Measuring the stereogenic remoteness in non-central chirality: a stereocontrol connectivity index for asymmetric reactions

• Ivan Keng Wee On,
• Yu Kun Choo,
• Sambhav Baid and
• Ye Zhu

Beilstein J. Org. Chem. 2025, 21, 1995–2006, doi:10.3762/bjoc.21.155

• biphenyl ether backbone (H vs Me, highlighted in grey), which is reflected by the relatively large values of the index [74]. Although we intend to avoid reaction intermediates in the assignment of the stereocontrol connectivity index, we recognize the limitations in cases that chemical bonds are cleaved

Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis

• Lihua Wei,
• Rui Yang,
• Zhifeng Shi and
• Zhiqiang Ma

Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151

• in intramolecular [7-exo] and [8-endo] cyclization, furnishing the 7-membered cyclic ether 40 and 8-membered cyclic ether 41, respectively. Finally, MOM deprotection produced (−)-heliannuol D (42) and (+)-heliannuol A (43). In 2002, Chênevert and co-workers completed the total synthesis of (S)-α

• deoxygenation of 200 and ketone reduction to give compound 201. Stereoselective hemiaminal ether formation promoted by BF3·Et2O with subsequent desilylation constructed the hexacyclic framework of alstrostine G, yielding compound 202. Finally, (+)-alstrostine G (203) was obtained through a two-step sequence. Zn

• , including (−)-ψ-akuammigine (Scheme 33) [81]. The synthesis commenced with dibenzoate 274, which underwent a Pd-catalyzed Trost desymmetrization using sulfonamide 275 and ligand 276. Deprotection of the resulting adduct furnished alcohol 277, which was subsequently converted to silyl enol ether 278 in two

Rhodium-catalysed connective synthesis of diverse reactive probes bearing S(VI) electrophilic warheads

• Scott Rice,
• Julian Chesti,
• William R. T. Mosedale,
• Megan H. Wright,
• Stephen P. Marsden,
• Terry K. Smith and
• Adam Nelson

Beilstein J. Org. Chem. 2025, 21, 1924–1931, doi:10.3762/bjoc.21.150

• the allylic ether C16 did not. It is remarkable that S(VI) electrophiles are tolerated. Eighteen substrate/co-substrate combinations gave, with at least one of the catalysts, an intermolecular product in >10% estimated yield (typically corresponding to >1 mg product). For all but one of these

Convenient alternative synthesis of the Malassezia-derived virulence factor malassezione and related compounds

• Karu Ramesh and
• Stephen L. Bearne

Beilstein J. Org. Chem. 2025, 21, 1730–1736, doi:10.3762/bjoc.21.135

• added dropwise at 0 °C. The reaction was then stirred for 2 h as the temperature rose from 0 °C to room temperature. The solution was then concentrated in vacuo to yield an oily residue that was co-evaporated with diethyl ether (3 × 10 mL) under vacuum to produce the desired compound 1 as a beige

3,3'-Linked BINOL macrocycles: optimized synthesis of crown ethers featuring one or two BINOL units

• Somayyeh Kheirjou,
• Jan Riebe,
• Maike Thiele,
• Christoph Wölper and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2025, 21, 1719–1729, doi:10.3762/bjoc.21.134

• ) [41][42][43] have been used for attaching the crown ether macrocycle, although this strategy has the advantage that the 2,2'-hydroxy groups remain intact and can be used for further binding or functionalization. Our group recently became interested in synthesizing BINOL derivatives featuring

• single precursor, but this is unnecessary if only macrocyclic bis-BINOL derivatives are desired. For this reason, we sought to find optimized syntheses for such BINOL-based macrocycles (see Figure 2). After investigating different synthetic routes (vide infra), we found that Williamson-type ether

• Unless otherwise stated, all BINOL derivatives were used as the (S)-enantiomers and the stereochemistry will not be mentioned further. Synthesis of macrocycles featuring one BINOL unit We first investigated the synthesis of crown ether-type macrocycles M1 which feature a single BINOL unit. Our previous

