Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

• additions to imines, comprising alcohols, thiols, phosphonates, diazoacetamides, peroxides, benzothiazolines and more as nucleophiles. Apart from reactant classes, the reactions also vary in additives, and solvent among others. Since these reactions all adhere to the same mechanism of enantioinduction, the

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

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

• N115, in the same experimental conditions. The Nafion-doped membrane with compound TP2 with a 1.0 wt % loading showed the highest proton conductivity with 84 mS·cm−1. Keywords: electrolyser; fuel cells; Nafion-modified membranes; phosphonates; proton exchange membranes; triazine; Introduction

• led to phosphonates 11 and 16, using diethyl phosphonate in the presence of a base, such as Et3N and NaOCH3, or even sodium metal, to obtain compound TP7 (Scheme 7). Unfortunately, these reactions afforded complex mixtures of products and by column chromatography was isolated only compound 20 in low

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• components, such as various acrylates, α,β-unsaturated acids, enones, enals, acrylamides, vinyl phosphonates, and vinyl sulfones. Various cesium salts of oxalates also performed well using this protocol. Isopropyl and tert-butyl groups present in an adjacent position of oxalates do not disturb the reaction

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• and Cheng et al. developed a convenient approach for the thiolation of β-keto phosphonates 89 by using N-(arylthio)phthalimides 14 under α,α-diaryl-ʟ-prolinols B organocatalytic system (Scheme 37) [71]. Sulfenylation of 3-aryloxindoles 91 with N-(arylsulfenyl)phthalimides 14 as the electrophilic

• thiophosphates, thiophosphinates and selenophosphates by reaction with the P(O)H moieties of H-phosphonates [105]. Conclusion To date, both metal-catalyzed and organocatalyzed C–S bond formations have been widely expanded. In particular, organocatalytic methodologies are effective for direct construction of

• acylation and acylthiolation. AlCl3-catalyzed synthesis of 3,4-bisthiolated pyrroles. α-Sulfenylation of aldehydes and ketones. Acid-catalyzed sulfetherification of unsaturated alcohols. Enantioselective sulfenylation of β-keto phosphonates. Organocatalyzed sulfenylation of 3‑substituted oxindoles

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

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

• ]. 2.2 Synthesis via [6 + 1] and [7 + 1] annulations The reactions of cyclohex-2-enone (87) and cyclohept-2-enone (88) with dimethyl phosphonate yielded dimethyl bicyclic phostone-phosphonates 89 and 90 under basic conditions in 59% yield via Michael addition, the nucleophilic hydrophosphonylation, and

Access to cyclopropanes with geminal trifluoromethyl and difluoromethylphosphonate groups

• Ita Hajdin,
• Romana Pajkert,
• Mira Keßler,
• Jianlin Han,
• Haibo Mei and
• Gerd-Volker Röschenthaler

Beilstein J. Org. Chem. 2023, 19, 541–549, doi:10.3762/bjoc.19.39

• . Phosphonates containing CF2 groups can sterically and electronically mimic oxygen, enabling the second dissociation constant, pKa2, to closer mirror those of the phosphates due to the electron-withdrawing effect of fluorine [39]. As a result, improved lipophilicity, metabolic stability or bioavailability of

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

• ]. Based on its structure, many other inhibitors have been developed, such as vinyl sulfones, fluoromethyl ketones, and semicarbazides [8][9]. These inhibitors covalently bind to the nucleophilic thiol group of Cys234 in the active site of cathepsin C via a thioether bond. Phosphonates have been identified

• the catalytic cysteine Cys234 [10]. Phosphonates, as well as their analogues phosphonic acids, can be modified in a number of ways, one of which is the introduction of a fluorine atom into their molecules by fluorination or alkylfluorination [11][12][13][14]. However, the reaction of β-aminoalcohols

• with nucleophilic deoxyfluorinating reagents often does not lead to the expected products with a fluorine atom in place of the –OH group. They usually undergo rearrangement, and intramolecular cyclization leading to products that are constitutional isomers [15]. The solvolysis reaction of phosphonates

Sequential hydrozirconation/Pd-catalyzed cross coupling of acyl chlorides towards conjugated (2E,4E)-dienones

• Benedikt Kolb,
• Daniela Silva dos Santos,
• Sanja Krause,
• Anna Zens and
• Sabine Laschat

