First DMAP-mediated direct conversion of Morita–Baylis–Hillman alcohols into γ-ketoallylphosphonates: Synthesis of γ-aminoallylphosphonates

• Marwa Ayadi,
• Haitham Elleuch,
• Emmanuel Vrancken and
• Farhat Rezgui

Beilstein J. Org. Chem. 2016, 12, 2906–2915, doi:10.3762/bjoc.12.290

• reaction; γ-ketoallylphosphonate; organophosphorus chemistry; Introduction Phosphonates and their derivatives are an important class of substances that have a wide range of applications in numerous areas such as medicinal [1][2][3] and agricultural chemistry [4][5]. Among them, multifunctional derivatives

• step protocol involves firstly the mesylation of corresponding alcohols and then the conversion of the intermediate mesylates into their halides. Further an Arbuzov reaction of alkyl phosphites with such halides affords the phosphonates. Interestingly, a direct conversion of common allyl alcohols into

• the corresponding phosphonates, with or without catalyst, was previously reported. Accordingly, Bodalski and co-workers [14] and then Swamy’s research group [15] described a direct route to allylphosphonates by treatment of Morita–Baylis–Hillman alcohols with chlorophosphites without any additive

Microwave-assisted synthesis of (aminomethylene)bisphosphine oxides and (aminomethylene)bisphosphonates by a three-component condensation

• Erika Bálint,
• Ádám Tajti,
• Anna Dzielak,
• Gerhard Hägele and
• György Keglevich

Beilstein J. Org. Chem. 2016, 12, 1493–1502, doi:10.3762/bjoc.12.146

• step is the nucleophilic addition of diethyl phosphite to the C=N bond of the imines resulting in phosphonates III or IV, respectively. Then, the elimination of an amine or ethanol and the addition of another unit of diethyl phosphite may lead to (aminomethylene)bisphosphonates (VI). If the amine is in

Towards potential nanoparticle contrast agents: Synthesis of new functionalized PEG bisphosphonates

• Souad Kachbi-Khelfallah,
• Maelle Monteil,
• Margery Cortes-Clerget,
• Evelyne Migianu-Griffoni,
• Jean-Luc Pirat,
• Olivier Gager,
• Julia Deschamp and
• Marc Lecouvey

Beilstein J. Org. Chem. 2016, 12, 1366–1371, doi:10.3762/bjoc.12.130

• bifunctional molecules substituted by amines, thiols, carboxylates, sulfonates, phosphonates or bisphosphonates [5][6][7]. Particularly, a strong interaction between the NPs and the phosphonic moiety was observed and more interestingly the best results were obtained with bisphosphonate products [8][9]. For the

Copper-catalyzed [3 + 2] cycloaddition of (phenylethynyl)di-p-tolylstibane with organic azides

• Mizuki Yamada,
• Mio Matsumura,
• Yuki Uchida,
• Masatoshi Kawahata,
• Yuki Murata,
• Naoki Kakusawa,
• Kentaro Yamaguchi and
• Shuji Yasuike

Beilstein J. Org. Chem. 2016, 12, 1309–1313, doi:10.3762/bjoc.12.123

• fully substituted 1,2,3-triazoles having group 15 (P, Bi) elements as substituents at the C-5 position was recently attempted. Li et al. reported that the cycloaddition of alkynylphosphonate with benzyl azide did not generate 1,2,3-triazolyl-5-phosphonates, but a three-component reaction of a terminal

• alkyne, an organic azide, and an H-phosphate in the presence of CuCl2 (10 mol %) and triethylamine (2 equiv) afforded the desired 1,2,3-triazolyl-5-phosphonates [23]. Fokin et al. carried out the reaction of ethynylbismuthane with organic azides using CuOTf (5 mol %) and isolated 5-bismuthano-1,2,3

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• heterocyclic phosphonates: (a) the direct electrophilic or nucleophilic phosphorylation of the heterocyclic systems and (b) the ring closure of phosphoryl-functionalized substrates through cyclization or cycloaddition reactions [14][15][16][17][18][19]. Multicomponent reactions (MCRs) constitute one of the

• . Some of these post-MCR transformations are: intramolecular cycloaddition reactions, Knoevenagel condensations, metathesis reactions, aza-Wittig reactions, Mitsunobu reactions, etc. [21]. Up to now, two review articles have been reported on azaheterocyclic phosphonates [22][23], but no overview article

• about the multicomponent synthesis of phosphono-substituted heterocycles has been reported so far. This review focuses on general multicomponent reactions as well as on modified MCR towards heterocyclic phosphonates. It is organized by the reaction types and covers literature published up to September

Synthesis, fluorescence properties and the promising cytotoxicity of pyrene–derived aminophosphonates

• Jarosław Lewkowski,
• Maria Rodriguez Moya,
• Anna Wrona-Piotrowicz,
• Janusz Zakrzewski,
• Renata Kontek and
• Gabriela Gajek

