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

• the reaction in the synthesis of indoles was later achieved by mean of ligand-free condition via the co-catalysis of Cu(eh)2 (copper(II) 2-ethylhexanoate) and TEMPO under oxygen atmosphere [68]. C(sp)–H bond amidation The C(sp)–H bond in terminal alkynes is more acidic than equivalent alkane and

• catalytic protocol was later developed by Mizuno et al. [74] for the amidation of terminal alkynes using lactam, sulfonamide or cyclic carbamates. The application of Cu(OH)2 as heterogeneous catalyst allowed the synthesis of ynamides 77 with moderate to excellent yield under air (Scheme 20). A latest work

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

• -substituted benzamides occurred predominantly at less sterically congested sites (3j, 3k). A ortho-substituted and a tetrahydronaphthalene derivative worked well, respectively, and provided moderate yields (3l, 3m). We also tested a variety of terminal alkynes as coupling partners with N-(quinolin-8-yl

• conditions: 1 (0.4 mmol), 2a (0.8 mmol), Cu(OAc)2 (0.4 mmol), K2CO3 (0.8 mmol), DMF (2 mL), 80 °C , 12 h, O2, isolated yield. Copper-mediated reaction of N-(quinolin-8-yl)benzamide with terminal alkynes. Reaction conditions: 1a (0.4 mmol), 2 (0.8 mmol), Cu(OAc)2 (0.4 mmol), K2CO3 (0.8 mmol), DMF (2 mL), 80

Synthesis of alpha-tetrasubstituted triazoles by copper-catalyzed silyl deprotection/azide cycloaddition

• Zachary L. Palchak,
• Paula T. Nguyen and
• Catharine H. Larsen

Beilstein J. Org. Chem. 2015, 11, 1425–1433, doi:10.3762/bjoc.11.154

• triazoles. A streamlined two-step approach to this uncommon class of hindered triazoles will accelerate exploration of their therapeutic potential. The superior activity of copper(II) triflate in the formation of triazoles from sensitive alkyne substrates extends to simple terminal alkynes. Keywords: azide

Design, synthesis and photochemical properties of the first examples of iminosugar clusters based on fluorescent cores

• Mathieu L. Lepage,
• Antoine Mirloup,
• Manon Ripoll,
• Fabien Stauffert,
• Anne Bodlenner,
• Raymond Ziessel and
• Philippe Compain

Beilstein J. Org. Chem. 2015, 11, 659–667, doi:10.3762/bjoc.11.74

• using mild basic conditions provided the target compounds 6a and 6b in good yields. Terminal alkynes located in the 2,6 positions were found to resonate at 3.32 ppm and the one in the pseudo meso position 8 resonates at 3.20 ppm. Fluorescent DNJ cluster synthesis Following a robust strategy developed in

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

• of these Michael acceptors and the low inherent nucleophilicity of the metal alkynylides. In 2010, Shibasaki and co-workers developed the asymmetric 1,4-addition of terminal alkynes to α,β-unsaturated thioamides [192]. In order to achieve this reaction, Shibasaki and co-workers used a soft Lewis acid

Direct access to pyrido/pyrrolo[2,1-b]quinazolin-9(1H)-ones through silver-mediated intramolecular alkyne hydroamination reactions

• Hengshuai Wang,
• Shengchao Jiao,
• Kerong Chen,
• Xu Zhang,
• Linxiang Zhao,
• Dan Liu,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2015, 11, 416–424, doi:10.3762/bjoc.11.47

• studied for the construction of heterocycles. We have reported on a highly efficient gold/silver-catalyzed intramolecular hydroamination of terminal alkynes in water for the synthesis of fused tricyclic xanthenes [34]. On the basis of this methodology, we have also afforded two fused benzimidazoles

Synthesis and chemosensing properties of cinnoline-containing poly(arylene ethynylene)s

• Natalia A. Danilkina,
• Petr S. Vlasov,
• Semen M. Vodianik,
• Andrey A. Kruchinin,
• Yuri G. Vlasov and
• Irina A. Balova

Beilstein J. Org. Chem. 2015, 11, 373–384, doi:10.3762/bjoc.11.43

• -protected diethynylcinnolines to be used as a starting material instead of unstable terminal alkynes. It also avoids an extra synthetic step. When we tried polycondensation of bis(trimethylsilyl)cinnolines 5a,b with diiodoarene 9 in the presence of Pd(PPh3)4/CuI as a catalytic system and KF/MeOH as a

