Recent applications of the divinylcyclopropane–cycloheptadiene rearrangement in organic synthesis

• Sebastian Krüger and
• Tanja Gaich

Beilstein J. Org. Chem. 2014, 10, 163–193, doi:10.3762/bjoc.10.14

• epoxides (see 304) were shown to undergo trans-cis isomerization followed by divinylepoxide rearrangement to give dihydrooxepine 305 at 125 °C. The necessary reaction temperature could be lowered using copper(II) catalysis, accelerating the reaction rate as well. The vinylepoxide–carbaldehyde rearrangement

Advancements in the mechanistic understanding of the copper-catalyzed azide–alkyne cycloaddition

• Regina Berg and
• Bernd F. Straub

Beilstein J. Org. Chem. 2013, 9, 2715–2750, doi:10.3762/bjoc.9.308

• solution-phase conditions (Scheme 2) [12]. In their standard procedure, the cost-efficient salt copper(II) sulfate pentahydrate is reduced in situ by ascorbic acid or sodium ascorbate in a solvent mixture of water and alcohol (“Sharpless–Fokin conditions”). Alternatively, copper(I) salts such as copper(I

• ][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42] and will not be subject of this article. Common reagents for CuAAC catalysis Common CuAAC precatalyst mixtures contain elemental copper, copper(II) salts or copper(I) species. In all cases, however, the catalytically active species contains

• ) than with the standard catalyst systems, i.e. copper(II) salts plus reducing agent or copper(I) salts [14]. This method can be significantly sped up by applying microwave radiation [43]. It is also beneficial to add copper(II) sulfate, but this is usually not mandatory as the patina on the copper

Copper-catalyzed trifluoromethylation of alkenes with an electrophilic trifluoromethylating reagent

• Xiao-Ping Wang,
• Jin-Hong Lin,
• Cheng-Pan Zhang,
• Ji-Chang Xiao and
• Xing Zheng

Beilstein J. Org. Chem. 2013, 9, 2635–2640, doi:10.3762/bjoc.9.299

• , the activation of III by Cu(I) led to the formation of radical intermediate A. Decomposition of this intermediate produces ((2-(2-iodophenyl)propan-2-yl)oxy)copper(II) (C) and a CF3 radical, which is trapped by alkenes to form the trifluoromethylated radical intermediate B. Subsequently, the radical

Ambient gold-catalyzed O-vinylation of cyclic 1,3-diketone: A vinyl ether synthesis

• Yumeng Xi,
• Boliang Dong and
• Xiaodong Shi

Beilstein J. Org. Chem. 2013, 9, 2537–2543, doi:10.3762/bjoc.9.288

• undesired hydration. This discovery will likely benefit many future developments that currently suffer from the common hydration side reaction. The application of copper(II) triflate as the effective additive not only improves the reactivity, but also provides another example for plausible bimetallic

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

• coworkers reported on the first Pd-catalyzed trifluoromethylation at C–H positions in aromatic compounds (Table 5) [67]. Pd(OAc)2 (10 mol %) was used as the catalyst, and Umemoto’s sulfonium tetrafluoroborate salt as the CF3 source rather than its triflate analogue. Trifluoroacetic acid and copper(II

• copper(II) acetates as catalyst and additive respectively, with Umemoto’s reagent [69]. Pivalic acid (vs TFA in the case of J.-Q. Yu et al.) as an additive gave the best results. Diversely functionalized substrates were converted to the corresponding benzotrifluorides with up to 83% yield (Table 7

• trifluoromethylation; indeed, all of them used the same electrophilic CF3 source, namely Togni’s benziodoxolone reagent. M. Sodeoka and coworkers reported on the trifluoromethylation of indoles with Togni’s hypervalent iodine reagent in the presence of catalytic copper(II) acetate [82]. No additives were necessary

Synthesis of enantiopure sugar-decorated six-armed triptycene derivatives

• Paola Bonaccorsi,
• Maria Luisa Di Gioia,
• Antonella Leggio,
• Lucio Minuti,
• Teresa Papalia,
• Carlo Siciliano,
• Andrea Temperini and
• Anna Barattucci

Beilstein J. Org. Chem. 2013, 9, 2410–2416, doi:10.3762/bjoc.9.278

• ), 125.3 (C-1,4,5,8,13,16), 52.9 (C-9,10), 52.1 (CH2); Anal. calcd for C26H20N18, C, 53.42; H, 3.45; found; C, 53.09; H, 3.58. General procedure for the azide–alkyne cycloaddition. Azide 3 (0.10 g, 0.17 mmol), the 2-propyn-1-yl β-D-glycopyranoside (0.84 mmol), copper(II) acetate (15 mg, 0.08 mmol) and

