Bicyclic Cyclopentenones Research Articles

Tandem Thio-Michael Addition/Remote Lactone Activation of 5-Hydroxymethylfurfural-Derived δ-Lactone-Fused Cyclopentenones.

The creation of structurally diverse chemical entities from fairly simple biorefinery products remains a challenge. In this work 5‐hydroxymethylfurfural (HMF) was identified as a key synthon for preparing highly complex cyclopentenones (CP) via tandem 1,4‐addition/elimination/remote lactone activation to external O‐ and N‐nucleophiles in δ‐lactone‐fused‐CPs hotspots. This scaffold was also reactive enough to be incorporated into model cysteine‐peptides in low concentrations, paving the way to a potential translation generating complexity in the synthesis of small peptides. The new enones also exhibited activity against intraerythrocytic Plasmodium falciparum (IC50=1.32 μm).

SeO2-Mediated Oxidative Transposition of Pauson-Khand Products.

Oxidative transpositions of bicyclic cyclopentenones mediated by selenium dioxide (SeO2) are disclosed. Treatment of Pauson-Khand reaction (PKR) products with SeO2 in the presence or absence of water furnishes di- and trioxidized cyclopentenones, respectively. Mechanistic investigations reveal multiple competing oxidation pathways that depend on substrate identity and water concentration. Functionalization of the oxidized products via cross-coupling methods demonstrates their synthetic utility. These transformations allow rapid access to oxidatively transposed cyclopentenones from simple PKR products.

Cobalt‐Catalyzed Carbonylative Cyclization of Allyl Propargyl Ethers with Benzene‐1,3,5‐triyl Triformate as the CO Source

AbstractA facile and efficient approach for the establishment of the cyclopentenone skeleton via cobalt‐catalyzed carbonylative cyclization of allyl propargyl ethers has been developed. Using benzene‐1,3,5‐triyl triformate (TFBen) as the CO source, various bicyclic cyclopentenones were synthesized in good yields (61–86%).

Rhodium(i)-catalyzed Pauson–Khand-type reaction using formic acid as a CO surrogate: an alternative approach for indirect CO2 utilization

As a bridging molecule for the conversion of CO2 to CO, formic acid is successfully applied to rhodium-catalyzed carbo- and hetero-Pauson–Khand-type reactions, affording moderate to high yields of bicyclic cyclopentenones.

Integration of CO2 Reduction with Subsequent Carbonylation: Towards Extending Chemical Utilization of CO2.

Currently, it still remains a challenge to amplify the spectrum of chemical fixation of CO2 , although enormous progress has been achieved in this field. In view of the widespread applications of CO in a myriad of industrial carbonylation processes, an alternative strategy is proposed in which CO2 reduction to CO is combined with carbonylation with CO generated ex situ, which affords efficiently pharmaceutically and agrochemically attractive molecules. As such, CO2 in this study was efficiently reduced by triphenysilane using CsF to CO in a sealed two-chamber reactor. Subsequently, palladium-catalyzed aminocarbonylation, carbonylative Sonogashira coupling of aryl iodides, and rhodium(I)-mediated Pauson-Khand-type reaction proceeded smoothly to yield amides, alkynones, and bicyclic cyclopentenones, respectively. Furthermore, the formed alkynones can further be successfully converted to a series of heterocycles, for example, pyrazoles, 3a-hydroxyisoxazolo[3,2-a]isoindol-8-(3aH)-one derivatives and pyrimidines in moderate yields. The striking features of this protocol include operational simplicity, high efficiency, and relatively broad application scope, which represents an alternative avenue for CO2 transformation.

Formation of Bicyclic Cyclopentenone Derivatives by Robinson-Type Annulation of Cyclic β-Oxoesters Containing a 1,4-Diketone Moiety

Robinson-type cyclopentannulations of cyclic β-oxoesters possessing a 1,4-diketone moiety are accomplished under four different Brønsted basic reaction conditions. Using pyrrolidine/acetic acid in DMSO, an oxohexahydrocyclopenta[a]indene (42%) and an N-Boc-protected oxohexahydrocyclopenta[c]pyridine derivative (62%) are obtained with retention of the ester moieties. The latter compound defines an interesting new scaffold for medicinal chemistry with three positions allowing further derivatizations. The use of KOtBu in DMSO or NaH in toluene leads to cyclopentene derivatives with either partial ester saponification and decarboxylation or displacement of the ester moiety within the carbon skeleton. With aqueous KOH, the cyclopentannulations are successful in almost all cases, but with the ester moieties cleaved off. The respective bicyclic and tricyclic products are obtained in good to excellent yields. The 1,4-diketone starting materials are prepared by cerium-catalyzed oxidative coupling of β-oxoesters with isopropenyl acetate. Alternatively, a two-step sequence consisting of α-propargylation followed by palladium-catalyzed alkyne hydration is used.

