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

Photocatalysis with organic dyes: facile access to reactive intermediates for synthesis

• Stephanie G. E. Amos,
• Marion Garreau,
• Luca Buzzetti and
• Jerome Waser

Beilstein J. Org. Chem. 2020, 16, 1163–1187, doi:10.3762/bjoc.16.103

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• reactions between N-phenyltetrahydroisoquinoline and dimethyl malonate, nitromethane, indoles, and dialkyl phosphonates furnished the α-substituted N-phenyltetrahydroisoquinolines in yields equal or better than with the originally used photocatalysts, such as eosin and Ir-complex [29][30][31] (Scheme 10

• ]. Che and co-workers showed that a variety of nucleophiles can be used for the α-functionalization of N-aryltetrahydroisoquinolines using a low Pd-TPFPP loading. This photocatalyst provided the α-aminonitriles in 71–85%, β-nitroamines in 72–83%, β-diester amines in 68–74%, and α-amino phosphonates in 63

Efficient synthesis of dipeptide analogues of α-fluorinated β-aminophosphonates

• Marcin Kaźmierczak and
• Henryk Koroniak

Beilstein J. Org. Chem. 2020, 16, 756–762, doi:10.3762/bjoc.16.69

• applications of fluorinated aminophosphonates and aminophosphonic acid derivatives, they exhibit antiviral [4][5], antibacterial [6] and antifungal [7] activities. Moreover, α-fluorinated phosphonates can be considered as hydrolytically stable mimics of naturally occurring phosphates [8]. Due to the fact that

• enzyme binding may depend on the C–F stereochemistry, the synthesis of such compounds with a specific configuration is very important [9][10][11]. α-Fluorinated phosphonates can be prepared by many different protocols [12][13][14][15][16]. Nucleophilic fluorination is one of the fundamental reactions in

Copper-catalyzed O-alkenylation of phosphonates

• Nuria Vázquez-Galiñanes,
• Mariña Andón-Rodríguez,
• Patricia Gómez-Roibás and
• Martín Fañanás-Mastral

Beilstein J. Org. Chem. 2020, 16, 611–615, doi:10.3762/bjoc.16.56

• /bjoc.16.56 Abstract Copper catalysis allows the direct oxygen alkenylation of dialkyl phosphonates with alkenyl(aryl)iodonium salts with selective transfer of the alkenyl group. This novel methodology proceeds with a wide range of phosphonates under mild conditions and gives straightforward access to

• valuable enol phosphonates in very good yields. Keywords: alkenylation; copper; C(sp2)–O bond formation; hypervalent iodine; phosphonates; Introduction Organophosphorus compounds represent an important class of products with a wide range of applications in biology, agriculture and synthetic organic

• chemistry [1][2][3]. In particular, O-alkenyl phosphonate esters (i.e., enol phosphonates) have been described as potent insecticides and show antifungal activity [4]. While several methods are available for the preparation of cyclic enol phosphonates [5][6][7][8][9][10], the synthesis of the acyclic

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• chlorides [20]. This ATRA reaction was carried out with various fluoroalkylsulfonyl chlorides, such as CFH2SO2Cl, CF2HSO2Cl, CF3SO2Cl, CF3CH2SO2Cl, and C4F9SO2Cl, electron-deficient alkenes, including α,β-unsaturated ketones, amides, esters, carboxylic acids, sulfones, and phosphonates (Scheme 4). In

[1,3]/[1,4]-Sulfur atom migration in β-hydroxyalkylphosphine sulfides

• Katarzyna Włodarczyk,
• Piotr Borowski and
• Marek Stankevič

Beilstein J. Org. Chem. 2020, 16, 88–105, doi:10.3762/bjoc.16.11

• phosphonate–phosphinate rearrangement of dimethyl phosphonates [50]. Other [1,3]-rearrangements of organophosphorus compounds include phosphoenolpyruvate formation from phosphonopyruvate [51], benzylphosphonium salt formation from the corresponding o-methylaryl-substituted precursors [52], or the formation of

