Calix[6]arene-based atropoisomeric pseudo[2]rotaxanes

• Carmine Gaeta,
• Carmen Talotta and
• Placido Neri

Beilstein J. Org. Chem. 2018, 14, 2112–2124, doi:10.3762/bjoc.14.186

• stoppering or catenation of such atropoisomeric pseudorotaxanes. Experimental ESI(+)–MS measurements were performed on a Micromass Bio-Q triple quadrupole mass spectrometer equipped with electrospray ion source, using a mixture of H2O/CH3CN (1:1) and 5% HCOOH as solvent. Flash chromatography was performed on

First thia-Diels–Alder reactions of thiochalcones with 1,4-quinones

• Grzegorz Mlostoń,
• Katarzyna Urbaniak,
• Paweł Urbaniak,
• Anna Marko,
• Anthony Linden and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2018, 14, 1834–1839, doi:10.3762/bjoc.14.156

• . In addition to anthraquinones 2b and 2c, the simple 1,4-benzoquinone (2a) was also tested in the reaction with thiochalcones 1. The reactions performed with 1a and 1b delivered the expected 4H-thiochromene-5,8-diones 4m,n, which were isolated in good yields using flash chromatography, but underwent

• menadione (2e) was completely consumed. The solvent was evaporated in vacuo and the crude mixtures were analyzed by 1H NMR first and subsequently purified by flash chromatography using dichloromethane (for 4a–n) or a mixture of petroleum ether and dichloromethane 1:1 (for 6) as the eluents. For products 4a

Heterogeneous acidic catalysts for the tetrahydropyranylation of alcohols and phenols in green ethereal solvents

• Ugo Azzena,
• Massimo Carraro,
• Gloria Modugno,
• Luisa Pisano and
• Luigi Urtis

Beilstein J. Org. Chem. 2018, 14, 1655–1659, doi:10.3762/bjoc.14.141

• , the mixture obtained by reacting 1f with 1.1 equiv of 2 and 3 mol ‰ of NH4HSO4@SiO2 in 2-MeTHF under dry Ar was filtered and dropwise added to a vigorously stirred freshly prepared solution of EtMgBr in the same solvent at rt. Aqueous work-up and flash chromatography afforded the desired tertiary

Lanyamycin, a macrolide antibiotic from Sorangium cellulosum, strain Soce 481 (Myxobacteria)

• Lucky S. Mulwa,
• Rolf Jansen,
• Dimas F. Praditya,
• Kathrin I. Mohr,
• Patrick W. Okanya,
• Joachim Wink,
• Eike Steinmann and
• Marc Stadler

Beilstein J. Org. Chem. 2018, 14, 1554–1562, doi:10.3762/bjoc.14.132

• ending up with 2.9 g of enriched methanol extract. This extract was purified further by Si-Flash chromatography (Grace Reveleris®) using an 80 g silica column, with dichloromethane (DCM)/acetone solvent gradient of 25% to 100% acetone in 23 min followed by 100% acetone for 13 min. This resulted in 9

Metal-free formal synthesis of phenoxazine

• Gabriella Kervefors,
• Antonia Becker,
• Chandan Dey and
• Berit Olofsson

Beilstein J. Org. Chem. 2018, 14, 1491–1497, doi:10.3762/bjoc.14.126

• 7, and could be easily isolated by flash chromatography in 91% yield. A shortening of the reaction time to 1 h profoundly increased the amount of byproduct to 52% (Table 1, entry 8). Surprisingly, the desired product 3 could be isolated in 58% yield from this experiment after prolonged storage of

Two new 2-alkylquinolones, inhibitory to the fish skin ulcer pathogen Tenacibaculum maritimum, produced by a rhizobacterium of the genus Burkholderia sp.

