Cu(I)-catalyzed N,N’-diarylation of natural diamines and polyamines with aryl iodides

• Svetlana P. Panchenko,
• Alexei D. Averin,
• Maksim V. Anokhin,
• Olga A. Maloshitskaya and
• Irina P. Beletskaya

Beilstein J. Org. Chem. 2015, 11, 2297–2305, doi:10.3762/bjoc.11.250

• group of Beletskaya [24][25][26][27]. It has been shown that the secondary dialkylamino groups in linear polyamines are practically inert and this allows a selective arylation of terminal primary amino groups. The exchange of expensive palladium accompanied with toxic ligands for a much cheaper copper

• catalyst is one of the main trends in modern catalytic chemistry. However, in spite of numerous works dealing with Cu(I)-catalyzed arylation of monoamines, there are scarce examples of the synthesis of N-arylpolyamines using this method. Han and coworkers for example showed the possibility to synthesize N

Recent developments in copper-catalyzed radical alkylations of electron-rich π-systems

• Kirk W. Shimkin and
• Donald A. Watson

Beilstein J. Org. Chem. 2015, 11, 2278–2288, doi:10.3762/bjoc.11.248

• , Zhu and co-workers have discovered a selective trans-carbohalogenation of aryl alkynes [41]. A tridentate amine was used as a ligand for the copper catalyst. Using these conditions, highly valuable vinyl bromides were synthesized in excellent yields. Various functionalized tertiary alkyl bromides

• such as TEMPO. Radical clock experiments provided ring-opened products, suggesting the presence of intermediate radicals. We propose that this reaction proceeds via a thermal redox process. We hypothesize that the alkyl radical is formed by transfer of a bromine atom from the alkyl halide to the copper

• catalyst. The resultant stabilized alkyl radical then undergoes coupling with a nitronate anion, forging the C–C bond. Single electron transfer from the resultant radical anion to the Cu(II) halide results in the observed product while simultaneously reducing the metal center to regenerate the catalyst. In

Recent advances in copper-catalyzed C–H bond amidation

• Jie-Ping Wan and
• Yanfeng Jing

Beilstein J. Org. Chem. 2015, 11, 2209–2222, doi:10.3762/bjoc.11.240

• enantioenriched products of type 16 [45]. In a subsequent study, by modifying the conditions using [MeCN]4Cu(I)PF6 as copper catalyst and 1,3-indanedione as the ligand, the sulfonamidation of primary benzylic C(sp3)–H bonds in toluene were successfully performed at 23 °C in the presence of 3-CF3C6H4CO3t-Bu, which

• undertake the amidation to provide indolinone product 28''. An important factor enabling the C–H bond transformation was the presence of the quinoline auxiliary which acted as a bidentate fragment to incorporate the copper catalyst and facilitate the bond cleavage and formation via intermediates A and B

• (Scheme 8). Almost at the same time, Ge et al. [53] reported a similar intramolecular C–H amidation for the synthesis of lactams using CuCl as copper catalyst. When substrates possessing more than one γ-alkyl C–H bond were used, as the case occurred in Kuninobu and Kanai’s work, the primary C–H was

Molecular-oxygen-promoted Cu-catalyzed oxidative direct amidation of nonactivated carboxylic acids with azoles

• Wen Ding,
• Shaoyu Mai and
• Qiuling Song

Beilstein J. Org. Chem. 2015, 11, 2158–2165, doi:10.3762/bjoc.11.233

• amines suggested that transamidation could be efficiently accomplished in the absence of the copper catalyst, pyridine and the versatile amines, including aromatic (29, 31–34, 36 and 37) and aliphatic (35, 38–40), primary (29, 31, 34, 37 and 40) and secondary (32, 33, 35, 36, 38 and 39). Even the amino

• (Scheme 8b). Based on the above control experiments, we postulated a tentative mechanism (Scheme 9). The copper catalyst was postulated to play dual roles in the initial activation of benzoic acid: (1) it acts as a Lewis acid to activate benzoic acid (1), making it vulnerable to nucleophilic attack and (2

