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

• formation of alkylidenecyclopropanes 58a (86%), 58b (60%) and 58c (84%). It is worth mentioning that despite the use of a strong base (KHMDS) and the acidity of the “vinylic” protons of cyclopropenes which is comparable to that of a terminal alkyne [62], cyclopropenylcarbinyl glycolates devoid of

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

• , terminal alkyne 1 (0.5 mmol), diacyl peroxide 2 (0.75 mmol), TMSN3 (90.4 mg, 0.75 mmol), CuCl (4.9 mg, 0.05 mmol) and CH2Cl2 (2 mL) were added, respectively. The reaction mixture was stirred vigorously for 10 h at 50 °C. Then, the reaction mixture was cooled to room temperature, poured into saturated

Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers

• Christian Schütz and
• Martin Empting

Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241

• , a novel competition assay employing ‘clickable’ active-site-labelling probes was developed. These compounds contain terminal alkyne moieties, which can be exploited for straightforward decoration via copper(I)-catalyzed alkyne–azide cycloaddition (CuAAC), the prototypic click reaction. This

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

• THF or DME was facilitated [49]. The molybdenum 2,4,6-trimethylbenzylidyne complex [MesC≡Mo{OC(CF3)2Me}3] (Figure 1, MoF6) represents the first alkyne metathesis catalyst capable of effective and highly selective terminal alkyne metathesis [49][51][52][53]. Later, a study was conducted to determine

• by a stoichiometric alkyne metathesis reaction of the ditungsten complex [(t-BuO)3W≡W(Ot-Bu)3] with MeC≡Ct-Bu (Scheme 1) [62]. Even though Schrock’s catalyst V was the most established alkyne metathesis catalyst for many years [63][64], it does not promote terminal alkyne metathesis efficiently and

Stereoselective total synthesis and structural revision of the diacetylenic diol natural products strongylodiols H and I

• Pamarthi Gangadhar,
• Sayini Ramakrishna,
• Ponneri Venkateswarlu and
• Pabbaraja Srihari

Beilstein J. Org. Chem. 2018, 14, 2313–2320, doi:10.3762/bjoc.14.206

• lithium(trimethylsilyl)acetylide to get the coupled product 24. The latter compound on further treatment with K2CO3 in MeOH [26] furnished the desilylated propargylic alcohol 19 (Scheme 2). The copper(I)-catalyzed Cadiot–Chodkiewicz [27] cross-coupling reaction between bromoalkyne 18 [28] and terminal

• alkyne 19 provided the corresponding diynes 25 and 25a in a 1:1 ratio. Though we had an option to proceed further with the mixture of 25 and 25a affording both enantiomers that could be separated later, we focused our attention towards the synthesis of the required chiral compound. Thus, the mixture of

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

• of Pd(OAc)2 in THF, and affords the dibenzoalkylidenefluorene 47 in an excellent 88% yield (Scheme 16). Ten years later, Huang, Wen and co-workers have demonstrated that, in the presence of both a terminal alkyne and a boronic acid, various cyclic diaryl-λ3-iodanes undergo a transition-metal

• non-symmetrical diaryl-λ3-iodanes raises the issue of regioselectivity. This strategy has been then extended to the preparation of alkyne-substituted alkylidenefluorenes 53 by replacing the arylboronic acid with a second equivalent of the terminal alkyne and performing the reaction at 35 °C (Scheme 18

• be resubmitted to the cyclization conditions in the presence of a different terminal alkyne, or an activated alkene. The same authors have then showed that the reaction of cyclic diaryl-λ3-iodanes in the presence of internal alkynes and the catalytic system Pd(OAc)2-PCy3 affords functionalized

[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

• mechanism). Copper-catalyzed reaction of sydnones with terminal alkynes A substantial breakthrough in the field of 3-arylsydnone-terminal alkyne cycloaddition was achieved by Taran’s group in 2013 [3]. They developed a regioselective Cu(I)-phenanthroline-catalyzed variant of this reaction (i.e., copper

