A journey in bioinspired supramolecular chemistry: from molecular tweezers to small molecules that target myotonic dystrophy

• Steven C. Zimmerman

Beilstein J. Org. Chem. 2016, 12, 125–138, doi:10.3762/bjoc.12.14

• report [8] of compound 2 containing two caffeine units linked by a rigid diyne spacer (Figure 2e). Whitlock noted that conventional bisintercalators such as 1 would have their affinity for oligonucleotides significantly reduced as a result of intramolecular π–π aromatic stacking. Whereas the diyne spacer

Asymmetric 1,4-bis(ethynyl)bicyclo[2.2.2]octane rotators via monocarbinol functionalization. Ready access to polyrotors

• Cyprien Lemouchi and
• Patrick Batail

Beilstein J. Org. Chem. 2015, 11, 1881–1885, doi:10.3762/bjoc.11.202

• dirotors in higher yield than our former [10][12] synthesis of 6 and with very diverse functional groups (Scheme 2). Hence, large quantities of the diyne diester dirotor, 9 are obtained (Scheme 2) providing ready, on-demand access to 10. The dirotors 3, 6 and 9 are synthesized by palladium-catalyzed

• solubility considerations, as it enhances the reactivity in the homocoupling reaction and also facilitates the purification of 9 by chromatography on silica gel. This yielded the dicarboxylate diyne dirotor 10 with the high purity required for the preparation of framework solids. Saponification of the ester

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

• -diiodobenzene with an excess amount of triisopropylsilylbutadiyne (47) followed by complexation with Co2(CO)8 furnished a pale yellow diyne 48. Exchange of the ligand with bis(diphenylphosphino)methane (dppm) afforded a bridged complex which is stable to fluoride ions. Subsequent desilylation, followed by

• to a Glaser–Eglinton coupling to generate the macrocyclic bisacetylene derivative 52 in 94% yield. Finally, diyne 52 was subjected to a hydrogenation sequence with 10% Pd/C under 1 atm pressure of H2 to generate cyclophane derivative 53 (92%). Alternatively, cyclophane 53 was also obtained by

• conformation that imparts helical chirality. Double helically twisted chiral cyclophanes are important macrocycles due to their potential applications in optics and electronics. Kawase and co-workers [121] have reported the synthesis of 8,14,30,36-tetramethoxy[2.0.2.0](1,6)naphthalenophane-1,19-diyne (102

Synthesis and chemosensing properties of cinnoline-containing poly(arylene ethynylene)s

• Natalia A. Danilkina,
• Petr S. Vlasov,
• Semen M. Vodianik,
• Andrey A. Kruchinin,
• Yuri G. Vlasov and
• Irina A. Balova

Beilstein J. Org. Chem. 2015, 11, 373–384, doi:10.3762/bjoc.11.43

• with 1,4-diiodo-2,5-bis(octyloxy)benzene (9). There are two main reactions of polycondensation that have been reported as synthetic approaches towards PAEs: the acyclic diyne metathesis polymerization (ADIMET) [55] and the Sonogashira coupling [56]. Both of them have their own advantages and drawbacks

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

• Martin C. N. Brauer Ricardo A. W. Neves Filho Bernhard Westermann Ramona Heinke Ludger A. Wessjohann Department of Bioorganic Chemistry, Leibniz Institute of Plant Biochemistry, Weinberg 3, D-06120 Halle/Saale, Germany 10.3762/bjoc.11.4 Abstract A library of ten 1,3-diyne-linked peptoids has been

• can be of peptidic origin [2][3]. As an example, Harran and co-workers synthesized a low-molecular weight C2-symmetric 1,3-diyne-linked peptide 1 which was able to mimic the function of Smac (second mitochondria-derived activator of caspase) protein by triggering caspase 8 activation as well as

• 44.0 ± 26.7, 44.0 ± 21.8 and 43.9 ± 23.0. Interestingly, compounds 8c and 8f showed almost no effect on bacterial growth, i.e., 1.3 ± 5.1% and 2.3 ± 13.5%, respectively, i.e., the diyne core fulfils its function as linker and spacer without itself negatively (or positively) influencing the specific

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• phenanthridine (Scheme 20) [44]. The synthesis by multicomponent tandem reaction/carbocyclization starts with the formation of a 4-aryl-3-arylethynylisoquinoline from 2-bromobenzaldehyde/tert-butylamine/1,3-diyne. The second (in situ) step is based on the ring closure, either via gold/silver-catalysed

Copper-promoted hydration and annulation of 2-fluorophenylacetylene derivatives: from alkynes to benzo[b]furans and benzo[b]thiophenes

