Tetrahedron Asymmetry

Pd-catalyzed enantioselective C–H arylation of phosphinamides with boronic acids for the synthesis of P-stereogenic compounds ()
Publication date: Available online 18 April 2017 Source:Tetrahedron: Asymmetry Author(s): Yuan-Hui Chen, Xu-Long Qin, Jing Guan, Zhi-Jun Du, Fu-She Han A Pd-catalyzed enantioselective C–H arylation of phosphinamides with aryl boronic acids is presented. With readily affordable amino acid derivatives as chiral ligands, the reaction proceeded efficiently to afford the P-stereogenic phosphinamides in up to 75% yield and with 99% ee under mild conditions. Most importantly, the reaction could be performed on a large scale for various substrates. This method provides an alternative and reliable way for accessing P-stereogenic phosphinamides. Graphical abstract image
>> Read More

Application of sulfonyl chlorides and chiral amines in the efficient synthesis of nonracemic sulfinamides ()
Publication date: Available online 18 April 2017 Source:Tetrahedron: Asymmetry Author(s): Karolina Kamińska, Elżbieta Wojaczyńska, Jacek Skarżewski, Andrzej Kochel, Jacek Wojaczyński A simple protocol that allows the preparation of separable epimeric sulfinamides from chiral amines and sulfonyl chlorides reduced in situ with triphenylphosphine in the presence of KOH is described. Using this method, tosyl chloride and nosyl chloride were successfully reacted with α-substituted primary amines to give five diastereomeric pairs, in certain cases accompanied by a small amount of the corresponding sulfonamide. Enantiopure products were isolated by column chromatography. The obtained enantiomerically pure sulfinamides were tested as organocatalysts in the asymmetric epoxide ring opening. Graphical abstract image
>> Read More

Hydrolase-mediated resolution of the hemiacetal in 2-chromanols: The impact of remote substitution ()
Publication date: Available online 18 April 2017 Source:Tetrahedron: Asymmetry Author(s): Declan P. Gavin, Aoife Foley, Thomas S. Moody, U.B. Rao Khandavilli, Simon E. Lawrence, Pat O'Neill, Anita R. Maguire Hydrolase-catalysed dynamic kinetic resolutions of chroman-2-ol and 3-methyl chroman-2-ol can be effected with up to 88% conversion and 92% ee through the use of organic solvents. Extension to the resolution of the tolterodine precursor 1 proved more challenging. The presence of the remote phenyl substituent had a significant impact on the resolution and it was not possible to achieve high enantioselectivity together with efficient conversion from the focussed panel of enzymes screened. Graphical abstract image
>> Read More

Asymmetric synthesis of 1,4-disubstituted 3-methylidenedihydroquinolin-2(1H)-ones ()
Publication date: Available online 17 April 2017 Source:Tetrahedron: Asymmetry Author(s): Marlena Pięta, Jacek Kędzia, Jakub Wojciechowski, Tomasz Janecki A series of enantiomerically pure or highly enriched (R)- or (S)-3-methylidenetetrahydroquinolin-2-ones was readily prepared by highly diastereoselective Michael additions of various Grignard reagents to quinolin-2(1H)-ones, containing an (R,R)- or (S,S)-di(1-phenylethylamino)phosphoryl group as chiral auxiliary, followed by Horner-Wadsworth-Emmons olefination of formaldehyde. An efficient synthesis of the starting (R,R)- and (S,S)-3-({di[(1-phenylethyl)amino]}phosphoryl)-1-alkyl-quinolin-2(1H)-ones is also described. The relative and absolute configurations of the intermediate adducts and final methylidenequinolinones were established by NMR and X-ray analysis. Graphical abstract image
>> Read More

Diastereoselective cycloaddition of (S)-N-(1-phenylethylimino)trifluoropropionate and trifluoroethylphosphonate with diazomethane ()
Publication date: Available online 13 April 2017 Source:Tetrahedron: Asymmetry Author(s): Yuliya V. Rassukana, Ludmyla V. Bezgubenko, Oleg V. Stanko, Eduard B. Rusanov, Irina B. Kulik, Petro P. Onys'ko The cycloaddition reaction of (S)-(α-phenylethylimino)trifluoropropionate with diazomethane leads to a diastereomeric mixture (4.5:1) of 5-trifluoromethyl-1,2,3-triazoline-5-carboxylates. Enantiopure diastereomers were isolated by column chromatography and converted into their respective non-racemic 2-trifluoromethyl-aziridine-2-carboxylates and carboxylic acids. The absolute configuration of newly formed stereogenic centers was determined by XRD analysis. The stereoselective reaction between (S)-N-(α-phenylethyl)trifluoroacetimidoylphosphonate and diazomethane produces a diastereomeric mixture (2.5:1) of 5-trifluoromethyltriazoline-5-phosphonates readily separated by column chromatography in diastereomerically pure forms. Graphical abstract image
>> Read More

