Bi- and trinuclear copper(I) complexes of 1,2,3-triazole-tethered NHC ligands: synthesis, structure, and catalytic properties

• Shaojin Gu,
• Jiehao Du,
• Jingjing Huang,
• Huan Xia,
• Ling Yang,
• Weilin Xu and
• Chunxin Lu

Beilstein J. Org. Chem. 2016, 12, 863–873, doi:10.3762/bjoc.12.85

• imidazolium backbone and N substituents. The copper–NHC complexes tested are highly active for the Cu-catalyzed azide–alkyne cycloaddition (CuAAC) reaction in an air atmosphere at room temperature in a CH3CN solution. Complex 4 is the most efficient catalyst among these polynuclear complexes in an air

• Inspired by the catalytic activity of Cu(I) species supported by NHC ligand in Cu-catalyzed azide–alkyne cycloaddition (CuAAC) reaction under mild conditions, copper complexes 2–6 were investigated in the CuAAC reaction of azide and phenylacetylene. Firstly, we compared the catalytic activity of different

Copper-mediated arylation with arylboronic acids: Facile and modular synthesis of triarylmethanes

• H. Surya Prakash Rao and
• A. Veera Bhadra Rao

Beilstein J. Org. Chem. 2016, 12, 496–504, doi:10.3762/bjoc.12.49

• triphenylmethane (11a). A plausible mechanism for the formation of triarylmethanes 11. Copper-catalyzed C–C bond formation synthesis of triarylmethane 10l. Synthesis of anti-breast-cancer agent intermediate 22. Screening of metal catalysts for the arylation reaction. Scope of the Cu-catalyzed arylation with

Enabling technologies and green processes in cyclodextrin chemistry

• Giancarlo Cravotto,
• Marina Caporaso,
• Laszlo Jicsinszky and
• Katia Martina

Beilstein J. Org. Chem. 2016, 12, 278–294, doi:10.3762/bjoc.12.30

• strongly disrupt bacterial membranes, and a series of persubstituted γ-CD derivatives bearing polyamino groups (77% yield) [55]. MW-promoted Cu-catalyzed click reaction for the preparation of second generation CD derivatives and hybrid structures The MW-promoted CuAAC between CD monoazides and acetylenic

Base metal-catalyzed benzylic oxidation of (aryl)(heteroaryl)methanes with molecular oxygen

• Hans Sterckx,
• Johan De Houwer,
• Carl Mensch,
• Wouter Herrebout,
• Kourosch Abbaspour Tehrani and
• Bert U. W. Maes

Beilstein J. Org. Chem. 2016, 12, 144–153, doi:10.3762/bjoc.12.16

• anilines resulting in the formation of 2-aryl-α-ketoacetamides was reported by Jiao [22] and a closely related intramolecular variant leading to isatins has been published by Ilangovan [23]. A remarkable Cu-catalyzed chemoselective oxidative C–C bond cleavage of methyl ketones was reported by the group of

• , entries 4 and 5). This interesting selectivity was further expanded on 6-(4-methylbenzyl)-2-methylpyrazine (18a). Pyrazine 18a features three possible positions for methylene oxidation: a benzyl, benzhydryl and a 1,4-diazinylmethyl moiety. When 18a was submitted to the Cu-catalyzed reaction conditions at

Carbon–carbon bond cleavage for Cu-mediated aromatic trifluoromethylations and pentafluoroethylations

• Tsuyuka Sugiishi,
• Hideki Amii,
• Kohsuke Aikawa and
• Koichi Mikami

Beilstein J. Org. Chem. 2015, 11, 2661–2670, doi:10.3762/bjoc.11.286

• Cu-catalyzed aromatic trifluoromethylation. The yield was determined by 19F NMR analysis using (trifluoromethoxy)benzene as an internal standard. Plausible mechanism of Cu-catalyzed aromatic trifluoromethylation [53]. Acknowledgements The financial support of the Ministry of Education, Culture

