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

• cinchona squaramide organocatalyst 7 with a linker (Scheme 1). The lipophilic unit from methyl gallate (8) was gained by following a literature procedure [32] with minor modifications. The octadecyl groups were attached to the hydroxy groups using Williamson-type ether synthesis. The octadecylated gallic

Active-metal template clipping synthesis of novel [2]rotaxanes

• Cătălin C. Anghel,
• Teodor A. Cucuiet,
• Niculina D. Hădade and
• Ion Grosu

Beilstein J. Org. Chem. 2023, 19, 1776–1784, doi:10.3762/bjoc.19.130

• presence of supramolecular interactions that pre-organize rotaxane’s components is crucial for an efficient synthesis. The precursors of rotaxanes are supramolecular architectures held together by numerous interactions leading to diverse motifs such as ammonium crown ether (ion-dipole, hydrogen bonding

• after filtration and solvent evaporation. The compound was purified by column chromatography (silica, toluene/petroleum ether = 1:4) to afford a white solid (1.44 g, 73%); mp 222–225 °C, Rf = 0.44 (silica, toluene/petroleum ether = 1:4). 1H NMR (CDCl3, 600 MHz) δ 7.23 (d, 3J = 8.6 Hz, 6H, HAr), 7.10

• (1.90 g, 92%); mp 72–73 °C, Rf = 0.47 (silica, ethyl acetate/petroleum ether = 1:3);1H NMR (CDCl3, 600 MHz) δ 7.49 (s, 1H, HAr), 7.42–7.36 (overlapped signals, 3H, HAr), 6.93 (s, 8H, HAr), 5.03 (s, 4H, CH2), 4.65 (d, 4H, 4J= 2.3 Hz, CH2(propargyl)), 2.52 (t, 4J = 2.3 Hz, CH2(propargyl)) ppm; 13C NMR

Selectivity control towards CO versus H₂ for photo-driven CO₂ reduction with a novel Co(II) catalyst

• Lisa-Lou Gracia,
• Philip Henkel,
• Olaf Fuhr and
• Claudia Bizzarri

Beilstein J. Org. Chem. 2023, 19, 1766–1775, doi:10.3762/bjoc.19.129

• -dissolving the powder in acetonitrile and layering on top of diethyl ether (Et2O). Slow diffusion of the antisolvent Et2O allowed the growth of magenta-colored crystals. Interestingly, two different sets of data could be solved, which is an indication that compound 1 has two polymorphs, 1a and 1b (Figure 2

• interested in the development of earth-abundant systems. In particular, we chose the heteroleptic complex [Cu(dmp)DPEPhos](BF4), where dmp is 2,9-dimethyl-1,10-phenanthroline and DPEPhos is bis[(2-diphenylphosphino)phenyl] ether, which had been already successfully employed in other artificial photosynthesis

Unprecedented synthesis of a 14-membered hexaazamacrocycle

• Anastasia A. Fesenko and
• Anatoly D. Shutalev

Beilstein J. Org. Chem. 2023, 19, 1728–1740, doi:10.3762/bjoc.19.126

• useful for the preparation of other polyunsaturated annulated 14-membered 1,2,4,8,9,11-hexaazamacrocycles. Experimental All solvents and liquid reagents purchased from commercial sources were distilled prior to use. Petroleum ether had a distillation range of 40–70 °C. 100% Hydrazine hydrate was used in

• under reflux for 23 h. After the reaction had completed (monitored by 1H NMR spectroscopy), the obtained solution was concentrated under water pump vacuum upon heating in a water bath at 65 °C. The product was extracted from the resulting dense brown oil by trituration 4 times with a mixture of ether

• (25 mL) and petroleum ether (50 mL), and 1 time with a mixture of ether (10 mL) and petroleum ether (20 mL) at room temperature. The extraction was considered as completed when the brown oil solidified. The product precipitated upon concentration of the combined extracts under reduced pressure. The

Tying a knot between crown ethers and porphyrins

• Maksym Matviyishyn and
• Bartosz Szyszko

Beilstein J. Org. Chem. 2023, 19, 1630–1650, doi:10.3762/bjoc.19.120

• Maksym Matviyishyn Bartosz Szyszko Faculty of Chemistry, University of Wrocław, 14 F. Joliot-Curie St., 50-383 Wrocław, Poland 10.3762/bjoc.19.120 Abstract Porphyrins and crown ether hybrids have emerged as a promising class of molecules composed of elements of a tetrapyrrole macrocycle and an

