Search

Alkyne‐carbonyl metathesis is a type of carbon‐carbon forming reaction involving the construction a carbon‐carbon double bond and a carbonyl group in one transformation. Herein, a Au(I)‐catalyzed ring‐closing alkyne‐carbonyl metathesis protocol has been developed to make densely substituted γ‐butenolides from propargyl α‐ketoesters. It features 100 % atom economy, excellent substrate flexibility and benign functional group tolerance. Mechanistic studies demonstrate that the coordinative interaction between the gold catalyst and the alkyne might initiate the transfer of an oxygen atom and the formation of the carbon‐carbon double bond. By using this gold‐catalyzed ring‐closing alkyne‐carbonyl metathesis as a key step reaction, four naturally occurring butenolide‐type compounds including decumbic acid (45 % yield for 3 steps), deoxyisosporothric acid (32 % yield for 5 steps), lichesterinic acid (34 % yield for 5 steps) and isomuronic acid (6 % yield for 8 steps) have been synthesized starting from commercially available starting materials. [ABSTRACT FROM AUTHOR]

Design and development of a domino cyclative approach for the synthesis of new polycyclic γ‐butenolides from β‐aryl‐Z‐enoate propargylic alcohols, through the interception of an intermediate of the Z‐enoate‐assisted Meyer–Schuster rearrangement, has been reported. A systematic NMR analysis of various derivatives of this class revealed and supported the potential atropisomerism associated with them. These molecules represent first examples of butenolide ring‐based atropisomeric compounds in organic chemistry. The synthetic process involves a synchronous construction of both rings with concurrent creation of the potential stereogenic rotational axis. [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]

A direct asymmetric vinylogous aldol reaction of nonactivated natural α-angelica lactone to isatins has been developed. With a N, N′-dioxide-Sc(OTf)3 complex as catalyst, a variety of δ-hydroxy butenolides bearing congested adjacent tetrasubstituted stereocenters were obtained in good yields with high diastereoselectivities and excellent enantioselectivities. Besides, a possible transition state was proposed to explain the origin of the asymmetric induction. [ABSTRACT FROM AUTHOR]

Full details of the total synthesis of the Schisandraceae nortriterpenoid natural product rubriflordilactone A are reported. Palladium- and cobalt-catalyzed polycyclizations were employed as key strategies to construct the central pentasubstituted arene from bromoendiyne and triyne precursors. This required the independent assembly of two AB ring aldehydes for combination with a common diyne component. A number of model systems were explored to investigate these two methodologies, and also to establish routes for the installation of the challenging benzopyran and butenolide rings. [ABSTRACT FROM AUTHOR]

A structural revision of clavilactone D, a potent inhibitor of protein tyrosine kinases, was achieved by total syntheses of two newly proposed structures. The syntheses relied on ring-opening/ring-closing metathesis, which transformed a cyclobutenecarboxylate into a γ-butenolide. The syntheses confirmed that the correct structure of clavilactone D has an amino group at C-3 instead of a hydroxy group at C-2 in the originally proposed structure. [ABSTRACT FROM AUTHOR]

An enantioselective formal C(sp2)−H vinylation of prochiral 2,2-disubstituted cyclopentene-1,3-dione is presented. This vinylative desymmetrization is realized by using a two-step procedure that consists of a catalytic enantioselective vinylogous Michael addition of deconjugated butenolides to cyclopentene-1,3-dione and a base-mediated decarboxylation. The overall process utilizes deconjugated butenolides as the source of the highly substituted vinyl unit. Five-membered carbocycles containing a remote all-carbon quaternary stereogenic center are obtained in good yields and with good to high enantioselectivities. [ABSTRACT FROM AUTHOR]