Recent advances in copper-catalyzed asymmetric coupling reactions

• Fengtao Zhou and
• Qian Cai

Beilstein J. Org. Chem. 2015, 11, 2600–2615, doi:10.3762/bjoc.11.280

• additives such as 4-(N,N-dimethylamino)pyridine caused an unexpected inversion of enantioselectivity in the Cu-catalyzed asymmetric desymmetrization of α,α-bis(2-iodobenzyl)glycines when (2S,3aS,7aS)-octahydro-1H­indole-2-carboxylic acid was used as chiral ligand [47] (Scheme 18). In 2015, Cai et al

• [59] and Diéguez [60]. In this review, we focus on the developments since 2008. Cu-catalyzed enantioselective allylic substitutions with aryl-, alkenyl-, and allenylboronates, alkylboron compounds Organoboron compounds have found extensive application in coupling reactions for the construction of C–C

• primary allyl chlorides to react with alkylborane (alkyl-9-BBN) for the generation of a quaternary carbon stereogenic center bearing three sp3-alkyl groups and a vinyl group with an ee up to 90% (Scheme 29). Cu-catalyzed enantioselective allylic substitutions with Grignard reagents Transition metal

Copper-catalysed asymmetric allylic alkylation of alkylzirconocenes to racemic 3,6-dihydro-2H-pyrans

• Emeline Rideau and
• Stephen P. Fletcher

Beilstein J. Org. Chem. 2015, 11, 2435–2443, doi:10.3762/bjoc.11.264

• same enantioselectivity and poor yield, yet have significantly different pathways. Conclusion The Cu-catalyzed AAA of alkylzirconium reagents to racemic heterocyclic electrophiles was explored. After extensive examination, two different methods for obtaining 3,6-dihydro-2H-pyran derivatives with

Copper-catalyzed asymmetric conjugate addition of organometallic reagents to extended Michael acceptors

• Thibault E. Schmid,
• Sammy Drissi-Amraoui,
• Christophe Crévisy,
• Olivier Baslé and
• Marc Mauduit

Beilstein J. Org. Chem. 2015, 11, 2418–2434, doi:10.3762/bjoc.11.263

• performance in terms of enantioselectivity, and was used in combination with Cu(OTf)2 in the 1,6-ACA of cyclic dienones of the type 30 (Scheme 6). NHC ligands also enabled a total regioselectivity and ees ranging from 58 to 91%. Given the efficiency of (R)-Binap L4 in Cu-catalyzed 1,4-ACA on α,β-unsaturated

• selectively afforded the 1,6-adduct 21 in 53% yield and 68% ee (Scheme 10). Displaying a similar reactivity, bicyclic Michael acceptor 40 led to compound 41 in 45% yield and 69% ee. In 2010, the Alexakis group explored the reactivity of α,β,γ,δ-unsaturated nitroolefins and nitroenynes in Cu-catalyzed ACA

• studied the reactivity of various β,γ-unsaturated α-ketoesters, which remain to date the only report dealing with such substrates in Cu-catalyzed ACA of trialkylaluminium [41]. Using the (R)-Binap-based system L4/CuTC, an excellent 1,4-selectivity was achieved with mono-unsaturated substrates. Dienic

Copper-catalyzed arylation of alkyl halides with arylaluminum reagents

• Bijay Shrestha and
• Ramesh Giri

Beilstein J. Org. Chem. 2015, 11, 2400–2407, doi:10.3762/bjoc.11.261

• Bijay Shrestha Ramesh Giri Department of Chemistry & Chemical Biology, The University of New Mexico, Albuquerque, NM 87131, USA 10.3762/bjoc.11.261 Abstract We report a Cu-catalyzed coupling between triarylaluminum reagents and alkyl halides to form arylalkanes. The reaction proceeds in the

• organoaluminum reagents could participate as nucleophile sources in Cu-catalyzed cross-coupling reactions. In this artcle, we show that triarylaluminum reagents are excellent coupling partners for Cu-catalyzed cross-coupling reactions. The reaction proceeds for the coupling with primary alkyl iodides and

• bromides (Table 2, entries 12 and 14) [43]. Based on literature reports and our recent mechanistic work on Cu-catalyzed cross-couplings [23][24][25], we propose a catalytic cycle for the current reaction (Scheme 2). It is evident from the optimization of reaction conditions that both NN-1 and LiCl improve

