Photocatalytic formation of carbon–sulfur bonds

• Alexander Wimmer and
• Burkhard König

Beilstein J. Org. Chem. 2018, 14, 54–83, doi:10.3762/bjoc.14.4

• ]. The thiyl radical was generated as reactive key intermediate from a variety of thiols by photooxidation using [Ru(bpz)3](PF6)2. Aliphatic and aromatic thiols react with aliphatic and aromatic alkenes and alkynes in high to excellent yields to the anti-Markovnikov addition adducts. However, an excess

• coupling of thiols with alkynes gave 1,2-dithioether. Later that year, Yadav and co-workers reported a new photoredox-catalyzed method for the preparation of β-ketosulfoxides (Scheme 6) [36]. The reaction proceeds again via a radical thiol–ene pathway, but oxygen plays a key role in this reaction. The

• conditions were not suitable for aliphatic alkynes as they do not undergo oxidative addition with the [NiI] sulfide complex. Miyake and co-workers described a very different approach for the C–S cross-coupling between aryl thiols and aryl halides (Scheme 24) [59]. In a mixture with caesium carbonate as a

Recent applications of click chemistry for the functionalization of gold nanoparticles and their conversion to glyco-gold nanoparticles

• Vivek Poonthiyil,
• Thisbe K. Lindhorst,
• Vladimir B. Golovko and
• Antony J. Fairbanks

Beilstein J. Org. Chem. 2018, 14, 11–24, doi:10.3762/bjoc.14.2

• substitution by reaction with NaN3 then resulted in AuNPs with mixed monolayers containing 52% N3- and 44% CH3-terminated alkanethiol ligands. A series of alkynes were synthesised, including derivatives of nitrobenzene (1), ferrocene (2), anthracene (3), pyrene (4), aniline (5), and polyethylene glycol (6) all

• ]. Following the work of Fleming et al., several groups have investigated the use of different conditions to try and increase the efficiency of the NCAAC on the surface of AuNPs. Limapichat et al. used other electron deficient alkynes (7–11) as substrates for the NCAAC, and observed that 75% of the azides on

• the AuNP surface underwent cycloaddition in 16 hours (Scheme 3) [52]. Ismaili et al. carried out the NCAAC with a number of terminal-acyl alkynes (1–5 and 12–17) under hyperbaric conditions (11000 atm pressure), and observed 80% or higher conversions within 15 to 24 hours (Scheme 4) [48]. AuNP surface

Acid-catalyzed ring-opening reactions of a cyclopropanated 3-aza-2-oxabicyclo[2.2.1]hept-5-ene with alcohols

• Katrina Tait,
• Alysia Horvath,
• Nicolas Blanchard and
• William Tam

Beilstein J. Org. Chem. 2017, 13, 2888–2894, doi:10.3762/bjoc.13.281

• includes the reduction to form alkane 8 [3], oxidative cleavage of the C=C bond to form 9 [4], ring-opening metathesis to form functionalized alkenes 10 and 11 [4], dihydroxylation to form diol 12 [5], ruthenium-catalyzed [2 + 2] cycloaddition with unsymmetrical alkynes to form regioisomers 13 and 14 [6

Synthetic mRNA capping

• Fabian Muttach,
• Nils Muthmann and
• Andrea Rentmeister

Beilstein J. Org. Chem. 2017, 13, 2819–2832, doi:10.3762/bjoc.13.274

• N7-position or a combination of both. (A) Functional moieties such as alkynes and azides can be enzymatically transferred to the N2-position using GlaTgs-Var. or N7-position using Ecm1 [88][89][90][91]. While transfer efficiencies decrease with increasing sterical demand when using GlaTgs-Var

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation and chlorination. Part 2: Use of CF₃SO₂Cl

• Hélène Chachignon,
• Hélène Guyon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2800–2818, doi:10.3762/bjoc.13.273

• introduction of the CF3 moiety and a Cl atom onto alkenes or alkynes. Kamigata’s group was the first to report such type of transformation in 1989 [23][24]. In the presence of RuCl2(PPh3)2 at 120 °C, a variety of styrene derivatives as well as cyclic and acyclic alkenes were converted into their

• -nitroalkenes because of the lower stability of the radical intermediate 38 generated. The variation of stability of this species also explained the higher yields obtained with β-nitrostyrene derivatives substituted by electron-withdrawing groups. Trifluoromethylation of alkynes: o-Azidoarylalkynes also proved

