular Pauson–Khand reactions of N-substituted maleimides with terminal alkynes are described, producing maleimide-fused cyclopentenones. The transformation differs from other intermolecular Pauson–Khand-type reactions of electron-deficient olefins, which react with Co₂(CO)₈ and alkynes to produce conjugated dienes, or generally require terminal, monosubstituted olefins to generate cyclopentenones. The reaction works well for N-benzyl, N-aryl, and N-alkyl substituted maleimides, and tolerates branching at the 3-position of the terminal alkyne. N–H maleimide, N–CO₂Me maleimide, and maleic anhydride do not take part in the transformation.     

Acid-Catalysed Rearrangements of α-Vinylcyclobutanones

The BF₃ · Et₂O- and the CH₃SO₃H-catalysed rearrangements of 10 α-vinylcyclobutanones have been examined. With little acid, the β,β-dialkyl derivatives 1 were transformed into linear dienones 2 and 3 ; with more acid, they were converted into cyclopentenones 4 by Nazarov cyclisation of initially formed 2/3 . The β-monoalkyl (including the β,γ-dialkyl) derivatives 7 rearranged only with a high acid concentration to afford the cyclopentenones 8 by 1,2-acyl migration. In the case of 7a , the cyclopentenone 8a was accompanied by the unexpected constitutional isomer 9a , which is explained by a reversible interconversion of the cyclobutanone 7a with its isomer 19 via a cyclopropane intermediate like 18 . In the case of the β,β-dialkyl derivative 5 , which contains an α-isobutenyl (instead of an α-vinyl) group, the acid-catalysed rearrangement product was the bicyclo[3. 1. 0]hexanone derivative 6 .     

CuCl-catalyzed reaction of zirconacyclopentenes with oxalyl chloride: a new pathway for the preparation of cyclopentenones

Zirconacyclopentenes, which are easily prepared from alkynes and EtMgBr (or ethylene) and Cp₂ZrCl₂, reacted with oxalyl chloride in the presence of catalytic amount of CuCl to give cyclopentenones in high yields. The reaction was performed conveniently in one pot from alkynes, EtMgBr, oxalyl chloride, and Cp₂ZrCl₂.     

Cationic bromonium complex: NBS/P(OPh)3 as an efficient catalyst for Nazarov cyclization

A general, catalytic method for Nazarov cyclization of dihydropyran derivatives has been developed. Cationic bromonium complex: NBS/P(OPh)₃ was identified as an efficient catalyst for the synthesis of a number of different cyclopentenones in high yields with an excellent level of diastereocontrol.     

Iridium-catalyzed cascade decarbonylation/highly enantioselective Pauson–Khand-type cyclization reactions

An easily accessible chiral iridium-BINAP complex can effect the cooperative processes of decarbonylation of an aldehyde and cascaded enantioselective Pauson–Khand-type reaction. A survey of ligands revealed that atropisomeric aryl-diphosphine ligands were superior to chiral alkyl-diphosphines in this dual catalysis. Applying the reaction conditions of [IrCl(COD)]₂/(S)-BINAP complex with nonylaldehyde as a CO surrogate at 100 °C in anhydrous dioxane solvent, various 1,6-enynes were transformed to the corresponding optically active bicyclic cyclopentenones with excellent enantioselectivities (up to 98% ee).     

Aqueous-phase, thermal Pauson-Khand reactions in the presence of surfactants

Efficient stoichiometric Pauson-Khand reactions were realized in water as the only solvent, and in the presence of surfactants as additives. Use of the cationic surfactant CTAB provided good yields of cyclopentenones from the thermal reactions of pre-formed dicobalthexacarbonyl complexes of enynes and alkynes. The water-CTAB medium was found to be less effective with Co₄(CO)₁₂ as the promoter of the reaction. Incidentally, these results have provided a strictly water-based PKR protocol under very mild and convenient conditions.     

One‐Pot Cascade Transformation of Glucal into Structurally Diverse Drug‐Like Scaffolds

A diversity‐oriented synthesis strategy to produce three types of structurally drug‐like N‐heterocyclic‐fused rings has been developed from abundant biomass‐derived d ‐glucal, aniline and water in a stereoselective manner. The overall transformation which entails a cascade of Ferrier reaction and 4π conrotatory imino‐Nazarov cyclization was performed in one‐pot allowing convenient preparation of scaffolds of high molecular complexity from relatively simple starting materials. While indoline‐fused products were readily accessible using ortho‐unsubstituted secondary anilines as substrates, reactions with ortho‐hydroxyl‐anilines furnished fused 1,4‐benzoxazines instead. In both cases, InBr₃ acted as the Lewis acid catalyst. By altering InBr₃ to Ln(OTf)₃, the indoline‐fused products could be further converted into tetrahydroquinoline‐fused cyclopentenones via ensuing retro‐ene rearrangement.     