• ) is observed in most cases when a terminal alkyne was used as a reactant. On the other hand, the recent discovery of Cu(I) catalysis in the sydnone–alkyne cycloaddition (CuSAC) enables regioselective formation of complementary 1,4-disubstituted or 5-halogeno-1,4-disubstituted pyrazoles under very mild

The first Pd-catalyzed Buchwald–Hartwig aminations at C-2 or C-4 in the estrone series

• Ildikó Bacsa,
• Dávid Szemerédi,
• János Wölfling,
• Gyula Schneider,
• Lilla Fekete and
• Erzsébet Mernyák

Beilstein J. Org. Chem. 2018, 14, 998–1003, doi:10.3762/bjoc.14.85

• -estrone 3-methyl ethers are also effective inhibitors [19]. Recently, we carried out the Pd-catalyzed C–C coupling of 2- and 4-iodo-13α-estrones as well as their 3-methyl ethers with p-substituted phenylacetylenes as terminal alkyne partners under microwave irradiation [20]. The regioisomerism markedly

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

• -dibromoalkenes in the presence of acetic acid. The electrolysis conditions in this transformation were optimized in order to avoid or minimize the formation of the terminal alkyne. The latter was obtained as the major product in the absence of a proton donor and its formation could be suppressed when performing

• Supporting Information File 1) and thus the electrolysis was carried out at the second wave potential. 9-Ethyl-3-ethynyl-9H-carbazole (2b) was obtained in 77% yield. Similarly, when starting from 1-(2,2-dibromovinyl)-4-methoxybenzene (1c), the corresponding terminal alkyne 2c was obtained in 62% yield

• solution (Pt cathode) yields selectively 2-ethynylnaphthalene or 2-(bromoethynyl)naphthalene in high yields, depending on the electrolysis conditions. In particular, by simply changing the working potential and the supporting electrolyte, the reaction can be directed towards the synthesis of the terminal

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

• nm) ATT-AuNPs, either using two-phase (water/toluene) [49], or one-phase (MeOH) Brust–Schiffrin methods (BSM) [80] both resulted in the formation of decomposed/aggregated particles. We postulate that perhaps reaction of HAuCl4 with the terminal alkyne [81] of ATT 33 might have interfered with the

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

• cycloaddition, CuAAC and RuAAC), the thiol–yne reaction, Diels–Alder reactions and the Sonogashira cross-coupling. While amino acids with a terminal alkyne in the side chain are well-known, the synthesis of their correlates where the carboxy group is replaced by a terminal alkyne is still tedious. Nevertheless

• from aldehydes. According to approach II, a metallated terminal alkyne is added to an N-sulfinylaldimine. In approach I, the organometallic nucleophile is transferring the amino acid side chain, in approach II, the amino acid side chain comes from the aldehyde incorporated in the imine. Results and

• 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

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

• -workers [9]. Experimentally, the vinylidene mechanism is revealed in the hydration of a terminal alkyne by producing an aldehyde (anti-Markovnikov type addition) as opposed to a methyl ketone (Markovnikov type addition; typical for π-activation mechanisms) [18]. Hydration reactions of 1 involving higher

• key vinylidene intermediate. a) Synthesis of complex (NEt4)2[WO(mnt)2] (1) [29]. b) Attempted catalytic hydration reaction with a terminal alkyne. a) Unexpected isolation of acetone 2,4-dinitrophenylhydrazone (10) from an attempted catalytic hydration of ethyne (acetylene gas) in the presence of 1. b

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

• triazole moiety (Scheme 37a) using benzyl halides, sodium azide and a terminal alkyne via an alumina-supported copper catalyst. Using 10 mol % of Cu/Al2O3, differently substituted phenyl acetylenes and aliphatic alkynes led to 70–96% yield of triazoles [152]. Phenyl boronic acids were also used to

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

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

• iodide 17 after O-acylation, iodination of the terminal alkyne and finally diimide-mediated syn-reduction [11]. Next, DDQ-mediated removal of the PMB protecting group yielded vinyl iodide 18. The synthesis of both fragments 13 and 18 set the stage for the Suzuki–Miyaura coupling which delivered the

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

• ], or oxidised to oxaziridines used as efficient chiral oxidising reagents [13][17][18][19]. The reaction of the oxoimide 3 with two equivalents of the lithium salt of a terminal alkyne leads to compounds 4 where two alkynyl substituents, a sulfonamide and a hydroxy group are found in vicinal positions