• to be interesting substrates for cascade reactions, allowing to obtain the 3-trifluoromethylated indole 39 albeit in low yield (Scheme 31) [40]. Chlorotrifluoromethylation of alkynes: In the continuity of their work on alkenes, Jung and Han got interested in the chlorotrifluoromethylation of internal

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• , pyrimidine, thiophene, etc. the Maiti group reported an alternative approach toward α-trifluoromethyl ketones starting from (hetero)arylacetylenes 7 and also aliphatic terminal alkynes 8 (Scheme 5) [24]. The trifluoromethyl radical was generated from CF3SO2Na as indicated earlier, oxygen from air was the

• iodotrifluoromethylation was previously achieved by means of gaseous CF3I until Liu and co-workers reported the convenient use of CF3SO2Na and iodide pentoxide, I2O5, in combination for the iodotrifluoromethylation of alkenes and alkynes (see later in the text) [42]. After an optimisation with 4-chlorostyrene, the

• although the increase of the steric hindrance caused a decrease in yields. On the other hand, the yields obtained with electron-poor potassium organotrifluoroborates were lower. In the same paper, the preparation of trifluoromethyl-substituted alkynes and alkenes from alkynyl- and alkenyltrifluoroborates

Preparation and isolation of isobenzofuran

• Morten K. Peters and
• Rainer Herges

Beilstein J. Org. Chem. 2017, 13, 2659–2662, doi:10.3762/bjoc.13.263

• + 8] and [4 + 6] additions [7][8][9][10]. Highly strained alkenes and alkynes have been trapped with isobenzofurans. 1,3-Diphenylisobenzofuran is the preferred trapping reagent for singlet oxygen and is used to quantify the generation of 1O2 in photodynamic therapy [4][11]. The most important

Electrophilic trifluoromethylselenolation of terminal alkynes with Se-(trifluoromethyl) 4-methylbenzenesulfonoselenoate

• Clément Ghiazza,
• Anis Tlili and
• Thierry Billard

Beilstein J. Org. Chem. 2017, 13, 2626–2630, doi:10.3762/bjoc.13.260

• the nucleophilic addition of Se-(trifluoromethyl) 4-methylbenzenesulfonoselenoate, a stable and easy-to-handle reagent, to alkynes is described. This reaction provides trifluoromethylselenylated vinyl sulfones with good results and the method was extended also to higher fluorinated homologs. The

• obtained compounds are valuable building blocks for further syntheses of fluoroalkylselenolated molecules. Keywords: alkynes; nucleophilic addition; perfluoroalkylselenolation; Se-(trifluoromethyl) 4-methylbenzenesulfonoselenoate; trifluoromethylselenolation; Introduction Over the last decades

• chlorine substituent opens the way to post-functionalization and thereby to syntheses of more elaborated compounds. However, the similar reaction with alkynes has failed and only a complex mixture was observed which is basically due to the high reactivity of CF3SeCl. To overcome this issue, we have

Palladium-catalyzed Heck-type reaction of secondary trifluoromethylated alkyl bromides

• Tao Fan,
• Wei-Dong Meng and
• Xingang Zhang

Beilstein J. Org. Chem. 2017, 13, 2610–2616, doi:10.3762/bjoc.13.258

• , developing efficient methods for the synthesis of such valuable structures has received less attention [10][11][12][13][14][15]. Commonly, fluoroalkylated alkenes can be prepared through fluoroalkyl radical addition of alkynes via an atom transfer pathway [16][17] or cross-coupling of alkenyl halides with

Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics

• Matthias Wünsch,
• David Schröder,
• Tanja Fröhr,
• Lisa Teichmann,
• Sebastian Hedwig,
• Nils Janson,
• Clara Belu,
• Jasmin Simon,
• Shari Heidemeyer,
• Philipp Holtkamp,
• Jens Rudlof,
• Lennard Klemme,
• Alessa Hinzmann,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2017, 13, 2428–2441, doi:10.3762/bjoc.13.240

• groups is accessible for the use as precursors of peptidomimetics. Keywords: amino acid analogous side chains; desilylation; Ellman’s chiral sulfinamide; intramolecular Huisgen reaction; peptidomimetics; propargylamines; rearrangement to α,β-unsaturated imines; Introduction Terminal alkynes display an

• Discussion Synthesis of propargylamines, general strategies To avoid side reactions of the terminal alkyne in approach I, internal alkynes were applied. Benzoate substituents were chosen as they are comparatively inert and convertible to peptidomimetics. At first, iodobenzene derivatives with an ester moiety

