Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• Grignard reagent 71 in the presence of a nickel phosphine complex 72 gave muscopyridine 73 in a single step (Scheme 11). This strategy has been applied to generate a variety of pyridinophanes by varying the chain length of the Grignard reagent. McMurry coupling: Kuroda and co-workers [99] have reported the

Synthesis of 1,2-cis-2-C-branched aryl-C-glucosides via desulfurization of carbohydrate based hemithioacetals

• Henok H. Kinfe,
• Fanuel M. Mebrahtu,
• Mandlenkosi M. Manana,
• Kagiso Madumo and
• Mokela S. Sokamisa

Beilstein J. Org. Chem. 2015, 11, 583–588, doi:10.3762/bjoc.11.64

• of hemithioacetal 3a in ethanol with freshly prepared Raney Nickel (W-2). However, the reaction led to the formation of the desired product in un-usable quantities along with randomly de-benzylated and other byproducts. Attempts for the exclusive synthesis of glucoside 4a using different strengths of

• Raney nickel and reaction conditions (solvent, temperature and reaction time) were all unsuccessful. Interestingly, during the course of the investigation it was noted that the reaction proceeded via the formation of a less polar intermediate (judged by TLC analysis). This intermediate was properly

• -1 Raney Nickel in acetone at ambient temperature with no evidence on the formation of glucoside 4a and ring contraction by sulfur extrusion. Consideration of the conditions required for the formation of the mixture of carbaldehydes 5a and 5a’ suggests that hydrogenolytic desulfurization of the C(sp2

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

• restricts the functional groups that can be present in the starting material. The SmI2-mediated method provides a useful alternative because this reagent is mild and highly tolerant of functional groups. Since it is well known that SmI2 causes the 1,4-reduction of α,β-unsaturated systems [172], nickel(II

• Jørgensen group reported the first aza-Michael addition of secondary aryl amines [234]. The authors obtained the 1,4-addition products in moderate to high yields and enantioselectivities by using a nickel–DBFOX–Ph [235][236] catalyst (Scheme 30). Other chiral ligands have been used in addition to chiral

Highly selective generation of vanillin by anodic degradation of lignin: a combined approach of electrochemistry and product isolation by adsorption

• Dominik Schmitt,
• Carolin Regenbrecht,
• Marius Hartmer,
• Florian Stecker and
• Siegfried R. Waldvogel

Beilstein J. Org. Chem. 2015, 11, 473–480, doi:10.3762/bjoc.11.53

• acidification and precipitation of remaining lignin. The latter represents a significant advantage compared with conventional work-up protocols of lignin solutions. Keywords: adsorption; electrochemistry; lignin; nickel; renewable resources; Introduction The biopolymer lignin is one of the most abundant and

• an elegant separation of the formed vanillin (1) from remaining lignin directly out of the basic reaction solution. Results and Discussion The electrochemical degradation of lignin in alkaline media is usually performed on nickel anodes. Utley et al. presented a very promising electrochemical

• formation of vanillin (1) and a novel as well as viable work-up concept exploiting strongly basic anion exchange resins. As renewable feedstock we employed alkaline lignin solutions. Alloys of cobalt and nickel as anodic material are suitable forming in situ electrochemically active MO(OH) coatings. Despite

Recent advances in the electrochemical construction of heterocycles

• Robert Francke

Beilstein J. Org. Chem. 2014, 10, 2858–2873, doi:10.3762/bjoc.10.303

• hydride in combination with a radical initiator such as AIBN. Peters and co-workers described an electrochemical alternative using cathodically generated nickel(I) complexes as mediators [41][42]. Under potentiostatic conditions (C.P.E. = controlled potential electrolysis) in a divided cell

(2R,1'S,2'R)- and (2S,1'S,2'R)-3-[2-Mono(di,tri)fluoromethylcyclopropyl]alanines and their incorporation into hormaomycin analogues

• Armin de Meijere,
• Sergei I. Kozhushkov,
• Dmitrii S. Yufit,
• Christian Grosse,
• Marcel Kaiser and
• Vitaly A. Raev

Beilstein J. Org. Chem. 2014, 10, 2844–2857, doi:10.3762/bjoc.10.302

• employment of the enantiomeric nickel(II) complexes (R)-10 and (S)-10 [18][19][20] in the synthesis of (2R,1R',2R')- and (2S,1R',2R')-3-(2-nitrocyclopropyl)alanine (5) for the native hormaomycin (1) [7][9], a completely analogous route was chosen towards (2R,1'S,2'R)- and (2S,1'S,2'R)-9a–c. This required the

• . Unfortunately, the diastereomers could not be separated by fractional crystallization as easily as was previously reported for the corresponding 3-(trans-2-nitrocyclopropyl)alanine derivatives [7]. The absolute configuration of the arbitrarily selected nickel(II) complexes (2S,1'R,2'S)-26a, (2S,1'R,2'S)-26b and

• (2R,1'R,2'S)-26b were determined by a single crystal X-ray structure analysis (see Figure 3 and Supporting Information File 1) [28]. The isolated nickel complexes 26a–c were decomposed by treatment with refluxing aqueous methanolic hydrogen chloride to give, after ion-exchange chromatography, the

Electrocarboxylation: towards sustainable and efficient synthesis of valuable carboxylic acids

• Roman Matthessen,
• Jan Fransaer,
• Koen Binnemans and
• Dirk E. De Vos

Beilstein J. Org. Chem. 2014, 10, 2484–2500, doi:10.3762/bjoc.10.260

• 8 and 9) [48][49]. Working under anhydrous conditions allows using another range of cathode materials, such as nickel, without being limited by the hydrogen overvoltage. The cathode metal has a large effect on the product distribution, acting as a catalyst [44][49]. Secondly, the absence of a

• increase the selectivity for the C6 product, dissolved nickel and iron redox mediators have been used [48][53][54]. The need for such organometallic complexes could be eliminated by direct electrocarboxylation on nickel or stainless steel cathode surfaces [49][50]. Substrates with an internal conjugated

• dicarboxylation can be achieved. Alkynes and olefins react according to similar pathways, although a separate mechanism has been proposed for selective monocarboxylation of alkynes using nickel mediators, usually with bipyridine or N,N,N′,N′,N′′-pentamethyldiethylenetriamine ligands [55][56][57][58][59][60

N–O Cleavage reactions of heterobicycloalkene-fused 2-isoxazolines

• Jaipal R. Nagireddy,
• Geoffrey K. Tranmer,
• Emily Carlson and
• William Tam

Beilstein J. Org. Chem. 2014, 10, 2200–2205, doi:10.3762/bjoc.10.227

• bond cleavage reactions of heterobicycloalkene-fused 3-methyl-2-isoxazolines were investigated. Optimal cleavage conditions were found with Raney nickel/AlCl3 mediation in aqueous methanol. The reaction provided a diverse collection of novel heterobicycle-fused β-hydroxyketones with good to excellent

• yields (66–95%) and without the need for chromatographic purification. Keywords: azabicycloalkene; β-hydroxyketone; 2-isoxazoline; oxabicycloalkene; Raney nickel; Introduction 2-Isoxazolines 1 are practical precursors to countless structural motifs found in nature. Various carbonyl compounds 2, β

• isoxazoline-cleavage methodology to the preparation of biologically active natural products, including novel antibacterial, antifungal and anticancer treatments [8][9][10][11]. Some common methods of reductive N–O bond cleavage in isoxazolines include hydrogenolysis using Raney nickel, reduction by LiAlH4

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