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

• oxidation without isolation) produce 5,5'-oxybis(furan-2(5H)-one) and 5,5 '-(oxybis(methylene))bis-2-furfural [127][128][129] (Scheme 42, path a). The antimicrobial agent 5-chloro-2(5H)-furanone was synthesized by reaction of HFO with thionyl chloride in 30% yield [130], or with phosphorus chloride in 70

• phosphorus oxide catalyst (VPO), furoic acid was also found to be a key intermediate (Scheme 44, route b) [149]. A photocatalytic access to succinic anhydride from furoic acid using catalytic porphyrin H2TPP in the presence of O2 and light was also reported [150]. Yang and Lv reported the oxidation of

Synthesis, biological and electrochemical evaluation of glycidyl esters of phosphorus acids as potential anticancer drugs

• Almaz A. Zagidullin,
• Emil R. Bulatov,
• Mikhail N. Khrizanforov,
• Damir R. Davletshin,
• Elvina M. Gilyazova,
• Ivan A. Strelkov and
• Vasily A. Miluykov

Beilstein J. Org. Chem. 2025, 21, 1909–1916, doi:10.3762/bjoc.21.148

• synthetic organic chemistry and pharmaceutical applications due to their diverse biological activities. In this study, we synthesized three novel glycidyl esters of phosphorus acids 1–3 via the condensation of chlorophosphine oxides or phosphorus oxychloride with glycidol in the presence of a base

• . These findings provide important insights into the synthesis, cytotoxic activity, and biochemical reactivity of glycidyl esters of phosphorus acids, underscoring their potential as lead structures for further development in anticancer drug discovery and pharmaceutical research. Keywords: alkylating

• agent; glycidyl ester; electrochemical evaluation; phosphorus-containing drug; Introduction Phosphorus-containing drugs represent a crucial category of therapeutic agents, extensively utilized in clinical practice due to their diverse pharmacological properties and applications [1][2][3][4]. These

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

• catalytic sites. The OH group on the phosphorus atom functions as a Brønsted acid site, while P=O serves as a Lewis base site, which enables the simultaneous activation of both nucleophiles and electrophiles in one reaction (Figure 1). The chiral properties of the catalysts are derived from the chiral

Influence of the cation in hypophosphite-mediated catalyst-free reductive amination

• Natalia Lebedeva,
• Fedor Kliuev,
• Olesya Zvereva,
• Klim Biriukov,
• Evgeniya Podyacheva,
• Maria Godovikova,
• Oleg I. Afanasyev and
• Denis Chusov

Beilstein J. Org. Chem. 2025, 21, 1661–1670, doi:10.3762/bjoc.21.130

• Chemical Technology of Russia, Miusskaya sq. 9, Moscow, 125047, Russia National Research University Higher School of Economics, Myasnitskaya St. 20, Moscow, 101000, Russia 10.3762/bjoc.21.130 Abstract Reducing agents with phosphorus–hydrogen bond, such as sodium hypophosphite, phosphite, and

• of the most actively applied reductants with phosphorus-hydrogen bond in industry, for example, in production of polymers [1], pharmaceuticals [2], electroless plating [3], metal corrosion prevention [4] and even food preservation [5]. NaH2PO2 is a non-toxic (LD50 7640 mg/kg – rat) (SDS Thermo Fisher

Wittig reaction of cyclobisbiphenylenecarbonyl

• Taito Moribe,
• Junichiro Hirano,
• Hideaki Takano,
• Hiroshi Shinokubo and
• Norihito Fukui

Beilstein J. Org. Chem. 2025, 21, 1454–1461, doi:10.3762/bjoc.21.107

• absence of carbonyl groups in bis-olefin 5 has been corroborated by Fourier transform infrared (FTIR) spectroscopy (Figure S16 in Supporting Information File 1). Compound 4 could be generated through the reaction of compound 3 with phosphorus ylide. However, a reliable reaction mechanism remains unclear

Advances in nitrogen-containing helicenes: synthesis, chiroptical properties, and optoelectronic applications

• Meng Qiu,
• Jing Du,
• Nai-Te Yao,
• Xin-Yue Wang and
• Han-Yuan Gong

Beilstein J. Org. Chem. 2025, 21, 1422–1453, doi:10.3762/bjoc.21.106

• ). Notably, when chalcogen-containing substrates were used, the process afforded phosphorus ester derivatives of aza[5]helicenes. The chiral nature of the products was confirmed by optical rotation and CD measurements. In parallel, Soni’s group established an efficient three-step synthesis of coumarin

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

• include the products 137 through Strecker reactions, aldol-type condensations and phosphorus ylide-based olefinations (135) with subsequent Michael additions (138), or sulphinimine and ketone additions (140 and 141, respectively). These common functionalisations are also well documented in a recent

