Preparation of conjugated dienoates with Bestmann ylide: Towards the synthesis of zampanolide and dactylolide using a facile linchpin approach

• Jingjing Wang,
• Samuel Z. Y. Ting and
• Joanne E. Harvey

Beilstein J. Org. Chem. 2015, 11, 1815–1822, doi:10.3762/bjoc.11.197

• 5b and 5c, respectively. While the reaction of 7b with aldehyde 8 in THF took 11 h to go to completion (62% isolated yield of 5b), the equivalent reaction in toluene required only 5 h (68% yield). Alcohol 7c was used to assess the compatibility of an unprotected, terminal alkyne in this linchpin

Synthesis of alpha-tetrasubstituted triazoles by copper-catalyzed silyl deprotection/azide cycloaddition

• Zachary L. Palchak,
• Paula T. Nguyen and
• Catharine H. Larsen

Beilstein J. Org. Chem. 2015, 11, 1425–1433, doi:10.3762/bjoc.11.154

• introduce a wide variety of substituents on 1,4-disubstituted 1,2,3-triazoles from the organic azide or terminal alkyne starting materials [1][2]. These Huisgen reactions [13] facilitate rapid drug screening by allowing for tracking in biological systems and the exploration of structure-activity

• relationships [10][14][15][16][17][18][19]. Propargylamines are a popular choice for the terminal alkyne component and form highly selective inhibitors (Figure 1) [2]. Due to the difficulty of forming tetrasubstituted propargylamines, the incorporation of deprotectable variants into triazoles is extremely rare

• assess whether conditions developed for in situ silyl deprotection would otherwise affect the azide when reacting with a simpler terminal alkyne (Scheme 2). As the copper-catalyzed cycloaddition of tert-butylacetylene and benzyl azide proceeds in 92% yield, decomposition of the benzyl azide or non-silyl

Selected synthetic strategies to cyclophanes

• Sambasivarao Kotha,
• Mukesh E. Shirbhate and
• Gopalkrushna T. Waghule

Beilstein J. Org. Chem. 2015, 11, 1274–1331, doi:10.3762/bjoc.11.142

• bromide gave the enyne product 166 (92%), which on further acylation of terminal alkyne with butanoyl chloride delivered compound 167 (82%). Then, it was subjected to an enyne metathesis with simple platinum salts such as PtCl2 and PtCl4 to give product 168 (79%). A subsequent reduction of the α,β

Single-molecule conductance of a chemically modified, π-extended tetrathiafulvalene and its charge-transfer complex with F₄TCNQ

• Raúl García,
• M. Ángeles Herranz,
• Edmund Leary,
• M. Teresa González,
• Gabino Rubio Bollinger,
• Marius Bürkle,
• Linda A. Zotti,
• Yoshihiro Asai,
• Fabian Pauly,
• Juan Carlos Cuevas,
• Nicolás Agraït and
• Nazario Martín

Beilstein J. Org. Chem. 2015, 11, 1068–1078, doi:10.3762/bjoc.11.120

• ), CuI, DIPEA) with trimethylsilylacetylene affords the symmetrically substituted exTTF 2 in good yield. Further removal of the trimethylsilyl group is easily achieved by treatment with potassium carbonate, yielding the free terminal alkyne 3 in quantitative yield. The introduction of the two anchor

Self-assembly of heteroleptic dinuclear metallosupramolecular kites from multivalent ligands via social self-sorting

• Christian Benkhäuser and
• Arne Lützen

Beilstein J. Org. Chem. 2015, 11, 693–700, doi:10.3762/bjoc.11.79

• (trimethylsilyl)acetylene into 7 in a yield of 85% [27]. Alkyne 7 was then subjected to a Negishi reaction with 2-bromopyridine (8) derived zinc organyl 9 to give the silyl-protected ethynylated bipyridine 10 in excellent yield of 99% which was subsequently desilylated under standard conditions to give terminal

• alkyne 11 in 96% yield [28]. Finally, a two-fold Sonogashira reaction with 1,3-diiodobenzene afforded the desired bis(2,2’-bipyridine) ligand 2 in quantitative yield. Metal coordination After the successful synthesis we prepared a DMSO solution of copper(I) ions, added it to the ligands (rac)-1 and 2

Design, synthesis and photochemical properties of the first examples of iminosugar clusters based on fluorescent cores

• Mathieu L. Lepage,
• Antoine Mirloup,
• Manon Ripoll,
• Fabien Stauffert,
• Anne Bodlenner,
• Raymond Ziessel and
• Philippe Compain