Beilstein J. Org. Chem. 2016, 12, 1229–1235, doi:10.3762/bjoc.12.117

• phosphonates. Recently, an Indian group [9] reported the synthesis of a number of N-aryl substituted, diethyl amino(pyrene-1-yl)methyl phosphonates and some preliminary studies on their fluorescence properties. Such a poor knowledge about these compounds is astonishing in the light of the fact that the

• attributed to each nucleus. Compounds were also characterized by melting point measurements. Jayaprakash et al. [9] reported the synthesis of several pyrene-derived aminophosphonates via a silica-catalyzed Kabachnik–Fields reaction. Among others, they synthesized three amino-phosphonates 3Bb–d, reporting

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• nitroalkene [67]. α,β-Unsaturated phosphonates and phosphine oxides Transition metal catalysts In 2006, Hayashi and co-workers reported the first conjugate addition–enantioselective protonation of allenes 165 bearing a phosphine oxide (Scheme 39) [68]. Incorporation of the phosphine oxide allowed for

• utilized by the pharmaceutical and agrochemical industries as α-amino acid analogues. Darses and co-workers reported a novel approach to the synthesis of enantioenriched α-amino phosphonates 170 via a rhodium(I) catalyzed enantioselective 1,4-addition of potassium aryltrifluoroborates 168 to

• dehydroaminophosphonates 169 (Scheme 40) [69]. α-Amino phosphonates 170 were obtained with high levels of enantioselectivity for electron-rich, neutral, and electron-poor aryltrifluoroborates 168. Electron-rich organoboron reagents (4-t-Bu, 4-MeO, and 3-MeO) gave slightly lower yields (51–77%) than the electron-poor

The aminoindanol core as a key scaffold in bifunctional organocatalysts

• Isaac G. Sonsona,
• Eugenia Marqués-López and
• Raquel P. Herrera

Beilstein J. Org. Chem. 2016, 12, 505–523, doi:10.3762/bjoc.12.50

• group studied the use of α,β-unsaturated acyl phosphonates as suitable electrophiles for this kind of reaction, using several bifunctional aminoindanol-based organocatalytic scaffolds as catalysts (Scheme 10) [39]. Hence, the authors demonstrated that acyl phosphonates can be used as efficient hydrogen

• of cis relationship between the hydroxy and amino groups (such as in catalyst 22) led to racemic mixtures (Scheme 10a). Under optimal conditions, the acyl phosphonates 24 reacted with indoles 2 in the presence of catalyst ent-4 providing the corresponding products 25 with high selectivity (up to 90

• external Brønsted acid. Proposed transition state TS7 for the Friedel–Crafts reaction of indole and α,β-unsaturated acyl phosphonates catalyzed by ent-4. Possible transition states TS8 and TS9 in the asymmetric addition of indoles 2 to the β,γ-unsaturated α-ketoesters 26 catalyzed by ent-4. Transition

Organocatalytic asymmetric Henry reaction of 1H-pyrrole-2,3-diones with bifunctional amine-thiourea catalysts bearing multiple hydrogen-bond donors

• Ming-Liang Zhang,
• Deng-Feng Yue,
• Zhen-Hua Wang,
• Yuan Luo,
• Xiao-Ying Xu,
• Xiao-Mei Zhang and
• Wei-Cheng Yuan

Beilstein J. Org. Chem. 2016, 12, 295–300, doi:10.3762/bjoc.12.31

• bifunctional multiple hydrogen-bond amine-thiourea-catalyzed Michael reaction of acetyl phosphonates with nitroolefins, giving a series of β-substituted nitro compounds with excellent stereoselectivity [34]. Therefore, as part of our research program aimed at establishing new methods for the construction of

Interactions of cyclodextrins and their derivatives with toxic organophosphorus compounds

• Sophie Letort,
• Sébastien Balieu,
• William Erb,
• Géraldine Gouhier and
• François Estour

Beilstein J. Org. Chem. 2016, 12, 204–228, doi:10.3762/bjoc.12.23

• commercial impacts during the last decades, phosphates, phosphonates, phosphinates, or phosphines being prominent in several fields. As an example, drugs bearing an organophosphorus moiety hold a significant place in chemotherapy for the treatment of various diseases. Nevertheless, the high polarity of these

• intermediate mechanism is usually involved. The formation of an inclusion-complex first occurs and then the secondary alkoxide of the host pseudo-intramolecularly attacks the phosphorus atom to form a covalent bond. Finally an alkoxide ion could react with the formed phosphonates to regenerate the CD secondary

Friedel–Crafts-type reaction of pyrene with diethyl 1-(isothiocyanato)alkylphosphonates. Efficient synthesis of highly fluorescent diethyl 1-(pyrene-1-carboxamido)alkylphosphonates and 1-(pyrene-1-carboxamido)methylphosphonic acid