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

• [1][2][3][4][5] due to the numerous applications of phosphorus-containing compounds in pharmaceuticals, biology, agrochemistry, organic synthesis, and materials science [6][7][8][9][10][11][12][13]. Among various organophosphorus compounds, β-ketophosphonates have received particular attention for

• ][35][36][37][38][39]. The primary benefit of these reactions is introducing phosphorus fragments under mild reaction conditions into a diverse array of compounds that are inaccessible for functionalization employing other traditional approaches. After the pioneering work of Ji and Wei on aerobic

• results and previous reports on copper(II) mediated oxyphosphorylation reactions [42][44][46][51][53], a plausible reaction mechanism is proposed (Scheme 5). The discovered transformation is unlikely to proceed via only a single route (see control experiments in Scheme 4), and the generation of phosphorus

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

• migratory insertion (407) (Scheme 86A) [145]. On the other hand, Werner and Liu (2020) reported a Mn-catalyzed coupling of alcohols and phosphorus ylide 408 to afford the corresponding E-isomers of cinnamate esters 409–411 via an acceptorless dehydrogenative coupling mechanism (Scheme 86B) [146]. In

Recent advances in the electrochemical synthesis of organophosphorus compounds

• Babak Kaboudin,
• Milad Behroozi,
• Sepideh Sadighi and
• Fatemeh Asgharzadeh

Beilstein J. Org. Chem. 2025, 21, 770–797, doi:10.3762/bjoc.21.61

• synthesis of various organophosphorus compounds through the formation of phosphorus–carbon, phosphorus–nitrogen, phosphorus–oxygen, phosphorus–sulfur, and phosphorus–selenium bonds. The impact of different electrodes is also discussed in this matter. Graphite, platinum, RVC, and nickel electrodes have been

• organophosphorus compounds, in which phosphorus is attached to carbon or heteroatom centers. In this article, we describe recent advances in electrochemical green methods for the synthesis of various organophosphorus compounds through the formation of phosphorus–carbon, phosphorus–nitrogen, phosphorus–oxygen

• , phosphorus–sulfur, and phosphorus–selenium bonds. The impact of different electrodes is also discussed in this matter. Graphite, platinum, reticulated vitreous carbon (RVC), and nickel electrodes have been used extensively for the electrochemical synthesis of organophosphorus compounds. Review

New advances in asymmetric organocatalysis II

• Radovan Šebesta

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

• commonly defined as a form of catalysis where a small organic molecule, an organocatalyst, accelerates a chemical reaction. Unlike previously regarded traditional catalysts involving metals or enzymes, organocatalysts are composed of nonmetal elements, such as carbon, hydrogen, nitrogen, oxygen, phosphorus

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

• sugar and phosphorus, e.g., 82, Figure 10) are of interest as non-hydrolysable isosteres, but a better match in terms of pKa and C–C–P angle is achieved with mono- or difluorophosphonates (e.g., 83–85, Figure 10) [143][144]. In the case of the monofluorophosphonates, conformational effects can also be

Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• byproducts (Scheme 26b) [76][78]. Because of the tendency of formaldehyde to generate these byproducts, several efforts have been made to optimize the chemoselectivity of the Kabachnik–Fields reaction. In this context, Zhao et al. proposed a more selective strategy for the synthesis of α-amino phosphorus

• compounds using dihalomethanes (Scheme 27) [79]. They developed a three-component reaction between amines (mainly tertiary amines), a dihalomethane, and a P(OH) species (like phosphonate, phosphinate, or secondary phosphine oxide) under catalyst-free conditions to afford α-amino phosphorus compounds 35. The

• products are very appealing biologically relevant scaffolds due to their structural similarity to aminocarboxylic acids [80]. Moreover, the stereochemistry at the phosphorus center is conserved during the reaction. The reaction could also be performed with CH2Br2 and CH2I2 as the C1 building blocks and

Structure and thermal stability of phosphorus-iodonium ylids

• Andrew Greener,
• Stephen P. Argent,
• Coby J. Clarke and
• Miriam L. O’Duill

Beilstein J. Org. Chem. 2024, 20, 2931–2939, doi:10.3762/bjoc.20.245

• functionalities they can transfer. In this study, a fundamental understanding of the thermal stability of phosphorus-iodonium ylids is obtained through X-ray diffraction, differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). Insights into the structural factors affecting thermal stability

• groups or delocalisation into a π-system results in crystalline, bench-stable reagents. In the absence of stabilising factors, rapid decomposition occurs [21][22][23]. In this study, we aim to gain a fundamental understanding of the factors that stabilise phosphorus-iodonium ylids 1 (Figure 1B) [24][25

• the rational design and synthesis of novel, unstabilised hypervalent iodine(III) compounds and expand the application of these powerful reagents in organic synthesis. Results and Discussion Structural data Twelve phosphorus-iodonium ylids were synthesised (Figure 2). X-ray diffraction data (XRD) of

