Chiral Cyclopentane Research Articles

Enantioselective Construction of Functionalized Cyclopentanes by a Relay Ring-Closing Metathesis and Chiral Amine (Thio)urea-Promoted Michael Addition

A relay strategy is described that permits ring-closing metathesis and bifunctional chiral amine (thio)urea-catalyzed Michael­ addition reactions to proceed in a one-pot fashion. The process offers an alternative approach to the synthesis of structurally diverse chiral cyclopentanes in good yields and good enantioselectivities.

Enantioselective cyclizations of silyloxyenynes catalyzed by cationic metal phosphine complexes.

The discovery of complementary methods for enantioselective transition metal-catalyzed cyclization with silyloxyenynes has been accomplished using chiral phosphine ligands. Under palladium catalysis, 1,6-silyloxyenynes bearing a terminal alkyne led to the desired five-membered ring with high enantioselectivities (up to 91% ee). As for reactions under cationic gold catalysis, 1,6- and 1,5-silyloxyenynes bearing an internal alkyne furnished the chiral cyclopentane derivatives with excellent enantiomeric excess (up to 94% ee). Modification of the substrate by incorporating an α,β-unsaturation led to the discovery of a tandem cyclization. Remarkably, using silyloxy-1,3-dien-7-ynes under gold catalysis conditions provided the bicyclic derivatives with excellent diastereo- and enantioselectivities (up to >20:1 dr and 99% ee).

ChemInform Abstract: Catalytic Asymmetric Synthesis of a Tertiary Benzylic Carbon Center via Phenol‐Directed Alkene Hydrogenation.

AbstractAn effective route to chiral cyclopentanes (II), useful precursors of a series of drugs, is reported.

ChemInform Abstract: Stereoselective Palladium-Catalyzed Cyclization on Carbohydrate Templates, e.g. (I), (III), (V). A Route to Chiral Cyclopentanes and Some Heterocyclic Analogs.

ChemInform Abstract: Stereoselective Palladium-Catalyzed Cyclization on Carbohydrate Templates, e.g. (I), (III), (V). A Route to Chiral Cyclopentanes and Some Heterocyclic Analogs.

ChemInform Abstract: Synthesis of Cyclic Valine Analogs.

Abstract Versatile and concise routes to both racemic and chiral cyclopentane analogs of valinol are described. These compounds are constrained analogs of a key amino acid found in the aspartyl protease inhibitors of HIV-1.

Stereocontrolled Preparation of Fully Substituted Cyclopentanes: Relevance to Total Synthesis

AbstractThis Microreview aims to identify important advances in the asymmetric synthesis of fully substituted five‐membered carbocyclic ring systems. Recent efforts directed towards the intricate and densely functionalized core substructures of three distinct classes of cyclopentane‐based natural products will be examined. Strategies featuring high levels of stereocontrol and/or conciseness in the total number of synthetic steps required to access complex natural product ring fragments are highlighted. Stereoselective Diels–Alder cycloaddition approaches to access functionalized norbornene intermediates as latent chiral cyclopentanes in the tradition of Corey's elegant prostaglandin studies are a recurring theme. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)

Asymmetric Construction of Quaternary Carbon Centers by Sequential Conjugate Addition of Lithium Amide and in Situ Alkylation: Utility in the Synthesis of (−)-Aspidospermidine

Chiral diether ligand-controlled asymmetric conjugate addition of a lithium amide to cyclopentenecarboxylate and subsequent in situ alkylation gave a chiral cyclopentane derivative bearing a quaternary carbon with high enantio- and diastereoselectivity. The cyclopentane derivative was converted successfully to (-)-aspidospermidine.

Multisubstituted Cyclopentanes by the Domino Michael-Henry Reaction

An organocatalytic and enantioselective domino Michael-Henry reaction yielding highly functionalized chiral cyclopentanes with four stereogenic centers (two quaternary and two tertiary stereocenters) is reported. Using cinchona alkaloid 1 as catalyst a variety of nitroalkanes can be employed in this transformation. Electron-withdrawing as well as electron-donating nitroolefins have a very limited influence on the stereoselectivity. The absolute configuration of the product was determined by X-ray crystallography.

Synthesis of Highly Functionalized Chiral Cyclopentanes by Catalytic Enantio‐ and Diastereoselective Double Michael Addition Reactions.

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.

Selective Ring Expansion Alkylation of Formyl[2.2.1]bicyclic Carbinols with C-Nucleophiles: A Unique Route to Cyclopentane Derivatives

Reactions of camphor-, and camphene-derived formyl [2.2.1]bicyclic carbinols with Grignard and organolithium reagents afford the corresponding regio- and stereospecific alkyl/aryl [3.2.1]bicyclic diols. Some of these bicyclic diols have been treated with lead tetraacetate to provide new chiral cyclopentane derivatives. A plausible mechanism of the ring expansion-alkylation reaction is proposed.

Synthesis of Highly Functionalized Chiral Cyclopentanes by Catalytic Enantio‐ and Diastereoselective Double Michael Addition Reactions

Do a double take: A novel highly enantio- and diastereoselective cascade double Michael reaction, in which two CC bonds and three contiguous stereogenic centers are formed, has been developed. The one-pot process, which was efficiently catalyzed by the chiral diphenylprolinyl trimethylsilyl (TMS) ether, is a facile approach to synthetically useful chiral cyclopentanes (see scheme).

