Direct synthesis of acyl fluorides from carboxylic acids using benzothiazolium reagents

• Lilian M. Maas,
• Alex Haswell,
• Rory Hughes and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2024, 20, 921–930, doi:10.3762/bjoc.20.82

• observed (yield = 72%) with analysis by chiral HPLC revealing no erosion of the enantiomeric ratio (er = 99:1). At this stage, the suitability of BT-SCF3-mediated deoxyfluorination for the one-pot formation of peptide linkages between amino acids was investigated (Scheme 3). Treatment of N-Boc-valine under

• Campbell (Newcastle University) for assistance with chiral HPLC measurements. Funding This work is funded by the Friedrich Ebert Stiftung (scholarship to L.M.M.) and the School of Natural and Environmental Sciences at Newcastle University (studentship to A.H.). Financial support from Deutsche

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

• enantiomers (P,P) and (M,M) were separated by chiral HPLC and displayed opposite circularly polarized luminescence (CPL) and electronic circular dichroism (ECD) properties. The addition of ZnCl2 switched the system from a compact conformation to an extended conformation, resulting in a modulation of the

Chiral phosphoric acid-catalyzed transfer hydrogenation of 3,3-difluoro-3H-indoles

• Yumei Wang,
• Guangzhu Wang,
• Yanping Zhu and
• Kaiwu Dong

Beilstein J. Org. Chem. 2024, 20, 205–211, doi:10.3762/bjoc.20.20

• spectroscopy and the ee values were determined by chiral HPLC. Structures of bioactive fluorinated indole derivatives. Proposed mechanism for the transfer hydrogenation reaction. Synthesis of chiral indolines via asymmetric reduction. Substrate scope of 3,3-difluoro-3H-indoles. Experiment at 2 mmol scale

Perspectives on push–pull chromophores derived from click-type [2 + 2] cycloaddition–retroelectrocyclization reactions of electron-rich alkynes and electron-deficient alkenes

• Michio Yamada

Beilstein J. Org. Chem. 2024, 20, 125–154, doi:10.3762/bjoc.20.13

• when the TCBD moiety was incorporated at the axial position of the subphthalocyanine (SubPc) core (Figure 3) [131]. Axially chiral SubPc–TCBD–aniline conjugates 59 and 60 were characterized via optical-resolution analysis through chiral HPLC using a Chiralpak IC column. The researchers unequivocally

• types of subporphyrin derivatives 61 and 62, wherein the subporphyrin skeleton was functionalized at its meso or axial position with the TCBD moiety (Figure 3). Although the optical resolution of 61 failed, they succeeded in achieving the optical resolution of 62 via chiral HPLC using a Chiralpak IC

A novel recyclable organocatalyst for the gram-scale enantioselective synthesis of (S)-baclofen

• Gyula Dargó,
• Dóra Erdélyi,
• Balázs Molnár,
• Péter Kisszékelyi,
• Zsófia Garádi and
• József Kupai

Beilstein J. Org. Chem. 2023, 19, 1811–1824, doi:10.3762/bjoc.19.133

• . Further details are available in Supporting Information File 1. The enantiomeric ratios of the samples were determined by chiral high-performance liquid chromatography (HPLC) measurements. The exact conditions of chiral HPLC are indicated in the experimental section of the corresponding compound

• the cyclohexyl derivative of Meldrum’s acid 15 to 4-chloro-trans-β-nitrostyrene (16).a Supporting Information Supporting Information File 28: Experimental part, NMR, IR, and chiral HPLC spectra. Acknowledgements The authors are grateful to Péter Bagi for his help with the chiral HPLC measurements

Acetaldehyde in the Enders triple cascade reaction via acetaldehyde dimethyl acetal

• Alessandro Brusa,
• Debora Iapadre,
• Maria Edith Casacchia,
• Alessio Carioscia,
• Giuliana Giorgianni,
• Giandomenico Magagnano,
• Fabio Pesciaioli and
• Armando Carlone

Beilstein J. Org. Chem. 2023, 19, 1243–1250, doi:10.3762/bjoc.19.92

• %) were added to a solution of 1 (10 mol %) in 2 mL of solvent (0.25 M) and allowed to stir for 48 hours at room temperature. Yields of isolated compounds are given. Diastereomeric ratio (dr) determined by 1H NMR analysis. Enatiomeric excess (ee) determined by chiral HPLC analysis. Original triple