Stereocontrolled self-assembly of luminescent lanthanide helicates and their enantiodifferentiation using Δ-TRISPHAT as the NMR resolving agent ()
Publication date: Available online 11 April 2017 Source:Tetrahedron: Asymmetry Author(s): Ting Zhang, Guang-Lu Zhang, Li-Peng Zhou, Xiao-Qing Guo, Qing-Fu Sun Self-assembled supramolecular lanthanide constructs have great potential in luminescent bioprobes/sensors. Stereoselectivity on the lanthanide assemblies is needed to facilitate chiroptical probes and sensors. Herein we report the stereocontrolled synthesis of M2L3-type (M=metal ion, L=organic ligand) lanthanide triple-helicates using a chiral-induction strategy, where the periphery point-chirality [(R,R) or (S,S)] of the organic ligands was transferred into the metal centered chirality (ΔΔ or ΛΛ), thus leading to the formation of topological chiral (P or M) helicates. Moreover, commercially available Δ-TRISPHAT proved to be an effective NMR chiral resolving agent to differentiate between the two enantiomers of the helicate. Graphical abstract image
>> Read More

Biotransformation of 3-azidomethyl-4-phenyl-3-buten-2-one and analogs by Saccharomyces cerevisiae: New evidence for an SN2′ mechanism ()
Publication date: Available online 9 April 2017 Source:Tetrahedron: Asymmetry Author(s): Bruno R.S. de Paula, Dávila Zampieri, J. Augusto R. Rodrigues, Paulo J.S. Moran (Z)-3-XCH2-4-(C6H5)-3-buten-2-one enones (X=SCN, N3, SO2Me, OC6H5) were synthesized and submitted to biotransformations using whole Saccharomyces cerevisiae cells. The enone (X=SCN) produced (R)-4-(phenyl)-3-methylbutan-2-one (R)-6 with 93% ee and enones (X=N3, SO2Me, OC6H5) yielded a mixture of (R)-6 and the corresponding CC bond reduction products. Biotransformation with enone (X=N3) mediated by Saccharomyces cerevisiae resulted in two products via two different routes: (i) the ketone (R)-4-azido-3-benzylbutan-2-one in 28% yield and with >99% ee by CC bond reduction; (ii) ketone (R)-6 in 51% yield and with 95% ee via cascade reactions beginning with azido group displacement by the formal hydride from flavin mononucleotide in an SN2′ type reaction followed by reduction of the newly formed CC bond. Graphical abstract image
>> Read More

1,1,1-Trifluoropropan-2-ammonium triflate enantiomers: stereoselective synthesis and direct use in reaction with epoxides ()
Publication date: Available online 31 March 2017 Source:Tetrahedron: Asymmetry Author(s): Gemma Packer, Julien Malassis, Neil Wells, Mark Light, Bruno Linclau A three-step synthesis of enantiomerically enriched 1,1,1-trifluoro-2-propanamine based on the use of a chiral sulfinamide auxiliary is described. The reduction of the geometrically pure Z-sulfinimine (NOE, HOE) with NaBH4 or l-Selectride leads to the corresponding (R)- or (S)-configured amine derivatives (X-ray crystallographic analysis) with 92–96% de. The typical models to explain the stereoselection for these reducing agents fail to rationalize the obtained stereoselectivities, and an in situ imine isomerization is proposed to occur. The direct use of the hydrochloric acid salt (with excess Et3N) of this poorly nucleophilic amine for epoxide opening reactions is not possible due to the higher nucleophilicity of chloride. Hence, a novel triflate salt is introduced, synthesized through ready sulfinamide hydrolysis with trimethylsilyl triflate, which can be used directly, without the need of isolating the pure amine beforehand. Graphical abstract image
>> Read More

Acylative kinetic resolution of racemic aromatic β-hydroxy esters catalyzed by chiral nucleophilic N-(1-arylethyl)benzoguanidines ()
Publication date: Available online 30 March 2017 Source:Tetrahedron: Asymmetry Author(s): Akira Yamada, Kenya Nakata, Isamu Shiina An efficient acylative kinetic resolution of racemic aromatic β-hydroxy esters with cyclohexanecarboxylic anhydride was achieved using newly designed (R)-N-methylbenzoguanidine ((R)-NMBG) derivatives. A series of (R)-NMBG derivatives was synthesized by modifying the original (R)-NMBG catalyst with the introduction of branched N-substituents containing a stereogenic center, and their catalytic performance was evaluated. (R,R)-N-(1-(β-1-Naphthyl)ethyl)benzoguanidine [(R,R)-NβNpEtBG] was found to function as an efficient acyl transfer catalyst for the reaction of a broad variety of substrates, regardless of the substituent type and substitution pattern. Graphical abstract image
>> Read More

Synthesis of chiral aza-bis(oxazolines) derived from (+)-camphor ()
Publication date: Available online 28 March 2017 Source:Tetrahedron: Asymmetry Author(s): Jaime González, Diego Martínez-Otero, Bernardo A. Frontana-Uribe, Erick Cuevas-Yañez Two novel chiral structurally azabis(oxazoline) ligands were synthesized using (+)-camphor as the starting material. Each of the ligands was prepared through the corresponding aminoalcohols. The structures of some crystalline derivatives were unambiguously established by X-ray analysis. Graphical abstract image
>> Read More

