Chiral Acetals Research Articles

ChemInform Abstract: Toward the Development of a General Chiral α-Substituted Acetate Enolate Synthon for Aldolization. DMAP- and NEt3-Promoted Oxazolidinethione “Deacylation”.

ChemInform Abstract: Toward the Development of a General Chiral α-Substituted Acetate Enolate Synthon for Aldolization. DMAP- and NEt3-Promoted Oxazolidinethione “Deacylation”.

ChemInform Abstract: An Efficient Method for the Synthesis of Enantiopure cis-α,β-Epoxy Acids.

Abstract Enantiopure cis -α,β-epoxy acids were prepared via a modified Darzen's reaction employing the titanium-mediated bromination–aldolization of chiral acetate thioimide enolate.

ChemInform Abstract: Aldol Reactions with Erythrulose Derivatives: Stereoselective Synthesis of Differentially Protected syn-α,β-Dihydroxy Esters.

Boron enolates of 1-O-silylated erythrulose 3,4-acetonides prepared with Brown's chloro-dicyclohexylborane/tertiary amine system have been shown to react with achiral aldehydes in a highly stereoselective way to yield a 1,2-syn/1,3-syn stereoisomer. Through oxidative cleavage of the aldol adducts with periodic acid hydrate, enantiopure syn-α,β-dihydroxy esters with either hydroxyl group differently protected have been prepared. These erythrulose derivatives therefore behave as a chiral hydroxy acetate (glycolate) enolate equivalent.

ChemInform Abstract: Concerted Catalytic Reactions for Conversion of Ketones or Enol Acetates to Chiral Acetates.

[reaction: see text] Enol acetates or ketones asymmetrically transformed to chiral acetates in high yields with high optical purities through multistep reactions catalyzed by a lipase and a ruthenium complex. 2,6-Dimethylheptan-4-ol was chosen as a suitable hydrogen donor, and 4-chlorophenyl acetate was used as an acyl donor for the conversion of ketones.

ChemInform Abstract: Stereocontrol Between Remote Atom Centers Using Chiral Acetals and Its Application to Asymmetric Syntheses of Natural Products

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 of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Synthesis of Chiral Acetals by Asymmetric Selenenylations

Asymmetric selenenylations of (E)-ethoxystyrene are described leading to chiral acetals. An efficient synthesis of such compounds including the determination of their absolute configuration is described.

Enantioselective Route to Aryl(1,3-butadien-2-yl)methanols: Formal Synthesis of (-)-Sporochnol A

Ti(IV)-promoted reaction of the chiral acetals derived from aromatic aldehydes with l-(tri-n-butyl)stannyl-2,3-butadiene followed by removal of the chiral auxiliary gave aryl(1,3-butadien-2-yl)methanols with high enantiomeric purity (>90% ee). The synthetic utility of this method was demonstrated by the formal synthesis of (-)-sporochnol A, a terpene possessing a chiral benzylic quaternary carbon center.

Retention of Configuration in Photolytic Decarboxylation of Peresters to Form Chiral Acetals and Ethers

Peresters generate ethers in good yields when photolyzed in the absence of solvent using short wavelength UV light. At -78 degrees C or below, the process proceeds predominantly with retention of configuration at the site adjacent to the carbonyl where the decarboxylation occurs, but increase in temperature results in loss of stereochemical control. Chiral acyclic acetals can be prepared using precursors derived from tartaric or malic acids.

Synthesis of racemic and chiral albicanol, albicanyl acetate and cyclozonarone: cytotoxic activity of ent-cyclozonarone

The total synthesis of racemic cyclozonarone ((±)-3) was achieved from E,E-farnesol (4) in an eight-step sequence in 6.6% overall yield. Albicanol ((±)-1) and its acetate ((±)-2) are intermediates. A similar sequence starting from natural (-)-drimenol (5) gave (+)-albicanol (1) and (+)-cyclozonarone (3) (42% and 11% yield, respectively). The cytotoxic activity of (+)-cyclozonarone was assayed and showed some selectivity towards MS-1 (mice endothelial cells).

Development of an Asymmetric Acetate Aldol Reaction with a Trifluoromethyl Ketone

We describe the discovery and development of a chiral auxiliary-controlled asymmetric acetate aldol reaction with a trifluoromethyl ketone. Chiral acetate 3d was prepared efficiently from (1S,2R)-1-amino-2-indanol. Reaction of the lithium enolate of 3d with trifluoromethyl ketone 2 afforded aldol adducts in 95% HPLC assay yield (by weight) with a 78:22 dr. The major isomer 5 was obtained via a robust crystallization method in 45% one-crop isolated yield with a >98.7:1.3 dr. Compound 5 was subjected to transesterification to give β-hydroxy ester 1. The cleaved auxiliary 7 was readily recovered by a direct crystallization/filtration method. Process optimization led to better volume efficiencies, improved isolation protocols, and less consumption of organic solvents, all contributing to enhanced throughput, reduced processing labor and time, as well as reduction in chemical wastes.

A Cation-Exchange Resin Promoted Imino Aldol Reaction of Chiral Alkoxyketene Silyl Acetals with α,β-Unsaturated Imines, Leading to a Facile Synthesis of β-Lactams.

