SEARCH · PubMed Health

Results for “Cyclization”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,081 records · Page 60Linked to original sources

PubMed2006

Au(I)-catalyzed cyclization of enynes bearing an olefinic cycle.

Gold(I)-catalyzed cyclization of enynes containing an olefinic cycle has been studied. The introduction of an olefinic ring instead of a terminal alkene in enynes dramatically increased the yield of the reaction. Enynes having an olefinic cycle were prepared by a rhodium-catalyzed intermolecular [4 + 2] cycloaddition of diynes with butadiene. Consecutive rhodium-catalyzed Diels-Alder/gold(I)-catalyzed cycloisomerization reactions were integrated in a one-pot reaction.

Journal Article↗

PubMed2006

Diastereoselective synthesis of enantiopure morpholines by electrophilic selenium-induced 6-exo cyclizations on chiral 3-allyl-2-hydroxymethylperhydro-1,3-benzoxazine derivatives.

Enantiopure morpholine derivatives have been prepared by selenocyclofunctionalization of chiral 3-allyl-2-hydroxymethyl-substituted perhydro-1,3-benzoxazine derivatives. The cyclization occurs in high yields and diastereoselection, although the temperature of the reaction and the structure of the substituent at C-2 and the substitution pattern of the double bond can modify the regio- and stereochemistry of the final products.

Journal Article↗

PubMed2007

Stereoselective formation of alpha-alkylidene cyclic carbonates via carboxylative cyclization of propargyl alcohols in supercritical carbon dioxide.

Carboxylative cyclization of propargyl alcohols in supercritical carbon dioxide (scCO2) containing P(n-C4H9)3 as a catalyst proceeded smoothly to give alpha-alkylidene-1,3-dioxolan-2-ones. Internal propargyl alcohols afforded Z-alkyl-idene cyclic carbonates exclusively. CO2 incorporation was markedly promoted under supercritical conditions, possibly due to the facile formation of a putative P(n-C4H9)3-CO2 adduct as a key intermediate.

Journal Article↗

PubMed1996

New Cobalt-Catalyzed Cycloisomerization of epsilon-Acetylenic beta-Keto Esters. Application to a Powerful Cyclization Reactions Cascade.

The full details of investigations into the cobalt(I)-catalyzed ene type reaction of epsilon-acetylenic beta-keto esters to form highly functionalized methylenecyclopentanes are described. The observed regio-, chemo-, and stereoselectivities support a process of cycloisomerization which controls the relative stereochemistry of two contiguous stereogenic centers. An efficient route to the basic skeleton of the phyllocladane family has been achieved via a one-pot sequence of cyclizations: ene type, [2 + 2 + 2], [4 + 2]. This new cascade created six carbon-carbon bonds and four rings in a totally stereoselective manner from an easily accessible acyclic polyunsaturated precursor.

Journal Article↗

PubMed1996

Oxidative Cyclization of Iodo Ketones. Synthesis of 6-Oxa-5alpha-pregnane-3,20-dione.

The steroidal delta- and gamma-iodo ketones 1 and 9 were converted to the cyclic hemiketals 3 and 10, by oxidation to the iodoso derivatives with m-CPBA. Spontaneous cyclization of the latter intermediates to the corresponding oxocarbenium ions, followed by stereoselective addition of water, rendered the hemiketals. Depending on the reaction conditions, the five-membered oxocarbenium ion derived from the gamma-iodo ketone 9 may add H(2)O or m-CPBA to give either the hemiketal or a Baeyer-Villiger type product 12, while the oxocarbenium derived from 1 gives exclusively the hemiketal. When the reaction was carried out in dry methanol, methyl ketals were formed. Use of this methodology allowed us to synthesize 6-oxa-5alpha-pregnanes with and without functionalization at C-19.

Journal Article↗

PubMed1996

Synthesis of an Azasteroid Using an Acyl Iminium Ion-Initiated Tandem Cyclization.

An acyl iminium ion-initiated tandem cyclization gave an unexpected dienone product, a seco-azasteroid (2). The factors governing the formation of 2 were investigated in an attempt to optimize its formation. The reaction was applied to a more elaborate system, resulting in the synthesis of the full steroid skeleton of 13-azaandrosta-1,4-diene-3,17-dione (3), which contains the unusual substitution of a chlorine atom for the axial 19-methyl.

Journal Article↗

PubMed1996

A Facile and Efficient Synthesis of Thieno[2,3-c]furans and Furo[3,4-b]indoles via a Pummerer-Induced Cyclization Reaction.