Approaches to stereoselective 1,1'-glycosylation

• Daniele Zucchetta and
• Alla Zamyatina

Beilstein J. Org. Chem. 2025, 21, 1700–1718, doi:10.3762/bjoc.21.133

• (reaction temperature −60 °C). Permanent ether-type protecting groups, such as benzyl, or those that require harsh acidic or basic conditions for removal, are often incompatible with the labile functional groups present in complex biomolecules derived from synthetic nonreducing disaccharides. To address

• variable ether- and ester-type protecting groups on the other, were obtained in yields of 64% and 72%, respectively (Scheme 9). Synthesis of aminosugar-containing nonreducing disaccharides proved being more challenging, as demonstrated by the use of 2-azido-2-deoxy 1-O-TMS-glycoside 105 as acceptor [71

• traditionally used glycosyl donor–acceptor pairs for the construction of α,α-1,1' glycosidic bonds involve benzyl ether- or acetyl-protected monosaccharide lactol acceptors and various types of glycosyl donors, such as thioglycosides, glycosyl imidates, glycosyl bromides and fluorides [51][64], several

Structural analysis of stereoselective galactose pyruvylation toward the synthesis of bacterial capsular polysaccharides

• Tsun-Yi Chiang,
• Mei-Huei Lin,
• Chun-Wei Chang,
• Jinq-Chyi Lee and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2025, 21, 1671–1677, doi:10.3762/bjoc.21.131

• -naphthylmethyl ether (Nap) protecting group was removed from disaccharide 10 using 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ) in a DCM/H2O (9:1) mixture, giving a 94% yield of disaccharide acceptor 11. To enhance solubility, the trimethylsilyl (TMS) group was selectively added at the less hindered 2-O

On the aromaticity and photophysics of 1-arylbenzo[a]imidazo[5,1,2-cd]indolizines as bicolor fluorescent molecules for barium tagging in the study of double-beta decay of ¹³⁶Xe

• Eric Iván Velazco-Cabral,
• Fernando Auria-Luna,
• Juan Molina-Canteras,
• Miguel A. Vázquez,
• Iván Rivilla and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2025, 21, 1627–1638, doi:10.3762/bjoc.21.126

• fluorescent moieties constitute promising candidates to detect Ba2+ cations [8][9] (Figure 2). Another essential component is an aza-crown ether of appropriate dimensions to capture the barium cation. In addition, one para-disubstituted phenyl (or aryl) group is installed to generate selective cation–π

• possible. The role of the crown ether and the para-phenylene moieties was also analyzed. The interactions of different sized crown ethers with Ba2+ and coordination with the aromatic ring modeled by means of benzene (14, highlighted in yellow in Scheme 2) were studied computationally. Although the

• -crown-6, namely the 1,4,7,10,13-pentaoxa-16-azacyclooctadecane moiety. We next investigated the coupling between the two components of the sensor gathered in Figure 2 at the free and Ba2+-bound states, namely the aza-crown ether-Ba2+-para-phenylene and the benzo[a]imidazo[5,1,2-cd]indolizine components

Facile synthesis of hydantoin/1,2,4-oxadiazoline spiro-compounds via 1,3-dipolar cycloaddition of nitrile oxides to 5-iminohydantoins

• Juliana V. Petrova,
• Varvara T. Tkachenko,
• Victor A. Tafeenko,
• Anna S. Pestretsova,
• Vadim S. Pokrovsky,
• Maxim E. Kukushkin and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 1552–1560, doi:10.3762/bjoc.21.118

• generated nitrile oxide seems to be less significant. It was found that the low solubility of products containing aromatic substituents in non-polar solvents allows for their isolation by washing the crude reaction mixture with diethyl ether to remove organic impurities and then with water to eliminate

• triethylamine hydrochloride. This method has proven to be simple and effective in most cases, with the exception of compound 5g. The moderate solubility of this compound in diethyl ether led to partial precipitation from the reaction mixture. It is worth noting that chromatographic purification is also possible

• congruence of the electronic properties of the substituents in the dipole and dipolarophile, as well as very low solubility of the product 5l in diethyl ether. An unexpected result was obtained during the 1,3-dipolar cycloaddition reaction between 2f and chloro oxime 4d. In contrast to reactions involving

