Showing papers on "Annulation published in 1998"

Synthesis of 2,3-Disubstituted Indoles via Palladium-Catalyzed Annulation of Internal Alkynes

Abstract: The palladium-catalyzed coupling of 2-iodoaniline and the corresponding N-methyl, -acetyl, and -tosyl derivatives with a wide variety of internal alkynes provides 2,3-disubstituted indoles in good-to-excellent yields. The best results are obtained by employing an excess of the alkyne and a sodium or potassium acetate or carbonate base plus 1 equiv of either LiCl or n-Bu4NCl, occasionally adding 5 mol % PPh3. The yields with LiCl appear to be higher and more reproducible than those obtained with n-Bu4NCl. The process is quite general as far as the types of substituents which can be accommodated on the nitrogen of the aniline and the two ends of the alkyne triple bond. The reaction is quite regioselective, placing the aryl group of the aniline on the less sterically hindered end of the triple bond and the nitrogen moiety on the more sterically hindered end. This methodology readily affords 2-silylindoles, which can be easily protodesilylated, halogenated, or reacted with alkenes and Pd(OAc)2 to produce 3-su...

A General Synthetic Approach to the (20S)-Camptothecin Family of Antitumor Agents by a Regiocontrolled Cascade Radical Cyclization of Aryl Isonitriles

Abstract: The power of radical reactions continues to increase! A cascade radical annulation route now allows perhaps the mildest and most general method for the synthesis of both known and new members of the camptothecin family (parent structure on the right) of antitumor agents.

Synthesis of the Pentacyclic Skeleton of the Aspidosperma Alkaloids Using Rhodium Carbenoids as Reactive Intermediates.

Abstract: A series of diazo amido keto esters prepared from N-alkenyl-substituted 3-carbalkoxy-2-piperidone derivatives was treated with rhodium(II) acetate. Attack of the amido carbonyl oxygen at the resultant rhodium carbenoid center produced a transient push−pull carbonyl ylide dipole which underwent an intramolecular dipolar cycloaddition reaction. A related annulation sequence was used to prepare the pentacyclic skeleton of the aspidosperma family of alkaloids. Synthesis of the required diazo imide was carried out from 3-carboxy-3-ethyl-2-piperidone and N-methyl-3-indoleacetic acid. Treatment of the diazo imide with rhodium(II) acetate afforded a transient 1,3-dipole which subsequently underwent cycloaddition across the indole π-bond. The resulting cycloadduct is the consequence of endo cycloaddition with respect to the dipole which is fully in accord with the lowest energy transition state. The cycloadduct was converted in three steps into desacetoxy-4-oxo-6,7-dihydrovindorosine. The stereochemistry of the fi...

Palladium-Catalyzed Annulation of Internal Alkynes by Arene-Containing Vinylic Iodides and Triflates

Abstract: In the presence of a palladium catalyst, internal alkynes undergo carboannulation by cyclic and acyclic vinylic iodides and triflates bearing a neighboring aromatic ring to produce a variety of carbocycles. For example, a number of 9,10-disubstituted-1,2,3,4-tetrahydrophenanthrenes have been prepared in good yields through the palladium-catalyzed annulation of internal alkynes by 2-phenyl-1-cyclohexenyl triflate (1) or 1-iodo-2-phenylcyclohexene (2). This annulation process is fairly general and highly regioselective. The process appears to involve oxidative addition of the vinylic substrate to Pd(0) to produce a vinylic palladium intermediate, which adds the carbon moiety to the less hindered end and the palladium to the more hindered end of the alkyne, followed by intramolecular ring closure onto the neighboring aryl group. The scope and limitations of this methodology are discussed.

Palladium-catalyzed annulation of allenes using functionally substituted vinylic halides

Abstract: Palladium catalyzes the regio- and stereoselective annulation of allenes by vinylic halides bearing alcohol-, amine-, sulfonamide-, carboxylic acid-, carboxamide- and carbanion-stabilizing groups to produce a variety of five- and six-membered-ring unsaturated heterocycles and carbocycles. The reaction appears to proceed by vinylic palladium formation and addition to the allene, followed by intramolecular nucleophilic displacement of the palladium. Six-membered rings are formed more readily than five-membered rings. The regioselectivity is generally high, with vinylic halides bearing alcohol, carboxylic acid, or carboxamide groups affording predominantly the product of intramolecular attack on the more substituted end of the π-allylpalladium intermediate, while amines and carbanions attack quite selectively at the less substituted end of the π-allylpalladium intermediate. Vinylic halides bearing tosylamides afford mixtures of regioisomers, where the predominant six-membered ring product arises by attack on...