• Dandan Li,
• Naoya Oku,
• Atsumi Hasada,
• Masafumi Shimizu and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2018, 14, 1446–1451, doi:10.3762/bjoc.14.122

• second fraction was then further fractionated by ODS flash chromatography and purified by HPLC to yield the eight metabolites 1–8. The molecular formula of 3 was established as C18H23NO based on a HRESITOFMS measurement (m/z 270.1855 [M + H]+, Δ +0.3 mmu). Analysis of 1H, 13C, and HSQC NMR spectra in

• successively partitioned between 60% MeOH (250 mL) and CH2Cl2 (250 mL × 3) and the latter between 90% aqueous MeOH (150 mL) and n-hexane (150 mL × 3). The aqueous MeOH layer, which concentrated the antibacterial activity against Tenacibaculum maritimum, was subjected to ODS flash chromatography (Ø 3 × 7 cm

Recyclable hypervalent-iodine-mediated solid-phase peptide synthesis and cyclic peptide synthesis

• Dan Liu,
• Ya-Li Guo,
• Jin Qu and
• Chi Zhang

Beilstein J. Org. Chem. 2018, 14, 1112–1119, doi:10.3762/bjoc.14.97

• cycle was collected and evaporated. Then the mixture was acidified with 3 N HCl and extracted with EtOAc, dried and concentrated in vacuo. The synthetic precursor of FPID 6 could be purified by flash chromatography in order to remove excess Fmoc-protected amino acids during the peptide coupling

Iodine(III)-mediated halogenations of acyclic monoterpenoids

• Laure Peilleron,
• Tatyana D. Grayfer,
• Joëlle Dubois,
• Robert H. Dodd and
• Kevin Cariou

Beilstein J. Org. Chem. 2018, 14, 1103–1111, doi:10.3762/bjoc.14.96

• concentrated under reduced pressure before purification by flash chromatography. General procedure B: bromo(trifluoro)acetoxylation To a solution of the geranyl derivative (1.0 equiv) in acetonitrile (0.07 M) cooled to 0 °C, PIFA (1.1 equiv) was added. A solution of tetra-n-butylammonium bromide (1.1 equiv) in

• , dried over MgSO4, filtered and concentrated under reduced pressure before purification by flash chromatography. General procedure C: bromohydroxylation To a solution of the geranyl derivative (1.0 equiv) in acetonitrile (0.1 M) cooled to −10 °C, DIB (1.4 equiv) was added. A solution of lithium bromide

• (1.6 equiv) in H2O (0.1 M) was then added dropwise over 5 min. After stirring at −10 °C for 10 min, the reaction mixture was diluted with EtOAc, filtered over alumina (EtOAc) and concentrated under reduced pressure before purification by flash chromatography. General procedure D: iodo(trifluoro

The first Pd-catalyzed Buchwald–Hartwig aminations at C-2 or C-4 in the estrone series

• Ildikó Bacsa,
• Dávid Szemerédi,
• János Wölfling,
• Gyula Schneider,
• Lilla Fekete and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 998–1003, doi:10.3762/bjoc.14.85

• aminations at C-2 or C-4 in the 13α-estrone series. Reactions were performed on a 0.25 mmol scale with 1.2 equiv of amine, 10 mol % Pd(OAc)2, 10 mol % X-Phos, at 100 °C, 10 min under microwave irradiation. Flash chromatography yields are reported. Two-step synthesis of 2-amino-13α-estra-1,3,5(10)-trien-17

Biocatalytic synthesis of the Green Note trans-2-hexenal in a continuous-flow microreactor

• Morten M. C. H. van Schie,
• Tiago Pedroso de Almeida,
• Gabriele Laudadio,
• Florian Tieves,
• Elena Fernández-Fueyo,
• Timothy Noël,
• Isabel W. C. E. Arends and
• Frank Hollmann

Beilstein J. Org. Chem. 2018, 14, 697–703, doi:10.3762/bjoc.14.58

• with DCM. The collected organic phase was dried over MgSO4, filtered and concentrated under reduced pressure. Purification of the isolated mixture was performed by flash chromatography on silica (pure DCM). The final product was obtained as colourless oil (200 mg). (E)-Hex-2-enal TLC (DCM) Rf 0.9; 1H

Enhanced quantum yields by sterically demanding aryl-substituted β-diketonate ancillary ligands

