Continuous gas/liquid–liquid/liquid flow synthesis of 4-fluoropyrazole derivatives by selective direct fluorination

• Jessica R. Breen,
• Graham Sandford,
• Dmitrii S. Yufit,
• Judith A. K. Howard,
• Jonathan Fray and
• Bhairavi Patel

Beilstein J. Org. Chem. 2011, 7, 1048–1054, doi:10.3762/bjoc.7.120

• /liquid–liquid/liquid synthesis of fluoropyrazoles from fluorine, hydrazine and diketone starting materials was constructed from nickel metal and narrow bore PTFE tubing as described previously [28][29] (Figure 1). Briefly, fluorine gas, diluted to 10% v/v solution in nitrogen was added via a mass flow

Nano copper oxide catalyzed synthesis of symmetrical diaryl sulfides under ligand free conditions

• K. Harsha Vardhan Reddy,
• V. Prakash Reddy,
• A. Ashwan Kumar,
• G. Kranthi and
• Y.V.D. Nageswar

Beilstein J. Org. Chem. 2011, 7, 886–891, doi:10.3762/bjoc.7.101

• [10][11], Alzheimer’s and Parkinson’s diseases [12]. During the last decades, transition and boron group metals, such as palladium [13][14][15][16][17][18], nickel [19][20], copper [21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37], iron [38], indium [39][40], lanthanum [41] and

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

• -ene [18][19]. The nickel-catalyzed reaction, however, leads to a complex mixture of products when monosubstituted allenes such as penta-1,2-diene and 1-phenylpropa-1,2-diene are employed [20]. On the other hand, a palladium-catalyzed dimerization reaction of monosubstituted allenes produces

• dimerization reaction, in contrast to the nickel-catalyzed reaction [18][19]. Next, we examined the consecutive double [4 + 2] cycloaddition reaction of the cross-conjugated trienes obtained in the present study. Triene 3a was treated with 4-phenyl-1,2,4-triazoline-3,5-dione (4, PTAD), a highly reactive

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

• has led to the search for a new approach. It was found that a catalytic quantity of Raney nickel in an aqueous potassium hydroxide solution gives the desired 4-hydroxy compound 141 cleanly and in high conversion (Scheme 29). Alternative routes to this key intermediate such as Ullmann-type reactions

• % aqueous sulfuric acid a rearrangement to furnish a mixture of the 3- and 5-nitro derivatives occurs, which unfortunately at this stage, could not be separated by crystallisation. However, when this mixture was subjected to catalytic hydrogenation with Raney nickel a separable mixture of the corresponding

Studies on Pd/NiFe₂O₄ catalyzed ligand-free Suzuki reaction in aqueous phase: synthesis of biaryls, terphenyls and polyaryls

• Sanjay R. Borhade and
• Suresh B. Waghmode

Beilstein J. Org. Chem. 2011, 7, 310–319, doi:10.3762/bjoc.7.41

• Sanjay R. Borhade Suresh B. Waghmode Department of Chemistry, University of Pune, Ganeshkhind, Pune-411007, India 10.3762/bjoc.7.41 Abstract Palladium supported on nickel ferrite (Pd/NiF2O4) was found to be a highly active catalyst for the Suzuki coupling reaction between various aryl halides and

• catalysis; nickel ferrite; polyaryls; Suzuki reaction; terphenyls; Introduction Recently, transition metal catalyzed cross-coupling protocols have generated immense interest owing to their versatile applications in organic synthesis [1][2][3][4]. The Pd catalyzed Suzuki reaction between aryl halides with

• first report describing the synthesis of polyaryls under these reaction conditions and with this catalyst. Results and Discussion Nickel ferrite samples were synthesized as reported earlier [42]. Loading of Pd on nickel ferrite was carried out by wet impregnation and subsequently reduced by the

Photocycloaddition of aromatic and aliphatic aldehydes to isoxazoles: Cycloaddition reactivity and stability studies

• Axel G. Griesbeck,
• Marco Franke,
• Jörg Neudörfl and
• Hidehiro Kotaka

Beilstein J. Org. Chem. 2011, 7, 127–134, doi:10.3762/bjoc.7.18

• materials, followed by hydrogenation of these substrates (Scheme 8). Variations of reaction temperature (−10 °C), reaction time (6 h, 1 h) and solvent (ethanol, ethyl acetate) led to the same results. Hydrogenation of 9a by Raney-nickel led to partial decomposition without any further reaction, whilst

Palladium- and copper-mediated N-aryl bond formation reactions for the synthesis of biological active compounds