Imino aldol reaction of chiral ketene silyl acetals derived from 3-hydroxybutanoates with α,β-unsaturated imines proceeds smoothly to give β-amino esters in good yields with high syn-selectivity under the influence of a cation-exchange resin. Subsequent treatment with tert-butylmagnesium chloride gave β-lactams in a highly stereoselective manner.

Development of Highly Stereoselective Reactions Using Lone Pairs of Oxygen Atoms

AbstractFor Abstract see ChemInform Abstract in Full Text.

Development of Highly Stereoselective Reactions Using Lone Pairs of Oxygen Atoms

Highly stereoselective reactions have been developed using lone pairs of oxygen atoms, in other words, the nucleophilic ability of oxygen atoms. They consist of five types of reactions: 1) asymmetric synthesis using acetals, 2) organic reactions via Beckmann fragmentation intermediates, 3) organic reactions via dication equivalents, 4) rearrangement of 2,3-epoxy-1-alcohol derivatives, and 5) organic reactions using orthoesters. In this review, asymmetric syntheses using acetals are described in detail. They are divided into four categories: 1) diastereoselective 1,2-addition(alkylation, reduction) to the alpha-keto acetals and their derivatives, 2) asymmetric carbon-carbon bond formation by a combination of Beckmann fragmentation and asymmetric synthesis using C2-symmetric chiral acetals, 3) asymmetric synthesis via chiral oxonium ions prepared by intramolecular haloetherification of chiral ene acetals having C2-symmetric hydrobenzoin, and 4) asymmetric desymmetrization of meso-1,2-, meso-1,3-, and meso-1,4-diols via chiral oxonium ions prepared by intramolecular haloetherification of chiral ene acetals derived from optically pure norbornen aldehyde derivatives, and their applications to asymmetric syntheses of biologically active natural products.

Synthesis and evaluation of 7-hydroxyindan-1-one-derived chiral auxiliaries

A series of novel chiral acetals were prepared from 7-hydroxyindan-1-one and a variety of substituted chiral nonracemic C2-symmetric 1,2-ethanediols (R = Me, Ph, CH2OMe, CH2OBn, CH2O(1-Np), and i-Pr). These acetals were evaluated as chiral auxiliaries for use in asymmetric synthesis. A high degree of stereochemical induction was observed in the diethylaluminum chloride-promoted Diels–Alder reaction of an acrylate derivative (R = i-Pr) with cyclopentadiene (91:9 dr). This demonstrated that these acetals could serve as effective chiral directors in asymmetric substrate-directed reactions.Key words: 7-hydroxyindan-1-one, chiral nonracemic C2-symmetric 1,2-diols, acetals, chiral auxiliaries, Diels–Alder reaction.

Stereoselective TiCl4‐Promoted Nucleophilic Substitution at C‐2 of (4S,5S)‐2‐Alkyl‐4‐methyl‐5‐trifluoromethyl‐1,3‐dioxolanes.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Lipase/Ruthenium‐Catalyzed Dynamic Kinetic Resolution of β‐Hydroxyalkylferrocene Derivatives.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Evidence for a nucleophilic anti-attack on the cleaved C(2)–oxygen bond in Cl 2AlH-catalyzed ring-opening of 2-substituted 1,3-dioxolanes

The Cl 2AlH-mediated ring-opening of 2-substituted cis-4-methyl-5-trifluoromethyl-1,3-dioxolanes was found to occur with regioselective cleavage of the O1–C2 bond by attack of the aluminum hydride from the direction anti to the departing oxygen. This stereochemical outcome, which appears to be unprecedented in the reductive cleavage of chiral acetals by aluminum reagents, is interpreted on the basis of theoretical calculations.

Lipase/Ruthenium-Catalyzed Dynamic Kinetic Resolution of β-Hydroxyalkylferrocene Derivatives

National Research Laboratory of Chirotechnology, Department of Chemistry, Division of Molecular and Life Sciences,Pohang University of Science and Technology, Kyungbuk 790-784, KoreaReceived March 11, 2004An efficient dynamic kinetic resolution of racemic β-hydroxyalkylferrocene and 1,1'-bis(β-hydroxyalkyl)-ferrocene derivatives was achieved using lipase/ruthenium-catalyzed transesterification in the presence of anacyl donor. The racemic β-hydroxyalkylferrocene derivatives were successfully transformed to thecorresponding chiral acetates of high optical purities in high yields.Key Words : Dynamic kinetic resolution (DKR), Enzyme/metal bicatalysis, Lipase, β-HydroxyalkylferroceneIntroductionThe chiral ferrocene derivatives have been widely used aschiral ligands in asymmetric synthesis,

Aminocyclopentadienyl Ruthenium Complexes as Racemization Catalysts for Dynamic Kinetic Resolution of Secondary Alcohols at Ambient Temperature.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Efficient One‐Step Aldol‐Type Reaction of Ketones with Acetals and Ketals Mediated by Dibutylboron Triflate/Diisopropylethyl Amine.

A highly efficient one-step Mukaiyama aldol-type reaction has been developed for the synthesis of β-alkoxy carbonyl compounds starting from ketones and acetals/ketals. The reaction is mediated by a combination of Bu2BOTf and i-Pr2NEt affording the products in high yields. Formation of the two possible diastereoisomers of the β-alkoxy ketones from the chiral acetals shows that the condensation takes place by an SN1 mechanism, involving prior opening of the acetal to an oxonium ion.