Showing papers on "Annulation published in 1994"
TL;DR: This two-step ring-forming sequence involved initial generation of the benzyl enamine through either a condensation or conjugate addition reaction with BnNH 2 , followed by aza-annulation with acryloyl chloride or acrylic anhydride.
Abstract: The aza-annulation of β-enamino carbonyl substrates with acrylate derivatives provides an efficient and convenient route for the regioselective construction of δ-lactams. This two-step ring-forming sequence involved initial generation of the benzyl enamine through either a condensation or conjugate addition reaction with BnNH 2 , followed by aza-annulation with acryloyl chloride or acrylic anhydride. Controlled by the rigid framework of the intermediate lactam, introduction of ring substituents was accomplished with high relative stereoselectivity. The carbonyl functionality, which was necessary to direct the regioselectivity of the aza-annulation reaction, was then transformed into a protected hydroxyl substituent through Baeyer-Villiger oxidation. The resultant δ-lactam product was used as a valuable intermediate in the synthesis of three natural products. Subsequent modification of this δ-lactam gave the naturally occuring α-mannosidase inhibitors (±)-mannonolactam and (±)-deoxymannojirimycin, while synthesis of the alkaloid (±)-prosopinine was accomplished through homologation of the lactam carbonyl
108 citations
TL;DR: In this paper, the effect of electron-withdrawing substituents on the annulation reaction with acryloyl chloride and subsequent hydrogenation process was investigated for the indolizidine ring system of Tashiromine.
Abstract: N-alkylenamines, stabilized through conjugation with an electron-withdrawing group, undergo aza-annulation with acryloyl chloride to provide a convergent route for the construction of six-membered nitrogen heterocycles. In addition to enhancing the C-alkylation process of annulation relative to the competing N-acylation process, the electron withdrawing substituent controlled the regioselectivity of alkene formation in both the intermediate enamine and in the unsaturated lactam product. A variety of functional groups, which include -COMe, -COPh, -CO 2 R, -CONHPh, -CN, -P(O) (OEt) 2 , and -SO 2 Ph, were used to determine the effect of the electron-withdrawing substituents upon both the annulation reaction with acryloyl chloride and the subsequent hydrogenation process. When the enamide annulation product was stabilized through conjugation with ester or amide substituents, catalytic hydrogenation of the aza-annulation product resulted in the formation of vicinal stereocenters with high cis selectivity. The utility of this methodology was demonstrated by application of the condensation/aza-annulation/hydrogenation sequence as the key for construction and stereochemical control of the indolizidine ring system of (±)-tashiromine
88 citations
TL;DR: In this article, a palladium catalyzed annulation reaction of diphenylacetylene with iodobenzene leads to 9,10-diphenylphenanthrene.
84 citations
TL;DR: In this article, the Domino coupling process is analyzed and a mechanistic rationale for the C-H activation at methoxy groups is developed. But the analysis is restricted to the case of ortho-iodoanisoles.
Abstract: By palladium catalysis substituted ortho-iodoanisoles (5, 8, 10, 13) are transformed either to annulated pyran (6) or furan derivatives (7, 9, 11, 14, 15), depending on the reactivity of additional substituents. The regiochemistry of the Domino coupling processes is analyzed and a mechanistic rationale developed. Key step is the C-H activation at methoxy groups
63 citations
51 citations
TL;DR: In this paper, the synthesis of 4-mono and 2,4-disubstituted pyrrolo- [2,1-f][1,2,4]triazines is described.
50 citations
TL;DR: In this article, the stereoselective formation of six-membered nitrogen heterocycles that contain an asymmetric quaternary carbon center was achieved through aza-annulation of β-enamino amide substrates with activated acrylate derivatives.
Abstract: The stereoselective formation of six-membered nitrogen heterocycles that contain an asymmetric quaternary carbon center was achieved through aza-annulation of β-enamino amide substrates with activated acrylate derivatives. Condensation of a racemic β-keto amide with an optically active primary amine, either (R)-α-methylbenzylamine or α-amino esters, generated the corresponding optically active tetrasubstituted secondary enamine, in which the enamine tautomer was stabilized through conjugation with an amide carbonyl. Treatment of the intermediate enamine with acryloyl chloride, acrylic anhydride, or sodium acrylate/ethyl chloroformate resulted in aza-annulation to give the corresponding δ-lactam with high diastereoselectivity (>96% de). For the variety of different β-enamino amide substrate classes examined in this reaction, the optimum method for activation of the acrylate derivative was the use of EtO2CCl. When aza-annulation was performed with an α-acetamido-substituted acrylate derivative, the stereose...
