Menthyl esterification allows chiral resolution for the synthesis of artificial glutamate analogs

• Kenji Morokuma,
• Shuntaro Tsukamoto,
• Kyosuke Mori,
• Kei Miyako,
• Ryuichi Sakai,
• Raku Irie and
• Masato Oikawa

Beilstein J. Org. Chem. 2021, 17, 540–550, doi:10.3762/bjoc.17.48

• ]. Chiral HPLC profiles for the separation of menthyl ester diastereomers 20* and 20. Conditions: 4.6 × 250 mm CHIRALPAK IC column, EtOH/hexane 1:19, 1 mL/min, 40 °C, 254 nm, tR 9.6, 11.8 min. Superimposed structures of the top 5 stable conformers (89.9% total population) generated by CONFLEX (MMFF94S) for

The synthesis of chiral β-naphthyl-β-sulfanyl ketones via enantioselective sulfa-Michael reaction in the presence of a bifunctional cinchona/sulfonamide organocatalyst

• Deniz Tözendemir and
• Cihangir Tanyeli

Beilstein J. Org. Chem. 2021, 17, 494–503, doi:10.3762/bjoc.17.43

• by chiral HPLC chromatography using Agilent instrument. All new products were further analyzed by LC/MS–HRMS–TOF or MALDI–ESI–TOFMS. Synthesis of organocatalyst 5 A solution of quinineamine 2 (226.40 mg, 0.70 mmol) and triethylamine (107 μL, 0.77 mmol) in CH2Cl2 was added to a screw-capped reaction

Synthesis of legonmycins A and B, C(7a)-hydroxylated bacterial pyrrolizidines

• Wilfred J. M. Lewis,
• David M. Shaw and
• Jeremy Robertson

Beilstein J. Org. Chem. 2021, 17, 334–342, doi:10.3762/bjoc.17.31

• configurationally unstable in aqueous solution. Chiral HPLC analysis of samples of pyrrolizixenamide A isolated from culture clearly indicated racemic specimens but also revealed the presence of the two C(7a)-hydroxylated derivatives whose presence in the mixture became enriched during purification. Taken together

Vicinal difluorination as a C=C surrogate: an analog of piperine with enhanced solubility, photostability, and acetylcholinesterase inhibitory activity

• Yuvixza Lizarme-Salas,
• Alexandra Daryl Ariawan,
• Ranjala Ratnayake,
• Hendrik Luesch,
• Angela Finch and
• Luke Hunter

Beilstein J. Org. Chem. 2020, 16, 2663–2670, doi:10.3762/bjoc.16.216

• difluorinated acid 20. Finally, coupling of the acid 20 with piperidine afforded the target compound 2 in moderate yield (Scheme 3). The enantiopurity of 2 was investigated using chiral HPLC. From a spectroscopically pure sample of 2, two HPLC peaks were observed, with an integral ratio of 99:1. It is assumed

Synthesis of monophosphorylated lipid A precursors using 2-naphthylmethyl ether as a protecting group

• Jundi Xue,
• Ziyi Han,
• Gen Li,
• Khalisha A. Emmanuel,
• Cynthia L. McManus,
• Qiang Sui,
• Dongmian Ge,
• Qi Gao and
• Li Cai

Beilstein J. Org. Chem. 2020, 16, 1955–1962, doi:10.3762/bjoc.16.162

• )-3-hydroxytetradecanoate (5) in 98% yield. The same hydrogenation reaction was carried out using the (S)-Ru(OAc)2(BINAP) catalyst. Then both the R and S products were compared using chiral HPLC to confirm the absolute configuration and enantiomeric purity (Figure S1, Supporting Information File 1

Bipyrrole boomerangs via Pd-mediated tandem cyclization–oxygenation. Controlling reaction selectivity and electronic properties

• Liliia Moshniaha,
• Marika Żyła-Karwowska,
• Joanna Cybińska,
• Piotr J. Chmielewski,
• Ludovic Favereau and
• Marcin Stępień

Beilstein J. Org. Chem. 2020, 16, 895–903, doi:10.3762/bjoc.16.81

• by means of chiral HPLC with CD detection, leading to enantioenriched samples of some boomerangs. The enantiomers of cR2O were found to racemize very fast, thus it was not possible to separate them. The cR3X systems, which contain a 7-membered ring, showed a remarkably diverse behavior. Enantiomers

Asymmetric synthesis of CF₂-functionalized aziridines by combined strong Brønsted acid catalysis

• Xing-Fa Tan,
• Fa-Guang Zhang and
• Jun-An Ma

Beilstein J. Org. Chem. 2020, 16, 638–644, doi:10.3762/bjoc.16.60

• dichloromethane/petroleum ether) to give CF2-substituted aziridine 4. The enantiomeric excess was determined by chiral HPLC analysis. See Supporting Information File 1 for the dissolution–filtration procedure for each compound. Preparation of chiral aziridines from fluorinated diazo reagents. Substrate scope of