A concise and efficient synthesis of benzimidazo[1,2-c]quinazolines through CuI-catalyzed intramolecular N-arylations

• Xinlong Pang,
• Chao Chen,
• Ming Li and
• Chanjuan Xi

Beilstein J. Org. Chem. 2015, 11, 2365–2369, doi:10.3762/bjoc.11.258

• (sp3) in 3a reacted through the Cu-catalyzed Ullmann reaction [18][19][20][21][22][23][24][25]. Inspired by the successful cyclization of quinazolin-4(3H)-imine 3a, further imines were prepared and subjected to the cyclization conditions. Notably, in this protocol, after work-up, the desired bromo

• drawing of 5, [C20H16F2N4O]·2Cl·H2O with 35% probability ellipsoids, showing the atomic numbering scheme. CuI-catalyzed synthesis of benzimidazo[1,2-c]quinazolines 4 by intramolecular N-arylation of bromo-substituted quinazolin-4(3H)-imine derivatives 3. Cu-catalyzed reaction of o-cyanoaniline (1a

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

• for lactam synthesis. Copper-catalyzed amidation/sulfonamidation of aryl C–H bonds. C–H amidation of pyridinylbenzenes and indoles. Mechanism of the Cu-catalyzed C2-amidation of indoles. Copper-catalyzed, 2-phenyl oxazole-assisted C–H amidation of benzamides. DG-assisted amidation/imidation of indole

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

• scope. The mechanistic studies reveal that oxygen plays an essential role in the success of the amidation reactions with copper peroxycarboxylate as the key intermediate. Transamidation occurs smoothly between azole amide and a variety of amines. Keywords: amidation; azoles; Cu-catalyzed; molecular

• unknown compounds generated; when the reactions were conducted under N2 atmosphere or air, the desired products were either not detected or reduced to 53%. With the optimized conditions in hand, we studied the scope and limitations of the Cu-catalyzed oxidative direct amidation reaction. First, we

• into the desired 3 via intermediate D along with the recycling of the Cu catalyst. Conclusion In conclusion, Cu-catalyzed oxidative direct amidation from nonactivated carboxylic acid with benzimidazoles under dioxygen atmosphere with molecular oxygen as an activating reagent has been described. Azole

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

• atmosphere (Scheme 2). In the same year, Shen and co-workers reported the Cu-catalyzed sp2 C–H chlorination of 2-arylpyridines by using the salt LiCl as a new chlorine source in the presence of CrO3 and Ac2O [34]. Due to the oxidizing potency of the CrO3, the application scope of the method was not broad

• acquired as dibromoanilines via double C–H bromination process. On the other hand, the chlorination was found less effective due to the presence of the side transformation and formation of N-acetylated byproducts [50]. In 2009, Stahl et al. [51] reported a Cu-catalyzed aerobic C–H halogenation protocol of

• promoted the 1,5-H abstraction and atom transfer process in the form of SET via free radical 71. In 2012, Lectka and co-workers [69] reported an interesting C–H fluorination method for alkynes 72 via a Cu-catalyzed aliphatic C(sp3)–H functionalization. Monofluorinated products 73 were obtained by employing

Copper-catalyzed aerobic radical C–C bond cleavage of N–H ketimines

• Ya Lin Tnay,
• Gim Yean Ang and
• Shunsuke Chiba

Beilstein J. Org. Chem. 2015, 11, 1933–1943, doi:10.3762/bjoc.11.209

• cleavage of N–H ketimines. Treatment of N–H ketimines having an α-sp3 hybridized carbon under Cu-catalyzed aerobic reaction conditions resulted in a radical fragmentation with C–C bond cleavage to give the corresponding carbonitrile and carbon radical intermediate. This radical process has been applied for

• of Grignard reagents to carbonitriles followed by protonation as one of the methods for in situ generation of N–H ketimines, which were directly subjected to Cu-catalyzed aerobic reactions without further purification [54]. In this way, biaryl N–H ketimines generated from biaryl-2-carbonitriles were