Solvent free, fast and asymmetric Michael additions of ketones to nitroolefins using chiral pyrrolidine–pyridone conjugate bases as organocatalysts ()
Publication date: Available online 24 March 2017 Source:Tetrahedron: Asymmetry Author(s): Chandan K. Mahato, Mrinalkanti Kundu, Animesh Pramanik New chiral organocatalysts are envisaged based on a pyrrolidine–pyridone conjugate and synthesized from commercially available proline employing standard protocols. These catalysts were found to be useful for asymmetric Michael additions of ketones to nitroolefins to afford the desired products in very good yields (up to 98%) with excellent diastereo- and enantioselectivities (>97:3 syn/anti and up to 98% ee) in very short reaction time compared with the existing reports. Graphical abstract image
>> Read More

New N,N-diamine ligands derived from (−)-menthol and their application in the asymmetric transfer hydrogenation ()
Publication date: Available online 21 March 2017 Source:Tetrahedron: Asymmetry Author(s): Piotr Roszkowski, Jan.K. Maurin, Zbigniew Czarnocki Natural (−)-menthol was applied to construction of mono-N-tosylated-1,2-diamine derivatives. The O-tosylation and elimination of the tosylate of the menthol intermediate led to trans-p-menth-2-ene. The unsaturated menth-2-ene was next transformed into a mixture of N-tosylaziridines, which upon reaction with sodium azide gave four isomeric azides. The reduction of the formed tosylazides on Pd/C gave new chiral mono-N-tosylated-1,2-diamines, which were used as ligands in the asymmetric transfer hydrogenation protocol on aromatic ketones and endocyclic imine. Graphical abstract image
>> Read More

Editorial board ()
Publication date: 15 March 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 3
>> Read More

Graphical contents list ()
Publication date: 15 March 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 3
>> Read More

Contributors to this issue ()
Publication date: 15 March 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 3
>> Read More

Evolution of synthetic routes towards homochiral Tapentadol ()
Publication date: 15 March 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 3 Author(s): Piotr P. Graczyk, Olga Zbrojkiewicz, Sven Nerdinger Analysis of the literature shows that the development of synthetic approaches to Tapentadol, an agonist of the μ-opioid receptor and norepinephrine reuptake inhibitor, has followed four, partially overlapping, phases. The most advanced approaches, based on stereoselective syntheses, appeared only after 2010. The majority of the chemistry examples presented in this review come from patent applications and as such have not been subjected to rigorous peer review, but may serve well as an inspiration to organic chemists for solving analogous synthetic problems. Graphical abstract image
>> Read More

Enantioselective Michael addition of aldehydes to nitroolefins catalyzed by pyrrolidine-HOBt ()
Publication date: 15 March 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 3 Author(s): Togapur Pavan Kumar, Mohammad Abdul Sattar, Sthanikam Siva Prasad, Kothapalli Haribabu, Cirandur Suresh Reddy The oxytriazole catalyst “pyrrolidine-HOBt” developed for asymmetric Michael addition of cyclohexanone to nitroolefins is now evaluated for the asymmetric Michael addition of aldehydes to nitroolefins under similar reaction conditions. The results of this study indicate that, the oxytriazole catalyst “pyrrolidine-HOBt” is equally effective in promoting the Michael addition of aldehydes to nitroolefins on employing benzoic acid as an additive. The desired products, γ-nitrocarbonyl compounds were obtained in good yields and high enantioselectivities. Graphical abstract image
>> Read More

Stereoselective synthesis of tacalcitol via (R)-MeCBS catalyzed borane reduction ()
Publication date: 15 March 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 3 Author(s): Hengrui Zhang, Wei Guo, Zhijie Fang A novel and efficient approach for the synthesis of 1α, 24(R)-dihydroxyvitamin D3 (tacalcitol) starting from readily available enone 1 has been achieved with high stereoselectivity. The key step involved in the synthesis of tacalcitol was the stereoselective reduction of enone 1 using borane as the reducing agent, and the effects of the critical reaction parameters such as temperature, various borane complexes have been examined. Finally, tacalcitol was obtained in five steps from enone 1 with an overall yield of 32% and a ratio of 24-R/S =95/5. Graphical abstract image
>> Read More

S-Substituted-2-mercaptobenzthiazolium-based chiral ionic liquids: efficient organocatalysts for enantioselective sodium borohydride reductions of prochiral ketones ()
Publication date: 15 March 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 3 Author(s): Avtar Singh, Harish Kumar Chopra Novel chiral ionic liquids having chirality in their cationic part have been synthesized for evaluation of their catalytic potential as organocatalysts in sodium borohydride reduction of prochiral ketones to yield optically active secondary alcohols. The chiral ionic liquids have been synthesized from the reaction of (−)-menthol or (−)-borneol, chloroacetic acid and S-methyl/benzyl-2-mercaptobenzthiazole. The synthesized chiral ionic liquids have been characterized by 1H, 13C NMR and Mass spectrometry. Moderate to excellent enantiomeric excess (ee>99%) has been obtained in asymmetric sodium borohydride reduction of prochiral ketones using these salts as chiral catalysts. Graphical abstract image
>> Read More