Beilstein J. Org. Chem. 2023, 19, 176–185, doi:10.3762/bjoc.19.17

• condensation of enals 6 with aldehydes 7a or ketones 7b [6][7][8][9][10][11], isomerization of alkynones 8 [12][13][14][15], Horner–Wadsworth–Emmons reaction of unsaturated phosphonates 9 and aldehydes 10 [16][17], and dehydrogenation of enones 11 [18]. Further, Claisen rearrangement of vinyl propargylic

Organophosphorus chemistry: from model to application

• György Keglevich

Beilstein J. Org. Chem. 2023, 19, 89–90, doi:10.3762/bjoc.19.8

• . elaborated a Lewis acid-catalyzed one-pot synthesis of phosphinates and phosphonates staring from pyridinecarboxaldehydes and diarylphosphine oxides [2]. This protocol is the analogy of the Pudovik reaction, followed by the phospha-Brook rearrangement applied mainly for the synthesis of phosphoric ester

An alternative C–P cross-coupling route for the synthesis of novel V-shaped aryldiphosphonic acids

• Stephen J. I. Shearan,
• Enrico Andreoli and
• Marco Taddei

Beilstein J. Org. Chem. 2022, 18, 1518–1523, doi:10.3762/bjoc.18.160

• three novel aryl diphosphonate esters which were subsequently transformed to phosphonic acids through silylation and hydrolysis. Keywords: arylphosphonic acids; cross-coupling reaction; phosphonate esters; transition-metal catalysis; Introduction Phosphonates and phosphonic acids are a very

• . Phosphonates can also be employed as organic linkers in combination with metal ions to afford coordination polymers and metal-organic frameworks (MOFs), or more aptly, metal phosphonate frameworks [19][20]. One of the main challenges in the synthesis of metal phosphonates is that the linkers are rarely

• acids presented in this work, we have obtained three novel and structurally related linkers for the preparation of metal phosphonates. Each of the linkers was obtained in good yield and with no considerable impurities identified during characterization. This series of linkers will allow to determine the

Synthesis and electrochemical properties of 3,4,5-tris(chlorophenyl)-1,2-diphosphaferrocenes

• Almaz A. Zagidullin,
• Farida F. Akhmatkhanova,
• Mikhail N. Khrizanforov,
• Robert R. Fayzullin,
• Tatiana P. Gerasimova,
• Ilya A. Bezkishko and
• Vasili A. Miluykov

Beilstein J. Org. Chem. 2022, 18, 1338–1345, doi:10.3762/bjoc.18.139

• bromides from one starting aryl aldehyde. Diethyl phosphite was allowed to react with appropriately substituted benzaldehydes in THF for 48 hours at 25 °C to afford diethyl (hydroxy(aryl)methyl)phosphonates 1, which were detected by 31P NMR spectroscopy in THF (21.4 ppm for 1a, 21.0 ppm for 1b, and 21.5

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• diastereomers 30a,b and 32a,b was obtained, respectively. trans-Isomers were formed as major products over cis-isomers (Scheme 12) [52]. Five- and six-membered N-containing heterocyclic phosphonates were synthesized by intramolecular cyclization of alkenyl α-aminophosphonates in a similar way with the treatment

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• , DCC/DMAP, DCC/1-hydroxybenzotriazole (HOBt), bromotris(dimethylamino)phosphonium hexafluorophosphate (BroP), or O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate (HBTU) and by 31P NMR analysis. The results indicated that the intermediates, benzotriazolyl phosphonates, were more

CF₃-substituted carbocations: underexploited intermediates with great potential in modern synthetic chemistry

• Anthony J. Fernandes,
• Armen Panossian,
• Bastien Michelet,
• Agnès Martin-Mingot,
• Frédéric R. Leroux and
• Sébastien Thibaudeau

Beilstein J. Org. Chem. 2021, 17, 343–378, doi:10.3762/bjoc.17.32

• progressive conversion of the starting material into the C6-derivative 64 (Scheme 18). Chen et al. reported the synthesis of C2-phosphorylated indoles via 1,2-phosphorylation of 3-indolylmethanols with H-phosphine oxides or H-phosphonates under Brønsted acid activation [72]. The scope of the reaction includes

