IBD-mediated oxidative cyclization of pyrimidinylhydrazones and concurrent Dimroth rearrangement: Synthesis of [1,2,4]triazolo[1,5-c]pyrimidine derivatives

• Caifei Tang,
• Zhiming Li and
• Quanrui Wang

Beilstein J. Org. Chem. 2013, 9, 2629–2634, doi:10.3762/bjoc.9.298

• ]. As outlined in Scheme 1, the conversion of 4,6-dihydroxypyrimidines 1 to the dichloro derivatives 2 was accomplished by refluxing in phosphorus oxychloride for 4 h in the presence of triethylamine in yields ranging from 75 to 90% [16][17]. After screening a set of conditions, 1-(6-chloropyrimidin-4

Recent advances in transition metal-catalyzed Csp²-monofluoro-, difluoro-, perfluoromethylation and trifluoromethylthiolation

• Grégory Landelle,
• Armen Panossian,
• Sergiy Pazenok,
• Jean-Pierre Vors and
• Frédéric R. Leroux

Beilstein J. Org. Chem. 2013, 9, 2476–2536, doi:10.3762/bjoc.9.287

• trifluoromethylated arenes in good yields, and a variety of functional groups is tolerated under the mild conditions of the process. The reaction with aryl bromides or triflates is less efficient. The success of this Pd-catalyzed trifluoromethylation is due to highly hindered phosphorus ligands like BrettPhos, which

Towards stereochemical control: A short formal enantioselective total synthesis of pumiliotoxins 251D and 237A

• Jie Zhang,
• Hong-Kui Zhang and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2013, 9, 2358–2366, doi:10.3762/bjoc.9.271

• (THF) was distilled prior to use from sodium benzophenone ketyl. Dichloromethane was distilled from phosphorus pentoxide. Silica gel (zhifu, 300–400 mesh) from Yantai silica gel factory (China) was used for column chromatography, eluting (unless otherwise stated) with ethyl acetate/petroleum ether (PE

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• carbamate formation of the starting material. Upon exposure of 223 to phosphorus pentoxide, the desired isoindolinone 224 was formed in 75% yield. Deprotection led to lactonamycinone (214), which was the substrate for a ytterbium triflate-catalyzed glycosylation to give 215 and 217, respectively

The chemistry of amine radical cations produced by visible light photoredox catalysis

• Jie Hu,
• Jiang Wang,
• Theresa H. Nguyen and
• Nan Zheng

Beilstein J. Org. Chem. 2013, 9, 1977–2001, doi:10.3762/bjoc.9.234

• nitrogen, oxygen, or phosphorus nucleophiles In addition to carbon nucleophiles, heteronucleophiles including nitrogen, oxygen, and phosphorus are susceptible to interception of the photogenically formed iminium ions. The Xiao group developed a highly diastereroselective route to substituted

The application of a monolithic triphenylphosphine reagent for conducting Ramirez gem-dibromoolefination reactions in flow

• Kimberley A. Roper,
• Malcolm B. Berry and
• Steven V. Ley

Beilstein J. Org. Chem. 2013, 9, 1781–1790, doi:10.3762/bjoc.9.207

• polymerisation protocol consistently gave a low pressure drop across the monoliths for use in flow reactions. The monoliths were calculated to have a phosphorus loading of 1.85 mmol of phosphorus per gram, resulting in approximately 4.63 mmol of phosphorus per monolith. Loading the monolith to give the active

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

• -diazidopyridazine reacts with nucleophilic phosphorus reagents, HE reactants, mainly in the tetrazole-form leading to the formation of tetrazolopyridazino-imidazophosphor esters or β-enaminophosphor esters. Biological assays Based on previous reports [24][25][26] that recognized the pyridazine nucleus is being

• ]pyridazine-phosphor derivatives was carried out. Thus, keeping the tetrazolopyridazine core structure intact, we studied the effect of different phosphorus-containing moieties on their antinociceptive and anti-inflammatory effects. Substrate 1 was also tested to reflect the effect of its transformations to

