Enantioselective Desymmetrization Research Articles

Catalytic enantioselective desymmetrization of COT-monoepoxide. Maximum deviation from coplanarity for an S(N)2'-cuprate alkylation.

[reaction: see text] The first alkylative and enantioselective ring-opening of COT-monoepoxide (1) without the occurrence of any ring-contraction-isomerization by the use of in situ-formed organocuprates is reported. Because of the particular geometric constraint of compound 1, this work reports the largest deviation from coplanarity between the pi-orbital of the double bond and the sigma-bond connecting the leaving group ever observed for an S(N)2'-cuprate alkylation.

Copper‐Catalysed Addition of Organometallic Reagents to Vinyl Diepoxides − A Novel Route to Oxa‐Bridged Systems and to Substituted Allylic Alcohols

AbstractThe copper‐catalysed addition of organometallic reagents (Grignard and dialkylzinc) to new vinyl diepoxides was examined. Cyclic vinyl diepoxides undergo clean SN2′ reactions to afford oxa‐bridged systems of various sizes after a domino intramolecular O‐alkylation reaction. Acyclic vinyl diepoxides are alkylated in good yields and with good regioselectivities, and a new catalytic enantioselective desymmetrization reaction to afford an enantioenriched allylic epoxy alcohol by the use of catalytic amounts of a copper phosphoramidite complex was demonstrated. Remarkable differences in terms of reactivity and selectivity are found when different organocopper reagents, generated in situ, are employed. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)

Lipase-catalyzed stereoselective resolution and desymmetrization of binaphthols

We have investigated the use of lipoprotein lipase enzymes from Pseudomonas sp. and Pseudomonas fluorescens for the enantioselective resolution and desymmetrization of racemic binaphthols. The reactions were carried out using a non-aqueous environment (iPr 2O/acetone/vinyl acetate), and yielded mono-acetate ester products of the parent unsubstituted substrate, the 6,6′-dibromo-substrate, and the 6,6′-dimethoxy-substrate with high enantiomeric selectivity.

A catalytic and enantioselective desymmetrization of meso cyclic allylic bisdiethylphosphates with organozinc reagents.

A catalytic and enantioselective desymmetrization of meso cyclic allylic bisdiethylphosphates with organozinc reagents.

A Catalytic and Enantioselective Desymmetrization of meso Cyclic Allylic Bisdiethylphosphates with Organozinc Reagents

A Catalytic and Enantioselective Desymmetrization of <i>meso</i> Cyclic Allylic Bisdiethylphosphates with Organozinc Reagents

Beyond Breaking the MirrorPlane: The Desymmetrisation of Centro­symmetric Moleculesas an Efficient Strategy for Asymmetric Synthesis

Enantioselective desymmetrisation is one of the most effective strategies for asymmetric synthesis. Typically, a meso starting material with an internal mirror plane is desymmetrised by reaction with a chiral reagent; excellent yields of products as single enantiomers may be obtained. In fact, this approach is amenable to the synthesis of compounds with any embedded improper element of symmetry (such as a centre of symmetry). This review concentrates on the strategies, which are available for the synthesis of centrosymmetric (and S 4-symmetric) molecules and describes methods for their desymmetrisation. Examples of syntheses of biologically active molecules and natural products are used.

Enantioselective Desymmetrization of Tropinone Derivatives by Hydroboration

N-Protected tropenone derivs. I (R = CO2Me, CBZ, Ts) prepd. from the resp. pyrroles and tetrabromoacetone, were used as starting materials for desymmetrization by hydroboration of the C-C double bond. Hydroboration of I with (-)-(Ipc)2BH followed by oxidn., however, gave the desired 6-hydroxylated product only in low yield due to byproduct formation. After acetalization of the carbonyl group in I, the corresponding acetals were desymmetrized with (Ipc)2BH and oxidative workup to chiral alcs. II in good yields with excellent enantiomeric excesses in most cases.

New Cyclization Reactions in Organic Syntheses

Recent development in the transition metal-catalyzed cyclization reactions for organic syntheses in the author's laboratories is summarized, which includes (i) novel silyl- carbocyclizations (SiCaCs) and carbonylative carbotricyclizations, (ii) intramolecular silyl- formylations and desymmerization of siloxydiynes by sequential double silylformylation, (iii) efficient total synthesis of (+)-prosopinine, (iv) enantioselective desymmetrization of aminodienes, and (iv) new and efficient routes to 1-azabicyclo(x.y.0)alkane amino acids. All these processes are catalyzed by Rh or Rh-Co complexes, and useful for rapid and efficient construction of a variety of heterocyclic and carbocyclic compounds. Mechanisms of these new carbocyclization and cyclohydrocarbonylation reactions are also discussed. It has been the central focus in modern organic synthesis to develop highly efficient catalytic processes for the syntheses of natural and unnatural compounds of medicinal interest or intermediates useful for functional materials. One of the most attractive approaches to such aims is to apply transition metal-cat- alyzed cyclization reactions for the transformations of simple starting materials into monocyclic, bicyclic, and polycyclic scaffolds that can be further elaborated into specific targets. This account describes new and useful cyclization processes based on silylcarbocyclization (SiCaC), silylformylation, and cyclohydrocarbonylation reactions, which have recently been developed in these laboratories and will find many applications in organic syntheses.

Enantioselective Desymmetrization of Meso Bicyclic Hydrazines: A Novel Approach to the Asymmetric Synthesis of Polysubstituted Amino Cyclopentanic Cores.

AbstractFor Abstract see ChemInform Abstract in Full Text.

ChemInform Abstract: Highly Enantioselective Desymmetrization of Anhydrides by Carbon Nucleophiles: Reactions of Grignard Reagents in the Presence of (‐)‐Sparteine.

AbstractChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Enantioselective desymmetrization of a phospholene meso-epoxide

Cinchona alkaloids serve as effective chiral bases in the enantioselective rearrangement of 3-phospholene epoxide. The reaction results in the formation of a P, C-chirogenic 3-hydroxy-2-phospholene derivative with up to 52% e.e. A stereochemical course for the epoxide rearrangement involving anti-β-proton abstraction is implied.

Enantioselective desymmetrization of meso bicyclic hydrazines: a novel approach to the asymmetric synthesis of polysubstituted amino cyclopentanic cores.

Catalytic asymmetric hydroboration can be successfully applied to meso bicyclic hydrazines. The resulting alcohols are of great synthetic interest and can lead in a straightforward manner to cyclopentanic diamino alcohols with good enantiomeric purity.

Highly enantioselective desymmetrization of anhydrides by carbon nucleophiles: reactions of Grignard reagents in the presence of (-)-sparteine.

Highly enantioselective desymmetrization of anhydrides by carbon nucleophiles: reactions of Grignard reagents in the presence of (-)-sparteine.

Highly Enantioselective Desymmetrization of Anhydrides by Carbon Nucleophiles: Reactions of Grignard Reagents in the Presence of (−)-Sparteine

Wo andere chirale Liganden scheiterten, konnte (−)-Spartein erfolgreich zur Komplexierung von Grignard-Reagentien verwendet werden, mit denen die Desymmetrisierung einer Reihe von Anhydriden mit guter Enantioselektivität gelang (bis zu 92 % ee; siehe Schema). Durch (−)-Spartein chiral modifizierte Organolithiumreagentien sind in der asymmetrischen Synthese gut etabliert, doch entsprechende (−)-Spartein-kontrollierte Reaktionen mit Grignard-Reagentien sind noch selten.

New cyclization reactions in organic syntheses

Abstract Recent development in the transition metal-catalyzed cyclization reactions for organic syntheses in the author's laboratories is summarized, which includes (i) novel silylcarbocyclizations (SiCaCs) and carbonylative carbotricyclizations, (ii) intramolecular silylformylations and desymmerization of siloxydiynes by sequential double silylformylation, (iii) efficient total synthesis of (+)-prosopinine, (iv) enantioselective desymmetrization of aminodienes, and (iv) new and efficient routes to 1-azabicyclo[x.y.0]alkane amino acids. All these processes are catalyzed by Rh or Rh­Co complexes, and useful for rapid and efficient construction of a variety of heterocyclic and carbocyclic compounds. Mechanisms of these new carbocyclization and cyclohydrocarbonylation reactions are also discussed.

Enantiodivergent Synthesis of Either Enantiomer of ABCDE-Ring Analogue of Antitumor Antibiotic Fredericamycin A via Intramolecular [4 + 2] Cycloaddition Approach

[reaction: see text] An intramolecular enantiodivergent synthesis of both enantiomers of the ABCDE-ring analogue 22 of fredericamycin A is reported. Key steps involve an intramolecular [4 + 2] cycloaddition of 17 and an aromatic Pummerer-type reaction of 19. A lipase-catalyzed enantioselective desymmetrization of prochiral diol 2 using 1-ethoxyvinyl 2-furoate 3 led to the pivotal intermediate (R)-4.

Lipase-catalyzed enantioselective desymmetrization of prochiral 3,3-bis(hydroxymethyl)oxindoles

Oxindoles 3b–d (91–98% ee) having a chiral quaternary carbon center at the C-3 position were prepared from readily available oxindoles 5a–c in 50–64% overall yields, in which an enantioselective desymmetrization of prochiral 1,3-diols 2b–d using a Candida rugosa lipase (Meito OF) and 1-ethoxyvinyl 2-furoate 1 was employed as the key step.

Enantioselective Desymmetrization ofmeso-Decalin Diallylic Alcohols by a New Zr-Based Sharpless AE Process: A Novel Approach to the Asymmetric Synthesis of PolyhydroxylatedCelastraceae Sesquiterpene Cores

Enantioselective Desymmetrization ofmeso-Decalin Diallylic Alcohols by a New Zr-Based Sharpless AE Process: A Novel Approach to the Asymmetric Synthesis of PolyhydroxylatedCelastraceae Sesquiterpene Cores

Enantioselective Desymmetrization of meso-Decalin Diallylic Alcohols by a New Zr-Based Sharpless AE Process: A Novel Approach to the Asymmetric Synthesis of Polyhydroxylated Celastraceae Sesquiterpene Cores

Enantioselective Desymmetrization of meso-Decalin Diallylic Alcohols by a New Zr-Based Sharpless AE Process: A Novel Approach to the Asymmetric Synthesis of Polyhydroxylated Celastraceae Sesquiterpene Cores

Enantioselective Desymmetrization of meso-Decalin Diallylic Alcohols by a New Zr-Based Sharpless AE Process: A Novel Approach to the Asymmetric Synthesis of Polyhydroxylated Celastraceae Sesquiterpene Cores AE=Asymmetric epoxidation. Grateful acknowledgement is made to the EPSRC for a QUOTA studentship (S.J.W.) and to Pfizer (Drs. Alan R. Brown and John P. Mathias) for financial support of this work.

Zirconium to the rescue! Eight contiguous chiral centers can be established with >95 % ee in the key step of an asymmetric synthetic approach to the cores of certain Celastraceae sesquiterpenes (see scheme). The route required the development of a new zirconium-modified Sharpless asymmetric epoxidation instead of the traditional titanium version. DIPT=diisopropyl tartrate.