Synthesis and quantitative structure–activity relationship study of substituted imidazophosphor ester based tetrazolo[1,5-b]pyridazines as antinociceptive/anti-inflammatory agents

• Wafaa M. Abdou,
• Neven A. Ganoub and
• Eman Sabry

Beilstein J. Org. Chem. 2013, 9, 1730–1736, doi:10.3762/bjoc.9.199

• intramolecular cyclization led to the product 7 (Scheme 2). Conversely, similar treatment of 1b with diethyl (methylthioalkyl)phosphonates 8a and 8b under the same reaction conditions yielded the fused diazaphospholo-substituted compounds 10a and 10b in 72 and 74% yield, respectively. The 31P NMR spectrum (CDCl3

• and 13); (4) like indomethacin, the tested phosphonates showed gradual increase in the second phase (after 270 min). LD50 of the most promising products In an acute-toxicity experiment, the most promising anti-inflammatory compounds 15, 7, and 13 were tested using the LD50 standard method in mice at

α-Bromodiazoacetamides – a new class of diazo compounds for catalyst-free, ambient temperature intramolecular C–H insertion reactions

• Åsmund Kaupang and
• Tore Bonge-Hansen

Beilstein J. Org. Chem. 2013, 9, 1407–1413, doi:10.3762/bjoc.9.157

• et al. reported the syntheses of an α-halodiazomethyl phosphonic acid dimethyl ester and an α-halodiazomethyl diphenyl phosphoxide, starting from the silver salts of the respective diazo compounds [10]. More recently, two novel protocols for the halogenation of diazoesters and -phosphonates have been

Efficient synthesis of β’-amino-α,β-unsaturated ketones

• Isabelle Abrunhosa-Thomas,
• Aurélie Plas,
• Nishanth Kandepedu,
• Pierre Chalard and
• Yves Troin

Beilstein J. Org. Chem. 2013, 9, 486–495, doi:10.3762/bjoc.9.52

• described in Scheme 3. In order to gain access to phosphonates 13, in a general and convergent process, two ways were investigated (Scheme 4). In route A, we planned to obtain the desired compound by using a similar strategy to that which we have described previously (see above): chiral induction was

Organocatalytic asymmetric addition of malonates to unsaturated 1,4-diketones

• Sergei Žari,
• Tiiu Kailas,
• Marina Kudrjashova,
• Mario Öeren,
• Ivar Järving,
• Toomas Tamm,
• Margus Lopp and
• Tõnis Kanger

Beilstein J. Org. Chem. 2012, 8, 1452–1457, doi:10.3762/bjoc.8.165

• , the increase in temperature resulted in a small drop in stereoselectivity for the model reaction with catalyst VII. The mechanism of the reaction is believed to be similar to that previously reported for 1,3-dicarbonyl compounds and acyl phosphonates [23]. Squaramide IX is a bifunctional catalyst that

Highly selective synthesis of (E)-alkenyl-(pentafluorosulfanyl)benzenes through Horner–Wadsworth–Emmons reaction

• George Iakobson and
• Petr Beier

Beilstein J. Org. Chem. 2012, 8, 1185–1190, doi:10.3762/bjoc.8.131

• good yields and high stereoselectivities. Follow-up transformations of the primary products provided (E)-1-alkenyl-(pentafluorosulfanyl)benzenes and 2-(2-arylethyl)-(pentafluorosulfanyl)anilines. Keywords: Horner–Wadsworth–Emmons reaction; pentafluorosulfanyl group; phosphonates; sulfurpentafluoride

• ][21][22]. Alkenyl substituted SF5-benzenes or SF5-containing stilbene derivatives are not known and would represent basic synthetic intermediates towards more elaborate structures. We envisioned a synthetic route towards these compounds through Horner–Wadsworth–Emmons (HWE) reaction of phosphonates 3

• . In contrast to most of the reactions with 3, phosphonate 4 gave exclusively E-isomers of 6 (Table 3). This improved selectivity can be explained by relative differences in the stabilities and reactivities of carbanions derived from phosphonates and reactive intermediates. In reactions of phosphoryl

Screening of ligands for the Ullmann synthesis of electron-rich diaryl ethers

• Nicola Otto and
• Till Opatz

Beilstein J. Org. Chem. 2012, 8, 1105–1111, doi:10.3762/bjoc.8.122

• , phosphinites, phosphonates, imines, diimines, oximes, oxime ethers and diketones were selected for the screening (Figure 2). Several of these compounds have been employed in diaryl ether syntheses before [22][23][24]. As a starting point, N,N-dimethylglycine (L1) introduced by Ma et al. [22][25] in combination

