A structural analysis of the complexes of (S,S)-dimethylpyridino-18-crown-6 with (R) and (S)-[α-(1-naphthyl)ethyl]ammonium perchlorate by NMR techniques and molecular modeling

Significant - interaction is found in the complexes of (S, S)-dimethylpyridino-18-crown-6 with (R)- and (S)-[-(1-naphthyl)ethyl]ammonium perchlorate. This finding is supported by the¹H NOESY NMR spectral technique, greater chemical shift changes of aromatic protons in both host and guest molecules upon complexation, and by molecular mechanics calculations. Because of the flexibility of the ligand, the tripod hydrogen bonding causes¹³C relaxation times of all periphery carbons to decrease without significant selectivity. Rotational energy barrier calculations of the methyl groups of the complexed ligand also show that the (S, S)-host-(R)-guest is the more stable complex.     

The use of (S)-(−)-1-(1-naphthyl)ethylamine as a resolving agent for α-methoxy fatty acids

A general method was developed for the diastereoselective resolution of α-methoxy fatty acids utilizing (S)-(−)-1-(1-naphthyl)ethylamine as resolving agent. The diastereomeric amides can be easily separated by silica gel column chromatography and/or capillary gas chromatography, thus allowing for a preparative and analytical method for determining the enantiomeric purity of naturally occurring and/or synthetic α-methoxy fatty acids. The first synthesis of the naturally occurring (R)-2-methoxyhexadecanoic acid was also accomplished in four steps starting from commercially available (±)-2-hydroxyhexadecanoic acid.     

The synthesis of (R)- and (S)-α-trifluoromethyl-α-hydroxycarboxylic acids via enzymatic resolutions

Kinetic resolution of 1,1,1-trifluoro-2-alkanone cyanohydrin acyl derivatives with Candida rugosa lipase afforded the remaining (R)-enantiomer in high selectivity (E from 30 to >200). Candida rugosa lipases from several suppliers were compared and found to differ remarkably in their selectivity. The (R)-enantiomer was hydrolyzed in one step to yield optically pure (R)-α-trifluoromethyl-α-hydroxycarboxylic acids in excellent yield. The (S)-acids were obtained in good e.e. by subtilisin-catalyzed resolution of the corresponding racemic esters followed by chemical hydrolysis of the remaining (S)-esters.     

Enantioselective synthesis of (S)- and (R)-α-methylserines: application to the synthesis of (S)- and (R)-N-Boc-N,O-isopropylidene-α-methylserinals

This report describes the synthesis of enantiomerically pure (S)- and (R)-α-methylserines on a multigram scale, starting from the Weinreb amide of 2-methyl-2-propenoic acid and using a stereodivergent synthetic route that involves a Sharpless asymmetric dihydroxylation reaction. As a synthetic application of these quaternary α-amino acids, they were used as starting materials in the synthesis of the well-known valuable homochiral (S)- and (R)-N-Boc-N,O-isopropylidene-α-methylserinal building blocks.     

Molecular recognition as shown by the solvent extraction of (R)- and (S)-[α-(1-naphthyl)ethyl] ammonium picrate or orange 2 by chiral pyridino-crown ethers

A solvent extraction technique was used to determine equilibrium constants for the reactions occurring when an aqueous phase containing [-(1-naphthyl)ethyl]ammonium ions [(R)- and (S-isomers] is equilibrated with a chloroform phase containing chiral substituted pyridino-18-crown-6 ligands. Selectivity coefficients and equilibrium constants for the interactions in chloroform solutions were calculated. The existence of two different types of ion pairs separated by the macrocycle molecule was detected from the UV spectra. One ion pair has a nearly complete separation of the picrate anion from the protonated amine by the ligand. The other has the picrate ion only partly separated from the cation by the macrocycle.     

An NMR study of inclusion complexes formed by α-cyclodextrin and (R)- or (S)-α-lipoic acid

A ¹H NMR study that explored the ability of α-cyclodextrin (α-CD) to preferentially bind (R)-α-lipoic acid is presented. The interaction between α-CD and (R)-α-lipoic acid was found to be stronger than that between α-CD and (S)-α-lipoic acid. Structures for the (R)-α-lipoic acid/α-CD and (S)-α-lipoic acid/α-CD inclusion complexes were constructed using restraints derived from ROESY spectra and MM2 molecular mechanics calculations. The models built for both complexes have the 1,2-dithiolane ring and the carboxyl moiety of α-lipoic acid oriented toward the secondary and primary hydroxy sides of α-CD, respectively.     

Efficient resolution of (±)-pantolactone by inclusion crystallization with the use of chiral 1,1,2-triphenylethane-1,2-diol

Enantioselective formation of crystalline 1 : 1 host—guest complexes with (R)-or (S)-1,1,2-triphenylethane-1,2-diol as a host compound allows efficient preparative resolution of (±)-pantolactone. Optically active pantolactones (98%ee) were obtained in 65–67% yield. Published inIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1489–1490, August, 2000.     