Synthesis of C-glycosyl phosphonate derivatives of 4-amino-4-deoxy-α-ʟ-arabinose

• Lukáš Kerner and
• Paul Kosma

Beilstein J. Org. Chem. 2020, 16, 9–14, doi:10.3762/bjoc.16.2

• Ara4N transferase reacted with the equatorial phosphodiester lipid, we opted to use lactone 4 as a suitable precursor for C-glycosyl phosphonates, based on literature precedents [10][20][21]. Thus, a modified Swern oxidation of lactol 3 with acetic anhydride in DMSO afforded a near-quantitative yield of

• precursors for the introduction of fluoromethyl phosphonates, which are the better bioisosters of phosphates [23][24][25]. Exo-glycal 8 was obtained in 74% yield when using methyl oxalyl chloride [26], which proved to be superior to the use of trifluoroacetic anhydride, which gave 8 in 57% yield [27]. The Z

• lipid A by ArnT. Phosphonate and glycal synthesis. Synthesis of methyl phosphonate 11 and octyl phosphonates 16 and 17. Supporting Information Supporting Information File 324: Experimental section, spectral data, and copies of 1H, 13C, and 31P NMR spectra of compounds 4, 6, and 8–17. Acknowledgements

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• a palladium catalyst (Scheme 9). Under these conditions, the fluorination of ethyl 2-cyano-2-phenylacetate afforded the product with highest enantiomeric excess (93%). In 2013, Kim’s group [46] described an enantioselective electrophilic fluorination of α-chloro-β-keto phosphonates with up to 95% ee

Synthesis of ([1,2,4]triazolo[4,3-a]pyridin-3-ylmethyl)phosphonates and their benzo derivatives via 5-exo-dig cyclization

• Aleksandr S. Krylov,
• Artem A. Petrosian,
• Julia L. Piterskaya,
• Nataly I. Svintsitskaya and
• Albina V. Dogadina

Beilstein J. Org. Chem. 2019, 15, 1563–1568, doi:10.3762/bjoc.15.159

• . Chemical shifts of the phosphorus nucleus for compounds 3–8 were registered in the range of δP 22–23 and 18–19 ppm for dimethyl а and diisopropyl phosphonates b, respectively. In the 1Н NMR spectra of products 3–8, the methylene unit was recorded as a doublet signal (δH 3.42–4.19 ppm) with a spin–spin

Synthesis of non-racemic 4-nitro-2-sulfonylbutan-1-ones via Ni(II)-catalyzed asymmetric Michael reaction of β-ketosulfones

• Alexander N. Reznikov,
• Anastasiya E. Sibiryakova,
• Marat R. Baimuratov,
• Eugene V. Golovin,
• Victor B. Rybakov and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2019, 15, 1289–1297, doi:10.3762/bjoc.15.127

• that the reaction of β-keto phosphonates with nitroalkenes in the presence of Ni(II) complexes with chiral vicinal diamines was carried out not only with excellent enantioselectivity, but also diastereoselectivity [55]. Moreover, β-keto sulfoxides react with nitroalkenes under catalysis by Ni(II

An improved synthesis of adefovir and related analogues

• David J. Jones,
• Eileen M. O’Leary and
• Timothy P. O’Sullivan

Beilstein J. Org. Chem. 2019, 15, 801–810, doi:10.3762/bjoc.15.77

• the synthesis of acyclic nucleoside phosphonates including mesylates [42], tosylates [16][43][44] and alkyl chlorides [45][46][47][48][49][50][51]. Alkylation reactions conducted with these electrophiles generally require higher temperatures. Furthermore, these reagents typically afford products in

Cross metathesis-mediated synthesis of hydroxamic acid derivatives

• Shital Kumar Chattopadhyay,
• Subhankar Ghosh and
• Suman Sil

Beilstein J. Org. Chem. 2018, 14, 3070–3075, doi:10.3762/bjoc.14.285

• CM-mediated synthesis of functionalized alkenes of various kinds continue to appear. For example, cross metathesis with acrylates [8][9][10], α,ß-unsaturated acid chlorides [11], acrylamides [12][13][14], vinyl sulfones [15], vinylphosphine oxides [16], vinyl phosphonates [17], enones [18], and

Pd-Catalyzed microwave-assisted synthesis of phosphonated 13α-estrones as potential OATP2B1, 17β-HSD1 and/or STS inhibitors