Synthesis of p-coumaroylquinic acids and analysis of their interconversion ()
Publication date: 15 March 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 3 Author(s): Anggy Lusanna Gutiérrez Ortiz, Federico Berti, Luciano Navarini, Angelo Monteiro, Marina Resmini, Cristina Forzato The synthesis of four isomers of p-coumaroylquinic acids was performed by esterification of p-acetylcoumaroylchloride with a suitably protected (−)-quinic acid. All isomers have been characterized by means of NMR spectroscopy and circular dichroism. Acyl migration was observed in the synthesis of 3-O-p-coumaroylquinic acid and 4-O-p-coumaroylquinic acid. Calculations on the most stable conformations of all isomers have also been performed to explain the acyl migration observed during the synthesis procedure. Graphical abstract image
>> Read More

Silver-catalyzed diastereo- and enantioselective Michael additions of 2-oxazoline- and 2-thiazoline-4-carboxylate to nitroalkenes ()
Publication date: 15 March 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 3 Author(s): Akihiro Koizumi, Yukiko Matsuda, Ryosuke Haraguchi, Shin-ichi Fukuzawa The silver/ThioClickFerrophos (a chiral ferrocenyl P,S-ligand)-catalyzed Michael additions of 2-oxazoline- and thiazoline-4-carboxylate to nitroalkenes were highly anti-selective and enantioselective and produced the corresponding adducts in high yields. Graphical abstract image
>> Read More

Efficient resolution of profen ethyl ester racemates by engineered Yarrowia lipolytica Lip2p lipase ()
Publication date: 15 March 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 3 Author(s): Doriane Gérard, Marc Guéroult, Leticia Casas-Godoy, Jean-Stéphane Condoret, Isabelle André, Alain Marty, Sophie Duquesne Enzyme-catalyzed enantiomer discrimination is still a great challenge for the development of industrial pharmaceutical processes. For the resolution of ibuprofen, naproxen and ketoprofen racemates, three major anti-inflammatory drugs, only lipases from Candida rugosa present a high selectivity if solvent and surfactant use is discarded. However, their catalytic activities are too low. In the present work, we demonstrate that the lipase Lip2p from the yeast Yarrowia lipolytica has a higher catalytic activity than C. rugosa lipases to hydrolyze the ethyl esters of ibuprofen, naproxen and ketoprofen, but its selectivity is not sufficient [E =52 (S); 11 (S) and 1.5 (R) respectively]. The enantioselectivity was further improved by site-directed mutagenesis, targeted at the substrate binding site and guided by molecular modelling studies. By investigating the binding modes of the (R)- and (S)-enantiomers in the active site, two amino acid residues located in the hydrophobic substrate binding site of the lipase, namely residues 232 and 235, were identified as crucial for enantiomer discrimination and enzyme activity. The (S) enantioselectivity of Lip2p towards ethyl ibuprofen esters was rendered infinite (E ≫300) by replacing V232 by an A or C residue. Substitution of V235 by C, M, S, or T amino acids led to a great increase in the (S)-enantioselectivity (E ≫300) towards naproxen ethyl ester. Finally, the variant V232F enabled the efficient kinetic resolution of ethyl ketoprofen ester enantiomers [(R)-enantiopreference; E ≫300]. In addition to the increase in selectivity, a remarkable increase in velocity by 2.6, 2.7 and 2.5times, respectively, was found for ibuprofen, naproxen and ketoprofen ethyl esters. Graphical abstract image
>> Read More

Synthesis and crystal structure of (S)-pindolol ()
Publication date: 15 March 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 3 Author(s): Alexander A. Bredikhin, Zemfira A. Bredikhina, Alexey V. Kurenkov, Dmitry B. Krivolapov Racemic 3-(4-indolyloxy)-1,2-propanediol 2 has been effectively resolved into (S)- and (R)-enantiomers by a preferential crystallization procedure. Non-racemic (S)-2 was converted into (S)-4-(2,3-epoxypropoxy)-1H-indole (S)-4 via a Mitsunobu reaction and then into (S)-pindolol (S)-1. The crystalline (S)-1 was studied by single crystal X-ray diffraction. A large number of symmetry independent molecules (Z′=6) led to a weakening of the system of strong intermolecular hydrogen bonds, which combined with a loose packing (PI=64.6%), may be the cause of the abnormally low melting point of (S)-1 as compared with rac-1. Graphical abstract image
>> Read More