Dynamic kinetic resolution of racemic N-phthalyl amino acids using (S)-α-methylpantolactone as the chiral auxiliary

A dynamic kinetic resolution of racemic N-phthalyl amino acids by stereoselective esterification was examined using (S)-α-methylpantolactone as the chiral auxiliary. The reaction of various racemic N-phthalyl amino acids with this chiral alcohol in the presence of both DCC and DMAP afforded predominantly the (S,S)-esters in nearly quantitative yield.     

Interconversion of (R) and (S)-α-hydroxy esters: precursors of (S) and (R)-o-benzyl-α-hydroxylamino acid esters of high optical purity

(R)- and (S)-α-hydroxy esters 5 are interconverted via their triflates 6 in high chemical as well as optical yields by reaction with dimethylformamide. The same triflates are efficiently converted into N-hydroxy-α-amino acid derivatives 7 of high optical purity.     

Enantioselective synthesis of (S)- and (R)-6-hydroxy-8-nonene-carboxylates by asymmetric catalysis: a formal synthesis of (R)-α-lipoic acid and its (S)-antipode

A short and efficient enantioselective synthesis of (S)- and (R)-configured 6-hydroxy-8-nonene-carboxylates — precursors to (R)-α-lipoic acid and its (S)-enantiomer — by allylation of alkoxycarbonyl substituted aldehydes with allyltrimethylstannane and BINOL/Ti(OiPr)₄ catalyst is described. The best results in terms of enantiomeric purity and yield are obtained employing 10 mol% of the titanium-species without molecular sieves.     

Halo-substituted (S)-N-(2-benzoylphenyl)-1-benzylpyrolidine-2-carboxamides as new chiral auxiliaries for the asymmetric synthesis of (S)-α-amino acids

The synthesis of new chiral auxiliaries (S)-N-(2-benzoylphenyl)-1-(3,4-dichlorobenzyl)-pyrrolidine-2-carboxamide (1a), (S)-N-(2-benzoylphenyl)-1-(pentafluorobenzyl)pyrrolidine-2-carboxamide (1b), and (S)-N-(2-benzoylphenyl)-1-(4-isopropoxytetrafluorobenzyl)pyrrolidine-2-carboxamide (1c) and their application in the asymmetric synthesis of amino acids using Ni^II complexes of their Schiff"s bases with alanine and glycine are described. Compound 1a is particularly appropriate for highly stereoselective synthesis of -methyl--amino acids with high enatiomeric purity (ee >95%).     

The imine (+)-pseudoephedrine glycinamide: a useful reagent for the asymmetric synthesis of (R)-α-amino acids

The new imine derived from Myers (+)-pseudoephedrine glycinamide can be diastereoselectively alkylated with alkyl halides at room temperature using NaOEt or LiO-tert-Bu as bases under phase transfer conditions. Hydrolysis to the corresponding alkylated products was easily achieved under mild conditions to afford (R)-α-amino acids.     

Deracemisation of α-amino acids—(R)- and (S)-phenylalanine from the same enantiomer of a homochiral auxiliary

Chiral auxiliary (3S)-N,N′-bis-(p-methoxybenzyl)-3-isopropylpiperazine-2,5-dione 1 was employed for the synthesis of both enantiomers of phenylalanine using a regioselective deprotonation/stereoselective reprotonation strategy. Modification of this approach enables the efficient deracemisation of (±)-phenylalanine.     

(S)-(−)-Fluorenylethylchloroformate (FLEC); preparation using asymmetric transfer hydrogenation and application to the analysis and resolution of amines

Fluorenylethylchoroformate (FLEC) is a valuable chiral derivatisation reagent that is used for the resolution of a wide variety of chiral amines. Herein, we describe an improved preparation of (S)-(−)-FLEC using an efficient asymmetric catalytic transfer hydrogenation as the key step. We also demonstrate the application of FLEC as a chiral Fmoc equivalent for chiral resolution, with facile deprotection, of tetrahydroquinaldines, and its capacity for inducing regioselective outcomes in nitration reactions.     

Acidic Derivative of Per(3,6-anhydro)-α-cyclodextrin: Preparation and a First Evaluation of Its Affinity for Lanthanides by 1 H NMR

We report on the first synthesis ofhexakis(2-O-carboxymethyl-3,6-anhydro)--cyclodextrin,an acidic derivative of per(3,6-anhydro)--cyclodextrin.Preliminary qualitative tests showed that thisnew compound would have greater affinity for lanthanides,cobalt and uranyl cations, thanfor sodium, potassium and calcium physiological ions.     

Asymmetric synthesis of (S)- and (R)-α-methylserine based on the chiral recyclable reagent (S)-N-(2-benzoyl-phenyl)-1-benzylpyrrolidine-2-carboxamide

Both enantiomers of -methylserine were synthesized with the use of Ni^II complexes based on the chiral recyclable reagent (S)-N-(2-benzoylphenyl)-1-benzylpyrrolidine-2-carboxamide. Intermediate diastereomeric complexes were separated by crystallization of their O-acetyl derivatives.