Construction of hexabenzocoronene-based chiral nanographenes

• Ranran Li,
• Di Wang,
• Shengtao Li and
• Peng An

Beilstein J. Org. Chem. 2023, 19, 736–751, doi:10.3762/bjoc.19.54

• determined for the enantiopure helicenes. For compound 12, the racemization barrier was 24.8 kcal mol−1 at 298 K, which provides a racemization half-life (t1/2) of 24.4 h. For compounds 11 and 13, neither racemization nor decomposition was observed by chiral HPLC after heating hexadecane solutions of each

• through oxidative cyclodehydrogenation and imine formation in a 72% yield. It was noted that no other regioisomer was detected for the asymmetrical precursor 30. The pair of enantiomers was confirmed by the racemic structure's single-crystal X-ray diffractometry and separated by chiral HPLC, and no

• structures were confirmed by single-crystal X-ray diffractometry and chiral HPLC. The rotational isomerization barrier of C6F4 ring for the analogue of 62, with two tert-butyl groups substituted by protons was determined as 24.6 kcal/mol at 40 °C with a half-life of t1/2 = 107 min. Employing the similar

A new oxidatively stable ligand for the chiral functionalization of amino acids in Ni(II)–Schiff base complexes

• Alena V. Dmitrieva,
• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2023, 19, 566–574, doi:10.3762/bjoc.19.41

• Information File 24: Experimental details, characterization, and copies of spectra. Acknowledgements Prof. Dr. Denis Chusov is acknowledged for chiral HPLC analyses performed in the A.N. Nesmeyanov Institute of Organoelement Compounds of RAS. Funding This work was supported by the Russian Foundation for

An accelerated Rauhut–Currier dimerization enabled the synthesis of (±)-incarvilleatone and anticancer studies

• Tharun K. Kotammagari,
• Sweta Misra,
• Sayantan Paul,
• Sunita Kunte,
• Rajesh G. Gonnade,
• Manas K. Santra and
• Asish K. Bhattacharya

Beilstein J. Org. Chem. 2023, 19, 204–211, doi:10.3762/bjoc.19.19

• The total synthesis of racemic incarvilleatone has been achieved by utilizing unexplored accelerated Rauhut–Currier (RC) dimerization. The other key steps of the synthesis are oxa-Michael and aldol reactions in a tandem sequence. Racemic incarvilleatone was separated by chiral HPLC and the

• Incarvillea younghusbandii (Figure 1). This plant is used in Chinese folk medicine to treat dizziness and anemia [1]. Zhang and co-workers [1] separated the racemic incarvilleatone in two individual enantiomers, (−)-incarvilleatone [(−)-1] and (+)-incarvilleatone [(+)-1] by performing chiral HPLC. The

Enantioselective total synthesis of putative dihydrorosefuran, a monoterpene with an unique 2,5-dihydrofuran structure

• Irene Torres-García,
• Josefa L. López-Martínez,
• Rocío López-Domene,
• Manuel Muñoz-Dorado,
• Ignacio Rodríguez-García and
• Miriam Álvarez-Corral

Beilstein J. Org. Chem. 2022, 18, 1264–1269, doi:10.3762/bjoc.18.132

• stereoselective kinetic resolution of allenol 3 via lipase AK-catalyzed acetylation [15]. In this way, unaltered, (−)-hydroxyallene 3 could be separated from (+)-acetyl derivative 9 through standard column chromatography (Scheme 3). Enantiomeric excesses of (−)-3 and (+)-9 were determined by chiral HPLC analyses

A Streptomyces P450 enzyme dimerizes isoflavones from plants

• Run-Zhou Liu,
• Shanchong Chen and
• Lihan Zhang

Beilstein J. Org. Chem. 2022, 18, 1107–1115, doi:10.3762/bjoc.18.113

• and 2 with respect to atropisomerism was assessed by chiral HPLC analysis and the comparison of experimental and calculated ECD spectra. While 1 showed a ≈3:1 atropisomer ratio, with the M-atropisomer being the major form, 2 did not exhibit a Cotton effect in the ECD measurement, suggesting that it is