The chemistry of isoindole natural products

• Klaus Speck and
• Thomas Magauer

Beilstein J. Org. Chem. 2013, 9, 2048–2078, doi:10.3762/bjoc.9.243

• copper(II) triflate-catalyzed Ullmann coupling furnished 136. Meroterpenoids: The term meroterpenoids describes a family of natural products with a mixed biosynthetic origin, partially derived from terpenoids and polyketides [129]. Several members of this class containing an isoindolinone motif, for

Coupling of C-nitro-NH-azoles with arylboronic acids. A route to N-aryl-C-nitroazoles

• Marta K. Kurpet,
• Aleksandra Dąbrowska,
• Małgorzata M. Jarosz,
• Katarzyna Kajewska-Kania,
• Nikodem Kuźnik and
• Jerzy W. Suwiński

Beilstein J. Org. Chem. 2013, 9, 1517–1525, doi:10.3762/bjoc.9.173

• ]. It involves several steps: transmetallation of boronic acid with a catalyst, coordination of the azole molecule to the Cu(II) species followed by oxidation of copper(II) into copper(III) in the presence of oxygen, and then reductive elimination releasing the product and Cu(I) complex. A regeneration

• ]. Basically, easily available simple copper(I) and copper(II) compounds, mostly salts, were investigated. The yields obtained for Cu(I) salts (Table 4, entries 1–3) were slightly lower than those achieved for Cu(II) salts (Table 4, entries 5–8). However, the differences are small, and it can be assumed that

Copper(II)-salt-promoted oxidative ring-opening reactions of bicyclic cyclopropanol derivatives via radical pathways

• Eietsu Hasegawa,
• Minami Tateyama,
• Ryosuke Nagumo,
• Eiji Tayama and
• Hajime Iwamoto

Beilstein J. Org. Chem. 2013, 9, 1397–1406, doi:10.3762/bjoc.9.156

• Eietsu Hasegawa Minami Tateyama Ryosuke Nagumo Eiji Tayama Hajime Iwamoto Department of Chemistry, Faculty of Science, Niigata University, Ikarashi-2 8050, Niigata 950-2181, Japan 10.3762/bjoc.9.156 Abstract Copper(II)-salt-promoted oxidative ring-opening reactions of bicyclic cyclopropanol

• derivatives were investigated. The regioselectivities of these processes were found to be influenced by the structure of cyclopropanols as well as the counter anion of the copper(II) salts. A mechanism involving rearrangement reactions of radical intermediates and their competitive trapping by copper ions is

• proposed. Keywords: copper(II) salt; cyclopropanol; electron transfer; free radical; radical ion probe; Introduction Radical ions are key intermediates in electron-transfer (ET) reactions of organic molecules [1][2][3][4][5] and they often undergo fragmentations to yield free radicals and ions [6][7][8

Selective copper(II) acetate and potassium iodide catalyzed oxidation of aminals to dihydroquinazoline and quinazolinone alkaloids

• Matthew T. Richers,
• Chenfei Zhao and
• Daniel Seidel

Beilstein J. Org. Chem. 2013, 9, 1194–1201, doi:10.3762/bjoc.9.135

• Matthew T. Richers Chenfei Zhao Daniel Seidel Department of Chemistry and Chemical Biology, Rutgers, The State University of New Jersey, Piscataway, New Jersey 08854, USA 10.3762/bjoc.9.135 Abstract Copper(II) acetate/acetic acid/O2 and potassium iodide/tert-butylhydroperoxide systems are shown

• were also explored. The use of Cu(OAc)2 and methanol, while appropriate for furnishing deoxyvasicine (2) from aminal 7, did not result in satisfactory yields of deoxyvasicinone (4, Table 1). Attempts to use other copper(I) or copper(II) salts and solvents under oxygen without the addition of acid to

• acetic acid in addition to oxygen and catalytic copper(II) salts was determined to prevent overoxidation of dihydroquinazolines, allowing access to these structures under mild conditions. A number of natural products and their analogues were obtainable by these methods, which should facilitate the

Methylidynetrisphosphonates: Promising C₁ building block for the design of phosphate mimetics

• Vadim D. Romanenko and
• Valery P. Kukhar

Beilstein J. Org. Chem. 2013, 9, 991–1001, doi:10.3762/bjoc.9.114

• diazomethylenebisphosphonate and diethyl phosphite in the presence of copper(II) bis(acetylacetonate) provides trisphosphonate ester 6 (Scheme 13). The yield is poor (20%) but the product can be isolated in the pure state and the method is presumably general (cf. [37]). The starting tetraalkyl diazomethylenebisphosphonates

