Chiral Diether Research Articles

Cyclic Model for the Asymmetric Conjugate Addition of Organolithiums with Enoates

The chiral diether ligand controlled asymmetric conjugate addition of organolithiums to nona-2,7-dienedioates preferentially proceeds via the s-cis conformation with coordination of the carbonyl oxygen atom to the lithium to give a lithium E-enolate intermediate. Subsequent intramolecular conjugate addition of the enolate also proceeds via a cyclic transition state involving the lithium and the s-cis-enoate, resulting in trans,trans-trisubstituted cyclohexanes with high enantiomeric excesses and yields.

Cyclic Model for the Asymmetric Conjugate Addition of Organolithiums with Enoates

The chiral diether ligand controlled asymmetric conjugate addition of organolithiums to nona-2,7-dienedioates preferentially proceeds via the <i>s</i>-<i>cis</i> conformation with coordination of the carbonyl oxygen atom to the lithium to give a lithium <i>E</i>-enolate intermediate. Subsequent intramolecular conjugate addition of the enolate also proceeds via a cyclic transition state involving the lithium and the <i>s</i>-<i>cis</i>-enoate, resulting in <i>trans</i>,<i>trans</i>-trisubstituted cyclohexanes with high enantiomeric excesses and yields.

A short synthesis of (+)-β-lycorane by asymmetric conjugate addition cascade

The chiral diether ligand-controlled asymmetric conjugate addition of organolithiums to nona-2,7-dienedioate and subsequent intramolecular conjugate addition of the enolate intermediate gave all-trans trisubstituted cyclohexanes with high ee and yields. Using this methodology, an efficient short asymmetric total synthesis of (+)-β-lycorane was accomplished in 33% overall yield through five steps from the dienedioate.

NMR studies on the structure of a lithium amide–chiral diether complex for an asymmetric reaction

The combination of a chiral diether ligand and a lithium benzyl(trimethylsilyl)amide is a powerful lithium amide reagent for asymmetric conjugate amination of enoate in a toluene solvent. The structure of the chiral diether–lithium amide complex in solution was analyzed by low-temperature NMR. 6Li NMR suggested the formation of a cyclic heterodimer. The stereochemical pathway is predictable based on the structure of the lithium amide–chiral diether complex.

NMR studies of a ternary complex reagent of lithium ester enolate, chiral diether, and lithium diisopropylamide in an asymmetric Michael reaction

A ternary complex reagent of lithium ester enolate–chiral diether–lithium diisopropylamide was formed in an equimolar mixture of these reagents in toluene based on low-temperature NMR spectroscopy. The use of [6Li,15N]-lithium diisopropylamide as a lithiodeprotonation and complexing reagent produced two sets of doublet peaks in 6Li NMR of a 1:1:1 mixture of lithium enolate–chiral diether–lithium diisopropylamide, indicating the formation of a ternary complex reagent.

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.

Chromium‐Mediated Dearomatization: Application to the Synthesis of Racemic 15‐Acetoxytubipofuran and Asymmetric Synthesis of Both Enantiomers

AbstractAn efficient dearomatization process of [Cr(arene)(CO)3] complexes initiated by a nucleophilic acetaldehyde equivalent is detailed. It generates in a one‐pot reaction three CC bonds and two stereogenic centers. This process allowed a rapid assembly of a cis‐decalin ring system incorporating a homoannular diene unit in just two steps starting from aromatic precursors (Scheme 2). The method was applied to the total synthesis of the eudesmane‐type marine furanosesquiterpene (±)‐15‐acetoxytubipofuran (2). Two routes were successfully used to synthesize the γ‐lactone precursor of the furan ring. The key step in the first approach was a Pd‐catalyzed allylic substitution (Scheme 3), while in the second approach, an Eschenmoser–Claisen rearrangement was highly successful (Scheme 4). The Pd‐catalyzed allylic substitution could be directed to give either the (normal) product with overall retention as major diastereoisomer or the unusual product with inversion of configuration (see Table). For the synthesis of the (−)‐enantiomer (R,R)‐2 of 15‐acetoxytubipofuran, an enantioselective dearomatization in the presence of a chiral diether ligand was implemented (Scheme 7), while the (+)‐enantiomer (S,S)‐2 was obtained via a diastereoselective dearomatization of an arene‐bound chiral imine auxiliary (Scheme 8). Chiroptical data suggest that a revision of the previously assigned absolute configuration of the natural product is required.

Asymmetric Reactions Based on Activation and Structure Control of Molecule — Asymmetric Reaction of Lithiated Nucleophiles

AbstractFor Abstract see ChemInform Abstract in Full Text.

Asymmetric reactions based on activation and structure control of molecule--asymmetric reaction of lithiated nucleophiles

The methodology we developed relies on an external chiral coordinating reagent that forms a deaggregated chelate complex with organolithium reagents. Under the positive control of a chiral dimethyl ether of stilbenediol 4, an asymmetric conjugate addition reaction of organolithium reagents with unsaturated imines and esters proceeded successfully to yield the corresponding addition products with reasonably high stereoselectivity. The sense of stereochemistry is predictable based on a coordination model. The methodology has been extended to a catalytic asymmetric 1,2-addition reaction of organolithium reagents with imines. An enantiotopic group differentiating the opening of cyclohexene oxide with organolithium was also mediated by a chiral ligand. The asymmetric Horner-Wadsworth-Emmons reaction of phosphonates and Peterson reaction of alpha-silylester with 4-substituted cyclohexanone were another successful extension of the methodology. A three-component reagent of lithium ester enolate, lithium amide, and chiral diether reacts with imines to afford beta-lactam with reasonably high enantioselectivity. Tridentate aminoether ligands were also shown to affect the catalytic asymmetric addition of lithium ester enoaltes to imines, giving beta-lactams with high enantioselectivity. Asymmetric conjugate addition of lithium amide to enoates was mediated by a chiral diether ligand to give the beta-aminoester with high yield and enatioselectivity. The methodology has been successfully applied to an asymmetric synthesis of biologically potent compounds. Dihydrexidine, a promising anti-Parkinsonism candidate, and salsolidine, a representative isoquinoline alkaloid, have been synthesized using asymmetric addition reactions of organolithium reagents as the key steps.

