Coupling of α,α-difluoro-substituted organozinc reagents with 1-bromoalkynes

• Artem A. Zemtsov,
• Alexander D. Volodin,
• Vitalij V. Levin,
• Marina I. Struchkova and
• Alexander D. Dilman

Beilstein J. Org. Chem. 2015, 11, 2145–2149, doi:10.3762/bjoc.11.231

• (Table 1, entry 5). The addition of various ligands, as well as the use of other copper salts, did not had a beneficial effect. Under the optimized conditions, a series of organozinc compounds 2 were coupled with bromoalkynes 3 (Table 2). Good yields of coupling products 4 were typically achieved. The

Copper-mediated synthesis of N-alkenyl-α,β-unsaturated nitrones and their conversion to tri- and tetrasubstituted pyridines

• Dimitra Kontokosta,
• Daniel S. Mueller,
• Dong-Liang Mo,
• Wiktoria H. Pace,
• Rachel A. Simpson and
• Laura L. Anderson

Beilstein J. Org. Chem. 2015, 11, 2097–2104, doi:10.3762/bjoc.11.226

• observed and isolated. Decreasing the amount of copper reagent to 1 equiv had little influence on the reaction and a screen of other common copper salts only resulted in diminished yields (Table 1, entries 2–7). Further reduction of the copper loading to 10–30 mol % of Cu(OAc)2 was tolerated without a

Effective ascorbate-free and photolatent click reactions in water using a photoreducible copper(II)-ethylenediamine precatalyst

• Redouane Beniazza,
• Natalia Bayo,
• Florian Molton,
• Carole Duboc,
• Stéphane Massip,
• Nathan McClenaghan,
• Dominique Lastécouères and
• Jean-Marc Vincent

Beilstein J. Org. Chem. 2015, 11, 1950–1959, doi:10.3762/bjoc.11.211

• copper salts, which should be avoided for in vivo applications and, when employed, by sodium ascorbate and/or its byproducts; (iii) side-reactions on the substrates due to the generation of reduced dioxygen-active species and/or reactive oxidized byproducts of ascorbate. In a seminal paper, Finn and

The facile construction of the phthalazin-1(2H)-one scaffold via copper-mediated C–H(sp²)/C–H(sp) coupling under mild conditions

• Wei Zhu,
• Bao Wang,
• Shengbin Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2015, 11, 1624–1631, doi:10.3762/bjoc.11.177

• of copper salts and N,N’-dual coordinated directing groups [18][19][20][21][22]. By the employment of a similar approach, our group reported a straightforward route to the isoquinolinone scaffold via copper-mediated C–H(sp2)/C–H(sp3) coupling [23]. In light of previous works, we envisioned the

• temperature (120 °C) with excessive copper salts (3 equivalents). In addition, failure to remove the directing group partly prevented the practicality and application of the transformation [22]. Herein, we reveal a copper-mediated direct C–H(sp2)-C–H(sp) bond construction and simultaneous annulations under

• milder conditions with less equivalents of copper salts and oxygen atmosphere at a lower temperature (80 °C). Even more important, the resulting products could be smoothly transformed into preconceived 4-benzylphthalazin-1(2H)-one derivatives with the removal of the directing group by treatment with

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

• Marcus Baumann and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

• ]. Importantly in this study, a flow reactor consisting of copper tubing maintained at 110 °C (6.2 minutes residence time) was employed as this would release small amounts of copper salts catalysing the regioselective triazole formation. A cautionary note regarding the potential of generating copper azide within

Chemoselective O-acylation of hydroxyamino acids and amino alcohols under acidic reaction conditions: History, scope and applications

• Tor E. Kristensen

Beilstein J. Org. Chem. 2015, 11, 446–468, doi:10.3762/bjoc.11.51

• hydrolysates [5]. Conversion of amino acids to their copper salts elegantly masks both amino acid functionalities, thus protecting them during a subsequent alkaline acylation reaction that targets the side-chain functionality selectively. The side-chain-acylated lysine can then be liberated by decomposition of

Cross-dehydrogenative coupling for the intermolecular C–O bond formation

• Igor B. Krylov,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2015, 11, 92–146, doi:10.3762/bjoc.11.13

• works, the oxidative coupling of alcohols, aldehydes, or formamides with 1,3-dicarbonyl compounds or phenols was accomplished in the presence of tert-butyl hydroperoxide and copper salts (Table 5). In most cases, the range of phenols applicable to the coupling is limited to 2-acylphenols. However, 2

Sequential decarboxylative azide–alkyne cycloaddition and dehydrogenative coupling reactions: one-pot synthesis of polycyclic fused triazoles

• Kuppusamy Bharathimohan,
• Thanasekaran Ponpandian,
• A. Jafar Ahamed and
• Nattamai Bhuvanesh