• Anna Wrona-Piotrowicz,
• Janusz Zakrzewski,
• Anna Gajda,
• Tadeusz Gajda,
• Anna Makal,
• Arnaud Brosseau and
• Rémi Métivier

Beilstein J. Org. Chem. 2015, 11, 2451–2458, doi:10.3762/bjoc.11.266

• amidophosphonates 3a–d in 87–94% isolated yield (Scheme 1). Therefore, the indirect route to these compounds described above proved very efficient. We did not attempt to prepare 3a–d via direct Friedel–Crafts-type reaction of pyrene with (isocyanato)alkyl phosphonates because these compounds are difficult to

Lewis acid-promoted hydrofluorination of alkynyl sulfides to generate α-fluorovinyl thioethers

• Davide Bello and
• David O'Hagan

Beilstein J. Org. Chem. 2015, 11, 1902–1909, doi:10.3762/bjoc.11.205

• example as illustrated in Figure 1, CF2-phosphonates became popular mimetics of the phosphate group [3][4], and vinyl fluorides were developed as analogues of the amide bond [5]. Difluorotoluene has proved to be a good spacial mimetic of the thymine base in thymidine, and has been shown to act as a

Pyridinoacridine alkaloids of marine origin: NMR and MS spectral data, synthesis, biosynthesis and biological activity

• Louis P. Sandjo,
• Victor Kuete and
• Maique W. Biavatti

Beilstein J. Org. Chem. 2015, 11, 1667–1699, doi:10.3762/bjoc.11.183

• effect [89]. Piperidinic phosphonates derivatives also showed the same enzyme inhibition (Figure 18) [90] and the only chemical resemblance with pyridoacridines is the piperidine ring. Since piperidine is related to pyridine, the dihydropyridone (C) and the pyridine (E) rings in the structure of 99 could

Synthesis of γ-hydroxypropyl P-chirogenic (±)-phosphorus oxide derivatives by regioselective ring-opening of oxaphospholane 2-oxide precursors

• Iris Binyamin,
• Shoval Meidan-Shani and
• Nissan Ashkenazi

Beilstein J. Org. Chem. 2015, 11, 1332–1339, doi:10.3762/bjoc.11.143

• compounds [26][38][39]. In our previous work, we investigated the reaction of 2-ethoxy-1,3,2-dioxaphospholane 2-oxide (2) with Grignard reagents, and showed that phosphonates were formed as single products via a regioselective endocyclic P–O bond cleavage [40][41][42]. In continuation of this work, we

Synthesis of tripodal catecholates and their immobilization on zinc oxide nanoparticles

• Franziska Klitsche,
• Julian Ramcke,
• Julia Migenda,
• Andreas Hensel,
• Tobias Vossmeyer,
• Horst Weller,
• Silvia Gross and
• Wolfgang Maison

Beilstein J. Org. Chem. 2015, 11, 678–686, doi:10.3762/bjoc.11.77

• ], carboxylates [5] and phosphates [6] as well as phosphonates [7] for metal and metal oxide surfaces. In addition, bifunctional catechols like dopamine or DOPA (L-3,4-dihydroxyphenylalanine, Figure 1B), have received considerable interest as anchor groups for important metal surfaces such as titanium oxide, iron

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

• phosphorous compounds: Optically active, phosphorous-containing compounds, most commonly phosphates, have been studied in the context of biology and medicine for decades. Due to the facile enzymatic cleavage of phosphates, phosphonates have been studied as phosphate mimics for many years [257][258]. Though

• the 1,4-addition of phosphites provides a direct route for accessing chiral phosphonates, there are only a few examples of this reaction [259][260][261][262][263][264]. In 2009, Wang and co-workers reported one of the first catalytic, enantioselective 1,4-addition of phosphites to α,β-unsaturated N

Synthesis of dinucleoside acylphosphonites by phosphonodiamidite chemistry and investigation of phosphorus epimerization

• William H. Hersh

Beilstein J. Org. Chem. 2015, 11, 184–191, doi:10.3762/bjoc.11.19

• , hydrolyzed to the H-phosphonates, and sulfurized to give the known mixture of diastereomeric phosphorothioates. The goal of this work was the measurement of the barrier to inversion of the acylphosphonites, which was expected to be low by analogy to the low barrier found in acylphosphines. However, the

Synthesis and immunological evaluation of protein conjugates of Neisseria meningitidis X capsular polysaccharide fragments

• Laura Morelli,
• Damiano Cancogni,
• Marta Tontini,
• Alberto Nilo,
• Sara Filippini,
• Paolo Costantino,
• Maria Rosaria Romano,
• Francesco Berti,
• Roberto Adamo and
• Luigi Lay

