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

Synthesis of medium and large phostams, phostones, and phostines

• Jiaxi Xu

Beilstein J. Org. Chem. 2023, 19, 687–699, doi:10.3762/bjoc.19.50

• ]thiophen-3-yl)methanol (23) and benzyl allylphosphonochlordiate (24) in the presence of triethylamine in diethyl ether via phosphonylation. It underwent a RCM reaction under the catalysis of Grubbs first generation catalyst in DCM, affording 2-(4-methylphenyl)benzothiophene-fused 2-(benzyloxy)-3,6,7,8,9,10

• ][17]. The Zn-catalyzed cross-coupling of dialkyl 2-bromo-1-methylethylphosphonates 68 and trimethylsilyl but-3-ynyl ether (69) generated dialkyl 5-hydroxy-1-methyl-3-methylenepentylphosphonates 70 in 66–73% yields under ultrasonic irradiation in THF at 45–50 °C for 45 min followed by treatment with

• ]oxaphosphinine 4-oxide and 1-phenyl-3,4-dihydronaphtho[1,8-cd][1,2]oxaphosphepine 1-oxide from 2-(naphthalen-1-yl)ethyl phenylphosphinate. Synthesis of 2-alkoxy-3,5-dimethylene-1,2-oxaphosphepane 2-oxides from dialkyl 2-bromo-1-methylethylphosphonates and trimethylsilyl but-3-ynyl ether. Synthesis of 14-methyl-2

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• Phebox-based rhodium complex (C3) to catalyze the tandem conjugate addition of a terminal alkene followed by reacting the bicyclic dienol silyl ether intermediate with Michael acceptors in a one-pot procedure (Scheme 50) [92]. The bridged cyclic products 196a,b, formed by a double Michael addition

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

• including the thiolation discussed above). Insertion of the t-Bu group also makes the (GlyNi)L7 complex more soluble in diethyl ether as compared to the parent (GlyNi)L1 complex (21.3 mg/1 mL vs <1 mg/1 mL in Et2O; see Figure 3). This is beneficial for electrosynthesis, simplifying the separation of the

• (right image) Ni–Schiff base derivatives with ligand L7. Saturated solutions of (GlyNi)L1 (left) and (GlyNi)L7 (right) in diethyl ether. The CV curves observed for (GlyNi)L7 and (ΔAlaNi)L7 in the anodic and cathodic regions (Pt, CH3CN, 0.1 M Bu4NBF4, 100 mV/s, vs Ag/AgCl/KCl(sat.)). Oxidation of (GlyNi

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• coordinate to the bicyclic alkene forming 91. Migratory insertion of the olefin affords 92 which undergoes intramolecular nucleophilic addition followed by protodemetalation and elimination of MHP to afford 94. Base-mediated ring opening of the bridging ether generates 95 which undergoes an elimination

• state, followed by coordination to the alkyne generates intermediate 109. Migratory insertion of the alkyne results in the ruthenacycle 110. Subsequent reductive elimination generates putative allyl vinyl ether 111 and regenerates the active ruthenium complex. The allyl vinyl ether intermediate

• those with hydrocarbon, ether, acetal, and ester functionalities; although, aniline nucleophiles only resulted in the one step asymmetric ring-opening (ARO) product under the standard reaction conditions. Fortunately, the authors noted the addition of triethylamine allowed for aniline nucleophiles to

Dipeptide analogues of fluorinated aminophosphonic acid sodium salts as moderate competitive inhibitors of cathepsin C

• Karolina Wątroba,
• Małgorzata Pawełczak and
• Marcin Kaźmierczak

Beilstein J. Org. Chem. 2023, 19, 434–439, doi:10.3762/bjoc.19.33

• diethyl ether in the next step should make precipitation more efficient [10]. This was done for compound 8a, but no improvement was observed. Much better results were obtained with additional double wash of the precipitate with methanol combined with evaporation of the solvent under reduced pressure. As a

Asymmetric synthesis of a stereopentade fragment toward latrunculins

• Benjamin Joyeux,
• Antoine Gamet,
• Nicolas Casaretto and
• Bastien Nay

Beilstein J. Org. Chem. 2023, 19, 428–433, doi:10.3762/bjoc.19.32

• between the two olefinic parts. After protection of the secondary alcohol as a para-methoxybenzyl (PMB) ether (78% yield of 14), the ketone (15) was installed in two steps from the epoxide (direct rearrangement attempts of the epoxide to form the ketone were unsuccessful). Thus, the epoxide was first

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• called cyclic diaryl ether heptanoids (DAEH). This review is intended to highlight the structure elucidation, biosynthesis, and biological activity of these compounds as well as the use of different strategies for their synthesis. Keywords: combretastatin D; corniculatolide; isocorniculatolide

