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Comprehensive Summary: Chiral phosphine‐catalyzed asymmetric (4+2) annulation of the amide‐based Morita–Baylis–Hillman (MBH) carbonates with β,γ‐unsaturated butenolides has been developed to give enantiomer‐enriched bicyclic δ‐lactam γ‐butyrolactone compounds. The amide‐based MBH carbonates were first used as acceptor and aza‐C4 synthon in phosphine catalysis. Under mild reaction conditions, a variety of amide‐based MBH carbonates and unsaturated butenolides were well tolerated to provide chiral bicyclic δ‐lactam γ‐butyrolactone derivatives in high yields with excellent enantioselectivities as well as diastereoselectivities. A plausible reaction mechanism was also proposed based on control experiments and DFT calculations. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: Chiral phosphine‐catalyzed asymmetric (4+2) annulation of the amide‐based Morita–Baylis–Hillman (MBH) carbonates with β,γ‐unsaturated butenolides has been developed to give enantiomer‐enriched bicyclic δ‐lactam γ‐butyrolactone compounds. The amide‐based MBH carbonates were first used as acceptor and aza‐C4 synthon in phosphine catalysis. Under mild reaction conditions, a variety of amide‐based MBH carbonates and unsaturated butenolides were well tolerated to provide chiral bicyclic δ‐lactam γ‐butyrolactone derivatives in high yields with excellent enantioselectivities as well as diastereoselectivities. A plausible reaction mechanism was also proposed based on control experiments and DFT calculations. [ABSTRACT FROM AUTHOR]

Herein, a novel switchable multipath cascade cyclization via chemodivergent reaction between readily available ketoamides and deconjugated butenolides was developed to efficiently synthesize γ-lactone fused γ-lactams and succinimide fused hemiketals. The Aldol/aza-Michael reaction and Aldol/imidation/hemiketalization reaction were enabled by catalytic amounts of two bases, namely tetramethyl guanidine and NaOAc. A wide range of substrate scope with diverse functional group compatibility was demonstrated to deliver the corresponding products with good yield and excellent diastereoselectivity (>60 examples). [ABSTRACT FROM AUTHOR]

Using 1-thioaurones and 1-azaaurones as electron-deficient oxa-dienes, an organocatalytic asymmetric aromatizing inverse electron-demand [4+2] cycloaddition with γ-deconjugated butenolides and azlactones was developed. A wide range of optically active benzothiophene-fused δ-lactones and indole-fused δ-lactones were obtained with desirable outcomes (up to 94% yield, >99 : 1 dr and 99% ee). [ABSTRACT FROM AUTHOR]

An iron‐catalyzed three‐component cyanoalkylsulfonylation of 2,3‐allenoic acids, K2S2O5, and the ring‐opening of cyclobutanone oxime esters is described. The radical tandem cyclization route allows access to diverse cyanoalkylsulfonylated butenolides in moderate to good yields under mild conditions. Moreover, the products are further converted, offering the corresponding derivatives. [ABSTRACT FROM AUTHOR]

Catalytic asymmetric cycloadditions of ambident Pd‐containing dipolar species with nucleophilic dipolarophiles, namely, inverse‐electron‐demand cycloadditions, are challenging and underdeveloped. Possibly, the inherent linear selectivity of Pd‐catalyzed intermolecular allylations and the lack of efficient chiral ligands are responsible for this limitation. Herein, two cycloadditions of such intermediates with deconjugated butenolides and azlactones were accomplished by using a novel chiral hybrid P,S‐ligand and hydrogen bonding. By doing so, highly functionalized, optically active dihydroquinol‐2‐ones were produced with generally high reaction efficiencies and selectivities. Preliminary DFT calculations were performed to explain the high enantio‐ and diastereoselectivities. [ABSTRACT FROM AUTHOR]