A general metal-free approach for the stereoselective synthesis of C-glycals from unactivated alkynes

• Shekaraiah Devari,
• Manjeet Kumar,
• Ramesh Deshidi,
• Masood Rizvi and
• Bhahwal Ali Shah

Beilstein J. Org. Chem. 2014, 10, 2649–2653, doi:10.3762/bjoc.10.277

• these methods use priorly activated terminal alkynes, e.g., silylacetylene, activated with various Lewis acids such as SnCl4, BF3·OEt2, TiCl4, I2, InBr3, and ZrCl4 [24][25][26][27][28][29][30], followed by a Ferrier type rearrangement [31][32][33][34] (Scheme 1). A consequence of the prior activation of

• ) resulted in the loss of yield (Table 1, entries 10–13). The scope of the present method was further expanded to a variety of alkynes and glycals (Scheme 2). It was established that the system was tolerant to a wide variety of electron-donating as well as electron-withdrawing terminal alkynes to give the

• , respectively, and with a high selectivity. The present results indicate the activation of terminal alkynes by TMSOTf forming trimethylsilylacetylenes [39]. In order to confirm the formation of trimethylsilylacetylenes, we attempted a control experiment involving the addition of molecular iodine instead of

Electrocarboxylation: towards sustainable and efficient synthesis of valuable carboxylic acids

• Roman Matthessen,
• Jan Fransaer,
• Koen Binnemans and
• Dirk E. De Vos

Beilstein J. Org. Chem. 2014, 10, 2484–2500, doi:10.3762/bjoc.10.260

• mixture, or through a proton/hydrogen radical abstraction from the reaction medium. The triple bond of alkynes is more active towards carboxylation than the olefin double bond [56]; furthermore, terminal alkynes are more reactive than internal alkynes [56][57][58], both leading to highly selective CO2

A small azide-modified thiazole-based reporter molecule for fluorescence and mass spectrometric detection

• Stefanie Wolfram,
• Hendryk Würfel,
• Stefanie H. Habenicht,
• Christine Lembke,
• Phillipp Richter,
• Eckhard Birckner,
• Rainer Beckert and
• Georg Pohnert

Beilstein J. Org. Chem. 2014, 10, 2470–2479, doi:10.3762/bjoc.10.258

• bioactive metabolites and selective labeling of proteins and other biomacromolecules. A common structural motif for such probes consists of a reporter that can be attached by copper(I)-catalyzed 1,2,3-triazole formation between terminal alkynes and azides to a reactive headgroup. Here we introduce the

Synthesis of trifluoromethyl-substituted pyrazolo[4,3-c]pyridines – sequential versus multicomponent reaction approach

• Barbara Palka,
• Angela Di Capua,
• Maurizio Anzini,
• Gyté Vilkauskaité,
• Algirdas Šačkus and
• Wolfgang Holzer

Beilstein J. Org. Chem. 2014, 10, 1759–1764, doi:10.3762/bjoc.10.183

• is presented. Hence, microwave-assisted treatment of 5-chloro-1-phenyl-3-trifluoromethylpyrazole-4-carbaldehyde with various terminal alkynes in the presence of tert-butylamine under Sonogashira-type cross-coupling conditions affords the former title compounds in a one-pot multicomponent procedure

Synthesis, characterization and DNA interaction studies of new triptycene derivatives

• Sourav Chakraborty,
• Snehasish Mondal,
• Rina Kumari,
• Sourav Bhowmick,
• Prolay Das and
• Neeladri Das

Beilstein J. Org. Chem. 2014, 10, 1290–1298, doi:10.3762/bjoc.10.130

• frameworks (MOFs) with applications including but not limited to catalysis and gas uptake/storage [37][38][39][40][41][42]. It is well known that terminal alkynes can be conveniently subjected to carboxylation using CO2 to yield the corresponding alkynyl carboxylic acids. As shown in Scheme 2, 2,6,14

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

• compounds in moderate to good yields under mild reaction conditions. Keywords: alkyne; azide; cycloaddition; cyclization; quinoline; Introduction The synthesis of N-sulfonylketenimines via CuAAC (copper-catalyzed azide–alkyne cycloaddition) between terminal alkynes and sulfonyl azides has staged for a

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

• proceeded regioselectively and the α-adducts 126b of several terminal alkynes 125b were formed. Air-oxidation during work-up resulted in the formation of the corresponding phosphine oxides 131. The products 131 were isolated in moderate yields with respect to the diphosphine 130 as limiting reagent. It was

