A systematic review on silica-, carbon-, and magnetic materials-supported copper species as efficient heterogeneous nanocatalysts in “click” reactions

• Pezhman Shiri and
• Jasem Aboonajmi

Beilstein J. Org. Chem. 2020, 16, 551–586, doi:10.3762/bjoc.16.52

• oxidized to Cu(II) species. Without using a ligand or a reducing agent, Cu(II) can oxidize alkynes to produce an undesired byproduct. Active copper catalysts can be prepared by reducing copper(II) sources, oxidizing copper metal, comproportionation of Cu(II) and Cu(0), or combination of copper salts and

• -functionalized silica 46 was added to the mixture, and this was heated to reflux to generate the catalyst 48. Several organic halides or epoxides, nonactivated alkynes, and sodium azide were reacted in an aqueous medium to provide triazoles or β-hydroxytriazoles using 1.0 mol % catalyst loading at 25 °C

• reflux conditions for one day. The resulting powder was filtered off, washed with methanol, and dried. Finally, excess copper was removed by the Soxhlet extraction method (Scheme 9). The 1,3-dipolar reaction of organic alkynes, organic bromides (or aryldiazonium salts or epoxides), and sodium azide

Controlling alkyne reactivity by means of a copper-catalyzed radical reaction system for the synthesis of functionalized quaternary carbons

• Goki Hirata,
• Yu Yamane,
• Naoya Tsubaki,
• Reina Hara and
• Takashi Nishikata

Beilstein J. Org. Chem. 2020, 16, 502–508, doi:10.3762/bjoc.16.45

• ; Introduction Terminal alkynes are undoubtedly useful functional groups for organic synthesis, and they can undergo a variety of reactions [1]. The C–C triple bond of an alkyne is suitable for addition reactions, whereas the terminal hydrogen atom is a good target for cross-coupling by using Sonogashira and

• related coupling reactions [2][3][4]. Although there are many reports on alkyne transformations, one recent development in this area has been the reaction of alkynes with tertiary alkyl electrophiles to produce functionalized quaternary carbon atoms via addition [5][6][7][8][9][10] or coupling [11][12][13

• ][14][15][16]. Recently, we have prepared quaternary carbon centers via radical reactions by using α-bromocarbonyl compounds (a tertiary alkyl source) and olefins or heteroatoms in the presence of a copper catalyst [17][18][19]. During our studies, we found that combinations of alkynes and tertiary

Aerobic synthesis of N-sulfonylamidines mediated by N-heterocyclic carbene copper(I) catalysts

• Faïma Lazreg,
• Marie Vasseur,
• Alexandra M. Z. Slawin and
• Catherine S. J. Cazin

Beilstein J. Org. Chem. 2020, 16, 482–491, doi:10.3762/bjoc.16.43

• area, reporting on the synthesis of the first heteroleptic bis-NHC and mixed NHC/phosphine copper(I) complexes [20][21][22]. Interestingly, these new copper-based complexes have shown excellent activity in the [3 + 2] cycloaddition reaction of azides/sulfonyl azides and alkynes (Scheme 1, right) [22

• . Various terminal aryl/alkyl-substituted alkynes were investigated in the presence of tosyl azide and diisopropylamine (Scheme 4). Under standard conditions, good to excellent yields were obtained. The presence of functional groups in para-position of the aryl ring leads to a decrease of the conversion to

• substrate, solvent-free conditions lead to 78% isolated yield at 40 °C. Diynes were also investigated and excellent isolated yields were achieved (92% and 85% for 11j and 11k, respectively). Regarding the alkyl-alkynes, longer reactions times as well as higher temperature were required to reach high

Recent advances in photocatalyzed reactions using well-defined copper(I) complexes

