Fluorohydration of alkynes via I(I)/I(III) catalysis

• Jessica Neufeld,
• Constantin G. Daniliuc and
• Ryan Gilmour

Beilstein J. Org. Chem. 2020, 16, 1627–1635, doi:10.3762/bjoc.16.135

• transformation [53]. Results and Discussion To explore the feasibility of generating α-fluoroketones from terminal alkynes via I(I)/I(III) catalysis, 4-pentynyl benzoate (1) was selected as the substrate for optimisation studies (Table 1). The inexpensive, commercially available p-TolI was used as an

An overview on disulfide-catalyzed and -cocatalyzed photoreactions

• Yeersen Patehebieke

Beilstein J. Org. Chem. 2020, 16, 1418–1435, doi:10.3762/bjoc.16.118

• groups that contain heteroatoms. Ogawa and co-workers reported a class of efficient diboration reactions. Under light irradiation, disulfide was used as the photocatalyst to facilitate the addition of bis(pinacolato)diboron (B2pin2) to terminal alkynes [19], and the corresponding diboryl alkenes were

Copper-based fluorinated reagents for the synthesis of CF₂R-containing molecules (R ≠ F)

• Louise Ruyet and
• Tatiana Besset

Beilstein J. Org. Chem. 2020, 16, 1051–1065, doi:10.3762/bjoc.16.92

• functionalization of alkyl bromides, alkyl mesylates, aryldiazonium salts [43] as well as electron-rich arenes [44] (Scheme 4). In 2015, the group of Qing investigated the oxidative difluoromethylation reaction of terminal alkynes with TMSCF2H via a copper-mediated reaction [45]. Using a stoichiometric amount of

• CuI, in the presence of t-BuOK and 9,10-phenanthraquinone, the functionalization of a panel of (hetero)aromatic and aliphatic terminal alkynes was achieved (Scheme 5). A good functional group tolerance was observed as alkynes bearing a cyano, ester, bromo or amino group among others were suitable

• substrates. Based on 19F NMR studies, the authors suggested the following mechanism: first the in situ generation of a CuCF2H complex from TMSCF2H in equilibrium with the corresponding cuprate (Cu(CF2H)2−) occurred followed by the reaction with terminal alkynes under basic conditions. The resulting

Recent applications of porphyrins as photocatalysts in organic synthesis: batch and continuous flow approaches

• Rodrigo Costa e Silva,
• Luely Oliveira da Silva,
• Aloisio de Andrade Bartolomeu,
• Timothy John Brocksom and
• Kleber Thiago de Oliveira

Beilstein J. Org. Chem. 2020, 16, 917–955, doi:10.3762/bjoc.16.83

• hydration of terminal alkynes to ketones can be photocatalyzed by rhodium(III) tetrakis(p-sulfonylphenyl)porphyrin (RhIIITSPP) [37]. The coupling between RhIII(TSPP) and terminal alkynes produced the β-carbonylalkylrhodium porphyrin as a photoactive intermediate, whose irradiation produced the PhCOCH2

• tetrahydroquinolines by reductive quenching. Selenylation and thiolation of anilines. NiTPP as photoredox catalyst in oxidative and reductive quenching, in comparison with other photocatalysts. C–O bond cleavage of 1-phenylethanol using a cobalt porphyrin (CoTMPP) under visible light. Hydration of terminal alkynes by

Copper-catalyzed O-alkenylation of phosphonates

• Nuria Vázquez-Galiñanes,
• Mariña Andón-Rodríguez,
• Patricia Gómez-Roibás and
• Martín Fañanás-Mastral

Beilstein J. Org. Chem. 2020, 16, 611–615, doi:10.3762/bjoc.16.56

• counterparts has received less attention. Current methodologies for the synthesis of acyclic mixed enol phosphonates include the Perkow-type reaction between phosphonites and α-halocarbonyl compounds [11], the mercury-catalyzed addition of phosphonic acid monoesters to terminal alkynes [12][13] and multistep