Beilstein J. Org. Chem. 2014, 10, 3031–3037, doi:10.3762/bjoc.10.321

• ∙5H2O (Cu2+ used for decarboxylative CuAAC) at 120 °C for 12 h. It failed to undergo the oxidative dehydrogenative coupling reaction and the triazole derivative 3a was isolated in 79–82% yield (Table 1, entries 1–1b). A similar reaction sequence was performed with different copper salts such as CuCl2

Exploration of C–H and N–H-bond functionalization towards 1-(1,2-diarylindol-3-yl)tetrahydroisoquinolines

• Michael Ghobrial,
• Marko D. Mihovilovic and
• Michael Schnürch

Beilstein J. Org. Chem. 2014, 10, 2186–2199, doi:10.3762/bjoc.10.226

• -diarylindoles were successfully reacted with N-Boc-THIQ to furnish 1,2,3-trisubstituted indoles as target compounds. Furthermore, regioselective N-arylation of protected and unprotected 1-(indol-3-yl)-THIQs was successfully conducted using either simple iron or copper salts as catalysts. Keywords: Buchwald

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

• catalysis (Table 16) [244]. Besides copper(I) iodide several other copper salts effectuated the reaction albeit in lower yields as did silver(I) iodide, palladium(II) chloride and platinum(II) chloride. Other transition metal catalysts such as gold(I) chloride, nickel(II) chloride and cobalt(II) chloride

Polyglycerol-functionalized nanodiamond as a platform for gene delivery: Derivatization, characterization, and hybridization with DNA

• Li Zhao,
• Yuki Nakae,
• Hongmei Qin,
• Tadamasa Ito,
• Takahide Kimura,
• Hideto Kojima,
• Lawrence Chan and
• Naoki Komatsu

Beilstein J. Org. Chem. 2014, 10, 707–713, doi:10.3762/bjoc.10.64

• 96 h. Diluted ammonia was dropped into the suspension to dissolve insoluble copper salts, giving a blue-gray suspension. The solid was collected by centrifugation and washed with 1% ammonia repeatedly. The washed sample was dialyzed against Milli-Q water to thoroughly remove ammonia. The resulting ND

Cu-Mediated trifluoromethylation of benzyl, allyl and propargyl methanesulfonates with TMSCF₃

• Xueliang Jiang and
• Feng-Ling Qing

Beilstein J. Org. Chem. 2013, 9, 2862–2865, doi:10.3762/bjoc.9.322

• ) could further improve the product yield to 49% (Table 1, entries 3 and 4). Other copper salts such as CuBr, CuCl, CuTc and CuOAc, were next screened, but none of them was better than CuI (Table 1, entries 5–8). Interestingly, when the benzyl methanesulfonate reacted with [CuCF3] generated in situ from

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

• reactions in the arsenal of organic chemistry. However, the mechanistic understanding of this reaction has lagged behind the plethora of its applications for a long time. As reagent mixtures of copper salts and additives are commonly used in CuAAC reactions, the structure of the catalytically active species

• precursor. However, with copper(II) acetate hydrate (1 mol %), complete conversion was observed within one hour under identical conditions. The authors thus point out the beneficial effect of carboxylate compared to other copper salts. This effect can most probably be explained by the basic character of the

• Sharpless and Fokin devised a new protocol starting from 1-iodoalkynes [156]. The great advantage compared to the procedures of Wu [157], Hsung [158] and Li [159] is that neither reactive electrophilic halogenating agents (such as NBS or iodine monochloride) nor stoichiometric amounts of copper salts need

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

• readily available nucleophilic trifluoromethyl source after decarboxylation at high temperature in the presence of stoichiometric amounts of copper salts [78][79]. In 2011, Y. M. Li et al. showed that the Cu-catalyzed C–CF3 bond formation of iodoarenes could be achieved by using a sodium salt of

• benzoyl peroxide (Scheme 8). The copper salts are believed to speed up the process by superimposing a redox chain to the radical chain [90]. 3.2.4 Trifluoromethylation of Csp2–H bonds by means of a nucleophilic CF3-source. To the best of our knowledge, there is only one report in the literature by L. Chu

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

• lower toxicity, easier to process and environmentally friendly. Next the catalytic activity of the copper salts was screened. Most known reports concerning N-arylation focus on Cu(OAc)2 salt [21][22], complexes of Cu(II) with different ligands [23][36], and heterocyclic copper-based catalysts [25][37

• presented in this paper make this route more valuable. Conclusion In conclusion, we have developed an efficient and simple method for the cross coupling of arylboronic acids with C-nitro-NH-azoles in the presence of a catalytic amount of simple copper salts. The reaction takes place in a protic solvent

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

• strong bases. Han et al. have recently shown the ability of copper salts, in conjunction with oxygen, to catalyze oxidations of 2-substituted tetrahydroquinazoline aminals to quinazolines [35] (Figure 2). In addition, Reddy and co-workers have developed a catalytic system in which 2,3-substituted

• , entry 5). A number of different copper salts, solvents and acids were then evaluated, but none of the changes led to a further improvement in yield. It appears that under certain conditions catalyst deactivation via copper oxide formation decreased the catalyst turnover and consequently product yields