• Mingbing Zhong,
• Xavier Pannecoucke,
• Philippe Jubault and
• Thomas Poisson

Beilstein J. Org. Chem. 2020, 16, 451–481, doi:10.3762/bjoc.16.42

• alkynes. [Cu(I)(dap)2]Cl was found to be the best catalyst for this transformation proceeding upon irradiation at 530 nm (green LED, Scheme 6) [22]. Indeed, the comparison of this Cu catalyst with [Ru(bpy)3]Cl2 and Ir(ppy)3 clearly demonstrated the higher efficiency, good yield, selectivity, and excellent

• of the ligand iodide for DAP (path III). Another possibility was the trapping of the radical with the iodine ligand of the [Cu(II)] catalyst (path IV). In 2019, Reiser’s group described a chlorosulfonylation reaction of alkenes and alkynes with [Cu(I)(dap)2]Cl or [Cu(II)(dap)2]Cl2 under visible light

• chlorosulfonylation of terminal alkenes and alkynes using the previously developed copper-based photocatalyst (Scheme 19) [35]. The reaction was tolerant to a broad range of arylchlorosulfonyl derivatives when the reaction was carried out with styrene, including sterically hindered and heteroaromatic substrates

Photophysics and photochemistry of NIR absorbers derived from cyanines: key to new technologies based on chemistry 4.0

• Bernd Strehmel,
• Christian Schmitz,
• Ceren Kütahya,
• Yulian Pang,
• Anke Drewitz and
• Heinz Mustroph

Beilstein J. Org. Chem. 2020, 16, 415–444, doi:10.3762/bjoc.16.40

Copper-promoted/copper-catalyzed trifluoromethylselenolation reactions

• Clément Ghiazza and
• Anis Tlili

Beilstein J. Org. Chem. 2020, 16, 305–316, doi:10.3762/bjoc.16.30

• could be trifluoromethylselenolated that way (Scheme 2) [13][15][16][17]. Mechanistically, the authors postulated the involvement of copper(I)/(III) oxidation states. Oxidative cross-coupling reactions between terminal alkynes using the [(bpy)CuSeCF3]2 complex were also undertaken by the same group to

• reagent was involved in several cross-coupling processes, including copper chemistry. In this context, in 2015, the group of Rueping reported an oxidative trifluoromethylselenolation process of terminal alkynes and boronic acid derivatives (Scheme 10) [27]. Using a stoichiometric amount of copper/ligand

• ClSeCF3 is generated in situ [33]. This strategy was then applied to the trifluoromethylselenolation of alkynes by using copper(I) acetylides [34]. With bipyridine as the ligand, the trifluoromethylselenolation of alkynes was reported to occur with moderate to very good yields. The conditions were

Recent developments in photoredox-catalyzed remote ortho and para C–H bond functionalizations

• Rafia Siddiqui and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 248–280, doi:10.3762/bjoc.16.26

• scaffolds in their structures [104][105][106][107]. By employing dual photoredox catalysis, in 2016, Fabry et al. reported the cyclization of substituted anilides with alkynes to produce indoles [108]. Unlike previously reported syntheses, viz, an indole synthesis by the Fagnou group utilizing a large

• thiolation. Synthesis of indoles via C–H cyclization of anilides with alkynes. Preparation of 3-trifluoromethylcoumarins via C–H cyclization of arylpropiolate esters. Monobenzoyloxylation without chelation assistance. Aryl-substituted arenes prepared by inorganic photoredox catalysis using 12a. Arylation of

Combination of multicomponent KA² and Pauson–Khand reactions: short synthesis of spirocyclic pyrrolocyclopentenones

• Riccardo Innocenti,
• Elena Lenci,
• Gloria Menchi and
• Andrea Trabocchi

Beilstein J. Org. Chem. 2020, 16, 200–211, doi:10.3762/bjoc.16.23

• basic nitrogen atoms [28]. The variation of the alkyne component proved to give the KA2 coupling adduct when aromatic terminal alkynes were used, as shown in Table 1, entries 1 and 2 for those containing phenyl and thienyl moieties, resulting in 82% and 74% yield for the KA2 step. Subsequent acylation