• Carolin Fischer and
• Burkhard Koenig

Beilstein J. Org. Chem. 2011, 7, 59–74, doi:10.3762/bjoc.7.10

• )TMEDA]2Cl2, omitting the base and working at room temperature [13][14]. Besides palladium and copper, nickel catalysis also allows the arylation of primary and secondary amines [15][16]. However, the three methods (Ullmann–Goldberg, Buchwald–Hartwig and Chan–Lam) have become standard procedures for N

Miniemulsion polymerization as a versatile tool for the synthesis of functionalized polymers

• Daniel Crespy and
• Katharina Landfester

Beilstein J. Org. Chem. 2010, 6, 1132–1148, doi:10.3762/bjoc.6.130

• polymerized via various heterophase polymerizations, including polymerization in miniemulsion. The first report on polymerization of ethylene in miniemulsion describes the synthesis of polyethylene nanoparticles in the presence of a nickel–ylide complex [10]. The catalyst was dissolved in toluene and

• ethylene and up to 3 mol % 1-butene. Small nanoparticles (~200 nm) could be obtained by ethylene polymerization with a nickel(II) keto–ylide complex with 10% solids content in direct miniemulsion [63]. The same group copolymerized ethylene and polar and non-polar α-olefins in miniemulsion with a P,O

Backbone tuning in indenylidene–ruthenium complexes bearing an unsaturated N-heterocyclic carbene

• César A. Urbina-Blanco,
• Xavier Bantreil,
• Hervé Clavier,
• Alexandra M. Z. Slawin and
• Steven P. Nolan

Beilstein J. Org. Chem. 2010, 6, 1120–1126, doi:10.3762/bjoc.6.128

• phosphanes, and more recently, has been used to study the electronic properties of NHCs [34]. However, the high toxicity of [Ni(CO)4] encouraged the search for analogous systems using different metals to determine the TEP. One of the most popular and suitable alternatives to nickel is a rhodium carbonyl

• (2050.3 cm−1) agrees well with the experimentally obtained value in the nickel system (2051.5 cm−1) [34]. Given their steric and geometric variability, evaluating the steric parameters of NHCs poses a more challenging task. One of the more recent methodologies defines a percent buried volume (%Vbur

Redox-active tetrathiafulvalene and dithiolene compounds derived from allylic 1,4-diol rearrangement products of disubstituted 1,3-dithiole derivatives

• Filipe Vilela,
• Peter J. Skabara,
• Christopher R. Mason,
• Thomas D. J. Westgate,
• Asun Luquin,
• Simon J. Coles and
• Michael B. Hursthouse

Beilstein J. Org. Chem. 2010, 6, 1002–1014, doi:10.3762/bjoc.6.113

• by two SN2 reactions with 1,2-dibromoethane in THF to yield 27(56% yield) after purification by column chromatography (eluting with 1:1 (v/v) CH2Cl2:petroleum ether). Dithiolate 24 was also generated from the analogous reaction with 3. On this occasion, treatment of 24 with excess nickel(II)chloride

• and tetrabutylammonium bromide afforded the nickel(II)dithiolato complex 28 (40% yield) after purification by recrystallisation from CH2Cl2 and hexane. Dithiolenes represent an important and well-studied class of molecular conductors [26] and we have previously studied thiophene-containing analogues

• solution. X-ray crystallographic data confirmed that the isolated nickel dithiolene was monoanionic and that only one of the two possible isomers of this product was isolated by the recrystallisation method (both non-fused thiophenes are on the same side of the fused framework). The molecular structure of

A perfluorocyclopentene based diarylethene bearing two terpyridine moieties – synthesis, photochemical properties and influence of transition metal ions

• Falk Wehmeier and
• Jochen Mattay

Beilstein J. Org. Chem. 2010, 6, No. 53, doi:10.3762/bjoc.6.53

• contrast to the iron(II) complex, the ditopic ligand seems to retain its photochromic properties in the cobalt(II) and nickel(II) complexes – synthesized from CoCl2 and [Ni(acac)2], respectively – although the photocyclisation takes much longer than with free 10a (about 5 minutes compared to ca. 30 seconds

• reversibility. It was shown that the presence of various transition metal ions significantly influences the photochromism of the bridging unit: While iron(II)-ions completely inhibit the photochromic reaction, cobalt(II) and nickel(II) appear to slow down the photoreaction considerably. Zinc(II)-ions, on the

Chemical synthesis using enzymatically generated building units for construction of the human milk pentasaccharides sialyllacto-N-tetraose and sialyllacto-N-neotetraose epimer