• Rebeka Jójárt,
• Szabolcs Pécsy,
• György Keglevich,
• Mihály Szécsi,
• Réka Rigó,
• Csilla Özvegy-Laczka,
• Gábor Kecskeméti and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 2838–2845, doi:10.3762/bjoc.14.262

• dialkyl phosphites (H-phosphonates) as the reagents, Pd(PPh3)4 as the catalyst and Et3N as the base [26]. Variations of the reaction have recently been published to prepare diverse functionalized phosphonates [27][28]. The C–P couplings have been performed not only under traditional thermal conditions

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• chemistry set-up, which requires a large amount of optimisation itself. A range of nucleophiles including nitroalkanes, cyanides, malonates and phosphonates are used to modify different N-aryltetrahydroisoquinolines. These products have the potential for quite a range of subsequent reactions for elaboration

Preparation of trinucleotide phosphoramidites as synthons for the synthesis of gene libraries

• Ruth Suchsland,
• Bettina Appel and
• Sabine Müller

Beilstein J. Org. Chem. 2018, 14, 397–406, doi:10.3762/bjoc.14.28

• advantages of solution chemistry and solid-phase methods. Thus, solid-supported acyl chloride or pyridinium tosylate as the activator of nucleoside-3'-O-H-phosphonates/phosphoramidites, and polystyrene-bound trimethylammonium periodate as oxidation reagent have been demonstrated to be superior for dimer and

Fluorescent nucleobase analogues for base–base FRET in nucleic acids: synthesis, photophysics and applications

• Mattias Bood,
• Sangamesh Sarangamath,
• Moa S. Wranne,
• Morten Grøtli and
• L. Marcus Wilhelmsson

Beilstein J. Org. Chem. 2018, 14, 114–129, doi:10.3762/bjoc.14.7

• product 9, which was used in the next step without isolation and 10 in 50% yield over three steps, respectively. Lastly, phosphitylation yielded the corresponding H-phosphonates 11 in 71% yield over two steps and 12 in 80% yield (Scheme 2). In 2001, tC was reported as a fluorescent nucleobase analogue [39

• deoxyribose phosphonates [41]. (a) Ac2O, pyridine, rt; (b) 2-mesitylenesulfonyl chloride, TEA, then 2-aminothiophenol or 2-aminophenol, DBU, rt, 27% and 54% yield, respectively, over two steps; (c) t-BuOK in EtOH, reflux, 38%; (d) NH3 in MeOH, rt, then 10 equiv of KF, EtOH, reflux; (e) 4,4´-dimethoxytrityl

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

Phosphonic acid: preparation and applications

• Charlotte M. Sevrain,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2017, 13, 2186–2213, doi:10.3762/bjoc.13.219

• group simultaneously to the formation of the P–C bond, are also surveyed. Among all these methods, the dealkylation of dialkyl phosphonates under either acidic conditions (HCl) or using the McKenna procedure (a two-step reaction that makes use of bromotrimethylsilane followed by methanolysis) constitute

• start from phosphonates (section 3 and Figure 1). However, other possibilities exist: the hydrolysis of dichlorophosphine or dichlorophosphine oxide (section 4), the hydrolysis of phosphonodiamide (section 5), the direct methods that make use of phosphorous acid (H3PO3) to create the P–C bond

• be noted that in many cases the purification occurs on the precursors of the phosphonic acid. As an example, dialkyl phosphonates (the diester derivatives of phosphonic acid) can be easily purified by chromatography on silica gel and diverse clean and efficient methods can be applied to produce

Synthesis of benzothiophene and indole derivatives through metal-free propargyl–allene rearrangement and allyl migration

• Jinzhong Yao,
• Yajie Xie,
• Lianpeng Zhang,
• Yujin Li and
• Hongwei Zhou

Beilstein J. Org. Chem. 2017, 13, 1866–1870, doi:10.3762/bjoc.13.181

• that are the key motif of many natural products and pharmaceuticals. Consequently, new and straightforward methods to access indoles are highly desirable [35][36]. We chose a propargyl phosphite rearrangement to achieve allenyl intermediates and aimed to synthetize indoles via allenyl phosphonates