Arylisoquinoline-derived organoboron dyes with a triaryl skeleton show dual fluorescence

• Vânia F. Pais,
• Tristan Neumann,
• Ignacio Vayá,
• M. Consuelo Jiménez,
• Abel Ros and
• Uwe Pischel

Beilstein J. Org. Chem. 2019, 15, 2612–2622, doi:10.3762/bjoc.15.254

• undertaken at 80 °C in C6D6 using a screw-cap NMR tube. Although significant changes were registered, a complete coalescence of the signals was not observed. The chiral HPLC analysis (see HPLC traces in Supporting Information File 1) demonstrated the high purity of compounds 16–19. The sharp peaks and

Synthesis, enantioseparation and photophysical properties of planar-chiral pillar[5]arene derivatives bearing fluorophore fragments

• Guojuan Li,
• Chunying Fan,
• Guo Cheng,
• Wanhua Wu and
• Cheng Yang

Beilstein J. Org. Chem. 2019, 15, 1601–1611, doi:10.3762/bjoc.15.164

• derivatives. The racemic mixtures of P5A-DPA and P5A-Py were respectively separated by chiral high-performance liquid chromatography (HPLC). As shown in Figure 3a, injection of a P5A-DPA solution onto a DAICEL CHIRALPAK IA chiral HPLC column afforded two well-separated peaks of almost equal areas at 8.8 min

• absorption at 385–460 nm and a quantum yield of 46.4%. The rotation of phenolic units was inhibited by introducing two bulky fluorophores in one of the phenolic units of pillar[5]arene, and the enantiomers were isolated by chiral HPLC. The absolute configurations of each fraction were determined by circular

• curves of DPA-6 and P5A-DPA at 420 nm, excited at 390 nm nanosecond LED, c = 1.0 × 10−5 M in CHCl3, 25 °C. (a) Chiral HPLC traces of P5A-DPA, (b), (c) the first and second fractions of P5A-DPA, detected by UV at 295 nm. Conditions: column, DAICEL CHIRALPAK IA; mobile phase: hexane/dichloromethane 35:65

Fluorine-containing substituents: metabolism of the α,α-difluoroethyl thioether motif

• Andrea Rodil,
• Alexandra M. Z. Slawin,
• Nawaf Al-Maharik,
• Ren Tomita and
• David O’Hagan

Beilstein J. Org. Chem. 2019, 15, 1441–1447, doi:10.3762/bjoc.15.144

• . Sulfone 8 was a relatively minor metabolite, at only 10% of sulfoxide 6. A chiral HPLC (IC column, solvent: 5% isopropanol in hexane; 1 mL/min) enantiomeric assay was conducted for sulfoxide 6 and the outcome compared with a racemic sample of 6, prepared by chemical oxidation of thioether 4 [22]. Although

• with very similar outcomes. In order to explore the stereoselectivity of this sulfoxidation, sulfoxide 11 isolated from the C. elegans incubation was analysed by chiral HPLC (IC column, solvent: 5% isopropanol in hexane; 1 mL/min). This was compared to a racemic reference sample of 11 prepared by

Ugi reaction-derived prolyl peptide catalysts grafted on the renewable polymer polyfurfuryl alcohol for applications in heterogeneous enamine catalysis

• Alexander F. de la Torre,
• Gabriel S. Scatena,
• Oscar Valdés,
• Daniel G. Rivera and
• Márcio W. Paixão

Beilstein J. Org. Chem. 2019, 15, 1210–1216, doi:10.3762/bjoc.15.118

• chromatography on silica gel using n-hexane/EtOAc as eluent. Enantiomeric excess (ee) was determined by chiral HPLC analysis through comparison with the authentic racemic material. Assignment of the stereoisomers was performed by comparison with literature data. Synthesis and characterization Prolyl pseudo

Alkylation of lithiated dimethyl tartrate acetonide with unactivated alkyl halides and application to an asymmetric synthesis of the 2,8-dioxabicyclo[3.2.1]octane core of squalestatins/zaragozic acids

• Herman O. Sintim,
• Hamad H. Al Mamari,
• Hasanain A. A. Almohseni,
• Younes Fegheh-Hassanpour and
• David M. Hodgson

Beilstein J. Org. Chem. 2019, 15, 1194–1202, doi:10.3762/bjoc.15.116

• subsequently those of Nagano [27] and of Li [28] for allylations, i.e., stereoretentive (contrasteric) alkylation. As noted above, Seebach recorded 97:3 er (by NMR using a chiral shift reagent) for a benzylated tartrate [18]; in the present case, chiral HPLC comparison of 17 with the corresponding adduct from