A Direct and Efficient Stereocontrolled Synthetic Route to the Pseudopterosins, Potent Marine Antiinflammatory Agents

Abstract: Described herein is a new synthetic route to pseudopterosin aglycone (3), a key intermediate for the synthesis of a group of antiinflammatory natural products including pseudopterosin A (1) and E (2). The pathway of synthesis starts with the abundant and inexpensive (S)-(−)-limonene and its long-known cyclic hydroboration product (4) and leads to the chiral hydroxy ketone 6. Conversion of 6 to 10 followed by a novel aromatic annulation produced 15 which underwent a highly diastereoselective cyclization to afford the protected pseudopterosin aglycone 16. The naturally occurring pseudopterosins such as 1 and 2 are readily available from this key intermediate.

Synthesis of Substituted Pyridines via Regiocontrolled [4 + 2] Cycloadditions of Oximinosulfonates

Abstract: Diels−Alder cycloadditions of oximinosulfonate 8 with a variety of 1,3-dienes proceed with regiochemistry opposite to that observed with conventional imino dienophiles, providing expeditious synthetic routes to substituted pyridines, tetrahydropyridines, and pyrrolines. The oximinosulfonate 8 is prepared in one convenient synthetic operation from Meldrum's acid and reacts with conjugated dienes at −78 °C in the presence of 2 equiv of dimethylaluminum chloride to afford [4 + 2] cycloadducts in good to excellent yield. Exposure of these cycloadducts to the action of NaOMe and N-chlorosuccinimide in methanol−THF at room temperature then produces substituted pyridines. The utility of this new two-step annulation protocol is demonstrated in total syntheses of the pyridine alkaloids fusaric acid and (S)-(+)-fusarinolic acid. Heating the [4 + 2] cycloadducts derived from 8 in a mixture of acetonitrile and pH 7 phosphate buffer induces an unusual Stieglitz-type rearrangement leading to the formation of interestin...

Rearrangement of 1-(1-Alkynyl)cyclopropanols to 2-Cyclopentenones via Their Hexacarbonyldicobalt Complexes. A New Use of Alkyne−Co2(CO)6 Complexes in Organic Synthesis

Abstract: A novel rearrangement of 1-(1-alkynyl)cyclopropanols to 2-cyclopenten-1-ones proceeded on complexation of their alkynyl part with octacarbonyldicobalt (Co2(CO8)). 1-(1-Alkynyl)cyclopropanols with a wide range of substituents on their alkyne terminus rearranged to the corresponding 3-substituted 2-cyclopenten-1-ones in good yield. In case of the reactions of 1-alkynylcyclopropanols with an alkyl substituent on the cyclopropane ring, either 4-substituted or 5-substituted 2-cyclopenten-1-ones could be selectively obtained by appropriate choice of stereochemistry and protective group of the substrates. This rearrangement was successfully applied to cyclopentenone annulation reactions onto cycloalkenes. An efficient synthesis of alkynyl-substituted bicyclo[n.1.0]alkanol derivatives from the corresponding cycloalkenes according to Danheiser's protocol was developed, and bicyclic cyclopentenones were obtained in moderate to good yield by applying to these the cobalt-mediated rearrangement. Furthermore, the rearr...

Highly Regio- and Stereoselective [3+2] Cyclopentanone Annulation Using a 3-(Alkylthio)-2-siloxyallyl Cationic Species

Abstract: A new synthetic method for functionalized cyclopentanones was developed on the basis of a [3+2] cycloaddition reaction of a 1-(methylthio)-2-siloxyallyl cationic species and olefins. Allyl acetates 1a and 1b, which are the precursors of the allyl cationic species, are easily prepared in three or four steps from commercially available compounds. Under the influence of EtAlCl2 or AlCl3, 1a or 1b reacted with various kinds of olefins such as enol ethers, vinyl sulfides, styrenes, and trialkylolefins to afford the corresponding cyclopentanones in good yields. It is noteworthy that the sterically more hindered regioisomer was predominantly formed in every case. Furthermore, the reactions of 1b with vinyl sulfides exhibited surprisingly high stereoselectivity, which can be rationalized by the six-membered transition state models involving an orbital interaction between the sulfur atom of the vinyl sulfide and the α-carbon of the allyl cation.

[3 + 4] Annulation of α,β-Unsaturated Acylsilanes with Enolates of α,β-Unsaturated Methyl Ketones: Scope and Mechanism

Abstract: Reactions of the E and Z isomers of (β-(trimethylsilyl)acryloyl)(tert-butyl)dimethylsilanes with lithium enolate of α,β-unsaturated methyl ketones at −80 to −30 °C afford cis-5,6- and trans-5,6-disubstituted 3-cyclohepetenones, respectively. The same [3 + 4] annulation is observed in the reaction of (β-(tri-n-butylstannyl)acryloyl)silanes. The annulation products are readily transformed into 4-cycloheptene-1,3-dione by treatment with NBS or mCPBA. The observed stereospecificity in the annulation is explained by the reaction pathway that involves an anionic oxy-Cope rearrangement of 1,2-divinylcyclopropanediol intermediate generated via Brook rearrangement of the 1,2-adduct of a lithium enolate. Isolation of vinylcyclopropanol derivative from the reaction of (β-(tri-n-butylstannyl)acryloyl)silanes with lithium enolate of 2‘-bromoacetophenone and its transformation into cycloheptenone derivative with LDA provide strong support for the proposed mechanism. Further support is obtained from the reactions of 1,2...

