Phosphazene-catalyzed desymmetrization of cyclohexadienones by dithiane addition

• Matthew A. Horwitz,
• Elisabetta Massolo and
• Jeffrey S. Johnson

Beilstein J. Org. Chem. 2017, 13, 762–767, doi:10.3762/bjoc.13.75

• of the dithiane moiety via Raney nickel-promoted desulfurization (Scheme 5). To observe any substrate conversion, it was necessary to use a hydrogen atmosphere. Under those conditions, though the dithiane function was removed, degradation occurred. Conclusion In conclusion, we have developed a

• tethered nucleophile. Scope of the transformation. Convex facial additions. Attempted oxidative deacylation. Attempted desulfurization with Raney nickel. Carbonyl deprotection conditions. Supporting Information Supporting Information File 247: Experimental procedures, characterization data and copies of

The reductive decyanation reaction: an overview and recent developments

• Jean-Marc R. Mattalia

Beilstein J. Org. Chem. 2017, 13, 267–284, doi:10.3762/bjoc.13.30

• charge on the carbon adjacent to the cyano group [76][77]. Transition-metal-catalyzed reductive decyanation Hydrogenation of α-aminonitriles The decyanation of α-aminonitriles with hydrogen present in an excess of Raney nickel was described by Husson and co-workers on oxazolidine derivatives [83][84

Facile synthesis of a 3-deazaadenosine phosphoramidite for RNA solid-phase synthesis

• Elisabeth Mairhofer,
• Elisabeth Fuchs and
• Ronald Micura

Beilstein J. Org. Chem. 2016, 12, 2556–2562, doi:10.3762/bjoc.12.250

• . Only when treated with hydrazine, nucleophilic substitution was observed and after reduction with Raney nickel the desired 3-deazaadenosine was isolated. Our own attempts towards direct ammonolysis failed as well. Additionally, the limited commercial availability of hydrazine and its inconvenience in

• . c) Anhydrous hydrazine, steam bath, 1 h, not isolated. d) Raney nickel, water, reflux, 1 h. Synthesis of c3A described by Montgomery et al. in 1977 [23]. The final step, displacement of the 2-chlorine atom by a hydrogen atom, remains problematic [24][25][26]. a) 1,2,3,5-Tetraacetyl-ß-D-ribofuranose

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• :36.5 to 67.5:32.5 er). To demonstrate the utility of the transformation, the sulfur–carbon bond of 26a was reduced using Raney nickel to access (S)-naproxen (27), an anti-inflammatory drug (Scheme 6b). Inspired by the work of Pracejus, Tan and colleagues applied their C2-symmetric guanidine catalyst 30

From steroids to aqueous supramolecular chemistry: an autobiographical career review

• Bruce C. Gibb

Beilstein J. Org. Chem. 2016, 12, 684–701, doi:10.3762/bjoc.12.69

• first step, the unoptimized desulfurization of 2-thio-6-methyluracil using Raney-Nickel to form 6-methyl-4-hydroxypyrimidine (Scheme 2). It turned out I was a wiz at this organic synthesis lark (as Derek liked to say). I took the yield from 73% to quantitative by doing what organic chemists do, changing

Total synthesis of panicein A₂

• Lili Yeung,
• Lisa I. Pilkington,
• Melissa M. Cadelis,
• Brent R. Copp and
• David Barker

Beilstein J. Org. Chem. 2015, 11, 1991–1996, doi:10.3762/bjoc.11.215

• . to provide ketone 12 in 66% yield [8]. The selective reduction of the olefin in α,β-unsaturated ketone 12 was then attempted using the Raney nickel catalyst under hydrogen as previously reported [8]; unfortunately no product 13 was formed. Following this, a range of conditions were employed to reduce

Synthesis and structures of ruthenium–NHC complexes and their catalysis in hydrogen transfer reaction

• Chao Chen,
• Chunxin Lu,
• Qing Zheng,
• Shengliang Ni,
• Min Zhang and
• Wanzhi Chen

Beilstein J. Org. Chem. 2015, 11, 1786–1795, doi:10.3762/bjoc.11.194

• expressed in Hz. Elemental analyses were performed by a Flash EA 1112 ThermoFinnigan analyzer. Synthesis of [Ru(L1)2(CH3CN)2](PF6)2 (1). A mixture of HL1(PF6) (306 mg, 1.0 mmol), excess Raney nickel (500 mg) in 10 mL MeCN was stirred at 80 °C for 24 h. After it was cooled to room temperature, the solution

• , C4H3N2, 2H), 4.17 (s, CH3, 3H), 2.41 (s, CH3CN, 6H); 13C NMR (100 MHz, DMSO-d6) δ 193.1 (Ru-C), 166.2, 159.8, 158.7, 128.6, 127.0, 120.0, 117.9, 37.7, 4.17. Synthesis of [RuL1(CH3CN)4](PF6)2 (2). A mixture of HL1(PF6) (153 mg, 0.5 mmol), excess Raney nickel (300 mg) in 10 mL MeCN was stirred at 80 °C for

• (1), [RuL1(CH3CN)4](PF6)2 (2) and [RuL2(CH3CN)3](PF6)2 (3) The ruthenium–NHC complexes 1 and 2 were synthesized by using the corresponding nickel–NHC complexes as the carbene transfer agent [36]. The reaction of imidazolium salt HL1(PF6) (L1 = 3-methyl-1-(pyrimidine-2-yl)imidazolylidene) with Raney

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

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

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

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

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

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

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

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

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

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

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

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