Enol Lactones Research Articles

Crystal structures of highly stabilized ylides: methyl(3-methoxy,2-methoxycarbonylbenzoyl) triphenyl- phosphoranylideneacetate and methyl(2-methoxycarb-6-nitrobenzoyl)triphenyl phos phoranyl ideneacetate and the salt methyl(triphenylphosphoranylidene)acetate tetrafluoroborate

At lower temperatures stabilized ylides react with unsymmetrically substituted phthalic anhydrides to give two acyclic adducts. When the reactions are allowed to proceed at higher temperature enol lactones are formed. Identification of the acyclic intermediates was necessary to understand the mechanism of these Wittig reactions. The transient species trapped in the reaction with trimethyloxonium tetrafluoroborate were unambiguously identified by crystallographic methods. The crystal structures of the tetrafluoroborate salt of methyl(triphenylphosphoranyl idene)- acetate (8), methyl(3-methoxy,2-methoxycarbonylbenzoyl)triphenylphosphoranylideneacetate (6β), and methyl(2-methoxycarbonyl,6-nitrobenzoyl)triphenylphosphoranylideneacetate (7α) were studied by X-ray diffraction. The ionic salt (8) is monoclinic, P21c,a= 12.640(5), b = 13.945(9), c = 14.825(6) Å, β = 125.32(3)°, Z = 4, and R = 0.065 (F >5.4 σ(F)). Crystal 6 β is monoclinic, P21c,a = 16.391(16), b = 9.029(6), c = 19.835(19) Å, β = 116.60(6)°, Z = 4, and R = 0.070 (F > 4.6 σ(F)), while crystal 7α is also monoclinic, P21c,a = 9.513(5), b = 9.361(3), c = 30.908(13) Å, β = 98.42(3)°, Z = 4, and R = 0.057 (F >5 σ(F)). In the BF 4- salt (12), the four P-C distances are equal (1.791(5)-1.801(7) Å) with identical tetrahedral angles. For the two triphenylphosphoranylideneacetate compounds, the fourth P-C(1) bond is shorter (1.762(6)-1.734(5) Å) than the three P-C(Ph) bonds (avg. 1.809(5) Å). The angles C(1)-P-C(Ph) are also larger (avg. 112.9(2)° for 6β and 111.9(2)° for 7α) than the C(Ph)-P-C(Ph) angles (avg. 105.8(2)° for 6 β and 106.9(2)° for 7α). These values suggest a multiple nature for the P-C(1) bond. In the nitro derivative, the nitro and the ester groups are disordered equally in positions 2 and 6. Key words: Wittig reactions, cyclic anhydrides, stabilized ylide, phosphoranylidenes, crystal structures.

New opportunities for α-ketenyl radicals in ring synthesis

Unsaturated acyl radicals are shown to be useful precursors to α-ketenyl radical intermediates which are then used in the synthesis of aromatic cyclic ketones. The behaviour of cyclopropyl acyl radicals is also described, in particular the 8- endo-trig cyclisation of 3-substituted cyclopropyl acyl radicals to give bicyclo[6.1.0]nonanones, and in the synthesis of cyclic enol lactones.

Enolization and Hydrolysis of 7-Nitroisochroman-3-one in Aqueous Solution: Generation of a Relatively Stable Lactone Enolate

The enolization and hydrolysis of the lactone 7-nitroisochroman-3-one (7-nitro-1,4-dihydro-3H-2-benzopyran-3-one, 1) has been studied in aqueous sodium hydroxide. In solutions of sufficient basicity ([NaOH] ≥ ca. 0.1 mM), 1 undergoes reversible deprotonation to form the corresponding enolate. Although ester hydrolysis accompanies enolization, observable quantities of the enolate persist for several seconds. Rate constants for deprotonation by hydroxide ion (k1 = 1.31(±0.06) × 104 M-1 s-1), protonation of the enolate by water (k-1 = 212 ± 24 s-1), and lactone hydrolysis (kOH = 19.0 ± 0.3 M-1 s-1) have been determined by monitoring the rates of formation and disappearance of the enolate. The kinetic data can be used to calculate the acid dissociation constant for 1 (pKa 11.98).

Synthesis of the C19 through C27 segment of okadaic acid using vinylogous urethane aldol chemistry: Part III

The synthesis of the C-19 through C-27 segment of the marine natural product okadaic acid was accomplished employing a highly enantio- and diasteroselective aldol coupling reaction of a chiral vinylogous urethane lactone enolate. The remainder of the carbon skeleton of this segment was constructed by a diastereoselective γ-oxygenated allylstannane addition. Formation of the tetrahydropyran ring was achieved utilizing a stereoselective electrophilic cyclization.

ChemInform Abstract: The Synthesis and Mechanism of Formation of Halogenated Enol Lactones.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

On the synthesis and the mechanism of formation of halogenated enol lactones

The synthesis of halo enol lactones from cyclic anhydrides via lactonization of the corresponding keto phosphoranes provides a direct route to these interesting compounds, which possess important biological properties and are useful intermediates in organic synthesis. In this paper we outline the syntheses of several halo enol lactones and discuss mechanistic consequences of these reactions on the understanding of Wittig reactions with cyclic anhydrides. Keywords: halolactonization, cyclic anhydrides, halo enol lactones, Wittig reaction mechanism.