49 citations
47 citations
TL;DR: The total synthesis of (±)-prosopinine is described in this paper, where aza-annulation was used to generate the six-membered nitrogen heterocycle, stereochemical control was achieved through the use of the δ-lactam template, and homologation of the lactam introduced the alkyl chain substituent on the piperidine ring.
36 citations
TL;DR: In this article, the annulation is believed to proceed through a sequence involving a stepwise alkylation at the γ position of 6 and an intramolecular Wittig reaction because of the fact that intermediate 11 was isolated.
Abstract: When (3-(ethoxycarbonyl)-2-ethoxy-2-propenylidene)triphenylphosphorane (6) was allowed to react with α-bromo ketones 8a-d in dichloromethane in the presence of Cs 2 CO 3 at room temperature, a [3+2] annulation occurred and led to the formation of the corresponding 2-ethoxycyclopentadienes 9a-d in excellent yields. Similarly, bromo thioester 8g underwent the annulation to give 4-(ethylthio)-cyclopentadiene 9g. Secondary bromides 2-bromo-3-pentanone and 2-bromocyclohexanone also afforded tetrasubstituted cyclopentadienes 9e and 9f in moderate yields when 2 equiv of 6 was used. The annulation is believed to proceed through a sequence involving a stepwise alkylation at the γ position of 6 and an intramolecular Wittig reaction because of the fact that intermediate 11 was isolated. The resulting 2-ethoxycyclopentadienes 9a-g were converted quantitatively into the corresponding cyclopentenones 10a-g upon mild acid treatment.Furthermore, alkylidenetriphenylphosphorane underwent a carbon elongation at both ends of the three-carbon unit via an alkylation-Wittig reaction sequence. (3-(tert-Butoxycarbonyl)-2-ethoxy-2-propenylidene)triphenylphosphorane (7) reacted first with alkyl halides and then with aldehydes in the presence of Cs 2 CO 3 to give enol ethers 23a-f, which were converted into α,β-unsatured ketones 20, 21, and 25c-f by hydrolysis of the enol ether and then decarboxylation. In this way, shogaol (29), the pungent principle component of ginger, was conveniently synthesized starting from 2-methoxy-4-methylphenol
33 citations
TL;DR: In this article, 2-3-Bis(phenylsulfonyl)-1,3-butadiene undergoes conjugate addition in the presence of carbanions giving rise to a variety of unsaturated sulfones.
Abstract: 2,3-Bis(phenylsulfonyl)-1,3-butadiene undergoes conjugate addition in the presence of carbanions giving rise to a variety of unsaturated sulfones. Reaction with lithium enolates proceeds via an allylic anionic intermediate which undergoes a subsequent elimination of phenylsulfinate anion to produce an allene. Generation of enolates from silyl enol ethers results in conjugate addition to the diene without subsequent elimination. Substituted cyclopentenyl sulfones are available via a [4+1] annulation reaction of the diene with various distabilized carbanions. The reaction involves a tandem addition-proton exchange-addition sequence. In the special case of 2,4-pentanedione, pyrans are formed, the isomeric identity of which depends upon the reaction conditions. 2-Alkylated 1,3-dicarbonyl compounds react with the activated diene to produce substituted allenes in high yield. Phenylsulfonyl alkenyl substituted allenes were conveniently prepared by a similar protocol and were found to serve as substrates for intramolecular [2+2] cycloaddition chemistry
TL;DR: In the presence of BF 3 -OEt 2 (0.2 molar equiv), the reactions of N-Cbz-α-amino aldehydes with allyltrimethylsilane produced pyrrolidines in good yields (70-80%), with high all-cis stereoselectivity at the C-2, C-3, and C-5 positions, along with small amounts of the expected homoallylic alcohols.
