Synthesis Of Γ-lactones Research Articles

Silver triflate-catalysed synthesis of γ-lactones from fatty acids

A silver(I)-based catalytic system was found to efficiently promote the double-bond isomerization of unsaturated fatty acids and at the same time to mediate the intramolecular addition of the carboxylate group to the isomerized double bond under selective formation of five-ring lactones. The resulting one-step isomerization–γ-lactonization process allows the direct conversion of unsaturated fatty acids into the corresponding γ-lactones in good yields.

Silylene transfer to α-keto esters and application to the synthesis of γ-lactones

Disubstituted α-hydroxy acids have been synthesized by metal-catalyzed silylene transfer to α-keto esters. A range of substituents are tolerated in the transformation with the exception of branched groups at the vinylic position. The α-hydroxy acid products can be converted into γ-lactones using a variety of lactonization conditions.

Synthesis of γ-lactones by desymmetrization. A synthesis of (−)-muricatacin

A short synthesis of the natural potent cytotoxic agent (−)-muricatacin 1 and related unsaturated lactones from a versatile common intermediate, dienedioate 2, derived from d-mannitol or tartaric acid, is described. The strategy depends upon the desymmetrization of 7 by dihydroxylation and elaboration of the hydroxy alkyl sidechain. A route to unsaturated lactones is also described using a cis selective Wittig reaction. Since the enantiomers of 2 are available from the corresponding tartaric acids, this method provides access to both enantiomers of the described compounds and a wide range of derivatives.

Samarium(II) iodide-induced cascade reaction for tricyclic γ-lactone synthesis from acyclic keto diesters

Cascade reaction involving reductive cyclization, Dieckmann condensation, and lactonization of E- and Z-dimethyl 2-methyl-8-oxoundec-2-enedioates and Z-dimethyl 2-methyl-7-oxodec-2-enedioate with samarium(II) iodide was found to stereospecifically produce cis and trans bicyclo[4.4.0]decane (decalin) ring systems and trans bicyclo[4.3.0]nonan (perhydroindane) ring system each consisting of γ-lactone, respectively.

A novel synthesis of γ-lactones by tandem epoxide opening-cyclization reaction mediated by samarium(II) diiodide

Various epoxy esters readily reacted with SmI 2 (2 equiv) in the presence of ethyl bromoacetate (1 equiv) and HMPA (6 equiv) under mild conditions (THF, −78 °C, 2 h, Ar) providing the corresponding γ-lactones via tandem epoxide opening-cyclization reaction in good to excellent yields.

Oxidative radical cyclisations for the synthesis of γ-lactones

The use of manganese(III) acetate in combination with copper(II) triflate allows the synthesis of [3.3.0]-bicyclic gamma-lactones from 4-pentenylmalonates in excellent yields.

Highly Stereoselective Aldol Reaction for the Synthesis of γ-Lactones Starting from Tartaric Acid

A simple stereoselective process for the synthesis of highly substituted gamma-lactones was developed based on aldol reactions between the enolate of dioxanes derived from tartaric acid and aldehydes. A range of aromatic and aliphatic aldehydes were reacted, in most cases achieving good yields and stereoselectivity. The limitations of this reaction were identified and a transition state is proposed.

Conjugate Addition of Lithium Ester Enolates to 1‐Chlorovinyl p‐Tolyl Sulfoxides: A Novel Synthesis of Functionalized Esters and Lactones Having a Tertiary or a Quaternary Carbon at the β‐Position.

AbstractFor Abstract see ChemInform Abstract in Full Text.

An Alternative Method for the Synthesis of γ-Lactones by Using Cesium Fluoride-Celite/Acetonitrile Combination

A variety of 2-(1-bromoalkyl) benzoic acids 4 undergo intramolecular nucleophilic substitution reaction when treated with a CsF-Celite as solid base in acetonitrile under reflux condition to give the corresponding cyclized phthalides in moderate to very good yield. These 2-(1-bromoalkyl) benzoic acids 4 are formed by the α-bromination of 2-alkylbenzoic acids 3 using N-bromosuccinimide and a catalytic amount of α,α′-azoisobutyronitrile in carbon tetrachloride under reflux.

Conjugate addition of lithium ester enolates to 1-chlorovinyl p-tolyl sulfoxides: a novel synthesis of functionalized esters and lactones having a tertiary or a quaternary carbon at the β-position

Addition of the lithium ester enolates to 1-chlorovinyl p-tolyl sulfoxides, which were synthesized from chloromethyl p-tolyl sulfoxide and ketones or aldehydes, gave esters having a tertiary or a quaternary carbon at the 3-position, and chlorine and sulfinyl groups at the 4-position in high to quantitative yields. The adducts were converted to various esters having methyl, formyl, and hydroxycarbonyl groups at the 3-position. A novel method for the synthesis of γ-lactones, including spiro-type γ-lactones and α-methylene γ-lactones, was realized from the adducts in good overall yields. The scope and limitations of this method and the mechanism of the reactions are also discussed.