Anti-inflammatory aromadendrane- and cadinane-type sesquiterpenoids from the South China Sea sponge Acanthella cavernosa

• Shou-Mao Shen,
• Qing Yang,
• Yi Zang,
• Jia Li,
• Xueting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 916–925, doi:10.3762/bjoc.18.91

• equipped with a DAD G1315D detector and an Agilent Eclipse XDB-C18 column (5 μm, 9.4 × 250 mm). In contrast, chiral HPLC separation was operated on the chromatography equipped with CHIRALPAK IB N-3 column (5 μm, 4.6 × 250 mm). All solvents used for CC and HPLC were analytical grade (Shanghai Chemical

• successively separated by Sephadex LH-20 CC (PE/CH2Cl2/MeOH, 2:1:1) and RP-HPLC (55% MeCN in H2O, 3.0 mL/min) to afford compound 6 (1.3 mg, tR = 12.4 min). The separation of racemic mixtures (4 and 5) was performed on chiral HPLC equipped with a CHIRALPAK IB N-3 column eluted with MeCN/H2O [4: 25:75, 5: 15:85

The asymmetric Henry reaction as synthetic tool for the preparation of the drugs linezolid and rivaroxaban

• Martin Vrbický,
• Karel Macek,
• Jaroslav Pochobradský,
• Jan Svoboda,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2022, 18, 438–445, doi:10.3762/bjoc.18.46

• de were observed and the presence of the major S-enantiomer in the products 1 and 2 was confirmed by chiral HPLC analysis. Moreover, an enhancement of the abundance of the major epimer in the nitroaldols 22, 24, and 26 as well as the amides 27 and 28 was examined. Generally, epimers represent pairs

Organocatalytic asymmetric nitroso aldol reaction of α-substituted malonamates

• Ekta Gupta,
• Narendra Kumar Vaishanv,
• Sandeep Kumar,
• Raja Krishnan Purshottam,
• Ruchir Kant and
• Kishor Mohanan

Beilstein J. Org. Chem. 2022, 18, 217–224, doi:10.3762/bjoc.18.25

• silica gel column chromatography. Enantioselectivities were determined by chiral HPLC analysis. Variation of ester moiety of malonamates and nitrosoarenes. General conditions: 1 (0.20 mmol), 2a (0.24 mmol), 3a (0.04 mmol), toluene (3.0 mL). Yields refer to isolated yields after silica gel column

• chromatography. Enantioselectivities were determined by chiral HPLC analysis. aReaction run for 6 h. Synthetic transformation. Optimization of the reaction conditions.a Supporting Information Supporting Information File 202: Detailed experimental procedures, complete characterization data for all compounds

Asymmetric organocatalytic Michael addition of cyclopentane-1,2-dione to alkylidene oxindole

• Estelle Silm,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2022, 18, 167–173, doi:10.3762/bjoc.18.18

• -protecting groups. Reaction conditions: 0.2 M solution of 1 (1 equiv), 2 (1 equiv), of catalyst D (0.1 equiv), chloroform, at room temperature; isolated yields after column chromatography; ee determined by chiral HPLC. Scope of the reaction (the relative configuration of the major diastereoisomer is depicted

• ). Reaction conditions: 0.2 M solution of 1 equiv of 1, 2 equiv of 2, 0.1 equiv of catalyst D, chloroform, at room temperature; isolated yields after column chromatography; ee determined by chiral HPLC. Comparison reactions of E- and Z-isomers (the relative configurations of the major diastereoisomers are

• depicted). Reaction conditions: 0.2 M solution of 1 equiv of 1, 2 equiv of 2, 0.1 equiv of catalyst D, chloroform, at room temperature; isolated yields after column chromatography; ee determined by chiral HPLC. Screening conditions for the reactiona. Epimerisation of 3a. Supporting Information Supporting

Regioselective synthesis of methyl 5-(N-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates as new amino acid-like building blocks

• Jolita Bruzgulienė,
• Greta Račkauskienė,
• Aurimas Bieliauskas,
• Vaida Milišiūnaitė,
• Miglė Dagilienė,
• Gita Matulevičiūtė,
• Vytas Martynaitis,
• Sonata Krikštolaitytė,
• Frank A. Sløk and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2022, 18, 102–109, doi:10.3762/bjoc.18.11

