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

Hypervalent organoiodine compounds: from reagents to valuable building blocks in synthesis

• Gwendal Grelier,
• Benjamin Darses and
• Philippe Dauban

Beilstein J. Org. Chem. 2018, 14, 1508–1528, doi:10.3762/bjoc.14.128

• ]. The use of this acid as an oxygen nucleophile, then, has been more fully investigated by the groups of Szabó and Sodeoka who have simultaneously described the copper-catalyzed benzoyloxy-trifluoromethylation of alkenes and alkynes using Togni’s reagent 5. The group of Szabó has first reported the use

• of copper(I) iodide as a catalyst for the regioselective difunctionalization of aromatic alkynes and alkenes with an optimal atom-economy (Scheme 4a) [34][35]. The transformation proceeds efficiently, particularly in the presence of an electron-donating substituent on the aromatic ring. The same

• complex. The group of Sodeoka, in parallel, has described the same 1,2-difunctionalization reaction of alkenes and alkynes with 5 in the presence of [Cu(MeCN)4]PF6 as the catalyst (Scheme 5a) [37]. It should be pointed out that this copper(I) complex was previously described by Szabó as a poor catalyst in

Three-component coupling of aryl iodides, allenes, and aldehydes catalyzed by a Co/Cr-hybrid catalyst

• Kimihiro Komeyama,
• Shunsuke Sakiyama,
• Kento Iwashita,
• Itaru Osaka and
• Ken Takaki

Beilstein J. Org. Chem. 2018, 14, 1413–1420, doi:10.3762/bjoc.14.118

• characters of organometallics depending on the central metals. Ni/Cr or Co/Cr-catalyzed NHK reaction. Functionalization of alkynes via carbocobaltation. Cyclization/borylation of alkynyl iodoarenes using the Co/Cr catalyst. Three-component coupling of aryl iodides, arenes, and aldehydes using Co/Cr catalyst

[3 + 2]-Cycloaddition reaction of sydnones with alkynes

• Veronika Hladíková,
• Jiří Váňa and
• Jiří Hanusek

Beilstein J. Org. Chem. 2018, 14, 1317–1348, doi:10.3762/bjoc.14.113

• as internal alkynes/cycloalkynes taken from literature since its discovery by Huisgen in 1962 up to the current date. Except enumeration of synthetic applications it also covers mechanistic studies, catalysis, effects of substituents and reaction conditions influencing reaction rate and

• regioselectivity. Keywords: alkynes; Cu(I) catalysis; [3 + 2]-cycloaddition; mechanism; regioselectivity; sydnones; Review Introduction Since Huisgen’s discovery of the [3 + 2]-cycloaddition between 3-substituted sydnones and both terminal as well as internal alkynes [1][2] many researchers have tried to utilize

• by Taran et al. [4]. In order to avoid duplication our review is therefore focused in more detail on thermal, photochemical as well as metal-catalyzed reactions of sydnones with alkynes and factors that influence the yield and ratio of both possible regioisomers and also the kinetics and mechanism of

Investigations of alkynylbenziodoxole derivatives for radical alkynylations in photoredox catalysis

• Yue Pan,
• Kunfang Jia,
• Yali Chen and
• Yiyun Chen

Beilstein J. Org. Chem. 2018, 14, 1215–1221, doi:10.3762/bjoc.14.103

• radical; alkynylbenziodoxoles; photoredox catalysis; radical alkynylation; Introduction The introduction of the alkynyl group to organic molecules is an important synthetic transformation in organic synthesis [1][2][3][4]. Recently, cyclic iodine(III) reagents (CIR)-substituted alkynes

• investigate their reactivity toward alkyl radical and acyl radical additions in photoredox catalysis. The mechanistic investigations were carried out to study the derivatization of BI-alkynes in radical acceptor and oxidative quencher reactivity, and the electron-rich benziodoxole derivatives demonstrated

• NMR spectra of BI-alkynes 3a–f were studied with the focus on the α-carbon, which position directly underwent α-radical addition [19]. The electron density of the α-carbon was decreased in 3a with electron-deficient 3,4-difluoro groups on the benziodoxole, and was increased for 3f with electron

Rapid transformation of sulfinate salts into sulfonates promoted by a hypervalent iodine(III) reagent

• Elsa Deruer,
• Vincent Hamel,
• Samuel Blais and
• Sylvain Canesi

Beilstein J. Org. Chem. 2018, 14, 1203–1207, doi:10.3762/bjoc.14.101

• tolerates spectator functionalities such as primary halides or alkynes (Table 2). We were disappointed to observe no reaction in the presence of tertiary alcohols such as tert-butanol (Table 2, entry n). However, the reaction proceeded efficiently with a hindered secondary neopentylic alcohol 5 despite the

Electrochemically modified Corey–Fuchs reaction for the synthesis of arylalkynes. The case of 2-(2,2-dibromovinyl)naphthalene