• for the desilylation of 6i to afford the free alkyne 7i in 66% yield. N-Sulfinyl propargylamines 6k and 6j, with perfluorinated side chains, required even milder desilylation conditions. KF in the presence of 18-crown-6 (GP-6) provided the free alkynes 7k and 7j in 29% and 52% yield, respectively

Synthesis, effect of substituents on the regiochemistry and equilibrium studies of tetrazolo[1,5-a]pyrimidine/2-azidopyrimidines

• Elisandra Scapin,
• Paulo R. S. Salbego,
• Caroline R. Bender,
• Alexandre R. Meyer,
• Anderson B. Pagliari,
• Tainára Orlando,
• Geórgia C. Zimmer,
• Clarissa P. Frizzo,
• Helio G. Bonacorso,
• Nilo Zanatta and
• Marcos A. P. Martins

Beilstein J. Org. Chem. 2017, 13, 2396–2407, doi:10.3762/bjoc.13.237

• reactions were planned between phenylacetylene and compounds 6a–c. The 1,2,3-triazole synthesis from the 1,3-dipolar cycloaddition reaction between 6a–c and terminal alkynes catalyzed by copper salts (CuAAC) [41][42][43] confirms that the reaction passes through an azide intermediate. In addition to mild

Is the tungsten(IV) complex (NEt₄)₂[WO(mnt)₂] a functional analogue of acetylene hydratase?

• Matthias Schreyer and
• Lukas Hintermann

Beilstein J. Org. Chem. 2017, 13, 2332–2339, doi:10.3762/bjoc.13.230

• acetylene. A critical assessment of, and a possible explanation for the earlier reported results are offered. The title question is answered with "no". Keywords: acetylene hydratase; alkynes; catalytic hydration; enzyme models; tungsten complexes; Introduction In 1985, the enzyme acetylene hydratase

• hydration (Scheme 2a), whereas alkynol cycloisomerization proceeds via rearrangement to a tungsten vinylidene complex and addition of the alcohol hydroxy group to the vinylidene α-carbon [18]. The vinylidene mechanism is related to that of ruthenium-catalyzed anti-Markovnikov hydration of terminal alkynes

• alkynes have not been reported [13] and substrate scope tests for acetylene hydratase have so far failed with higher alkynes [6]. We wished to test the potential activity and regioselectivity of complex 1 for hydration of higher terminal alkynes, as an extension to our studies of ruthenium-catalyzed anti

Synthesis of substituted Z-styrenes by Hiyama-type coupling of oxasilacycloalkenes: application to the synthesis of a 1-benzoxocane

• James R. Vyvyan,
• Courtney A. Engles,
• Scott L. Bray,
• Erik D. Wold,
• Christopher L. Porter and
• Mikhail O. Konev

Beilstein J. Org. Chem. 2017, 13, 2122–2127, doi:10.3762/bjoc.13.209

• ] and oxasilacycloalkenes (cyclic siloxanes, cf. Figure 1) [6][7][8] is an excellent method to prepare stereodefined alkenes. The cyclic siloxanes can be prepared in a number of ways: hydrosilylation of alkynes [11][12][13], semihydrogenation of silyl alkynes [14], ring-closing metathesis (RCM) [15][16

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• palladium salts (Pd(OAc)2 or Pd(PPh3)4) and DABCO (1,4-diazabicyclo[2.2.2]octane) various acetylenes and aryl halides were coupled to obtain the Sonogashira coupling products in excellent yields (near quantitative, Scheme 10a). The reactions were reported for aliphatic alkynes as well. In Scheme 10b, an

• example of a double Sonogashira reaction is shown [60]. Oxidative cross-dehydrogenative coupling Copper-catalyzed mechanochemical oxidative cross-dehydrogenative coupling (CDC) reactions [61][62][63][64][65][66] of tetrahydroisoquinolines with alkynes and indoles was reported by Su and co-workers (Scheme

•  11) using 2,3-dichloro-5,6-dicyanoquinone (DDQ) as an efficient oxidant [67]. Su and co-workers have also reported an asymmetric version of the CDC reaction between terminal alkynes and sp3 C–H bonds under high speed ball milling conditions [68]. Several optically active 1-alkynyl

Synthesis of benzothiophene and indole derivatives through metal-free propargyl–allene rearrangement and allyl migration