• Rebecca Pittkowski and
• Thomas Strassner

Beilstein J. Org. Chem. 2018, 14, 664–671, doi:10.3762/bjoc.14.54

• )propane-1,3-dione (495 mg, 1.4 mmol) were added, and the mixture was stirred for 24 hours at room temperature and then for six hours at 110 °C; all volatiles were removed in vacuo, the crude product was washed with water and purified by flash chromatography (silica gel, DCM/isohexanes 3:1). Afterwards, it

• (II) (300 mg, 0.8 mmol) together with potassium tert-butanolate (180 mg, 1.6 mmol) and the β-diketonate 1,3-bis(2,3,5,6-tetramethylphenyl)propane-1,3-dione (540 mg, 1.6 mmol). The crude product was washed with water, isolated by flash chromatography (silica gel, DCM/isohexanes 4:1), and washed with

Synthesis of a sucrose-based macrocycle with unsymmetrical monosaccharides "arms"

• Karolina Tiara,
• Mykhaylo A. Potopnyk and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2018, 14, 634–641, doi:10.3762/bjoc.14.50

• residue was purified by flash chromatography (hexanes–ethyl acetate, 70:30) to afford pure product 15 (318 mg, 1.02 mmol, 63%) as a white solid. TLC [hexanes–AcOEt (2:1)]: Rf = 0.3; [α]D22 +28.5; 1H NMR δ 8.18 (d, J = 9.3 Hz, 2H, ArH), 6.99 (d, J = 9.3 Hz, 2H, ArH), 6.03 (ddd, J5,4 = 6.0 Hz, J5,6 = 10.7

• cooling to rt, water (15 mL) and DCM (15 mL) were added, the layers were separated, and the aqueous one was extracted with DCM (3 × 10 mL). Combined organic solutions were washed with water (10 mL) and brine (10 mL), dried, concentrated, and the crude productwas purified by flash chromatography (hexanes

• , the layers were separated, and the aqueous one was extracted with DCM (3 × 10 mL). Combined organic solutions were washed with water (10 mL) and brine (10 mL), dried, concentrated, and the product was isolated by flash chromatography (hexanes–ethyl acetate, 25:75) to afford 24 (120 mg, 0.08 mmol, 64

Diastereoselective auxiliary- and catalyst-controlled intramolecular aza-Michael reaction for the elaboration of enantioenriched 3-substituted isoindolinones. Application to the synthesis of a new pazinaclone analogue

• Romain Sallio,
• Stéphane Lebrun,
• Frédéric Capet,
• Francine Agbossou-Niedercorn,
• Christophe Michon and
• Eric Deniau

Beilstein J. Org. Chem. 2018, 14, 593–602, doi:10.3762/bjoc.14.46

• 6b–d highlighted the diastereoselection of the reaction was highly dependent of the starting benzamide substitution, 44 to 60% de being obtained for 3b–d. Finally, whereas diastereoisomers issued from 6b could be separated by flash chromatography, this was not possible for products 3c and d

• . Cyclisation of chiral benzamides (R)-7a–e and (R)-8 led to isoindolinones (2R)-4a–e, (2R)-5 in good yields and average to good diastereoselectivities (Scheme 3). In some cases, purification by flash chromatography afforded products 4b, 4c and 5 in higher diastereomeric purity. In order to access to the

• isoindolinones (3S)-1 and (3S)-2. Synthesis of parent benzamides 6–8. Synthesis of isoindolinones 3a–d, 4a–e, 5; isolated yield, de by HPLC and 1H NMR. aAfter flash chromatography on silica gel (EtOAc/hexanes 3:7) and crystallization from hexanes/toluene; bafter flash chromatography.on silica gel (EtOAc/hexanes

High-yielding continuous-flow synthesis of antimalarial drug hydroxychloroquine

• Eric Yu,
• Hari P. R. Mangunuru,
• Nakul S. Telang,
• Caleb J. Kong,
• Jenson Verghese,
• Stanley E. Gilliland III,
• Saeed Ahmad,
• Raymond N. Dominey and
• B. Frank Gupton