The alpha-thiocarbocation generated from the Pummerer reaction of an o-heteroaroyl-substituted sulfoxide is intercepted by the adjacent keto group to produce an alpha-thio-substituted heteroaromatic isobenzofuran. In the presence of a suitable dienophile, the reactive o-xylylene undergoes a Diels-Alder cycloaddition followed by an acid-catalyzed ring-opening and aromatization to give heteroaromatic naphthalene derivatives. This one-pot procedure occurs smoothly with electron-deficient dienophiles. The tandem Pummerer cyclization-cycloaddition sequence also occurs intramolecularly using unactivated alkenyl tethers of variable length. With acetylenic dienophiles, the primary cycloadducts undergo in situ ring-opening to produce hydroxynaphthalene derivatives. In the absence of a dienophile, it was possible to prepare 4-(ethylthio)-6-phenylthieno[2,3-c]furan and 1-ethyl-4-(phenylsulfonyl)-4H-furo[3,4-b]indole. Various synthetic approaches were used for the preparation of the requisite thiophene- and indole-derived sulfoxide precursors. The facility of the tandem Pummerer-Diels-Alder reaction was very dependent on the experimental conditions used to promote the reaction. The best results were achieved by employing a mixture of acetic anhydride and toluene which contained a catalytic quantity of p-toluenesulfonic acid. The presence of the acid effectively drives the reaction in the desired direction by preventing formation of the acetoxy sulfide, which corresponds to the normal Pummerer product.

Journal Article↗

PubMed1996

Total Synthesis of (+/-)-Deethylibophyllidine: Studies of a Fischer Indolization Route and a Successful Approach via a Pummerer Rearrangement/Thionium Ion-Mediated Indole Cyclization.

The total synthesis of (+/-)-deethylibophyllidine is described, proceeding in eight steps from 4-(methoxyphenyl)ethylamine in 5% overall yield (Scheme 6). In terms of sequential annulation, the strategy involves the following operations: E --> DE --> ABDE --> ABCDE (Scheme 1). The key steps in the synthesis are the stereoselective formation of octahydroindol-6-ones by acid treatment of dihydroanisole derivatives, the regioselective Fischer indolization to obtain octahydropyrrolo[3,2-c]carbazoles, and the tandem process consisting of Pummerer rearrangement upon a beta-amino sulfoxide and thionium ion cyclization upon a beta-indole position of a 2,3-disubstituted indole to generate the quaternary spiro center. Attempts to effect the construction of the pentacyclic framework by means of Fischer indolization of the octahydropyrrolo[3,2,1-hi]indol-6-one resulted in failure (Scheme 2).

Journal Article↗

PubMed1996

Photoinduced Electron Transfer Reactions of alpha-Cyclopropyl- and alpha-Epoxy Ketones. Tandem Fragmentation-Cyclization to Bi-, Tri-, and Spirocyclic Ketones.

Reductive photoinduced electron transfer (PET) reactions have been performed with various bicyclic alpha-cyclopropyl-substituted ketones and tertiary amines. The reaction resulted in a regioselective cleavage of one cyclopropyl bond under formation of an exocyclic radical with an endocyclic enolate unit. In the case of bicyclic ketones with an unsaturated side chain, various bicyclic, spirocyclic, and tricyclic products are accessible via radical cyclization, depending on the position of the alkenyl substituent. In addition to triethylamine, N-silylated amines have also been used as electron donors, leading to a variety of compounds, among them are silylated fragmentation products, indicating that a proton is transferred from not only the amine radical cation but also the cationic silyl group. The intramolecular Paternó-Büchi reaction has also been studied for cyclopropane derivatives of the jasmone type leading to tetracyclic oxetanes. Finally, alpha-epoxy-substituted ketones have been investigated under PET conditions, yielding ring-opened products.

Journal Article↗

PubMed1996

Syntheses of Strychnos and Aspidospermatan-Type Alkaloids. 8. Selective Total Syntheses of Mossambine and 14-epi-Mossambine by a Radical Cyclization Reaction(1).

Mossambine (6) was obtained by a six-step reaction sequence from the indoloazepine ester 7. Radical cyclization of the tetracyclic vinyl iodide 12a provided a racemic pentacyclic ketone 16E, which could be converted to either enantiomer by condensation with (S or R)-N,S-dimethyl-S-phenylsulfoximine and selective pyrolysis of the resulting diastereomeric alcohols 18 and 19 or 20 and 21. Selective reductions of the resolved (or racemic) ketone 16E provided mossambine (6) and its hydroxy epimer 17.

