Chiral Butenolides Research Articles

Total Synthesis of (−)-Lepadiformine A via Radical Translocation–Cyclization Reaction

Total synthesis of (-)-lepadiformine A featuring construction of the 1-azaspiro[4.5]decane skeleton by a highly diastereoselective radical translocation-cyclization reaction of a γ-lactam derivative bearing a chiral butenolide moiety is described. The enantioselective construction of butenolide is conducted via Krische's catalytic asymmetric allylation protocol. After the radical translocation-cyclization reaction, a hydroxymethyl group at the C-13 position was stereoselectively introduced by a one-pot partial reduction-allylation protocol of the unprotected lactam derivative. Finally, the total synthesis is completed by formation of a C ring.

Lewis Acid‐Catalyzed Stereoselective α‐Addition of Chiral Aldehydes to Cyclic Dienol Silanes: Aqueous Synthesis of Chiral Butenolides

AbstractThe stereoselective α‐addition to cyclic dienol silanes has rarely been exploited, in contrast to the well‐studied γ‐addition of conjugated butenolides. In this study, an unprecedent catalytic Mukaiyama aldol α‐addition of 2‐trimetylsiloxy furan to optically pure aldehydes in water‐containing solvents is reported. The synthetic utility of this concept was demonstrated in the efficient synthesis of six bioactive natural products: vitexolide D, curcucomosin C, villosin, chinensine C, (+)‐coronarin E and (E)‐labda‐7,11,13‐trien‐16,15‐olid.magnified image

A Sequential Pd-AAA/Cross-Metathesis/Cope Rearrangement Strategy for the Stereoselective Synthesis of Chiral Butenolides.

A practical and highly enantio- (up to 94:6 er) and diastereoselective (up to >20:1 dr) synthesis of γ-butenolides bearing two adjacent stereogenic centers is reported featuring a sequential direct palladium-catalyzed asymmetric allylic alkylation/( E)-selective cross-metathesis/[3,3]-sigmatropic Cope rearrangement from readily available α-substituted (5 H)-furan-2-ones.

Chiral VAPOL Imidodiphosphoric Acid-Catalyzed Asymmetric Vinylogous Mannich Reaction for the Synthesis of Butenolides

Chiral butenolides were synthesized by the enantioselective vinylogous Mannich reaction. Chiral (VAPOL)-type imidodiphosphoric acids are efficient catalysts for the asymmetric vinylogous Mannich (AVM) reaction of aldimines and trimethylsiloxyfuran in toluene. Under the optimized conditions, a series of butenolides were obtained with high yields (up to 98%) and enantioselectivities (up to 97% ee) as well as excellent diastereoselectivities (up to 99:1 dr).

Synthesis of (-)-Muricatacin from Tri-O-acetyl-d-glucal

The total synthesis of (–)-muricatacin is achieved using commercially available tri-O-acetyl- d -glucal as the starting material. The structure of the intermediate chiral butenolide is established unambiguously by X-ray crystallographic analysis, which consequently leads to correction of a previous structural misassignment.

Highly enantioselective direct vinylogous Michael addition of γ-substituted deconjugated butenolides to maleimides catalyzed by chiral squaramides

Highly enantioselective direct vinylogous Michael reactions of γ-aryl-substituted deconjugated butenolides with maleimides, catalyzed by only 1 mol% bifunctional squaramides derived from cinchona alkaloids, were achieved with excellent yields (up to 96%) and enantioselectivities (up to 97% ee). This protocol features a very low catalyst loading, mild reaction conditions and provides a potential and effective method for the construction of optically active chiral butenolides with adjacent quaternary and tertiary stereocenters.

ChemInform Abstract: An Approach to the Stereocontrolled Synthesis of Polysubstituted Chiral Butenolides and γ-Lactones.

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Stereocontrolled Total Synthesis of (−)-Kainic Acid. Regio- and Stereoselective Lithiation of Pyrrolidine Ring with the (+)-Sparteine Surrogate

[reaction: see text] A stereocontrolled total synthesis of (-)-kainic acid is described. cis-3,4-Disubstituted pyrrolidine ring was constructed by [3 + 2] cycloaddition of azomethine ylide with chiral butenolide. The crucial introduction of carboxyl group at the C-2 position was executed by regio- and stereoselective lithiation of the pyrrolidine ring in the presence of a (+)-sparteine surrogate followed by trapping with carbon dioxide.

The furan approach to oxacycles. Part 5: Synthesis of a chiral butenolide, building block towards biologically interesting natural products

We describe an efficient new approach for the synthesis of a chiral butenolide that is based on the oxidation of a chiral furan ring with singlet oxygen in the presence of Hünig’s base, followed by Luche reduction and in situ lactonization.

Stereocontrol in Alkyne Cyclocarbonylation Reactions Promoted by a Bioxazoline Palladium(ii) Complex

Insertion of 1,2-disubstituted alkynes into [Pd(CH3)(CO)(BIOX)]+[B{3,5-(CF3)2C6H3}4]- (1), where BIOX=(4S,4'S)-(-)-4,4',5,5'-tetrahydro-4,4'-bis(1-methylethyl)-2,2'-bioxazole, leads to the formation of five-membered palladacycles, which, by reaction with carbon monoxide, produce a mixture of two diastereomeric forms of a palladium complex containing an eta3-allylic gamma-lactone ligand. On leaving the mixture in solution, one isomer was converted into the other, reaching a diastereomeric excess of up to 94 %. The steric and electronic factors responsible for the epimerization process were investigated by theoretical methods. Cleavage of the eta3-allyl--palladium bond by nucleophiles allowed highly substituted chiral butenolides to be synthesized in good enantiomeric excess.

