A quantitative approach to nucleophilic organocatalysis

• Herbert Mayr,
• Sami Lakhdar,
• Biplab Maji and
• Armin R. Ofial

Beilstein J. Org. Chem. 2012, 8, 1458–1478, doi:10.3762/bjoc.8.166

• comparison reveals that the nucleophilicities of the NHCs 41–43 do not differ fundamentally from those of other organocatalysts, e.g., triphenylphosphine (10b), DMAP (39), and DABCO (38) [96]. The considerably lower nucleophilicity of the triazolylidene 43 compared with the imidazolylidene 42 can be

A novel asymmetric synthesis of cinacalcet hydrochloride

• Veera R. Arava,
• Laxminarasimhulu Gorentla and
• Pramod K. Dubey

Beilstein J. Org. Chem. 2012, 8, 1366–1373, doi:10.3762/bjoc.8.158

• simply by heating 12 in 48% aqueous HBr solution under reflux for 15 h. The obtained crude was purified by passing it through a silica gel plug with n-hexane to afford 5 in 82% yield. Iodide 6 was prepared by reacting 12 with molecular iodine in the presence of triphenylphosphine and imidazole in CH2Cl2

• ); 13C NMR (CDCl3/TMS) δ 141.36, 131.87, 130.67 (q, CF3), 128.83, 125.07, 123.03, 33.70, 33.67, 32.52. Preparation of 1-(3-iodopropyl)-3-trifluoromethylbenzene (6): Compound 12 (50.0 g, 0.244 mol) was dissolved in CH2Cl2 (150.0 mL) and imidazole (2.0 g, 0.029 mol) and triphenylphosphine (70.64 g, 0.269

Synthesis of a novel chemotype via sequential metal-catalyzed cycloisomerizations

• Bo Leng,
• Stephanie Chichetti,
• Shun Su,
• Aaron B. Beeler and
• John A. Porco Jr.

Beilstein J. Org. Chem. 2012, 8, 1338–1343, doi:10.3762/bjoc.8.153

• synthesis of alkynyl o-benzaldehydes: 2-(3-(but-2-ynyloxy)prop-1-ynyl)benzaldehyde. To a solution of 2-bromobenzaldehyde (2.0 g, 10.8 mmol) and 1-(prop-2-ynyloxy)but-2-yne (1.4 g, 13 mmol) in Et3N (68 mL), was added tetrakis(triphenylphosphine)palladium(0) (0.38 g, 0.32 mmol). The reaction mixture was

Synthesis of diverse indole libraries on polystyrene resin – Scope and limitations of an organometallic reaction on solid supports

• Kerstin Knepper,
• Sylvia Vanderheiden and
• Stefan Bräse

Beilstein J. Org. Chem. 2012, 8, 1191–1199, doi:10.3762/bjoc.8.132

• calculated as if complete conversion had taken place. GP 3 - Suzuki reaction: Under an argon atmosphere, one equiv of the respective 7-bromo-1H-indole-6-carboxymethyl-polystyrene is suspended in DMF (0.1 mmol/mL) together with 0.10 equiv of tetrakis(triphenylphosphine)palladium and two equiv of boronic acid

• 10.0 mol % bis(triphenylphosphine)palladium(II) chloride, 15.0 mol % copper(I) iodide and one equiv of triphenylphosphine. Then, two equiv of triethylamine and 2.5 equiv of 4-ethynylanisole are added and the mixture is agitated for two days at 80 °C. After cooling down to room temperature, 10 mL of a

• , one equiv of the respective 7-bromo-1H-indole-6-carboxymethyl-polystyrene is suspended in DMF (0.1 mmol/mL) together with 10.0 mol % bis(triphenylphosphine)palladium(II) chloride, 15.0 equiv of lithium chloride and one equiv of triphenylphosphine. Then, three equiv of tributyl(vinyl)tin are added and

Parallel solid-phase synthesis of diaryltriazoles

• Matthias Wrobel,
• Jeffrey Aubé and
• Burkhard König

Beilstein J. Org. Chem. 2012, 8, 1027–1036, doi:10.3762/bjoc.8.115

• of regioisomers in reaction 3. Instead of the 1,4-disubstituted triazoles obtained from copper(I) catalysis, the complex pentamethylcyclopentadienylbis(triphenylphosphine)ruthenium(II) chloride leads to 1,5-disubstituted triazole compounds [19]. 4-(Azidomethyl)benzoic acid functionalized Wang resin 7

