Ni-promoted reductive cyclization cascade enables a total synthesis of (+)-aglacin B

• Si-Chen Yao,
• Jing-Si Cao,
• Jian Xiao,
• Ya-Wen Wang and
• Yu Peng

Beilstein J. Org. Chem. 2025, 21, 2548–2552, doi:10.3762/bjoc.21.197

• followed by reaction with CH(OMe)3 afforded acetal 17, which was then subjected to a CH2Cl2 solution of TMSOTf and iPr2NEt. A mixture of enol methyl ethers 18 were thus produced by an elimination reaction. Eventually, a site-selective bromination of the double bond over the electron-rich benzene rings with

Rotaxanes with integrated photoswitches: design principles, functional behavior, and emerging applications

• Jullyane Emi Matsushima,
• Khushbu,
• Zuliah Abdulsalam,
• Udyogi Navodya Kulathilaka Conthagamage and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2345–2366, doi:10.3762/bjoc.21.179

• anti-counterfeiting materials. Credi and co-workers recently introduced photoswitchable axles containing azobenzene units to control the threading and dethreading of macrocycles such as crown ethers and cyclodextrins. Although these systems are pseudorotaxanes, they are noteworthy for their potential

Halogenated butyrolactones from the biomass-derived synthon levoglucosenone

• Johannes Puschnig,
• Martyn Jevric and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2025, 21, 2297–2301, doi:10.3762/bjoc.21.175

• been reported in a 12-step procedure starting with glucose in an overall yield of 2% [24]. Enol esters [25], enolates [26], enamines [27][28], and silyl enol ethers [29], some of which can be derived from LGO, have been used in electrophilic fluorination and trifluoromethylation strategies. It was

Pathway economy in cyclization of 1,n-enynes

• Hezhen Han,
• Wenjie Mao,
• Bin Lin,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2025, 21, 2260–2282, doi:10.3762/bjoc.21.173

• derivatives 31 (Scheme 7, path b). This work provided a novel approach for constructing substituted naphthalene and indene frameworks via gold-catalyzed cycloisomerization of 1,5-enynes. In 2016, Liu et al. achieved the stereoselective syntheses of furofuran and furopyran scaffolds from propargyl vinyl ethers

• (Scheme 8, path b). The substituent-controlled gold(I)-catalyzed cycloisomerization of propargyl vinyl ethers provides a highly efficient platform for the divergent synthesis of functionalized furofuran and furopyran. Meanwhile, the preliminary antifungal assessment of these compounds underscored the

• identical reaction conditions. In 2016, the Liu group achieved unconventional Au(I)-catalyzed 6-endo-trig cyclization by modulating the angle strain of the enol ether (Scheme 29) [41]. In previous studies [42], propargylic vinyl ethers 140 underwent Au(I)-catalyzed propargyl-Claisen rearrangement to form an

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

Aryl iodane-induced cascade arylation–1,2-silyl shift–heterocyclization of propargylsilanes under copper catalysis

• Rasma Kroņkalne,
• Rūdolfs Beļaunieks,
• Armands Sebris,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2025, 21, 1984–1994, doi:10.3762/bjoc.21.154

• species are limited to aryl- [7][8][10] or heteroaryl groups [7][8]. In one example methyl ethers were used [9]. Under [Pd]-catalyzed conditions a syn-type addition is observed [8][11], while [Cu] catalysts promote anti-addition [7][10]. In substrates prone to cationic rearrangements (or hydride shifts

Chiral phosphoric acid-catalyzed asymmetric synthesis of helically chiral, planarly chiral and inherently chiral molecules

• Wei Liu and
• Xiaoyu Yang

Beilstein J. Org. Chem. 2025, 21, 1864–1889, doi:10.3762/bjoc.21.145

• chiral cyclohexylidene oxime ethers with high enantioselectivity [56]. In 2024, through the utilization of this method, Liu and co-workers disclosed the enantioselective synthesis of inherently chiral 7-membered tribenzocycloheptene oximes 76 through CPA 18-catalyzed asymmetric condensation between 7

Research progress on calixarene/pillararene-based controlled drug release systems

• Liu-Huan Yi,
• Jian Qin,
• Si-Ran Lu,
• Liu-Pan Yang,
• Li-Li Wang and
• Huan Yao

Beilstein J. Org. Chem. 2025, 21, 1757–1785, doi:10.3762/bjoc.21.139

• macrocycles such as crown ethers [43], cyclodextrins, and cucurbiturils, CAs and PAs have unique advantages. Their synthesis is simple (one-step completion), and they have adjustable conformations and π-electron-rich cavities [44][45], enabling efficient recognition of electron-deficient or neutral guest

• applications. This section will focus on the structural features and applications of CAs and PAs. 1.1 CAs: structure and properties CAs are the third generation of supramolecular hosts [40], succeeding cyclodextrins and crown ethers. They are macrocycles composed of phenolic units condensed with formaldehyde