• ) reaction of such mixed substituted compounds. Results and Discussion For the preparation of the diynes 4, a 2:1 ratio (or slightly larger for complete reaction) of the lithium salt of a terminal alkyne and of the oxoimide 3 is applied. The ratio should, however, not be increased too much. For instance

An eco-compatible strategy for the diversity-oriented synthesis of macrocycles exploiting carbohydrate-derived building blocks

• Sushil K. Maurya and
• Rohit Rana

Beilstein J. Org. Chem. 2017, 13, 1106–1118, doi:10.3762/bjoc.13.110

• ratio of integration of the terminal alkyne proton in the propargyl building block and the characteristic triazole–alkene proton in the cyclo-adducts. The click reaction proceeds under various conditions with a plenty of sources of Cu(I) [19]. We have selected copper iodide (CuI) as Cu(I) source for the

A strategic approach to [6,6]-bicyclic lactones: application towards the CD fragment of DHβE

• Tue Heesgaard Jepsen,
• Emil Glibstrup,
• François Crestey,
• Anders A. Jensen and
• Jesper Langgaard Kristensen

Beilstein J. Org. Chem. 2017, 13, 988–994, doi:10.3762/bjoc.13.98

• terminal alkyne with n-BuLi and subsequent quenching with ethyl chloroformate provided the desired ester 3 in 43% yield. The subsequent stereoselective addition of lithium iodide [17] provided the Z-vinyl iodide 4 in 76% yield with no trace of the undesired E-isomer. After extensive screening (see

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

• % yield implies that the deprotonation of 6a is faster than the elimination from 4a. Since 6a is an intermediate compound of the reaction, we optimized the reaction conditions using terminal alkyne 6a as the substrate instead of styryl bromide (4a), following a three-step one-pot procedure (see Scheme 2

• ). Alkyne 6g, having a styryl group afforded compound 5n in 53% yield (as a mixture of E and Z isomers in a 5:1 ratio, respectively; Table 4, entry 7) and the aliphatic terminal alkyne 6h failed to react under the selected conditions (Table 4, entry 8). In order to apply the present methodology to the one

Effect of the ortho-hydroxy group of salicylaldehyde in the A³ coupling reaction: A metal-catalyst-free synthesis of propargylamine

• Sujit Ghosh,
• Kinkar Biswas,
• Suchandra Bhattacharya,
• Pranab Ghosh and
• Basudeb Basu

Beilstein J. Org. Chem. 2017, 13, 552–557, doi:10.3762/bjoc.13.53

• salicylaldehyde has been explored, which presumably activates the Csp–H bond of the terminal alkyne leading to the formation of propargylamines in good to excellent yields, thus negating the function of the metal catalyst. This observation is hitherto unknown, tested for a variety of salicylaldehyde, amine and

• acetylene, established as a general protocol, and is believed to be of interest for synthetic chemists from green chemistry. Keywords: A3 coupling; metal-catalyst-free; propargylamine; salicylaldehyde; terminal alkyne; Introduction Propargylamines are important synthetic intermediates for the preparation

• ], 3-aminobenzofurans [12], aminoindolizines [13], 2-aminoimidazoles [14], oxazolidinones [15], and quinolines [16] (Scheme 1). Because of diverse applications of propargylamine, several methods are developed among which the three–component reaction of aldehyde, amine and terminal alkyne, commonly

Investigation of the action of poly(ADP-ribose)-synthesising enzymes on NAD⁺ analogues

• Sarah Wallrodt,
• Edward L. Simpson and
• Andreas Marx

Beilstein J. Org. Chem. 2017, 13, 495–501, doi:10.3762/bjoc.13.49

• introducing small, terminal alkyne functionalities at common sites of the adenine base. Upon successful incorporation into PAR, these alkynes serve as handles for copper(I) catalysed azide–alkyne click reaction (CuAAC) [22] with fluorescent dyes. Terminal alkynes are the smallest possible reporter group that

Chemical probes for competitive profiling of the quorum sensing signal synthase PqsD of Pseudomonas aeruginosa