• preliminary work, resin 7 was therefore reacted with internal alkynes 14a–c and pentamethylcyclopentadienylbis(triphenylphosphine)ruthenium(II) chloride as catalyst in DMF at 70 °C overnight followed by TFA cleavage [20]. LC–MS analysis of the crude product revealed the formation of compounds 15a–c in high

• ) was preswollen in dimethylformamide (2 mL/100 mg resin) for 2 h at room temperature. Subsequently, the catalyst complex pentamethylcyclopentadienylbis(triphenylphosphine)ruthenium(II) chloride, Cp·RuCl(PPh3)2, (5 mol %) and either a terminal or an internal alkyne (4 equiv) were added. After the

Toward unidirectional switches: 2-(2-Hydroxyphenyl)pyridine and 2-(2-methoxyphenyl)pyridine derivatives as pH-triggered pivots

• Christina Tepper and
• Gebhard Haberhauer

Beilstein J. Org. Chem. 2012, 8, 977–985, doi:10.3762/bjoc.8.110

• the bipyridine 9 with 2-methoxyphenylboronic acid or 2-hydroxyphenylboronic acid, respectively, using tetrakis(triphenylphosphine)palladium(0) and potassium carbonate as a base in dioxane. In the resulting switches 10 and 13 the more stable diastereomeric conformations should be those in which the

• absorption spectra were recorded with a Jasco J-815 spectrophotometer. 2-(2-Methoxyphenyl)-3-methylpyridine (7): To a solution of 2-bromo-3-methylpyridine (184 mg, 1.07 mmol), 2-methoxyphenylboronic acid (151 mg, 0.99 mmol) and tetrakis(triphenylphosphine)palladium(0) (45 mg, 3.9 mol %) in dioxane (10 mL), a

• , 184.0768; found, 184.0815. Methoxyphenylpyridine switch (10): To a solution of dibromide 9 (20 mg, 0.022 mmol) and tetrakis(triphenylphosphine)palladium(0) (1 mg, 3.9 mol%) in dioxane (3 mL), a saturated potassium carbonate solution (0.2 mL) was added. The mixture was purged with argon for 10 min and

Carbohydrate-auxiliary assisted preparation of enantiopure 1,2-oxazine derivatives and aminopolyols

• Marcin Jasiński,
• Dieter Lentz and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2012, 8, 662–674, doi:10.3762/bjoc.8.74

• by treatment with tetrabromomethane in the presence of triphenylphosphine gave no satisfactory results, possibly due to the formation of the corresponding oxirane and its diverse, subsequent reactions. Conclusion We achieved the efficient synthesis of enantiopure hydroxylated tetrahydro-2H-1,2

Liquid-crystalline nanoparticles: Hybrid design and mesophase structures

• Gareth L. Nealon,
• Romain Greget,
• Cristina Dominguez,
• Zsuzsanna T. Nagy,
• Daniel Guillon,
• Jean-Louis Gallani and
• Bertrand Donnio

Beilstein J. Org. Chem. 2012, 8, 349–370, doi:10.3762/bjoc.8.39

• nm diameter were first synthesised and isolated with a triphenylphosphine protective layer, followed by the addition of thiols 68–12 (Figure 3). The authors estimated the number of ligands attached to the NPs after the exchange process to be ~150–215, which indicated a very dense packing on the

Improved syntheses of high hole mobility phthalocyanines: A case of steric assistance in the cyclo-oligomerisation of phthalonitriles

• Daniel J. Tate,
• Rémi Anémian,
• Richard J. Bushby,
• Suwat Nanan,
• Stuart L. Warriner and
• and Benjamin J. Whitaker

Beilstein J. Org. Chem. 2012, 8, 120–128, doi:10.3762/bjoc.8.14

• flame-dried flask purged with argon was added triphenylphosphine (44.61 g, 0.170 mol), imidazole (16.16 g, 0.255 mol) and anhydrous diethyl ether/acetonitrile (125 mL/125 mL). The stirred reaction mixture was cooled (0 °C, ice bath) and 3-methylbutanol (7.50 g, 0.085 mol) was added. After 10 min, iodine

• -methylbutyl)phthalonitrile (6e) To a flame-dried flask, under an argon atmosphere, were added bis(triphenylphosphine)nickel(II) dichloride (1.18 g, 1.82 mmol), triphenylphosphine (0.95 g, 3.6 mmol) and anhydrous THF (40 mL). n-Butyllithium (1.45 mL, 3.64 mmol, 2.5 M in hexanes) was added to the stirred