Ambident reactivity of enolizable 5-mercapto-1H-tetrazoles in trapping reactions with in situ-generated thiocarbonyl S-methanides derived from sterically crowded cycloaliphatic thioketones

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Marcin Palusiak,
• Heinz Heimgartner,
• Marta Denel-Bobrowska and
• Agnieszka B. Olejniczak

Beilstein J. Org. Chem. 2025, 21, 1508–1519, doi:10.3762/bjoc.21.113

• a striking difference observed in the reactions performed in petroleum ether and in methanol is presented in Scheme 3 [22]. This amazing effect was studied in detail and discussed in later publications by R. Huisgen et al. [24][25]. Two dispiro-thioketones 7c and 7d, which are also known [26][27

Reactions of acryl thioamides with iminoiodinanes as a one-step synthesis of N-sulfonyl-2,3-dihydro-1,2-thiazoles

• Vladimir G. Ilkin,
• Pavel S. Silaichev,
• Valeriy O. Filimonov,
• Tetyana V. Beryozkina,
• Margarita D. Likhacheva,
• Pavel A. Slepukhin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2025, 21, 1397–1403, doi:10.3762/bjoc.21.104

• precipitate was filtered off and washed with cold ethanol and diethyl ether. Preparation of 2-sulfonyl-2,3-dihydro-1,2-thiazoles 3 (general procedure). Method A. The corresponding thioamide 1 (1.0 equiv) and DCM (1 mL) was added to an oven-dried standard microwave vial with a volume of 10 mL. The resulting

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• was generally accepted that this cyclic ether is planar but this myth was eventually debunked by Luger and Buschmann in 1984 who carried out the first X-ray analysis of oxetane [2] and calculated a small puckering angle of 8.7° at 140 K, which is much smaller than the approximate 30° puckering angle

• an alkoxide anion producing an ether (Scheme 2) [35]. Although this seems to be a relatively simple, straightforward reaction, the yields are often low due to the competing Grob fragmentation (Scheme 2) which, besides being entropically favoured, might also be favoured by the thermodynamic stability

• by trans-hydrostannation [50] of the corresponding alkyne precursors, so this report potentially introduced a new method for oxetane synthesis through an intramolecular Chan–Lam-type coupling. Due to the high reactivity of the exocyclic enol ether induced by the ring strain, 2-alkylidene

Synthesis of β-ketophosphonates through aerobic copper(II)-mediated phosphorylation of enol acetates

• Alexander S. Budnikov,
• Igor B. Krylov,
• Fedor K. Monin,
• Valentina M. Merkulova,
• Alexey I. Ilovaisky,
• Liu Yan,
• Bing Yu and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2025, 21, 1192–1200, doi:10.3762/bjoc.21.96

• from diisopropyl H-phosphonate (2a) was confirmed by HRMS analysis of the crude reaction mixture. Finally, vinyl azide 4a and silyl enol ether 4b were introduced into standard reaction conditions (Scheme 4, reaction 3). However, no phosphorylation product 3a was observed. On the basis of the obtained

Selective monoformylation of naphthalene-fused propellanes for methylene-alternating copolymers

• Kenichi Kato,
• Tatsuki Hiroi,
• Seina Okada,
• Shunsuke Ohtani and
• Tomoki Ogoshi

Beilstein J. Org. Chem. 2025, 21, 1183–1191, doi:10.3762/bjoc.21.95

• led to recovery of starting material or a complicated mixture probably owing to the modestly electron-rich and sterically demanding naphthalene α-positions (Table S202, entries 1–3, Supporting Information File 1). By contrast, a combination of dichloromethyl methyl ether and TiCl4 (Rieche reaction

• [3.3.3], diformylated product [3.3.3]_2CHO was obtained in 5.1% yield. In expectation of successful multifold formylation, the equivalents of dichloromethyl methyl ether and TiCl4 were doubled (Table 1, entry 4). The yield of [3.3.3]_2CHO modestly increased to 25% with a slight decrease in the yield of