Enantioselective synthesis of fatty acid amide hydrolase inhibitors with 1,3-disubstituted butan-2-one scaffold ()
Publication date: 15 March 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 3 Author(s): Tom R. Sundermann, Matthias Lehr Fatty acid amide hydrolase is a key enzyme in the inactivation of the analgesic and anti-inflammatory endocannabinoid anandamide. Previously, the chiral compound 1-(1H-benzotriazol-1-yl)-3-(4-phenylphenoxy)butan-2-one was identified as a potent inhibitor of fatty acid amide hydrolase and is therefore of interest as a potential agent against pain and inflammation. Two different approaches for the enantioselective synthesis of fatty acid amide hydrolase inhibitors with a 1,3-disubstituted butan-2-one scaffold were carried out. The first one uses the chiral epoxide 2-[1-(4-phenylphenoxy)ethyl]oxirane with an (R)- or (S)-configuration at the exocyclic stereocenter as central intermediates. These substances were obtained by separation of the non-stereoselectively synthesized epoxide into its racemic diastereomers by reversed phase chromatography followed by Jacobsen’s hydrolytic kinetic resolution of each enantiomer with the (S)-configured oxirane ring. Furthermore, a chiral pool based enantioselective synthesis was developed. In that case, the starting compound for both target enantiomers was methyl 3,4-O-isopropylidene-l-threonate. In comparison to the first approach, the chiral pool synthesis consisted of more steps, but generated the enantiomers with much better enantiomeric excess. Biological evaluation showed that the (R)-enantiomer inhibits isolated fatty acid amide hydrolase with a 200-fold higher activity than the (S)-enantiomer. Graphical abstract image
>> Read More

Using enantioselective dispersive liquid–liquid microextraction for the microseparation of trans-cyclohexane-1,2-diamine enantiomers ()
Publication date: 15 March 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 3 Author(s): Majid Hashemi, Mohammad Reza Hadjmohammadi A new chiral separation system effective for the enantioselective extraction of racemic trans-cyclohexane-1,2-diamine is presented. Enantioselective dispersive liquid–liquid microextraction has been used for the chiral microseparation of trans-cyclohexane-1,2-diamine, with a chiral azophenolic crown ether being identified as a versatile chiral selector. The influence of various process conditions on the extraction performance was studied experimentally. It was found that the operational selectivity in one extraction step is mainly related to the type and volume of the solvents, chiral selector concentration, extraction time, temperature of sample solution, and pH. At optimum conditions (300μL of diethyl ether as the extraction solvent 1mL of methanol as the disperser solvent, with 5mmolL−1 chiral selector concentration, pH of the sample equal to 4.5, 30min extraction time and a temperature of 10°C), the distribution ratio of (R,R)- and (S,S)-trans-cyclohexane-1,2-diamine was 18.3 and 1.8, respectively, while the enantioselectivity value of 10.2 was found at the optimum condition. Graphical abstract image
>> Read More

Solvent-induced chirality switching in the enantioseparation of regioisomeric hydroxyphenylpropionic acids via diastereomeric salt formation with (1R,2S)-2-amino-1,2-diphenylethanol ()
Publication date: 15 March 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 3 Author(s): Koichi Kodama, Jun Nagata, Nobuhiro Kurozumi, Hiroaki Shitara, Takuji Hirose The enantioseparation of three hydroxyphenylpropionic acid isomers via diastereomeric salt formation with (1R,2S)-2-amino-1,2-diphenylethanol has been demonstrated. The racemates of all three acid isomers were successfully separated with high efficiency (0.56–0.84) after single crystallization. For 2-hydroxy-3-phenylpropionic acid 4, the configuration of the less-soluble salt was controlled by the crystallization solvent: the (R)-4 salt was crystallized from water, while 2-propanol afforded the (S)-4 salt. The chiral recognition mechanism of the three acids was discussed based on the crystal structures of the diastereomeric salts. Graphical abstract image
>> Read More

Chiral terpene auxiliaries IV: new monoterpene PHOX ligands and their application in the catalytic asymmetric transfer hydrogenation of ketones ()
Publication date: 15 March 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 3 Author(s): Anna Kmieciak, Marek P. Krzemiński New PHOX ligands, derived in three steps from (1R,2S,3R,5R)-3-amino-apopinan-2-ol 1 and (1R,2R,3S,5R)-3-amino-pinan-2-ol 2 were applied as chiral ligands for the formation of ruthenium catalysts. The catalysts were used in asymmetric transfer hydrogenations of prochiral ketones producing the corresponding alcohols in moderate to high yields and enantioselectivity. Graphical abstract image
>> Read More

Enantioselective enzymatic resolution of racemic alcohols by lipases in green organic solvents ()
Publication date: 15 March 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 3 Author(s): Abderahmane Belafriekh, Francesco Secundo, Stefano Serra, Zeineddine Djeghaba The effects of two eco-friendly solvents, 2-methyltetrahydrofuran (MeTHF) and cyclopentyl methyl ether (CPME), on the enzyme activity and enantioselectivity of Novozym 435, Candida rugosa lipase (CRL), Porcine pancreas lipase (PPL), Lipase AK, Lipase PS, and Lipozyme, a series of commercial lipases, in the enantioselective transesterfications of racemic menthol, racemic sulcatol and racemic α-cyclogeraniol were studied. Vinyl acetate was chosen as the acyl donor and the reactions were carried out at water activity 0.06. The activity of lipases in CPME was similar to that observed in other largely employed organic solvents [toluene and tert-butyl methyl ether (MTBE)], and was slightly lower in MeTHF. However, for most of the lipases tested, the enantioselectivity was higher in the eco-friendly solvents. Lipase AK exhibited a high enantioselectivity (E =232) for the resolution of racemic menthol but the reaction rate was low. Lipase formulation (the enzyme was frozen and lyophilized in potassium phosphate buffer without and with 5% (w/v) of sucrose, d-mannitol, or methoxy poly(ethylene glycol)) was tested with this lipase in order to improve its activity, which increased up to 4.5 times, compared to the untreated enzyme. CALB was found to be a useful biocatalyst for the resolution of racemic sulcatol, where high activity and enantioselectivity were obtained (E ≥1000). For the resolution of the racemic primary alcohol α-cyclogeraniol, most of the lipases tested were active but not enantioselective, except lipase PS which displayed a moderate enantioselectivity (E =19). The effect of the presence of a low percentage of two ionic liquids (ILs) 1-Butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide ([BMIM][TFSI]) (5% (v/v)) and 1-Butyl-3-methylimidazoliumtetrafluoroborate ([BMIM][BF4]) (1% (v/v)) in the medium was also investigated. Only in the case of CRL the ILs slightly increased the enantioselectivity from E =91 to E =103 and E =120 for [BMIM][TFSI] and [BMIM][BF4], respectively. However, in all cases ILs caused a decrease of enzyme activity. Graphical abstract image
>> Read More