Beilstein J. Org. Chem. 2015, 11, 659–667, doi:10.3762/bjoc.11.74

• carefully degassed conditions and the desired protected cluster 12b could be obtained in 56% yield after purification on silica gel (Scheme 2). The major side-product observed which could not be isolated in pure form may correspond to CuAAC reaction of the azido iminosugar 4a with the terminal alkyne

Direct access to pyrido/pyrrolo[2,1-b]quinazolin-9(1H)-ones through silver-mediated intramolecular alkyne hydroamination reactions

• Hengshuai Wang,
• Shengchao Jiao,
• Kerong Chen,
• Xu Zhang,
• Linxiang Zhao,
• Dan Liu,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2015, 11, 416–424, doi:10.3762/bjoc.11.47

• activation of the terminal alkyne moiety of the substrate with AgOTf to generate the Ag–alkyne π complex I (or its tautomer II). Subsequently, the Ag–alkyne π complex I or II is converted into complex III through a nucleophilic attack of the nitrogen atom of the amide, and then produces the final product

Formation of nanoparticles by cooperative inclusion between (S)-camptothecin-modified dextrans and β-cyclodextrin polymers

• Thorbjørn Terndrup Nielsen,
• Catherine Amiel,
• Laurent Duroux,
• Kim Lambertsen Larsen,
• Lars Wagner Städe,
• Reinhard Wimmer and
• Véronique Wintgens

Beilstein J. Org. Chem. 2015, 11, 147–154, doi:10.3762/bjoc.11.14

• (I) compared to alkynes, stabilized with TBTA (Scheme 2). In order to maintain a reductive environment 15 mol % sodium ascorbate was added. The “click” conjugation was achieved within 24 hours at ambient temperature. The complete conversion of terminal alkyne protons with corresponding appearance of

Articulated rods – a novel class of molecular rods based on oligospiroketals (OSK)

• Pablo Wessig,
• Roswitha Merkel and
• Peter Müller

Beilstein J. Org. Chem. 2015, 11, 74–84, doi:10.3762/bjoc.11.11

• defined a 1,2,3-triazole containing linkage between two piperidine rings as the flexible joint F, which should be easily accessible by copper-catalyzed cycloaddition between an azide G and a terminal alkyne H (CuAAC, “Click” reaction) [16]. Primary alcohols I serve as “protected” azides accessible by

• , the PMB group was cleaved by DDQ to give the orthogonally protected trispiro rod 8 (Scheme 1). To demonstrate the capability of the approach outlined in Figure 3 we selectively activated both sides of building block 8 either by introduction of an azide group (9) or liberation of the terminal alkyne by

Synthesis of antibacterial 1,3-diyne-linked peptoids from an Ugi-4CR/Glaser coupling approach

• Martin C. N. Brauer,
• Ricardo A. W. Neves Filho,
• Bernhard Westermann,
• Ramona Heinke and
• Ludger A. Wessjohann

Beilstein J. Org. Chem. 2015, 11, 25–30, doi:10.3762/bjoc.11.4

• were obtained in good yields. The next step was the copper-catalysed homocoupling (Glaser reaction) of the terminal alkyne functions. Albeit several protocols are reported for this reaction, the CuCl-catalyzed method recently described by Jia and co-workers was utilised to access the C2-symmetric 1,3

Sequential decarboxylative azide–alkyne cycloaddition and dehydrogenative coupling reactions: one-pot synthesis of polycyclic fused triazoles

• Kuppusamy Bharathimohan,
• Thanasekaran Ponpandian,
• A. Jafar Ahamed and
• Nattamai Bhuvanesh

Beilstein J. Org. Chem. 2014, 10, 3031–3037, doi:10.3762/bjoc.10.321

• cycloaddition, CuAAC) between an organic azide and a terminal alkyne is a well-established strategy for the construction of 1,4-disubstituted 1,2,3-triazoles [1][2][3][4]. In a recent development, this decarboxylative coupling reaction was well documented for the generation of C–C bonds [5]. This method has

A general metal-free approach for the stereoselective synthesis of C-glycals from unactivated alkynes

• Shekaraiah Devari,
• Manjeet Kumar,
• Ramesh Deshidi,
• Masood Rizvi and
• Bhahwal Ali Shah

Beilstein J. Org. Chem. 2014, 10, 2649–2653, doi:10.3762/bjoc.10.277

• challenge. We reasoned that the development of a strategy which in situ activates the terminal alkyne and further catalyzes the reaction without the aid of other Lewis acids might be a solution to this problem. Thus, in continuation of our efforts [36][37][38], we describe a highly stereoselective TMSOTf