1,2,3-Triazoles as leaving groups in S_NAr–Arbuzov reactions: synthesis of C6-phosphonated purine derivatives

• Kārlis-Ēriks Kriķis,
• Irina Novosjolova,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 193–202, doi:10.3762/bjoc.17.19

• . Keywords: Arbuzov reaction; 2,6-bistriazolylpurines; nucleophilic aromatic substitution; purinylphosphonates; Introduction Acyclic nucleoside phosphonates (ANPs) are an important compound class due to their biological activity profile [1][2][3][4][5][6]. Compounds bearing a phosphonate moiety in their N9

• , the synthesis of C8-phosphonates of 7- and 9-deazapurines via C–H phosphonation has been reported [17]. On the other hand, azolylpurines are an important compound class that combines two recognized structural motifs of drug design – purines and azoles. Derivatives of this class are known for their

• toluene, MeCN, and DCM, and in the presence of 1–20 equiv of P(OEt)3, the formation of the desired phosphonates 4 was not observed (Scheme 6). We started an optimization of the reaction conditions using substrate 6d, and reactions in neat phosphite at various temperatures were tried (Table 2). The

Silver-catalyzed synthesis of β-fluorovinylphosphonates by phosphonofluorination of aromatic alkynes

• Yajing Zhang,
• Qingshan Tian,
• Guozhu Zhang and
• Dayong Zhang

Beilstein J. Org. Chem. 2020, 16, 3086–3092, doi:10.3762/bjoc.16.258

• others concerning the silver-catalyzed phosphonofluorination of alkenes [24][25][26], we herein present a general silver-catalyzed regio- and stereoselective phosphonofluorination of alkynes using Selectfluor® and phosphonates as reactants (Scheme 1). This new silver-catalyzed approach to fluorinated

• that no product was obtained (Scheme 6) [30]. Conclusion In conclusion, a novel method for the synthesis of β-fluorophosphonates through the direct phosphonofluorination of alkynes with Selectfluor® and H-phosphonates under mild reaction conditions has been successfully developed. Owing to its broad

Metal-free synthesis of biarenes via photoextrusion in di(tri)aryl phosphates

• Hisham Qrareya,
• Lorenzo Meazza,
• Stefano Protti and
• Maurizio Fagnoni

Beilstein J. Org. Chem. 2020, 16, 3008–3014, doi:10.3762/bjoc.16.250

• reports described that in some cases biaryls may be obtained in variable yields starting from biaryl phosphates [52], biaryl phosphonates II [53][54][55][56], and triaryl phosphates [57][58][59][60][61] (Scheme 1d, path b). In search for alternative ways for the preparation of biaryls under photoinduced

• photoextrusion from benzene sulfonamides I and phosphonates II, and e) photoextrusion from diaryl- (III) and triaryl (IV) phosphates. Metal-free photochemical synthesis of biaryls 2 and 4. Photoreactivity of aryl phosphates 1 and 3 in protic media. Optimization of the reaction conditions. Emission data of

Convenient access to pyrrolidin-3-ylphosphonic acids and tetrahydro-2H-pyran-3-ylphosphonates with multiple contiguous stereocenters from nonracemic adducts of a Ni(II)-catalyzed Michael reaction

• Alexander N. Reznikov,
• Dmitry S. Nikerov,
• Anastasiya E. Sibiryakova,
• Victor B. Rybakov,
• Evgeniy V. Golovin and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2020, 16, 2073–2079, doi:10.3762/bjoc.16.174

• University, Leninskie Gory, 1, 119991, Mosсow, Russian Federation 10.3762/bjoc.16.174 Abstract A new synthetic strategy toward nonracemic phosphoryl-substituted pyrrolidines and tetrahydropyranes with three and five contiguous stereocenters is presented. Readily available β-keto phosphonates react with

• conjugated nitroolefins in the presence of a chiral Ni(II) complex to give nitro keto phosphonates with two stereocenters with excellent enantioselectivity and moderate to high diastereoselectivity. These products were used for a reductive cyclization leading to pyrrolidin-3-ylphosphonic acid and for

• reactions with aldehydes yielding tetrahydropyranylphosphonates as individual stereoisomers. These nonracemic heterocycles containing phosphoryl moieties are useful for designing new pharmacologically active compounds. Keywords: asymmetric catalysis; Michael addition; phosphonates; pyrrolidines