Design, stereoselective synthesis and computational calculations of novel hybrid compounds via Pauson-Khand reactions ()
Publication date: 15 March 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 3 Author(s): Selçuk Gümüş, Nezir Aslan, Nalan Nuriye Büyükadalı, Ayşegül Gümüş A series of novel chiral hybrid compounds between benzofuran and bicyclic cyclopentenone and also benzothiophene and bicyclic cyclopentenone have been designed and synthesized. Chiral enynes derived from enantiomerically enriched homoallyl and homopropargyl alcohols were converted into bicyclic cyclopentenone structures by intramolecular Pauson-Khand reactions. This strategy provides a facile access to various bicyclic cyclopentenones substituted with benzofuran or benzothiophene ring systems in good yields. In addition to the experimental work, the ground state geometries of the hybrid compounds were optimized using Density Functional Theory applications at the B3LYP/6-31G(d,p) level in order to obtain information about the 3D geometries and electronic structure. Graphical abstract image
>> Read More

Stereochemistry abstracts ()
Publication date: 15 March 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 3
>> Read More

Tetrahedron: Asymmetry Reports ()
Publication date: 15 March 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 3
>> Read More

Cumulative author index ()
Publication date: 15 March 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 3
>> Read More

A review on the synthetic approaches of rivaroxaban: An anticoagulant drug ()
Publication date: Available online 11 March 2017 Source:Tetrahedron: Asymmetry Author(s): Tanzeela Abdul Fattah, Aamer Saeed Rivaroxaban is an effective and potent oral anti-coagulant drug approved by US FDA in 2008 and is widely used in the treatment of thromboembolic ailments, deep venous thrombosis, pulmonary embolism, myocardial infarction, cerebral stroke, angina pectoris, and transitory ischemic attacks. This review comprehensively provides an overview of the various asymmetric synthetic methods employed for the synthesis of rivaroxaban in high yields and stereoselectivity describing the various chiral synthons used in the synthetic process along with pros and cons of each method. In addition, methods for the industrial production of rivaroxaban have been highlighted in the manuscript. Graphical abstract image
>> Read More

Editorial board ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2
>> Read More

Graphical contents list ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2
>> Read More

Contributors to this issue ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2
>> Read More

The role of hydrazide compounds in asymmetric synthesis ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2 Author(s): Ghodsi Mohammadi Ziarani, Vaezeh Fathi Vavsari Asymmetric synthesis is one of the important topics in organic synthesis. Hydrazide compounds are valuable substrates in the fields of both chemical reactions and medicinal chemistry due to their chemical reactivity and biological activities, respectively. In this review, the role of hydrazides as substrates and/or chiral catalysts are investigated in the asymmetric organic reactions to gain chiral products. Graphical abstract image
>> Read More

Stereoselective synthesis of modified cysteines ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2 Author(s): Jaime Gracia-Vitoria, Iñaki Osante, Carlos Cativiela This review provides an overview of the literature concerning the stereoselective synthesis of a large group of modified cysteines. The different synthetic approaches are classified according to the bonds formed to build the cysteine backbone skeleton. Graphical abstract image
>> Read More

First total synthesis of the highly potent antitumor lactones 8-chlorogoniodiol and parvistone A: Exploiting a bioinspired late-stage epoxide ring-opening ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2 Author(s): Perla Ramesh, Yarram Narasimha Reddy, Thatikonda Narendar Reddy, Navuluri Srinivasu The first protecting group-free total syntheses of the highly potent antitumor chlorinated styryllactone secondary metabolites 8-chlorogoniodiol, parvistone A, and one analogue 8-epi-parvistone A, have been accomplished from commercially available trans-cinnamaldehyde in five steps with high overall yields. The chlorine-bearing stereogenic center of these silent secondary metabolites was introduced via a bioinspired late-stage regioselective epoxide ring-opening strategy. Maruoka asymmetric allylation, acrylation, ring-closing metathesis and asymmetric epoxidation, greatly facilitate the synthesis of the key intermediates goniothalamin oxide and (6S,7S,8S)-isogoniothalamin oxide. Graphical abstract image
>> Read More