C–H bond halogenation catalyzed or mediated by copper: an overview

• Wenyan Hao and
• Yunyun Liu

Beilstein J. Org. Chem. 2015, 11, 2132–2144, doi:10.3762/bjoc.11.230

• , which allowed the synthesis of various 2-(o-haloaryl)pyridines with improved selectivity towards mono-halogenation in the presence of a copper catalyst [35]. As outlined in Scheme 4, the presence of molecular oxygen as the alternative oxidant enabled most entries providing monohalogenated products with

• -pyridyl)sulfonyl could be easily removed by treatment with elemental Mg in MeOH. More recently, Shi and co-workers [39] reported the ortho-C–H halogenation of aryl-2-carboxamides 10 using PIP (2-(pyridine-2-yl)isopropylamine) as DG. As shown in Scheme 7, the copper catalyst combined with NXS (X = Cl, Br

• copper-catalyst. Later on, Li and co-workers [54] developed an effective method of aerobic oxidative bromination of electron-rich arenes 35 by making use of 1 mol % Cu(NO3)2 as catalyst and 1.1 equiv HBr as additive. Brominated arenes 36 could be acquired with excellent conversions and para-bromination

Eosin Y-catalyzed visible-light-mediated aerobic oxidative cyclization of N,N-dimethylanilines with maleimides

• Zhongwei Liang,
• Song Xu,
• Wenyan Tian and
• Ronghua Zhang

Beilstein J. Org. Chem. 2015, 11, 425–430, doi:10.3762/bjoc.11.48

• derivatives under organic dye Eosin Y catalysis. Swan and Roy reported the reaction using benzoyl peroxide as catalyst at low temperature as early as 1968 [42]. In 2011, Miura and co-workers achieved this transformation using a copper catalyst and air as the terminal oxidant [43]. Bian and co-workers

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

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

• in presence and in absence of a copper catalyst. Interestingly, the byproduct 13 was formed in 83% conversion (GC–MS) without adding a catalyst to the reaction under neat conditions. Pathways to intermediate 8 for routes E and F The third potential substrates for formation of target structure 1 are

Photoswitchable precision glycooligomers and their lectin binding

• Daniela Ponader,
• Sinaida Igde,
• Marko Wehle,
• Katharina Märker,
• Mark Santer,
• David Bléger and
• Laura Hartmann

Beilstein J. Org. Chem. 2014, 10, 1603–1612, doi:10.3762/bjoc.10.166

• equiv of sugar azide, 20 mol % sodium ascorbate and 20 mol % CuSO4 per alkyne group were dissolved in DMF/H2O, added to the resin and shaken for 4 hours. Excess reagents as well as the copper catalyst were removed by washing with a 23 mM solution of sodium diethyl dithiocarbamate in DMF as well as water

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

• copper catalyst [56]. The product 14b was obtained in good yield with retention of configuration at the phosphorus center (Scheme 9). Other chiral phosphine boranes 13 were reacted similarly. This protocol is limited to the availability of these chiral substrates. Protocols for the enantioselective cross

• coupling of several vinyl bromides 75b and chlorides with 25d (Table 10). These reactions proceeded without the addition of zinc [167]. Copper: The group of Buchwald has reported one example of a copper catalyst to accomplish the phosphination of the vinyl halide 94 (Scheme 26) [168]. The protocol uses CuI

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

• structure of the putative dinuclear copper catalyst remains unknown [18] and is thus abbreviated by [L2nCu2]2+ (A; all charges and numbers of ligands have been consistently accounted for in a stoichiometric “book-keeping” fashion, but are not meaningful, as anionic ligands might also be present in the

• reaction mixture). Under various reaction conditions, it has been observed that the CuAAC reaction mixtures show a transient yellow colour upon addition of the copper catalyst (precursor) to the substrates’ solution. This colour has been attributed to the formation of polynuclear organocopper species [42

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

• bond cleavage of Togni's reagent in presence of the copper catalyst to produce a highly electrophilic species (intermediate A). Then, the acrylate derivative coordinates to the iodonium salt A leading to intermediate B with generation of hydrogen fluoride, followed by an intramolecular reaction between