• and pairing steps proved to proceed in good yield, thus furnishing the corresponding spirocyclopentenone derivatives 5 and 9 with an aromatic appendage at the carbonyl alpha carbon. On the contrary, when aliphatic alkynes were applied in the KA2 process, no reaction with allylamine and cyclohexanone

Extension of the 5-alkynyluridine side chain via C–C-bond formation in modified organometallic nucleosides using the Nicholas reaction

• Renata Kaczmarek,
• Dariusz Korczyński,
• James R. Green and
• Roman Dembinski

Beilstein J. Org. Chem. 2020, 16, 1–8, doi:10.3762/bjoc.16.1

• confirmed that the Nicholas reaction can be carried out in a nucleoside presence, leading to a divergent synthesis of novel metallo-nucleosides enriched with alkene, arene, arylketo, and heterocyclic functions, in the deoxy and ribo series. Keywords: alkynes; 5-alkynyluridines; C–C-bond formation; dicobalt

Construction of trisubstituted chromone skeletons carrying electron-withdrawing groups via PhIO-mediated dehydrogenation and its application to the synthesis of frutinone A

• Qiao Li,
• Chen Zhuang,
• Donghua Wang,
• Wei Zhang,
• Rongxuan Jia,
• Fengxia Sun,
• Yilin Zhang and
• Yunfei Du

Beilstein J. Org. Chem. 2019, 15, 2958–2965, doi:10.3762/bjoc.15.291

• ][76][77], converting alkynes and alkenes to ketones [78], oxidizing alcohols to aldehydes [79][80], as well as in the direct α-hydroxylation of ketones [81]. Furthermore, it could also be used to realize oxidative C–C [82], C–N [83], and C–O [84] bond formations. However, to the best of our knowledge

Palladium-catalyzed Sonogashira coupling reactions in γ-valerolactone-based ionic liquids

• László Orha,
• József M. Tukacs,
• László Kollár and
• László T. Mika

Beilstein J. Org. Chem. 2019, 15, 2907–2913, doi:10.3762/bjoc.15.284

• the product isolation procedure. In addition, it is well-established that the presence of Cu(I) salt can promote the in situ formation of some Cu(I) acetylides, which can readily undergo oxidative homocoupling of alkynes even in their slight excess in the reaction mixture [15][38][39]. Thus, the

Influence of the cis/trans configuration on the supramolecular aggregation of aryltriazoles

• Sara Tejera,
• Giada Caniglia,
• Rosa L. Dorta,
• Andrea Favero,
• Javier González-Platas and
• Jesús T. Vázquez

Beilstein J. Org. Chem. 2019, 15, 2881–2888, doi:10.3762/bjoc.15.282

• "click" chemistry [16][17][18] of azides and alkynes catalyzed by Cu(I) salts, the CuAAC reaction. Self-assembling properties were not observed for any of the prepared monotriazoles, namely the 4-substituted 1-glucopyranosyltriazoles 1a–g and 2a–g (Scheme 1) [15]. However, most ditriazoles 7a–g and 8a–g

• from the corresponding alkynes and diazides 5 and 6, respectively. In this context, it was required to isolate 5 and 6 before the coupling reaction could be performed. Compounds 9 and 10 (Scheme 3) were obtained in good yields by treatment of 7f and 8f, respectively, with sodium methoxide in CH2Cl2

Iodine-mediated hydration of alkynes on keto-functionalized scaffolds: mechanistic insight and the regiospecific hydration of internal alkynes

• Zachary Lee,
• Brandon R. Jones,
• Nyochembeng Nkengbeza,
• Michael Phillips,
• Kayla Valentine,
• Alexis Stewart,
• Brandon Sellers,
• Nicholas Shuber and
• Karelle S. Aiken

Beilstein J. Org. Chem. 2019, 15, 2747–2752, doi:10.3762/bjoc.15.265

• hydration reaction of alkynes serves as a green alternative to metal-catalyzed procedures. Previous work has shown that this method works well with terminal alkynes on keto-functionalized scaffolds, including 1,3-dicarbonyls and their heteroatom analogues. It was hypothesized that the reaction proceeds

