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

• . Kamigata et al. in the case of ruthenium catalysts, where isomeric mixtures of α- and β-functionalized pyrroles were produced [101][104]. In 2001, Q.-Y. Chen and coworkers also reported a nickel-catalyzed methodology, with perfluoroalkyl chlorides as perfluoroalkylating reagents and in the presence of

• discussed for its Pd-catalyzed variant, is also catalyzed by nickel complexes (Scheme 11) [71]. Actually, the nickel-based systems provided higher yields than the palladium-based one (see section 3.1.3). Considering control voltamperometric experiments, a Ni(II)/Ni(III) catalytic cycle seemed to be

Micro-flow synthesis and structural analysis of sterically crowded diimine ligands with five aryl rings

• Shinichiro Fuse,
• Nobutake Tanabe,
• Akio Tannna,
• Yohei Konishi and
• Takashi Takahashi

Beilstein J. Org. Chem. 2013, 9, 2336–2343, doi:10.3762/bjoc.9.268

• , Yokohama 227-8502, Japan 10.3762/bjoc.9.268 Abstract Sterically crowded diimine ligands with five aryl rings were prepared in one step in good yields using a micro-flow technique. X-ray crystallographic analysis revealed the detailed structure of the bulky ligands. The nickel complexes prepared from the

• identical, although N=C–N–C=N was not in a common plane. These features were similar to that of 3b. A complexation of the synthesized ligands 3b and 3c with nickel(II) was performed (Scheme 3) in accordance with a reported procedure [38]. An equimolar amount of NiBr2(dme) (dme = 1,2-dimethoxyethane) and the

• synthesized ligands were mixed in CH2Cl2 and stirred for 4 h at room temperature. Free ligands 3b or 3c were not observed by 1H NMR analysis of the obtained crude mixtures. NMR characterization of the complexes 12 and 13 was poor due to the paramagnetic nature of the pseudo-tetrahedral nickel centers. In the

Cyclopamine analogs bearing exocyclic methylenes are highly potent and acid-stable inhibitors of hedgehog signaling

• Johann Moschner,
• Anna Chentsova,
• Nicole Eilert,
• Irene Rovardi,
• Philipp Heretsch and
• Athanassios Giannis

Beilstein J. Org. Chem. 2013, 9, 2328–2335, doi:10.3762/bjoc.9.267

• catalyst in benzene yielded previously described exo-cyclopamine 2 and its C25 epimer 5. Deprotection with Raney-nickel (EtOH, 78 °C) and then sodium naphthalenide (DME, −78 °C, 41% over two steps) furnished 25-epi-exo-cyclopamine 5 in 3% overall yield from 3. A first set of exo-cyclopamine analogs with a

• ) reductive removal of the so-obtained acetate (Et3SiH, BF3·Et2O, −78 °C to −20 °C, 79%). Removal of the benzyl ether, reduction of the azide moiety and concomitant alkylation was then all effected in one pot by using Raney-nickel in EtOH to give analog 8, an F-ring-opened exo-cyclopamine derivative in 27

• , quant. (3:1 dr); (e) Raney-nickel (W2), EtOH, 78 °C, 5 min; (f) sodium naphthalenide, DME, −78 °C, 30 min, 41% over two steps; (g) DDQ, DCE/phosphate buffer (pH 7), 40 °C, 95 min, 86%; (h) sodium naphthalenide, DME, −78 °C, 1 h, 79%; (i) Raney-nickel (W2), EtOH, 37%; (j) DDQ, DCE/phosphate buffer (pH 7

An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

A reductive coupling strategy towards ripostatin A

• Kristin D. Schleicher and
• Timothy F. Jamison

Beilstein J. Org. Chem. 2013, 9, 1533–1550, doi:10.3762/bjoc.9.175

• construct the C9−C10 bond by a nickel(0)-catalyzed coupling reaction of an enyne and an epoxide, followed by rearrangement of the resulting dienylcyclopropane intermediate to afford the skipped 1,4,7-triene. A cyclopropyl enyne fragment corresponding to C1−C9 has been synthesized in high yield and

• demonstrated to be a competent substrate for the nickel(0)-catalyzed coupling with a model epoxide. Several synthetic approaches toward the C10−C26 epoxide have been pursued. The C13 stereocenter can be set by allylation and reductive decyanation of a cyanohydrin acetonide. A mild, fluoride-promoted