• regenerates the copper catalyst, thus allowing the catalytic turnover (Figure 1). 2.2 Iron catalysis Similarly to the work of J. Hu and colleagues using copper catalysis, the group of Z.-Q. Liu reported on the decarboxylative difluoromethylation of α,β-unsaturated carboxylic acids. However, the latter used

• with regeneration of CuI. To perform the reaction catalytically, the use of a diamine ligand was necessary to enhance the electron density at the metal center, thus increasing the rate of σ-bond metathesis. In this way, the copper catalyst is regenerated faster and avoids in situ decomposition of the

Microwave-assisted synthesis of 5,6-dihydroindolo[1,2-a]quinoxaline derivatives through copper-catalyzed intramolecular N-arylation

• Fei Zhao,
• Lei Zhang,
• Hailong Liu,
• Shengbin Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2013, 9, 2463–2469, doi:10.3762/bjoc.9.285

• stoichiometric quantities of copper catalyst and low to moderate yields [20]. A recent breakthrough to overcome these drawbacks involves the use of appropriate ligands such as diamines and amino acids [21][22][23][24] that can enhance the activity of the copper catalysts and accelerate the reactions. As a result

Bromination of hydrocarbons with CBr₄, initiated by light-emitting diode irradiation

• Yuta Nishina,
• Bunsho Ohtani and
• Kotaro Kikushima

Beilstein J. Org. Chem. 2013, 9, 1663–1667, doi:10.3762/bjoc.9.190

• reported to give high reactivity and selectivity. The combination of CBr4 with a copper catalyst at high temperature also achieves effective bromination of hydrocarbons [27]. We have focused on CBr4, which is solid and easy to handle, as a bromine source. CBr4 has been used in organic synthesis to give

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

• research. The reaction does not take place without a base (Table 2, entry 2) or in the absence of copper catalyst (Table 2, entry 7). A parameter influencing chemical yields to a greater extent was the applied solvent/base system. Sodium hydroxide (pKa = 15.7) [41] and triethylamine (Et3N) (pKa = 10.9) [42

• -pyrazole (3a).a Influence of the solvent/base system on the yield of 3a.a The influence of copper catalyst on the yield of 3a.a Coupling of 1a with arylboronic acids 2a–n.a Cross coupling of C-nitro-NH-azoles 1a–e with 2a.a Supporting Information Supporting Information File 345: Experimental procedures

Enantioselective reduction of ketoimines promoted by easily available (S)-proline derivatives

• Martina Bonsignore,
• Maurizio Benaglia,
• Laura Raimondi,
• Manuel Orlandi and
• Giuseppe Celentano

Beilstein J. Org. Chem. 2013, 9, 633–640, doi:10.3762/bjoc.9.71

• ]. A simple combination of amino acid and copper catalyst provided an easily tunable system for synthesizing a range of propargylamines with high enantioselectivity. A key element of the elevate enantioselectivity was the hydrogen bonding between the chiral amino acid and the substrate, while high

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

• at sub-mol % levels of copper catalyst [23][45][77][78][88]. DMDETA proved to be at least as efficient as DMEDA and in addition has the ability to render the catalyst tolerant to air. The reaction order of copper (0.7) lacked the nonlinear behavior previously reported for DMEDA [78], indicating that

Copper-catalyzed CuAAC/intramolecular C–H arylation sequence: Synthesis of annulated 1,2,3-triazoles

• Rajkumar Jeyachandran,
• Harish Kumar Potukuchi and
• Lutz Ackermann

Beilstein J. Org. Chem. 2012, 8, 1771–1777, doi:10.3762/bjoc.8.202

• Rutjes [68] as well as Sharpless [69] elegantly devised alternative approaches exploiting 1-haloalkynes [70], we became interested in exploring a single [71][72][73] inexpensive copper catalyst for one-pot reaction sequences comprising a 1,3-dipolar cycloaddition along with an intramolecular C–H bond