• only ≈25% of tartrate 7 in an impure state. In contrast to the unsuccessful propylation with LiHMDS/LiCl mentioned above, following our modified Seebach‘s protocol, propylation could be achieved to give propylated tartrate 33a [12] (Scheme 9), in 66% yield and 97:3 er by chiral HPLC, with the trans

• , propylation of the monopropylated tartrate 33a can be achieved in 34% yield, if the reaction mixture is warmed to −50 °C (Scheme 10). Chiral HPLC comparison of the trans-dipropylated material 34a obtained as the byproduct from the alkylation of tartrate acetonide 7, and from propylation of the monopropylated

New α- and β-cyclodextrin derivatives with cinchona alkaloids used in asymmetric organocatalytic reactions

• Iveta Chena Tichá,
• Simona Hybelbauerová and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2019, 15, 830–839, doi:10.3762/bjoc.15.80

• Information File 288: Experimental procedures, characterization data, copies of NMR spectra and chiral HPLC analysis. Supporting Information File 289: 2D NMR spectra of compounds 4a–d and 5a–d. Supporting Information File 290: 2D NMR spectra of compounds 8a–d, 9a–d and 11. Acknowledgements The work has been

A chemoenzymatic synthesis of ceramide trafficking inhibitor HPA-12

• Seema V. Kanojia,
• Sucheta Chatterjee,
• Subrata Chattopadhyay and
• Dibakar Goswami

Beilstein J. Org. Chem. 2019, 15, 490–496, doi:10.3762/bjoc.15.42

• reused the recovered lipase in ionic liquid at least three times without any significant loss of enzyme activity. The % ee of the (R)-5 and (S)-4 were determined from chiral HPLC analyses (150 mm × 4.6 mm, 5 μm, chiral AD-H column, 5% isopropanol/hexane @ 1.0 mL min−1, UV detection at 254 nm). The

Silanediol versus chlorosilanol: hydrolyses and hydrogen-bonding catalyses with fenchole-based silanes

• Falco Fox,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2019, 15, 167–186, doi:10.3762/bjoc.15.17

• . The enantiomeric excess is determined by chiral HPLC analysis (see Supporting Information File 1). General procedure for addition of silyl ketene acetals 11 to 1-chloroisochroman (18) to product 19: In a heat dried Schlenk tube 1-chloroisochroman (18, 0.15 mmol, 0.3 mL of 0.5 M in toluene) was solved

• NaOMe (0.2 mL, 0.5 M in MeOH), concentrated in vacuo and purified by silica gel flash column chromatography (n-hexane/Et2O 9:1). The enantiomeric excess is determined by chiral HPLC analysis (see Supporting Information File 1). General procedure for addition of silyl ketene acetals 11 to chromone 20 to

• acetate 9:1). The enantiomeric excess is determined by chiral HPLC analysis (see Supporting Information File 1). Hydrogen-bonding silanediols, i.e., di(1-naphthyl)silanediol (1) [39], silanediols 2 [41][42][43], binaphthylsilanediol derivatives 3 [45][46] and 4 [47][48] and novel biphenyl-2,2

Green synthesis of new chiral 1-(arylamino)imidazo[2,1-a]isoindole-2,5-diones from the corresponding α-amino acid arylhydrazides in aqueous medium

• Nadia Bouzayani,
• Jamil Kraїem,
• Sylvain Marque,
• Yakdhane Kacem,
• Abel Carlin-Sinclair,
• Jérôme Marrot and
• Béchir Ben Hassine

Beilstein J. Org. Chem. 2018, 14, 2923–2930, doi:10.3762/bjoc.14.271

• –m. Diastereoisomeric (dr) and enantiomeric (er) ratio were determined by chiral HPLC (see Supporting Information File 3). Proposed partial mechanism with a selectivity model. Synthesis of the α-amino acid arylhydrazides 3a–m. Optimization of the reaction conditions for the cyclocondensation of 2

Some mechanistic aspects regarding the Suzuki–Miyaura reaction between selected ortho-substituted phenylboronic acids and 3,4,5-tribromo-2,6-dimethylpyridine

• Piotr Pomarański,
• Piotr Roszkowski,
• Jan K. Maurin,
• Armand Budzianowski and
• Zbigniew Czarnocki

Beilstein J. Org. Chem. 2018, 14, 2384–2393, doi:10.3762/bjoc.14.214

• asymmetric synthesis of various substituted arylpyridine derivatives. Unfortunately, separation using chiral HPLC columns were unsuccessful and therefore, the racemic mixtures of these atropisomers were examined by 1H NMR spectroscopy with a chiral solvating agent ((+)-(R)-tert-butyl(phenyl)phosphinothioic

A novel and practical asymmetric synthesis of eptazocine hydrobromide

• Ruipeng Li,
• Zhenren Liu,
• Liang Chen,
• Jing Pan,
• Kuaile Lin and
• Weicheng Zhou

Beilstein J. Org. Chem. 2018, 14, 2340–2347, doi:10.3762/bjoc.14.209

• alkylation.a Optimization of oxidation conditions. Optimization of Mannich cyclization.a Supporting Information Supporting Information File 400: 1H NMR and MS spectra of 3, 4, 8–15, 13C NMR spectra of 4, 12, 13, chiral HPLC chromatograms of 4, 1H NMR, MS and HPLC chromatograms of 1.