• triphenylphosphine was extracted. The title compound [24] was isolated as colourless needles (3.51 g, 72%) by increasing the polarity to 10% EtOAc/hexane (v:v). Rf ~ 0.30; mp (petroleum ether) 62–63 °C; IR (neat): 2957 (C–H), 2936 (C–H), 2872 (C–H), 2226 (CN), 1468 (C=C), 1459 (C=C) cm−1; 1H NMR (CDCl3, 500 MHz) δ

Binding of group 15 and group 16 oxides by a concave host containing an isophthalamide unit

• Jens Eckelmann,
• Vittorio Saggiomo,
• Svenja Fischmann and
• Ulrich Lüning

Beilstein J. Org. Chem. 2012, 8, 11–17, doi:10.3762/bjoc.8.2

• sulfoxides were chosen as guests, namely pyridine-N-oxide (PyNO) [18][19] and triphenylphosphine oxide (TPPO). PyNO showed the same behaviour as DMSO, i.e., large CIS for concave host 1, and small CIS for the linear compound (Figure 2, PyNO, endo-CH, 0.34 ppm for 1 and 0.14 ppm for 2). In contrast, with TPPO

• and its non-macrocyclic model 2. Expansion of a part of the 1H NMR spectra (200 MHz, 298 K) of pure 1 and 2 in CD2Cl2 (bottom) and after addition of TBACl, DMSO, pyridine-N-oxide (PyNO), triphenylphosphine oxide (TPPO), from bottom to top, respectively. NH proton (red circles), endo-CH proton (red

Sexithiophenes as efficient luminescence quenchers of quantum dots

• Christopher R. Mason,
• Yang Li,
• Paul O’Brien,
• Neil J. Findlay and
• Peter J. Skabara

Beilstein J. Org. Chem. 2011, 7, 1722–1731, doi:10.3762/bjoc.7.202

• compound 6 (2.10 g, 4.26 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.12 g, 0.099 mmol) in dry tetrahydrofuran (50 mL) under dry nitrogen, and heated under reflux for 16 h. The solution was allowed to cool and the crude product precipitated with petroleum ether (40–60 °C). The crude product was

• -butyllithium (2.5 M in hexanes, 0.80 mL, 2.0 mmol), zinc(II)chloride (0.27 g, 2.0 mmol) in dry tetrahydrofuran (20 mL), compound 6 (2.27 g, 4.60 mmol) and tetrakis(triphenylphosphine)palladium(0) (0.13 g, 0.11 mmol) in dry tetrahydrofuran (60 mL). The product was isolated by column chromatography (silica

• (136 mg, 0.16 mmol) and tetrakis(triphenylphosphine)palladium(0) (10 mg, 0.008 mmol) in toluene (20 mL) under dry nitrogen, was added, subsequently, a suspension of 4-(dimethylamino)phenylboronic acid (35 mg, 0.21 mmol) in ethanol (25 mL) and a solution of anhydrous sodium carbonate (45 mg, 0.42 mmol

The application of a monolithic triphenylphosphine reagent for conducting Appel reactions in flow microreactors

• Kimberley A. Roper,
• Heiko Lange,
• Anastasios Polyzos,
• Malcolm B. Berry,
• Ian R. Baxendale and
• Steven V. Ley

Beilstein J. Org. Chem. 2011, 7, 1648–1655, doi:10.3762/bjoc.7.194

• 2NY, UK 10.3762/bjoc.7.194 Abstract Herein we describe the application of a monolithic triphenylphosphine reagent to the Appel reaction in flow-chemistry processing, to generate various brominated products with high purity and in excellent yields, and with no requirement for further off-line

• purification. Keywords: Appel reaction; bromination; flow chemistry; solid-supported reagent; triphenylphosphine monolith; Introduction Flow chemistry is well-established as a useful addition to the toolbox of the modern research chemist, with advantages accrued through increased efficiency, reproducibility

• interest in using monolithic supports to facilitate key chemical transformations [20][21][22][23][24][25][26][27][28][29][30][31]. We recently reported on the development of a new monolithic triphenylphosphine reagent and its use in the Staudinger aza-Wittig reaction in flow [32][33]. Here we discuss the

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

• in 59% yield (Scheme 8). Miura subsequently disclosed the Cu(I)-catalyzed direct arylation of 5-arylated oxazoles with aryl iodides by employing triphenylphosphine ligand and sodium carbonate base (Scheme 8) [46]. Recently, You et al. reported convenient conditions for Cu(I)-catalyzed direct