Facile synthesis of 7-alkyl-1,2,3,4-tetrahydro-1,8-naphthyridines as arginine mimetics using a Horner–Wadsworth–Emmons-based approach

• Rhys A. Lippa,
• John A. Murphy and
• Tim N. Barrett

Beilstein J. Org. Chem. 2020, 16, 1617–1626, doi:10.3762/bjoc.16.134

• chromatographic purification (Scheme 2). Results and Discussion Based on applications of phosphonates derived from 2-methylpyridine and 2-methlylquinoline derivatives in Horner–Wadsworth–Emmons olefinations [13][14][15], it was proposed that similar a methodology could be applied to 7-methyl-1,2,3,4-tetrahydro

• taking place (Scheme 8) [24][25][26]. The autoxidation of phosphonates under THF/potassium tert-butoxide has been reported previously [27]. In order to circumvent racemisation of aldehyde 22 during the Horner–Wadsworth–Emmons olefination, alkylation of phosphoramidate 13 was explored using commercially

The McKenna reaction – avoiding side reactions in phosphonate deprotection

• Katarzyna Justyna,
• Joanna Małolepsza,
• Damian Kusy,
• Waldemar Maniukiewicz and
• Katarzyna M. Błażewska

Beilstein J. Org. Chem. 2020, 16, 1436–1446, doi:10.3762/bjoc.16.119

• compounds, with one representing the phosphonate, and the other containing a functional group, which could undergo a side reaction under the reaction conditions. As the first class of compounds, representing the phosphoryl group, we used phosphonates 8 and 9 (Figure 1). As the second class of model

• water and 1 equiv of TEA. Section 3: N-Alkylation As reported in the original paper [1], the McKenna reaction required up to 2 h at room temperature for simple phosphonates. However, depending on the structure of the phosphonate, longer reaction times are required, and the reaction is commonly carried

• expected, our studies using phosphonates 9a,b showed that as the concentration of ethyl bromide increases (Scheme 1), the formation of the N-alkylated product 20 was observed (Scheme 4), for compound 9a as well as for the α-fluorinated analog 9b (7–10% within 24 h, at 35 °C, monitored by 31P NMR

Highly selective Diels–Alder and Heck arylation reactions in a divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles from 2-formylpyrrole

• Carlos H. Escalante,
• Eder I. Martínez-Mora,
• Carlos Espinoza-Hicks,
• Alejandro A. Camacho-Dávila,
• Fernando R. Ramos-Morales,
• Francisco Delgado and
• Joaquín Tamariz

Beilstein J. Org. Chem. 2020, 16, 1320–1334, doi:10.3762/bjoc.16.113

• phosphonates 15a–c to afford derivatives 8a–f in high yields (Table 1, entries 1–6). For the synthesis of pyrroles 8g,h (R1 = Ac), pyrroles 13c and 13e were subjected to condensation reactions at a higher temperature, with acetone as the nucleophile (instead the phosphonate 15) in the presence of KOH as the

Synthesis, antiinflammatory activity, and molecular docking studies of bisphosphonic esters as potential MMP-8 and MMP-9 inhibitors

• Abimelek Cortes-Pacheco,
• María Adelina Jiménez-Arellanes,
• Francisco José Palacios-Can,
• José Antonio Valcarcel-Gamiño,
• Rodrigo Said Razo-Hernández,
• María del Carmen Juárez-Vázquez,
• Adolfo López-Torres and
• Oscar Abelardo Ramírez-Marroquín

Beilstein J. Org. Chem. 2020, 16, 1277–1287, doi:10.3762/bjoc.16.108

• , angiogenesis, and metastasis in cancer [12][13][14][15], pointing at bisphosphonates as potential treatments for cancer and other inflammation-related diseases. In this respect, MMP inhibition by phosphonates or bisphosphonates has been previously studied through computational or X-ray diffraction analyses to

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

• example, based on N-containing heterocycles (isoxazolones, pyrazolones, pyrazolidin-3,5-diones, and 1,2,3-triazolones [52]), sulfones [65], and phosphonates [54] (Scheme 8). Based on the data of EPR spectroscopy [35][38][49][50][66] and quantum chemical calculations [67], the maximum spin density in