One-pot activation–alkynylation–cyclization synthesis of 1,5-diacyl-5-hydroxypyrazolines in a consecutive three-component fashion

• Christina Görgen,
• Katharina Boden,
• Guido J. Reiss,
• Walter Frank and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2019, 15, 1360–1370, doi:10.3762/bjoc.15.136

• substrate 4 all different types of (hetero)aromatic, aliphatic, and alicyclic substituents R3 are well tolerated in the sequence (Table 3, entries 1–10). The alkynes 2 can bear electron-donating and electron-withdrawing substituents R2 (Table 3, entries 1, 11–14), however, for the electron-poor cyano

Steroid diversification by multicomponent reactions

• Leslie Reguera,
• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Daniel G. Rivera

Beilstein J. Org. Chem. 2019, 15, 1236–1256, doi:10.3762/bjoc.15.121

• required a high temperature set by classic heating or microwave irradiation. Using cholic acid as carboxylic acid component, Cui and co-workers [37] developed a novel MCR resembling the Ugi-4CR, but relying on the reactivity of ynamides as surrogates of the isocyanide component. Ynamides are alkynes with a

Multicomponent reactions (MCRs): a useful access to the synthesis of benzo-fused γ-lactams

• Edorta Martínez de Marigorta,
• Jesús M. de Los Santos,
• Ana M. Ochoa de Retana,
• Javier Vicario and
• Francisco Palacios

Beilstein J. Org. Chem. 2019, 15, 1065–1085, doi:10.3762/bjoc.15.104

• (Scheme 4). In this case, copper catalyst and alkynes are also used but, unlike the above method, alkynes 18 are monosubstituted. The third component is an indole or pyrrole derivative 19 and the result of the reaction is a 3,3-disubstituted isoindolinone derivative 20, which contains a newly formed

• conjugate addition of benzamide nitrogen onto the 2-ynamide generates the final cyclization product 24 through allene intermediate 28. Taking into account that the reaction does not take place with internal alkynes, the authors conclude that a terminal alkyne is necessary for the formation of the first

• alkynylpalladium complex 25 in the proposed pathway. Other benzoic acid derivatives such as those bearing a formyl substituent at the ortho position also take part in several multicomponent cyclizations leading to isoindolinones. Thus, 2-formylbenzoate 29, primary amines 2 and terminal alkynes 18 react under

Easy, efficient and versatile one-pot synthesis of Janus-type-substituted fullerenols

• Marius Kunkel and
• Sebastian Polarz

Beilstein J. Org. Chem. 2019, 15, 901–905, doi:10.3762/bjoc.15.87

• reacts the fastest and the reaction was completed after 20 min. Strong foaming indicates the completion of the reaction. Almost no byproduct could be isolated here. Of special interest for this reaction are compounds with additional functional groups like alkynes or bromides that can be reacted with

Diastereo- and enantioselective preparation of cyclopropanol derivatives

• Marwan Simaan and
• Ilan Marek

Beilstein J. Org. Chem. 2019, 15, 752–760, doi:10.3762/bjoc.15.71

• 3 were easily prepared through the well-known RhII-catalyzed decomposition of diazo esters in the presence of alkynes to give cyclopropenyl esters 1. Reduction of 1 using DIBAL-H afforded cyclopropenyl alcohols 2 and subsequent protection of the primary alcohols gave 3 in good yields (Scheme 3

Synthesis of 2H-furo[2,3-c]pyrazole ring systems through silver(I) ion-mediated ring-closure reaction

• Vaida Milišiūnaitė,
• Rūta Paulavičiūtė,
• Eglė Arbačiauskienė,
• Vytas Martynaitis,
• Wolfgang Holzer and
• Algirdas Šačkus

Beilstein J. Org. Chem. 2019, 15, 679–684, doi:10.3762/bjoc.15.62

• alkynylation/cyclization reaction between 2-iodophenol and (triethoxysilyl)alkynes [20]. In recent years silver and gold salts have found application as versatile and mild catalysts to access the benzo[b]furan ring system through intramolecular cyclization of 2-alkynylphenol substrates [21], including