Combination of gold catalysis and Selectfluor for the synthesis of fluorinated nitrogen heterocycles

• Antoine Simonneau,
• Pierre Garcia,
• Jean-Philippe Goddard,
• Virginie Mouriès-Mansuy,
• Max Malacria and
• Louis Fensterbank

Beilstein J. Org. Chem. 2011, 7, 1379–1386, doi:10.3762/bjoc.7.162

• triphenylphosphine gold chloride (16 µmol, 7.4 mg, 0.05 equiv) were loaded under a flow of argon. These solids were dried under vacuum at 70–80 °C for 2 h. A mixture of cyclic enamines (0.3 mmol, 72 mg, 1 equiv) was then added, followed by anhydrous MeCN (12 mL), under a flow of argon. The mixture was stirred at rt

Bromine–lithium exchange: An efficient tool in the modular construction of biaryl ligands

• Laurence Bonnafoux,
• Frédéric R. Leroux and
• Françoise Colobert

Beilstein J. Org. Chem. 2011, 7, 1278–1287, doi:10.3762/bjoc.7.148

• reaction could be modified in favor of the 2,2'-bis(diphenylphosphino)biphenyls 8 [27] which were still contaminated with varying amounts of phosphafluorenes 9 and triphenylphosphine (Table 2). Conclusion In the present work, we showed how completely regioselective bromine–lithium exchange reactions on

Gold(I)-catalyzed synthesis of γ-vinylbutyrolactones by intramolecular oxaallylic alkylation with alcohols

• Michel Chiarucci,
• Mirko Locritani,
• Gianpiero Cera and
• Marco Bandini

Beilstein J. Org. Chem. 2011, 7, 1198–1204, doi:10.3762/bjoc.7.139

• . With the less bulky triphenylphosphine ligand, the corresponding cationic gold(I) complex (i.e., PPh3AuNTf2) led to an increase in the isolated yield up to 52%, although the diastereoselection remained elusive (≈ 1:1, entry 3). After demonstrating that the Au(III) catalysis promoted the cyclization in

The Eschenmoser coupling reaction under continuous-flow conditions

• Sukhdeep Singh,
• J. Michael Köhler,
• Andreas Schober and
• G. Alexander Groß

Beilstein J. Org. Chem. 2011, 7, 1164–1172, doi:10.3762/bjoc.7.135

• agent, the mechanism of extraction via intermediate ionic states also seems plausible. Nevertheless, the Eschenmoser coupling reaction requires the addition of a base and a thiophilic agent in the most cases. Here, triphenylphosphine- or trialkyl-phosphite-derivatives are usually employed to promote the

Amine-linked diglycosides: Synthesis facilitated by the enhanced reactivity of allylic electrophiles, and glycosidase inhibition assays

• Ian Cumpstey,
• Jens Frigell,
• Elias Pershagen,
• Tashfeen Akhtar,
• Elena Moreno-Clavijo,
• Inmaculada Robina,
• Dominic S. Alonzi and
• Terry D. Butters

Beilstein J. Org. Chem. 2011, 7, 1115–1123, doi:10.3762/bjoc.7.128

• [34], as described previously [6], with only one equivalent of the sulfonylating agent so as to avoid bis-sulfonamide formation. Mixing equimolar equivalents of the erythro allylic alcohol 1 and the glucose-6-nosylamide 6 with DIAD and triphenylphosphine resulted in a smooth coupling reaction to give

Synthesis, reactivity and biological activity of 5-alkoxymethyluracil analogues

• Lucie Brulikova and
• Jan Hlavac

Beilstein J. Org. Chem. 2011, 7, 678–698, doi:10.3762/bjoc.7.80

• derivatives of 2'-deoxyuridine 28, 2'-fluoro-2'-deoxyuridine 29 and uridine 30 (Scheme 4). The authors utilized the known palladium acetate-triphenylphosphine-catalyzed reaction of 5-iodo-2'-deoxyuridine with vinyl acetate for the preparation of 5-vinyl-2'-deoxyuridine (9) [14]. However, attempts to prepare 2

Synthesis of cross-conjugated trienes by rhodium-catalyzed dimerization of monosubstituted allenes

• Tomoya Miura,
• Tsuneaki Biyajima,
• Takeharu Toyoshima and
• Masahiro Murakami