• oligo(ethylene glycol) segment. These hybrid systems constitute a broad group of compounds, including crowned porphyrins, crownphyrins, and calixpyrrole-crown ether systems forming Pacman complexes with transition metals. Their unique nature accustoms them as excellent ligands and hosts capable of

• metals. In this perspective article, the overview of both the early designs of porphyrin-crown ether hybrids, as well as the most recent advances in the synthesis and characterisation of this remarkable group of macrocyclic systems, are addressed. The discussion covers the strategies employed in

Radical chemistry in polymer science: an overview and recent advances

• Zixiao Wang,
• Feichen Cui,
• Yang Sui and
• Jiajun Yan

Beilstein J. Org. Chem. 2023, 19, 1580–1603, doi:10.3762/bjoc.19.116

• necessary. MF-ROMP, also termed photo-ROMP, is a novel technique to polymerize cyclic olefins. It begins with the reductive quenching of an photoexcited photocatalyst (PC) at an enol ether initiator to produce a radical cation carrier [90]. Then, the carrier undergoes cyclic addition with a cyclic olefin

• (Scheme 12B). Boydston and co-workers [91], systematically studied various pyrylium and thiopyrylium PCs (Scheme 13). It is necessary for these PCs having a high excited-state redox potential to oxidize the enol ether initiators. A range of enol ether initiators that has been successfully applied in metal

• functionalization of optically active polymers [106]. Theato and co-workers introduced vinyl/alkyne-bearing poly(vinyl ether)s [107], poly(vinylcyclopropanes) [108], and poly(allyl 2-ylideneacetate) [109] as promising new platforms compatible to thiol–ene chemistry. Atom transfer radical addition (ATRA) is another

Cyclodextrins permeabilize DPPC liposome membranes: a focus on cholesterol content, cyclodextrin type, and concentration

• Ghenwa Nasr,
• Hélène Greige-Gerges,
• Sophie Fourmentin,
• Abdelhamid Elaissari and
• Nathalie Khreich

Beilstein J. Org. Chem. 2023, 19, 1570–1579, doi:10.3762/bjoc.19.115

• exposed to the native CDs (α-CD, β-CD, γ-CD) and four β-CD derivatives: the randomly methylated-β-CD (RAMEB), the low methylated-β-CD (CRYSMEB), the hydroxypropyl-β-CD (HP-β-CD) and the sulfobutyl ether-β-CD (SBE-β-CD) at different CD/DPPC molar ratios (1:1, 10:1, and 100:1). The membrane permeability was

• methylated-β-CD (CRYSMEB), the hydroxypropyl-β-CD (HP-β-CD), and the sulfobutyl ether-β-CD (SBE-β-CD). A schematic representation of the chemical structure of the native CDs and their dimensions is depicted in Figure 1, reprinted with permission from [21]. The structures of β-CD derivatives and their degrees

• hydroxypropyl-β-CD (HPBCD, DS = 5.6) were provided by Roquette Frères (Lestrem, France). Sulfobutyl ether-β-CD (SBE-β-CD, DS = 6.5) was provided by LIGAND Pharmaceuticals (San Diego, CA, USA). Dipalmitoylphosphatidylcholine (DPPC) and trizma base (buffer reagent) were purchased from Sigma-Aldrich, Switzerland

Lewis acid-promoted direct synthesis of isoxazole derivatives

• Dengxu Qiu,
• Chenhui Jiang,
• Pan Gao and
• Yu Yuan

Beilstein J. Org. Chem. 2023, 19, 1562–1567, doi:10.3762/bjoc.19.113

• TLC monitoring. Upon completion, the solution was cooled to room temperature and the solvent was removed under vacuum directly. The crude residue was purified by column chromatography on silica gel (ethyl acetate/petroleum ether 40:1) to afford product 3a with 87% yield. Natural products and drug

Synthesis and biological evaluation of Argemone mexicana-inspired antimicrobials

• Jessica Villegas,
• Bryce C. Ball,
• Katelyn M. Shouse,
• Caleb W. VanArragon,
• Ashley N. Wasserman,
• Hannah E. Bhakta,
• Allen G. Oliver,
• Danielle A. Orozco-Nunnelly and
• Jeffrey M. Pruet

Beilstein J. Org. Chem. 2023, 19, 1511–1524, doi:10.3762/bjoc.19.108

• . Conversion of naphthols to naphthylamines is typically achieved through a three-step sequence whereby the naphthol is first O-alkylated with 2-bromo-2-methylpropionamide and this ether undergoes a Smiles rearrangement to the hydroxyamide, which is hydrolyzed to the free naphthylamine [44][45]. It has