• Yibiao Li,
• Liang Cheng,
• Xiaohang Liu,
• Bin Li and
• Ning Sun

Beilstein J. Org. Chem. 2014, 10, 2886–2891, doi:10.3762/bjoc.10.305

• annulation of 1,3-diynes, which have great synthetic potential in medicine and materials sciences [38][39][40]. For extensions, we used 1,4-bis(2-fluorophenyl)buta-1,3-diyne as a substrate to investigate the possibility of this transformation. Similar to (2-(2-fluorophenyl)ethynyl)benzene, 1,4-bis(2

• -fluorophenyl)buta-1,3-diyne was able to offer the corresponding annulation products 2s in 78% yield (Scheme 3). To gain a deeper mechanistic understanding of the present catalytic process, the direct intramolecular annulation of 1-bromo-2-(2-(2-fluorophenyl)ethynyl)benzene and 1-chloro-2-(2-(2-fluorophenyl

Selenium halide-induced bridge formation in [2.2]paracyclophanes

• Laura G. Sarbu,
• Henning Hopf,
• Peter G. Jones and
• Lucian M. Birsa

Beilstein J. Org. Chem. 2014, 10, 2550–2555, doi:10.3762/bjoc.10.266

• proposed reaction mechanism, the reaction of 4,13-diyne 12 with 2 equivalents of selenium dichloride or selenium dibromide provided only (17E,19E)-diene 13 and 15; again, no traces of tetrahalide derivatives were identified (Table 2, entries 2 and 5). The addition of phenylselenyl chloride to 12 provides

Macrocyclic bis(ureas) as ligands for anion complexation

• Claudia Kretschmer,
• Gertrud Dittmann and
• Johannes Beck

Beilstein J. Org. Chem. 2014, 10, 1834–1839, doi:10.3762/bjoc.10.193

• . Results and Discussion The synthesis of the two macrocyclic diphenylureas 1 and 2 proceeds straightforward from the respective 2,2’-diamino derivatives of diphenylethyne (tolane) and diphenylbuta-1,3-diyne with carbonyldiimidazole (Scheme 1). In both cases, the cyclization products were selectively formed

Improving the reactivity of phenylacetylene macrocycles toward topochemical polymerization by side chains modification

• Simon Rondeau-Gagné,
• Jules Roméo Néabo,
• Maxime Daigle,
• Katy Cantin and
• Jean-François Morin

Beilstein J. Org. Chem. 2014, 10, 1613–1619, doi:10.3762/bjoc.10.167

• the formation of PDA-based nanorods. Nonetheless, the polymerization of diyne units within PAMs to give covalent nanorods and nanotubes is very slow and gives low yields of polymerization, generally too low to be determined accurately [38][39]. In order to increase the efficiency of polymerization

• , the incorporation of external diyne chains on the PAMs core have been realized [31]. This design allowed us to increase the yield of polymerization to 15%. However, the addition of external diyne units is synthetically tedious and a more efficient strategy to significantly increase the yield of the

• PAM scaffold (≈15% yield). This result suggests that the diyne units in PAM2 are in a more suitable orientation than PAM1 to undergo a topochemical polymerization, although gelation properties and XRD result seem to suggest otherwise. It is also possible that the apparent yield increase comes from a

Silver and gold-catalyzed multicomponent reactions

• Giorgio Abbiati and
• Elisabetta Rossi

Beilstein J. Org. Chem. 2014, 10, 481–513, doi:10.3762/bjoc.10.46

• arylacetylenes 87, carbon dioxide and 3-bromo-1-aryl-1-propynes 88 (Scheme 40) [104]. In the reaction sequence a 1,6-diyne was generated in situ and cyclized to afford the two possible regioisomeric compounds. The level of regioselectivity can be enhanced by the tuning of electronic properties of the reactant

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

• methodologies [25][26][27] were developed. Copper-free reaction protocols [28][29][30][31][32][33][34][35][36][37][38][39][40][41] are highly promising for industrial applications as the presence of copper could lead to the formation of diyne byproducts, causing an irreversible loss of precious material, and

Flexible synthesis of anthracycline aglycone mimics via domino carbopalladation reactions

• Markus Leibeling and
• Daniel B. Werz

Beilstein J. Org. Chem. 2013, 9, 2194–2201, doi:10.3762/bjoc.9.258

• The choice of the right diyne is crucial for a successful synthesis of the target compound. Preliminary investigations had shown that both dialkynes with benzylic hydroxy functionalities and 1,2-bis(2-propynyl)benzene did not yield viable results in the domino reaction. The selective installation of

Recent advances in transition-metal-catalyzed intermolecular carbomagnesiation and carbozincation