Design, stereoselective synthesis and computational calculations of novel hybrid compounds via Pauson-Khand reactions

A series of novel chiral hybrid compounds between benzofuran and bicyclic cyclopentenone and also benzothiophene and bicyclic cyclopentenone have been designed and synthesized. Chiral enynes derived from enantiomerically enriched homoallyl and homopropargyl alcohols were converted into bicyclic cyclopentenone structures by intramolecular Pauson-Khand reactions. This strategy provides a facile access to various bicyclic cyclopentenones substituted with benzofuran or benzothiophene ring systems in good yields. In addition to the experimental work, the ground state geometries of the hybrid compounds were optimized using Density Functional Theory applications at the B3LYP/6-31G(d,p) level in order to obtain information about the 3D geometries and electronic structure.

ChemInform Abstract: Catalytic Enantioselective Quick Route to Aldol‐Tethered 1,6‐ and 1,7‐Enynes from ω‐Unsaturated Aldehydes.

AbstractDirect cross‐aldol reaction between ω‐unsaturated aldehydes and propargylic aldehydes is developed to yield functionalized 1,6‐ and 1,7‐enynes and the conversion of these products to bicyclic cyclopentenone derivatives by Pauson—Khand reaction is demonstrated.

Sequential Allylic Substitution/Pauson–Khand Reaction: A Strategy to Bicyclic Fused Cyclopentenones from MBH-Acetates of Acetylenic Aldehydes

An efficient approach for the construction of novel bicyclic fused cyclopentenones starting from Morita-Baylis-Hillman (MBH) acetates of acetylenic aldehydes with flexible scaffold diversity has been achieved using a two-step reaction sequence involving allylic substitution and the Pauson-Khand reaction. This strategy provided a facile access to various bicyclic cyclopentenones fused with either a carbocyclic or a heterocyclic ring system in good yield.

ChemInform Abstract: Rh(I)‐Catalyzed Cyclocarbonylation of Enynes with Glyceraldehyde: An Available Carbonyl Source Derived from Sugar Alcohols.

AbstractOptically active glyceraldehyde acetonide (II) is employed for the Rh‐catalyzed cyclocarbonylation of various enynes to produce bicyclic cyclopentenone derivatives.

ChemInform Abstract: Intramolecular Pauson—Khand Reaction Catalyzed by Oxime‐Derived Palladacycles.

AbstractOxime‐derived palladacycles with a pyridine co‐ligand are tested and PACY is found to be optimal for the synthesis of bicyclic cyclopentenones.

Rh(I)-Catalyzed Cyclocarbonylation of Enynes with Glyceraldehyde: An Available Carbonyl Source Derived from Sugar Alcohols

Catalytic cyclocarbonylation reactions using a glyceraldehyde derivative as a carbonyl source are described. The rhodium(I)-catalyzed reaction of enynes with glyceraldehyde acetonide gave bicyclic cyclopentenones as the products. This presents an interesting use of a sugar alcohol derived carbon resource as well as a convenient procedure for the cyclocarbonylation of enynes.

ChemInform Abstract: Bicyclic Cyclopentenones via the Combination of an Iridium‐Catalyzed Allylic Substitution with a Diastereoselective Intramolecular Pauson—Khand Reaction.

Enantioselective syntheses of bicyclic cyclopentenones are described. Key steps are an iridium-catalyzed allylic substitution and an intramolecular diastereoselective Pauson–Khand reaction. The diastereoselectivity of the Pauson–Khand reaction was found to be crucially dependent on the unit connecting the propargylic and the olefinic parts of the precursor. Very high degrees of diastereoselection were obtained with an NBoc unit as connector. This methodology has been illustrated by application within an enantioselective formal total synthesis of (−)--kainic acid.