Application of N-heterocyclic carbene–Cu(I) complexes as catalysts in organic synthesis: a review

• Nosheen Beig,
• Varsha Goyal and
• Raj K. Bansal

Beilstein J. Org. Chem. 2023, 19, 1408–1442, doi:10.3762/bjoc.19.102

• . Two complexes, 61 and 65 (see Scheme 21), were found equally efficient. The products were obtained in 95 to 99% yield and the range of functionalities tolerated included nitro, nitrile, ether, carbonyl, alcohol, and amine [35]. Gautier and co-workers studied the effect of the addition of aromatic N

• -naphthol moiety 193 afforded the highest yield and enantioselectivity. On protecting the hydroxy group in the ligand as methyl ether, the reaction efficiency decreased remarkably. However, on using NHC ligands without oxygen atom, such as analogues of 193, IMes, and SIMes, no conversion occurred. 2.8 C(sp2

One-pot nucleophilic substitution–double click reactions of biazides leading to functionalized bis(1,2,3-triazole) derivatives

• Hans-Ulrich Reissig and
• Fei Yu

Beilstein J. Org. Chem. 2023, 19, 1399–1407, doi:10.3762/bjoc.19.101

• conditions found were studied with a second model reaction in order to examine its suitability for the synthesis of potential carbohydrate mimetic precursors (Scheme 3). Sodium azide, benzyl bromide (5) and enantiopure bicyclic 1,2-oxazin-4-one derivative 6 [53] which bears a propargylic ether moiety as

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

• Marco Antonio G. B. Gomes Alicia Bauduin Chloe Le Roux Romain Fouinneteau Wilfried Berthe Mathieu Berchel Helene Couthon Paul-Alain Jaffres Univ. Brest, CNRS, CEMCA UMR 6521, 6 Avenue Victor Le Gorgeu, 29238 Brest, France 10.3762/bjoc.19.96 Abstract Ether lipids are compounds present in many

• living organisms including humans that feature an ether bond linkage at the sn-1 position of the glycerol. This class of lipids features singular structural roles and biological functions. Alkyl ether lipids and alkenyl ether lipids (also identified as plasmalogens) correspond to the two sub-classes of

• naturally occurring ether lipids. In 1979 the discovery of the structure of the platelet-activating factor (PAF) that belongs to the alkyl ether class of lipids increased the interest in these bioactive lipids and further promoted the synthesis of non-natural ether lipids that was initiated in the late 60’s

Organic thermally activated delayed fluorescence material with strained benzoguanidine donor

• Alexander C. Brannan,
• Elvie F. P. Beaumont,
• Nguyen Le Phuoc,
• George F. S. Whitehead,
• Mikko Linnolahti and
• Alexander S. Romanov

Beilstein J. Org. Chem. 2023, 19, 1289–1298, doi:10.3762/bjoc.19.95

• mineral oil with diethyl ether and dried prior to use. 5H-Benzo[d]benzo[4,5]imidazo[1,2-a]imidazole (benzoguanidine) was obtained according to the literature protocol [10] while 2,4,5,6-tetrafluoroisophthalonitrile was purchased from Fluorochem Ltd. and used as received. 1H and 13C{1H} NMR spectra were

• /petroleum ether into dichloromethane solution for 4BGIPN at room temperature. Crystals were mounted in oil on a MiTeGen loop and fixed on the diffractometer in a cold nitrogen stream. Data were collected using dual wavelength Rigaku FR-X rotating anode diffractometer using Cu Kα (λ = 1.54146 Å) radiation

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• Hui Yu Feng Xu Department of Pharmacy, Shi zhen College of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou 550200, P. R. China School of Mathematics and Information Science, Guiyang University, Guiyang, Guizhou 550005, P. R. China 10.3762/bjoc.19.94 Abstract Ether derivatives

• become a major strategy for ether functionalization. This review covers C–H/C–H cross-coupling reactions of ether derivatives with various C–H bond substrates via non-noble metal catalysts (Fe, Cu, Co, Mn, Ni, Zn, Y, Sc, In, Ag). We discuss advances achieved in these CDC reactions and hope to attract

• interest in developing novel methodologies in this field of organic chemistry. Keywords: alkylation; cross-dehydrogenation coupling; ether; non-noble metals; Introduction Since the 1970s, organic chemists have developed many selective cross-coupling methods for the construction of C–C bonds, such as the

Metal catalyst-free N-allylation/alkylation of imidazole and benzimidazole with Morita–Baylis–Hillman (MBH) alcohols and acetates