Beilstein J. Org. Chem. 2018, 14, 583–592, doi:10.3762/bjoc.14.45

• was purified using flash chromatography with DCM/Et3N/MeOH 95:3:2 to give a white solid (0.263 g, 78%). 1H NMR (600 MHz, CDCl3) δ 8.48 (d, J = 5.4 Hz, 1H), 7.93 (d, J = 5.4 Hz, 1H), 7.70 (d, J = 9.2 Hz, 1H), 7.34 (dd, J = 8.8, 7.3 Hz, 1H), 6.39 (d, J = 5.4 Hz, 1H), 4.96 (d, J = 7.5 Hz, 1H), 3.70 (sx

Novel amide-functionalized chloramphenicol base bifunctional organocatalysts for enantioselective alcoholysis of meso-cyclic anhydrides

• Lingjun Xu,
• Shuwen Han,
• Linjie Yan,
• Haifeng Wang,
• Haihui Peng and
• Fener Chen

Beilstein J. Org. Chem. 2018, 14, 309–317, doi:10.3762/bjoc.14.19

• monoester, without further purification by flash chromatography. Chloramphenicol-base-derived bifunctional organocatalysts. Design of new chloramphenicol base amide organocatalysts. Synthesis of bifunctional amide catalysts 7a–q. Asymmetric synthesis of (S)-GABOB (13). Conditions screening for asymmetric

From dipivaloylketene to tetraoxaadamantanes

• Gert Kollenz and
• Curt Wentrup

Beilstein J. Org. Chem. 2018, 14, 1–10, doi:10.3762/bjoc.14.1

• exhibit axial chirality [21], as has been demonstrated by 1H NMR spectroscopy using the optically active shift reagent Eu(hfc)3 [19]. The enantiomers of the dicarboxylic acid 11 have been separated by flash chromatography of their diastereomeric salts with 1-phenethylamine, and the structures of the acids

Recent progress in the racemic and enantioselective synthesis of monofluoroalkene-based dipeptide isosteres

• Myriam Drouin and
• Jean-François Paquin

Beilstein J. Org. Chem. 2017, 13, 2637–2658, doi:10.3762/bjoc.13.262

• isomers had to be separated by flash chromatography. In 2014, Sano and co-workers reported a selective synthesis of Xaa-ψ[CF=C]-Pro with a new cyclopentanone derivative 20 bearing a bulky 2-(4-methyl-2,6,7-trioxabicyclo[2.2.2]octan-1-yl) group (OBO), which favoured the formation of the (E)-isomer in the

• starting from the commercially available protected chiral hydroxyl ester 75. Reduction to the aldehyde followed by coupling with bromodifluoropropene gave two diastereoisomers 76a and 76b separable by flash chromatography. Then, the copper-catalyzed defluorinative allylic alkylation using Grignard reagents

• -alkylation on the γ,γ-difluoro-α,β-unsaturated δ-lactam 86. Unfortunately, the α-alkylation provided a mixture of diastereoisomers 87a and 87b which was separable by flash chromatography. The dipeptide isostere 88 was finally obtained after the opening of the lactam 87b in acidic conditions and N-Boc

An efficient synthesis of a C₁₂-higher sugar aminoalditol

• Łukasz Szyszka,
• Anna Osuch-Kwiatkowska,
• Mykhaylo A. Potopnyk and
• Sławomir Jarosz

Beilstein J. Org. Chem. 2017, 13, 2146–2152, doi:10.3762/bjoc.13.213

• phases were separated, and the aqueous layer was extracted with CH2Cl2 (3 × 20 mL). The combined organic solutions were washed with water (30 mL) and brine (30 mL), dried, concentrated, and the crude material was purified by flash chromatography (hexanes/ethyl acetate 5:1 to 2:1) to afford 13 (0.19 g

Iodoarene-catalyzed cyclizations of N-propargylamides and β-amidoketones: synthesis of 2-oxazolines

• Somaia Kamouka and
• Wesley J. Moran

Beilstein J. Org. Chem. 2017, 13, 1823–1827, doi:10.3762/bjoc.13.177

• mixture extracted with CH2Cl2. The organic layers were combined and dried with MgSO4, filtered and concentrated under vacuum. The product was purified by flash chromatography (9:1 petroleum ether/EtOAc) to provide oxazoline 6. See Supporting Information File 1 for full experimental details. Examples of