• through a 5-exo-dig neighboring group participation (NGP) cyclization and an α-iodo intermediate. The work described herein probes the existence of the intermediate through NMR investigations and explores the scope of the hydration process with internal alkynes. The NMR experiments confirm the existence

• of the α-iodo intermediate, and methodology studies demonstrate that alkyl-capped, asymmetric, internal alkynes undergo a regiospecific hydration, also via the 5-exo-dig NGP pathway. Keywords: α-iodo intermediate; internal alkyne; iodine-mediated hydration; neighboring group participation

Fluorinated maleimide-substituted porphyrins and chlorins: synthesis and characterization

• Valentina A. Ol’shevskaya,
• Elena G. Kononova and
• Andrei V. Zaitsev

Beilstein J. Org. Chem. 2019, 15, 2704–2709, doi:10.3762/bjoc.15.263

• 1,2,3-triazole heterocycles via the copper-catalyzed azide–alkyne cycloaddition reaction (CuAAC) between alkynes and azides, developed independently by Sharpless [41] and Meldal [42]. In addition to the applications of triazoles as pharmacophores in the potential biologically active molecules, these

Emission solvatochromic, solid-state and aggregation-induced emissive α-pyrones and emission-tuneable 1H-pyridines by Michael addition–cyclocondensation sequences

• Natascha Breuer,
• Irina Gruber,
• Christoph Janiak and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2019, 15, 2684–2703, doi:10.3762/bjoc.15.262

• -pyrones from acid chlorides, terminal alkynes and dialkyl malonates. Consecutive pseudo-four-component alkynylation–Michael addition–cyclocondensation (AMAC) synthesis of 1H-pyridines 5a and an aniline derivative. Consecutive pseudo-four-component alkynylation–Michael addition–cyclocondensation (AMAC

• ) synthesis of 1H-pyridines 5a from acid chlorides 1, terminal alkynes 2 and ethyl cyanoacetate (4). Model system for the optimization of the Michael addition–cyclocondensation reaction step to 1H-pyridine 5a or/and α-pyrone 6a. Formation of α-pyrone 6a and 1H-pyridine 5a at 20 °C. Formation of α-pyrone 6a

AgNTf₂-catalyzed formal [3 + 2] cycloaddition of ynamides with unprotected isoxazol-5-amines: efficient access to functionalized 5-amino-1H-pyrrole-3-carboxamide derivatives

• Ziping Cao,
• Jiekun Zhu,
• Li Liu,
• Yuanling Pang,
• Laijin Tian,
• Xuejun Sun and
• Xin Meng

Beilstein J. Org. Chem. 2019, 15, 2623–2630, doi:10.3762/bjoc.15.255

• use of an inexpensive catalyst, simple reaction conditions, simple work-up without column chromatographic purification for most of products and high yields. Keywords: [3 + 2] cycloaddition; isoxazole; pyrrole; silver catalysis; ynamide; Introduction Silver-catalyzed transformations of alkynes have

• attracted much attention over the past decade [1][2]. As a powerful π-activator, silver can promote various reactions of alkynes in high efficiencies [3][4][5][6][7][8]. Generally speaking, the proceeding of these reactions involves the activation of alkyne bond by coordination of [Ag] and then the

• -mediated reactions of alkynes (Scheme 1, path b). In 2007, Echavarren and co-workers have developed an intramolecular cyclopropanation reaction of 1,6-enynes by silver catalysis, involving probably the generation of a silver-carbene species [15]. Wang and co-workers reported a range of propargylic esters

1,5-Phosphonium betaines from N-triflylpropiolamides, triphenylphosphane, and active methylene compounds

• Vito A. Fiore,
• Chiara Freisler and
• Gerhard Maas

Beilstein J. Org. Chem. 2019, 15, 2603–2611, doi:10.3762/bjoc.15.253

• their isolation and structural characterization are still less common. A very convenient access to such betaines is provided by the nucleophilic addition of tertiary phosphanes to electron-deficient alkenes, alkynes and allenes (phospha-Michael addition), which generates the betaines as reactive