Recent advances in direct C–H arylation: Methodology, selectivity and mechanism in oxazole series

• Cécile Verrier,
• Pierrik Lassalas,
• Laure Théveau,
• Guy Quéguiner,
• François Trécourt,
• Francis Marsais and
• Christophe Hoarau

Beilstein J. Org. Chem. 2011, 7, 1584–1601, doi:10.3762/bjoc.7.187

• , tosylates, mesylates and phosphonates. Research efforts in this field are now focused on mechanism considerations since the broad diversity of catalytic metalation pathways represents undoubtedly an attractive tool for regioselectivity and the development of novel methodologies. Up until very recently

Highly efficient cyclosarin degradation mediated by a β-cyclodextrin derivative containing an oxime-derived substituent

• Michael Zengerle,
• Florian Brandhuber,
• Christian Schneider,
• Franz Worek,
• Georg Reiter and
• Stefan Kubik

Beilstein J. Org. Chem. 2011, 7, 1543–1554, doi:10.3762/bjoc.7.182

• phosphates and phosphonates [15][16][17][18], including the highly neurotoxic organophosphonates (OP) sarin and soman [19][20][21]. While α-cyclodextrin, the cyclodextrin containing six anhydroglucose units along the ring, was shown to be most effective for sarin [17][22], the larger β-cyclodextrin with the

Lithium phosphonate umpolung catalysts: Do fluoro substituents increase the catalytic activity?

• Anca Gliga,
• Bernd Goldfuss and
• Jörg M. Neudörfl

Beilstein J. Org. Chem. 2011, 7, 1189–1197, doi:10.3762/bjoc.7.138

• Anca Gliga Bernd Goldfuss Jorg M. Neudorfl Department für Chemie, Universität zu Köln, Greinstr. 4, D-50939 Köln, Germany 10.3762/bjoc.7.138 Abstract Fluorinated and nonfluorinated phosphonates are employed as precatalysts in lithium phosphonate catalyzed cross benzoin couplings. Surprisingly, a

• ; lithium phosphonates; umpolung; Introduction Since the discovery of the cyanide catalyzed benzoin reaction by Liebig and Wöhler in 1832 [1], acyloin-type reactions evolved as powerful tools for couplings of acylanion equivalents with carbon electrophiles. In addition to cyanide [2][3][4][5] and

• nucleophilic carbene catalysts (e.g. thiazolium salts) [6][7][8][9][10][11][12][13][14][15][16][17], lithium phosphonates were found to catalyze cross acyloin type couplings of acylsilanes with aldehydes [18]. The catalytic cycle proposed by Johnson et al. [18] (Scheme 1) suggests that a potential

Regioselective ester cleavage during the preparation of bisphosphonate methacrylate monomers

• Kamel Chougrani,
• Gilles Niel,
• Bernard Boutevin and
• Ghislain David

Beilstein J. Org. Chem. 2011, 7, 364–368, doi:10.3762/bjoc.7.46

• the phosphonic acids by using first trimethylsilyl bromide followed by a methanolysis step [27]. The first step is known to transform alkyl phosphonates into the corresponding trimethylsilyl phosphonates which are then cleaved to the phosphonic acids under hydrolytic conditions [28]. Phosphonates 1c

• residual HBr. The next challenge was to cleave the trimethylsilyl phosphonates selectively, without affecting alkyl carboxylates, under controlled conditions of both temperature and solvent [23] since alkyl esters including acrylate or methacrylate esters are sensitive to hydrolytic conditions [29

• ]. According to McKenna's recent results, the use of methanol instead of water should achieve the selective deprotection of these trimethylsilyl phosphonates [30]. Our results are summarized in Table 1. The crude silyl esters 1b–7b were dissolved in methanol and stirred for 2 h at ambient temperature

Approaches towards the synthesis of 5-aminopyrazoles

• Ranjana Aggarwal,
• Vinod Kumar,
• Rajiv Kumar and
• Shiv P. Singh

Beilstein J. Org. Chem. 2011, 7, 179–197, doi:10.3762/bjoc.7.25

• phosphonates (TFMCPs) 111 with arylhydrazines have been studied: TFMCPs 111 can be used as precursors of 2,3-dihydro-1H-pyrazoles 114 modified by both trifluoromethyl and diethoxyphosphoryl groups. Arylhydrazines add rapidly to the alkene double bond of 111 (X = CF3) at room temperature to produce an adduct

α,β-Aziridinylphosphonates by lithium amide-induced phosphonyl migration from nitrogen to carbon in terminal aziridines