• excellent regioselectivity and good stereoselectivity as the Z-isomers, (Z)-133, were preferentially formed with Z/E ratios around 80/20. This method could not be performed on alkynes with an internal triple bond, only terminal alkynes were accessible. A catalytic amount of Co(acac)2 in combination with

• the thermal activated hydrophosphination was from Mimeau and Gaumont and described the use of a microwave reactor [254]. This reaction is performed with secondary phosphine–borane complexes 13j and terminal alkynes 125d. Mimeau and Gaumont demonstrated that the regioselectivity of the

Visible light mediated intermolecular [3 + 2] annulation of cyclopropylanilines with alkynes

• Theresa H. Nguyen,
• Soumitra Maity and
• Nan Zheng

Beilstein J. Org. Chem. 2014, 10, 975–980, doi:10.3762/bjoc.10.96

• . Hindered cyclopropylanilines, such as those possessing an ortho-isopropyl group, were satisfactorily converted to the annulation products (6 and 12). With respect to the other annulation partner, terminal alkynes substituted with an electron-withdrawing group were typically required for the annulation

• process. Alkyl-substituted terminal alkynes and internal alkynes were not reactive under the optimized conditions. This reactivity trend towards alkynes is consistent with that exhibited in intermolecular addition of nucleophilic carbon-based radicals to alkynes [31][32][33]. In addition to

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

• ] employing the superbase system DMSO/KOH/H2O in the terminal cyclization step [33]. The same approach was applied to butadiynes that were formed by oxidative dimerization of arylalkynes with a Cu/Fe catalyst [34]. Apart from using reactive terminal alkynes as starting materials the major drawbacks of this

• represents a highly intriguing combination of a cross-coupling and an oxidation reaction in a one-pot fashion [37]. By this approach we can efficiently avoid the major disadvantage of starting from terminal alkynes, which are occasionally unstable and tend to undergo polymerization. Based upon the

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• -diphenylphosphino-2-aminocyclohexane–Au(I) complex 20 (Figure 2), AgNTf2 as an additive, toluene as a solvent, rt, and a concentration of imine above 0.2 M. The obtained ee ranged from 41 to 95%. In a similar approach, Strand and co-workers [44] worked out a new entry to oxazoles 21 starting from terminal alkynes

• review on organosilver compounds by Pouwer and Williams exhaustively highlights all these aspects of silver chemistry [100]. For example, functionalized propiolic acids can be selectively prepared by an AgI catalyzed carboxylation of terminal alkynes with CO2 under ligand free conditions with the

• intermediacy of an organosilver compound, namely silver acetilide (Csp–Ag) [101]. The direct carboxylation of active C–H bonds of (hetero)arenes [102] and terminal alkynes [103] with CO2 in the presence of copper or gold-based catalysts has also been reported. However, these latter transformations require

Practical synthesis of aryl-2-methyl-3-butyn-2-ols from aryl bromides via conventional and decarboxylative copper-free Sonogashira coupling reactions

• Andrea Caporale,
• Stefano Tartaggia,
• Andrea Castellin and
• Ottorino De Lucchi

Beilstein J. Org. Chem. 2014, 10, 384–393, doi:10.3762/bjoc.10.36

• complicates the recycling of the palladium catalyst since the two metals are difficult to separate. Sonogashira reactions can be used for the syntheses of terminal alkynes from aryl halides through the coupling with an alkyne source such as trimethylsilylacetylene (TMSA) or 2-methyl-3-butyn-2-ol (4) in

• presence of a Cu/Pd bimetallic catalyst, followed by the basic cleavage of the protecting group [42][43][44][45][46]. Terminal alkynes are often used as starting materials for the synthesis of disubstituted acetylenes through a second coupling process with another aryl halide. Decarboxylative couplings

• obtained in a one-pot protocol with a considerable reduction of synthetic and purification steps with respect to traditional procedures [51][52][62]. Instead, when looking to the preparation of terminal alkynes from propiolic acid derivatives, the Cu-catalyzed protodecarboxylation of alkynoic acids [67][68

Synthesis of 3,4-dihydro-1,8-naphthyridin-2(1H)-ones via microwave-activated inverse electron-demand Diels–Alder reactions

• Salah Fadel,
• Youssef Hajbi,
• Mostafa Khouili,
• Said Lazar,
• Franck Suzenet and
• Gérald Guillaumet