• Jinzhong Yao,
• Yajie Xie,
• Lianpeng Zhang,
• Yujin Li and
• Hongwei Zhou

Beilstein J. Org. Chem. 2017, 13, 1866–1870, doi:10.3762/bjoc.13.181

• heterocycles are not well-documented [30][31]. Recently, our group explored the utilization of β-sulfonium carbanions for the preparation of thiophene derivatives [19]. Alkynes were treated with acyl chloride under Sonogashira reaction conditions and the expected β-sulfonium carbanions were obtained in a one

• °C for 12 h. With the optimized reaction conditions in hand, we turned our attention to study the reaction scope and limitations of this reaction; the results are shown in Figure 2. A series of alkynes substituted with an electron-withdrawing group participated in this reaction smoothly to give the

Iodoarene-catalyzed cyclizations of N-propargylamides and β-amidoketones: synthesis of 2-oxazolines

• Somaia Kamouka and
• Wesley J. Moran

Beilstein J. Org. Chem. 2017, 13, 1823–1827, doi:10.3762/bjoc.13.177

• -phenylpentanoic acid (3, Scheme 1a–c) [14]. These three cyclizations exemplify three different proposed reaction pathways, i.e., iodine(III) activation of alkenes, alkynes and ketones. These cyclizations can be rendered enantioselective by the generation of non-racemic chiral iodine(III) species from chiral

• iodoarenes [15][16][17]. We wished to develop this cyclization methodology further and investigate the cyclization of the amide functional group on to alkynes and methylene groups adjacent to ketones in analogy to our previous work (Scheme 1d). This would provide two complementary routes to substituted 2

Development of a method for the synthesis of 2,4,5-trisubstituted oxazoles composed of carboxylic acid, amino acid, and boronic acid

• Kohei Yamada,
• Naoto Kamimura and
• Munetaka Kunishima

Beilstein J. Org. Chem. 2017, 13, 1478–1485, doi:10.3762/bjoc.13.146

• materials, such as α-haloketones and primary amides [8], alkynes and nitriles [9], amines and α,β-unsaturated carbonyl compounds [10], etc. [11] have been reported. However, these reactions are often conducted under harsh reaction conditions and multistep syntheses of the starting materials are needed. ii

Photocatalyzed synthesis of isochromanones and isobenzofuranones under batch and flow conditions

• Manuel Anselmo,
• Lisa Moni,
• Hossny Ismail,
• Davide Comoretto,
• Renata Riva and
• Andrea Basso

Beilstein J. Org. Chem. 2017, 13, 1456–1462, doi:10.3762/bjoc.13.143

• intramolecular fashion, with the nucleophilic group appropriately displayed by one of the reagents. By inspection of the literature data, we were surprised to find only one example where benzothiophenes were obtained by reacting o-methylthioarenediazonium salts with alkynes under green light irradiation [4]. We

Synthesis of novel 13α-estrone derivatives by Sonogashira coupling as potential 17β-HSD1 inhibitors

• Ildikó Bacsa,
• Rebeka Jójárt,
• János Wölfling,
• Gyula Schneider,
• Bianka Edina Herman,
• Mihály Szécsi and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2017, 13, 1303–1309, doi:10.3762/bjoc.13.126

• -catalyzed C–C coupling reactions. Some Sonogashira couplings on estrane, but not on the 13α-estrane core have been performed at C-2, -3, -11, -16 and -17. To the best of our knowledge, 4-coupled regioisomers have not been synthesized to date [19]. Couplings of steroidal alkynes with small molecular halides

• are already described, and reactions of steroidal halides or triflates with small molecular alkynes also exist [20]. Certain phenethynyl estrone derivatives described in the literature possess substantial biological activities. Möller et al. performed the couplings of 2-iodoestrone-3-acetate with

• semihydrogenation of internal alkynes may be achieved by two main catalytic methods: with molecular hydrogen using Lindlar’s catalyst [25][26] or by transfer hydrogenation with hydrogen donors [27][28]. Additionally, alkynes undergo reduction with diimide to produce cis-alkenes [29]. Li et al. carried out the

Total synthesis of elansolids B1 and B2

• Liang-Liang Wang and
• Andreas Kirschning

Beilstein J. Org. Chem. 2017, 13, 1280–1287, doi:10.3762/bjoc.13.124

• first synthesis of elansolid B2 (3). The key for improvement was to abandon the two Sonogashira reactions along with the syn-reductions of the two alkynes. Instead, we planned to utilize the Suzuki–Miyaura and the Stille reactions and two Z-configured vinyl iodides to assemble the (Z,E,Z)-triene unit