Pyridine-promoted dediazoniation of aryldiazonium tetrafluoroborates: Application to the synthesis of SF₅-substituted phenylboronic esters and iodobenzenes

• George Iakobson,
• Junyi Du,
• Alexandra M. Z. Slawin and
• Petr Beier

Beilstein J. Org. Chem. 2015, 11, 1494–1502, doi:10.3762/bjoc.11.162

• compounds are accessed mainly by the reactions of arylmagnesium or aryllithium species with trialkylboronates [43][44], Pd- or Cu-catalyzed borylations of aryl halides using B2pin2, H-Bpin [45][46][47][48][49][50] or R2N-BH2 [51], direct borylations via aromatic C–H bond activations [52][53][54][55][56][57

Orthogonal dual-modification of proteins for the engineering of multivalent protein scaffolds

• Michaela Mühlberg,
• Michael G. Hoesl,
• Christian Kuehne,
• Jens Dernedde,
• Nediljko Budisa and
• Christian P. R. Hackenberger

Beilstein J. Org. Chem. 2015, 11, 784–791, doi:10.3762/bjoc.11.88

• engineer multivalent glycoprotein conjugates, we have used the incorporation of non-canonical amino acids (NCAA) [13] by supplementation based incorporation (SPI) [14][15][16][17] in auxotroph expression systems followed by the chemoselective Cu-catalyzed azide–alkyne cycloaddition (CuAAC) to attach

An unusually stable chlorophosphite: What makes BIFOP–Cl so robust against hydrolysis?

• Roberto Blanco Trillo,
• Jörg M. Neudörfl and
• Bernd Goldfuss

Beilstein J. Org. Chem. 2015, 11, 313–322, doi:10.3762/bjoc.11.36

• intramolecular palladium-catalyzed alkyl–aryl cross-coupling reaction [13] and in Pd-catalyzed allylic substitutions [14]. Several of the highly sterically hindered BIFOP derivatives were employed as ligands in Cu-catalyzed 1,4-additions [15]. Similar chelating fencholates [16][17][18][19][20][21][22] (Scheme 1

Conjugates of methylated cyclodextrin derivatives and hydroxyethyl starch (HES): Synthesis, cytotoxicity and inclusion of anaesthetic actives

• Lisa Markenstein,
• Antje Appelt-Menzel,
• Marco Metzger and
• Gerhard Wenz

Beilstein J. Org. Chem. 2014, 10, 3087–3096, doi:10.3762/bjoc.10.325

• ] and its Cu+-catalyzed version, called click reaction [31][32], is of special interest because this coupling proceeds rapidly and specific in aqueous media and tolerates many functional groups. Mono-6-azido-6-deoxy-β-CD was already coupled by the click reaction to propargylated dextrane by Nielsen et

• propargyl ether leading to a highly water soluble polymer 3 with DSHES(propargyl) = 0.55. Coupling of the CD azides 1a and 1b to the propargylated HES was performed by Cu+-catalyzed [2 + 3] cycloaddition, the so-called click reaction, leading to the corresponding triazol groups (Scheme 3). The standard

Copper-promoted hydration and annulation of 2-fluorophenylacetylene derivatives: from alkynes to benzo[b]furans and benzo[b]thiophenes

• Yibiao Li,
• Liang Cheng,
• Xiaohang Liu,
• Bin Li and
• Ning Sun

Beilstein J. Org. Chem. 2014, 10, 2886–2891, doi:10.3762/bjoc.10.305

• nucleophilic annulation process (Scheme 1b) [24]. But this method involves a two-step process and the usage of two different metal salts may complicate further processing. The direct design of a Pd or Cu-catalyzed one-pot synthesis of benzo[b]thiophenes from 2-bromoalkynylbenzenes and a thiol derivative has