Phenylsilane as an effective desulfinylation reagent

• Wanda H. Midura,
• Aneta Rzewnicka and
• Jerzy A. Krysiak

Beilstein J. Org. Chem. 2017, 13, 1513–1517, doi:10.3762/bjoc.13.150

• therefore a subject of our interest. To extend the investigations on the reduction of esters using a reagent with tolerance for other functional groups present in the structure, we applied a hydrosilylation methodology (Scheme 1). Various cyclopropyl phosphonates were subjected to the reaction with an

• a continuation of our studies on asymmetric cyclopropanation of vinyl phosphonates using (S)-dimethylsulfonium(p-tolylsulfinyl)methylide and its further application. It was formed as a single diastereomer with full stereoselectivity. To determine the relative configuration of the obtained structure

Synthesis of oligonucleotides on a soluble support

• Harri Lönnberg

Beilstein J. Org. Chem. 2017, 13, 1368–1387, doi:10.3762/bjoc.13.134

• derivatives 2-ethyl- and 2-benzylthiotetrazole [8] or 4,5-dicyanoimidazole [9]. The activator has a dual role donating a proton to the departing dialkylamino group and attacking as an anionic species on phosphorus [10]. Nucleoside H-phosphonates are, in turn, converted in situ to reactive mixed anhydrides

• oligonucleotides and most of these attempts have concerned the preparation of phosphorothioate ODNs, as discussed below. The only successful synthesis of unmodified ODNs was based on oxidative coupling of alkyl H-phosphonates on a PEG support [65]. The 3´-terminal nucleoside was immobilized to a PEG support via a

Transition-metal-catalyzed synthesis of phenols and aryl thiols

• Yajun Liu,
• Shasha Liu and
• Yan Xiao

Beilstein J. Org. Chem. 2017, 13, 589–611, doi:10.3762/bjoc.13.58

• phosphonates were compatible with the hydroxylation condtions, while monoalkyl phosphonate gave the phosphoryl lactone as product. Exploration of substrate scope showed that both electron-donating groups (such as Me, OMe) and electron-withdrawing groups (such as F, Cl, Br, CF3) are tolerable. 1.2.2.3 Phenol as

• hydroxylation of aryl ketones. Pd(OAc)2 catalyzed hydroxylation of aryl ketones. Pd(TFA)2-catalyzed hydroxylation of aryl phosphonates. Hydroxy group directed hydroxylation. [Ru(O2CMes)2(p-cymene)] catalyzed hydroxylation of benzamides and aryl ketones. [RuCl2(p-cymene)]2-catalyzed hydroxylation of benzamides

Revaluation of biomass-derived furfuryl alcohol derivatives for the synthesis of carbocyclic nucleoside phosphonate analogues

• Bemba Sidi Mohamed,
• Christian Périgaud and
• Christophe Mathé

Beilstein J. Org. Chem. 2017, 13, 251–256, doi:10.3762/bjoc.13.28

• some of the products have shown interesting antiviral activities. As part of our studies on carbocyclic nucleoside phosphonates [6] as potential anti-HIV agents [7][8], we envisioned to use bio-sourced racemic (+/−)-4-O-protected 2-cyclopentenone for the synthesis of hitherto unknown carbocyclic

• transposition giving rise to carbocyclic nucleoside phosphonates having structural similarity with carbonucleosides belonging to the neplanocin family. All the newly synthesized compounds were evaluated for their antiviral properties against HIV-1, Zika virus, Dengue-2 virus, HSV-1, HSV-2 and Chikungunya virus

The synthesis of α-aryl-α-aminophosphonates and α-aryl-α-aminophosphine oxides by the microwave-assisted Pudovik reaction

• Erika Bálint,
• Ádám Tajti,
• Anna Ádám,
• István Csontos,
• Konstantin Karaghiosoff,
• Mátyás Czugler,
• Péter Ábrányi-Balogh and
• György Keglevich

Beilstein J. Org. Chem. 2017, 13, 76–86, doi:10.3762/bjoc.13.10

• -aminophosphonates 6a–c, 7a–c and 8a–c. The results are collected in Table 4. The dialkyl ((butylamino)(chlorophenyl)methyl)phosphonates (6–8, a–c) were prepared in yields of 72–94% (Table 4, entries 1–9). There were no observable differences in the reactivities, as compared to the unsubstituted model compound 1a