A novel organocatalytic approach to γ,γ‐disubstituted butenolides is described. It is based on a fully site‐selective functionalization of 5‐alkylidenefuran‐2(5H)‐ones via trienamine‐mediated [4+2]‐cycloaddition with α,β,γ,δ‐diunsaturated aldehydes. The developed methodology proceeds with excellent stereocontrol and constitutes a unique example of trienamine chemistry with vinylogous dienophiles. Importantly, the reaction has very broad scope and allows for the introduction of substituents also in the α‐ or the β‐position of the butenolide ring. Usefulness of the products obtained has been confirmed in the intramolecular Stetter reaction leading to polycyclic product. A new organocatalytic cycloaddition for the synthesis of γ,γ‐disubstituted butenolides utilizing 5‐alkylidenefuran‐2(5H)‐ones as dienophiles is described. The developed approach applies the principle of vinylogy with the trienamine‐mediated [4+2]‐cycloaddition occurring chemoselectively at the more hindered double bond of the starting 5‐alkylidenefuran‐2(5H)‐one. [ABSTRACT FROM AUTHOR]

Cardenolides are composed of a steroid nucleus and a five-membered unsaturated lactone (butenolide) ring at C-17β. It is assumed that the butenolide ring is formed from a pregnane 21- O -malonyl hemiester after a condensation reaction between the methylenic group of the malonic acid residue and the C-20 carbonyl of the pregnane scaffold. Here, the formation of the butenolide ring was studied starting from pregnane 21- O -malonyl hemiesters with and without a hydroxyl group in position C-14β. Efficient lactonization was only achieved in the case of the 14β-hydroxylated derivative. The reaction involves: 1) formation of an intramolecular hydrogen bond between the C-20 carbonyl group and the 14β-hydroxyl group which stabilizes a negatively charged intermediate and/or increases the positive character of the C-20 carbonyl carbon, 2) nucleophilic attack that enables efficient lactonization by release of water, and 3) subsequent decarboxylation. We provide chemical and mechanistic evidence that 14β-hydroxylation would precede lactonization in cardenolide biosynthesis. [ABSTRACT FROM AUTHOR]

We developed a new approach to γ-lactols and methylene-γ-lactols based upon the radical cyclization of aluminium acetals obtained by reduction of α-bromoesters with DIBAL-H. The cyclic aluminium acetals resulting from the cyclization process could engage in situ in further functionalization, as illustrated by the Oppenauer-type oxidation to give the corresponding lactones and γ-butenolides. The preparation of butenolides using this strategy compared favourably with the direct, tin-mediated cyclization of α-bromoesters, for which side reactions such as epimerization via [1,5]-HAT processes have been observed. [ABSTRACT FROM AUTHOR]

The first total synthesis of a chromodorolide diterpenoid is described. The synthesis features a bimolecular radical addition/cyclization/fragmentation cascade that unites butenolide and trans-hydrindane fragments while fashioning two C -C bonds and stereoselectively forming three of the ten contiguous stereocenters of chromodorolide B. [ABSTRACT FROM AUTHOR]

A total synthesis of huperzine R was accomplished. Intramolecular cycloaddition of a nitrile oxide and reductive cleavage of the resulting isoxazoline induced sequential cleavage of the C-C and C-O bonds to form the characteristic bicyclic lactam core with an enone moiety. Construction of the butenolide moiety from the enone afforded huperzine R. [ABSTRACT FROM AUTHOR]

Polysubstituted butenolides were obtained in good to high yields from α-bromoesters derived from propargyl alcohols by a one-pot reaction involving the radical cyclization of α-bromo aluminium acetals, followed by the oxidation of the resulting cyclic aluminium acetals in an Oppenauer-type process and migration of the exocyclic CC bond into the α,β-position. Comparison with the direct cyclization of α-bromoesters at high temperature and under high dilution conditions is described. Deuterium-labelling experiments allowed us to uncover 'invisible' 1,5-hydrogen atom transfers (1,5-HATs) that occur during these cyclization processes, together with the consequences of the latter in the epimerization of stereogenic centres. Compared to the classical approach, the cyclization of aluminium acetals proved to be highly chemoselective and its efficiency was illustrated by the short total syntheses of optically enriched γ-butenolides isolated from Plagiomnium undulatum and from Kyrtuhrix maculans. [ABSTRACT FROM AUTHOR]