Synthesis of Highly Functionalized Chiral Cyclopentanes by Catalytic Enantio‐ and Diastereoselective Double Michael Addition Reactions

Nimm zwei: Mit einer neuartigen hoch enantio- und diastereoselektiven doppelten Michael-Reaktion lassen sich in einer Reaktionskaskade zwei C-C-Bindungen und drei benachbarte stereogene Zentren erzeugen. Dieser Eintopfprozess, der effizient durch den chiralen Diphenylprolinyl(trimethylsilyl)ether katalysiert wird, eröffnet einen einfachen Zugang zu chiralen Cyclopentanderivaten (siehe Schema). Supporting information for this article is available on the WWW under http://www.wiley-vch.de/contents/jc_2001/2007/z700485_s.pdf or from the author. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

Total Syntheses of Iso‐, Neuro‐ and Phytoprostanes: New Insight in Lipid Chemistry

AbstractFor Abstract see ChemInform Abstract in Full Text.

A “Substrate‐Divergent” Approach to Chiral Cyclopentanes and Cyclohexanes from a Common Precursor Based on Levoglucosan.

AbstractFor Abstract see ChemInform Abstract in Full Text.

A ‘substrate-divergent’ approach to chiral cyclopentanes and cyclohexanes from a common precursor based on levoglucosan

Acyclic 1,3-dithianes 8 and 9 were transformed to cyclopentane derivative 12 and cyclohexane derivative 10, respectively, by treatment with BuLi.

Asymmetric Synthesis of 2‐Alkenyl‐1‐cyclopentanols via Tin—Lithium Exchange and Intramolecular Cycloalkylation.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Asymmetric synthesis of 2-alkenyl-1-cyclopentanols via tin-lithium exchange and intramolecular cycloalkylation.

[reaction: see text] We report a method for the synthesis of chiral cyclopentanes using tin-lithium exchange and cycloalkylation reactions. The sec-butyllithium/(-)-sparteine-mediated deprotonation of an alkyl carbamate and subsequent substitution furnishes a highly enantioenriched stannane as a stable carbanion equivalent. It was transformed into suitable cyclization precursors, which underwent tin-lithium exchange and stereoselective cycloalkylation when reacted with n-butyllithium, giving highly enantioenriched cyclopentanes in very good yields. A kinetic resolution was observed with a higher substituted stannane.

Catalytic enantioselective synthesis of prostaglandin E(1) methyl ester using a tandem 1,4-addition-aldol reaction to a cyclopenten-3,5-dione monoacetal.

Conjugate addition reactions are among the most important carbon-carbon bond formation reactions in organic synthesis, and considerable progress has been made in the development of asymmetric Michael additions and 1,4-additions of organometallic reagents. Recently, highly enantioselective copper-catalyzed conjugate addition reactions of diorganozinc reagents to enones have been reported. Among the various chiral ligands introduced for this purpose phosphoramidite 4, developed in our laboratories, shows nearly complete stereocontrol in the reaction of (functionalized) dialkylzinc (R2Zn) reagents with six-, sevenand eightmembered cycloalkenones. On the basis of this methodology, catalytic routes are now available to enantiomerically pure products, embedding cyclohexane and larger rings in their structure. In contrast, the catalytic enantioselective 1,4-addition to 2-cyclopentenone is a major challenge, particularly because chiral cyclopentane structures are ubiquitous in natural products. Employing TADDOL-based phosphoramidite ligands we obtained up to 62% ee when the Et2Zn addition to 2-cyclopentenone was run in the presence of molecular sieves. Furthermore, with using chiral bidentate phosphoramidite ligands, the enantioselectivity improved to 83%. Chan reached 89% ee using a diphosphite ligand, whereas Pfaltz enhanced the enantioselectivity in this addition to 94%. Recently Hoveyda reported ee values up to 97% using a chiral peptide-based phosphine ligand in the 1,4addition of diethylzinc to 2-cyclopentenone. Although these catalysts give excellent enantioselectivities, the isolated yields for the 3-substituted cyclopentanones are often moderate. Possible reasons are the lower reactivity of 2-cyclopentenone in comparison with other cyclic enones, the side-reactions of the resulting zinc enolate with the starting material and the high volatility of the 1,4-addition product. Performing the reaction in the presence of an aldehyde increases the yield considerably.

Total Synthesis of Marine Oxylipin Bacillariolides I–III

Marine oxylipin bacillariolides I–III were synthesized from ( R)-malic acid, using diastereoselective one-pot formation of the chiral cyclopentane derivative from the anion of allyl phenyl sulfone and chiral epoxymesylate as the key reaction.

Synthesis of Chiral Polyfunctionalised Cyclopentanes from the Diels–Alder Adduct of Furan and Maleic Anhydride

Chiral polyfunctionalised cyclopentanes have been readily obtained in ~65% enantiomeric excess via a stereo-specific Wagner–Meerwein rearrangement induced by bromination of derivatives of the exo-cis Diels–Alder adduct of furan and maleic anhydride, combined with desymmetrisation of a meso intermediate by pig liver esterase.