• desired 2-phenyl-2H-furo[2,3-c]pyrazole was obtained in a significantly higher yield (47%, Table 1, entry 3). Some of the most effective catalysts for the electrophilic activation of alkynes under homogeneous conditions are gold(I) [35] and silver(I) [36] salts or complexes, and a broad range of versatile

• -furo[2,3-c]pyrazoles starting from commercially available 1-phenylpyrazol-3-ol. Iodination of the latter compound with iodine in DMF smoothly afforded 1-phenyl-4-iodopyrazol-3-ol, which can undergo a Pd-catalyzed coupling with terminal alkynes to give the corresponding 4-alkynyl-3-hydroxy-1-phenyl-1H

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• groups of relatively high energy level with the potential of multiple reactivity are employed, for instance nitriles, isonitriles or alkynes [1][2][3][4][5][6][7][8][9]. Not surprisingly, simple or functionalized allenes have also been used in multicomponent processes and – dependent on the substitution

Cyclopropene derivatives of aminosugars for metabolic glycoengineering

• Jessica Hassenrück and
• Valentin Wittmann

Beilstein J. Org. Chem. 2019, 15, 584–601, doi:10.3762/bjoc.15.54

• , azides and alkynes can be visualized by the Staudinger ligation [8] or the azide–alkyne cycloaddition, that can be performed either copper-catalyzed [9][10] or strain-promoted [11][12]. Another type of reporter group that has been proven to be a valuable tool are electron-rich or strained alkenes, that

Intramolecular cascade annulation triggered by rhodium(III)-catalyzed sequential C(sp²)–H activation and C(sp³)–H amination

• Liangliang Song,
• Guilong Tian,
• Johan Van der Eycken and
• Erik V. Van der Eycken

Beilstein J. Org. Chem. 2019, 15, 571–576, doi:10.3762/bjoc.15.52

• components (such as olefins, alkynes) stands out for the construction of carbo(hetero)cycles from easily available starting materials [7][8][9][10]. Compared to aromatic C(sp2)–H bonds, studies on activation of vinylic C(sp2)–H bonds have been less explored, due to an intrinsic inactivity, tended to undergo

Dirhodium(II)-catalyzed [3 + 2] cycloaddition of N-arylaminocyclopropane with alkyne derivatives

• Wentong Liu,
• Yi Kuang,
• Zhifan Wang,
• Jin Zhu and
• Yuanhua Wang

Beilstein J. Org. Chem. 2019, 15, 542–550, doi:10.3762/bjoc.15.48

• optimized reaction conditions. The terminal alkynes with electron-withdrawing groups reacted smoothly to produce the desired products, while alkyl-substituted terminal aldehydes, such as pent-1-yne (2b, Table 3, entry 1), did not produce the cycloaddition product [22][23][24]. tert-Butyldimethylsilyl

• -protected propargyl alcohol 2c had a greatly reduced reactivity (Table 3, entry 2) and the obtained yield was less than 10%. For aromatic terminal alkynes, moderate yields (Table 3, entries 3–6) were obtained regardless of the electron-donating or electron-withdrawing groups, indicating the electronic

• substrates. For 2-methylbut-1-en-3-yne (2i) containing both terminal alkenes and alkynes, the activity of the olefin was greater than that of the alkyne, which favors alkene cycloaddition products with a ratio of 89:11. The observed selectivity of product 4i is similar to that previously reported [11] (Table

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• afford alkylidenecyclopropane 63 (92%, Scheme 22) [61]. The Ireland–Claisen rearrangement was then extended to a challenging class of cyclopropylcarbinyl glycolates possessing gem-difluoro substitution at C3 [65]. Gem-difluorocyclopropenes are accessible by difluorocyclopropenation of alkynes with

A novel and efficient synthesis of phenanthrene derivatives via palladium/norbornadiene-catalyzed domino one-pot reaction

• Yue Zhong,
• Wen-Yu Wu,
• Shao-Peng Yu,
• Tian-Yuan Fan,
• Hai-Tao Yu,
• Nian-Guang Li,
• Zhi-Hao Shi,
• Yu-Ping Tang and
• Jin-Ao Duan