The Pauson-Khand reaction as a new entry to the synthesis of bridged bicyclic heterocycles: application to the enantioselective total synthesis of (−)-alstonerine

The first application of the Pauson-Khand reaction (PKR) to the synthesis of azabridged bicyclic structures is described. Compounds containing azabicyclo[3.3.1]nonane and azabicyclo[3.2.1]octane rings fused to cyclopentenones were efficiently constructed via the PKR of cis-2,6-disubstituted N-acyl piperidine enyne substrates, many of which can be readily prepared from 4-methoxypyridine in a few steps. Moreover, the PKR of cis-2,6-disubstituted piperazine enynes allowed the preparation of diazabicyclo[3.3.1]nonanes fused to cyclopentenones. This new strategy for the synthesis of azabridged bicyclic frameworks was exploited as a key step in a concise, enantioselective total synthesis of the macroline alkaloid (−)-alstonerine.     

Prostanoids: LXXVI. Synthesis and Specific Features of Reductive Dechlorination with the System Zn-NH4Cl-MeOH of Some 3-N-, O-, S-, Cl-, and Alkyl-substituted 2-Chloro-4,4-ethylenedioxycyclopent-2-en-1-ones Ozonolysis of 3-Caren-5-one

Reaction of a number of 3-N-, O-, S-, Cl-, and alkyl-substituted 2-chloro-4,4-ethylenedioxycyclopent-2-en-1-ones with Zn in NH₄Cl-MeOH medium were investigated.The expected or partially transformed dehydrochlorination products were isolated. An exclusive chemical stability of 3N-containing cyclopentenones was disclosed. This phenomenon was understood as originating from stabilizing n-d-p-interaction of electrons belonging to heteroatoms in the planar C¹(O)-C²(Cl)-C³ 3(N) fragment contained in the molecules of the compounds.     

Facile Synthesis of 4‐Functionalized Cyclopentenones

1-8-Diazabicyclo[5.4.0]undec-7-ene(DBU)‐catalyzed Michael addition of nitroalkanes to dicyclopentadienone (1) followed by flash vacuum pyrolysis (FVP) provided a high‐yielding synthesis of extremely pure 4‐nitroalkyl cyclopentenones (3). The optimized Nef reaction of the nitro adducts (2) provided 4‐ketoalkyl cyclopentenones (5) in the similar way.     

The Morita?Baylis?Hillman Reaction of Chiral Highly Oxygenated Cyclopent‐2‐enones

The Morita? Baylis? Hillman (MBH) reactions of (4S,5R,7R,8R)‐ and (4R,5R,7R,8R)‐4‐hydroxy‐7,8‐dimethoxy‐7,8‐dimethyl‐6,9‐dioxaspiro[4.5]dec‐2‐en‐1‐ones ( 2 and 3 , resp.) with aldehydes using various catalysts were studied. A combination of Bu₃P/phenol in THF was found being optimum conditions giving the corresponding MBH adducts with high diastereoisomeric ratios. After separation, each stereomerically pure isomer of the MBH adducts was subjected to hydrolysis employing 1% aq. CF₃COOH (TFA) in a water bath of an ultrasonic cleaner to afford the corresponding polyhydroxylated cyclopentenones in good yields.     

Unusual Formal [1+4] Annulation through Tandem P(NMe2)3‐Mediated Cyclopropanation/Base‐Catalyzed Cyclopropane Rearrangement: Facile Syntheses of Cyclopentenimines and Cyclopentenones

An unusual formal [1+4] annulation of α‐dicarbonyl compounds with 1,1‐dicyano‐1,3‐dienes has been realized, leading to facile syntheses of cyclopentenimines and cyclopentenones in a unique manner. Mechanistic investigation implies that this reaction takes place through a P(NMe₂)₃‐mediated cyclopropanation followed by a base‐catalyzed cyclopropane rearrangement. It therefore represents an unprecedented [1+4] annulation mode involving Kukhtin–Ramirez adducts.     

Sur le role fondamental du cation alcalin dans les reductions par les hydrures metalliques—utilisation de coordinats macrocycliques—IV : Regioselectivite et reduction des enones conjuguees

The competition between 1,2 and 1,4-addition in the metal hydride reduction of conjugated cyclohexenones and cyclopentenones in aprotic media is affected by solvent, nature of cation (Li⁺ or Na⁺), and of anion (AlH₄^? or BH₄^?). In protic media, effects of salt concentration, and the nature of the salt are observed. Three competitive reaction pathways are proposed to account for the results and methods for the selective reduction of conjugated enones are proposed. Some reactions were run free of alkaline cation by use of macrocyclic ligands.