Synthesis of γ-Lactones and Ascorbic Acid Analogues by Diastereoselective Hydrogenation of α-Hydroxy-γ-alkylidenebutenolides

The cyclization of 1,3-bis(trimethylsilyloxy)-1,3-butadienes with oxalyl chloride afforded functionalized γ-alkylidene-α-hydroxybutenolides, which were transformed into cis-configured γ-lactones by diastereoselective hydrogenation. (© Wiley-VCH Verlag GmbH, 69451 Weinheim, Germany, 2002)

An improved method for the synthesis of γ-lactones using sodium bromate and sodium hydrogen sulfite

o-Alkylbenzenecarboxylic acids are treated with a sodium bromate and sodium hydrogen sulfite reagent under a two-phase system using ethyl acetate as solvent, under mild conditions to give the corresponding cyclized phthalides in moderate to satisfactory yield. Intermediately the α-brominated alkylbenzenecarboxylic acids are formed by the in situ generated hypobromous acid. These α-brominated acids undergo an intramolecular nucleophilic substitution reaction to afford the corresponding γ-lactones.

Synthesis of γ-lactones and unsaturated bis γ-lactones via Cu–Fe-mediated reductive cyclization of di- and tri-α-halogenated carboxylic esters

A new synthetic route to γ-substituted γ-butyrolactones from alkenes and α-dichloro ester, in the presence of CuCl (catalytic) and Fe(0) (stoichiometric) in acetonitrile, was established. A study of this reaction has demonstrated that the overall process consists of the following reaction steps: (a) addition of the dichloro ester to the olefin via CuCl catalysis; (b) selective reduction of the α-chloro atom in the resulting adduct by Fe(0); (c) cyclization of the resulting γ-chloro ester to γ-butyrolactone. Yields were improved by first carrying out step (a), then steps (b) and (c) in one pot. Selectivity was improved in the presence of a small amount of water. α-Trichloro esters also generated the γ-substituted γ-butyrolactone, albeit in lower yields and selectivity. The latter reaction gave rise to the formation of interesting by-products, namely new unsaturated bis-lactones.

Radical addition of 2-iodoalkanamide or 2-iodoalkanoic acid to alkenols using a water-soluble radical initiator in water. A facile synthesis of γ-lactones

Heating a mixture of 2-iodoacetamide and 5-hexen-1-ol in water at 75 °C in the presence of a water-soluble radical initiator, 4,4′-azobis(4-cyanopentanoic acid), provided γ-(4-hydroxybutyl)-γ-lactone in 95% yield. The use of 2-iodoacetic acid in place of 2-iodoacetamide also gave the same γ-lactone in 93 % yield.

Enantioselective synthesis of γ-lactones from thioglycolic acid: Syntheses of (−)-muricatacin and 5- epi-(−)-muricatacin

An approach for the enantioselective synthesis of functionalized γ-lactones and its application to the syntheses of (−)-muricatacin 1a and 5- epi-(−)-muricatacin 1b is reported. A sequential oxidation of the intermediate 4 with m-chloroperoxybenzoic acid was conducted to realize the reaction mechanism.

Triethylborane-mediated atom-transfer cyclisation of 2-iodo-N-(prop-2-enyl)acetamides and related compounds

The 2-iodo-N-(prop-2-enyl)acetamides 1, upon treatment with triethylborane (0.2–0.6 mol equiv.) in boiling benzene, undergo iodine atom-transfer cyclisation to give the 4-(iodomethyl)pyrrolidin-2-ones 2 in high yields. The method has been applied to the synthesis of γ-lactones.

A novel one-step synthesis of γ-lactones from olefins and phenyliodonium(ethoxycarbonyl)nonafluorobutylsulfonylmethanide catalyzed by copper(II) triflate

The reaction of phenyliodonio(ethoxycarbonylnonafluorobutylsulfonyl)methanide ( 4) with alkenes 2 in the presence of copper(II) triflate affords γ-butyrolactones 7 in good yields.

Samarium(II) Diiodide Induced Intramolecular Coupling Reaction of Haloacetals Leading to the Synthesis of γ-Lactones

Samarium(II) Diiodide Induced Intramolecular Coupling Reaction of Haloacetals Leading to the Synthesis of γ-Lactones

An efficient synthesis of γ-lactones as precursors of hydroxyethylene dipeptide isostere

An efficient and stereocontrolled synthesis of γ-lactones as precursors of the hydroxyethylene dipeptide isostere has been developed, starting from readily available 5-oxotetrahydrofuran-2-carboxylic acid 6.

Synthesis of γ-lactones from intermediate 2-(γ-hydroxyacyl)-imidazoles by N-methylation and base-catalyzed C  C bond cleavage. Application to the synthesis of (±)- cavernosine

Reaction of the allyl anions of O-trialkylsilyl- N-alkyl-2-(1′-hydroxyprop-2′-enyl)imidazoles with aldehydes and ketones gives products of α- and γ-attack. Greater steric hindrance in the anion (triisopropylsilyl vs t-butyldimethylsilyl) and in the aldehyde or ketone favours the γ-products. Sequential desilylation, N-methylation and treatment with base resulted in cleavage of these products to γ-lactones. The method was applied to the synthesis of (±)-cavernosine.