• ]. We report now on three-component reactions of alkynes 1 with triphenylphosphane and active methylene compounds, leading to phosphonium betaines which are structurally different from those shown in Scheme 1. Results and Discussion Synthesis of betaines 3 The combination of equimolar amounts of

Formation of alkyne-bridged ferrocenophanes using ring-closing alkyne metathesis on 1,1’-diacetylenic ferrocenes

• Celine Bittner,
• Dirk Bockfeld and
• Matthias Tamm

Beilstein J. Org. Chem. 2019, 15, 2534–2543, doi:10.3762/bjoc.15.246

• with high yields whilst giving full conversion of the terminal alkynes. Furthermore, the solvent-dependant reactivity of 2a towards Ag(SbF6) is investigated, leading to oxidation and formation of the ferrocenium hexafluoroantimonate 4 in dichloromethane, whereas the silver(I) coordination polymer 5 was

• isolated from THF solution. Keywords: alkyne metathesis; ferrocene; homogeneous catalysis; molybdenum; terminal alkynes; Introduction Alkyne metathesis, the reversible making and breaking of carbon–carbon triple bonds, is clearly gaining more attention. Not only could a great number of active catalysts

• ]. Only recently, we were able to present a molybdenum complex decorated with hexafluoro-tert-butoxide ligands [MesC≡Mo{OC(CH3)(CF3)2}3] (MoF6; Mes = 2,4,6-trimethylphenyl) which proved to be highly active in the metathesis of internal and even terminal alkynes [42][43][44]. The same accounts for the

Self-assembled coordination thioether silver(I) macrocyclic complexes for homogeneous catalysis

• Zhen Cao,
• Aline Lacoudre,
• Cybille Rossy and
• Brigitte Bibal

Beilstein J. Org. Chem. 2019, 15, 2465–2472, doi:10.3762/bjoc.15.239

• of the two L2·(AgOTf)2 stereoisomers highlighted their different geometry. The catalytic activity of all silver(I) complexes was effective under homogeneous conditions in two tandem addition/cycloisomerization of alkynes using 0.5–1 mol % of catalytic loading. Keywords: coordination macrocycle

• reactions of alkynes. Results and Discussion Synthesis of silver(I) complexes Ligand 1 was synthesized in one step, from commercially available 9,10-dibromoanthracene and 2-(methylthio)phenylboronic acid, using a Suzuki–Miyaura cross-coupling reaction. Notably, the yield was low (26%) [55], and the X-ray

• complexes 1a–d were evaluated as homogeneous catalysts in two tandem addition/cycloisomerization reactions using alkynes 2 and 3. 2-Alkynylbenzaldehyde 2 [58][59] was chosen as the first model substrate for a cyclization reaction in the presence of methanol as a second nucleophile. This tandem addition

Combining the Ugi-azide multicomponent reaction and rhodium(III)-catalyzed annulation for the synthesis of tetrazole-isoquinolone/pyridone hybrids

• Gerardo M. Ojeda,
• Prabhat Ranjan,
• Pavel Fedoseev,
• Lisandra Amable,
• Upendra K. Sharma,
• Daniel G. Rivera and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2019, 15, 2447–2457, doi:10.3762/bjoc.15.237

• synthesis of isoquinolones using an N-methoxyamide as directing group for the ortho-position and alkynyl bromide to achieve the regioselective cyclization (Scheme 1B) [31]. In parallel, our group has developed Ru(II) and Rh(III)-catalyzed inter- and intramolecular annulations of aromatic rings with alkynes

• acids to allow the subsequent reaction with alkynes based on the C(sp2)–H activation of these aryl or vinyl moieties. As depicted in Table 1, we chose the tetrazolic substrate 1a for the optimization of the catalytic addition of diphenylacetylene (3a), a process involving the metal-catalyzed ortho-C–H