• decarboxylation enables construction of the C15−C16 bond by an aldol reaction. The product of this transformation is of the correct oxidation state and potentially three steps removed from the targeted epoxide fragment. Keywords: catalysis; natural product; nickel; reductive coupling; ripostatin A; synthesis

Controlled synthesis of poly(3-hexylthiophene) in continuous flow

• Helga Seyler,
• Jegadesan Subbiah,
• David J. Jones,
• Andrew B. Holmes and
• Wallace W. H. Wong

Beilstein J. Org. Chem. 2013, 9, 1492–1500, doi:10.3762/bjoc.9.170

• , we were inspired by the work of a number of research groups, in which polymerization was externally initiated from an active tolyl-functionalized nickel complex 3 (Scheme 1a) [8][9][22]. The tolyl–nickel species 3 is soluble and shows good stability in THF in an inert environment. Further, polymers

• reagent concentrations (Table 1). Gel-permeation chromatography (GPC) analysis in toluene (against polystyrene standards) revealed the formation of polymer with number-average molecular weights (Mn) ranging from 5 to 40 kg/mol. The Mn values increased linearly with nickel catalyst content, providing

• weights could only be achieved in the PFA reactors (Table 2, entries 3–5). This suggests that the nickel-catalyzed polymerization is incompatible with the stainless-steel reactor and we speculate that the nickel content in stainless steel may be the cause of the incompatibility especially at the elevated

Intramolecular carbonickelation of alkenes

• Rudy Lhermet,
• Muriel Durandetti and
• Jacques Maddaluno

Beilstein J. Org. Chem. 2013, 9, 710–716, doi:10.3762/bjoc.9.81

• skeleton was achieved by using NiBr2bipy catalysis. Keywords: alkenes; carbometallation; carbonickelation; cyclization; Heck-type reaction; nickel catalysis; Introduction Carbometalation is a reaction involving the addition of an organometallic species to a nonactivated alkene or alkyne to form a new

• pharmaceutical and agrochemical intermediates using nonactivated olefins with high regio- and stereoselectivity [7]. Besides the typical intermolecular version, some intramolecular variants were developed leading to useful heterocycles [8][9][10]. Even if palladium is very efficient, nickel appears to be among

• the most promising metallic substitutes [11]. However, the tedious preparation of Ni(0) complexes such as Ni(cod)2 explains that nickel chemistry is hardly perceived as a realistic alternative to palladium, except in electrochemical processes [12][13]. Nevertheless, some nickel-catalyzed Heck

Some aspects of radical chemistry in the assembly of complex molecular architectures

• Béatrice Quiclet-Sire and
• Samir Z. Zard

Beilstein J. Org. Chem. 2013, 9, 557–576, doi:10.3762/bjoc.9.61

• capture of nitrogen-centred radicals, the degenerative transfer of xanthates and related thiocarbonylthio derivatives, chain processes based on the chemistry of sulfonyl radicals, and electron transfer from metallic nickel to halides and oxime esters. These new reactions can be readily harnessed for the

• of radicals by electron transfer from metallic nickel A final topic in this brief overview concerns the use of electron transfer from metallic nickel as a means for producing and capturing radicals from selected substrates. The underlying principle is quite simple. It hinges on the observation that

• with plain nickel powder and diminishing the acidity of the medium by addition of a cosolvent allows the cyclisation to proceed. The resulting secondary radical 158 is not sufficiently electrophilic in character to be reduced by the metal and can be trapped by various external reagents, as exemplified

Efficient Cu-catalyzed base-free C–S coupling under conventional and microwave heating. A simple access to S-heterocycles and sulfides

• Silvia M. Soria-Castro and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2013, 9, 467–475, doi:10.3762/bjoc.9.50

• compounds. The formation of C–S bonds can also be accomplished in good to excellent yields by transition-metal catalysis [10][11], mainly using palladium [12], copper [13][14][15][16], nickel [17][18] and iron [19][20] salts. Aryl coupling reactions employing different palladium species as catalysts

Spin state switching in iron coordination compounds

• Philipp Gütlich,
• Ana B. Gaspar and
• Yann Garcia

Beilstein J. Org. Chem. 2013, 9, 342–391, doi:10.3762/bjoc.9.39

• ), manganese(III), and nickel were found to exhibit thermal ST phenomena [31][32][33]. But practically no example of thermal ST with coordination compounds of the 4d and 5d transition metal series has been reported up to now, which is well understood on the basis of ligand field theory [34][35]. The purpose of

Recent advances in transition-metal-catalyzed intermolecular carbomagnesiation and carbozincation

