Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

• phosphate group reacted with aryl Grignard, as a Kumada–Tamao-Corriu cross-coupling, in the presence of a nickel catalyst [90]. Aryl dialkyl phosphate, which was readily obtained by the AT reaction from phenol as shown in Scheme 31 [91], can be employed for the production of aryl phosphonate by applying a

• et al. [95] reports the amination of either triaryl phosphate or dialkyl aryl phosphate catalyzed by nickel organometallic complexes. It is an additional illustration of the use of aryl phosphate, which can be readily obtained by AT reactions. Beside the use of phosphorus species as a substrate in

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

• restricted to benzylic and allylic coupling partners. Ager and Laneman have synthesized tertiary phosphine oxide 23 through the nickel-catalyzed coupling of benzyl bromide (21a) with diphenylphosphine chloride (22a) (Scheme 7) [53]. However oxidation occurred during work-up. The group of Togni has

• ][94][95][96], palladium [97][98][99] or nickel [100][101][102][103][104] complexes. Other catalysts that have been less investigated are iron [105][106][107], rhodium [108][109][110], lanthanides [111][112][113][114], copper [115] and alkaline-earth metals [114][116]. The catalyst activates either the

• hydrophosphination of vinyl nitriles catalyzed by a dicationic nickel complex (Table 3). The method is based on the activation of the electrophile. It was suggested that complexation of the nitrile 50 to the chiral nickel Lewis acid activates the double bond towards 1,4-addition of the phosphine 25b. A final proton

A new building block for DNA network formation by self-assembly and polymerase chain reaction

• Holger Bußkamp,
• Sascha Keller,
• Marta Robotta,
• Malte Drescher and
• Andreas Marx

Beilstein J. Org. Chem. 2014, 10, 1037–1046, doi:10.3762/bjoc.10.104

• interactions and induced by nickel ions on the mica surface. More information about the DNA network character was observed taking the first derivative of the height output channel resulting in Figure 4E. The principle of this mathematic operation is to assume a local maximum at an edge resulting from cross

Towards allosteric receptors – synthesis of β-cyclodextrin-functionalised 2,2’-bipyridines and their metal complexes

• Christopher Kremer,
• Gregor Schnakenburg and
• Arne Lützen

Beilstein J. Org. Chem. 2014, 10, 814–824, doi:10.3762/bjoc.10.77

• were prepared starting from commercially available 4-amino-2-chloropyridine (4) and 2-amino-6-bromopyridine (5), respectively. After protection of the amino functions as 2,5-dimethylpyrroles, pyridines 6 and 7 were transformed into the corresponding 2,2’-bipyridines 8 and 9 via a nickel-catalysed homo

First synthesis of meso-substituted pyrrolo[1,2-a]quinoxalinoporphyrins

• Dileep Kumar Singh and
• Mahendra Nath

Beilstein J. Org. Chem. 2014, 10, 808–813, doi:10.3762/bjoc.10.76

• provided an inseparable mixture of products. Instead, nitroporphyrin 2 was successfully reduced to 5-(3-amino-4-(pyrrol-1-yl)phenyl)-10,15,20-triphenylporphyrin (3) in the presence of nickel boride, generated in situ by the reaction of NiCl2 and NaBH4 in a CH2Cl2/MeOH mixture at 25 °C. Finally, the

Asymmetric total synthesis of a putative sex pheromone component from the parasitoid wasp Trichogramma turkestanica

• Danny Geerdink,
• Jeffrey Buter,
• Teris A. van Beek and
• Adriaan J. Minnaard

Beilstein J. Org. Chem. 2014, 10, 761–766, doi:10.3762/bjoc.10.71

•  2) [24]. The use of 1.2 equiv of BF3·Et2O led to 9 in 84% isolated yield. Reduction of 9 with freshly prepared Raney nickel and subsequent desilylation afforded 10 over two steps in 73% yield. To introduce the desired E,E-diene present in 2 and 1, we realized that the procedure reported by

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• keteneimines 57 [77] or in [3 + 3] processes with dimethyl cyclopropane-1,1-dicarboxylates 59 [78]. Both these reactions are co-catalyzed, the former by silver triflate and copper bromide and the latter by silver triflate and nickel(II) perchlorate (Scheme 30 and Scheme 31). In [3 + 2]-cycloaddition reactions

• -catalyzed process described in Scheme 31 takes advantage of the usual formation of 43 which undergoes a [3 + 3]-cycloaddition reaction with cyclopropanes 59 under nickel perchlorate catalysis. Cycloaddition reactions of activated cyclopropanes with nitrones under Lewis acid catalysis have been previously