Interaction of Dihydropyridines and Nucleophiles with Carbene Complexes of Chromium: Diastereo‐ and Enantioselective Synthesis of Polycyclic Butenolides.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Interaction of Dihydropyridines and Nucleophiles with Carbene Complexes of Chromium: Diastereo‐ and Enantioselective Synthesis of Polycyclic Butenolides

AbstractThe interaction of N‐methyldihydropyridine with carbene complexes of chromium promotes their spontaneous homologation upon addition of a hydride to the carbene carbon and an insertion of CO. This is followed in the case of complexes tethered to a triple bond by cascade insertions of the triple bond and of a CO ligand giving finally butenolides. The scope of the reaction has been established with its limitations, together with the stereochemical outcome, which is discussed. [5.5], [5.6], [5.7] bicyclic and tricyclic systems have been synthesised together with chiral butenolides starting from chiral carbene complexes. Most of the new structures have been assessed by X‐ray crystallography. This transformation was first extended to dihydronicotinamides, to chiral dihydropyridines such as dihydronicotines which led to the butenolides in an enantioselective way, and to other sources of hydrides. Second, a series of nucleophiles such as alkoxides, alkyllithium and alkylmagnesium compounds led also to polycyclic, substituted butenolides. Moreover, the final lactone enolates could be trapped with oxygen and gave unsaturated lactonols. The key point in all of these reactions is the formation of tetrahedral intermediates upon interaction of the nucleophiles with the carbene carbon. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

Straightforward synthesis of two pairs of enantiomeric butenolides 3-tetradecyl- and 3-hexadecyl-5-methyl-2(5H)-furanone.

Based on the synthetic method of optically active 3-alkyl-5-methyl-2(5H)-furanones from lactic acid, two pairs of chiral butenolides 3-tetradecyl- and 3-hexadecyl-5-methyl-2(5H)-furanone have been straightforwardly synthesized from methyl stearate and methyl palmitate respectively by aldol condensation with (R)- or (S)-O-tetrahydropyranyl lactal prepared from corresponding ethyl lactate and beta-elimination.

Base-catalyzed epimerization of the butenolide in annonaceous acetogenins.

The elusive epimerization process in the chiral butenolide moiety of Annonaceous acetogenins was examined under several sets of conditions commonly used for elimination leading to the alpha, beta-unsaturated lactone and the results provide practical guidance in choosing elimination conditions.

The use of furans in natural product syntheses

Abstract

A novel total synthesis of (+)-himbacine, a potent antagonist of the muscarinic receptor of M 2 subtype

The title total synthesis was achieved by a method featuring highly stereoselective intermolecular Diels-Alder reaction of the tetrahydroisobenzofuran 5 with the chiral butenolide 6 as the key step. The cycloadduct 4 was converted to the title alkaloid by way of the known sulfone 2 in 17 steps. The title total synthesis was achieved by a method featuring highly stereoselective intermolecular Diels-Alder reaction as the key step. [Display omitted]

An unexpected photoadduct of N-carbomethoxymethylpyrrolidine with a chiral butenolide and benzophenone: X-ray structure and synthetic utility

The regio- and stereoselective photoinduced addition of N-carbomethoxymethylpyrrolidine to 5(S)- tert-butyldimethylsiloxymethyl-furan-2(5H)-one in the presence of benzophenone yields 3(R)-[N-(diphenylhydroxymethyl)carbo methoxymethylpyrrolidin-2′-yl]-4(S)- tert-butyldimethylsiloxymethyl)-butan-4-olides (epimeric at C-2′), and we report the X-ray structure of the major adduct together with its conversion into the 1-azabicyclo[4.3.0]-nonane ring system.

Ab Initio Study of Endo/Exo and Diastereofacial Selectivities in Diels-Alder Reactions between Chiral Butenolides and Cyclopentadiene.

Diels-Alder reactions of cyclopentadiene with crotonolactone and beta-angelica lactone have been studied using ab initio methods at the MP3/6-31G//RHF/3-21G and MP2/6-31G//RHF/6-31G levels. The transition states corresponding to the formation of different stereoisomers and diastereoisomers have been located. The results obtained show that the correct endo/exo selectivity is only obtained when polarization functions are included in the basis set. However, syn/antiselectivity is correctly described at all levels of calculation.

New entry to chiral butenolide synthons. Application to expeditious syntheses of (+)-nephrosteranic acid, (+)- trans-whisky lactone, and (+)- trans-cognac lactone

A new entry to chiral butenolide synthons starting with iodolactonization of the readily available, homochiral N-benzyl- N-methyl-3-hydroxy-4-pentenamide ( 1) and its application to the syntheses of (+)-nephrosteranic acid ( 5), (+)- trans-whisky lactone ( 6), and (+)- trans-cognac lactone ( 7) are described.

Lewis acid catalyzed diels-alder cycloadditions of chiral butenolides to cyclopentadiene: Endo/exo stereoselectivity.

The influence of several Lewis acids as catalysts in the Diels-Alder cycloadditions of cyclopentadiene to (R)-β-angelica lactone, 1, and (S)-5-hydroxymethyl-2(5H)-furanone, 2, respectively, have been investigated. The best results have been provided by the pair ZnCl 2/EtAlCl 2 for 1 and by Znl 2 for dienophile 2, enhancing significantly the rate and the stereoselectivity of these reactions and affording the corresponding endo adducts in 80–90% yields.