A convenient synthesis of enantiopure (4aS,7aR)-1,4,4a,7a-tetrahydrocyclopenta[c]pyran-3,7-dione

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Nickel(0)‐Catalyzed Enantioselective Annulations of Alkynes and Arylenoates Enabled by a Chiral NHC Ligand: Efficient Access to Cyclopentenones

Cyclopentenones are versatile structural motifs of natural products as well as reactive synthetic intermediates. The nickel‐catalyzed reductive [3+2] cycloaddition of α,β‐unsaturated aromatic esters and alkynes constitutes an efficient method for their synthesis. Here, nickel(0) catalysts comprising a chiral bulky C₁‐symmetric N‐heterocyclic carbene ligand were shown to enable an efficient asymmetric synthesis of cyclopentenones from mesityl enoates and internal alkynes under mild conditions. The bulky NHC ligand provided the cyclopentenone products in very high enantioselectivity and led to a regioselective incorporation of unsymmetrically substituted alkynes.     

The intermolecular Pauson-Khand reaction

Five membered carbocycles are important building blocks for many biologically active molecules. Moreover, substituted cyclopentenones (e.g. cyclopentenone prostaglandins) exhibit characteristic biological activity. The efficiency and atom economy of the Pauson-Khand reaction render this process potentially one of the most attractive methods for the synthesis of such compounds. Although it was discovered in its intermolecular form, the scope of the intermolecular Pauson-Khand reaction has always been limited by the poor reactivity and selectivity of the alkene component. The past decade, especially the last three years, has seen concerted efforts to broaden the scope of this reaction. In this overview, we provide a comprehensive and critical coverage of the intermolecular Pauson-Khand reaction based on the reactivity characteristics of different classes of alkenes and a rationalization of successes and misfortunes in this area.     

One‐Pot Transformation of Simple Furans into 4‐Hydroxy‐2‐cyclopentenones in Water

A highly efficient one‐pot transformation of readily accessible furans into 4‐hydroxy‐2‐cyclopentenones in H₂O, using singlet oxygen as oxidant, has been developed.     

Preparation of 2,4-disubstituted cyclopentenones by enantioselective iridium-catalyzed allylic alkylation: synthesis of 2'-methylcarbovir and TEI-9826

A broadly applicable synthesis of chiral 2- or 2,4-substituted cyclopent-2-enones has been developed by combining asymmetric iridium-catalyzed allylic alkylation reactions and ruthenium-catalyzed ring-closing metathesis. Enantiomeric excesses (ee values) in the range of 95-99 % ee have been achieved. This method offers a straightforward access to biologically active prostaglandins of the PGA type. As an example, an enantioselective synthesis of the prostaglandin-analogue 13,14-dihydro-15-deoxy-Delta(7)-prostaglandin-A1-methyl ester (TEI-9826) has been carried out. Furthermore, the carbonucleoside 2'-methylcarbovir has been prepared from O-protected 4-hydroxymethyl-2-methyl-cyclopent-2-enone by Pd-catalyzed allylic amination.     

Cytotoxicity of novel cross-conjugated arylated cyclopentene-1,3-diones

Novel 2,4-dichloro-5-phenylcyclopent-4-ene-1,3-dione and 5-aryl-4-chlorocyclopent-4-ene-1,3-dione were synthesized by the Suzuki–Miyaura or Friedel–Crafts reactions of the di- and trichlorocyclopentenone monoketals and subsequent hydrolysis of the ketal function. Condensation of these diones with (hetero)aromatic aldehydes afforded multifunctional 1,3-cyclopentenediones that showed anticancer activity.Keywords: organochlorine compounds, cyclopentenones, ketals, Suzuki–Miyaura reaction, Friedel–Crafts reaction, Knoevenagel condensation, aldehydes, cross-conjugated cyclopentene-1,3-diones, cytotoxicity.     

Synthesis and Applications of Hajos–Parrish Ketone Isomers

Numerous natural products possess ring systems and functionality for which Hajos–Parrish ketone isomers with a transposed methyl group (termed “iso‐Hajos–Parrish ketones”) would be of value. However, such building blocks have not been exploited to the same degree as the more typical Hajos–Parrish hydrindane. An efficient three‐step synthesis of such materials was fueled by a simple method for the rapid preparation of highly functionalized cyclopentenones, several of which are new chemical entities that would be challenging to access through other approaches. Furthermore, one iso‐Hajos–Parrish ketone was converted into two distinct natural product analogues and one natural product. As one indication of the value of these new building blocks, that latter target was obtained in 10 steps, having previously been accessed in 18 steps using the Hajos–Parrish ketone.