• macrocycles and their synthesis finds several examples described in the literature and has already been the subject of review articles [2][3][4]. More recently, cyclic diaryl ether heptanoids (DAEH) [5], another class of macrocycles has been attracting attention not only because of their structural and

• would give compounds 12 and 13. A coupling reaction would give the corresponding diaryl ether Int-2, in a similar way to that suggested by Pettit, which could be selectively reduced to afford the corresponding seco-acid (intermediates Int-3 and Int-4). Subsequent macrolactonization would give the

Discrimination of β-cyclodextrin/hazelnut (Corylus avellana L.) oil/flavonoid glycoside and flavonolignan ternary complexes by Fourier-transform infrared spectroscopy coupled with principal component analysis

• Nicoleta G. Hădărugă,
• Gabriela Popescu,
• Dina Gligor (Pane),
• Cristina L. Mitroi,
• Sorin M. Stanciu and
• Daniel Ioan Hădărugă

Beilstein J. Org. Chem. 2023, 19, 380–398, doi:10.3762/bjoc.19.30

• corresponding flavanones hesperetin and naringenin and the flavonol quercetin, respectively. These compounds have a disaccharide moiety connected to the aglycones through an ether linkage with the hydroxy groups in the 7 and 3 positions (Figure 1a). On the other hand, silibinins (the main components of

• with 300 mL of anhydrous petroleum ether (ACS reagent, 40–60 °C boiling range, Sigma-Aldrich, St. Louis, MO, USA). The extract was distilled and evaporated to dryness until no petroleum ether remained. The oil separation yield was ≈50%. The hazelnut oil was kept at −20 °C until further analyses and β

Group 13 exchange and transborylation in catalysis

• Dominic R. Willcox and
• Stephen P. Thomas

Beilstein J. Org. Chem. 2023, 19, 325–348, doi:10.3762/bjoc.19.28

• ) methoxide (102) underwent Ga‒O/B‒C exchange with allyl-Bpin 103 to give MeOBpin and an allylic gallium(I) species 104, which reacted with the oxocarbenium 103 to give the allylic ether 105 and regenerate the GaI catalyst 99 (Scheme 25). Using allenylBpin, the selective propargylation of acetals was also

Synthesis, α-mannosidase inhibition studies and molecular modeling of 1,4-imino-ᴅ-lyxitols and their C-5-altered N-arylalkyl derivatives

• Martin Kalník,
• Sergej Šesták,
• Juraj Kóňa,
• Maroš Bella and
• Monika Poláková

Beilstein J. Org. Chem. 2023, 19, 282–293, doi:10.3762/bjoc.19.24

• in two steps from known ʟ-ribitol 1 [34] in good overall yield. Next, it was converted to the C-5 deoxygenated N-benzylpyrrolidine 6 via trityl ether cleavage, tosylation of the deprotected OH group, and reduction of the tosylate 5. Hydrogenolysis of the N-benzyl group in 6 followed by a removal of

• -benzyl group with the Cbz group, trityl ether hydrolysis, oxidation of the liberated OH group, and stereoselective addition of MeMgBr to the resulting aldehyde functionality. Hydrogenolysis of the Cbz protecting group in 13 followed by N-alkylation afforded pyrrolidines 14–16 which after acidic

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

• protection of the alcohol function as a silyl ether leading to diene 71, the RCM was performed in refluxing hexane and dactylol (72) was isolated in 17% overall yield after silyl ether removal [18][37]. Asteriscanolide (2), isolated in 1985 from the hexane extract of the plant Astericus aquaticus, is a

• exo Diels–Alder cycloaddition, which resulted in compound 159. The enol ether was oxidized by ceric ammonium nitrate (CAN) to deliver intermediate 160, which was further subjected to an iron-catalyzed hydrogen atom transfer generating tricyclic intermediate 161. Further functionalization permitted the

Investigation of cationic ring-opening polymerization of 2-oxazolines in the “green” solvent dihydrolevoglucosenone

• Solomiia Borova and
• Robert Luxenhofer

Beilstein J. Org. Chem. 2023, 19, 217–230, doi:10.3762/bjoc.19.21

• full monomer conversion. Monomer conversion was monitored by 1H NMR spectroscopy. After complete monomer consumption, the reaction was terminated by adding 3.0 equiv of water and left to react overnight at 45 °C. The polymer was purified by precipitation from cold diethyl ether (Et2O) or direct

• dialysis against water overnight, followed by lyophilization. The resulting polymer was obtained as a slightly yellow powder. The synthesis of 2-ethyl-3-methyloxazolinium triflate was carried out as follows: 30 mL of dry diethyl ether were placed in a dry round-bottomed flask and methyl