Organocatalyzed enantioselective desymmetrization of aziridines and epoxides

• Ping-An Wang

Beilstein J. Org. Chem. 2013, 9, 1677–1695, doi:10.3762/bjoc.9.192

• chiral complexation of the phosphorus/silicon cation, and then followed by an attack with the chloride ion in an SN2 fashion to furnish chlorohydrin enantioselectively (Figure 14). From this description, the activation of SiCl4 was depending on the formation of the chiral complexation of the phosphorus

Palladium(II)-catalyzed Heck reaction of aryl halides and arylboronic acids with olefins under mild conditions

• Tanveer Mahamadali Shaikh and
• Fung-E Hong

Beilstein J. Org. Chem. 2013, 9, 1578–1588, doi:10.3762/bjoc.9.180

• tautomerization, which generates a less stable phosphinous acid (RR'POH) species. Subsequently, its coordination to the metal center through the phosphorus atom forms a phosphinous acid–metal complex [54][55][56]. Thus, the resulting transition-metal complex might function as an active catalyst in various C–C

Homolytic substitution at phosphorus for C–P bond formation in organic synthesis

• Hideki Yorimitsu

Beilstein J. Org. Chem. 2013, 9, 1269–1277, doi:10.3762/bjoc.9.143

• review article covers emerging, powerful synthetic approaches to organophosphorus compounds by homolytic substitution at phosphorus with a carbon-centered radical. Phosphination reagents include diphosphines, chalcogenophosphines and stannylphosphines, which bear a weak P–heteroatom bond for homolysis

• reactions such as nucleophilic substitution of P–X compounds with organometallic reagents, nucleophilic substitution of alkyl halides with phosphorus nucleophiles, and nucleophilic addition to polar unsaturated bonds. Recent advances in transition-metal catalysis have realized catalytic cross-coupling

• reactions of aryl halides with H–P compounds [5][6][7] and catalytic addition to nonpolar unsaturated carbon–carbon bonds [8][9][10][11]. In the field of radical chemistry, the addition of phosphorus radicals, mainly from H–P compounds, onto carbon–carbon multiple bonds [12][13][14][15] has held a special

Amyloid-β probes: Review of structure–activity and brain-kinetics relationships

• Todd J. Eckroat,
• Abdelrahman S. Mayhoub and
• Sylvie Garneau-Tsodikova

Beilstein J. Org. Chem. 2013, 9, 1012–1044, doi:10.3762/bjoc.9.116

Methylidynetrisphosphonates: Promising C₁ building block for the design of phosphate mimetics

• Vadim D. Romanenko and
• Valery P. Kukhar

Beilstein J. Org. Chem. 2013, 9, 991–1001, doi:10.3762/bjoc.9.114

• prepared in good yield by the Arbuzov reaction of trimethylsilyl esters of trivalent phosphorus acids with the easily accessible 2,6-di-tert-butyl-4-(dichloromethyl)phenol. In the next step, the bisphosphonate 16 was oxidized with K3Fe(CN)6 into quinone methide 17 in 91% yield. Further addition of diethyl

• isosteric character relative to pyrophosphate. In particular, the P–C–P geometry (both the P–C bond distance and the P–C–P angle) is close to the geometry in the methylenebisphosphonate salts while the phosphorus–phosphorus distance is close to that observed for methylenebisphosphonates and pyrophosphate

• phosphate-based processes. In particular, some heterocyclic compounds functionalized by trisphosphonate substituents merit in-depth biological study. A further practical potential for trisphosphonate compounds is the development of new phosphorus-containing dendrimers and related species. Considerable

Preparation and ring-opening reactions of N-diphenylphosphinyl vinyl aziridines

• Ashley N. Jarvis,
• Andrew B. McLaren,
• Helen M. I. Osborn and
• Joseph Sweeney