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

Computational design for enantioselective CO₂ capture: asymmetric frustrated Lewis pairs in epoxide transformations

• Maxime Ferrer,
• Iñigo Iribarren,
• Tim Renningholtz,
• Ibon Alkorta and
• Cristina Trujillo

Beilstein J. Org. Chem. 2024, 20, 2668–2681, doi:10.3762/bjoc.20.224

• new intermediate (Min5) is stabilised, in which the oxygen of CO2 has attacked the electrophilic carbon of PO, and the oxygen atom of PO interacts with the LB. This mechanism is exclusive to phosphorus-containing FLPs, as nitrogen does not support this type of reactivity. Subsequently, the

• intermediate undergoes reorganization, leading to Min2. Surprisingly, family 5, having phosphorus as the Lewis base, presents a different reactivity from the other families (Figure S3, Supporting Information File 1). Compounds F5_PB_H and F5_PB_CF3 react following mechanism 3 (Figure 5C), but the reaction

• kcal·mol−1. Remarkably, among the most efficient catalysts within this group of FLPs those with a nitrogen LB stand out. This phenomenon could be attributed to the exceptional stability of the covalent adduct formed between phosphorus-based FLPs and CO2. The second group comprises compounds that undergo

Anion-dependent ion-pairing assemblies of triazatriangulenium cation that interferes with stacking structures

• Yohei Haketa,
• Takuma Matsuda and
• Hiromitsu Maeda

Beilstein J. Org. Chem. 2024, 20, 2567–2576, doi:10.3762/bjoc.20.215

• ) packing structures and (ii) enlarged views for the columnar structures. In (i), cation and anion are represented in cyan and magenta colors, respectively. In (ii), brown, pink, yellow, blue, yellow green, orange, and green (spherical) refer to carbon, hydrogen, boron, nitrogen, fluorine, phosphorus, and

• +-Cl−, (b) 2+-BF4−, and (c) 2+-PF6−. Atom color code: yellow, green, orange, and green (spherical) refer to boron, fluorine, phosphorus, and chlorine, respectively. (i) Single-crystal X-ray structures and (ii) interaction energies for the pairs (a) 2+-Cl−, (b) 2+-BF4−, and (c) 2+-PF6−. In (i), the

Efficacy of radical reactions of isocyanides with heteroatom radicals in organic synthesis

• Akiya Ogawa and
• Yuki Yamamoto

Beilstein J. Org. Chem. 2024, 20, 2114–2128, doi:10.3762/bjoc.20.182

• yields. In the case of tert-butyl and benzyl isocyanides, the substituents on the nitrogen of imidoyl radical 2 (R = t-Bu or PhCH2, E = Et2P or Ph2P) were eliminated to give cyanophosphines (R’2P–CN, Scheme 7) [38]. On the other hand, we attempted a photoinduced addition of phosphorus–phosphorus

• in which phosphorus-centered radicals generated from diarylphosphine oxides by Mn(OAc)3-assisted oxidation [94] or the photoredox system [95][96][97] were used in the radical cyclization reaction of 2-isocyanobiaryls (Scheme 24). Yadav and Sigh et al. reported the direct synthesis of 6-sulfonylated

• photoredox system. Phenanthridine synthesis induced by phosphorus-centered radicals. Phenanthridine synthesis induced by sulfur-centered radicals. Phenanthridine synthesis induced by boron-centered radicals. Phenanthridine synthesis by oxidative cyclization of 2-aminobiaryls. Acknowledgements The authors

Regioselective alkylation of a versatile indazole: Electrophile scope and mechanistic insights from density functional theory calculations

• Pengcheng Lu,
• Luis Juarez,
• Paul A. Wiget,
• Weihe Zhang,
• Krishnan Raman and
• Pravin L. Kotian

Beilstein J. Org. Chem. 2024, 20, 1940–1954, doi:10.3762/bjoc.20.170

• favorable under conditions A. Postulating that O or N-dative interactions with phosphorus were responsible for the high N2-selectivity in an analogous fashion to conditions A, we searched for intermediates and TSs that included this possibility. No O–P or N2–P-coordinated intermediates were found. The

Syntheses and medicinal chemistry of spiro heterocyclic steroids

• Laura L. Romero-Hernández,
• Ana Isabel Ahuja-Casarín,
• Penélope Merino-Montiel,
• Sara Montiel-Smith,
• José Luis Vega-Báez and
• Jesús Sandoval-Ramírez

Beilstein J. Org. Chem. 2024, 20, 1713–1745, doi:10.3762/bjoc.20.152

• size and type of targeted cycle, ranging from four- to seven-membered rings, and encompasses heterocycles containing oxygen, nitrogen, sulfur, and/or phosphorus atoms. In instances where the stereochemistry of the new spiro centre remains undetermined, it is omitted. Additionally, the review excludes