• , imines, sulfur-containing groups, or alkyl chains) significantly expands their multifunctionality and broadens their application scope. Notably, CAs can be readily modified into amphiphilic macrocycles that can self-assemble with guests, and it exhibits superior advantages over crown ethers and

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

• ). Keywords: BINOL; chirality; crown ethers; macrocycles; supramolecular chemistry; Introduction Crown ethers are at the heart of supramolecular chemistry [1]. Ever since their discovery in 1960, a vast number of different crown ethers has been synthesized and their interactions with guest molecules have

• been studied. The pioneering works in this area by Cram, Lehn and Pedersen marked the beginning of modern supramolecular chemistry and were honoured with the Nobel Prize in Chemistry in 1987 [2][3][4]. Soon, it was realized that chiral crown ethers are highly promising host molecules for

• enantioselective molecular recognition. Different chiral backbones were used for the construction of such chiral crown ethers, especially chiral 1,2-diols such as tartaric acid [5][6][7][8], propane-1,2-diol [9][10][11][12][13], cyclohexane-1,2-diol [14], carbohydrates [15], 1,1'-binapthyl-2,2'-diol (BINOL) [16

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

• groups, as in the imidate donor 29, instead of benzyl ethers, was fully compatible and resulted in the exclusive formation of β-mannosyl-α-glucoside 30 [57]. This approach was successfully applied to the synthesis of a nonreducing disaccharide moiety of evernimicin, an octasaccharide antibiotic that

• -protected lactols with a defined anomeric configuration for use as glycosyl acceptors, with the limitation that the protecting groups had to be stable under acidic conditions, therefore, benzyl or 2-naphthylmethyl ethers were used. Glycosylation of the thioglycoside donor 152 with the TMS-protected α-lactol

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

• 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

• efficiency of crown ethers as components in cation-selective fluorescent probes has been extensively explored [7][30], to the best of our knowledge no previous computational DFT studies on the selectivity of crown ethers of different sizes with Ba2+ have been reported. Therefore, we explored (Scheme 2A) the

• binding between this cation and 12-crown-4 (16a, n = 1), 15-crown-5 (16b, n = 2), 18-crown-6 (16c, n = 3) and 21-crown-7 (16d, n = 4), to form Ba2+·crown ethers 15a–d. We compared the corresponding binding energies by means of the following isodesmic equation: Where the different terms correspond to Gibbs

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

• base [5]. In fact, its hydrogen-bond-accepting ability is even stronger than that of the other 3-, 5- and 6-membered cyclic ethers, as well as the carbonyls of aldehydes, ketones, esters and carbonates [6][7][8]. The only better carbonyl-based hydrogen-bond acceptors are amides, carbamates and ureas [9

• , vinyl, ethynyl or sulphide are sufficient if a superbase such as LIDAKOR or LICKOR is used (Scheme 16) [54][55]. The reaction tends to be remarkably regioselective (in terms of the epoxide opening) and stereoselective, however, it should be treated with caution in case of allyl ethers as they can also

• the precursor 60 from diazomalonate based on a Rh-catalysed O–H insertion, and further applied this cyclisation methodology to a preparation of tetrasubstituted oxetanes 62, including bicyclic analogues. In 2024, Liu, Shi, Wei and co-workers published the first radical cyclisation of ethers leading to

Recent advances and future challenges in the bottom-up synthesis of azulene-embedded nanographenes

• Bartłomiej Pigulski

Beilstein J. Org. Chem. 2025, 21, 1272–1305, doi:10.3762/bjoc.21.99

• alkenes: A bismuth-catalysed cyclization of alkenes has been demonstrated as an efficient synthetic tool for the creation of benzenoid PAHs [89]. Murai and co-workers applied this approach to the synthesis of azulene-embedded nanographenes (Scheme 18) [90]. Vinyl ethers 133a–d were cyclized using Bi(OTf)3

Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

• heteroatom for the synthesis of functionalized oxindoles was also reported in 2013 [3]. In this study, DBU was employed as a ligand and TBHP as an oxidant. A series of ethers, including 1,2-dimethoxyethane, THF, 1,4-dioxane, tetrahydro-2H-pyran, 2,3-dihydrobenzofuran, tetrahydro-2H-thiopyran, and N

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

• synthetic step distinguishes them from the less accessible substituted vinylarenes, alkynes, cinnamic and α,β-alkynyl carboxylic acids, as well as vinyl azides. In addition, compared to similar silyl and alkyl enol ethers, enol acetates are more resistant to solvolysis, which prevents unwanted side

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

• previous report of possible cation binding via mass spectrometry experiments [17], we were intrigued by the potential of HIM binding smaller cations such as lithium and sodium. While the previous authors suggested metal cations bind at the oxygen-rich core in a similar fashion to crown ethers, our

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

• tertiary enamides is employed. Inspired by Wang’s earlier work, Zhang and Tu’s group developed a tandem cyclization/Mannich reaction to construct this architecture [35]. However, unlike the electron-rich arenes, the use of silyl enol ethers to terminate the second cyclization of the acyliminium