Beilstein J. Org. Chem. 2013, 9, 852–859, doi:10.3762/bjoc.9.98

• reported direct synthesis of a vinyl aziridine bearing a phosphorus group on nitrogen [40]. Encouraged by this promising result, we next examined the scope of the reaction by using the same anion and N-Dpp imines derived from 4-bromo- and 4-fluorobenzaldehyde, furfural and 2,2-dimethylpropionaldehyde

Kinetics and mechanism of the anilinolysis of aryl phenyl isothiocyanophosphates in acetonitrile

• Hasi Rani Barai and
• Hai Whang Lee

Beilstein J. Org. Chem. 2013, 9, 615–620, doi:10.3762/bjoc.9.68

• . Keywords: anilinolysis; cross-interaction constant; deuterium kinetic isotope effects; phosphoryl transfer reaction; reactive intermediates; Y-aryl phenyl isothiocyanophosphates; Introduction The nucleophilic substitution reactions of tetracoordinate phosphorus have been studied extensively

• , experimentally and theoretically, in our lab. Two main types of displacement processes are well known in neutral phosphoryl transfer reactions: a stepwise mechanism involving a trigonal bipyramidal pentacoordinate (TBP-5C) intermediate and a concerted displacement at phosphorus through a single pentacoordinate

• TSb-H and TSf. The anilinolyses of tetracoordinate phosphorus with the Cl– leaving group have been extensively studied in this lab, and the obtained data of primary normal DKIEs involving deuterated anilines are rationalized by TSf-type in which hydrogen bonding of an amine hydrogen atom occurs on the

Asymmetric Diels–Alder reaction with >C=P– functionality of the 2-phosphaindolizine-η¹-P-aluminium(O-menthoxy) dichloride complex: experimental and theoretical results

• Rajendra K. Jangid,
• Nidhi Sogani,
• Neelima Gupta,
• Raj K. Bansal,
• Moritz von Hopffgarten and
• Gernot Frenking

Beilstein J. Org. Chem. 2013, 9, 392–400, doi:10.3762/bjoc.9.40

• extensively in the characterization of azaphospholes and their [2 + 4] cycloadducts due to their characteristic 13C–31P coupling constants [30][31][32]. In view of this, the 13C NMR spectrum of a representative product 8a was recorded. The signals of the carbon atoms directly bonded to the phosphorus atom

• formation of the cationic species 13 (Scheme 4). Furthermore, it has been established by X-ray crystal structure studies that Cr(CO)5 is coordinated to the phosphorus atom only, and no chelate complex involving the σ2,λ3-P atom and carbonyl oxygen atom is formed [27]. As reported recently, the DFT

• calculations reveal that the activation energy of the DA reaction is lowered only if the aluminium catalyst is coordinated to the phosphorus atom; when it is coordinated to the carbonyl oxygen atom, the activation energy barrier is rather high as compared to that for the DA reaction of the uncomplexed 2

Inclusion of the insecticide fenitrothion in dimethylated-β-cyclodextrin: unusual guest disorder in the solid state and efficient retardation of the hydrolysis rate of the complexed guest in alkaline solution

• Dyanne L. Cruickshank,
• Natalia M. Rougier,
• Raquel V. Vico,
• Susan A. Bourne,
• Elba I. Buján,
• Mino R. Caira and
• Rita H. de Rossi

Beilstein J. Org. Chem. 2013, 9, 106–117, doi:10.3762/bjoc.9.14

• elongate the cavity of the CD molecules and provide a slightly larger pocket in which the fenitrothion molecules can situate themselves. Furthermore, the methyl groups have the ability to block the entering hydroxide ions, thereby preventing nucleophilic attack at the phosphorus atom. From the X-ray

• disordered components within host molecule B were evident. The relative population of each was unknown and required an analysis of the initial electron-density peak heights for the phosphorus atoms of each component. Guest components B, C and E had initial phosphorus electron-density peaks of 4.66, 3.07 and