• consisting of copper(I)-catalyzed [3 + 2]-azide–alkyne cycloadditions (CuAAC) and intramolecular C–H bond arylations. Notably, the optimized copper catalyst accelerated two mechanistically distinct transformations, which set the stage for the formation of up to one C–C and three C–N bonds in a chemo- and

Arylglycine-derivative synthesis via oxidative sp³ C–H functionalization of α-amino esters

• Zhanwei Xu,
• Xiaoqiang Yu,
• Xiujuan Feng and
• Ming Bao

Beilstein J. Org. Chem. 2012, 8, 1564–1568, doi:10.3762/bjoc.8.178

• copper catalyst could not improve the yield of 3a (Table 1, entries 3 and 4). The solvents were then screened (Table 1, entries 5–10). The best result was observed when CH2Cl2 was used as the solvent (79%, Table 1, entry 5). Therefore, the subsequent reactions of naphthols and phenols with ethyl 2

Synthesis of 2,6-disubstituted tetrahydroazulene derivatives

• Zakir Hussain,
• Henning Hopf,
• Khurshid Ayub and
• S. Holger Eichhorn

Beilstein J. Org. Chem. 2012, 8, 693–698, doi:10.3762/bjoc.8.77

• '-carbonyldiimidazole, tert-butyl alcohol and DBU to afford ester 3 in quantitative yield. The ester 3 was then subjected to carbene addition by treatment with ethyl diazoacetate in the presence of a copper catalyst [17] in THF under reflux. The carbene adduct 4 was obtained as the major product, as a colorless oil in

Thiophene-based donor–acceptor co-oligomers by copper-catalyzed 1,3-dipolar cycloaddition

• Stefanie Potratz,
• Amaresh Mishra and
• Peter Bäuerle

Beilstein J. Org. Chem. 2012, 8, 683–692, doi:10.3762/bjoc.8.76

• –donor type, in which thiophene moieties work as donor and 1,2,3-triazoles as acceptor units. In this respect, terminally ethynylated (oligo)thiophenes were coupled to halogenated (oligo)thiophenes in the presence of sodium azide and a copper catalyst. Optoelectronic properties of various thiophene-1,2,3

Nano copper oxide catalyzed synthesis of symmetrical diaryl sulfides under ligand free conditions

• K. Harsha Vardhan Reddy,
• V. Prakash Reddy,
• A. Ashwan Kumar,
• G. Kranthi and
• Y.V.D. Nageswar

Beilstein J. Org. Chem. 2011, 7, 886–891, doi:10.3762/bjoc.7.101

• -smelling thiols as the main drawback, which leads to environmental and safety problems. To overcome these problems, Zhou [43] and coworkers recently reported an efficient C–S bond formation by the reaction of potassium thiocyanate and aryl halides in the presence of a copper catalyst and a ligand in

Gold-catalyzed naphthalene functionalization

• Pedro J. Pérez,
• M. Mar Díaz-Requejo and
• Iván Rivilla

Beilstein J. Org. Chem. 2011, 7, 653–657, doi:10.3762/bjoc.7.77

• % with respect to the diazo compound). Similarly to the previous results, the fused norcaradiene 3a (Scheme 5) was exclusively and quantitatively formed using the copper catalyst 1a, whilst the use of 1b afforded a mixture of three products in a 60:20:20 ratio. The major product was identified as the 3a

Efficient 1,4-addition of α-substituted fluoro(phenylsulfonyl)methane derivatives to α,β-unsaturated compounds

• G. K. Surya Prakash,
• Xiaoming Zhao,
• Sujith Chacko,
• Fang Wang,
• Habiba Vaghoo and
• George A. Olah

Beilstein J. Org. Chem. 2008, 4, No. 17, doi:10.3762/bjoc.4.17

• enones can be used to introduce difluoromethylene moiety while Kumadaki and coworkers [21][22] have used bromodifluoroacetate with a copper catalyst to introduce the CF2 functionality. There also exist few reports on the 1,4-addition of monofluoromethylene moieties to α,β-unsaturated compounds [23][24