• Kei Murakami and
• Hideki Yorimitsu

Beilstein J. Org. Chem. 2013, 9, 278–302, doi:10.3762/bjoc.9.34

• reagents (Scheme 54) [147]. They assumed that the active species were organocuprates and that the radical character of carbocupration enabled bulky sec- or tert-alkylmagnesium reagents to be employed. Chromium-catalyzed carbomagnesiation of 1,6-diyne (Scheme 55) [148] and 1,6-enyne (Scheme 56) [149] also

• provided interesting organomagnesium intermediates through cyclization reactions [150]. Treatment of 1,6-diyne 5j with methallylmagnesium reagent in the presence of chromium(III) chloride afforded bicyclic product 5k in excellent yield. In the proposed mechanism, the chromium salt was firstly converted to

Highly stereocontrolled synthesis of trans-enediynes via carbocupration of fluoroalkylated diynes

• Tsutomu Konno,
• Misato Kishi and
• Takashi Ishihara

Beilstein J. Org. Chem. 2012, 8, 2207–2213, doi:10.3762/bjoc.8.249

• equiv of LHMDS in −78 °C for 1 h gave the corresponding trifluoromethylated diyne in an excellent yield. This diyne was found to be a good substrate for the carbocupration with various higher-ordered cyanocuprates to give the corresponding vinylcuprates in a highly regio- and stereoselective manner. The

• ; carbometallation; diyne; enediyne; fluorine; highly regioselective; highly stereoselective; Introduction trans-Enediynes (trans-hex-3-ene-1,5-diynes), as shown in Figure 1, are well-recognized as one of the most important building blocks because they are frequently utilized for the synthesis of π-conjugated

• convenient and efficient access to trifluoromethylated enediynes by the highly regio- and stereoselective carbocupration reaction of trifluoromethylated diyne with various organocuprates (Scheme 1). Results and Discussion Our initial studies began with the preparation of trifluoromethylated diyne derivatives

The chemistry of bisallenes

• Henning Hopf and
• Georgios Markopoulos

Beilstein J. Org. Chem. 2012, 8, 1936–1998, doi:10.3762/bjoc.8.225

• -dibromobisallenes 74 by treating the highly substituted diyne diols 73 with phosphorus tribromide in benzene (Scheme 15) [58][59][60][61][62][63]. The details of these often overlooked seminal publications were recently studied by Parkhurst and Swager. According to these authors the 1,6-dibromide is produced first

• reaction. In this case the diketone 107 was obtained by a Zn/Cu-couple-induced coupling reaction between excess phenacyl bromide (105) and the enyne 106 (Scheme 27) [83]. Besides 107 its diyne and propargylallene dimers were produced, requiring a chromatographic separation of the product mixture. The

Enantioselective total synthesis of (R)-(−)-complanine

• Krystal A. D. Kamanos and
• Jonathan M. Withey

Beilstein J. Org. Chem. 2012, 8, 1695–1699, doi:10.3762/bjoc.8.192

• cesium carbonate, copper iodide and tetrabutylammonium iodide. The resulting skipped diyne 2 was selectively reduced to homoconjugated all-Z-diene 1, with subsequent Swern oxidation affording aldehyde 3, in 86% yield from 2, as a key intermediate in the total synthesis. With 3 in hand, attention was then

Synthesis of a novel chemotype via sequential metal-catalyzed cycloisomerizations

• Bo Leng,
• Stephanie Chichetti,
• Shun Su,
• Aaron B. Beeler and
• John A. Porco Jr.

Beilstein J. Org. Chem. 2012, 8, 1338–1343, doi:10.3762/bjoc.8.153

• diversity; cycloisomerization; cyclopropane; diyne; isochromene; π-acid; Introduction Our laboratory has an ongoing interest in discovering transformations that afford novel chemotypes [1][2][3][4]. To this end, we have developed a reaction screening paradigm that enables the discovery of new reaction

• yield (Table 1, entry 1). m-Methyl- and naphthyl-containing substrates 10 and 12 afforded polycyclic cyclopropanes 11 and 13 in 48 and 51% yields, respectively (Table 1, entries 2 and 3). We next explored substitution of the pendant alkyne. Reaction with cyclohexane diyne 14 afforded the fused

A ferrocene redox-active triazolium macrocycle that binds and senses chloride

• Nicholas G. White and
• Paul D. Beer

Beilstein J. Org. Chem. 2012, 8, 246–252, doi:10.3762/bjoc.8.25

• -ray crystallography (Figure 1). The structure of 3 shows that the diyne unit appears to enforce a reasonably rigid geometry on the rest of the macrocycle, due to its sterically demanding nature, which may help to constrain the anion binding cleft and lead to selective anion binding. In contrast, the

