Intramolecular Cascade Research Articles

Epoxides to α-Mercapto-γ-lactones via Ionic Liquid Promoted Mercaptoacetylative Ring-Opening-Ring-Closing Cascade

Task-specific ionic liquid promoted {[Bmim]OH} one-pot synthesis of α-mercapto-γ-lactones is reported. The present protocol involves regioselective epoxide ring opening and intramolecular translactonisation cascade. A variety of epoxides undergo this ring-opening-ring-closing cascade with 2-methyl-2-phenyl-1,3-oxathiolan-5-one to afford α-mercapto-γ-lactones diastereoselectively in good to excellent yields. After isolation of the product, the ionic liquid [Bmim]OH could be easily recovered and reused without any loss of efficiency.

Thiophene-fused phospholo[3,2-b]phospholes and their dichalcogenides: Synthesis and structure–photophysical properties relationships

The PCl3-promoted intramolecular cascade cyclization produced a series of thiophene-fused phospholo[3,2-b]phosphole derivatives, including non-oxidized 2, dioxides 3, and disulfides 4. These derivatives exhibit significantly red-shifted absorptions and fluorescences compared with their benzene-fused analogues. Among the thiophene-fused series, the non-oxidized 2 has the highest fluorescence quantum yield of 0.95. This trend is in contrast to that observed for the benzene analogues, in which a dioxide derivative shows the most intense fluorescence.

ChemInform Abstract: Total Synthesis of (.+-.)-Aspidospermidine.

(±)-Aspidospermidine (1) has been synthesized from readily available methyl 3-ethyl-2-oxocylopentanecarboxylate (17) in 5.9% yield over 13 steps. The key step of the synthesis is an intramolecular cascade reaction that simultaneously forms the B, C, and D rings of 1. A high-yielding method of closing the remaining E ring is also described.

Efficient Total Synthesis of (S)‐14‐Azacamptothecin

An efficient total synthesis of (S)-14-azacamptothecin has been accomplished in 10 steps and 56% overall yield from 5H-pyrano[4,3-d]pyrimidine 8. A mild Hendrickson reagent-triggered intramolecular cascade cyclization, a highly enantioselective dihydroxylation, and an efficient palladium-catalyzed transformation of an O-allyl into N-allyl group are the key steps in the synthesis. This work provides a much higher overall yield than the previous achievement and shows sound flexibility for the further applications that will lead to new bioactive analogues.

Intramolecular Cascade C-S Bond Formation: Regioselective Synthesis of Substituted Benzothiazoles

Carbon-fluorine bond fission has been coupled with C-S bond formation under metal-free conditions, which is seldom reported in the literature. The intramolecular C-S bond formation reaction takes place by fission of the carbon-fluorine bond in situ, and is believed to proceed through an SNAr mechanism. The approach represents a practical and atom-economical approach for regio­selective and metal-free cascade synthesis of substituted benzothiazoles. This one-pot, environmentally benign protocol involves 2-fluoroanilines, benzoyl chlorides and Lawesson’s reagent under microwave irradiation (5 min) or conventional thermal conditions (3 h).

Gold‐Catalyzed Intramolecular Alkyne Cycloisomerization Cascade: Direct Synthesis of Aryl‐Annulated[a]carbazoles from Aniline‐Substituted Diethynylarenes

AbstractAniline‐substituted diethynylarenes, which are readily synthesized through Sonogashira coupling reactions from commercially available 1,2‐dihaloarenes, directly produce aryl‐ and heteroaryl‐annulated[a]carbazoles by the gold‐catalyzed intramolecular cascade hydroamination/cycloisomerization without producing theoretical by‐products. This new atom‐economical route is easily applicable to various aryl‐annulated[a]carbazoles containing an alkyl, aryl or ester substituent.

