Enol Lactones Research Articles

Enantioselective Enol Lactone Synthesis under Double Catalytic Conditions

Under the ‘double-catalytic condition’ protocol using the (R,R)-DBFOX/Ph complex of nickel(II) perchlorate hexahydrate and tetra­methyl-piperidine, enol lactones were formed with high enantioselectivity. The mechanism proceeds via an enantioselective Michael addition followed by enolization of the diketone moiety, then cyclization with concomitant displacement of the pyrazole auxiliary. Catalyst loadings can be reduced to 2 mol% and use of β-hydroxy-lactones instead of the diketone is also reported.

Enantioselective Enol Lactone Synthesis under Double Catalytic Conditions.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Synthesis of Iodoenol Lactone Derivatives from the Baylis—Hillman Adducts Using Iodolactonization Protocol.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Observations on the reactivity of thiyl radicals derived from 3,6-epidithiodiketopiperazine-2,5-diones and related congeners

A range of thiyl radicals derived from the reduced form of epidithiodiketopiperazines (ETPs) act as polarity reversal catalysts for the hydrosilylation of an enol lactone but not for H-atom abstraction from a model ribose ester.

Enantioselective Enol Lactone Synthesis under Double Catalytic Conditions

[reaction: see text] The reaction of dimedone with 1-(2-alkenoyl)-4-bromo-3,5-dimethylpyrazoles in THF, catalyzed by catalytic amounts of both DBFOX/Ph-nickel(II) perchlorate trihydrate and 2,2,6,6-tetramethylpiperidine, in the presence of acetic anhydride in THF produces the corresponding enol lactones in high enantioselectivities through enantioselective Michael additions followed by cyclization with removal of the pyrazole auxiliary. Other related nucleophile precursors can be successfully applied in the enantioselective enol lactone synthesis under the double catalytic conditions.

α,β-Unsaturated and cyclopropyl acyl radicals, and their ketene alkyl radical equivalents. Ring synthesis and tandem cyclisation reactions

Treatment of the alpha,beta-unsaturated selenyl esters 12 and 14 with Bu(3)SnH-AIBN produces the corresponding 2-cyclohexenones 13 and 15 respectively via presumed alpha-ketene alkyl radical intermediates, viz. 10. By contrast, the 2,7-diene esters 34 and 39 undergo tandem radical cyclisations producing diquinanes, e.g.(76%), and the corresponding allene-substituted alpha,beta-unsaturated selenyl ester 48 gives the cyclooctadienone 56 on treatment with Bu(3)SnH-AIBN in refluxing benzene. The selenyl ester 19 derived from chrysanthemic acid produces a mixture of the gamma,delta-unsaturated aldehyde 22 and the corresponding dimer 25a on treatment with Bu(3)SnH-AIBN. Furthermore, in the presence of methanol the only product from this reaction was the bis(methyl ester) dimer 25b, thereby lending further credence to the involvement of ketene alkyl radical intermediates in these reactions, and in the aforementioned reactions involving 2,6- and 2,7-diene selenyl esters. Treatment of the cyclopropane selenyl esters and , containing keto- and oxy-group functionality in their side-chains, with Bu(3)SnH-AIBN led to excellent syntheses of the enol lactone 66 (76%) and the trans-fused bicyclo[6.1.0]nonane 67 (80-95%) respectively.

Synthesis of Iodoenol Lactone Derivatives from the Baylis-Hillman Adducts Using Iodolactonization Protocol