Assignment of the absolute configuration of hydroxy acids using 1H NMR spectroscopy: a simple and rapid approach ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2 Author(s): Sandeep Kumar Mishra, N. Suryaprakash A simple, rapid and highly effective protocol for assigning the absolute configuration of various chiral α-hydroxy acids and their derivatives has been established by involving the coupling of 2-formylphenylboronic acid with (R)-[1,1-binaphthalene]-2,2-diamine, and 2-formylphenylboronic acid with (S)-[1,1-binaphthalene]-2,2-diamine as chiral derivatizing agents. The absence of aliphatic peaks from the derivatizing agent together with the large chemical shift separation between the discriminated diastereomer peaks, with a systematic change in the direction of the displacement of peaks for an enantiomer in a particular diastereomer complex, allows the unambiguous assignment of absolute configuration. Graphical abstract image
>> Read More

Highly enantioselective Biginelli reactions using methanopyroline/thiourea – based dual organocatalyst systems: asymmetric synthesis of 4-substituted unsaturated aryl dihydropyrimidines ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2 Author(s): Han Yu, Peng Xu, Huihong He, Jun Zhu, Hualin Lin, Sheng Han A series of novel chiral 3,4-dihydropyrimidin-2-(1H)-ones and -thiones (DHPMs) was developed via asymmetric Biginelli reactions catalyzed by a methanopyroline/thiourea – based dual organocatalyst system, providing excellent yield (90–96%) and high enantioselectivities (92–99% ee). Furthermore, novel epoxides with three stereogenic centers are disclosed, which might have application in the field of drugs and pharmaceuticals. Graphical abstract image
>> Read More

Convenient synthesis of memantine analogues containing a chiral cyclopropane skeleton as a sigma-1 receptor agonist ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2 Author(s): Tetsuya Ezawa, Yuya Kawashima, Takuya Noguchi, Seunghee Jung, Nobuyuki Imai We have achieved a convenient enantioselective synthesis of memantine analogues containing a chiral cyclopropane skeleton as a sigma-1 receptor agonist in 19–40% overall chemical yields from the corresponding 2-arylbut-2-ene-1,4-diols with moderate to excellent asymmetric yields via regioselective acetylation using porcine pancreas lipase, catalytic enantioselective Simmons-Smith reactions, and amidation in aqueous organic solvent. This synthetic route is more efficient and less expensive than conventional methods. Graphical abstract image
>> Read More

Enantioselective chlorinative aldol reaction of α-substituted acroleins catalyzed by chiral phosphine oxides ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2 Author(s): Shunsuke Kotani, Takuya Hanamure, Hirono Nozaki, Masaharu Sugiura, Makoto Nakajima The enantioselective chlorinative aldol reaction of α-substituted acroleins with aldehydes catalyzed by chiral phosphine oxides is described. A hypervalent silicon complex-derived chloride adds to the α-substituted acroleins to form the corresponding silyl enol ethers in situ, which subsequently reacts with aldehydes to produce the α-chloromethyl aldol adducts bearing a quaternary stereogenic center in good yields and stereoselectivities. When activated by a phosphine oxide catalyst, trichlorosilyl triflate acts as an effective promoter for the chlorinative aldol reaction as well as the chloride source; this discovery enabled the enantioselective chlorinative aldol reaction of α-substituted acroleins. Graphical abstract image
>> Read More

Total syntheses of 9-epoxyfalcarindiol and its diastereomer ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2 Author(s): Yun Zhou, Yanli Huang, Shuoning Li, Pengfei Yang, Jiangchun Zhong, Jingwei Yin, Kaijie Ji, Yanqing Yang, Ning Ye, Lifeng Wang, Mingan Wang, Min Wang, Qinghua Bian The first total syntheses of 9-epoxyfalcarindiol 1a and its diastereomer 1b have been achieved. Central to our approach were the Zn-cyclopropane-based amino alcohol catalyzed enantioselective alkynylation of acrolein, the diastereoselective addition of a diynic ester to an epoxy aldehyde, and the asymmetric Sharpless epoxidation of allylic alcohol catalyzed with L-(+)-diethyl tartrate and Ti(OiPr)4. Graphical abstract image
>> Read More

Stereoselective E/Z-photoisomerization of cyclooctene using 2,4-pentanediol chiral tether ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2 Author(s): Kuifeng Song, Morifumi Fujita, Tadashi Okuyama, Takashi Sugimura The photoisomerization, epoxidation, and cyclopropanation of chiral 2,4-pentanediol tethered cyclooctene were explored to examine the stereocontrollability of the tether. Photoisomerization of (2R,4R)-2,4-pentanediol-tethered cyclooctene achieved a de of 20% at a high Z/E ratio of 0.80 at 25°C, while (2S,4R)-2,4-pentanediol-tethered cyclooctene yielded a lower de in spite of an even higher Z/E ratio. The epoxidation and cyclopropanation of 2,4-pentanediol tethered cyclooctene resulted in lower stereoselectivity compared with those of vinyl ether. We propose that the low de of the reactions of 2,4-pentanediol tethered cyclooctene is not attributable to the low stereocontrollability of 2,4-pentanediol tether, but due to the conformational multiplicity of the reactant site. Graphical abstract image
>> Read More