Formal Synthesis of Haouamine A

Haoumine A is isolated from the marine ascidian Aplidium haouarianum and shows strong anticancer activity in human colon carci­noma cell lines HT-29. This formal synthesis of ­haouamine A presents a concise route to Baran’s intermediate, the indenotetrahydropyridine K, ­using an intramolecular cascade Mizoroki-Heck reaction as a key step. For a total synthesis, see: J. Am. Chem. Soc. 2006, 128, 3908.

Transformation of Reactive Isochromenylium Intermediates to Stable Salts and Their Cascade Reactions with Olefins

Transformation of reactive isochromenylium intermediates to the corresponding storable and stable reagents has been achieved, and a number of isochromenylium tetrafluoroborates (ICTBs, 1) have been conveniently prepared and characterized. Direct metal-free treatment of isochromenylium tetrafluoroborate 1a with olefins afforded a variety of polycyclic frameworks 4 via mild cascade reactions. Starting from the prefunctionalized o-alkynylbenzaldehydes, a one-pot metal-free procedure of intramolecular cascade annulation to 2,3-dihydrophenanthren-4(1H)-one derivatives was also developed.

Formal Total Synthesis of Haouamine A

A synthesis of the indenotetrahydropyridine unit of haouamine A is described. The construction of a diaryl quaternary center and tricyclic framework of this compound was achieved by an intramolecular cascade Mizoroki-Heck reaction.

Total synthesis of (5R,6R,8R,9S)-(−)-5,9Z-indolizidine 221T using sulfinimine-derived N-sulfinyl β-amino ketones

The first total asymmetric synthesis of the poison frog alkaloid (-)-221T, a 5,6,8-trisubstituted indolizidine is described. The key core piperidine ring was constructed via an acid catalyzed intramolecular cascade Mannich cyclization reaction of a N-sulfinyl syn-alpha-methyl beta-amino ketone and crotonaldehyde. The beta-amino ketone was prepared via the reaction of prochiral lithium Weinreb amide enolate with an enantiopure N-2,4,6-triisopropylphenylsulfinyl imine.

Coordination-Induced Intramolecular Double Cyclization: Synthesis of Boron-Bridged Dipyridylvinylenes and Dithiazolylvinylenes

Di(heteroaryl)acetylenes having a pyridyl or thiazolyl as theheteroaryl group underwent a reaction with bromodibenzoborole toproduce coordination complexes, which were further treated withwater to promote the intramolecular cascade double cyclization toproduce the dibenzoborolyl-bridged ladder di(heteroaryl)vinylenes.For the thiazolyl derivative, further derivatization at the terminalpositions produced a bis(dimesitylboryl)-substituted derivative.The ladder molecules prepared showed an intense emission in thefluorescence spectra as well as reversible reduction waves at lowreduction potentials in the cyclic voltammetry.

Bis-Phosphoryl-Bridged Stilbenes Synthesized by an Intramolecular Cascade Cyclization

Bis-phosphoryl-bridged stilbenes have been synthesized using an intramolecular cascade cyclization. They show intense blue fluorescences at longer wavelengths with higher quantum yields compared to those of the known element-bridged stilbenes. In addition, they have much lower reduction potentials due to the inductive effect of phosphoryl groups. The incorporation of the phosphoryl moiety is an effective way for the construction of highly electron-accepting pi-conjugated systems.

Precursorchemistry with Metalalkoxides and their Use for Nano-Scaled Materials

The synthesis of nano-scaled materials using several variations of the single source precursor concept in sol–gel and chemical vapour deposition techniques is demonstrated. Mono- and biphasic ceramics and cermets (metallic phases incorporated in a metal oxide phase) are addressed. The materials prepared are all nanocrystalline in a range from 5 to 50nm. The ceramics belong inter alia to the spinel and perowskite-type. In the biphasic ceramic systems, especially NdAlO3 in Al2O3 is highlighted. In the cermet family Ge, Sn and Pb in either their oxide matrices or in perowskite matrices (M´MO3, M´ = Ca, Sr, Ba; M = Ge, Sn, Pb) and Al and Ga in Al2O3 or Ga2O3 matrices are discussed. Two general concepts are presented in more detail: 1) the arrangement of mutually dependent ligands in the precursor molecule, to facilitate intra-molecular cascade or domino reactions, and 2) the role of metastable phases for physical patterning. The temperature and pressure dependent formation of aluminum/aluminum oxide composites and their structural consequences leading to zero-dimensional ball-shape spheres or to one-dimensional nano-wires is shown as well as the core shell structures of such composites.