An efficient Pd–NHC catalyst system in situ generated from Na₂PdCl₄ and PEG-functionalized imidazolium salts for Mizoroki–Heck reactions in water

• Nan Sun,
• Meng Chen,
• Liqun Jin,
• Wei Zhao,
• Baoxiang Hu,
• Zhenlu Shen and
• Xinquan Hu

Beilstein J. Org. Chem. 2017, 13, 1735–1744, doi:10.3762/bjoc.13.168

• extracted with MTBE (5 mL × 2) and the organic layers combined, dried over anhydrous Na2SO4, and concentrated under vacuum. Finally, the resulted residual were purified by flash chromatography on silica to afford the desired cross-coupling alkene products. The purity of the obtained products was confirmed

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

Effect of uridine protecting groups on the diastereoselectivity of uridine-derived aldehyde 5’-alkynylation

• Raja Ben Othman,
• Mickaël J. Fer,
• Laurent Le Corre,
• Sandrine Calvet-Vitale and
• Christine Gravier-Pelletier

Beilstein J. Org. Chem. 2017, 13, 1533–1541, doi:10.3762/bjoc.13.153

• ) and allyl bromide (1.5 equiv). The suspension was stirred at 50 °C for 12 h, filtered and concentrated in vacuo. The resulting residue was submitted to flash chromatography (elution conditions mentioned below) to afford the corresponding N-allyl compound. General procedure for the oxidation of uridine

• h. The reaction was then quenched by addition of a saturated aqueous solution of NH4Cl (40 mL) and THF was removed in vacuo. The aqueous phase was extracted with EtOAc and the combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo. The crude foam was purified by flash

• chromatography. C-5’ configuration of nucleoside derivatives and related biological activity. 1H NMR of (5’R)-16 and (5’S)-16 and of a (5’R)/(5’S)-16 mixture. 1H NMR of (5’R)-17 and (5’S)-17 and example of configuration determination for a pure isolated compound with unknown configuration. Hypothetical Cram

Synthesis of oligonucleotides on a soluble support

• Harri Lönnberg

Beilstein J. Org. Chem. 2017, 13, 1368–1387, doi:10.3762/bjoc.13.134

• precipitation from water and one flash chromatography (Scheme 11). Detritylation was carried out with HCl in a 2:5 (v/v) mixture of MeOH and DCM. The acid was neutralized with pyridine, the mixture concentrated to oil and subjected to flash column chromatography on silica gel. For subsequent coupling, the

• desired commercial block was used in 50% excess and DCI as an activator. After standard I2 oxidation, the support-bound material was precipitated from water. The precipitation was quantitative, but some reagents and byproducts, above all DCI, coprecipitated with the support. The flash chromatography after

An improved preparation of phorbol from croton oil

• Alberto Pagani,
• Simone Gaeta,
• Andrei I. Savchenko,
• Craig M. Williams and
• Giovanni Appendino

Beilstein J. Org. Chem. 2017, 13, 1361–1367, doi:10.3762/bjoc.13.133

• purification of a crude mixture of ethanol solvates of phorboids by reverse-phase preparative flash chromatography or by countercurrent chromatography were developed [15][16][17]. The recovery of the triesters could be improved by first treating croton oil with acidic methanol to selectively remove the 20-acyl

Aqueous semisynthesis of C-glycoside glycamines from agarose

• Juliana C. Cunico Dallagnol,
• Alexandre Orsato,
• Diogo R. B. Ducatti,
• Miguel D. Noseda,
• Maria Eugênia R. Duarte and
• Alan G. Gonçalves

Beilstein J. Org. Chem. 2017, 13, 1222–1229, doi:10.3762/bjoc.13.121

• in warm MeOH (50 mL), filtered through a borosilicate sintered funnel and dried under reduced pressure. Finally the crude was submitted to flash chromatography (Silica Gel 60, Eluent: MeOH/2 M NH4OH 6:1) to give the pure glycamine. Physical data and spectral assignments Compound 3: [α]D: −23.0 (c 1.0