A small azide-modified thiazole-based reporter molecule for fluorescence and mass spectrometric detection

• Stefanie Wolfram,
• Hendryk Würfel,
• Stefanie H. Habenicht,
• Christine Lembke,
• Phillipp Richter,
• Eckhard Birckner,
• Rainer Beckert and
• Georg Pohnert

Beilstein J. Org. Chem. 2014, 10, 2470–2479, doi:10.3762/bjoc.10.258

• , fluorescent and MS techniques. Conclusion We introduce the azide-modified thiazole-based reporter molecule BPT (1) with superior properties for fluorescence, UV and MS detection compared to other common reporters. BPT (1) can be easily synthesized and attached to terminal alkyne-modified molecules via CuAAC

Synthesis and solvodynamic diameter measurements of closely related mannodendrimers for the study of multivalent carbohydrate–protein interactions

• Yoann M. Chabre,
• Alex Papadopoulos,
• Alexandre A. Arnold and
• René Roy

Beilstein J. Org. Chem. 2014, 10, 1524–1535, doi:10.3762/bjoc.10.157

• (18H), and the terminal alkyne protons (9H) at δ 4.16, 3.87, and 2.48 ppm, respectively. Toward the last and further extended 9-mer 21, a convergent strategy was rather adopted (Scheme 4). This strategy has the clear advantages of providing an easier purification process from partially substituted end

An economical and safe procedure to synthesize 2-hydroxy-4-pentynoic acid: A precursor towards ‘clickable’ biodegradable polylactide

• Quanxuan Zhang,
• Hong Ren and
• Gregory L. Baker

Beilstein J. Org. Chem. 2014, 10, 1365–1371, doi:10.3762/bjoc.10.139

• with low cost. Malonate has a low pKa of ~13 and can be easily deprotonated and alkylated by mild bases such as sodium/potassium alkoxides without deprotonating a terminal alkyne. Conveniently, both malonate and propargyl alcohol are commercially available in bulk quantities. Herein, we report one

Preparation of phosphines through C–P bond formation

• Iris Wauters,
• Wouter Debrouwer and
• Christian V. Stevens

Beilstein J. Org. Chem. 2014, 10, 1064–1096, doi:10.3762/bjoc.10.106

Isocyanide-based multicomponent reactions towards cyclic constrained peptidomimetics

• Gijs Koopmanschap,
• Eelco Ruijter and
• Romano V.A. Orru

Beilstein J. Org. Chem. 2014, 10, 544–598, doi:10.3762/bjoc.10.50

Practical synthesis of aryl-2-methyl-3-butyn-2-ols from aryl bromides via conventional and decarboxylative copper-free Sonogashira coupling reactions

• Andrea Caporale,
• Stefano Tartaggia,
• Andrea Castellin and
• Ottorino De Lucchi

Beilstein J. Org. Chem. 2014, 10, 384–393, doi:10.3762/bjoc.10.36

• acetylene after reductive elimination. The activated acetylide species for the coupling process is generated from the reaction of a terminal alkyne with copper in the presence of a base and is transferred on the palladium site via transmetallation. In order to improve the efficacy of the reaction, several

• derived from the starting aryl bromides in a 2–5% yield range. Likely, the acetone protecting group is cleaved from protected terminal alkyne even under such mild conditions and therefore, the terminal alkyne generated in situ couples with another molecule of the starting aryl bromide to provide the

Synthesis of 3,4-dihydro-1,8-naphthyridin-2(1H)-ones via microwave-activated inverse electron-demand Diels–Alder reactions

• Salah Fadel,
• Youssef Hajbi,
• Mostafa Khouili,
• Said Lazar,
• Franck Suzenet and
• Gérald Guillaumet

Beilstein J. Org. Chem. 2014, 10, 282–286, doi:10.3762/bjoc.10.24

• electron-demand Diels–Alder reaction from 1,2,4-triazines bearing an acylamino group with a terminal alkyne side chain. Alkynes were first subjected to the Sonogashira cross-coupling reaction with aryl halides, the product of which then underwent an intramolecular inverse electron-demand Diels–Alder

Synthesis and biological activity of N-substituted-tetrahydro-γ-carbolines containing peptide residues

• Nadezhda V. Sokolova,
• Valentine G. Nenajdenko,
• Vladimir B. Sokolov,
• Daria V. Vinogradova,
• Elena F. Shevtsova,
• Ludmila G. Dubova and
• Sergey O. Bachurin