Organocatalytic enantioselective conjugate addition of aldehydes to maleimides in deep eutectic solvents ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2 Author(s): Jesús Flores-Ferrándiz, Rafael Chinchilla The conjugate enantioselective addition of aldehydes, mainly α,α-disubstituted, to maleimides leading to enantioenriched succinimides, has been achieved in recyclable deep eutectic solvents at room temperature. Enantiomerically pure carbamate-monoprotected trans-cyclohexane-1,2-diamines are used as organocatalysts, affording high yields and up to 94% ee of the final succinimides. The product can be extracted from the deep eutectic solvent, which retains the chiral organocatalyst, allowing both the solvent and catalyst to be reused. Graphical abstract image
>> Read More

An investigation towards the diastereoselective synthesis of 3-acetoxy/methoxy/phthalimido-β-lactams using chiral imines ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2 Author(s): Aman Bhalla, Garima Modi, S.S. Bari, Anu Kumari, Dipika Narula, Shiwani Berry The efficient diastereoselective synthesis of 3-acetoxy/methoxy/phthalimido-β-lactams 2/2′, 3/3′ and 4/4′ respectively was performed using chiral imines 1 obtained from chiral amines. Factors (solvent, temperature, substituent, steric bulk) influencing the stereoselectivity and the diastereomeric ratio were also studied in detail. The diastereoselectivity of the two isomers was determined from the ratio of integral values of doublets of C3–H and C4–H and from the integral values of H in –CH(Me/Et)Ph/Np of the two diastereomers. Representative pairs of cis-diastereomers were separated by efficient column chromatography. Graphical abstract image
>> Read More

‘On water’ organocatalyzed enantioselective synthesis of highly functionalized cyclohexanones with an all-carbon quaternary centre from allylidene malononitriles and enones ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2 Author(s): Ganga B. Vamisetti, Raghunath Chowdhury, Mukesh Kumar, Sunil K. Ghosh An organocatalyzed endo [4+2] cycloaddition between enones as pro-diene and allylidene malononitrile as dienophile leading to cyclohexanones with two 1,3-related stereogenic centres and an all-carbon quaternary centre has been developed. The reactions were performed under ‘green reaction’ conditions using water as the reaction medium and ambient conditions. When allylidene cyanoacetate was used as the dienophile, cyclohexanones with three contiguous stereogenic centres, one of which is an all-carbon quaternary centre, were formed. The products were obtained in high yield and with acceptable diastereo- and enantioselectivity. Graphical abstract image
>> Read More

Enantioselective synthesis of new chiral 2-aziridinyl phosphonates and studies of their biological activities ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2 Author(s): Özdemir Dogan, Sıdıka Polat Çakır, Nurzhan Beksultanova, Nurten Altanlar, Duygu Şimşek, Hasan Karabıyık A new series of chiral aziridinyl phosphonates has been synthesized and evaluated for antibacterial and antifungal activities. For the synthesis, a Gabriel-Cromwell reaction was used to form aziridinyl phosphonates in 52–83% yield. In order to evaluate antibacterial and antifungal activities, MIC values were measured. Although most of the compounds showed insignificant activity, two of them provided low to moderate antifungal activity. Graphical abstract image
>> Read More

Novel MOP-type H8-binaphthyl monodentate phosphite ligands and their applications in transition metal-catalyzed asymmetric 1,4-conjugate additions and hydroformylations ()
Publication date: 15 February 2017 Source:Tetrahedron: Asymmetry, Volume 28, Issue 2 Author(s): Mi Tian, Zeng-bo Pang, Hai-feng Li, Lai-lai Wang A new series of monodentate phosphites based on the rigid, axially chiral monoesterified H8-BINOL, which are easy to prepare from the readily accessible phosphorylating reagents (S a)- or (R a)-1,1′-binaphthyl-2,2′-diylchlorophosphite and (S a)- or (R a)-1,1′-H8-binaphthyl-2,2′-diylchlorophosphite, have been synthesized. All ligands were purified on a silica gel column under a nitrogen atmosphere with moderate yields, and were white solids and air-stable at room temperature. These ligands afforded good to excellent enantioselectivities in the Cu-catalyzed 1,4-conjugate addition of 2-cyclohexenone with nucleophiles Et2Zn (96% ee) and with Ph2Zn (65% ee), 2-cyclopentenone with Et2Zn (95% ee), 2-cycloheptenone with Et2Zn (76% ee), and 5,6-dihydro-2H-pyran-2-one with Et2Zn (90% ee). In the Rh-catalyzed asymmetric hydroformylation of styrene, these ligands showed a chemoselectivity of >99% in aldehydes, and a satisfactory branched over linear ratio (96/4). Moreover, the sense of the enantiodiscrimination of the products was mainly determined by the configuration of the BINOL-based or H8-BINOL-based phosphocycle. Graphical abstract image
>> Read More

Site Search