The natural product paracaseolide A is a tetracyclic dilactone containing six adjacent stereocentres. Its skeleton occupies a unique structural space among the >200,000 characterized secondary metabolites. Six different research groups have reported a chemical synthesis of this compound, five of which used a thermal, net Diels-Alder [4+2] cycloaddition and dehydration at 110 °C to access the target by dimerization of a simple butenolide precursor. Here, we report that this dimerization proceeds under much milder conditions and with a different stereochemical outcome than previously recognized. This can be rationalized by invoking a bis-pericyclic transition state. Furthermore, we find that spontaneous epimerization, necessary to correct the configuration at one key stereocentre, is viable and that natural paracaseolide A is racemic. Together, these facts point to the absence of enzymatic catalysis (that is, Diels-Alderase activity) in the cycloaddition and strongly suggest that a non-enzyme-mediated dimerization is the actual event by which paracaseolide A is produced in nature. [ABSTRACT FROM AUTHOR]

Preliminary results related to the development of [2 + 2 + 1]-oxa-hetero-Pauson-Khand cycloaddition strategy toward the Securinega alkaloids are reported. The critical tricyclic BCD-ring core was assembled in only nine linear steps from cheap 4-hydroxy-L-proline. The study provides valuable insight into the scope of a rare hetero-Pauson-Khand reaction, a powerful tool for the rapid construction of butenolide-containing natural products. [ABSTRACT FROM AUTHOR]

A novel method for the preparation of the spirocyclic Δβ,γ-butenolides is presented. The developed strategy is based on a trienamine-mediated [4+2]-cycloaddition between (E)-3-alkylidene- 5-arylfuran-2(3H)-ones and 2,4-dienals. Target products containing three contiguous centres including one quaternary are efficiently formed in a highly enantiomerically enriched form in the presence of the silyl-protected diphenylprolinol aminocatalyst. [ABSTRACT FROM AUTHOR]

Thetotal synthesis of distomadines A and B, two structurally uniquetetracyclic quinolines, is described. The route features a three-stepprocess to access the pyranoquinoline butenolide rings via a Suzukicross coupling of a 5-bromo-4-methoxycarbonylmethoxyquinoline witha vinyl boronate, followed by an α-ketohydroxylation and doublecyclization by intramolecular aldol condensation and lactonization.Subsequent manipulation of the side chain to introduce the guanidinefragment completed the synthesis of distomadine B, whereas the distomadineA congener resulted from decarboxylation of a late-stage intermediate. [ABSTRACT FROM AUTHOR]

• New applications of fluoroalkylphosphonium salts. • (Phenylthio)difluoromethylation of 2,3-allenoic acids. • Tandem radical addition/intramolecular reaction. • Facile synthesis of (phenylthio)difluoromethylated butenolides. The photoredox catalyzed difluoro(phenylthio)methylation of 2,3-allenoic acids with {difluoro(phenylthio)methyl}triphenylphosphonium triflate was investigated. A series of 4-aryl-2,3-allenoic acids underwent tandem radical difluoro(phenylthio)methylation/intramolecular cyclization to afford previously unknown 4-difluoro(phenylthio)methylated butenolides, which could be converted to the corresponding difluoro(phenylthio)methylated furan-2(3 H)-one and difluoro(phenylsulfonyl)methylated butenolide derivatives. [Display omitted] [ABSTRACT FROM AUTHOR]

An AuI/AuIII catalytic system was found to be effective for the cascade oxidative arylation and cyclization of allenoates with arylboronic acids to give the corresponding cyclic adducts in moderate yields. This reaction system constitutes a new method for the synthesis of β-aryl-γ-butenolides under mild conditions. Based on the previous mechanistic studies, a proposed AuI/AuIII redox catalytic cycle has been outlined. [ABSTRACT FROM AUTHOR]

Remarkable reactivity reversal stratagem in 3,4-disubstituted butenolides under acidic conditions is described. Design of a suitably substituted multifunctional butenolide followed by an acid-catalyzed chemo- and diastereoselective intramolecular ring closure via the reactivity umpolung has been demonstrated to accomplish a concise total synthesis of paeonilide. Overall, the present protocol involves one-pot reduction of an α,β-unsaturated carbon–carbon double bond and intramolecular nucleophilic insertion of oxygen function at the electron-rich γ-position of butenolide. The involved mechanistic aspects have also been discussed. [ABSTRACT FROM AUTHOR]