• Kei Murakami and
• Hideki Yorimitsu

Beilstein J. Org. Chem. 2013, 9, 278–302, doi:10.3762/bjoc.9.34

• [96][97] where carbometalation is followed by carbon–carbon bond cleavage. Firstly, the oxidative addition of methylenecyclopropane to the reduced nickel(0) may yield 3A or 3C. The subsequent isomerization would proceed to form 3B or 3D, respectively, and then reductive elimination would afford the

• corresponding organomagnesium intermediate 3i or 3j. Carbomagnesiation and carbozincation of unfunctionalized alkynes and alkenes Carbomagnesiation and carbozincation of simple alkynes has been a longstanding challenge. In 1978, Duboudin reported nickel-catalyzed carbomagnesiation of unfunctionalized alkynes

• , such as phenylacetylenes and dialkylacetylenes (Scheme 26) [98]. Although this achievement is significant as an intermolecular carbomagnesiation of unreactive alkynes, the scope was fairly limited and yields were low. In 1997, Knochel reported nickel-catalyzed carbozincation of arylacetylenes (Scheme

Iron-containing mesoporous aluminosilicate catalyzed direct alkenylation of phenols: Facile synthesis of 1,1-diarylalkenes

• Satyajit Haldar and
• Subratanath Koner

Beilstein J. Org. Chem. 2013, 9, 49–55, doi:10.3762/bjoc.9.6

• ][23]. In general, the reaction shows β-selectivity, and there are only a few reports available concerned with α-substituted products [24][25][26]. Sabarre and Love reported a one-pot rhodium-catalyzed alkyne hydrothiolation followed by a nickel-catalyzed Kumada-type cross coupling with Grignard

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

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

• selectivity is determined by η2-coordination. The behavior of 24 towards nickel catalysts has been studied by Pasto and Huang (Scheme 54) [143]. In the presence of Ni(PPh3)3 24 trimerizes to the unusual ten-membered polyene 219. When the reaction is carried out with Ni(COD)2 (COD = 1,5-cyclooctadiene) both

New efficient ligand for sub-mol % copper-catalyzed C–N cross-coupling reactions running under air

• Per-Fredrik Larsson,
• Peter Astvik and
• Per-Ola Norrby

Beilstein J. Org. Chem. 2012, 8, 1909–1915, doi:10.3762/bjoc.8.221

• common choices such as palladium and nickel. With a few exceptions [23][45], the catalytic loading is still in the range of 5–20 mol %. We have shown recently that in many cases sub-mol % of copper is enough to catalyze several transformations [76][77]. By keeping the ligand (DMEDA) concentration high

Self-assembled organic–inorganic magnetic hybrid adsorbent ferrite based on cyclodextrin nanoparticles

• Ângelo M. L. Denadai,
• Frederico B. De Sousa,
• Joel J. Passos,
• Fernando C. Guatimosim,
• Kirla D. Barbosa,
• Ana E. Burgos,
• Fernando Castro de Oliveira,
• Jeann C. da Silva,
• Bernardo R. A. Neves,
• Nelcy D. S. Mohallem and
• Rubén D. Sinisterra

Beilstein J. Org. Chem. 2012, 8, 1867–1876, doi:10.3762/bjoc.8.215

• technologies, including ferrofluids [7], magnetic separators [8], magnetic resonance imaging [9], hyperthermia [10], and water treatment [4]. Nickel-zinc ferrites (Fe-Ni/Zn) are one of these versatile magnetic materials, since these systems present high magnetic saturation, Curie temperature and chemical

• Reagents and ferrite synthesis βCD was obtained from Xiamen Mchem, Xiamen (China). Salts used for the ferrite synthesis (FeSO4·7H2O, NiSO4·6H2O and ZnSO4·7H2O) were obtained from Merck Laboratory and used without further purification. Magnetic nanoparticles of nickel/zinc (Fe-Ni/Zn) and nickel/zinc

Copper-catalyzed CuAAC/intramolecular C–H arylation sequence: Synthesis of annulated 1,2,3-triazoles

• Rajkumar Jeyachandran,
• Harish Kumar Potukuchi and
• Lutz Ackermann

Beilstein J. Org. Chem. 2012, 8, 1771–1777, doi:10.3762/bjoc.8.202

• ][16]. This streamlining of organic synthesis has predominantly been accomplished with palladium [4][5][6][7][8][9][10][11][12][13][14][15][16], rhodium [17][18][19] or ruthenium [20][21][22] complexes [4][5][6][7][8][9][10][11][12][13][14][15][16]. However, less expensive nickel, cobalt, iron or