Abstract: In the presence of BF 3 -OEt 2 (0.2 molar equiv), the reactions (-10 o C, CH 2 Cl 2 ) of N-Cbz-α-amino aldehydes with allyltrimethylsilane produced pyrrolidines in good yields (70-80%), with high all-cis stereoselecti- vity at the C-2, C-3, and C-5 positions, along with small amounts of the expected homoallylic alcohols
TL;DR: A concise tropolone annulation applicable to rubrolone C ring introduc- tion is detailed based on the room-temperature cycloaddition rea- ction of the cyclopropenone ketal with the oxygenated diene.
Abstract: A concise tropolone annulation applicable to rubrolone C ring introduc- tion is detailed based on the room-temperature [4+2] cycloaddition rea- ction of the cyclopropenone ketal (10) with the oxygenated diene (9). Conversion of the sensitive [4+2] cycloadduct (11) to the norcaradiene (18), low temperature electrocyclic rearrangement to a cycloheptatrie- none ketal, and tautomerization to (12) provided a fully oxygenated tropolone analogous to that found in rubrolone
TL;DR: A total synthesis of the antimicrobial, structurally unusual sesterterpenoid (±)-palauolide was described in this article, where the synthesis was carried out using 3,6-dimethyl-2-cyclohexen-1-one annulation.
Abstract: A total synthesis of the antimicrobial, structurally unusual sesterterpenoid (±)-palauolide (1) is described. Methylenecyclohexane annulation of 3,6-dimethyl-2-cyclohexen-1-one (4) afforded a mixtu...
TL;DR: In this paper, the first total synthesis of the diterpene quinones aegyptinones A and B via an extremely direct route was described, which should easily accommodate the production of gram quantities of each compound.
Abstract: This paper describes the first total syntheses of the diterpene quinones aegyptinones A and B via an extremely direct route which should easily accommodate the production of gram quantities of each compound. The key step in the synthetic strategy involves the application of a recently developed «second-generation» photochemical aromatic annulation method for the construction of highly substituted aromatic systems. The synthesis of one of the annulation components, the diazo ketone 6, was achieved using a Diels-Alder-based benzannulation strategy employing cyanoallene and the dienamine 13. Cyanoallene proved to be uniquely effective for this cycloaddition, which either failed or proceeded in poor yield using several substituted acetylenes as dienophiles. The pivotal aromatic annulation reaction was accomplished by irradiating a solution of the diazo ketone 5 and the readily available siloxyalkyne 4 in a Pyrex vessel with a 450-W medium-pressure Hanovia lamp at room temperature for 17-20h. The desired tricyclic phenol 3 was produced in 58-70% yield and was then converted to aegyptinone B (2) by treatment with tetra-n-butylammonium fluoride in the presence of oxygen. Finally, cyclization to generate aegyptinone A was accomplished in high yield by brief exposure of 2 to an ethanolic solution of concentrated sulfuric acid at room temperature. Overall, this strategy provides efficient routes (six and seven steps, respectively) to aegyptinones A and B which should facilitate the systematic investigation of the pharmacological activity of these novel diterpenes
TL;DR: In this paper, the substituted decalones 2 and 3 were transformed into (−)-Ambrox® via modification of the sidechain, methylation, conversion of the isopropenyl group and cyclization.
TL;DR: Two conjugate addition/annulation methodologies for S-(+)-carvone are reported, which gave decalone 2e stereoselectively in very high yield and base catalyzed Robinson annulation with MVK and dehydration.
TL;DR: The reaction of 3-iminoprop-1-enylamines 1 with pentacarbonyl(1-methoxyprop-2-enylidene)chromium(0) complexes leads stereoselectively to substituted 5H-6,7-dihydroazepines in high yields; the process takes place at low temperature and is thought to involve a tandem imine cyclopropanation-Cope rearrangement.
Abstract: The reaction of 3-iminoprop-1-enylamines 1 with pentacarbonyl(1-methoxyprop-2-enylidene)chromium(0) complexes leads stereoselectively to substituted 5H-6,7-dihydroazepines in high yields; the process takes place at low temperature and is thought to involve a tandem imine cyclopropanation–Cope rearrangement.
TL;DR: The skeleton of the resulting compounds, which have potential as analgesics, is closely similar to that of the parent morphinan, although there is a novel annulation of the nitrogen-containing ring which is further expanded to an oxazepine.