A convenient and general synthesis of various 4-substituted 3-iodocoumarins and 4,5-disubstituted 3-iodobutenolides is described via an exclusive 6-endo-dig iodocyclization of 3-ethoxy-1-(2-alkoxyphenyl)-2-yn-1-ols and 5-endo-dig iodocyclization of 1-alkoxy-4-ethoxy-3-yn-1,2-diols, respectively. The reaction is carried out under very mild conditions using I2 in CH2Cl2 or toluene at room temperature. Oxygens in OMe and OMOM groups were used as efficient nucleophiles for this intramolecular cyclization to obtain the products in good to excellent yields. [ABSTRACT FROM AUTHOR]

Allylic cyclopropenecarboxylates undergo ring expansion reactions to give 2-allyloxyfuran intermediates, which subsequently rearrange to Δβ,γbutenolides via a Claisen rearrangement or to the corresponding Δα,βbutenolides via further Cope rearrangement. Also described are methods for chirality transfer in the rearrangement of nonracemic allylic esters. [ABSTRACT FROM AUTHOR]

Goniobutenolides A (1) and B (2), crassalactone D (3), 4-epi-crassalactone D (4), and the corresponding 7-epimers have been synthesized starting from d-glucose. The key step in the synthesis of 1and 2is a new one-pot sequence comprised of a Z-selective Wittig olefination/lactonization/β-elimination. Preparation of 3and 4included the final 5-endo-trig spirocyclization of 1and 2. The synthesized products were evaluated for their in vitro antiproliferative activity against selected tumor cell lines. [ABSTRACT FROM AUTHOR]

Abstract: A highly diastereoselective synthesis of heritol and heritonin by intramolecular cyclization on a preformed sensitive butenolide functionality is described. [Copyright &y& Elsevier]

A new route to 1,6-dioxaspiro[4.4]non-3-en-2-ones is established by bromoetherification of dihydroxybutenolides. An asymmetric total synthesis of 8-epi-crassalactone D starting from methyl cinnamate has been accomplished. [ABSTRACT FROM AUTHOR]

4-Alkyl- and 4-(ω-chloroalkyl)-1,3-bis(trimethylsilyl­oxy)buta-1,3-dienes were prepared from ethyl acetoacetate in three steps. Their cyclization with oxalyl chloride allowed an efficient synthesis of 4-alkyl- and 4-(ω-chloroalkyl)-5-alkylidenebuten­olides. [ABSTRACT FROM AUTHOR]

Abstract: A number of pulvinic acid natural products were prepared based on Suzuki cross coupling reactions of α-hydroxy-γ-alkylidenebutenolides which are readily available by cyclization of 1,3-bis-silyl enol ethers with oxalyl chloride. The formal total synthesis of pulvinic acid, atromentic acid, gomphidic acid and of 4-hydroxypulvinic acid, 4′-hydroxypulvinic acid and iso-gomphidic acid are reported. In addition, total syntheses of pinastric acid, xerocomic acid and variegatic acid were accomplished. [Copyright &y& Elsevier]

The article discusses research related to organic chemistry. Topics include the synthesis of fused-ring structures in organic diradicals such as diethynyl heptazethrene using palladium catalysts, an attempt at asymmetric acetylide addition synthesis of a propargyl alcohol diastereoisomer with similar spectra to that of the antibacterial natural butenolide trocheliophorolide B, and the equilibrium between zinc ester homoenolates and cyclopropanol alkoxides.

A reference of the article "Chemoselective Access to Substituted Butenolides via a Radical Cyclization Pathway: Mechanistic Study, Limits and Application" by A. Boussonniere and others published in a 2016 issue of journal "Pure and Applied Chemistry."

Review: 64 refs. [ABSTRACT FROM AUTHOR]

The cover page for the 2015 issue of "Chemistry: A European Journal" is presented.

Tandem vinylogous addition/lactonization/Wittig reaction of trifluoromethyl ketones with allylic carbonates provides γ-butenolides. [ABSTRACT FROM AUTHOR]