Stabilized haloylides: synthesis and reactivity

This paper describes simple and successful methods for the preparation of stabilized halogenated phosphoylides and discusses their stability, reactivity, and utility in organic synthesis. Preparations of several halogenated compounds including pharmaceutically interesting enol lactones are reported. Keywords: halogenated stabilized ylides, preparation, structure, stability, reactivity, applications; vinylic halides, halo enol lactones.

Desymmetrization of Benzoic Acid in the Context of the Asymmetric Birch Reduction−Alkylation Protocol. Asymmetric Total Syntheses of (−)-Eburnamonine and (−)-Aspidospermidine

The highly diastereoselective potassium in ammonia reduction−ethylation (EtI) of the chiral 2-(trimethylsilyl)benzamide 1b to give 1,4-cyclohexadiene 3 is the key step in asymmetric syntheses of (−)-eburnamonine (4) and (−)-aspidospermidine (5). Cyclohexadiene 3 was converted to cyclohexanone 7, which provided the trimethylsilyl-substituted butyrolactone 9 utilized for the synthesis of 4 and butyrolactone 13 required for the synthesis of 5. The preparation of 9 depended upon the completely regioselective silicon-directed Baeyer−Villiger oxidation 7 → 8; Baeyer−Villiger oxidation of the cyclohexenone 10 also was regioselective to give the desired enol lactone 11 in 92% yield. Remarkable diastereoselectivity was observed for the kinetically controlled cyclization of the acyl imminium ion derived from the vinyl-substituted carboxaldehyde 16b; treatment of 16b with 5 equiv of CF3CO2H in CH2Cl2 at −55 °C gave an 18:1 mixture of 17 and its C(3) β-epimer in 93% yield. The oxidation of alcohol 18 containing sensi...

Synthesis of a Vitamin D3Hydrindan Ring−Side-Chain Building Block, Involving Tandem Conjugate Addition and Alkylation Reactions

Vitamin D3 hydrindan ring−side-chain building block 4 (racemic) has been synthesized from ketene acetal 12 (derived from 6-methylheptanoic acid), 2-methylcyclopent-2-en-1-one (13), allyl methyl carbonate, and dimethyl methylphosphonate. The Mukaiyama−Michael conjugate addition of 12 and 13 yielded the adduct 11 (lk) accompanied by ca. 10% of its diastereomer. Allylation of 11 with allyl methyl carbonate in the presence of palladium catalyst afforded 10. The latter was transformed into enol lactone 26, which on treatment with 2 equiv of lithium dimethyl methylphosphonate and then 1 equiv of acetic acid provided 4.

ChemInform Abstract: A Novel Catalyst with a Cuboidal PdMo3S4 Core for the Cyclization of Alkynoic Acids to Enol Lactones.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Haloenol lactones as inactivators and substrates of aldehyde dehydrogenase.

Human aldehyde dehydrogenase (EC 1.2.1.3) isozymes E1 and E2 were irreversibly inactivated by stoichiometric concentrations of the haloenol lactones 3-isopropyl-6(E)-bromomethylene tetrahydro-pyran-2-one and 3-phenyl-6(E)-bromomethylene tetrahydropyran-2-one. No inactivation occurred with the corresponding nonhalogenated enol lactones. Both the dehydrogenase and esterase activities were abolished. Activity was not regained on dialysis or treatment with 2-mercaptoethanol. The inactivation was subject to substrate protection: NAD afforded protection which increased in the presence of the aldehyde-substrate competitive inhibitor chloral. Saturation kinetics gave positive gamma-axis intercepts, allowing the determination of binding constants. Inactivation stiochiometry determined with 14C-labeled 3-(1-naphthyl)-6(E)-iodomethylene tetrahydropyran-2-one was found to correspond to the active-site number. The nonhalogenated lactone, 3-(1-naphthyl)-6(E)-methylene tetrahydropyran-1-one was shown to be a substrate for aldehyde dehydrogenase via its esterase function. Inactivation and enzymatic hydrolysis occurred within a similar time frame. Opening of the lactone ring to form enzyme-acyl intermediate with active site cysteine appears to be a necessary prerequisite to inactivation, since halogen in the lactone ring is nonreactive. Thus, the inactivation of aldehyde dehydrogenase by haloenol lactones is mechanism-based. Inactivation by haloenol lactones occurs in a manner analogous to that of chymotrypsin with which aldehyde dehydrogenase shares esterase activity and binding of haloenol lactones at the active site.

A New Route to γ-Arylidenebutyrolactones via a tandem carbopalladation-heterocyclisation sequence: a formal synthesis of U-68,215

Benzo-annulated enol lactones are obtained in good yields from pentynoic acids 3- or 5-substituted with an iodo-aryl moiety by palladium-catalyzed cyclization of their potassium carboxylates. Using this approach, an efficient new route to U-68,215 is described.