• Michaela Prothiwa,
• Dávid Szamosvári,
• Sandra Glasmacher and
• Thomas Böttcher

Beilstein J. Org. Chem. 2016, 12, 2784–2792, doi:10.3762/bjoc.12.277

• protein reactive groups, which have been reported to exhibit selectivity for active site cysteines [19] (Supporting Information File 1, Figure S1). Each probe was equipped with a terminal alkyne handle for in-gel analysis by fluorescence tagging via click chemistry with a corresponding rhodamine azide

A versatile route to polythiophenes with functional pendant groups using alkyne chemistry

• Xiao Huang,
• Li Yang,
• Rikard Emanuelsson,
• Jonas Bergquist,
• Maria Strømme,
• Martin Sjödin and
• Adolf Gogoll

Beilstein J. Org. Chem. 2016, 12, 2682–2688, doi:10.3762/bjoc.12.265

• cross-coupling reactions, cycloaddition reactions, radical reactions and reductive addition reactions. A terminal alkyne can also react as nucleophile or serve as synthon for pyrrole rings [24][25]. Thus we here fuse the rich alkyne chemistry to the EDOT backbone, resulting in a novel EDOT derivative

• , these functionalizations require only readily available starting materials. A related concept, i.e., attachment of a terminal alkyne moiety to the polymerizable thiophene derivative ProDOT, an EDOT analogue, and its utilization for “click“ chemistry has been reported [28]. However, this involved an

• ) indicated the attachment of phthalimide to the PEDOT backbone (Supporting Information File 1, Figure S40). Conclusion In conclusion, we have introduced a new functional pyEDOT featuring a terminal alkyne which endows EDOT or PEDOT functionalization with the rich chemistry of alkynes. We exemplify this

Application of Cu(I)-catalyzed azide–alkyne cycloaddition for the design and synthesis of sequence specific probes targeting double-stranded DNA

• Svetlana V. Vasilyeva,
• Vyacheslav V. Filichev and
• Alexandre S. Boutorine

Beilstein J. Org. Chem. 2016, 12, 1348–1360, doi:10.3762/bjoc.12.128

• and its target dsDNA sequence fragment used in our previous work are shown on Figure 5. In addition to the terminal alkyne group, an amine group was introduced into the α-position of the γ-aminobutyric acid linker (Figure 5B). This provides versatility for labelling of MGBs. For example, the terminal

• -TFOs [17] and from fluorescent properties of TINA, which facilitate the electrophoretic analysis of reaction mixtures. Thus, we inserted two TINA moieties into antiparallel TFO according to our previous results. Three TINA-containing TFOs 20–22 possessing 3'-terminal alkyne groups (Figure 11) that

• alkyne can be used for labelling of MGB with a fluorophore using "click chemistry" and the amino group can be used to conjugate the probe to TFO or to another polyamide [15] and vice versa. Synthesis of modified polyamides, containing an azide or alkyne group The following polyamides (11–14, Figure 6

Copper-catalyzed [3 + 2] cycloaddition of (phenylethynyl)di-p-tolylstibane with organic azides

• Mizuki Yamada,
• Mio Matsumura,
• Yuki Uchida,
• Masatoshi Kawahata,
• Yuki Murata,
• Naoki Kakusawa,
• Kentaro Yamaguchi and
• Shuji Yasuike

Beilstein J. Org. Chem. 2016, 12, 1309–1313, doi:10.3762/bjoc.12.123

• fully substituted 1,2,3-triazoles having group 15 (P, Bi) elements as substituents at the C-5 position was recently attempted. Li et al. reported that the cycloaddition of alkynylphosphonate with benzyl azide did not generate 1,2,3-triazolyl-5-phosphonates, but a three-component reaction of a terminal

• alkyne, an organic azide, and an H-phosphate in the presence of CuCl2 (10 mol %) and triethylamine (2 equiv) afforded the desired 1,2,3-triazolyl-5-phosphonates [23]. Fokin et al. carried out the reaction of ethynylbismuthane with organic azides using CuOTf (5 mol %) and isolated 5-bismuthano-1,2,3