Beilstein J. Org. Chem. 2019, 15, 291–298, doi:10.3762/bjoc.15.26

• reaction may cause skin damage to experimenters. Alternatively, alkynes (Scheme 1b) played an important role in the synthesis of phenanthrene scaffolds under transition metal catalysis [9]. However, this protocol required complicated procedures, harsh reaction conditions and was incompatible with many

Copper(I)-catalyzed tandem reaction: synthesis of 1,4-disubstituted 1,2,3-triazoles from alkyl diacyl peroxides, azidotrimethylsilane, and alkynes

• Muhammad Israr,
• Changqing Ye,
• Munira Taj Muhammad,
• Yajun Li and
• Hongli Bao

Beilstein J. Org. Chem. 2018, 14, 2916–2922, doi:10.3762/bjoc.14.270

• from alkyl diacyl peroxides, azidotrimethylsilane, and terminal alkynes is reported. The alkyl carboxylic acids is for the first time being used as the alkyl azide precursors in the form of alkyl diacyl peroxides. This method avoids the necessity to handle organic azides, as they are generated in situ

• ], derived from the Huisgen’s 1,3-dipolar cycloaddition of azides and alkynes [22], has conceivably emerged as the premier example of click chemistry. Generally, organic azides are used as the azido source in most of the CuAAC reactions (Scheme 1a) [23]. However, the organic azides with low molecular weight

• reagents and enriched organic azide sources for CuAAC reaction are still highly required. Herein, we report a novel CuAAC reaction, using aliphatic carboxylic acids as the alkyl source [36], and TMSN3 as the azide source (Scheme 1b). Because TMSN3 can react with alkynes to form the CuAAC reaction product

Domino ring-opening–ring-closing enyne metathesis vs enyne metathesis of norbornene derivatives with alkynyl side chains. Construction of condensed polycarbocycles

• Ritabrata Datta and
• Subrata Ghosh

Beilstein J. Org. Chem. 2018, 14, 2708–2714, doi:10.3762/bjoc.14.248

• system. Domino metathesis of oxa- and aza-norbornenes with alkyne side chains [38][39][40] as well as norbornene derivatives having ether linked alkynes [41][42] in combination with Diels–Alder reaction of the resulting 1,3-dienes have been investigated to construct polycycles with heteroatoms. In spite

Synthesis and biological evaluation of 1,2-disubstituted 4-quinolone analogues of Pseudonocardia sp. natural products

• Stephen M. Geddis,
• Teodora Coroama,
• Suzanne Forrest,
• James T. Hodgkinson,
• Martin Welch and
• David R. Spring

Beilstein J. Org. Chem. 2018, 14, 2680–2688, doi:10.3762/bjoc.14.245

• natural products. The chemistry developed towards the allylic alcohols 5 and 6, outlined in Scheme 1, seemed ideal to this end. A range of alkynes 10 could undergo Sonogashira coupling with the commercially available acid chloride 9. The resultant ynones 11 could then undergo conjugate addition with

• shown to be unsuccessful in infecting the lungs of mice [18]. Being able to prevent the production of pyocyanin could therefore be of great therapeutic benefit. Results and Discussion In the implementation of the strategy outlined in Scheme 1, alkynes 10a and 10b were first subjected to Sonogashira

• coupling with commercially available acid chloride 9 according to the previously reported conditions (Scheme 2) [12]. These alkynes were chosen so as to allow access to valuable SAR data regarding the side chain of the natural products 1–8. Commercially available alkyne 10a would ultimately lead to a

Cobalt- and rhodium-catalyzed carboxylation using carbon dioxide as the C1 source

• Tetsuaki Fujihara and
• Yasushi Tsuji

Beilstein J. Org. Chem. 2018, 14, 2435–2460, doi:10.3762/bjoc.14.221

• carboxylation of allylarenes when a suitable ligand is used. In the presence of zinc powder, the Co-catalyzed carboxyzincation of alkynes and the four-component coupling reaction between alkyne, acrylates, CO2, and zinc proceed in an efficient manner. Visible-light-driven hydrocarboxylation reactions are shown

• transmetalation between D and AlMe3, with the concomitant regeneration of methyl-Co(I) A (step d). Carboxyzincation of alkynes The good reactivity and high functional-group compatibility of organozinc compounds render them as important reagents in organic synthesis [38][39]. For their preparation, direct and