Exploration of an epoxidation–ring-opening strategy for the synthesis of lyconadin A and discovery of an unexpected Payne rearrangement

• Brad M. Loertscher,
• Yu Zhang and
• Steven L. Castle

Beilstein J. Org. Chem. 2013, 9, 1179–1184, doi:10.3762/bjoc.9.132

• [27]. Epoxide 17 was then subjected to ring-opening reactions with vinyl Grignard reagents in the presence of various copper salts. Surprisingly, only trace amounts of the desired product were detected, with recovered starting material and multiple byproducts typically comprising the majority of the

Synthesis of phenanthridines via palladium-catalyzed picolinamide-directed sequential C–H functionalization

• Ryan Pearson,
• Shuyu Zhang,
• Gang He,
• Nicola Edwards and
• Gong Chen

Beilstein J. Org. Chem. 2013, 9, 891–899, doi:10.3762/bjoc.9.102

• cyclization and oxidation steps can be performed in one step to give the phenanthridines in a shorter procedure. A variety of oxidants, such as 1,4-benzoquinone (BQ), KMnO4, ceric ammonium nitrate (CAN), and copper salts were examined [46]. The combination of PhI(OAc)2 (2 equiv) and Cu(OAc)2 (2 equiv

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

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

• %. Structurally comparable bisallene diols could be prepared, as shown by Krause and Poonoth [80][81], from bisoxiranes 100 by opening these with Grignard reagents in the presence of copper salts; this is again a double SN2'-process (Scheme 25). The resulting derivatives 101 are useful precursors for a double

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

• ; ligands; Introduction Copper-catalyzed heteroatom cross-coupling reactions (C–N, C–O and C–S) are important synthetic tools in modern organic synthesis [1][2][3][4][5][6]. Even though copper salts have been known to catalyze these transformations for a long period of time (i.e., the Ullmann [7] and

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

• –t and either copper or ruthenium-catalyzed [2 + 3] cycloadditions. The three reactions and the obtained products 11 (reaction 1), 12 (reaction 2) and 13 (reaction 3) are summarized in Table 2. Reaction 1 follows the established protocol and, gave after removal of the copper salts with a solution of

Recent advances in carbocupration of α-heterosubstituted alkynes

• Ahmad Basheer and
• Ilan Marek

Beilstein J. Org. Chem. 2010, 6, No. 77, doi:10.3762/bjoc.6.77

• CuBr was used instead of CuI, the yield was better although the regioselectivity of the reaction was slightly decreased (8a/8b = 93/7 in 82% yield). The best compromise was to use Et2Zn with a soluble copper salts such as CuBr•2 LiBr or CuCN•2LiBr (or LiCl). In both cases, the β-isomer 8a was obtained

Shelf-stable electrophilic trifluoromethylating reagents: A brief historical perspective

• Norio Shibata,
• Andrej Matsnev and
• Dominique Cahard

Beilstein J. Org. Chem. 2010, 6, No. 65, doi:10.3762/bjoc.6.65

• or copper salts no cyclization occurs [22]. A number of sulfonium salts were obtained, in particular 16 and 17, which were evaluated as trifluoromethylating agents for β-ketoesters and dicyanoalkylidenes. The cyclopropyl-substituted reagent 17 gave slightly better yields than the phenyl-substituted

New amphiphilic glycopolymers by click functionalization of random copolymers – application to the colloidal stabilisation of polymer nanoparticles and their interaction with concanavalin A lectin

• Otman Otman,
• Paul Boullanger,
• Eric Drockenmuller and
• Thierry Hamaide

Beilstein J. Org. Chem. 2010, 6, No. 58, doi:10.3762/bjoc.6.58

• copper salts with ethyl xanthogenate or cation exchange resin. Moreover, sodium ascorbate is far easier to remove in contrast to DIPEA or bipyridine and additionally, it would not be of any great consequence if some residual sodium ascorbate remained in the medium. The resulting grafted copolymers were

• ) containing 50 mg of potassium ethyl xanthogenate to remove the copper salts. After filtration through celite and evaporation to dryness, the desired mannose-functionalized copolymer was obtained as a pale yellow solid in 73% yield. 1H NMR (CD3OD, 500 MHz): δ (ppm) 8.06 (H-12), 5.8 (H-1), 5.10 (H-10), 4.6

Pd-catalyzed decarboxylative Heck vinylation of 2-nitrobenzoates in the presence of CuF₂

• Lukas J. Gooßen,
• Bettina Zimmermann and
• Thomas Knauber

Beilstein J. Org. Chem. 2010, 6, No. 43, doi:10.3762/bjoc.6.43

• step, may not hold true for electron-deficient benzoic acids. Instead, an additional decarboxylation catalyst is required to convert these substrates into the corresponding aryl metal species. Besides silver(I), we expected that copper salts should also mediate this step, as this metal has been used by