Superstructures of fluorescent cyclodextrin via click-reaction

• Arkadius Maciollek,
• Helmut Ritter and
• Rainer Beckert

Beilstein J. Org. Chem. 2013, 9, 827–831, doi:10.3762/bjoc.9.94

• µmol) sodium ascorbate and 18 mg (73.5 µmol) copper(II) sulfate pentahydrate were suspended in 5 mL dimethylformamide in a pressure-resistant microwave test tube provided with a magnetic stirring bar. The tube was sealed and placed in the microwave and irradiated at 140 °C and 100 W for 30 min. The

Intramolecular carbolithiation of N-allyl-ynamides: an efficient entry to 1,4-dihydropyridines and pyridines – application to a formal synthesis of sarizotan

• Wafa Gati,
• Mohamed M. Rammah,
• Mohamed B. Rammah and
• Gwilherm Evano

Beilstein J. Org. Chem. 2012, 8, 2214–2222, doi:10.3762/bjoc.8.250

• nucleophiles. By using a slightly modified Hsung’s procedure, a series of N-allyl-ynamides 1 could be readily prepared in acceptable yields using a combination of copper(II) sulfate pentahydrate (40 mol %) and 1,10-phenanthroline (80 mol %) with potassium phosphate in refluxing toluene, the major side reaction

Palladium-catalyzed dual C–H or N–H functionalization of unfunctionalized indole derivatives with alkenes and arenes

• Gianluigi Broggini,
• Egle M. Beccalli,
• Andrea Fasana and
• Silvia Gazzola

Beilstein J. Org. Chem. 2012, 8, 1730–1746, doi:10.3762/bjoc.8.198

• cyclization of alkenylindoles by Pd(II) catalysis under carbonylative conditions [81][82]. This approach, based on the use of copper(II) chloride as oxidant, has been applied to 2- and 3-alkenylindoles, resulting in a domino process that involves an alkenylation/carboxylation sequence (Scheme 23). Thus

• requires an oxidation by the copper(II) salt to the Pd(II) species, which is then suitable to restart a new catalytic cycle. Recently, the oxidative Pd(II)-catalyzed strategy for the cyclization of alkenylindoles has been extended to the intramolecular domino reactions of indolylallylamides by using the

Parallel solid-phase synthesis of diaryltriazoles

• Matthias Wrobel,
• Jeffrey Aubé and
• Burkhard König

Beilstein J. Org. Chem. 2012, 8, 1027–1036, doi:10.3762/bjoc.8.115

• example of a more complex alkyne. The azide–alkyne [3 + 2] cycloaddition was catalyzed with copper(II) sulfate pentahydrate and L-ascorbic acid in DMF overnight at room temperature. A solution of EDTA was added to remove the remaining copper cations from the resin. Resin cleavage under acidic conditions

• L-ascorbic acid (0.5 equiv) as reducing agent and copper(II) sulfate pentahydrate (10 mol %). After the terminal alkyne (4 equiv) was added, the reaction mixture was stirred for 22 h at room temperature. The resin was washed with dimethylformamide, methanol and dichloromethane (each solvent 2 mL/100

Regioselective chlorination and bromination of unprotected anilines under mild conditions using copper halides in ionic liquids

• Han Wang,
• Kun Wen,
• Nurbiya Nurahmat,
• Yan Shao,
• He Zhang,
• Chao Wei,
• Ya Li,
• Yongjia Shen and
• Zhihua Sun

Beilstein J. Org. Chem. 2012, 8, 744–748, doi:10.3762/bjoc.8.84

• reported several decades ago with chloride salts of several transition metals [5]. Copper(II) chloride (1) was found to be one of the best reagents for this transformation, which yielded mostly the para-chlorinated product with minor ortho- and dichlorinated products. The mechanism was believed to be

Facile synthesis of nitrophenyl 2-acetamido-2-deoxy-α-D-mannopyranosides from ManNAc-oxazoline

• Karel Křenek,
• Petr Šimon,
• Lenka Weignerová,
• Barbora Fliedrová,
• Marek Kuzma and
• Vladimír Křen

Beilstein J. Org. Chem. 2012, 8, 428–432, doi:10.3762/bjoc.8.48

• ] affording oxazoline 3 in 75% yield. The glycosylation of phenol and p-nitrophenol with oxazoline 3 was extensively tested. We tested a large array of reaction conditions, including variation of catalyst (copper(II) chloride [12][15], 2,2-diphenyl-1-picrylhydrazyl, zinc chloride, tin(IV) chloride) and

A ferrocene redox-active triazolium macrocycle that binds and senses chloride

• Nicholas G. White and
• Paul D. Beer

Beilstein J. Org. Chem. 2012, 8, 246–252, doi:10.3762/bjoc.8.25

• , C≡CH), 1.87 (m, 4H, trz-CH2-CH2); 13C NMR (CDCl3) δ 147.3, 120.6, 83.9, 82.7, 69.9, 69.6, 69.0, 49.5, 28.1, 24.6, 18.0; HRMS–ESI (m/z): [M + Na]+ calcd for C26H28N6Fe·Na, 503.1617; found, 503.1614. Bis(triazole) macrocycle 3 The bis(alkyne) 2 (0.120 g, 0.250 mmol) and copper(II) acetate monohydrate

