Chiral Quaternary Ammonium Salts Research Articles

Synthesis of α-diazo-β-hydroxyesters through a one-pot protocol by phase-transfer catalysis: application to enantioselective aldol-type reaction and diastereoselective synthesis of α-amino-β-hydroxyester derivatives

The one-pot synthesis of α-diazo-β-hydroxyesters from sodium azide under phase-transfer-catalyzed conditions has been achieved. This protocol includes three different chemical transformations promoted by a single catalyst in each step to give products in good to excellent yields. The reaction was applied to a catalytic asymmetric aldol-type reaction using α-diazoesters with aldehydes in the presence of a chiral quaternary ammonium salt and gave products with up to 81% ee. The diastereoselective transformation of the products to chiral α-amino-β-hydroxyester derivatives is also described.

Asymmetric Michael Addition of Glycine Imines via Quaternary Ammonium Ion Catalysis.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Asymmetric Michael addition of glycine imines via quaternary ammonium ion catalysis

The asymmetric Michael addition of glycine imine esters to simple α,β-unsaturated ketones via PTC is investigated. It is found that by employing 1 mol % of a chiral quaternary ammonium salt, derived from α-methylnaphthylamine in conjunction with Cs 2CO 3, high enantioselectivities can be obtained in conjugate additions involving simple alkylvinylketones.

Highly Enantioselective Phase-Transfer-Catalyzed Alkylation of Protected α-Amino Acid Amides toward Practical Asymmetric Synthesis of Vicinal Diamines, α-Amino Ketones, and α-Amino Alcohols

Highly enantioselective alkylation of protected glycine diphenylmethyl (Dpm) amide 1 and Weinreb amide 10 has been realized under phase-transfer conditions by the successful utilization of designer chiral quaternary ammonium salts of type 4 as catalyst. Particularly, remarkable reactivity of the chiral ammonium enolate derived from 1b and 4c allowed the reaction with less reactive simple secondary alkyl halides with high efficiency and enantioselectivity. An additional unique feature of this chiral ammonium enolate is its ability to recognize the chirality of beta-branched primary alkyl halides, which provides impressive levels of kinetic resolution and double stereodifferentiation during the alkylation, allowing for two alpha- and gamma-stereocenters to be controlled. Combined with the subsequent reduction using LiAlH4 in cyclopentyl methyl ether (CPME), this system offers a facile access to structurally diverse optically active vicinal diamines. Furthermore, the optically active alpha-amino acid Weinreb amide 11 can be efficiently converted to the corresponding amino ketone by a simple treatment with Grignard reagents. In addition, reduction and alkylation of the optically active alpha-amino ketone into both syn and anti alpha-amino alcohols with almost complete relative and absolute stereochemical control have been achieved. With (S,S)- and (R,R)-4 in hand, the present approach renders both enantiomers of alpha-amino amides including Weinreb amides readily available with enormous structural variation and also establishes a general and practical route to vicinal diamines, alpha-amino ketones, and alpha-amino alcohols with the desired stereochemistry.

Catalytic Enantioselective Fluorination of α‐Cyano Esters by Phase‐Transfer Catalysis Using Chiral Quaternary Ammonium Salts.

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A simple catalytic route to naproxen

We report herein the asymmetric synthesis of naproxen involving catalytic enantioselective methylation for the first time. The reaction is conducted in a solid–liquid biphasic system using chiral quaternary ammonium salts.

Enantioselective Alkylation of β‐Keto Esters by Phase‐Transfer Catalysis Using Chiral Quaternary Ammonium Salts.

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Highly Enantioselective Dimerization of α,β‐Enones Catalyzed by a Rigid Quaternary Ammonium Salt.

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Development of Highly Diastereo‐ and Enantioselective Direct Asymmetric Aldol Reaction of a Glycinate Schiff Base with Aldehydes Catalyzed by Chiral Quaternary Ammonium Salts.

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Catalytic Enantioselective Fluorination of α-Cyano Esters by Phase-Transfer Catalysis Using Chiral Quaternary Ammonium Salts

Catalytic Enantioselective Fluorination of α-Cyano Esters by Phase-Transfer Catalysis Using Chiral Quaternary Ammonium Salts

Asymmetric Phase‐Transfer Catalysis Utilizing Chiral Quaternary Ammonium Salts: Asymmetric Alkylation of Glycine Imines.

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Asymmetric Michael Reaction Promoted by New Chiral Phase‐Transfer Catalysts.

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Enantioselective alkylation of beta-keto esters by phase-transfer catalysis using chiral quaternary ammonium salts.