Beilstein J. Org. Chem. 2014, 10, 155–162, doi:10.3762/bjoc.10.13

• of mitochondria but possessed some inhibitory effect on the mitochondria permeability transition. The original N-substituted-tetrahydro-γ-carbolines containing an terminal alkyne group demonstrated a high prooxidant activity, whereas their conjugates with peptide fragments slightly inhibited both

• membrane potential, mitochondrial permeability transition and lipid peroxidation. Results and Discussion The starting N-substituted tetrahydro-γ-carbolines 3a–d containing a terminal alkyne group were prepared in good yields by heating compounds 1a–d [12][13] with propargyl acrylate (2) in the presence of

• described the conjugation of N-substituted tetrahydro-γ-carbolines containing a terminal alkyne group 3a–d with various azidopeptides 5 (prepared by Ugi multicomponent reaction) through the Cu(I)-catalyzed Huisgen 1,3-dipolar cycloaddition. The activity of the obtained compounds on rat liver mitochondria

Triphenylene discotic liquid crystal trimers synthesized by Co₂(CO)₈-catalyzed terminal alkyne [2 + 2 + 2] cycloaddition

• Bin Han,
• Ping Hu,
• Bi-Qin Wang,
• Carl Redshaw and
• Ke-Qing Zhao

Beilstein J. Org. Chem. 2013, 9, 2852–2861, doi:10.3762/bjoc.9.321

• trimers using Co2(CO)8-catalyzed terminal alkyne [2 + 2 + 2] cycloaddition reaction is reported. The trimers consist of three triphenylene discotic units linked to a central 1,2,4-trisubstituted benzene ring via flexible spacers. The trimers were synthesized in the yields up to 70% by mixing the monomers

• and stabilization of the discotic columnar mesophase. Conclusion The synthesis and mesomorphism of two new mono-functionalized triphenylene discotic monomers and four discotic trimers is reported. The trimers have been successfully synthesized for the first time by using a Co2(CO)8-catalyzed terminal

• alkyne [2 + 2 + 2] cycloaddition reaction in moderate yields. Three of the four 1,2,4-trisubstituted benzene-cored discotic trimers have shown stable Colho and Colro mesophases and wide mesophase ranges including room temperature. The connecting linker group to the triphenylene and the spacer length to

Total synthesis of the endogenous inflammation resolving lipid resolvin D2 using a common lynchpin

• John Li,
• May May Leong,
• Alastair Stewart and
• Mark A. Rizzacasa

Beilstein J. Org. Chem. 2013, 9, 2762–2766, doi:10.3762/bjoc.9.310

• stereoisomer analogues of RvD2 (1). Removal of the TIPS group with TBAF gave terminal alkyne 12. Alkyne 12 then underwent smooth hydrozirconation utilizing the procedure reported by Negishi [24] were ZrCp2HCl is generated in situ by reduction of ZrCp2Cl2 with DIBALH in THF. Iodinolysis of the zirconium species

Advancements in the mechanistic understanding of the copper-catalyzed azide–alkyne cycloaddition

• Regina Berg and
• Bernd F. Straub

Beilstein J. Org. Chem. 2013, 9, 2715–2750, doi:10.3762/bjoc.9.308

• Huisgen’s azide–alkyne cycloaddition (CuAAC reaction). In fact, the catalytic effect of copper ions had first been mentioned by L’Abbé in 1984 [7], but had henceforth been overlooked until Meldal presented a copper(I)-catalyzed solid-phase synthesis of 1,2,3-triazoles. In this procedure, the terminal alkyne

Ambient gold-catalyzed O-vinylation of cyclic 1,3-diketone: A vinyl ether synthesis

• Yumeng Xi,
• Boliang Dong and
• Xiaodong Shi

Beilstein J. Org. Chem. 2013, 9, 2537–2543, doi:10.3762/bjoc.9.288

• [22]. The internal alkyne (1-phenyl-1-propyne), which was usually much less reactive than the terminal alkyne, was also tested. As expected, no reaction occurred at room temperature under the optimal conditions. To our delight, the desired products 8 were obtained while refluxing at 60 °C for 48 h

Gold(I)-catalyzed enantioselective cycloaddition reactions

• Fernando López and
• José L. Mascareñas

Beilstein J. Org. Chem. 2013, 9, 2250–2264, doi:10.3762/bjoc.9.264

• a nucleophilic intramolecular attack of the carboxy moiety on the activated alkyne. 1,2-Migration of the ester affording a gold–carbene of type A is usually preferred when a terminal alkyne is used [38][39][40]. Based on this concept, several groups have shown that the resulting carbenoid