• obtained as a mixture of two diastereomers in a 7:3 ratio, with the phosphorus atom adopting different configurations. Only one isomer of 109 could be isolated. The in vitro cytotoxicity of mixtures of isomers 108 and 109 was evaluated against three tumour cell lines: HeLa, MDA-MB-361, and MDA-MB-453

Chemo-enzymatic total synthesis: current approaches toward the integration of chemical and enzymatic transformations

• Ryo Tanifuji and
• Hiroki Oguri

Beilstein J. Org. Chem. 2024, 20, 1693–1712, doi:10.3762/bjoc.20.151

• utilizing the successfully overexpressed Diels–Alderase, MaDA (Scheme 5C). The chemical synthesis of 54, tri-O-acetylated precursor of the diene component 48, commenced from phenol 50. Iodination and O-acetylations of 50 followed by coupling with phosphorus ylide 51 afforded aryl iodide 52. Subsequent

New triazinephosphonate dopants for Nafion proton exchange membranes (PEM)

• Fátima C. Teixeira,
• António P. S. Teixeira and
• C. M. Rangel

Beilstein J. Org. Chem. 2024, 20, 1623–1634, doi:10.3762/bjoc.20.145

• the 31P atoms is observed as a singlet for both phosphorus atoms (Figure 2) and the carbon atom bonded to the chlorine atom is observed at 167.8 ppm. Also, the reaction with diethyl [hydroxy(4-aminophenyl)methyl]phosphonate (14) only afforded the disubstituted derivative TP3 (Scheme 5), despite the

• to chlorine, and the singlet signal of the phosphorus atom at the 31P NMR spectrum. The synthesis of the corresponding 4-hydroxyphenylphosphonate derivatives followed the same strategy of the amino counterparts’ preparation (Scheme 6). The initial reaction between cyanuric acid (1) and diethyl 4

• the molecule, with magnetically equivalent phosphorus atoms. The synthesis of other 4-hydroxyphenyltriazinephosphonate derivatives TP5 and TP6, starting from diethyl [(4-hydroxyphenyl)methyl]phosphonate (7) and tetraethyl [(4-hydroxyphenyl)methylene]bisphosphonate (13), were carried out using the same

Switchable molecular tweezers: design and applications

• Pablo Msellem,
• Maksym Dekthiarenko,
• Nihal Hadj Seyd and
• Guillaume Vives

Beilstein J. Org. Chem. 2024, 20, 504–539, doi:10.3762/bjoc.20.45

• using metal complexes as switching units (Figure 20). This concept named “weak link approach” (WLA) [78] uses square planar d8-transition metal complexes with two hemilabile bidentate ligands composed of a strong binding site (phosphorus) and a weaker one (generally sulfur, oxygen, selenium, or nitrogen

Using the phospha-Michael reaction for making phosphonium phenolate zwitterions

• Matthias R. Steiner,
• Max Schmallegger,
• Larissa Donner,
• Johann A. Hlina,
• Christoph Marschner,
• Judith Baumgartner and
• Christian Slugovc

Beilstein J. Org. Chem. 2024, 20, 41–51, doi:10.3762/bjoc.20.6

• ]. Concerning the 13C chemical shift for the aliphatic carbons directly attached to the phosphorus atom a slight down-field shift is found for 2a–i (24–20 ppm, 1JPC ≈ 64 Hz) when compared to similar alkyltriphenylphosphonium bromides (20–18 ppm, 1JPC ≈ 54 Hz) [37]. Finally, the 31P NMR shift (against H3PO4, 85

• phosphonium phenolates are largely unaffected by changing a phenyl group for an alkyl group like in 2a–i. Also other similarly substituted phosphonium salt species give the phosphorus signal in the range of 26–19 ppm [28][37][38]. For comparison, the phosphine 1 exhibits a 31P NMR shift of −29.7 ppm [35]. In

• phosphorus signal for 2d). Stability tests were also performed in two different deuterated solvents, CDCl3 and DMSO-d6. No air or moisture exclusion was applied. The tests were performed at room temperature and at 60 °C. 1H and 31P NMR spectra of the solutions were taken after 24, 48 and 72 h. At room

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

• sections also include some examples of non-phosphorus glycosylated antitumor ether lipids (GAEL) but more details on the biology of these ether lipids can be found elsewhere [49][50][51]. The synthesis of analogues of archaeal ether lipids is not included herein but the reader can refer to other articles

• which the acyl group can shift easily from the sn-2 to the sn-3 position. Noteworthy, the preparation of 8.2 was achieved in 3 steps from phosphorus trichloride and by using choline tetraphenylborate (prepared from choline chloride) [87] instead of the choline p-toluenesulfonate salt to improve the