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

• in “click” reactions of organic halides, terminal alkynes, and sodium azide. High yields of various triazole products were obtained when using 10 mg of the catalyst 78 in water at reflux for 30 min (Scheme 15). Moreover, this synergistic dual catalyst was also investigated in the stepwise generation

• heterogeneous nanocatalyst in “click” reactions for the multicomponent synthesis of triazole products in water with ultrasound irradiation and 0.017 mol % catalyst loading. As such, a series of aryl/alkyl-substituted oxiranes was treated with sodium azide and nonactivated terminal alkynes, giving 1,2,3-triazole

• to be highly active in [3 + 2] cycloaddition reactions of halides, nonactivated terminal alkynes, and sodium azide (Scheme 21). Copper(I) ions were attached to the surface of carbon graphene as outlined in Scheme 21. Therein, GO was generated by Hummer’s method, and ascorbic acid was used to produce

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

•  1, entry 4). We will discuss the proposed reaction mechanism later in the text, but the formation of 3a-I via ATRA could be important for the alkynylation reaction. Generally, the Sonogashira coupling requires both a Pd catalyst and a Cu co-catalyst [2][3][4]. However, couplings with terminal

• alkynes can be carried out in the absence of the Pd catalyst [23][24][25][26][27][28][29][30][31][32]; this is the so-called Castro–Stephens reaction [33]. The effect of the base was very important for producing the main product 3a (Table 1, entries 5–8). If the reaction was performed in the presence of a

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

• arylcopper(I) species was the key intermediate. Terminal alkynes were also investigated under similar reaction conditions (Scheme 13) [37]. Aromatic and π-activated aliphatic substrates led to the desired products in moderate to very good yields. Moreover, vinyl sulfone derivatives were formed when the

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

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

• room temperature. Previous work by our group has shown that terminal alkynes on keto scaffolds undergo iodine-mediated hydration to form 1,4-diketo products 2 (Scheme 1) [15]. At that time, our studies revealed that a keto group must be present in the substrate, as the hydration requires neighboring

• spectrum for α-iodo intermediate 9 in CD3CN in the range of 0.90–5.00 ppm (for 1H NMR signals) and −1.0–77.0 ppm (for 13C NMR signals), respectively. Proposed mechanism for the iodine-mediated hydration of terminal alkynes 1 [15]. Possible outcomes of the iodine-mediated hydration of asymmetric, internal

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

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

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

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

• domino reaction of aldehydes 1, 2-aminopyridines (2-APs) 3 and terminal alkynes 2, catalyzed by CuI and co-catalyzed by the NaHSO4·SiO2 system (Scheme 1). The reaction performed with CuI alone gave a moderate yield of the product (only 45%) whereas NaHSO4·SiO2 alone was unable to complete the reaction

• reaction to the product of 4-bromo-substituted nitrostyrylisoxazole 48a (Scheme 18). The attractive feature was successful substitution of the bromo atom with terminal alkynes. Different alkynes applied gave a good yield of up to 81%. This reaction provided a direct and efficient method to produce highly

• coupling reaction for the synthesis of 2-triazolylimidazo[1,2-a]pyridine 74 (Scheme 26) [31]. The reaction involved the use of copper oxide as a catalyst and sodium ascorbate as a reducing agent using triazolyl aldehyde 73, amidine 3 and terminal alkynes 2 as reaction substrates at 70 °C (Scheme 26). Here

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

• 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

• 106. Oxindoles The simplest protocol for the multicomponent assembly of oxindole heterocycles is the palladium-catalysed reaction involving carbon monoxide, in addition to terminal alkynes, arylboronic acids and alkyl iodides, which has been applied to the preparation of fluorinated 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