• Dirk Schmidt and
• Joachim Thiem

Beilstein J. Org. Chem. 2010, 6, No. 18, doi:10.3762/bjoc.6.18

• side products and separated by chromatography but these were not further characterized. Reduction of the 2′′′-azido to the 2′′′-amino group with nickel boride [12][13] followed by peracetylation gave 8 in 81% yield (Scheme 1). 1H NMR spectrum contained a doublet for H-1″ at δ 4.96 (J1″2″ = 8.0 Hz) and

• give the β,1-4-linked pentasaccharide derivative 13 in 53% yield. In addition, the corresponding α,1-4-linked pentasaccharide was obtained in 8% yield. Finally, the azido group was reduced by the nickel boride method with sodium borohydride, nickel chloride and boric acid [12][13]. During this step

Prediction of reduction potentials from calculated electron affinities for metal-salen compounds

• Sarah B. Bateni,
• Kellie R. England,
• Anthony T. Galatti,
• Handeep Kaur,
• Victor A. Mendiola,
• Alexander R. Mitchell,
• Michael H. Vu,
• Benjamin F. Gherman and
• James A. Miranda

Beilstein J. Org. Chem. 2009, 5, No. 82, doi:10.3762/bjoc.5.82

• [10] for both sets of metal-salens. Results and Discussion The 19 metal-salens comprising the training set are shown in Figure 1. The metals used in the training set include nickel, cobalt, copper, iron, zinc, and palladium. Included in the training set are the parent metal-salens (no substitution

• around the salen ligand), as well as metal-salens with various electron-donating and electron-withdrawing groups around the periphery of the salen ligand. Figure 2 shows that there is a good linear correlation between the computed EA and the Hammett parameter σp for the substituents [11]. Only nickel

• of electron-withdrawing groups and lead to larger EAs. Figure 3 shows that there is a good linear correlation between the experimental reduction potential (Epc) and EA for each of nickel, cobalt, and copper. Iron, zinc, and palladium were again excluded due to having only one point each in the

Iridium-catalyzed asymmetric ring-opening reactions of oxabicyclic alkenes with secondary amine nucleophiles

• Dingqiao Yang,
• Ping Hu,
• Yuhua Long,
• Yujuan Wu,
• Heping Zeng,
• Hui Wang and
• Xiongjun Zuo

Beilstein J. Org. Chem. 2009, 5, No. 53, doi:10.3762/bjoc.5.53

• metal catalysts may be used for asymmetric ring-opening reactions of oxabicyclic alkenes. These include complexes of copper [20][21][22][23][24][25], palladium [14][15][26][27][28][29][30][31], iron [32], and nickel [33][34][35][36]. Recently, we reported for the first time iridium-catalyzed asymmetric

Pd/C- Mediated synthesis of indoles in water

• Mohosin Layek,
• Udaya Lakshmi,
• Dipak Kalita,
• Deepak K. Barange,
• Aminul Islam,
• K. Mukkanti and
• Manojit Pal

Beilstein J. Org. Chem. 2009, 5, No. 46, doi:10.3762/bjoc.5.46

• corresponding sulfonic acid 5 which on treating with PCl5 provided the sulfonyl chloride derivative 6. On reaction with aqueous methylamine compound 6 provided the methanesulfonamide derivative 7, the nitro group of which was reduced in the presence of Raney nickel to yield the corresponding aniline derivative

• ), 58.5, 24.8, 24.4; HRMS (ESI): calcd for C9H13N2O4S (M+H)+ 245.0595, found 245.0592. Preparation of 2-(4-amino-phenyl)ethanesulfonic acid methylamide (8): A solution of compound 7 (1.55 g, 6.3 mmol) was dissolved in 1:1 methanol/ethyl acetate (30 mL) and hydrogenated in the presence of Raney nickel (1.5

2-Phenyl- tetrahydropyrimidine- 4(1H)-ones – cyclic benzaldehyde aminals as precursors for functionalised β²-amino acids

• Markus Nahrwold,
• Arvydas Stončius,
• Anna Penner,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2009, 5, No. 43, doi:10.3762/bjoc.5.43

• . Chemoselective reduction of 10 was carried out by reaction with sodium borohydride in the presence of Ni(OAc)2. The “nickel boride” formed as black precipitate serves as a highly active hydrogenation catalyst, whereas an excess of NaBH4 serves as hydrogen source [45][46]. The reaction reaches completion within