Cycloadditionen von 6H‐1,3,4‐Oxadiazin‐6‐onen (4,5‐Diaza‐α‐pyronen), 15.Reaktionen von 6H‐1,3,4‐Oxadiazin‐6‐onen mit Norbornadien. Ein neuer Weg zu 3,6‐disubstituierten α‐Pyronen

AbstractCycloadditions of 6H‐1,2,4‐Oxadiazin‐6‐ones (4,5‐Diaza‐α‐pyrones), 15.Part 14: Ref.[1]. — Reactions of 6H‐1,3,4‐Oxadiazin‐6‐ones with Norbornadiene. A New Route to 3,6‐Disubstituted α‐Pyrones Upon reaction with norbornadiene, ten disubstituted 1,3,4‐oxadiazin‐6‐ones 1 were converted into 3,6‐disubstituted α‐pyrones 6. For this purpose, solutions of the substrates were treated with boron trifluoride‐ether or trifluoroacetic acid. The smooth formation of 6 was also observed when a γ‐oxo ketene, initially generated by heating a solution of the substrates in the absence of boron trifluoride–ether, was allowed to react with the Lewis acid. Without use of an acid, only 6f could be obtained free from further compounds, whereas in the other cases enol lactones and 1:2 products of the types 8 and 7 were formed additionally. Oxadiazinone 1j gave enol lactone 10 in the noncatalysed reaction.

Palladium-mediated intramolecular cyclization of substituted pentynoic acids. A new route to γ-arylidenebutyrolactones

Benzo-annulated enol lactones are obtained in good yields from pentyonic acids 3- or 5- substituted with an iodo-aryl moiety by palladium-catalyzed cyclization of their potassium carboxylates.

The behaviour of qinghaosu (artemisinin) in the presence of non-heme iron(II) and (III)

In aprotic solvents with FeCl3, FeCl3N-Acetyl cysteine or FeCl2, qinghaosu (artemisinin) undergoes rearrangement to give the tetrahydrofuran acetate, 4-hydroxydesoxoqinghoasu or the enol lactone as the major product depending on the amount of catalyst used and the polarity of the reaction medium.

Synthesis of 7α-substituted androstenediones by a 1,4-conjugate addition approach

Oxidation of enol lactone 9 with Pd(OAc) 2 gave enone 8, which underwent stereoselective 1,4-conjugate addition with a series of cuprates affording the 7α-ketones 10–12 in excellent yield. Subsequent saponification and cyclization gave enol lactones 13–15, which can be transformed into the testosterone derivatives by treatment with 2.1 eq of LiCH 2P(O)(OMe) 2.

ChemInform Abstract: Synthesis of Cyclic Acylated Enamino Esters from Enol Lactones, 4‐Keto Amides, and 5‐Hydroxy Lactams.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Efficient Synthesis of the Ring System in Hemibrevetoxin-B via Lactone Enol Triflate Method

Efficient Synthesis of the Ring System in Hemibrevetoxin-B via Lactone Enol Triflate Method

Occurrence of Some Chlorinated Enol Lactones and Cyclopentene-1,3-Diones in Chlorine-Treated Waters

Enol lactones (5-dichloromethylene-2-furanones) and 2,2-dichlorocyclopentene-1,3-diones, a total of six compounds, were synthesized and subsequently qualitatively and quantitatively determined in a sample of chlorination stage liquor from the bleaching of softwood kraft pulp (CBL), in chlorine-treated natural humic water (HW), and in three samples of drinking water treated with various disinfectants (DW1-3). All the compounds could be observed in the samples, in concentrations ranging from 2 to 170 μg/L in CBL, from 7 to 65 ng/L in HW, and at most a few nanograms per liter in DW1-3. The compounds were found to be weakly mutagenic in the Ames assay (strain TA100 without metabolic activation). The contribution of the compounds to the total mutagenicity in the studied samples was negligible. The compounds were unstable in aqueous solutions at pH 7.0, and under these conditions they were in part converted to 5-(dichloromethyl)-5-hydroxy-2-furanones. In acidified methanol, the enol lactones were partially converted to 5-(dichloromethyl)-5-methoxy-2-furanones.

Synthesis of Cyclic Acylated Enamino Esters from Enol Lactones, 4-Keto amides, and 5-Hydroxy Lactams

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTSynthesis of Cyclic Acylated Enamino Esters from Enol Lactones, 4-Keto amides, and 5-Hydroxy LactamsA. D. Abell, M. D. Oldham, and J. M. TaylorCite this: J. Org. Chem. 1995, 60, 5, 1214–1220Publication Date (Print):March 1, 1995Publication History Published online1 May 2002Published inissue 1 March 1995https://doi.org/10.1021/jo00110a026RIGHTS & PERMISSIONSArticle Views574Altmetric-Citations15LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (953 KB) Get e-AlertsSupporting Info (2)»Supporting Information Supporting Information Get e-Alerts