• trifluoromethanesulfonate (2.38 g, 14.50 mmol, 1.2 equiv) was added. The mixture was cooled in an ice bath. Then, 2-ethyl-2-oxazoline (1.20 g, 12.10 mmol, 1.0 equiv) was added slowly. A slight turbidity of the solution was observed. Over time an oily and colorless liquid phase was formed. The diethyl ether phase was

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• ]. At 0 °C, attempts to generate the ‘ortho-lithiated’ dithiins resulted in quantitative ring opening, giving the dimethylated derivative 22 as the sole product (Scheme 6b). The lithiated 1,4-dithiins are also not stable at −70 °C in diethyl ether, and cannot be alkylated using methyl iodide. With a

Synthesis and characterisation of new antimalarial fluorinated triazolopyrazine compounds

• Kah Yean Lum,
• Jonathan M. White,
• Daniel J. G. Johnson,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2023, 19, 107–114, doi:10.3762/bjoc.19.11

• yields. This paper reports additional and more thorough Diversinate™ studies on three phenethyl ether substituted triazolopyrazine scaffolds, with a particular focus on incorporating the fluoro fragments -CF3, -CF2H and -CF2Me into the OSM Series 4 structures via LSF chemistry. The new library of

• of an ether linker on the pyrazine ring, with a two methylene unit chain length between the heterocyclic core and benzylic substituent, improved the potency of these compounds [16]. Hence, scaffolds 1–3 were then converted into a series of ether-linked triazolopyrazines with phenethyl alcohol or

• studies (Supporting Information File 1, S51, S52, and S54), which confirmed the structure assignment. Compounds 4–6 were known OSM compounds that displayed good selective activity with IC50 values of <1 µM [16][21], whereas 7–9 are new ether derivatives without a phenyl ring that were synthesised for SAR

Practical synthesis of isocoumarins via Rh(III)-catalyzed C–H activation/annulation cascade

• Qian-Ci Gao,
• Yi-Fei Li,
• Jun Xuan and
• Xiao-Qiang Hu

Beilstein J. Org. Chem. 2023, 19, 100–106, doi:10.3762/bjoc.19.10

• %), AgSbF6 (6.9 mg, 10 mol %), HOAc (60.0 mg, 1.0 mmol) and DCE (2 mL) under N2 atmosphere. Then, the reaction mixture was stirred at 100 °C for 16 h. The crude product was purified by flash chromatography on silica gel (petroleum ether/ethyl acetate 5:1) directly to give the desired products 3. (Note: a

Revisiting the bromination of 3β-hydroxycholest-5-ene with CBr₄/PPh₃ and the subsequent azidolysis of the resulting bromide, disparity in stereochemical behavior

• Christian Schumacher,
• Jas S. Ward,
• Kari Rissanen,
• Carsten Bolm and
• Mohamed Ramadan El Sayed Aly

Beilstein J. Org. Chem. 2023, 19, 91–99, doi:10.3762/bjoc.19.9

• (80%), and 9 (8%), Scheme 2. Their polarities were so similar that they merged during color development on the hot TLC plate. Compounds 4 and 9 displayed in petroleum ether Rf values of 0.75 and 0.78, respectively. Finally, the two compounds could be separated by flash chromatography on silica gel of

• different mesh numbers. Single crystals of both were obtained by slow evaporation from diethyl ether. The less polar, minor material gave ice-white needles, and an X-ray single crystal structure determination revealed the product to be cholesta-3,5-diene (9, Figure 3). The 1H NMR data of 9 are in full

• interpretations of 4, 5 and 9 as well as those of follow-up compounds [10][11] need to be corrected as shown in (Figure 6). Experimental General information Cholesterol was purchased from Advent/India, CBr4 was purchased from Sigma-Aldrich while, NaN3 and PPh3 were purchased from Across. Diethyl ether was

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• time, some members have been recognized as potent topoisomerase inhibitors and have been used as anticancer drugs [106]. To access the rich diversity of this class, Zhu’s group recently applied a Fukuzumi salt ([Mes–Acr–Me]BF4)-mediated photochemical oxidation of dicinnamyl ether derivative 225 in the

• presence of appropriate additives (Scheme 18). According to the postulated mechanism, the reaction is initiated by an SET of the dicinnamyl ether substrate to Fukuzumi’s salt 233, leading to radical cation 216. Earlier findings of the same group [107] revealed that substitution on the aryl groups is the

• quenchers (e.g., PhSSPh) to the reaction mixture. When monosubstitution of the aryl group is present, the formed radical cation, the product of the photooxidation of the cinnamyl ether, readily cyclizes to cyclobutene radical cation 217. The latter cleaves the benzylic C–C bond to produce the 1,4-radical