Recent advances in the gold-catalyzed additions to C–C multiple bonds

• He Huang,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2011, 7, 897–936, doi:10.3762/bjoc.7.103

• . Disubstituted 1,6-diynes furnished the (Z)-cyclopentylidene derivative 239 stereoselectively [117]. Monosubstituted terminal diyne afforded the cyclopentene derivative 240, while the diterminal 1,6-diyne produced a cyclohexenone derivative 241 (Scheme 43). Cheong and co-workers demonstrated that 1,5-allenynes

• Friedel–Crafts/furan–yne cyclization/heteroenyne metathesis was developed for the highly efficient construction of phenanthrene derivatives 270 [144]. Both AuCl3 and PPh3AuCl are effective catalysts for all the processes in the reaction and a variety of diyne substrates 271 could be used (Scheme 48

Au(I)/Au(III)-catalyzed Sonogashira-type reactions of functionalized terminal alkynes with arylboronic acids under mild conditions

• Deyun Qian and
• Junliang Zhang

Beilstein J. Org. Chem. 2011, 7, 808–812, doi:10.3762/bjoc.7.92

• hand, the more electron-rich 4-methoxyphenylboronic acid produced the lowest yield, likely due to a competing oxidation of the boronic acid by Selectfluor® [27][30]. Gratifyingly, a number of potentially reactive functionalities, such as tertiary amine, 4-methylbenzenesulfonate, 1,6-enyne and 1,6-diyne

Construction of cyclic enones via gold-catalyzed oxygen transfer reactions

• Leping Liu,
• Bo Xu and
• Gerald B. Hammond

Beilstein J. Org. Chem. 2011, 7, 606–614, doi:10.3762/bjoc.7.71

• the diacid 1,6-diyne (R1 = R2 = COOH) was employed in the reaction, only the esterified product (R1 = R2 = COOMe) was isolated, albeit in low yield. The authors also carried out this gold-catalyzed transformation in an ionic liquid [49]. This modification enabled the separation of the gold catalyst

Allene chemistry

• Kay M. Brummond

Beilstein J. Org. Chem. 2011, 7, 394–395, doi:10.3762/bjoc.7.50

• ...” [1]. I first became interested in allenes as a graduate student with Professor Ray Funk at Pennsylvania State University while working on the preparation of ene–diyne systems. Interestingly, I always seemed to isolate allenes instead of the compounds I was hoping to obtain. My interests in allenes

Recent advances in the development of alkyne metathesis catalysts

• Xian Wu and
• Matthias Tamm

Beilstein J. Org. Chem. 2011, 7, 82–93, doi:10.3762/bjoc.7.12

• metathesis polymerization (ROAMP) and acyclic diyne metathesis polymerization (ADIMET) are known (Scheme 2). In contrast to olefin metathesis, the number of catalysts for alkyne metathesis is far more limited. The first catalyst for alkyne metathesis was a heterogeneous system based on WO3/silica, which was

• = NMe2) was hardly successful in the presence of 2 mol % of the catalyst, whereas 14e was isolated in 90% yield with a catalyst loading of 5 mol %. Further detailed studies are required to fully explain this ostensibly odd behavior. Catalyst 5 was used in the RCAM of 6,15-dioxaeicosa-2,18-diyne (15) and

(−)-Complanine, an inflammatory substance of marine fireworm: a synthetic study

• Kazuhiko Nakamura,
• Yu Tachikawa and
• Daisuke Uemura

Beilstein J. Org. Chem. 2009, 5, No. 12, doi:10.3762/bjoc.5.12

• acetylene 4 in 51% yield [7]. The bromomagnesium salt of 4 generated with EtMgBr was successively treated with 1-iodopent-2-yne in the presence of CuI to give the corresponding diyne compound 5 in 43% yield [8]. The partial reduction was achieved by using Lindlar catalyst to give the desired Z olefin, which

• ), 1.69 (1H, m), 1.57 (4H, m), 0.84 (3H + 3H, t, J = 7.6 Hz, overlapped). Synthesis of diyne 5: To a solution of the alkyne (4, 445 mg, 2.45 mmol) in THF (2.0 ml), 1.6 M solution of ethylmagnesium bromide (Aldrich, 2.45 ml, 3.92 mmol) was added under N2, and the resulting solution was stirred at ambient

• extractive workup and column chromatography (SiO2, hexane/ethyl acetate 98 : 2 to 95 : 5) gave the desired diyne compound 5 as a pale yellow oil (258 mg, 43%). 5: [α]D26 +2.7 (c 0.26, CHCl3); HRMS (ESI) calcd for C16H24O2Na [(M + Na)+] 271.1674, found 271.1696; 1H NMR (600 MHz, CDCl3) δ 4.17 (1H, m), 4.09