Recently, we have reported the preparation of benzocycloheptene derivatives from the intramolecular Friedel-Crafts reaction of triple bond-tethered methyl cinnamates. In the reaction, we could not obtain any lactone derivatives, which could be formed via the intramolecular attack of the oxygen atom of ester moiety to the activated triple bond by the acid catalyst (Scheme 1). We think that there may be a certain competition between arene moiety and ester group as nucleophiles toward the activated triple bond. From the previous results we concluded that the arene moiety is more nucleophilic than the oxygen atom of ester toward the in-situ generated vinyl cation. In order to increase the nucleophilicity of the oxygen atom of ester group we decided to hydrolyze the ester into acid and to examine the feasibility of iodolactonization in the presence of NaHCO3 as shown in Scheme 1. From the reaction, we could expect the formation of two types of lactones, 5-membered iodoenol lactone or 6membered α-pyrone. Iodoenol lactone derivatives have been studied extensively due to their usefulness as synthetic intermediates and their biological activities. Low molecular weight αpyrones have been shown to be potent HIV-1 protease inhibitors. Recently, Larock and Rossi have reported an elegant synthesis of isocoumarins and α-pyrones via electrophilic cyclization. We were stimulated by their works and envisioned that we could synthesize suitably substituted α-pyrones or iodoenol lactone derivatives starting from the Baylis-Hillman adducts as mentioned in Scheme 1. The starting material 1 was prepared from Baylis-Hillman acetate according to our previous paper. Base hydrolysis of 1 was carried out using LiOH in aqueous THF at room temperature to give 2 in 53-69% yields. The use of KOH or NaOH was less efficient. With 2 in our hands, we initially examined the reaction with iodine in the presence of NaHCO3 in CH3CN, which is a typical condition for the iodolactonization. Unfortunately, complex mixtures were observed on TLC. Among the various conditions, we finally found that the use of THF as solvent afforded the desired iodoenol lactones 3 in moderate to good yields (56-90%). The formation of 3 can be explained as iodolactonization involving iodonium intermediate (I) via 5-exo-dig manner as shown in Scheme 2. We could not find nor isolate the corresponding six-membered α-pyrones, which can be formed via 6-endo-dig fashion. As the other electrophile source we examined H2SO4 and N-bromosuccinimide (NBS) in order to check the possibility for the synthesis of protonor bromine-attached enol lactones. Fortunately, desired compounds were synthesized in moderate yields. As shown in Scheme 3, bromolactonization of 2a (THF, NBS, NaHCO3) gave the bromoenol lactone 4 in 72% yield. Sulfuric acid-mediated cyclization of 2c in acetonitrile afforded enol lactone 5 in 53% yield at

(‐)‐Parasantonic Acid and Its Enol Lactone, (+)‐Parasantonide: Observation of the Rare Acid‐to‐Acid Catemeric Hydrogen‐Bonding Mode in a γ,ε‐Diketocarboxylic Acid.

AbstractFor Abstract see ChemInform Abstract in Full Text.

A General Synthesis of Substituted Indoles from Cyclic Enol Ethers and Enol Lactones.

AbstractFor Abstract see ChemInform Abstract in Full Text.

(-)-Parasantonic acid and its enol lactone, (+)-parasantonide: observation of the rare acid-to-acid catemeric hydrogen-bonding mode in a gamma,epsilon-diketocarboxylic acid.

The title diketo acid, (-)-alpha,3a,7-trimethyl-5,8-dioxo-1,4-ethanoperhydropentalene-1-acetic acid, C(15)H(20)O(4), is shown to aggregate in the solid state as acid-to-acid hydrogen-bonded catemers, whose chains follow 2(1) screw axes from each carboxyl H atom to the C=O group of a neighboring carboxyl group [O.O = 2.672 (4) A and O.H-O = 173 degrees ]. Two parallel counterdirectional screw-related single-strand hydrogen-bonded chains pass through the cell in the a direction. Two intermolecular C=O.H-C close contacts are present in this compound. Both this diketo acid and its enol lactone, (+)-parasantonide [systematic name: (-)-alpha,3a,7-trimethyl-5-oxo-1,4-ethenoperhydropentalene-1,8-carbolactone], C(15)H(18)O(3), have an R configuration at the methylated chiral center adjacent to the carboxyl group, unlike the precursor from which they are derived, viz. (-)-santonic acid.

Preparation of large ring acetylenic lactones by iodo lactonisation

Reaction of ω-ene-7-yne carboxylic acids with (biscollidine)iodine(I) hexafluorophosphate led to large ring acetylenic lactones. In the case of 5- or 6-yne carboxylic acids, iodo enol lactones were preferentially obtained.