Beilstein J. Org. Chem. 2014, 10, 2367–2376, doi:10.3762/bjoc.10.247

• glycosyl hydrogenphosphonates (H-phosphonates) intermediates for the installation of the phosphodiester linkages [28]. We were confident that the use of the non-participating and electron-withdrawing azido group could strongly enhance the stability of the anomeric phosphodiester linkages. However, we

• derivative very similar to 5 but protected as a 4,6-O-benzylidene acetal also led to an anomeric mixture, suggesting that conformational factors might be also involved. In addition, the treatment of this mixture with salicylchlorophosphite produced a mixture of anomeric H-phosphonates, indicating that no

• -phosphonates [25]. An additional improvement in α-H-phosphonate 7 formation was achieved by carrying out the reaction under microfluidic conditions. The Micro Reactor Technology (MRT) is gaining increasing attention for drug discovery. Some of its various possible advantages when compared to more conventional

Organophosphorus chemistry

• Paul R. Hanson

Beilstein J. Org. Chem. 2014, 10, 2087–2088, doi:10.3762/bjoc.10.217

• phosphinoyl-indoles and phosphinoyl-isocoumarins and new chemistries of H-phosphonates. The Thematic Series also details work on new metathesis-based reactions of vinyl phosphonates and phosphate tethers, novel phosphorus-based ligands in asymmetric catalysis, novel rasta resin–triphenylphosphine oxides and

Pyrrolidine nucleotide analogs with a tunable conformation

• Lenka Poštová Slavětínská,
• Dominik Rejman and
• Radek Pohl

Beilstein J. Org. Chem. 2014, 10, 1967–1980, doi:10.3762/bjoc.10.205

• detection of alkylating agents, such as dialkyl phosphonates; blue color). The course of the reactions and the purity of the prepared compounds were determined by LC–MS using a Waters AutoPurification System with a 2545 Quaternary Gradient Module and a 3100 Single Quadrupole Mass Detector using a Luna C18

Relay cross metathesis reactions of vinylphosphonates

• Raj K. Malla,
• Jeremy N. Ridenour and
• Christopher D. Spilling

Beilstein J. Org. Chem. 2014, 10, 1933–1941, doi:10.3762/bjoc.10.201

• phosphorus; relay; vinyl phosphonate; Introduction Over the last two decades, we have developed reactions for the formation of chiral non-racemic γ-substituted vinylphosphonates [1][2][3][4][5][6][7][8][9]. In particular, carbonate derivatives 1 (phosphono allylic carbonates) of allylic hydroxy phosphonates

• with 5 equivalents of allyl bromide and 5 mol % TBAI in refluxing toluene for 36 hours to give a 76% conversion with 1.8:1 ratio of mono- to diallylated vinyl phosphonates 20a and 20b (Scheme 5). The products were isolated by silica gel chromatography to give 46% yield of mono-allyl and 27% yield of

• heterocycles (Scheme 8) [23][24]. The mode of cyclization depends upon the geometry and substitution of the vinylphosphonate. It was proposed that (E) diallyl vinylphosphonates would prefer to form the 5-membered ring oxaphosphole 30 and therefore, like the corresponding mono-allyl phosphonates, should engage

Glycosystems in nanotechnology: Gold glyconanoparticles as carrier for anti-HIV prodrugs

• Fabrizio Chiodo,
• Marco Marradi,
• Javier Calvo,
• Eloisa Yuste and
• Soledad Penadés

Beilstein J. Org. Chem. 2014, 10, 1339–1346, doi:10.3762/bjoc.10.136

• transport (a major reservoir for HIV) [29] and some alkyl and alkyloxyalkyl esters of nucleotides or acyclic nucleoside phosphonates have been explored in clinical studies [30]. In order to obtain the ester derivatives, 11-(acetylthio)undecanoic acid, obtained from 11-bromoundecanoic acid and potassium

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

• , phosphonates, phosphinates and phosphate derivatives, etc.) are out of the scope of this review. Review Preparation of alkylphosphines via formation of a C(sp3)–P bond Reaction of organometallic reagents with halophosphines One of the main approaches to synthesize a carbon–phosphorus bond involves the

Regioselective S_N2' Mitsunobu reaction of Morita–Baylis–Hillman alcohols: A facile and stereoselective synthesis of α-alkylidene-β-hydrazino acid derivatives

• Silong Xu,
• Jian Shang,
• Junjie Zhang and
• Yuhai Tang

Beilstein J. Org. Chem. 2014, 10, 990–995, doi:10.3762/bjoc.10.98

• [13][14], ethers [15][16], amines [17][18], thioethers [19], phosphonates [20][21], alkyl groups [22][23], and so on. In this context, however, reports on the conversion of MBH alcohols into hydrazine derivatives are scanty. In 2009, Nair and co-workers [24] reported an interesting reaction of MBH