Preparation of mixed trialkyl alkylcarbonate derivatives of etidronic acid via an unusual route

• Petri A. Turhanen,
• Janne Weisell and
• Jouko J. Vepsäläinen

Beilstein J. Org. Chem. 2012, 8, 2019–2024, doi:10.3762/bjoc.8.228

• column with dry eluent (dried with MgSO4) was not successful due to selective hydrolysis of the carbonate moiety from the phosphorus end. However, according to the 31P NMR spectrum, compound 3b was stable for at least 3 h in methanol solution containing 2 equiv 1 M HCl, indicating that some kind of

• catalysis is needed to hydrolyze the carbonate moiety from the phosphorus end. One possible reaction mechanism to account for this unusual conversion is shown in Scheme 2. Based on general chemical knowledge, the first intermediate in this reaction cascade must be compound 6 (Z = Me, Z’ = Na, H or CO2R

• ), since in general OH and ONa groups react readily with chloroformates, forming the corresponding carbonates. However, the formed carbonate structure at the phosphorus end seems to be unstable since only rearranged products 3 could be isolated. Moreover, in the case of sterically more hindered isobutyl

Tricyclic flavonoids with 1,3-dithiolium substructure

• Lucian G. Bahrin,
• Peter G. Jones and
• Henning Hopf

Beilstein J. Org. Chem. 2012, 8, 1999–2003, doi:10.3762/bjoc.8.226

• [30]. This behavior opens the way for the synthesis of various substituted 1,3-dithiolic rings, especially those with a 2-ylidene moiety resulting from a C-nucleophile attack. Furthermore, by using oxygen, sulfur, phosphorus, or nitrogen nucleophiles, interesting and novel structures can in principle

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

Beilstein J. Org. Chem. 2012, 8, 1936–1998, doi:10.3762/bjoc.8.225

• heteroaromatic thiol 64 provides the sulfur-substituted bisallene derivative 65 in good yields. Likewise, the stable diallenes 66 carrying phosphorus-containing substituents were obtained by heating the diols 63 with R52PCl [51][52][53][54]. How critically the substituents in the 3- and 4-position determine the

• -dibromobisallenes 74 by treating the highly substituted diyne diols 73 with phosphorus tribromide in benzene (Scheme 15) [58][59][60][61][62][63]. The details of these often overlooked seminal publications were recently studied by Parkhurst and Swager. According to these authors the 1,6-dibromide is produced first

Regioselective synthesis of 7,8-dihydroimidazo[5,1-c][1,2,4]triazine-3,6(2H,4H)-dione derivatives: A new drug-like heterocyclic scaffold

• Nikolay T. Tzvetkov,
• Harald Euler and
• Christa E. Müller

Beilstein J. Org. Chem. 2012, 8, 1584–1593, doi:10.3762/bjoc.8.181

• main challenge in the synthesis of 23–25 was the construction of the 1,2,4-triazine ring. Direct reaction of 13–15 with hydrazine hydrate failed, and only the corresponding hydrazides were formed. Therefore, the C5 carbonyl group of 13–15 was regioselectively thionated with phosphorus pentasulfide in

• phosphorus pentasulfide in dioxane for four hours. As reported in the literature, we observed only the preferred C4 thiocarbonyl product while the thionation of 5-unsubstituted hydantoin yields a mixture of 2- and 4-thionated products, indicating that the 5-dimethyl substitution was responsible for

Metal–ligand multiple bonds as frustrated Lewis pairs for C–H functionalization

• Matthew T. Whited

Beilstein J. Org. Chem. 2012, 8, 1554–1563, doi:10.3762/bjoc.8.177

• Fryzuk [62][63][64]. With a coordinatively unsaturated and electron-rich center, this species exhibits some reactivity that is similar to the isoelectronic Vaska's complex [65], such as oxidative addition of methyl iodide. It also reacts in dipolar fashion with an in-situ-generated phosphorus ylide to