Rhodium‐Catalyzed Carbonylation of Norbornene under Water—Gas‐Shift Reaction Conditions. Selective Formation of Co‐Dimeres with Lactone Terminus.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Rhodium-Catalyzed Carbonylation of Norbornene under Water–Gas-Shift Reaction Conditions. Selective Formation of Co-dimeres with Lactone Terminus

Abstract Carbonylation of norbornene in the presence of a rhodium carbonyl catalyst under water–gas-shift reaction conditions gave a norbornene–carbon monoxide co-dimer having an enol–lactone structure in a high yield.

A general synthesis of substituted indoles from cyclic enol ethers and enol lactones.

[reaction: see text] X = CH2, C[double bond]O, R2 = H, alkyl. A general method was developed for the one-pot synthesis of highly functionalized indoles from simple, commercially available aryl hydrazines and cyclic enol ethers. Enol lactones were also used as substrates, affording substituted indole acetic acid or indole propionic acid derivatives. This procedure affords 2,3-disubstituted indoles as single regioisomers from the appropriately substituted enol ether or enol lactone. This method was highlighted in the efficient synthesis of the antimigraine drug sumitriptan and the antiinflammatory drug indomethacin.

Synthesis of Cubane-Type Mo3NiS4 Clusters and Their Catalytic Activity for the Cyclization of Alkynoic Acids to Enol Lactones

Treatment of the cationic incomplete cubane-type sulfido complex [(Cp*Mo)3(μ2-S)3(μ3-S)][PF6] (2; Cp* = η5-C5Me5) with [Ni(cod)2] (cod = 1,5-cyclooctadiene) afforded the heterobimetallic μ,η2:η2-cod double-cubane-type cluster [{(Cp*Mo)3(μ3-S)4Ni}2(μ,η2:η2-cod)][PF6]2 (3), which further reacted with dimethyl acetylenedicarboxylate (dmad) to produce [(Cp*Mo)3(μ3-S)4Ni(η2-dmad)][PF6] (4). Cluster 3 or 4 showed high catalytic activity for the intramolecular cyclization of various alkynoic acids to give enol lactones in the presence of Et3N.

Facile Synthesis of 3‐Alkylidene‐3H‐isobenzofuranones from the Baylis—Hillman Reaction of 2‐Carboxybenzaldehyde.

AbstractFor Abstract see ChemInform Abstract in Full Text.

A New Method for Enol Lactone Synthesis by a Michael Addition/Cyclization Sequence.

AbstractFor Abstract see ChemInform Abstract in Full Text.

An approach to the total synthesis of the marine ascidian metabolite perophoramidine via a halogen-selective tandem Heck/carbonylation strategy.

A halogen-selective tandem intramolecular Heck/carbonylation reaction has been developed for the construction of the C,E,F-ring system and the C20 quaternary center found in perophoramidine (1). This process can be effected in good yields in the presence of both the chlorine and bromine atoms found in the natural product. In addition, it is possible to introduce the quaternary center at C4 in a stereoselective manner by a lactone enolate alkylation, using NaH and allyl bromide. [reaction: see text]

A new method for enol lactone synthesis by a Michael addition/cyclization sequence

Reactions of cyclic 1,3-dicarbonyl compounds with 1-(2-alkenoyl)-4-bromo-3,5-dimethylpyrazoles under the double catalytic activation conditions using both catalytic amounts of Lewis acid and amine catalysts provide a new direct synthetic route to enol lactones. Thus, 1,3-cyclohexanedione is allowed to react with 4-bromo-1-crotonoyl-3,5-dimethylpyrazole, in tetrahydrofuran at room temperature in the presence of both catalytic amounts (10 mol% each) of nickel(II) perchlorate hexahydrate and 2,2,6,6-tetramethylpiperidine, to give 4,7,7-trimethyl-3,4,5,6,7,8-hexahydrobenzopyran-2( H),5-dione in a good yield. This reaction does not proceed or is too slow under the reaction conditions other than the double catalytic activation conditions.

α‐Phosphono Lactone Analogues of Farnesyl Pyrophosphate: An Asymmetric Synthesis via Ring‐Closing Metathesis.

AbstractFor Abstract see ChemInform Abstract in Full Text.