Bicyclic Cyclopentenones via the Combination of an Iridium‐ Catalyzed Allylic Substitution with a Diastereoselective Intramolecular Pauson–Khand Reaction

AbstractEnantioselective syntheses of bicyclic cyclopentenones are described. Key steps are an iridium‐catalyzed allylic substitution and an intramolecular diastereoselective Pauson–Khand reaction. The diastereoselectivity of the Pauson–Khand reaction was found to be crucially dependent on the unit connecting the propargylic and the olefinic parts of the precursor. Very high degrees of diastereoselection were obtained with an NBoc unit as connector. This methodology has been illustrated by application within an enantioselective formal total synthesis of (−)‐α‐kainic acid.

Utilization of Aldoses as a Carbonyl Source in Cyclocarbonylation of Enynes

The reaction of enynes with acetyl-masked aldoses in the presence of a rhodium(I) catalyst resulted in cyclocarbonylation, thus avoiding the direct use of carbon monoxide, to afford bicyclic cyclopentenones. In rhodium catalysis, aldoses serve as a carbon monoxide equivalent by donating their carbonyl moieties on the acyclic aldehyde form to enynes. A variety of aldoses, including D-glucose, D-mannose, D-galactose, D-xylose, and D-ribose, can be used as a carbonyl source. Using the method, a wide variety of enynes were cyclocarbonylated in 22-67% yields. An asymmetric variant also proceeded with moderate to high enantioselectivity.

Rhodium‐Catalyzed Pauson–Khand‐Type Reaction Using Alcohol as a Source of Carbon Monoxide

Three in one pot! Bicyclic cyclopentenones have been synthesized from enynes in alcohol in the presence of a rhodium catalyst through a newly developed auto-tandem catalytic reaction. This process combines three mechanistically distinctive reactions—an oxidation of alcohols, a decarbonylation of aldehydes, and a carbonylative [2+2+1] cycloaddition (see scheme; dppp=propane-l,3-diylbis(diphenylphosphane)).

A Facile Synthesis of N‐[2‐(Trifluoromethyl)allyl]amides and Their Transformation into Angularly Trifluoromethylated Bicyclic Cyclopentenones.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 200 leading journals. To access a ChemInform Abstract, please click on HTML or PDF.

A Facile Synthesis of N-[2-(Trifluoromethyl)allyl]amides and Their Transformation into Angularly Trifluoromethylated Bicyclic Cyclopentenones

Abstract On treatment with sec-BuLi at −105 °C, 2-bromo-3,3,3-trifluoropropene undergoes rapid lithium–halogen exchange to generate thermally unstable 1-(trifluoromethyl)vinyllithium, which reacts with N-tosylimines to afford N-[2-(trifluoromethyl)allyl]amides in high yield. Propargylation of the amides, followed by the Pauson–Khand reaction, readily provides pyrrolidine ring-fused cyclopentenones with an angular trifluoromethyl group.

A Simple Procedure for the Synthesis of Functionalized 1,3-Butadienes and Cyclopentenones from Fischer Carbene Complexes

Consecutive treatment of alkenyl carbene complexes with lithium enolates derived from methyl ketones and iodine leads to functionalized 1,3-butadiene derivatives containing both electron-donating and electron-withdrawing groups. Functionalized bicyclic cyclopentenones are easily available by sequential treatment of dihydropyranyl carbene complexes with lithium enolates, iodine, and catalytic amounts of copper(II) triflate.

Iridium-catalyzed cascade decarbonylation/highly enantioselective Pauson–Khand-type cyclization reactions

An easily accessible chiral iridium-BINAP complex can effect the cooperative processes of decarbonylation of an aldehyde and cascaded enantioselective Pauson–Khand-type reaction. A survey of ligands revealed that atropisomeric aryl-diphosphine ligands were superior to chiral alkyl-diphosphines in this dual catalysis. Applying the reaction conditions of [IrCl(COD)] 2/( S)-BINAP complex with nonylaldehyde as a CO surrogate at 100 °C in anhydrous dioxane solvent, various 1,6-enynes were transformed to the corresponding optically active bicyclic cyclopentenones with excellent enantioselectivities (up to 98% ee).