• -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

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

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

• (Table 1, entries 12–14). With the optimized reaction conditions in hand, the scope of the terminal alkynes was screened and the results are depicted in Scheme 2. First, the reactivity of various substituted terminal arylalkynes was examined. Only 1,4-regioisomeric products were formed with good to

• additive-free CuAAC reaction for the synthesis of 1,4-disubstituted 1,2,3-triazoles directly from a variety of readily accessible substrates such as alkyl diacyl peroxides, azidotrimethylsilane, and terminal alkynes. The alkyl carboxylic acids are for the first time being used as the alkyl azide precursors

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

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

• . The hydroarylation reaction further extended to pyrroles for selective monoalkenylation using [Cp*Co(CH3CN)3](SbF6)2 as the catalyst [55]. In contrast, branched-selective hydroarylation of terminal alkynes was achieved by Li et al. The addition of arenes 7 to propargyl alcohols, protected propargyl

• limited to terminal alkynes. Additionally, they applied this methodology to design a mitochondria-targeted imaging dye from electron-withdrawing formyl-substituted indoles and alkynes. Later, Maji’s group reported an N-tert-butyl amide-directed mono- and di-alkenylation reactions using a cobalt catalyst

• )-catalyzed hydroarylation of terminal alkynes with arenes. Co(III)-catalyzed hydroarylation of alkynes with amides. Co(III)-catalyzed C–H alkenylation of arenes. Co-catalyzed alkylation of substituted benzamides with alkenes. Co-catalyzed switchable hydroarylation of styrenes with 2-aryl pyridines. Co

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

•  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

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

• –I motif (Scheme 22) [62]. Hence aryl- and alkyl-substituted terminal alkynes can be coupled via a Sonogashira reaction when PPh3 is used as ligand, while the use of diphenylphosphinoferrocenyl ligand (dppf) allows the Heck-type coupling of acrylates, vinyl ketones and electron-poor styrene

[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

• irradiation to give only 29% of dimethyl 1,3-diphenylpyrazole-4,5-dicarboxylate while in a wetted-wall photo reactor (Normag) the yield is increased up to 84% (at 17 °C in DCM). Thermal reaction of sydnones with terminal alkynes As early as in his first work [1] dealing with sydnone–alkyne cycloaddition

• with alkyl propiolates (cf. Table 4, entries 6, 7, 23–29, 33, 34, 50–55, 58, 118, 141) and acylalkynes (Table 4, entry 142). Other terminal alkynes, for which the calculated lower HOMO–LUMO energy gaps correspond to the type III mechanism (especially phenylacetylenes, alkylacetylenes

• °C) can contribute to a substantial drop of selectivity. It is also known that some sydnones start to decompose at temperatures exceeding 180 °C [74] which can cause lowering of the pyrazole yield. From a synthetic point of view, the cycloaddition with terminal alkynes represents a very good strategy

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

Progress in copper-catalyzed trifluoromethylation

• Guan-bao Li,
• Chao Zhang,
• Chun Song and
• Yu-dao Ma

Beilstein J. Org. Chem. 2018, 14, 155–181, doi:10.3762/bjoc.14.11

• Trifluoromethylated acetylenes were widely used in medicinal, agrochemical, and material science. In 2010, Qing and coworkers [60] firstly reported a copper-mediated trifluoromethylation of terminal alkynes using TMSCF3 as a trifluoromethyl source. (Scheme 39). At the beginning of the experiment, undesired diyne

• same group [61] developed an improved procedure for the efficient copper-mediated trifluoromethylation of terminal alkynes (Scheme 40). This reaction was conducted at room temperature with a smaller amount of TMSCF3. However, the above-mentioned reaction still required stoichiometric amounts of copper

• TMSCF3 (2 equiv) to the mixture afforded CuCF3. And both terminal alkynes and the rest of TMSCF3 were added to the reaction mixture slowly using a syringe pump. Various arylalkynes bearing electron-donating or -withdrawing groups were converted to the desirable products in good to high yields (Scheme 41