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

• -atom or nitrene-group transfer and formation of (PNP)Ir–N2 [78], and this reaction was utilized in catalytic C–H functionalization (see below). More recently, Hillhouse's nickel carbenes and imides have been shown to exhibit similar reactivity with organic azides, though reaction with CO2 has not been

Approaches to α-amino acids via rearrangement to electron-deficient nitrogen: Beckmann and Hofmann rearrangements of appropriate carboxyl-protected substrates

• Sosale Chandrasekhar and
• V. Mohana Rao

Beilstein J. Org. Chem. 2012, 8, 1393–1399, doi:10.3762/bjoc.8.161

• -trihydroxycyclohexane. This is accessible via Raney-Nickel catalyzed hydrogenation of phloroglucinol, the trans-orthoesterification being catalyzed by BF3 etherate. The trioxaadamantyl group is extremely stable particularly under neutral and basic conditions [16]. Moreover, the trioxaadamantyl group can be selectively

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

• Raney nickel did not provide full conversion to the respective anilines. Furthermore, the reaction mixtures contained products 7 and 8. At higher pressure (20 atm), complete nitro group and C=C reduction of stilbenes 5 and 6 to compounds 7 and 8, respectively, took place (Table 4). Several other

Two-directional synthesis as a tool for diversity-oriented synthesis: Synthesis of alkaloid scaffolds

• Kieron M. G. O’Connell,
• Monica Díaz-Gavilán,
• Warren R. J. D. Galloway and
• David R. Spring

Beilstein J. Org. Chem. 2012, 8, 850–860, doi:10.3762/bjoc.8.95

• final step in the synthesis was a diastereoselective reduction of the double bond with hydrogen gas and Raney-nickel. This was achieved in a moderate 57% yield and with good (~10:1) diastereoselectivity by complexing the nitrogen lone pair with tosic acid, effectively blocking the undesirable face of

• % yield of the nitroketone. Two-directional synthesis of diketone 18 in this fashion did not prove to be feasible; however, it was achieved in good yield by Michael addition of the nitroketone anion to phenylvinylketone. Subjecting diketone 18 to H2 gas and Raney-nickel then reduced the nitro group and

Synthetic glycopeptides and glycoproteins with applications in biological research

• Ulrika Westerlind

Beilstein J. Org. Chem. 2012, 8, 804–818, doi:10.3762/bjoc.8.90

• functional groups. After ligation the side-chain thiol could be removed by Raney nickel treatment. Employing the desulfurization methodology, thiol amino acids could be converted to alanine, valine, phenylalanine and threonine residues [71][72][73][74][75][76]. As an alternative to Raney nickel reduction, a

Sonogashira–Hagihara reactions of halogenated glycals

• Dennis C. Koester and
• Daniel B. Werz

Beilstein J. Org. Chem. 2012, 8, 675–682, doi:10.3762/bjoc.8.75

• enynes was achieved by selective reduction of the triple bond by making use of Raney nickel (Table 3). We found that the electron-rich enol ether moiety remains untouched, when reaction times of less than four hours were chosen in the case of the enynes 9e–9h. It should be noted that methanol was a

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

• bis-alkylation of thiophene (1), oxidation to the corresponding sulfone 3, and treatment with fumaronitrile (Scheme 1, top line). However, for most of the phthalonitriles we have made, we have found that a much better route is the nickel-catalysed reaction of an alkylzinc iodide with the bistriflate

• -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

Synthesis of highly functionalized β-aminocyclopentanecarboxylate stereoisomers by reductive ring opening reaction of isoxazolines

• Melinda Nonn,
• Loránd Kiss,
• Reijo Sillanpää and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2012, 8, 100–106, doi:10.3762/bjoc.8.10

•  3). Combinations of NaBH4 (as a mild and selective reducing agent) with cobalt, nickel, iridium or rhodium halide have previously been employed for cleavage of the isoxazoline ring system, which is otherwise inert to NaBH4 without such metal halide additives [50]. Accordingly, we investigated 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

• with arylboronic acids providing the arylazolylpalladium complex, which delivers the product (Scheme 27b and Scheme 28b). Rhodium- and nickel-catalyzed direct arylation of oxazoles with halides The methodology for the Rh(I)-catalyzed direct substitutive coupling of azoles with halides was developed by