Mitomycins syntheses: a recent update

• Jean-Christophe Andrez

Beilstein J. Org. Chem. 2009, 5, No. 33, doi:10.3762/bjoc.5.33

• to an aziridine. The thiophenyl component was then removed with Raney nickel, which provided an elegant way to introduce the N-methyl group of the aziridine. Compound 44 was then treated with (trimethylsilyl)methyl lithium to install the exocyclic olefin via Peterson’s method. The p

• reacted with the terminal olefin to form the eight membered ring 121 (Scheme 35). Easy cleavage of the nitrogen–oxygen bond was realized using Raney nickel and the unsaturated ketone 122 was obtained in good yield. It is known that when a medium-sized ring is being generated by the INOC process none of

• give compound 194. The allyl group was cleaved using nickel chloride and triethylaluminium and fragmentation with iodosobenzene and iodine afforded compound 195. The formyl group was hydrolyzed and the azide was introduced using diphenylphosphoryl azide (DPPA) to give 187. The azide 189 was then

From discovery to production: Scale- out of continuous flow meso reactors

• Peter Styring and
• Ana I. R. Parracho

Beilstein J. Org. Chem. 2009, 5, No. 29, doi:10.3762/bjoc.5.29

• environmental and economic burden on the process. Previously, we have described a series of catalysts based on nickel(II) and palladium(II) that have functionalised salen-acac (salenac) ligands that were functionalised such that they could be covalently bound to organic or inorganic polymer supports [6][7][8][9

• Suzuki and Heck coupling reactions at elevated temperatures while the nickel catalyst is active in the Kumada coupling [11][12] reaction at room temperature in batch (Scheme 1) and continuous flow reactors. In the latter, the catalyst is packed into a 3 mm diameter glass reactor tube of length 25 mm and

• was packed with nickel immobilised onto Merrifield resin (mean average particles size of 45 μm when dry and 72 μm when wet in THF), with approximately 3% nickel loading. A syringe pump (RAZAL A-99) was used to pump a pre-determined volume of the solution of known concentrations at different flow rates

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

• with moderate to good enantioselectivities (up to 78% ee) when the reaction was carried out in the presence of DBFOX-Ph (11 mol%), Ni(ClO4)2·6H2O (10 mol%) and 2,6-lutidine (0 or 1.0 equiv) in CH2Cl2. Keywords: fluorination; enantioselective; nickel; Lewis acid; catalyst; Background Enantioselective

Total synthesis of the indolizidine alkaloid tashiromine

• Stephen P. Marsden and
• Alison D. McElhinney

Beilstein J. Org. Chem. 2008, 4, No. 8, doi:10.1186/1860-5397-4-8

• phosphorane [17] or nickel-catalysed 1,2-metallate rearrangement of lithiated dihydropyran [18]. Our approach was informed by the prior work by our own group [19][20][21][22][23][24] and others [25][26][27][28][29][30][31][32][33][34][35][36][37][38] on the use of olefin metathesis to generate functionalised

Analogues of amphibian alkaloids: total synthesis of (5R,8S,8aS)-(−)-8-methyl- 5-pentyloctahydroindolizine (8-epi-indolizidine 209B) and [(1S,4R,9aS)-(−)-4-pentyloctahydro- 2H-quinolizin- 1-yl]methanol

• Joseph P. Michael,
• Claudia Accone,
• Charles B. de Koning and
• Christiaan W. van der Westhuyzen

Beilstein J. Org. Chem. 2008, 4, No. 5, doi:10.1186/1860-5397-4-5

• Raney nickel [25] in boiling ethanol to give (−)-(5R,8S,8aS)-8-methyl-5-pentyloctahydroindolizine (8-epi-indolizidine 209B) 9 in 74% yield. The spectroscopic data for this product agreed with those reported for the racemate. Support for the cis-relationship of the hydrogen atoms at C-5 and C-8a in all

• cis-hydrogenation of 39. While it would have been desirable to conclude this investigation by preparing (1S,4R,9aS)-4-pentyloctahydro-2H-quinolizine 42, the ring homologue of 8-epi-indolizidine 209B, this target eluded us. Attempts to reduce the corresponding methanesulfonate of 41 with Raney nickel

A convenient allylsilane- N-acyliminium route toward indolizidine and quinolizidine alkaloids

• Roland Remuson

Beilstein J. Org. Chem. 2007, 3, No. 32, doi:10.1186/1860-5397-3-32

• were the conversion of 7b into its dithiolane and subsequent desulfurisation using Raney nickel. The synthesis of (-)-indolizidine 167B 1 has been achieved in 7 steps with a 17% overall yield from ethyl (3R)-3-aminohexanoate 2 with an enantiomeric excess of 93%. [19] I 1.2 Intermolecular cyclisation