• Olfa Mhasni,
• Jalloul Bouajila and
• Farhat Rezgui

Beilstein J. Org. Chem. 2023, 19, 1251–1258, doi:10.3762/bjoc.19.93

• under reflux (for 5a) or in a Dean–Stark apparatus (for 4a). After completion (TLC), the reaction mixture was cooled, washed with brine, and dried. The toluene was removed and the residue was purified by column chromatography on silica gel (acetone/ether 8:2) to give the pure N-substituted imidazole 6a

• mL) was added. The mixture was washed with brine and dried. Finally, the solvent was removed and the residue was purified by column chromatography on silica gel, using acetone/ether as eluent, to give the pure imidazole derivative 8. Medicines containing an imidazole nucleus. Synthesis of N

Selective construction of dispiro[indoline-3,2'-quinoline-3',3''-indoline] and dispiro[indoline-3,2'-pyrrole-3',3''-indoline] via three-component reaction

• Ziying Xiao,
• Fengshun Xu,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 1234–1242, doi:10.3762/bjoc.19.91

• solvent by rotatory evaporation at reduced pressure, the residue was subjected to column chromatography (silicon gel, 300–400 mesh) with petroleum ether and ethyl acetate (v/v = 1:1) to give the pure product for analysis. Ethyl rel-(3R,3'S,4'R)-1,1''-dibenzyl-5,5''-dichloro-7',7'-dimethyl-2,2'',5'-trioxo

• mixture was heated at 50 °C for seven hours. After removing the solvent by rotatory evaporation at reduced pressure, the residue was subjected to column chromatography (silicon gel, 300–400 mesh) with petroleum ether and ethyl acetate (v/v = 4:1) to give the pure product for analysis. rel-(3R,3'S,4'R)-1,1

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• bonding occurring between the Lewis basic ether and a σ-hole on the electropositive iodine (Scheme 14, inset). These results suggest that with iodonium ylides, ortho-substituents impose an electronic effect (compare 62a vs 62b and 62b vs 62c), contrary to the steric effect observed for radiofluorination

• of diaryliodonium salts [136][140]. Incorporation of a Lewis basic ether that could participate in secondary bonding with iodine was critical, and further improvements were realized when this Lewis base was not deactivating the ring (62c vs 62d). From these examples, the evidence suggests that σ

• even impacted the chemoselectivity of its subsequent reactions. Examples of this include the ortho-substituted iodoarene-derived ylides used in blue LED photoreactions between ylides and amines (Scheme 7) and radiofluorinations (Scheme 14), where ortho-ether moieties positively influenced the

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

Five new sesquiterpenoids from agarwood of Aquilaria sinensis

• Hong Zhou,
• Xu-Yang Li,
• Hong-Bin Fang,
• He-Zhong Jiang and
• Yong-Xian Cheng

Beilstein J. Org. Chem. 2023, 19, 998–1007, doi:10.3762/bjoc.19.75

• separated by a MCI gel CHP 20P column eluted with gradient aqueous MeOH (50–100%) to provide nine portions (Fr.1–Fr.9). Fr.6 (144.0 g) was separated into fourteen fractions (Fr.6.1–Fr.6.14) by a silica gel column with petroleum ether/EtOAc (50:1–0:1). Fr.6.3 (1.3 g) was further divided into four parts (Fr

• .6.3.1–Fr.6.3.4) by a vacuum liquid chromatography (VLC) on a silica gel column with petroleum ether/acetone (50:1–3:7) as solvents. Fr.6.3.1 (808.5 mg) was subjected to preparative thin-layer chromatography (PTLC) (dichloromethane) to give Fr.6.3.1.1–Fr.6.3.1.7, of which Fr.6.3.1.4 (255.9 mg) was

• column washed with petroleum ether/EtOAC (50:1–1:1). Among them, Fr.6.5.7 (355.7 mg) was subjected to PTLC (petroleum ether/acetone 5:1) to give Fr.6.5.7.1–Fr.6.5.7.7. Fr.6.5.7.1 (34.3 mg) was purified by semi-preparative HPLC on SEP Basic 120 C18 (aqueous MeOH, 65%) to give compound 9 (4.9 mg, tR = 9.4

The unique reactivity of 5,6-unsubstituted 1,4-dihydropyridine in the Huisgen 1,4-diploar cycloaddition and formal [2 + 2] cycloaddition

• Xiu-Yu Chen,
• Hui Zheng,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2023, 19, 982–990, doi:10.3762/bjoc.19.73