• rendered isoquinolone hybrid 4v in a very good yield. However, the reaction with 1,2-di(pyridin-3-yl)ethyne was not successful, nor was the employment of aliphatic alkynes or the terminal phenylacetylene. Finally, aiming at producing tetrazole hybrids including other heterocyclic moieties, the reaction was

Recent advances in transition-metal-catalyzed incorporation of fluorine-containing groups

• Xiaowei Li,
• Xiaolin Shi,
• Xiangqian Li and
• Dayong Shi

Beilstein J. Org. Chem. 2019, 15, 2213–2270, doi:10.3762/bjoc.15.218

• trifluoromethylation before 2011, and Besset [21] focused on the direct introduction of fluorinated groups into alkenes and alkynes. Then, Toste [1] covered advances in catalytic enantioselective fluorination, mono‑, di‑, and trifluoromethylation, and trifluoromethylthiolation reactions. Recently, Zhang [14] offered a

• ]. The resulting chiral trifluoromethylated alkynes were acquired with high regioselectivity and stereospecificity (ees up to >99%). Furthermore, this reaction showed a broad substrate scope, as well as excellent functional-group compatibility (Scheme 57). A possible mechanism was proposed: firstly

Click chemistry towards thermally reversible photochromic 4,5-bisthiazolyl-1,2,3-triazoles

• Chenxia Zhang,
• Kaori Morinaka,
• Mahmut Kose,
• Takashi Ubukata and
• Yasushi Yokoyama

Beilstein J. Org. Chem. 2019, 15, 2161–2169, doi:10.3762/bjoc.15.213

• important difference is that Ru(I) catalysts work on the disubstituted alkynes to give 1,4,5-trisubstituted triazoles (Scheme 1) [18][19]. When both substituents of an internal alkyne are aromatic groups, the triazoles thus formed include the hexatriene motif in the structure. Although a number of

Vicinal difunctionalization of alkenes by four-component radical cascade reaction of xanthogenates, alkenes, CO, and sulfonyl oxime ethers

• Shuhei Sumino,
• Takahide Fukuyama,
• Mika Sasano,
• Ilhyong Ryu,
• Antoine Jacquet,
• Frédéric Robert and
• Yannick Landais

Beilstein J. Org. Chem. 2019, 15, 1822–1828, doi:10.3762/bjoc.15.176

• a single operation [1][2][3][4][5]. Needless to say, the contribution by radical chemistry is not trivial [5][6][7]. While alkenes and alkynes have served as efficient radical donor/acceptor type C2 synthons in multicomponent radical reactions, CO and isonitriles were shown to react as donor

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

• more. It was observed that most of the methods utilize 2-aminopyridines as one of the starting materials due to its binucleophilic nature; associated with exocyclic amino group and endocyclic pyridinium nitrogen [19]. Recently, A3 coupling of alkynes, aldehydes, and aminopyridines have been developed

• . The Pd-catalyzed Sonogashira reaction has successfully constructed arylated internal alkynes that are important intermediates in organic synthesis, molecular electronics and polymers [56]. C–N bond forming reactions between aryl halides and amines/amides/sulfonamides have been extensively studied in

• high level of functional group compatibility, intramolecular alkylations, inter and intramolecular C–H bond activation and regio/stereoselective homocoupling of alkynes [71][72][73]. Group of Cho and Chang have unprecedentedly reported a Rh catalytic system for facile addition of heteroarenes to both

Borylation and rearrangement of alkynyloxiranes: a stereospecific route to substituted α-enynes

• Ruben Pomar Fuentespina,
• José Angel Garcia de la Cruz,
• Gabriel Durin,
• Victor Mamane,
• Jean-Marc Weibel and
• Patrick Pale

Beilstein J. Org. Chem. 2019, 15, 1416–1424, doi:10.3762/bjoc.15.141

• coupling reactions of either terminal or organometallic alkynes with vinyl halides or of alkynyl halides with vinylic organometallics [20]. However, both routes may lead to mixtures of stereoisomers and synthetic approaches to stereodefined substituted α-enynes remain scarce and thus still represent a