• blocks was developed. Regioisomeric methyl 5-(N-Boc-cycloaminyl)-1,2-oxazole-4-carboxylates were prepared by the reaction of β-enamino ketoesters (including azetidine, pyrrolidine or piperidine enamines) with hydroxylamine hydrochloride. Unambiguous structural assignments were based on chiral HPLC

• hydroxylamine hydrochloride in methanol (Scheme 1). Synthesized compounds 4b–g exhibited optical activity, and the corresponding (R)- or (S)-enantiomers rotated the plane of plane-polarized light in opposite directions. The enantiomeric purity of chiral compounds 4b–g was assessed via chiral HPLC analysis of

Bifunctional thiourea-catalyzed asymmetric [3 + 2] annulation reactions of 2-isothiocyanato-1-indanones with barbiturate-based olefins

• Jiang-Song Zhai and
• Da-Ming Du

Beilstein J. Org. Chem. 2022, 18, 25–36, doi:10.3762/bjoc.18.3

• an Agilent 6520 Accurate-Mass Q-TOF MS system equipped with an electrospray ionization (ESI) source. Optical rotations were measured with a Krüss P8000 polarimeter at the indicated concentration with the units of g/100 mL. Enantiomeric excesses were determined by chiral HPLC analysis using an Agilent

Unsaturated fatty acids and a prenylated tryptophan derivative from a rare actinomycete of the genus Couchioplanes

• Shun Saito,
• Kanji Indo,
• Naoya Oku,
• Hisayuki Komaki,
• Masashi Kawasaki and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2021, 17, 2939–2949, doi:10.3762/bjoc.17.203

• -octadienoic acid (5), and one prenylated tryptophan derivative, 6-(3,3-dimethylallyl)-N-acetyl-ʟ-tryptophan (6). The enantiomer ratio of 4 was determined to be approximately S/R = 56:44 by a recursive application of Trost’s chiral anisotropy analysis and chiral HPLC analysis of its methyl ester. Compounds 1–5

• . (S)-MPA ester of 7R enantiomer 4'd: 1H NMR data was identical to those of 4'a. Chiral HPLC analysis A 0.2 μL-portion of 4', dissolved in iPrOH, was injected into a cellulose tribenzoate-coated silica gel column (CHIRALCEL OB-H, 4.6 mm × 250 mm, Daicel Co.) eluted with n-hexane/iPrOH (4:1) at 0.5 mL

• recorded on a Bruker micrOTOF spectrometer. Silica gel 60 (spherical) (Kanto Chemical Co., Inc.) was used for silica gel column chromatography. Cosmosil 75C18-PREP (Nacalai Tesque, Inc.) was used for ODS column chromatography. Routine HPLC separations were performed on an Agilent HP1200 system, and chiral

Synthetic strategies toward 1,3-oxathiolane nucleoside analogues

• Umesh P. Aher,
• Dhananjai Srivastava,
• Girij P. Singh and
• Jayashree B. S

Beilstein J. Org. Chem. 2021, 17, 2680–2715, doi:10.3762/bjoc.17.182

• THF and phosphate-buffered saline (PBS). The reaction used 64 and 3q as starting materials and was stereocontrolled efficiently, providing an enantiomeric excess of about >99%. The subsequent N-glycosylation further provided enantiopure lamivudine (1). Hu et al. [60] explained that chiral HPLC and

• a cis/trans ratio of 1.3:1 for the nucleoside intermediate 79a. Further, the nucleoside intermediate 79a was deprotected using a type of basic resin. This gave the cis-diastereomer 3TC (1), which was purified by chiral HPLC, resulting in an ee value of 70% (Scheme 28). Further developments in the

Organocatalytic asymmetric Michael/acyl transfer reaction between α-nitroketones and 4-arylidenepyrrolidine-2,3-diones

• Chandrakanta Parida and
• Subhas Chandra Pan

Beilstein J. Org. Chem. 2021, 17, 1447–1452, doi:10.3762/bjoc.17.100

• 2 (0.1 mmol), 10 mol % VII in 0.6 mL 1,2-dichloroethane were reacted at 25 °C for 12 hours. Yields correspond to isolated yields after silica gel column chromatography and ees were determined by chiral HPLC. Catalyst screening and optimization of the reaction conditions. Scope of α-nitroketones 2 in

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

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