• useful methods such as the transition-metal-catalyzed carbozincation of alkynes that affords stereodefined alkenylzinc compounds have been developed. To date, a variety of organozinc reagents (RZnX and R2Zn: R = aryl, alkyl, alkenyl, alkynyl, allyl, and benzyl groups) have been used in these reactions

Efficient catalytic alkyne metathesis with a fluoroalkoxy-supported ditungsten(III) complex

• Henrike Ehrhorn,
• Janin Schlösser,
• Dirk Bockfeld and
• Matthias Tamm

Beilstein J. Org. Chem. 2018, 14, 2425–2434, doi:10.3762/bjoc.14.220

• cleaving the W≡W bond in W2F3 with 1-phenyl-1-propyne. The catalytic alkyne metathesis activity of these metal complexes was determined in the self-metathesis, ring-closing alkyne metathesis and cross-metathesis of internal and terminal alkynes, revealing an almost equally high metathesis activity for the

• bimetallic tungsten complex W2F3 and the alkylidyne complex WPhF3. In contrast, Mo2F6 displayed no significant activity in alkyne metathesis. Keywords: alkylidyne complexes; alkyne metathesis; catalysis; terminal alkynes; tungsten; Introduction While the field of olefin metathesis has seen significant

• the metal tungsten, terminal alkynes at room temperature [54]. Our studies clearly display a strong dependency of the catalytic alkyne metathesis activity on the metal-alkoxide combination. The electrophilicity of the metal sites can be controlled by the number of fluorine atoms of the ancillary

Catalyst-free synthesis of 4-acyl-NH-1,2,3-triazoles by water-mediated cycloaddition reactions of enaminones and tosyl azide

• Lu Yang,
• Yuwei Wu,
• Yiming Yang,
• Chengping Wen and
• Jie-Ping Wan

Beilstein J. Org. Chem. 2018, 14, 2348–2353, doi:10.3762/bjoc.14.210

• numerous organic compounds [24][25][26][27][28]. The amazingly rapid and broad permeation of 1,2,3-triazoles to multidisciplinary areas can majorly be attributed to the occurrence of robust synthetic methods toward this heterocycle. The copper-catalyzed click [3 + 2] cycloaddition of azides and alkynes [29

• cycloaddition of azides with activated dipolarophiles such as strained cyclic alkynes, enamines, enolates, electron-deficient olefins, ylides, iminium cations and alkyne anions, etc., have been identified as reliable approaches to access 1,2,3-triazole scaffolds with multiple substitution patterns [39][40][41

Hydroarylations by cobalt-catalyzed C–H activation

• Rajagopal Santhoshkumar and
• Chien-Hong Cheng

Beilstein J. Org. Chem. 2018, 14, 2266–2288, doi:10.3762/bjoc.14.202

• alkenes, which required a stoichiometric amount of oxidant. Herein, we wish to review the cobalt-catalyzed hydroarylation of alkynes, alkenes, allenes, enynes, imines, and isocyanates. These reactions usually proceed via either an oxidative addition of Ar–H to a low-valent cobalt to form A1 intermediate

• catalysts. Review 1. Hydroarylation of alkynes 1.1 Low-valent cobalt-catalyzed hydroarylation of alkynes Hydroarylation of alkynes is an efficient method to synthesize aromatic alkenes in a highly atom-economical way [44]. In 1994, Kisch and co-workers developed the first cobalt-catalyzed hydroarylation of

• alkynes with azobenzenes 1 to synthesize dialkenated products 2 (Scheme 4) [32]. The reaction resulted in an anti-addition of the C–H bond with alkynes using the cobalt(I) catalysts CoH(N2)(PPh3)3 or CoH3(PPh3)3 under neat reaction conditions. After fifteen years, Yoshikai and co-workers developed a low

Applications of organocatalysed visible-light photoredox reactions for medicinal chemistry