Journal Article↗

PubMed1996

Generation of 6-(Trifluoromethyl)-4,5-dihydro-2(3H)-pyridone and the Application to Synthesis of Some Fused Nitrogen Heterocycles Carrying a Trifluoromethyl Group on the Bridgehead Position via Radical Cyclization of Dihydropyridones.

Staudinger/aza-Wittig reaction of 6,6,6-trifluoro-5-oxohexanoyl azide with PPh(3) or PBu(3) was examined. A reactive intermediate acyl imine 1 was trapped by methanol. Without nucleophile, isomerized enamide form 3 was obtained. N-Iodobenzoylation and N-haloalkylation of 3 and following radical cyclization via the 5-exo or 6-exo mode gave benzoindolizidinone, indolizidinone, and quinolizidinone derivatives 10-14, which have a trifluoromethyl group at the bridgehead position adjacent to nitrogen. Although LiAlH(4) reduction of 10 and 11 gave a mixture of saturated benzoindolizidine 15 and amino alcohol 16, reduction with BH(3)/THF selectively gave the desired 15 and indolizidine 17 from 13.

Journal Article↗

PubMed1996

Mn(III)-Based Oxidative Free-Radical Cyclizations of Unsaturated Ketones.

Mn(III)-based oxidative free-radical cyclization of unsaturated ketones is a versatile synthetic procedure with broad applicability. For example, oxidation of cyclopentanone 1a with 2 equiv of Mn(OAc)(3).2H(2)O and 1 equiv of Cu(OAc)(2).H(2)O in AcOH at 80 degrees C for 1.5 h affords 75% of bicyclo[3.2.1]oct-3-en-8-one 8a and 15% of bicyclo[3.2.1]oct-2-en-8-one 9a. Bridged bicyclic ketones that cannot enolize further are isolated in good yield. Monocyclic beta,gamma-unsaturated ketones that can enolize are oxidized further to give gamma-acetoxy enones. The formation of bicyclo[3.3.1]non-2-en-9-one (57a) in 52% yield from 2-allylcyclohexanone (56a) suggests that kinetically controlled enolization is the rate-determining step in alpha-keto radical formation. A wide variety of examples delineating the scope, limitations, and stereoselectivity of this reaction are presented.

Journal Article↗

PubMed1997

Synthesis of Linear and Angular Triquinane Skeletons by O-Stannyl Ketyl-Promoted Fragmentation-Cyclization Reactions of alpha-Keto Cyclopropanes.

Several investigations of rigid alpha-keto cyclopropane cleavage by O-stannyl ketyls are summarized herein. Tricyclo[3.3.0.0(2,8)]octan-3-one ring systems were treated with nBu(3)SnH, which produced different ring-cleavage products depending on the location and type of substituent present. An examination of both radical-stabilizing substituents and stereoelectronic factors was initiated to understand what factors bias bond cleavage in a configurationally restricted alpha-ketocyclopropane via O-stannyl ketyls. A preference for cleavage of the cyclopropane bond with the best orbital overlap with the ketyl radical sp(2)-orbital even in the presence of radical stabilizing groups is indicated by these results. An O-stannyl ketyl ring scission-cyclization resulted in the novel synthesis of either a linear or an angular triquinane skeleton depending on the length and location an alkene tether on the tricyclo[3.3.0.0(2,8)]octan-3-one precursor.

Journal Article↗

PubMed1997

Asymmetric Oxidative Cyclization of o-Phenolic Oxime-Esters: First Synthesis of Enantiomerically Enriched Spiroisoxazoline Methyl Esters.

A new method for the synthesis of enantiomerically enriched cyclohexadienone spiroisoxazoline (-)-2a has been described. Asymmetric intramolecular oxidative cyclization of the o-phenolic oxime-ester 1c using a novel optically active tertiary alcohol (-)-3 as a chiral auxiliary proceeded smoothly to afford cyclohexadienone spiroisoxazoline 2c in 83% yield. Opitcally active tertiary alcohol (-)-3 was synthesizied from racemic (1S,8R,9R,10R)-8-phenyl-1-decalol (4) by optical resolution. Removal of the chiral auxiliary in 2c with CF(3)COOH followed by methylation gave methyl ester (-)-2a in 74% ee (71% chemical yield) having S-configuration. The absolute configuration of 2awas determined by the synthesis of the marine natural product (+)-aerothionin.