• temperature for two hours. After removing the solvent by rotatory evaporation at reduced pressure, the residue was subjected to column chromatography with petroleum ether and ethyl acetate (v/v = 5:1) as eluent to give the pure product for analysis. Trimethyl 4-benzyl-3-methyl-1-phenyl-4,4a,13b,13c-tetrahydro

• acetylenedicarboxylate (0.9 mmol), 5,6-unsubstituted 1,4-dihydropyridine (0.3 mmol) in acetonitrile (5.0 mL) was heated a reflux for three hours. After removing the solvent by rotatory evaporation at reduced pressure, the residue was subjected to column chromatography with petroleum ether and ethyl acetate (v/v = 6:1

Aromatic C–H bond functionalization through organocatalyzed asymmetric intermolecular aza-Friedel–Crafts reaction: a recent update

• Anup Biswas

Beilstein J. Org. Chem. 2023, 19, 956–981, doi:10.3762/bjoc.19.72

• benzofuran-2(3H)-one derivative 144 having an aza-quaternary stereocenter. The achiral Lewis acid tris(pentafluorophenyl)borane was required as additive in the reaction system to enhance the chemical yield and enantioselectivity. After two additional steps, i.e., demethylation of the phenolic ether and ester

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• ] used the heterogeneous catalyst H3PW12O40/SiO2 for the Clauson–Kaas synthesis of N-substituted pyrrole derivatives 63 (Scheme 30) by the reaction of amines 62 with 2,5-dimethoxytetrahydrofuran (2) in petroleum ether at reflux conditions in 60–93% yields (method 1) and MW-assisted solvent-free

• conditions in 90–96% yields (method 2). The optimization of the reaction conditions was performed in search of suitable conditions for this condensation reaction. Various acid catalysts (SiO2, HPA, HPA/SiO2, catalyst loadings (1 mol %, 2 mol %, 2.5 mol %, 0.3 g), solvent-systems (petroleum ether 40/60

• , toluene, n-hexane, acetonitrile) and reaction conditions (room temperature, 60 °C, reflux, and MW (power 5, 8 or 10), were studied. Among these, the optimized reaction conditions for method 1 are 2.5 mol % HPA/SiO2 as catalyst in refluxing petroleum ether, whereas the optimized conditions for method 2 are

Cyclodextrins as building blocks for new materials

• Miriana Kfoury and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2023, 19, 889–891, doi:10.3762/bjoc.19.66

• containing CDs. Three clinical trials have demonstrated the use of CDs in the treatment of COVID-19. Two of them use the sulfobutyl ether β-CD/remdesivir inclusion complex and the third applies the α-CD/sulforaphane inclusion complex called Sulforadex® [6]. The approved Janssen vaccine against SARS-CoV-2

• represented in the pharmaceutical market, in at least 130 marketed products [2]. Examples of the use of CDs in medicines are β-CD in cetirizine tablets and cisapride suppositories, γ-CD in a minoxidil solution, HP-β-CD in itraconazole antifungal, in intravenous and oral solutions, sulfobutyl ether β-CD in

Light-responsive rotaxane-based materials: inducing motion in the solid state

• Adrian Saura-Sanmartin

Beilstein J. Org. Chem. 2023, 19, 873–880, doi:10.3762/bjoc.19.64

• different flexibility. The crown ether derivative acts as a chassis in order to fix the thread. A ferrocenyl group attached at one of the ends of the linear component serves as a photosensitizer allowing the absorption of visible light. The different substitution induced different types of deformations

Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• the synthesis of intermediate stilbenes 61 by Wittig coupling. The authors elected to use a Pd2dba3/DPEphos (L4)/Cs2CO3 system (dba = dibenzylideneacetone; DPEphos = bis[(2-diphenylphosphino)phenyl] ether) in toluene after catalyst and ligand screening. Cyclisation of several substituted 2,2

• methyl ether aromatic substituents were tolerated. Unsymmetrical 10,11-dihydro-5H-dibenzo[b,f]azepine derivatives 71 have been synthesised by ortho-bromination of functionalised dihydrostilbenes 67, followed by intramolecular cyclisation using Buchwald–Hartwig amination (Scheme 14) [54]. The pathway

• prepared by Wittig methylenation of commercially available bis(2-formylphenyl) ether (119), whereas a formylation–Wittig methylenation sequence of commercial diphenylsulfone (120) and protected bis(2-bromophenyl)amine 121 afforded the S- and N-tethered diene, respectively. Ruthenium (2nd generation Hoveyda