Although catalytic asymmetric conjugate addition reactions have remarkably advanced over the last two decades, the application of less electrophilic α,β-unsaturated carboxylic acid derivatives in this useful reaction manifold remains challenging. Herein, we report that α,β-unsaturated 7-azaindoline amides act as reactive electrophiles to participate in catalytic diastereo- and enantioselective vinylogous conjugate addition of γ-butyrolactones in the presence of a cooperative catalyst comprising of a soft Lewis acid and a Brønsted base. Reactions mostly reached completion with as little as 1 mol % of catalyst loading to give the desired conjugate adducts in a highly stereoselective manner. [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]

A procedure that enables high yielding access to phosphonic γ-(hydroxyalkyl)butenolides with excellent regio-, diastereo- and enantiocontrol is reported. The simultaneous construction of up to two adjacent quaternary stereogenic centers by a catalytic asymmetric vinylogous Mukaiyama aldol reaction unites biologically and medicinally relevant entities, namely α-hydroxy phosphonates and γ-(hydroxyalkyl)butenolides. This is achieved by utilizing a readily available chiral copper-sulfoximine catalyst showing a broad functional group tolerance for both the electrophilic and nucleophilic reactants. A discussion about potential factors affecting the observed level of enantioselectivity, which stems from the enantiopure sulfoximine ligand, is also included. [ABSTRACT FROM AUTHOR]

A new stereocontrolled total synthesis of the configurationally labile C37-norcarotenoid pyrrhoxanthin in enantiopure form has been completed. A highly stereoselective Horner-Wadsworth-Emmons (HWE) condensation of a C17-allylphosphonate and a C20-aldehyde was used as the last conjunctive step. Both a Sonogashira reaction to form the C17-phosphonate and the final HWE condensation proved to be compatible with the sensitive C7-C10 enyne E configuration. Regioselective (5- exo-dig) silver-promoted lactonization reactions of three alternative pent-2-en-4-ynoic acid precursors with increased complexity, including a fully functionalized C20-fragment, were explored for the preparation of the γ-alkylidenebutenolide fragment. This survey extends the existing methodologies for the preparation of oxygen-containing carotenoids (xanthophylls) and streamlines the synthesis of additional members of the C37-norcarotenoid butenolide family of natural products. [ABSTRACT FROM AUTHOR]

Adding value: The direct vinylogous Michael addition of γ‐substituted butenolides with a series of 3‐aroyl acrylates and 1,2‐diaroylethylenes has been demonstrated. This organocatalytic method delivers highly enantio‐ and diastereomerically pure γ,γ‐disubstituted butenolides with adjacent quaternary and tertiary stereocenters (see scheme). [ABSTRACT FROM AUTHOR]

The lichen-derived glycoconjugate gobienine A is structurally more complex than most glycolipids isolated from higher plants by virtue of the all- cis substituted γ-lactone substructure embedded into its macrocyclic frame. A concise entry into this very epimerization-prone and hence challenging structural motif is presented, which relies on an enantioselective cyanohydrin formation, an intramolecular Blaise reaction, a palladium-catalyzed alkoxycarbonylation, and a diastereoselective hydrogenation of the tetrasubstituted alkene in the resulting butenolide. This strategy, in combination with ring-closing olefin metathesis for the formation of the macrocyclic perimeter, allowed the proposed structure of gobienine A ( 1) to be formed in high overall yield. The recorded spectral data show that the structure originally attributed to gobienine A is incorrect and that it is not the epimerization-prone ester site on the butanolide ring that is the locus of misassignment; rather, the discrepancy must be more profound. [ABSTRACT FROM AUTHOR]

Vinylogous reactions: The direct asymmetric vinylogous conjugate additions of γ‐aryl‐ and alkyl‐substituted butenolides to enones was realized for the first time by a designed and tested metal/organo dual‐activation strategy, in which two effective metal/organo cooperative catalytic systems have been built (see scheme). [ABSTRACT FROM AUTHOR]

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

A correction to the article "Development of Metal/Organo Catalytic Systems for Direct Vinylogous Michael Reactions to Build Chiral γ,γ-Disubstituted Butenolides" by D. Yang and L. Wang that was published in the previous issue is presented.