Catalytic enantioselective alkylation promoted by a quaternary ammonium salt from cinchonine as a phase transfer catalyst is described. Treatment of cyclo beta-keto esters with alkyl halide under mild reaction conditions afforded the corresponding alpha-alkylated beta-keto esters in moderate to excellent yields with high enantiomeric excesses

Highly enantioselective dimerization of alpha,beta-enones catalyzed by a rigid quaternary ammonium salt.

[reaction: see text] The chiral quaternary ammonium salt 1 served as a phase-transfer catalyst for the enantioselective dimerization of alpha,beta-enones, providing a route for the asymmetric syntheses of chiral 1,5-dicarbonyl compounds and alpha-alkylated gamma-keto acids.

Poly(ethylene glycol) Supported Chiral Quaternary Ammonium Salts as Phase‐Transfer Catalysts for Catalytic Enantioselective Synthesis of α‐Amino Acids.

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Enantioselective Iodolactonization Catalyzed by Chiral Quaternary Ammonium Salts Derived from Cinchonidine.

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Development of highly diastereo- and enantioselective direct asymmetric aldol reaction of a glycinate Schiff base with aldehydes catalyzed by chiral quaternary ammonium salts.

A highly efficient direct asymmetric aldol reaction of a glycinate Schiff base with aldehydes has been achieved under mild organic/aqueous biphasic conditions with excellent stereochemical control, using chiral quaternary ammonium salt 1b as a phase-transfer catalyst. The initially developed reaction conditions, using 2 equiv of aqueous base (1% NaOH (aq)), exhibited inexplicably limited general applicability in terms of aldehyde acceptors. The mechanistic investigation revealed the intervention of an unfavorable yet inevitable retro aldol process involving the chiral catalyst. On the basis of this information, a reliable procedure has been established by use of a catalytic amount of 1% NaOH (aq) and ammonium chloride, which tolerates a wide range of aldehydes to afford the corresponding anti-beta-hydroxy-alpha-amino esters almost exclusively in an essentially optically pure form.

Highly Enantioselective Synthesis of No‐Carrier‐Added 6‐[18F]Fluoro‐L‐dopa by Chiral Phase‐Transfer Alkylation

Abstract[18F]Fluoro‐L‐dopa, an important radiopharmaceutical for positron emission tomography (PET), has been synthesized using a phase‐transfer alkylation reaction. A chiral quaternary ammonium salt derived from a Cinchona alkaloid served as phase‐transfer catalyst for the enantioselective alkylation of a glycine derivative. The active methylene group of this Schiff‐base substrate was deprotonated with cesium hydroxide and rapidly alkylated by the 2‐[18F]fluoro‐4,5‐dimethoxybenzyl halide (X = Br, I). The reaction proceeded with high yield (> 90%) at 0 °C or room temperature in various solvents such as toluene or dichloromethane. Preparation of the [18F]alkylating agent on a solid support was developed. After labelling, the labeled [18F]fluoroveratraldehyde was trapped on a tC18 cartridge and then converted on the cartridge into the corresponding benzyl halide derivatives by addition of aqueous sodium borohydride and gaseous hydrobromic or ‐iodic acid. Hydrolysis and purification by preparative HPLC made 6‐[18F]fluoro‐L‐dopa ready for human injection in a 25−30% decay‐corrected radiochemical yield in a synthesis time of 100 min. The product was found to be chemically, radiochemically and enantiomerically pure (ee > 95%). (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2004)

Poly(ethylene glycol) Supported Chiral Quaternary Ammonium Salts as Phase-Transfer Catalysts for Catalytic Enantioselective Synthesis of α-Amino Acids

and Sun Chul Huh Department of Chemistry, Soonchunhyang University, Asan P.O. Box 97, Chungnam 336-600, KoreaReceived December 26, 2003Key Words : Phase-transfer, Polymer supported catalyst, α-Amino acids, Chiral ammonium salt, AsymmetricreactionsThe enantioselective synthesis of α-amino acids usingchiral phase transfer catalysts derived from cinchona alkaloidshas been widely studied over the last decade.

Enantioselective iodolactonization catalyzed by chiral quaternary ammonium salts derived from cinchonidine.

Chiral quaternary ammonium salts derived from cinchonidine have been applied to catalyze the stereoselective iodolactonizations of trans-5-aryl-4-pentenoic acids leading to a mixture of two regioselectively iodolactonized products with fair to excellent yield (37-98%) and moderate enantioselectivity (exo = 42.0% ee, endo = 31.0% ee) under mild conditions. This work is the first example of asymmetric iodolactonization reaction in the presence of less than a stoichiometric amount of chiral reagent.