Beilstein J. Org. Chem. 2014, 10, 282–286, doi:10.3762/bjoc.10.24

• envisaged to evaluate the reactivity of internal alkynes towards the inverse electron-demand Diels–Alder reaction. To reach this goal, we decided to functionalize the alkynes 6–9 employing the Sonogashira cross-coupling reaction. Preparation of aryl-N-triazinylpentynamides The terminal alkynes 6–9 were then

Triphenylene discotic liquid crystal trimers synthesized by Co₂(CO)₈-catalyzed terminal alkyne [2 + 2 + 2] cycloaddition

• Bin Han,
• Ping Hu,
• Bi-Qin Wang,
• Carl Redshaw and
• Ke-Qing Zhao

Beilstein J. Org. Chem. 2013, 9, 2852–2861, doi:10.3762/bjoc.9.321

• applied to the synthesis of hexabenzocoronene DLCs through diarylethyne cyclotrimerization [51]. In this paper, we report four star-shaped DLC trimers with triphenylene discotic units by using a Co2(CO)8-catalyzed terminal alkynes [2 + 2 + 2] cycloaddition, and the trimers exhibit ordered rectangular

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

• this byproduct can be prevented by using copper(I) bromide instead of the iodide salt. This reactivity of 1-haloalkynes is in accordance with the observation that 5-iodo-1,2,3-triazoles are formed as byproducts, when CuI is used as catalyst in CuAAC reactions of azides and terminal alkynes as has been

• incorporation of iodide in CuAAC reactions of terminal alkynes mediated by CuI (1.0 equivalent) by adequate choice of the base present in the reaction mixture [141]. With a ratio of alkyne/azide/DMAP/CuI = 1.0/3.0/0.3/1.0, they obtained 96% of the 5-iodotriazole and 4% of the Glaser coupling product. Dzyuba has

• to be employed. Instead the presence of amine bases such as triethylamine or tris[(tert-butyl)triazolylmethyl]amine (TTTA) greatly accelerates the highly selective formation of the 5-iodo-1,4-disubstituted-1,2,3-triazoles (Scheme 14). Despite the many similarities to the CuAAC reaction of terminal

Garner’s aldehyde as a versatile intermediate in the synthesis of enantiopure natural products

• Mikko Passiniemi and
• Ari M.P. Koskinen

Beilstein J. Org. Chem. 2013, 9, 2641–2659, doi:10.3762/bjoc.9.300

• metal-acetylide with terminal alkynes, such as 40. The phosphine ligand had to be monodentate; bidentate ligands gave a lot lower yields. Their catalyst system worked very efficiently with many carbonyl electrophiles, also with Garner’s aldehyde (R)-1. The reaction of 1 with 40 gave 41 with high

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

• aromatic alkenes with electrophilic trifluoromethylation reagents in the presence of copper and base. Results and Discussion Previously, we reported that copper powder or cuprous iodide could promote trifluoromethylation of heteroaromatics, arylboronic acids or terminal alkynes with trifluoromethyl

Gold(I)-catalyzed 6-endo hydroxycyclization of 7-substituted-1,6-enynes

• Ana M. Sanjuán,
• Alberto Martínez,
• Patricia García-García,
• Manuel A. Fernández-Rodríguez and
• Roberto Sanz

Beilstein J. Org. Chem. 2013, 9, 2242–2249, doi:10.3762/bjoc.9.263

• the reaction of commercially available 2-methyl-1-propenylmagnesium bromide with 2-bromobenzyl bromide in the presence of CuI and 2,2’-bipyridyl [32]. This aryl bromide could be coupled with selected terminal alkynes by using cesium carbonate as a base and PdCl2(MeCN)2/XPhos as a catalytic system [33

Flexible synthesis of anthracycline aglycone mimics via domino carbopalladation reactions

• Markus Leibeling and
• Daniel B. Werz

Beilstein J. Org. Chem. 2013, 9, 2194–2201, doi:10.3762/bjoc.9.258

• installation of a suitable leaving group sets the stage for the introduction of the first silylacetylene. Four different terminal alkynes 21 (a: Si = TMS; b: Si = SiMe2Ph; c: Si = SiMe2Bn; d: Si = Si(iPr)2H) were employed. Best results with yields of over 80% were obtained by the use of acetylene 21a

• , SiMe2Bn and Si(iPr)2OMe groups (Scheme 5). The best results were obtained with TMS-substituents. Although the SiMe2Ph-substituted product was not synthesized under optimal reaction conditions the desired product was formed in high yield. In addition, terminal alkynes were tolerated in the reaction