Self-assembly of metallosupramolecular rhombi from chiral concave 9,9’-spirobifluorene-derived bis(pyridine) ligands

• Rainer Hovorka,
• Sophie Hytteballe,
• Torsten Piehler,
• Georg Meyer-Eppler,
• Filip Topić,
• Kari Rissanen,
• Marianne Engeser and
• Arne Lützen

Beilstein J. Org. Chem. 2014, 10, 432–441, doi:10.3762/bjoc.10.40

• in our previous work (see [35]).) (S)-1, however, was reacted in a nickel-catalysed Kumada cross-coupling reaction to furnish 2,2’-dimethylated spirobifluorene (S)-4 which was then brominated twice to afford tetrafunctionalised spirobifluorene (S)-5. Finally, (S)-5 could be transformed into the

A new manganese-mediated, cobalt-catalyzed three-component synthesis of (diarylmethyl)sulfonamides

• Antoine Pignon,
• Erwan Le Gall and
• Thierry Martens

Beilstein J. Org. Chem. 2014, 10, 425–431, doi:10.3762/bjoc.10.39

• in a significant decrease of the reaction efficiency, thus indicating the prevalent role of the catalyst. This was confirmed by the absence of the coupling product when the reaction was conducted in the absence of cobalt bromide (Table 1, entry 19). Another nickel-based catalyst, e.g., NiBr2bpy, was

Boron-substituted 1,3-dienes and heterodienes as key elements in multicomponent processes

• Ludovic Eberlin,
• Fabien Tripoteau,
• François Carreaux,
• Andrew Whiting and
• Bertrand Carboni

Beilstein J. Org. Chem. 2014, 10, 237–250, doi:10.3762/bjoc.10.19

• proved to give the best yields, probably due to the higher reactivity of the corresponding hydrazones. Furthermore, the double bond of 29 was selectively hydrogenated under palladium on charcoal, while hydrogenolysis of the hydrazine moiety occurred in the presence of Raney nickel (Scheme 22). Following

The renaissance of organic radical chemistry – deja vu all over again

• Corey R. J. Stephenson,
• Armido Studer and
• Dennis P. Curran

Beilstein J. Org. Chem. 2013, 9, 2778–2780, doi:10.3762/bjoc.9.312

• homolytic aromatic substitution (BHAS) [3], b) photoredox catalysis [4][5][6][7][8], c) redox chemistry using Bu4NI in combination with t-BuOOH [9], d) transition metal catalyzed processes where radicals are suggested to interact directly with copper, nickel, zinc, palladium, gold and so on [10][11][12][13

New syntheses of 5,6- and 7,8-diaminoquinolines

• Maroš Bella and
• Viktor Milata

Beilstein J. Org. Chem. 2013, 9, 2669–2674, doi:10.3762/bjoc.9.302

• -diaminoquinoline [7]. Another approach is based on the amination of 7-nitroquinoline in position 8 with hydroxylamine under basic conditions. The resulting 8-amino-7-nitroquinoline was reduced with SnCl2·2H2O [8] or hydrazine hydrate on Raney nickel as a catalyst [9] to obtain 7,8-diaminoquinoline. In the last

• the Skraup reaction of 4-nitroaniline produces 6-nitroquinoline as a sole product in moderate yield (47%). The latter, on treatment with hydroxylamine hydrochloride in the presence of KOH [11] followed by the reduction with hydrazine hydrate on Raney nickel, provided 5,6-diaminoquinoline in almost

• recrystallisation from toluene (Scheme 1). The temperature of the chlorination (90 °C) was found to be crucial, since heating of the reaction mixture under reflux led to a rapid decomposition. The catalytic hydrogenation of 6-chloroderivative 2 using 10% palladium on charcoal or Raney nickel did not afford 7,8

Garner’s aldehyde as a versatile intermediate in the synthesis of enantiopure natural products

• Mikko Passiniemi and
• Ari M.P. Koskinen

Beilstein J. Org. Chem. 2013, 9, 2641–2659, doi:10.3762/bjoc.9.300

• reactivity of the metalated nucleophiles and also the metal’s capability of coordination. Montgomery studied the nickel-catalyzed reductive additions of α-aminoaldehydes with silylalkynes (Scheme 20) [76]. The reduction of TMS-alkyne 53 was performed with a trialkylsilane and a Ni(COD)2 catalyst ligated with

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