Beilstein J. Org. Chem. 2011, 7, 578–581, doi:10.3762/bjoc.7.67

• been developed. Among these, transition-metal-catalyzed dimerization of allenes presents a unique entry to substituted cross-conjugated trienes. For example, a nickel(0)/triphenylphosphine complex catalyzes a dimerization reaction of 3-methylbuta-1,2-diene to afford 2,5-dimethyl-3,4-bismethylenehex-1

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

• Marcus Baumann,
• Ian R. Baxendale,
• Steven V. Ley and
• Nikzad Nikbin

Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

• good yield (Scheme 34) [51]. More recently, Zhong and co-workers [52] reported a highly efficient one-pot procedure starting from N-acylated α-aminonitriles 173. The desired 2,4,5-trisubstituted imidazole core 178 is formed in high yield in the presence of carbon tetrachloride and triphenylphosphine

• (Scheme 35). Mechanistic studies showed that the related imidoyl compounds do not themselves undergo ring closure to form imidazoles and it was therefore proposed that the reaction between carbon tetrachloride and triphenylphosphine to generate dichlorotriphenylphosphorane and (dichloromethylene

Photoinduced homolytic C–H activation in N-(4-homoadamantyl)phthalimide

• Nikola Cindro,
• Margareta Horvat,
• Kata Mlinarić-Majerski,
• Axel G. Griesbeck and
• Nikola Basarić

Beilstein J. Org. Chem. 2011, 7, 270–277, doi:10.3762/bjoc.7.36

• the laboratory according to a known procedure [56]. Phthalimide, triphenylphosphine, lithium aluminum hydride (LAH) and diethyl azodicarboxylate (DEAD) were obtained from commercial sources. All photochemical experiments were performed in a Rayonet photochemical reactor equipped with 300 nm lamps. 4

• triphenylphosphine (2.00 g, 7.63 mmol) in THF (60 mL) was added over a 1 h period. The reaction mixture was stirred at rt in the dark and under a nitrogen atmosphere for 12 h. After the reaction was complete, the solvent was evaporated, and the crude product purified by column chromatography on silica gel with

An easy assembled fluorescent sensor for dicarboxylates and acidic amino acids

• Xiao-bo Zhou,
• Yuk-Wang Yip,
• Wing-Hong Chan and
• Albert W. M. Lee

Beilstein J. Org. Chem. 2011, 7, 75–81, doi:10.3762/bjoc.7.11

• -trimethylbenzene with sodium azide in DMSO afforded the corresponding bis-azide. Transformation of the crude bis-azide into bis-isothiocyanate 3 was achieved by treatment with triphenylphosphine in the presence of CS2. The “fluorophore–spacer–receptor” sensing motif for carboxylate was incorporated into the

Kinetics and mechanism of vanadium catalysed asymmetric cyanohydrin synthesis in propylene carbonate

• Michael North and
• Marta Omedes-Pujol

Beilstein J. Org. Chem. 2010, 6, 1043–1055, doi:10.3762/bjoc.6.119

• largely be located on silicon as shown in Figure 8a. This was found to be the case (ρ = +0.4) for asymmetric cyanohydrin synthesis catalysed by bimetallic aluminium(salen) complex 6 in the presence of triphenylphosphine oxide [83][84], indicating that most of the catalysis in this case was due to

• activation of the TMSCN by the triphenylphosphine oxide rather than activation of the aldehyde by the metal(salen) complex. In contrast, reactions catalysed by complex 1 gave a Hammett plot with a reaction constant of +2.4, indicating that there was a significant increase in negative charge at the benzylic

• significantly (from +1.6 to +0.4) when the solvent is changed from dichloromethane to propylene carbonate. The results obtained in propylene carbonate are almost identical to those previously obtained with complex 6 and triphenylphosphine oxide as catalyst [52], and are entirely consistent with a significant

Synthesis of 5-(6-hydroxy-7H-purine-8-ylthio)- 2-(N-hydroxyformamido)pentanoic acid

• Yanmei Zhang,
• Greg Elliot,
• Adrian Saldanha,
• Igor Tsigelny,
• Dennis Carson and
• Wolf Wrasidlo

Beilstein J. Org. Chem. 2010, 6, 742–747, doi:10.3762/bjoc.6.93

• 8 with triphenylphosphine in carbon tetrabromide resulted in the bromide 9 [5][6], which was coupled to mercaptopurine 9’ in the presence of sodium hydride in DMF to yield 10 [7][8] in excellent yield. Removal of the N-Troc group with zinc in acetic acid gave intermediate 11 and subsequent N