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• conditions were feasible for the synthesis of glycosyl azides which are highly useful precursors for N-linked glycans [95] or Cu-catalyzed cycloadditions with alkynes (as shown above) [85]. By using tetrabutylammonium chloride and an amine base the highly reactive chlorinated intermediate forms that can be

Synthesis of alkynyl-substituted camphor derivatives and their use in the preparation of paclitaxel-related compounds

• M. Fernanda N. N. Carvalho,
• Rudolf Herrmann and
• Gabriele Wagner

Beilstein J. Org. Chem. 2017, 13, 1230–1238, doi:10.3762/bjoc.13.122

• reduction, and ring enlargement. One isomeric dialkyne additionally allows for the isolation of a pentacyclic compound lacking the ring enlargement step, which we have proposed as a potential intermediate in the catalytic cycle. Keywords: alkynes; camphor derivatives; catalysis; cycloisomerisation

• all atoms of the starting material are found in the product, and thus fulfil an important requirement of “green chemistry” [31]. However, a different Pt(II)-catalysed reaction cascade was observed for 4c, with adamantyl groups at the alkynes. Here, the annulation step is followed by a C–H bond

• formed propargyl group is isomerized to an allene moiety, obviously due to the excess of the strongly basic lithium salt [35]. This unexpected monosubstitution remains unexplained and is not applicable as basis for a general selective synthesis of monoalkynylcamphor derivatives. Alkynes can also be

Transition-metal-free one-pot synthesis of alkynyl selenides from terminal alkynes under aerobic and sustainable conditions

• Adrián A. Heredia and
• Alicia B. Peñéñory

Beilstein J. Org. Chem. 2017, 13, 910–918, doi:10.3762/bjoc.13.92

• halides. Successive reaction with terminal alkynes in the presence of t-BuOK affords the corresponding alkyl alkynyl selenide in moderate to good yields. Finally, this methodology allowed the synthesis of 2-alkylselanyl-substituted benzofuran and indole derivatives starting from convenient 2-substituted

• acetylenes. Keywords: alkynyl selenide; electrophilic cyclization; nucleophilic substitution; potassium selenocyanate; terminal alkynes; Introduction Alkynyl selenides, as many other selenium compounds, have potential anti-oxidant activities, and may play a role in certain diseases such as cancer, heart

• under Cu catalysis [26][27][28][29], from terminal alkynes in the presence of bases and Cu [30][31][32][33], Fe [34][35] or In [36] catalysis, or with t-BuOK without of transition metal [37] have been reported. In general, these methodologies require selenyl halides or diselenides as starting materials

Nucleophilic and electrophilic cyclization of N-alkyne-substituted pyrrole derivatives: Synthesis of pyrrolopyrazinone, pyrrolotriazinone, and pyrrolooxazinone moieties

• Işıl Yenice,
• Sinan Basceken and
• Metin Balci

Beilstein J. Org. Chem. 2017, 13, 825–834, doi:10.3762/bjoc.13.83

• -nitrobenzene with trimethylsilylacetylene under the Sonogashira coupling conditions followed by hydrolysis of the trimethylsilyl groups with K2CO3 resulted in the formation of 10a and 10b [26][27][28]. Fortunately, terminal alkynes can be easily converted into bromoalkynes with N-bromosuccinimide in the

Continuous-flow processes for the catalytic partial hydrogenation reaction of alkynes

• Carmen Moreno-Marrodan,
• Francesca Liguori and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2017, 13, 734–754, doi:10.3762/bjoc.13.73

• Carmen Moreno-Marrodan Francesca Liguori Pierluigi Barbaro Consiglio Nazionale delle Ricerche, Istituto di Chimica dei Composti Organo Metallici, Via Madonna del Piano 10, 50019 Sesto Fiorentino, Firenze, Italy 10.3762/bjoc.13.73 Abstract The catalytic partial hydrogenation of substituted alkynes

• to August 2016 are discussed in terms of reactor design. A comparison with batch and industrial processes is provided whenever possible. Keywords: alkynes; heterogeneous catalysis: hydrogenation; flow; liquid-phase; Introduction The catalytic partial hydrogenation of alkynes to alkenes in the

• liquid phase is a reaction of high relevance to the manufacture of a multitude of fine chemicals [1] including pharmaceutical building blocks, agrochemicals, food additives, flavours and fragrances [2][3]. It is also crucial in the bulk polymer industry to achieve the complete elimination of alkynes and