Enhancing chemical synthesis planning: automated quantum mechanics-based regioselectivity prediction for C–H activation with directing groups

• Julius Seumer,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2025, 21, 1171–1182, doi:10.3762/bjoc.21.94

• activation [34]. Overview of the predictive workflow: For the shown substrate on the left, three unique activation sites are possible (labelled “Ha−c” with two directing groups, a pyridine (blue) and an oxime-ether (red) group. The latter has two potentially directing atoms, nitrogen and oxygen. The

Synthetic approach to borrelidin fragments: focus on key intermediates

• Yudhi Dwi Kurniawan,
• Zetryana Puteri Tachrim,
• Teni Ernawati,
• Faris Hermawan,
• Ima Nurasiyah and
• Muhammad Alfin Sulmantara

Beilstein J. Org. Chem. 2025, 21, 1135–1160, doi:10.3762/bjoc.21.91

• reacted with deprotonated diethyl malonate to obtain compounds 36 and ent-36 in 95 and 92% yield, respectively, over two steps from 34 and ent-34. The diols 28 (85%) and ent-28 (90%) were isolated after reduction of their parent malonates 36 and ent-36 using LiAlH4 in ether. Following several experiments

• LiAlH4 in ether to form alcohol 40 (89%) (Scheme 3). The primary alcohol 40 was then converted to its iodide derivative 42 (89%), from which single crystals were obtained, and its structure was determined unequivocally by XRD crystallography. Iodide 42 was then reacted with sodium phenylsulfinate in DMF

• % yield over three steps. This compound was isolated in its pure form as a white solid after recrystallization from ethanol, confirmed by HPLC and NMR. In parallel, the primary alcohol group of ent-38 was protected as a TBDMS ether, and the acetate group was converted to a tosyl ester by hydrolyzing the

Gold extraction at the molecular level using α- and β-cyclodextrins

• Susana Santos Braga

Beilstein J. Org. Chem. 2025, 21, 1116–1125, doi:10.3762/bjoc.21.89

• , led to the quick formation of co-precipitates when added to aqueous solutions of β-CD and KAuBr4 (both at 5 mM): dibutyl carbitol, isopropyl ether, chloroform, dichloromethane, hexane, benzene, and toluene [51]. The most effective one was dibutyl carbitol (DBC), which caused 99.7% precipitation when

Supramolecular assembly of hypervalent iodine macrocycles and alkali metals

• Krishna Pandey,
• Lucas X. Orton,
• Grayson Venus,
• Waseem A. Hussain,
• Toby Woods,
• Lichang Wang and
• Kyle N. Plunkett

Beilstein J. Org. Chem. 2025, 21, 1095–1103, doi:10.3762/bjoc.21.87

• further understand the complexation with metal cations, separate co-crystals of HIM 1 with LiBArF20 and NaBArF24 were obtained by vapor diffusion of diethyl ether into acetone. The details of the co-crystallization experiment are provided in the crystallographic information section of Supporting

Salen–scandium(III) complex-catalyzed asymmetric (3 + 2) annulation of aziridines and aldehydes

• Linqiang Wang and
• Jiaxi Xu

Beilstein J. Org. Chem. 2025, 21, 1087–1094, doi:10.3762/bjoc.21.86

• . Petroleum ether (PE, 60–90 °C fraction) and ethyl acetate (EA) were used as eluent. Reactions were monitored by thin-layer chromatography (TLC) on GF254 silica gel plates (0.2 mm) from Anhui Liangchen Silicon Material Co., Ltd. The plates were visualized by UV light. 1H NMR (400 MHz) and 13C NMR (101 MHz

• , dried over sodium sulfate, and freshly distilled prior to use. All solid aldehydes were used after recrystallization from petroleum ether (PE, 60–90 °C fraction) or a mixture of ethanol and water. All dialkyl 3-aryl-1-sulfonylaziridine-2,2-dicarboxylates 1 were synthesized by previously reported

• with a syringe and the mixture was stirred at 55 °C for 24 h. After gradually cooling to room temperature and removal of the solvent under reduced pressure, the crude residue was purified by basic aluminum oxide column chromatography with petroleum ether/ethyl acetate 1:10 to 3:7 (v/v) as eluent to

Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

• formation of an active α-ketenyl phosphorus ylide 345 (Scheme 77A) [130]. Similarly, Lin and co-workers (2024) employed PPh3 to selectively catalyze the esterification reaction of cyclopropenone 309 and amides to give the corresponding esters 346–348 containing an oxime ether in good yields (Scheme 77B

Recent total synthesis of natural products leveraging a strategy of enamide cyclization

• Chun-Yu Mi,
• Jia-Yuan Zhai and
• Xiao-Ming Zhang

Beilstein J. Org. Chem. 2025, 21, 999–1009, doi:10.3762/bjoc.21.81

• cyclopentane ring, dihydroxylation, and oxidation of the diol to a diketone, produced intermediate 25 in its enol form. From this common intermediate, regioselective etherification at the less hindered position formed an enol ether. Final reduction of both the amide and the ketone using alane completed the

On the photoluminescence in triarylmethyl-centered mono-, di-, and multiradicals

• Daniel Straub,
• Markus Gross,
• Mona E. Arnold,
• Julia Zolg and
• Alexander J. C. Kuehne

Beilstein J. Org. Chem. 2025, 21, 964–998, doi:10.3762/bjoc.21.80

A convergent synthetic approach to the tetracyclic core framework of khayanolide-type limonoids

• Zhiyang Zhang,
• Jialei Hu,
• Hanfeng Ding,
• Li Zhang and
• Peirong Rao

Beilstein J. Org. Chem. 2025, 21, 926–934, doi:10.3762/bjoc.21.75

• .) of 24 led only to epimerization at C10 or slow decomposition of the starting material (see Supporting Information File 1, Table S1). Pleasingly, treating 24 with HMDS and TMSI regioselectively generated the expected TMS enol ether [46], which underwent a Li/Si exchange in the presence of MeLi

• H2O under neutral conditions merely resulted in decomposition (Table 1, entry 10). To our delight, photoirradiation of the corresponding methyl ether 31 at 254 nm in the presence of AcOH at 20 °C led to a smooth cyclization, followed by spontaneous elimination, which produced the desired 10 as the

Dicarboxylate recognition based on ultracycle hosts through cooperative hydrogen bonding and anion–π interactions

• Wen-Hui Mi,
• Teng-Yu Huang,
• Xu-Dong Wang,
• Yu-Fei Ao,
• Qi-Qiang Wang and
• De-Xian Wang

Beilstein J. Org. Chem. 2025, 21, 884–889, doi:10.3762/bjoc.21.72

• target ultracyclic hosts. The synthesized ultracycles were fully characterized by spectrometric and elemental analysis (Scheme 1 and Schemes S1‒S3 in Supporting Information File 1). Single crystals of B4aH were obtained by slow vapor diffusion of ethyl ether into an acetonitrile/chloroform 1:1 (v/v

Unraveling cooperative interactions between complexed ions in dual-host strategy for cesium salt separation

• Zhihua Liu,
• Ya-Zhi Chen,
• Ji Wang,
• Qingling Nie,
• Wei Zhao and
• Biao Wu

Beilstein J. Org. Chem. 2025, 21, 845–853, doi:10.3762/bjoc.21.68

• binding Na+ and K+ by oligourea foldamers and macrocycles [37][38][39]. However, in the solid−liquid extraction of Li2SO4 in DMSO, addition of crown ether did not help to increase the extraction efficiency. This is because ion-dipole interactions are negligible in high polar solvent, and Li+ binding is

• to be slightly upfield-shifted in comparison to that of the free crown ether, indicating Cs+ binding, consistent with their extraction efficiency. The relatively upfield shifted chemical shift for the Cs3PO4 complex may indicate strong cooperative interaction upon solid–liquid extraction. To

• understand cooperative interactions between complexed ions, we tried to grow the crystal structure of studied salts. Fortunately, single crystals of Cs2CO3 and Cs3PO4 complexes were obtained by slow vapor diffusion from acetonitrile and diethyl ether. Notably, clearly stronger ion-dipole interactions of