• Michael K. Bogdos,
• Emmanuel Pinard and
• John A. Murphy

Beilstein J. Org. Chem. 2018, 14, 2035–2064, doi:10.3762/bjoc.14.179

• the [3 + 2]-cycloaddition of electron-poor alkynes and 2H-azirines [60]. The reaction is performed under blue LED irradiation and using acridinium salts as a photocatalyst (Scheme 15). With respect to 2H-azirine the scope of the reaction is demonstrated to be relatively broad, with aromatics

• , benzothiophenes and benzimidazoles seen in many drugs. In another demonstration of the value of diazonium salts, the König group have published a protocol for the synthesis of substituted benzothiophenes using Eosin Y photocatalysis, starting from o-methylthioarenediazonium salts and substituted alkynes (Scheme

•  20) [65]. The scope of the substrates demonstrated is quite broad, with substituted aromatic and aliphatic alkynes being used and a variety of substituents tolerated on the diazonium salt starting material. Terminal alkynes selectively formed 2-substituted benzothiophenes, whereas the

Artificial bioconjugates with naturally occurring linkages: the use of phosphodiester

• Takao Shoji,
• Hiroki Fukutomi,
• Yohei Okada and
• Kazuhiro Chiba

Beilstein J. Org. Chem. 2018, 14, 1946–1955, doi:10.3762/bjoc.14.169

• , artificial functional groups such as alkynes or azides must be pre-installed into the respective biomolecules. Thus generated linkages are also artificial, possibly causing significant perturbation from their native forms, which generally affect bioactivities negatively. Arguably, naturally occurring

Efficient catenane synthesis by cucurbit[6]uril-mediated azide–alkyne cycloaddition

• Antony Wing Hung Ng,
• Chi-Chung Yee,
• Kai Wang and
• Ho Yu Au-Yeung

Beilstein J. Org. Chem. 2018, 14, 1846–1853, doi:10.3762/bjoc.14.158

• macrocycles will be ensured. One example is the use of an active metal template, in which the macrocyclization is mediated by the metal ion inside the cavity of a metal-coordinating macrocycle [20]. Cucurbit[6]uril (CB[6]) has also been demonstrated to bind to ammonium-containing azides and alkynes and to

Recent advances in hypervalent iodine(III)-catalyzed functionalization of alkenes

• Xiang Li,
• Pinhong Chen and
• Guosheng Liu

Beilstein J. Org. Chem. 2018, 14, 1813–1825, doi:10.3762/bjoc.14.154

• , α-functionalization of carbonyl compounds, spirocyclizations, as well as functionalization of alkenes and alkynes [10][11][12][13][14][15][16][17]. In recent years, especially the functionalization of alkenes has attracted much attention [18][19][20] and in some cases, hypervalent iodine(III

Synthesis of spirocyclic scaffolds using hypervalent iodine reagents

• Fateh V. Singh,
• Priyanka B. Kole,
• Saeesh R. Mangaonkar and
• Samata E. Shetgaonkar

Beilstein J. Org. Chem. 2018, 14, 1778–1805, doi:10.3762/bjoc.14.152

• )-mediated spirocyclization of aryl alkynes 24 to spirolactones 26 by the reaction with bis(iodoarene) 25 in the presence of mCPBA. Bridged iodine(III)-mediated spirocyclization of phenols 27 to spirodienones 29. Iodine(III)-mediated spirocyclization of arnottin I (30) to its spirocyclic analogue arnottin II

• cyclization of para-substituted phenols 102 to spirocarbocyclic compounds 104 using Koser reagent 103. Iodine(III)-mediated spirocyclization of aryl alkynes 105 to spirocarbocyclic compound 106 by the reaction with bis(iodoarene) 25 in the presence of mCPBA. Iodine(III)-mediated spirocarbocyclization of ortho

DFT calculations on the mechanism of copper-catalysed tandem arylation–cyclisation reactions of alkynes and diaryliodonium salts

• Tamás Károly Stenczel,
• Ádám Sinai,
• Zoltán Novák and
• András Stirling

Beilstein J. Org. Chem. 2018, 14, 1743–1749, doi:10.3762/bjoc.14.148

• stereoselectivity of the reaction and it also excludes the formation of vinyl-cation intermediates. The obtained results could serve as a useful and more general description of the mechanism of the carboarylation–ring closure strategy based on the utilisation of alkynes and diaryliodonium salts, beyond the selected