Scaffold Diversity through Intramolecular Cascade Reactions of Solid-Supported Cyclic N-Acyliminium Intermediates

The solid-phase synthesis of pharmacologically interesting heterocycles is presented. The formation of a series of (5,5)-, (5,6)-, (6,5)-, and (6,6)-fused bicyclic ring systems was systematically studied by implementation of a common strategy involving N-acyliminium intermediates. These are highly reactive and transformed further in intramolecular cascade reactions with strong as well as weak C, N, S, and O-nucleophiles. The methodology was successfully applied to the conversion of peptidomimetics into constrained small molecule core structures, such as the hexahydropyrrolo[2,1- b][1,3]oxazines, generally with full control of diastereoselectivity (>20:1) and in purities above 90%.

A Strategy for the Synthesis of 2,3‐Disubstituted Indoles Starting from N‐(o‐Halophenyl)allenamides.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

The rhodium(II) carbenoid cyclization–cycloaddition cascade of α-diazo dihydroindolinones for the synthesis of novel azapolycyclic ring systems

Tandem carbonyl ylide formation–1,3-dipolar cycloaddition of α-diazo N-acetyl-tetrahydro-β-carbolin-1-one derivatives occur efficiently in the presence of a dirhodium catalyst to afford bimolecular cycloadducts in high yield. The Rh(II)-catalyzed reaction also takes place intramolecularly to give products derived from trapping of the carbonyl ylide dipole with a tethered alkene. The power of the intramolecular cascade sequence is that it rapidly assembles a pentacyclic ring system containing three new stereocenters and two adjacent quaternary centers stereospecifically in a single step and in high yield.

Utilization of Some Novel Cascade Reactions for the Synthesis of Various Hydroxylated Phenanthridones

A highly efficient synthesis of the hydroxylated phenanthridone system is described. The synthesis features the ready preparation of the Amaryllidaceae alkaloid skeleton by a Stille intramolecular Diels-Alder furan cycloaddition cascade. A lithium hydroxide induced fragmentation reaction was used to introduce the required it-bond in ring C.

Development of Novel Type of Transition Metal‐Catalyzed Cascade Reactions Utilizing Small Ring Systems and the Applications

AbstractFor Abstract see ChemInform Abstract in Full Text.

Development of novel type of transition metal-catalyzed cascade reactions utilizing small ring systems and the applications

This review summarizes the novel type of palladium-catalyzed cascade ring expansion reactions of cyclobutanols with various unsaturated bonds. The intramolecular cascade ring expansion-cyclizations of isopropenylcyclobutanol proceeds smoothly in the presence of the palladium (II) complex. The diastereoselectivity of the obtained naphthohydrindans can be controlled by the choice of the reaction solvents. As an application utilizing this reaction, total synthesis of (+)-equilenin has been achieved. The reaction of allenylcyclobutanols with a iodoalkenyl side chain with a palladium (0) catalyst produces the cyclized products that have seven- and eight-membered rings. The reaction can be successfully applied to the stereospecific synthesis of alpha-substituted cyclopentanones with a quaternary carbon stereocenter. The cyclobutanols containing a propargylic component react with phenols in the presence of the palladium (0) catalyst to afford the phenoxy-substituted cyclopentanones via a nucleophilic addition-ring expansion process. The reaction also proceeds stereospecifically to afford the corresponding products with high efficiency.

Diastereoselective Pd/In Bimetallic Inter—Intramolecular (Class 2) Cascade Reactions of Allenyl‐Imines and Aryl Iodides.

AbstractFor Abstract see ChemInform Abstract in Full Text.