Harnessing tethered nitreniums for diastereoselective amino-sulfonoxylation of alkenes

• Shyam Sathyamoorthi,
• Appasaheb K. Nirpal,
• Dnyaneshwar A. Gorve and
• Steven P. Kelley

Beilstein J. Org. Chem. 2025, 21, 947–954, doi:10.3762/bjoc.21.78

• alkene side product, presumably arising from mesylate elimination (Table 4, entry 4). In general, the functional group tolerance of the reaction was good, and aryl halogens, aryl CF3 moieties, and benzyl ethers were fully compatible (Table 4, entries 7 and 8). Where applicable, stereoarrays could be

New advances in asymmetric organocatalysis II

• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 766–769, doi:10.3762/bjoc.21.60

• prominent Hayashi–Jørgensen catalyst. This prolinol silyl ether was independently discovered by the respective Hayashi and Jørgensen research teams in 2005 [13][14]. Interestingly, the use of prolinol alkyl ethers for asymmetric Michael additions, although at the time added in a stoichiometric manner, has

Acyclic cucurbit[n]uril bearing alkyl sulfate ionic groups

• Christian Akakpo,
• Peter Y. Zavalij and
• Lyle Isaacs

Beilstein J. Org. Chem. 2025, 21, 717–726, doi:10.3762/bjoc.21.55

• supramolecular chemistry involves the synthesis of macrocyclic hosts and studies of their molecular recognition properties. The most widely studied macrocyclic host systems include those created entirely by covalent bonds (crown ethers, cyclodextrins, calixarenes, cyclophanes, pillararenes, cucurbit[n]urils (CB

Origami with small molecules: exploiting the C–F bond as a conformational tool

• Patrick Ryan,
• Ramsha Iftikhar and
• Luke Hunter

Beilstein J. Org. Chem. 2025, 21, 680–716, doi:10.3762/bjoc.21.54

• scaffolds – alkanes – then we will progress to ethers, alcohols, sugars, amines (and their derivatives), carbonyl compounds, peptides, and finally sulfur-containing compounds. By arranging the material in this way, we hope that newcomers to the field might be able to readily envisage ways to apply these

• macrocycle [74][75]. 2 Ethers We now turn our attention from alkanes to what is arguably the simplest heteroatom-containing functional group: the ether. The presence of oxygen within a carbon chain offers several new opportunities for engagement by an introduced fluorine atom. First, we will consider what

• pendant aryl moiety, is better for target-binding and hence 41 is a ≈10-fold more potent inhibitor of BACE-1 than 40. Several further examples of cyclic ethers will be examined in section 5 (sugars). The anomeric effect applies in acyclic ethers, too. Consider the non-fluorinated scaffold, Ph–O–CH3 (42

Asymmetric synthesis of β-amino cyanoesters with contiguous tetrasubstituted carbon centers by halogen-bonding catalysis with chiral halonium salt

• Yasushi Yoshida,
• Maho Aono,
• Takashi Mino and
• Masami Sakamoto

Beilstein J. Org. Chem. 2025, 21, 547–555, doi:10.3762/bjoc.21.43

• -workers developed chiral amine 1 with an electron-deficient iodine atom, which catalyzed the Mannich reaction in excellent yields and enantioselectivities [17]. In 2020, Huber and co-workers reported the bis(iodoimidazolium) 2-catalyzed Mukaiyama–aldol reaction of carbonyl compounds with enol silyl ethers

The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

• , respectively. Thakur and co-worker implemented the use of a nitrogen-rich tetrazole-linked ether group for a similar 1,2-trans stereodirecting property [160]. In this respect, they introduced the use of (1N/2N)-methylated tetrazole methyl (MeTetMe) ethers as a C-2 protecting group for glycosyl donors which was

Synthesis of disulfides and 3-sulfenylchromones from sodium sulfinates catalyzed by TBAI

• Zhenlei Zhang,
• Ying Wang,
• Xingxing Pan,
• Manqi Zhang,
• Wei Zhao,
• Meng Li and
• Hao Zhang

Beilstein J. Org. Chem. 2025, 21, 253–261, doi:10.3762/bjoc.21.17

• intermediate in the reaction. When the asymmetric thiosulfonate was used as the substrate, unexpectedly a mixture of three disulfide ethers rather than a single disulfide was obtained under the standard reaction conditions (Scheme 5, reaction 1), which led us to conclude that the reaction might be a process in

Hydrogen-bonded macrocycle-mediated dimerization for orthogonal supramolecular polymerization

• Wentao Yu,
• Zhiyao Yang,
• Chengkan Yu,
• Xiaowei Li and
• Lihua Yuan

Beilstein J. Org. Chem. 2025, 21, 179–188, doi:10.3762/bjoc.21.10

• cucurbituril [18], cyclodextrin [19], and calix[4]pyrrole [20], as well as flexible crown ethers [10][21]. Few two-dimensional (2D) shape-persistent macrocyclic compounds are used for this purpose. One difficulty in realizing 2D macrocycle-based orthogonal assembly is that the construction motif must be