Enantioselective phase-transfer catalyzed alkylation of 1-methyl-7-methoxy-2-tetralone: an effective route to dezocine

• Ruipeng Li,
• Zhenren Liu,
• Liang Chen,
• Jing Pan and
• Weicheng Zhou

Beilstein J. Org. Chem. 2018, 14, 1421–1427, doi:10.3762/bjoc.14.119

• and MS spectra of catalysts C1–C17 and chiral HPLC diagrams of 3. 1H NMR, 13C NMR, MS spectra of 3. 1H NMR, MS spectra HPLC diagrams of dezocine.

Enantioselective dioxytosylation of styrenes using lactate-based chiral hypervalent iodine(III)

• Morifumi Fujita,
• Koki Miura and
• Takashi Sugimura

Beilstein J. Org. Chem. 2018, 14, 659–663, doi:10.3762/bjoc.14.53

• determined by 1H NMR using an internal standard. The ee of 3 was determined by chiral HPLC analysis. The results for the yields and ee are summarized in Table 1. The reaction of styrene (1a) with 4a gave the 1,2-dioxytosylated product 3a with 70% ee of the (S)-isomer (Table 1, entry 1). An ee of equal to or

Copper-catalyzed asymmetric methylation of fluoroalkylated pyruvates with dimethylzinc

• Kohsuke Aikawa,
• Kohei Yabuuchi,
• Kota Torii and
• Koichi Mikami

Beilstein J. Org. Chem. 2018, 14, 576–582, doi:10.3762/bjoc.14.44

• under reduced pressure. The residue was purified by silica gel column chromatography to give p-nitrobenzoylated alcohol 2’. The enantiomeric excess was determined by chiral HPLC analysis. (S)-3-Ethoxy-1,1,1-trifluoro-2-methyl-3-oxopropan-2-yl 4-nitrobenzoate (2a’) The yield of alcohol 2a (86%) was

Mechanochemical enzymatic resolution of N-benzylated-β³-amino esters

• Mario Pérez-Venegas,
• Gloria Reyes-Rangel,
• Adrián Neri,
• Jaime Escalante and
• Eusebio Juaristi

Beilstein J. Org. Chem. 2017, 13, 1728–1734, doi:10.3762/bjoc.13.167

• enantioenriched (R)-N-benzylated-β3-amino acid (R)-2a was observed, recovering 51% of enantioenriched starting material. It could be established by chiral HPLC that the ee of the product amounted 80% (Table 1, entry 1). This assay demonstrated that enzymatic hydrolysis can indeed be carried out under HSBM

Base-promoted isomerization of CF₃-containing allylic alcohols to the corresponding saturated ketones under metal-free conditions

• Yoko Hamada,
• Tomoko Kawasaki-Takasuka and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2017, 13, 1507–1512, doi:10.3762/bjoc.13.149

• chirality transmission (CT) on the basis of the chiral HPLC analysis (Table 4, entries 1, 4, and 5). Unanimous formation of (R)-stereoisomers at the 3 position of 7 from (R,E)-6 led to confirmation that the proton attached to C1 was migrated to C3 from its si face, thus from the same back side if (R,E)-6

Construction of highly enantioenriched spirocyclopentaneoxindoles containing four consecutive stereocenters via thiourea-catalyzed asymmetric Michael–Henry cascade reactions

• Yonglei Du,
• Jian Li,
• Kerong Chen,
• Chenglin Wu,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2017, 13, 1342–1349, doi:10.3762/bjoc.13.131

• chiral HPLC analysis of major diastereomer. The dr values were determined by 1H NMR analysis. Method A: with 10 mol % of d as a catalyst, −20 °C, 12 h. Method B: with 10 mol % of d as a catalyst, −10 °C, 24 h. A plausible mechanism. Optimization for the reaction conditionsa. Supporting Information

Studies directed toward the exploitation of vicinal diols in the synthesis of (+)-nebivolol intermediates

• Runjun Devi and
• Sajal Kumar Das

Beilstein J. Org. Chem. 2017, 13, 571–578, doi:10.3762/bjoc.13.56

• chromans have become attractive synthetic targets in academia and pharmaceutical industry [1]. Nebivolol (1, Figure 1) is a chroman-based antihypertensive drug that was first reported in the racemic form [2][3]. Chiral HPLC was subsequently employed to access various stereoisomers of 1 in enantiomerically