Highly efficient cyclosarin degradation mediated by a β-cyclodextrin derivative containing an oxime-derived substituent

• Michael Zengerle,
• Florian Brandhuber,
• Christian Schneider,
• Franz Worek,
• Georg Reiter and
• Stefan Kubik

Beilstein J. Org. Chem. 2011, 7, 1543–1554, doi:10.3762/bjoc.7.182

• ][41]. The alkyne 6 required for the synthesis of 2a was obtained from propargyl bromide and 3-formylpyridine oxime (Scheme 6), and those for 2b, 2c, and 2d, following the routes shown in Scheme 7. Reaction of these alkynes with 4 in the presence of copper(II) sulfate, sodium ascorbate and tris[(1

Synthesis and oxidation of some azole-containing thioethers

• Andrei S. Potapov,
• Nina P. Chernova,
• Vladimir D. Ogorodnikov,
• Tatiana V. Petrenko and
• Andrei I. Khlebnikov

Beilstein J. Org. Chem. 2011, 7, 1526–1532, doi:10.3762/bjoc.7.179

• dismutase-like activity of copper(II) complexes with bis(pyrazole) ligands [5][6]. Copper(II) complexes with azole-derived thioether ligands were proposed as models for type I copper proteins [7]. The sulfur atom in a thioether spacer gives an additional possibility for modification of the ligand structure

Development of the titanium–TADDOLate-catalyzed asymmetric fluorination of β-ketoesters

• Lukas Hintermann,
• Mauro Perseghini and
• Antonio Togni

Beilstein J. Org. Chem. 2011, 7, 1421–1435, doi:10.3762/bjoc.7.166

• malonic esters with elemental fluorine in the presence of hydrated copper(II) nitrate at the 10 mol % level [73]. Still, the generality and synthetic potential of Lewis acid catalyzed α-halogenations of carbonyl compounds were not established. Reactivity screening: Fluorination of β-ketoesters in the

Amines as key building blocks in Pd-assisted multicomponent processes

• Didier Bouyssi,
• Nuno Monteiro and
• Geneviève Balme

Beilstein J. Org. Chem. 2011, 7, 1387–1406, doi:10.3762/bjoc.7.163

• added to the reaction medium with concomitant addition of 10 mol % of Cu(OTf)2 necessary to complete the cyclization step. The proposed mechanism involves formation of an imine intermediate, which attacks the triple bond activated by the copper(II) complex. The resulting iminium was finally trapped by

Ugi post-condensation copper-triggered oxidative cascade towards pyrazoles

• Aurélie Dos Santos,
• Laurent El Kaim,
• Laurence Grimaud and
• Caroline Ronsseray

Beilstein J. Org. Chem. 2011, 7, 1310–1314, doi:10.3762/bjoc.7.153

• Pyrazolidinones were prepared in a two-step sequence starting from α-hydrazonocarboxylic acids. After a four-component Ugi coupling, the resulting hydrazone was engaged in a copper triggered [3 + 2] cycloaddition/aerobic oxidation cascade. Keywords: aerobic oxidation; copper(II); [3 + 2] cycloaddition; hydrazone

• , cyclocondensations and organometalic couplings, there was no existing description of radical processes on such adducts. Thus, we decided to undertake various studies using xanthate transfer [8][9][10], Mn(III) or copper(II) triggered oxidative couplings [11][12]. We recently reported a new synthesis of fused

• triggered either by copper acetate or acetic acid [24][25][26][27][28][29]. The resulting pyrazoline A may be oxidized by copper(II) salts forming intermediate D after addition of water [30][31]. Two alternative paths may then be observed from D: Ring-opening leading to azo or hydrazono derivatives such as

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

• ]. For this reaction 2-amino-5-methylpyridine (228) was condensed with an aldehyde to form an intermediate imine to which is added a terminal alkyne in the presence of copper(I) chloride. A copper(II) triflate catalyst is then used to promote a Lewis acid promoted 5-exo-dig heteroannulation to furnish

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

• Buchwald [6][7] and Hartwig [8][9] has been a major breakthrough in this field. More recently, Chan [10] and Lam [11][12] introduced the copper-mediated arylation of N-nucleophiles using stoichiometric copper(II) acetate and boronic acids. Collman improved the procedure using catalytic amounts of [Cu(OH

• , was achieved by reacting 9-N-purines 91 with an excess of arylboronic acid 92 in the presence of copper(II) acetate, molecular sieves and phenanthroline (Scheme 22). Bakkestuen and Gundersen showed that electron-donating and electron-withdrawing substituents on the arylboronic acid were tolerated