• David. M. Hodgson and
• Zhaoqing Xu

Beilstein J. Org. Chem. 2010, 6, 978–983, doi:10.3762/bjoc.6.110

• methods [4][5][6], of which ring-closure following either Sharpless aminohydroxylation of α,β-unsaturated phosphonates [7], or α-halophosphonate addition to sulfinimines [8] constitute notable asymmetric approaches, albeit principally leading to β-aryl substituted α,β-aziridinylphosphonates. Arising from

Recent advances in carbocupration of α-heterosubstituted alkynes

• Ahmad Basheer and
• Ilan Marek

Beilstein J. Org. Chem. 2010, 6, No. 77, doi:10.3762/bjoc.6.77

• ). The two alkyl groups on the cuprate reagent could be eventually transferred when the reaction was performed in THF instead of Et2O. The same trend was found for the carbocupration of alkynyl phosphine oxide [31] and alkynyl phosphonates [32]. In the latter case, when R2 = Ph, only one isomer was

• -isomers. This effect can even be reinforced when an additional chelating unit is present (pyridylSi, phosphonates, sulfoxides, sulfones, sulfoximines). The resulting vinyl copper species can react with a large variety of electrophiles leading to functionalized adducts in a straightforward manner that can

Molecular recognition of organic ammonium ions in solution using synthetic receptors

• Andreas Späth and
• Burkhard König

Beilstein J. Org. Chem. 2010, 6, No. 32, doi:10.3762/bjoc.6.32

Synthesis of phosphonate and phostone analogues of ribose-1-phosphates

• Pitak Nasomjai,
• David O'Hagan and
• Alexandra M. Z. Slawin

Beilstein J. Org. Chem. 2009, 5, No. 37, doi:10.3762/bjoc.5.37

• fluorometabolism in S. cattleya. Keywords: 5-fluoro-5-deoxyribose-1-phosphate; fluorometabolite biosynthesis; phosphonates; phostone; ribose-1-phosphate; Introduction Fluoroacetate (1) and 4-fluorothreonine (2) are unusual secondary metabolites in that they contain a fluorine atom. They are elaborated by the

• -phosphate 5 where the linking phosphate oxygen has been replaced by a methylene group and for 9 the fluorine has been replaced by OH (see Figure 1). These phosphonates were considered as candidate inhibitors for either the PNP or the isomerase enzyme, with potential utility as tools to interrogate the

• enzyme which converts 5 to 6 during the biosynthesis. Results and Discussion The target phosphonates 8 and 9 have been prepared by routes A and B as shown in Scheme 1 and Scheme 2 respectively. The routes start either from D-ribonic-γ-lactone (12) or D-ribose (13). For each route the key synthetic steps

DBFOX- Ph/metal complexes: Evaluation as catalysts for enantioselective fluorination of 3-(2-arylacetyl)-2-thiazolidinones

• Takehisa Ishimaru,
• Norio Shibata,
• Dhande Sudhakar Reddy,
• Takao Horikawa,
• Shuichi Nakamura and
• Takeshi Toru

Beilstein J. Org. Chem. 2008, 4, No. 16, doi:10.3762/bjoc.4.16

• fluorination of a wide range of substrates, including β-keto esters, β-keto phosphonates, oxindoles [38][40][43][51][53][56][57]. They have also recently reported the enantioselective fluorination of 3-(2-arylacetyl)-2-thiazolidinones with their extended catalytic system, NiCl2-BINAP/R3SiOTf-lutidine with high

Unexpected degradation of the bisphosphonate P-C-P bridge under mild conditions

• Petri A. Turhanen and
• Jouko J. Vepsäläinen

Beilstein J. Org. Chem. 2008, 4, No. 7, doi:10.1186/1860-5397-4-7

• tetraesters (see Scheme 3 route a), since e.g., 1c, are prepared from phosphites, H-P(O)(OMe)2, and phosphonates, MeCOP(O)(OMe)2, or route b resembling the rearrangement process [19]. The driving force in both reactions is the formation of three charged molecules from one P-C-P compound since this is a highly

New modification of the Perkow reaction: halocarboxylate anions as leaving groups in 3-acyloxyquinoline- 2,4(1H,3H)-dione compounds

• Oldřich Paleta,
• Karel Pomeisl,
• Stanislav Kafka,
• Antonín Klásek and
• Vladislav Kubelka

Beilstein J. Org. Chem. 2005, 1, No. 17, doi:10.1186/1860-5397-1-17

• out[3] (product 2) via the intramolecular Wittig synthesis using a bromoacetyl derivative of the starting 3-hydroxyquinolinediones (1, Scheme 1). Unlike haloalkanes and halocycloalkanes that undergo nucleophilic substitution reaction with trialkyl phosphites to afford the corresponding phosphonates