• Fabiana Pandolfi,
• Isabella Chiarotto and
• Marta Feroci

Beilstein J. Org. Chem. 2018, 14, 891–899, doi:10.3762/bjoc.14.76

• ; Introduction Terminal alkynes, due to the considerable triple-bond strength (839 kJ mol−1), are characterized by a moderate thermodynamic reactivity [1]. Nevertheless, both the C–C triple bond and the terminal C–H bond can be efficiently and selectively activated by metal or metal-free catalysts. Therefore

• , terminal alkynes can be considered as raw material (thus an important resource). The use of terminal alkynes, activated by catalysts, as building blocks or intermediates in the synthesis of a large number of chemicals is extensively summarized in recent reviews [1][2][3]. The recently published papers

• confirm the present interest in the chemistry of terminal alkynes, e.g., in the synthesis of sulfinamides and isothiazoles [4], 1,3-enynes [5], α-monosubstituted propargylamines [6], 2-substituted pyrazolo[5,1-a]isoquinolines [7], etc. Terminal alkynes can be prepared by dehydrohalogenation of vicinal

Cobalt-catalyzed directed C–H alkenylation of pivalophenone N–H imine with alkenyl phosphates

• Wengang Xu and
• Naohiko Yoshikai

Beilstein J. Org. Chem. 2018, 14, 709–715, doi:10.3762/bjoc.14.60

• of alkynes has also been explored as an alternative approach for C–H alkenylation [10]. Despite the significant progress made, each of these C–H alkenylation manifolds has some critical limitations. For example, the dehydrogenative Heck reaction is often limited to activated monosubstituted alkenes

• (e.g., acrylates), and is challenging with unactivated and multisubstituted alkenes [11]. The hydroarylation of alkynes does not allow for the introduction of cycloalkenyl groups because of the unavailability of the corresponding alkynes. In light of such limitations, a coupling between arene

AuBr₃-catalyzed azidation of per-O-acetylated and per-O-benzoylated sugars

• Jayashree Rajput,
• Srinivas Hotha and
• Madhuri Vangala

Beilstein J. Org. Chem. 2018, 14, 682–687, doi:10.3762/bjoc.14.56

• their operationally simple, safe and neutral reaction conditions, had widely contributed to the development of new glycosylation methods. Gold(I) and gold(III) complexes are usually alkynophilic [2], carbophilic and oxophilic because of their affinity towards the alkynes’ and C–O π systems [3][4][5][6

Addition of dithi(ol)anylium tetrafluoroborates to α,β-unsaturated ketones

• Yu-Chieh Huang,
• An Nguyen,
• Simone Gräßle,
• Sylvia Vanderheiden,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2018, 14, 515–522, doi:10.3762/bjoc.14.37

• procedure for the synthesis of diene dithioacetals. A similar reaction using α-carbonyl substituted ketene dithioacetals for an addition to alkynes under iron catalysis was shown by Liu et al. before and was used for the synthesis of δ-lactams and lactones by 6-endo annulation [35]. Our approach reveals

Continuous multistep synthesis of 2-(azidomethyl)oxazoles

• Thaís A. Rossa,
• Nícolas S. Suveges,
• Marcus M. Sá,
• David Cantillo and
• C. Oliver Kappe

Beilstein J. Org. Chem. 2018, 14, 506–514, doi:10.3762/bjoc.14.36

• 1,4-disubstituted triazoles 8 through click reaction between 2-azidomethyl-4,5-diaryloxazoles and alkynes in the presence of a copper(I) catalyst (Scheme 2). The authors were able to synthesize an array of small-molecule peptidomimetics that inhibited Porphyromonas gingivalis biofilm formation [34

One-pot preparation of 4-aryl-3-bromocoumarins from 4-aryl-2-propynoic acids with diaryliodonium salts, TBAB, and Na₂S₂O₈

• Teppei Sasaki,
• Katsuhiko Moriyama and
• Hideo Togo

Beilstein J. Org. Chem. 2018, 14, 345–353, doi:10.3762/bjoc.14.22

• -vinylphenols at 110 °C [19], the FeCl3-catalyzed areneselenyl-cyclization of aryl 2-alkynoates with ArSeSeAr at rt [20], and the Rh-catalyzed annulation of arylthiocarbamates with alkynes/AgOTf/Cu(OAc)2 at 120 °C [21]. As examples of the transition-metal-free construction of the coumarin skeleton, the Brønsted

Fluorogenic PNA probes

• Tirayut Vilaivan

Beilstein J. Org. Chem. 2018, 14, 253–281, doi:10.3762/bjoc.14.17

• uracils have also been extensively studied as fluorescent nucleobases in the context of aegPNA. Modifications have invariably been made at the 5-position of uracil, which could be functionalized by various aromatics or alkynes via palladium-catalyzed cross couplings of the corresponding iodouridine