Design, Synthesis, and Application of a C2 Symmetric Chiral Ligand for Enantioselective Conjugate Addition of Organolithium to α,β-Unsaturated Aldimine

A C2 symmetric chiral diether ligand, (1R,2R)-1,2-dimethoxy-1,2-diphenylethane, was designed and synthesized on the basis of the concept of an asymmetric oxygen atom. Mediated by the chiral diether, high enantioselectivities were achieved in conjugate addition of organolithiums to naphthaldehyde imine and cyclic and acyclic α,β-unsaturated aldimines. The absolute configuration of the product is predictable by the model.

Spectroscopic Characterization of (Iodomethyl)zinc Reagents Involved in Stereoselective Reactions: Spectroscopic Evidence That IZnCH2I Is Not Zn(CH2I)2 + ZnI2 in the Presence of an Ether

We have shown that low-temperature 13C NMR spectroscopy is an extremely powerful technique for characterizing the (iodomethyl)zinc-derived reagents involved in the cyclopropanation reactions. This technique has allowed us to spectroscopically characterize and unambigously differentiate the Furukawa reagent (EtZnCH2I), the Simmons−Smith reagent (IZnCH2I), and the Wittig reagent (Zn(CH2I)2). Unique spectra are obtained for each of these reagents when they are complexed to a chiral diether. We have also demonstrated that IZnCH2I is not converted into Zn(CH2I)2 + ZnI2 in CD2Cl2 in the presence of a chiral complexing agent. Furukawa's reagent “EtZnCH2I”, however, is in equilibrium with Et2Zn and Zn(CH2I)2, and it eventually decomposes into PrZnI and EtZnI at room temperature. The decomposition of Zn(CH2I)2 into IZnCH2I and of IZnCH2I into ZnI2 was monitored by NMR. We have also demonstrated that the general trends observed for the various equilibria involving (iodomethyl)zinc-derived reagents follow those observed with ethylzinc-derived organometallic compounds.

ChemInform Abstract: Synthesis of Chiral Diether and Tetraether Phospholipids: Regiospecific Ring Opening of Epoxy Alcohol Intermediates Derived from Asymmetric Epoxidation.

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Synthesis of Chiral Diether and Tetraether Phospholipids: Regiospecific Ring Opening of Epoxy Alcohol Intermediates Derived from Asymmetric Epoxidation

Diether and tetraether phospholipids have been synthesized using chiral epoxy alcohol starting materials (e.g. glycidol 3-nitrobenzenesulfonate esters or tert-butyldiphenylsilyl ethers). These chiral precursors provide control over the stereochemistry, substitution patterns, and steric properties of the phosphoglycerol backbone. Configuration at the sn-2 glycerol carbon was controlled by asymmetric epoxidation of allyl alcohol followed by acid-catalyzed, regioselective opening of the oxirane ring using excess aliphatic n-alcohols to give mono-O-alkylated glycerol intermediates in good yields. 9 figs., 5 tabs.

ChemInform Abstract: Novel Strategy of Using a C2 Symmetric Chiral Diether in the Enantioselective Conjugate Addition of an Organolithium to an α,β‐Unsaturated Aldimine.

ChemInformVolume 21, Issue 5 Preparative Organic Chemistry ChemInform Abstract: Novel Strategy of Using a C2 Symmetric Chiral Diether in the Enantioselective Conjugate Addition of an Organolithium to an α,β-Unsaturated Aldimine. K. TOMIOKA, K. TOMIOKA Fac. Pharm. Sci., Univ. Tokyo, Bunkyo, Tokyo 113, Jap.Search for more papers by this authorM. SHINDO, M. SHINDO Fac. Pharm. Sci., Univ. Tokyo, Bunkyo, Tokyo 113, Jap.Search for more papers by this authorK. KOGA, K. KOGA Fac. Pharm. Sci., Univ. Tokyo, Bunkyo, Tokyo 113, Jap.Search for more papers by this author K. TOMIOKA, K. TOMIOKA Fac. Pharm. Sci., Univ. Tokyo, Bunkyo, Tokyo 113, Jap.Search for more papers by this authorM. SHINDO, M. SHINDO Fac. Pharm. Sci., Univ. Tokyo, Bunkyo, Tokyo 113, Jap.Search for more papers by this authorK. KOGA, K. KOGA Fac. Pharm. Sci., Univ. Tokyo, Bunkyo, Tokyo 113, Jap.Search for more papers by this author First published: January 30, 1990 https://doi.org/10.1002/chin.199005074AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume21, Issue5January 30, 1990 RelatedInformation

Novel strategy of using a C2 symmetric chiral diether in the enantioselective conjugate addition of an organolithium to an .alpha.,.beta.-unsaturated aldimine

Novel strategy of using a C2 symmetric chiral diether in the enantioselective conjugate addition of an organolithium to an .alpha.,.beta.-unsaturated aldimine