Abstract: 5a, 11b-Propanonaphtho[1,2-e][1,2]oxazepines have been prepared from dihydro-7,14-cyclocodeinone by the following reaction path: nucleophilic cyclopropane-ring opening, N-oxide formation, Cope reaction and intramolecular O-alkylation. The skeleton of the resulting compounds which have potential as analgesics, is closely similar to that of the parent morphinan, although there is a novel annulation of the nitrogen-containing ring which is further expanded to an oxazepine.
TL;DR: In this paper, the unsaturated keto lactone was used as an intermediate in the total synthesis of drimane sesquiterpenes, which was shown to be an excellent intermediate for the 3β-acetoxydrimenin.
TL;DR: In this article, a concise stereoselective synthesis of the general furofuran lignan precursor (±)-Samin 1 has been achieved through a radical annulation reaction in good overall yield.
TL;DR: In this paper, the amidoalkylation reaction of methyl 4-methoxy-2-imidazolidinone-4-carboxylates or methyl 4methoxyl-2.oxazolidine-4.carboxyclic-nodes using allylsilanes as nucleophiles in the presence of TiCl 4 affords three carbon ring annulation products 5 and 9 via a [3+2] cycloaddition.
TL;DR: In this paper, a quinone aminal structure with a lithiated cyanophthalide was proposed to lead to a Quinone stabilized epoxide in the dynemicin series.
TL;DR: Some novel furogamma lactams have been synthesised by one step condensation of arylaminomalonates with substituted furyl acryloyl chlorides and are found to exhibit Gram-positive and Gram-negative antibacterial activity at very high concentrations.
TL;DR: Malonic esters, β-keto-ester and other methylene-active compounds react with the 7-iodo-2-heptenoic acid methyl ester 2 in presence of cesium carbonate to give six-membered ring products 5, through a tandem alkylation-Michael addition reaction as mentioned in this paper.
TL;DR: Alkylation of the methylenecyclopropane 1 with 4-alkynyl iodides followed by a free-radical mediated intramolecular methylENecyCLopentane annulation composes a quick and efficient new diquinane synthesis.
TL;DR: In this paper, the effect of annulation on the 13C NMR of the imidazole ring is discussed, and a 3-acyl-2-azabicyclo[2.2.1]hept-5-enes with phenyl isocyanate, phenyl-isothiocyanates, and ethoxycarbonyl isothiocyclate followed by cyclization reactions under basic conditions are obtained.
Abstract: The reactions of 3-acyl-2-azabicyclo[2.2.1]hept-5-enes with phenyl isocyanate, phenyl isothiocyanate, and ethoxycarbonyl isothiocyanate followed by cyclization reactions under basic conditions respectively provided a hydantoin, a thiohydantoin, and a 1,3-dihydro-2H-imidazole-2-thione incorporated with the azabicyclic skeleton. Treatment of the imidazolethione with Raney nickel gave a phenyl-substituted imidazole fused with 2-azabicyclo[2.2.1]hept-2-ene. The effect of annulation on the 13C NMR of the imidazole ring is discussed.
TL;DR: In this article, the synthesis of 5,6-O-(2-propylidene)-N-desalanyl-N-[(4-methylphenyl)methanesulfonyl]actinobolin (37) is reported.
Abstract: The synthesis of 5,6-O-(2-propylidene)-N-desalanyl-N-[(4-methylphenyl)methanesulfonyl]actinobolin (37) is reported. The carbocyclic ring of 37 is constructed by a novel [3+3] annulation method involving sequential two-electron and one-electron allylation with the conjunctive reagent 5. The 4-amino-4,6-dideoxy-D-galactose derivative 25 is efficiently prepared from D-glucose and coupled with 5. The key step in the annulation is the diastereoselective 6-endo-trig radical cyclization of the unusual thiocarbamate 32. The stereoselectivity is postulated to result from the acetonide protecting group in 32. The conversion of 37 into actinobolin has been previously established
TL;DR: In this paper, two effective synthetic approaches to (±)-euryfuran 1 are described, one synthetic route makes use of sequential furan ring transfer reaction type I and type III as key steps followed by Eschenmoser-type [3,3]sigmatropic rearrangement, and another route proceeded through furanring transfer reaction Type I and annulation with ethyl vinyl ketone subsequently.
TL;DR: In this paper, an improved annulation sequence is presented, making use of the one-pot cyclization of 5-nitropentan-2-one and cyclopent-2enone diesters to afford 7-methyl-4-nitro-1-oxohydrindene derivatives.