• ) imide [42]. Formal [2 + 2] cycloaddition of methyl isocyanate at a ruthenium silylene [58]. Oxygen-atom transfer from phenyl isocyanate to a cationic terminal borylene [60]. Coupling of a phosphorus ylide with an iridium methylene [62]. Reactions of (PNP)Ir═C(H)Ot-Bu with oxygen-containing

Impact of cyclodextrins on the behavior of amphiphilic ligands in aqueous organometallic catalysis

• Hervé Bricout,
• Estelle Léonard,
• Christophe Len,
• David Landy,
• Frédéric Hapiot and
• Eric Monflier

Beilstein J. Org. Chem. 2012, 8, 1479–1484, doi:10.3762/bjoc.8.167

• the cyclohexyl protons and H-3 suggesting a deep phosphane inclusion into the CD cavity. For the other phosphanes, mixtures of supramolecular complexes could be detected because of the additional inclusion of the phosphorus-bound phenyl groups into the CD cavities (ESI). It should be noted that the

Cation affinity numbers of Lewis bases

• Christoph Lindner,
• Raman Tandon,
• Boris Maryasin,
• Evgeny Larionov and
• Hendrik Zipse

Beilstein J. Org. Chem. 2012, 8, 1406–1442, doi:10.3762/bjoc.8.163

• donors. This was explored for phosphanes which possess a nitrogen-containing moiety. Table 3 lists results for phosphanes containing a direct phosphorus–nitrogen bond. In the case of phosphanes with a second nucleophilic position (e.g., nitrogen atom) all MCA values are calculated for the reaction at the

• phosphorus atom, if not mentioned otherwise. The largest increase in MCA value compared to the reference of trimethylphosphane (70) is obtained through the introduction of the pyrrolidino substituent present in phosphanes 148, 154 and 157. Introduction of the first pyrrolidino group as in phosphane 148 leads

• piperidine (139) and azepane (145). Aside from phosphanes with a direct phosphorus–nitrogen bond, a variety of phosphanes with nitrogen-containing substituents can be envisioned in which P- and N-centers are separated by at least one carbon atom. Results for these phosphanes are listed in Table 4. All MCA

Chiral multifunctional thiourea-phosphine catalyzed asymmetric [3 + 2] annulation of Morita–Baylis–Hillman carbonates with maleimides

• Hong-Ping Deng,
• De Wang,
• Yin Wei and
• Min Shi

Beilstein J. Org. Chem. 2012, 8, 1098–1104, doi:10.3762/bjoc.8.121

• 3a (Table 1, entry 6). The allylic phosphorus ylide species can be recognized in spectra c from the combination of 2d and TP (1:1) (Figure 2, also see Figure SI-1 in the Supporting Information File 1) [59]. As reported before [15][51], TP attacks MBH carbonate to afford allylic phosphorus ylide I

• , which attacked the maleimide to produce intermediate II (Scheme 2). Since there is a steric effect between the phenyl group and the benzyl group in intermediate II-B, allylic phosphorus ylide I using its Si-face to attack maleimide is favored (intermediate II-A). Undergoing Michael addition and

Reduction of benzylic alcohols and α-hydroxycarbonyl compounds by hydriodic acid in a biphasic reaction medium

• Michael Dobmeier,
• Josef M. Herrmann,
• Dieter Lenoir and
• Burkhard König

Beilstein J. Org. Chem. 2012, 8, 330–336, doi:10.3762/bjoc.8.36

• . Experimental Representative experimental procedure: The alcohol (1 mmol, 1 equiv) is dissolved in 4 mL of toluene. Red phosphorus (0.4 mmol), followed by concentrated hydriodic acid (57% w/w; 3.0 mmol, 3 equiv) is added and the reaction mixture is heated to 80 °C for the stated time, allowed to cool to rt and