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.     

Regio- and stereoselective methods for the conversion of (2S,3R)-β-phenylglycidic acid esters to taxoids and other enantiopure (2R,3S)-phenylisoserine esters

A novel efficient method was proposed for the synthesis of enantiopure precursors of taxane-containing cytostatics, i.e., methyl esters of (2R,3S)- and (2S,3R)-N-benzoylphenylisoserine and similar taxoid esters. The method is based on the regio- and stereoselective hydrobromolysis of the corresponding trans-β-phenyl glycidate enatiomers, consecutive reactions of O-acylcarbamoylation of the obtained 3-bromohydrins, intramolecular cyclization to 4-phenyloxazolidin-2-one-5-carboxylic acid derivatives, and oxazolidinone ring opening.     

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)-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.     

Electroreductive five- and six-membered cyclization of aromatic β- and γ-imino esters derived from (S)-aspartic acid and (S)-glutamic acid

The electroreduction of aromatic β-dimethylcarbamoyl-β-imino esters, prepared from (S)-aspartic acid, in the presence of chlorotrimethylsilane gave five-membered cyclized products, 1-benzoyl-4-hydroxy-5-aryl-N,N-dimethylpyrrolidine-2-carboxamides and 5-(dimethylcarbamoyl)-2-aryl-1H-pyrrol-3-yl benzoates, depending on the post-treatment after the electroreduction. The electroreduction of aromatic γ-dialkylcarbamoyl-γ-imino and γ-methoxylmethyl-γ-imino esters, prepared from (S)-glutamic acid, and following transformation gave six-membered cyclized products, 1-benzoyl-5-hydroxy-N,N-dialkyl-6-phenylpiperidine-2-carboxamides and 3-hydroxy-6-(methoxymethyl)-2-phenylpiperidin-1-yl)(phenyl)methanones, respectively.     

Synthesis of optically pure (R)- or (S)-α-fluoro-α-methyl-β-ketoesters

A number of optically pure (R)- or (S)-α-fluoro- α-methyl-β-ketoesters were prepared by the reaction of the optically pure acid chlorides made from the corresponding (R)- or (S)-α-fluoro-α-methylmalonic acid monoethyl esters with alkyl (or aryl) cuprates.     

Synthesis of alkylN-(α-amidomethyl)glycinates from glycine esters,aroylamides, and formaldehyde

A one-step synthesis of alkylN-(-amidomethyl)glycinates from glycine esters or their salts, formaldehyde, and aroylamides was developed. The effect of the structure of the amide component and the reaction conditions on the yields of the products was investigated.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 6, pp. 1078–1080, June, 1994.     

Efficient synthesis of (−)-(R)- and (+)-(S)-rolipram

A novel, efficient and protecting group free enantioselective synthetic approach of (?)-(R)-1 and (+)-(S)-rolipram 2 is described employing the organocatalyzed asymmetric Michael addition, Henry condensation, Wittig olefination and reductive lactamization reactions as key steps.     

Synthesis of (4R)-α-Terpineol

Thesynthesisofopticallyactivecompoundsisanimportantissueinmodemorgan-icchendstry-7-Terpineol,anaturalproductisolatedfrompetitgrainoil,longleafpineoi1andcaeputoill'J,hasbeenasynthetictargetduringthecourseofourstudiesontheasymmetriccatalisedDiels-AlderreactionlvInthispaper,l-phenylsulfOnyl-3-buten-2-one(l)wasusedasthesulfOnyl-functionalizedche1atingenoneforthesynthesischiral2-Terpineol(5)byaasymmetriccata1isedDiels-Alderreaction.TherouteforthesynthesisofopticallyaCtivea-Terpineo1(5)isshownin…     

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.     

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.     

Versatile Approach for the Asymmetric Synthesis of (R)‐ and (S)‐Massoialactones

A general synthetic approach to both enantiomers, (R)‐ and (S)‐massoialactones, has been devised from commercially available (S)‐butane‐1,2,4‐triol.     

Preparative asymmetric synthesis of (R)- and (S)-α-methylserine Ni(II) complex with a Schiff base of α-alanine and (S)-2-[(N-benzylprolyl)amino]benzophenone

The kinetic and thermodynamic diastereoselectivity of the hydroxymethylation of the alanine fragment in the Ni(II) complex of the Schiff base of alanine and (S)-2-[(N-benzylprolyl)amino]benzophenone (BBP) was studied. Optically pure (R)- and (S)--methylserines were synthesized.Translated from Izvestiya Akademii Nauk SSSR, Seriya Khimicheskaya, No. 5, pp. 1175–1180, May, 1991.     

A simple synthesis of (−)-(R)-ipsdienol and (−)-(S)-ipsenol

A short and efficient synthesis of the unnatural enantiomer of (+)-(S)-ipsdienol 1 and (−)-(S)-ipsenol 2 is presented via an asymmetric allylboration. The synthesis was achieved by using a one-pot reduction–methylenation of an exo-methylene lactone intermediate.     

Optically active α-hydroxy-α-(tetrahydroquinoxalin-3-on-2-yl)esters by ring transformation of (R,R)-diethyl oxirane-2,3-dicarboxylate

The reaction of (R,R)-diethyl oxirane-2,3-dicarboxylate 6 with o-phenylendiamines 7 and 1,8-diaminonaphthalene gave optically active (2R,2′S)-2-hydroxy-2-(3-oxo-1,2,3,4-tetrahydroquinoxalin-2-yl)-acetates 8 or (2R,2′S)-2-hydroxy-2-(3-oxo-1,2,3,4-tetrahydronaphtho[1.8-ef][1.4]diazepin-2-yl)-acetate 9, respectively, in a regio and stereoselective manner. o-Phenylendiamines 7 with an electron-donating substituent gave other regioisomers to the electron-poor 7. Together with previous investigations in this field the present results demonstrate a dependence of the mode of the reaction of glycidates with o-phenylendiamines on the substituents at the glycidate.     

Diastereoselective palladium(0)-catalyzed azidation of 1-alkenylcyclopropyl esters: asymmetric synthesis of (−)-(1R,2S)-norcoronamic acid

Palladium(0)-catalyzed azidation of (1R,2S)-1-(1-alkenyl)2-methylcyclopropyl esters 10a,b proceeds with complete retention of configuration to provide, after reduction of the azide and oxidative cleavage of the allylic double bond, the (1R,2S)-norcoronamic acid 22 (>99% e.e.).     

Synthesis ofN-(amidomethyl)- andN- (imidomethyl)-α-amino acid esters by reactions of α-amino acid esters with formaldehyde and amides or imides

Reactions of hydrochlorides of glycine, alanine, phenylalanine, L-isolcucinc, and L-valine esters with aromatic and heteroaromatic carboxamides afforded hydrochlorides of the correspondingN-(amidomethyl)--amino acid esters.N-(Phthalimidomethyl)--amino acid esters were obtained by reactions of -amino acid esters containing free amino groups with formaldehyde and phthalimide, The¹H NMR studies demonstrated that the chiral centers of -amino acids may be retained in the course of condensation. Reactions of the Mannish bases obtained and their hydrochlorides with acetic anhydride and tosyl chloride afforded the correspondingN-aryl andN-sulfonyl derivatives.Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 7, pp, 1761–1769, July, 1996.     

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.