A simple copper-catalyzed two-step one-pot synthesis of indolo[1,2-a]quinazoline

• Chunpu Li,
• Lei Zhang,
• Shuangjie Shu and
• Hong Liu

Beilstein J. Org. Chem. 2014, 10, 2441–2447, doi:10.3762/bjoc.10.254

• in a good yield (Table 2, entry 15). Halogen-substituted (F, Cl) substrates 3 also provided the desired products with moderate yields (Table 2, entries 16 and 17). Conclusion In conclusion, we have developed a simple and efficient Cu-catalyzed methodology for the synthesis of indolo[1,2-a]quinazoline

Expeditive synthesis of trithiotriazine-cored glycoclusters and inhibition of Pseudomonas aeruginosa biofilm formation

• Meriem Smadhi,
• Sophie de Bentzmann,
• Anne Imberty,
• Marc Gingras,
• Raoudha Abderrahim and
• Peter G. Goekjian

Beilstein J. Org. Chem. 2014, 10, 1981–1990, doi:10.3762/bjoc.10.206

• -triazine (2) as a key precursor [37]. The glycosyl units were incorporated via Cu(I)-catalyzed Huisgen cycloaddition with protected or unprotected glycosyl azides. We first investigated the Cu-catalyzed azide–alkyne cycloaddition (CuAAC) of acetyl protected β-D-galactopyranosyl azide 3 [38], to tris

One-pot stereoselective synthesis of α,β-differentiated diamino esters via the sequence of aminochlorination, aziridination and intermolecular S_N2 reaction

• Yiwen Xiong,
• Ping Qian,
• Chenhui Cao,
• Haibo Mei,
• Jianlin Han,
• Guigen Li and
• Yi Pan

Beilstein J. Org. Chem. 2014, 10, 1802–1807, doi:10.3762/bjoc.10.189

• directly from cinnamate esters using N,N-dichloro-p-toluenesulfonamide and benzylamine as nitrogen sources. The key transformations include a Cu-catalyzed aminohalogenation and aziridination, followed by an intermolecular SN2 nucleophilic ring opening by benzylamine. The reactions feature a wide scope of

• , the reaction could be conducted in a one-pot model, under operationally convenient conditions [36][37][38][39] through Cu-catalyzed aminohalogenation, aziridination and intermolecular SN2 nucleophilic ring opening without isolation of haloamine intermediate (Scheme 1). Results and Discussion According

• results, a proposed reaction mechanism for this one-pot reaction is illustrated in Scheme 4, which contains the sequence of aminochlorination, aziridination and followed by the SN2 nucleophilic ring-opening. The first step is the Cu-catalyzed aminochlorination reaction of methyl cinnamate 1a resulting in

Triazol-substituted titanocenes by strain-driven 1,3-dipolar cycloadditions

• Andreas Gansäuer,
• Andreas Okkel,
• Lukas Schwach,
• Laura Wagner,
• Anja Selig and
• Aram Prokop

Beilstein J. Org. Chem. 2014, 10, 1630–1637, doi:10.3762/bjoc.10.169

• -containing substrates for our strategy, i.e., azide-functionalized titanocenes, have been reported in the literature. One aspect of our study is to establish if such complexes are stable and readily available in high yield. It should be noted that only a single example of a Cu-catalyzed 1,3-dipolar

Tandem Cu-catalyzed ketenimine formation and intramolecular nucleophile capture: Synthesis of 1,2-dihydro-2-iminoquinolines from 1-(o-acetamidophenyl)propargyl alcohols

• Gadi Ranjith Kumar,
• Yalla Kiran Kumar,
• Ruchir Kant and
• Maddi Sridhar Reddy

Beilstein J. Org. Chem. 2014, 10, 1255–1260, doi:10.3762/bjoc.10.125

Rapid pseudo five-component synthesis of intensively blue luminescent 2,5-di(hetero)arylfurans via a Sonogashira–Glaser cyclization sequence

• Fabian Klukas,
• Alexander Grunwald,
• Franziska Menschel and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2014, 10, 672–679, doi:10.3762/bjoc.10.60

• approach are clearly the extended reaction times (3–6 d) and the removal of the catalyst after the coupling step. Recently, we became particularly interested in sequentially Pd-catalyzed processes [35] starting from (hetero)aryl iodides [36]. In particular, the Pd–Cu-catalyzed Sonogashira–Glaser sequence