Journal Article↗

PubMed1997

Total Syntheses of (-)-Mesembrane and (-)-Mesembrine via Palladium-Catalyzed Enantioselective Allylic Substitution and Zirconium-Promoted Cyclization.

4-Arylhexahydroindole derivatives 5 were synthesized from 2-arylcyclohexenyl allylamine derivatives 4, which have a large protecting group on nitrogen, using zirconium-promoted cyclization. Reaction of 4e with Cp(2)ZrBu(2), followed by treatment with MeMgBr and then O(2), gave 2a in 63% yield by a one-pot reaction, since the approach of O(2) to zirconium was prevented by the aryl group. The total syntheses of (+/-)-mesembrane and (+/-)-mesembrine were achieved starting from 2a. To synthesize these natural products in a chiral form, the starting allylamine derivative 24 (80% yield, 86% ee, recrystallized from MeOH, 99% ee with 79% recovery) was prepared from allyl carbonate 22a and N-tosylallylamine 23 using palladium-catalyzed asymmetric amination in the presence of (S)-BINAPO as a chiral ligand. (-)-Mesembrane and (-)-mesembrine were synthesized from this allylamine 24.

Journal Article↗

PubMed1997

Syntheses of Strychnan- and Aspidospermatan-Type Alkaloids. 9.(1) The Enantioselective Generation of Tetracyclic ABCE Intermediates by a Tandem Condensation, [3,3]-Sigmatropic Rearrangement, and Cyclization Sequence.

Reactions of substituted acroleins with the tryptophan-derived benzyl 2-(benzylamino)-3-[3-[2-[(methoxycarbonyl)methyl]indolyl]]propionate gave tetracyclic hexahydro-1H-pyrrolo[2,3-d] intermediates with stereoselective placement of substituents for cyclization to pentacyclic Strychnos alkaloids. The benzyl ester moiety was readily removed by formation of a corresponding nitrile and reduction, thus providing enantioselective syntheses of the tetracyclic compounds.

Journal Article↗

PubMed1998

Total Syntheses of (+/-)-Deethylibophyllidine Using a Crisscross Annulation: Ring Cleavage of Octahydroindolo[2,3-a]quinolizines Followed by Tandem Cyclizations of Octahydroazecino[5,4-b]indoles.

The total synthesis of (+/-)-deethylibophyllidine (1) is described. Three different sequences provide this pentacyclic alkaloid using a common strategy involving a crisscross annulation. Key steps include (i) C/D ring cleavage of a 2-formyloctahydroindolo[2,3-a]quinolizine to obtain octahydroazecino[5,4-b]indoles, via either a chloroformate induced process or a quaternary ammonium salt formation followed by treatment with lithium, and (ii) a tandem process consisting of an intramolecular Pictet-Spengler double cyclization upon a beta-indole position of a 2,3-disubstituted indole to generate the quaternary spiro center of the pentacyclic skeleton of ibophyllidine alkaloids. Attempts to extend the procedure to the construction of the pentacyclic framework of (+/-)-ibophyllidine result in very low yield.

Journal Article↗

PubMed1999

Synthesis of Bridgehead Nitrogen Heterocycles via Cyclization of alpha-Ammonio 5-Hexenyl Radicals.

Ring-closure of the 2,2-dimethyl-2-azonia-5-hexenyl radical (4) proceeds smoothly and efficiently to give the 5-exo isomer essentially quantitatively, in accordance with predictions based on MP4SDTQ/6-31G ab initio calculations on the thermodynamic stability of alpha-ammonio radicals. The corresponding 5-hexynyl radical species 15 and its 6-phenyl derivative 19 display similar behavior affording the analogous 5-exo-3-methylenepyrrolidinium salts in high yield. In none of these cases were the products of reduction were detected. All of the radical intermediates were generated conveniently by treatment of the iodomethyl and/or phenylselenomethyl salts with tributyltin hydride. Application of this procedure to monocyclic precursors such as 1-methyl-1-iodomethyl-4-methylene-1-azoniacyclohexyl iodide (31) provided an attractive entry into quaternary derivatives of the 1-azabicyclo[2.2.1]heptyl system in good yield via a three-step sequence from 1-methylpiperidone. Dequaternization of the bicyclic salts so obtained unexpectedly leads to rupture of one of the rings rather than loss of the N-methyl group. The 1-azabicyclo[2.2.1]heptane could be accessed readily via tin hydride-induced cyclization of the corresponding N-phenylethylammonium salt 54, followed by Hofmann elimination with potassium tert-butoxide.

Journal Article↗