Cycloaddition Reaction of Mesoionic Betaines as an Approach toward Trialkylindoline Alkaloids.

Abstract: Intramolecular 1,4-dipolar cycloaddition of an anhydro-4-hydroxy-2-oxo-1,3-thiazium hydroxide across a tethered indole π-bond has been used for the construction of the pentacyclic skeleton of epi-16,17-dihydroeburnamenine. The reaction of 3-ethyl-3-(alkenyl)piperidinones with diketene and trimethylsilyl triflate in benzene at ambient temperature produced annulated pyridones in good yield. The initial reaction involved formation of a N-acetoacetylated amide which was further converted to the pyridone with TMSOTf. The overall process was found to proceed with complete stereospecificity. Treating a sample of 3-ethyl-3-[(E)-4-phenyl-3-butenyl]-2-piperidone with diketene and TMSOTf produced a cycloadduct in 63% yield whose stereochemistry was elucidated by a X-ray crystallographic study. The epimeric Z-isomer produced a different stereoisomer of the annulated dihydropyridone. The mechanism of the annulation involves a TMSOTf induced cyclization followed by proton removal and generation of a cross-conjugated he...

Tetrabutylammonium Fluoride Promoted Novel Reactions of o-Carborane: Inter- and Intramolecular Additions to Aldehydes and Ketones and Annulation via Enals and Enones

Abstract: The addition of o-carborane (1) to aldehydes 2 proceeded very smoothly in the presence of aqueous tetrabutylammonium fluoride (TBAF; 3 equiv) at room temperature, giving the corresponding carbinols 3 in high yields. The TBAF-mediated reaction was applied to the intramolecular cycloaddition of o-carboranyl aldehydes and ketones 4, and the corresponding five-, six-, and seven-membered carboracycles were obtained in good-to-high yields. Further, [3 + 2] annulation between o-carborane (dianionic C2 synthons) and α,β-unsaturated aldehydes and ketones (dicationic C3 synthons) proceeded very smoothly in the presence of TBAF to give the corresponding five-membered carbocycles in good-to-high yields. Detailed mechanistic studies revealed that the [3 + 2] annulation proceeded through kinetically controlled 1,2-addition and thermodynamically controlled 1,4-addition.

Total Synthesis of (+/-)-Tremulenolide A and (+/-)-Tremulenediol A via a Stereoselective Cyclopropanation/Cope Rearrangement Annulation Strategy.

Abstract: Short total syntheses of (±)-tremulenolide A (1) and (±)-tremulenediol A (2) are described. The critical step is a dirhodium tetracarboxylate-catalyzed tandem cyclopropanation/Cope rearrangement between the vinyldiazoacetate 4 and the 2(Z),4(E)-hexadiene 5. This step results in full control of the relative stereochemistry at the three stereogenic centers that exist in the natural products. Due to problems with alkene face selectivity, the approach was not amenable to an efficient asymmetric synthesis of 1 and 2.

Ring-Closing Metathesis in Carbohydrate Annulation.

Abstract: Even eight-membered rings (such as in 2) can be formed by ring-closing metathesis of glucose derivatives such as 1. Enantiomerically pure tricyclic spiro compounds can also be prepared.

Effect of heteroaromatic annulation with five-membered rings on the photochromism of 2H- [1] -benzopyrans

Abstract: Photochromic properties (colorability, UV-VIS spectra of photo-merocyanines, rate constant of thermal bleaching) of chromenes annulated with different five-membered azaheterocycles or with furan cycles were investigated under flash photolysis. All the compounds, i.e., the 7H-pyrano[2,3-g]benzazoles 4–6, the 7H-pyrano[3,2-e]benzazoles 7–10, the 7H-pyrano[3,2-e]indoles 11–12, the 3H-pyrano[3,2-a]carbazole 13, the 8H-pyrano [2,3-e] indole 14 and the 3H-furano [ 3,2-f]chromenes 15–18 undergo reversible photochromic reaction at room temperature. They are compared with naphthopyranic parents 1–3. Whatever the structure of the heteroaromatic moiety, the annulation of the benzopyrans leads to the splitting into two bands of the electronic absorption spectra of the photoinduced forms with a significant bathochromic shift, a feature of interest for variable optical absorption systems. Unfortunately, diaryl-substituted azolo-fused chromenes exhibit decreased colorabilities. Furofused benzopyrans are particularly interesting with respect to naphthopyran parents owing to the bathochromically shifted and broadened absorption spectra of photoinduced forms and slightly enhanced colorabilities.