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

• Scheme 1 would streamline the synthesis of alpha-tetrasubstituted triazoles 6. In the first step, our solvent-free copper-catalyzed three-component coupling of cyclohexanone (1), amines 2, and alkynes 3 provides high yields of silyl-protected propargylic amines 4 [24][25]. Trimethylsilyl (TMS) acetylene

• was not stable in the presence of the copper(II) chloride catalyst, and triethylsilylacetylene did not convert cleanly to product. Triisopropylsilyl (TIPS) acetylene was found to be superior to tert-butyldimethylsilylacetylene as a source of silylated tetrasubstituted propargylic amines. Although TMS

• starting materials, cyclohexanone (1), 4-methylpiperidine (2a), and TIPS-acetylene (3). As there are no added ligands, solvents, promoters, or excess starting materials, the sole byproduct in the formation of tetrasubstituted propargylamine 4a is one equivalent of water [25]. The second step links silyl

Synthesis of γ-hydroxypropyl P-chirogenic (±)-phosphorus oxide derivatives by regioselective ring-opening of oxaphospholane 2-oxide precursors

• Iris Binyamin,
• Shoval Meidan-Shani and
• Nissan Ashkenazi

Beilstein J. Org. Chem. 2015, 11, 1332–1339, doi:10.3762/bjoc.11.143

• . Further heating did not provide higher conversion. Following hydrolytic work-up and flash chromatographic purification the product was identified as allene 5f, rather than acetylene 5h, due to propargyl–allene rearrangement (Scheme 5). Most characteristic are the 13C NMR chemical shift of HC=C=CR at

• serve as the catalytic base that prompts the rearrangment. The 1,3-hydrogen shift in a P-propargyl system is well established [51]. In an attempt to prevent this rearrangement we applied an acetylene substituted with the bulky TMS group [58], which may be easily removed at a later stage, and formed the

• formed regioselectivly. Synthesis of acetylene and allene phosphine oxides. Synthesis of γ-hydroxypropyl (±)-phosphinatesa and related compounds. Synthesis of γ-hydroxypropyl (±)-phosphine oxidesa. Supporting Information Supporting Information File 66: Experimental details, characterization data and 1H

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

• Glaser–Eglinton coupling of the terminal acetylene groups provided complex 49 in 47% yield as fine, deep maroon crystals. In connection with the cyclophane synthesis, Kotha and Waghule [92] demonstrated the use of the Glaser–Eglinton coupling as a key step. The dipropargylated compound 51 was subjected

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

Hetero-Diels–Alder reactions of hetaryl and aryl thioketones with acetylenic dienophiles

• Grzegorz Mlostoń,
• Paulina Grzelak,
• Maciej Mikina,
• Anthony Linden and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2015, 11, 576–582, doi:10.3762/bjoc.11.63

• acetylenic dienophiles, other easily available acetylenes were used in the reaction with 1a. In all reactions attempted with phenylacetylene, (pyridin-2-yl)acetylene, and (tert-butyl)acetylene, no conversion of 1a was observed as evidenced by the blue color of the reaction mixture even after 24 h

• . Unfortunately, the experiments performed under the described conditions (THF, LiClO4, temp.) with (trifluoromethyl)acetylene and (diethoxyphosphoryl)acetylene, activated by the presence of strongly electron-withdrawing substituents, were also unsuccessful. Some of the thiopyran derivatives 4 and 5 obtained in

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

• the PAE 10b with an additional acetylene fragment differed from the absorption spectrum of the PAE 10a by a small bathochromic shift (≈7 nm) of two absorption bands and an additional absorption band at 266 nm (Figure 6). The fluorescence emission spectra of the same solutions (Figure 7) were recorded

2-(1-Hydroxypropyn-2-yl)-1-vinylpyrroles: the first successful Favorsky ethynylation of pyrrolecarbaldehydes

• A. V. Ivanov,
• V. S. Shcherbakova,
• I. A. Ushakov,
• L. N. Sobenina,
• O. V. Petrova,
• A. I. Mikhaleva and
• B. A. Trofimov

Beilstein J. Org. Chem. 2015, 11, 228–232, doi:10.3762/bjoc.11.25

• .11.25 Abstract 1-Vinylpyrrole-2-carbaldehydes react with acetylene at atmospheric pressure in a NaOH/EtOH/DMSO system at 7–10 °C to afford 2-(1-hydroxypropyn-2-yl)-1-vinylpyrroles in 53–94% yield. Thus, the first base-mediated direct ethynylation of pyrrolecarbaldehydes with free acetylene under

• modified conditions of the Favorsky reaction has been implemented to pave an expedient route to important biomolecules containing a pyrrole ring. Keywords: acetylene; ethynylation; Favorsky reaction; 1-vinylpyrrole-2-carbaldehyde; Introduction Functionalized pyrroles bearing a terminal acetylenic moiety

• pyrrole-2-carbaldehyde with acetylene under conditions, well suited for the synthesis of secondary acetylenic alcohols (KOH/H2O/DMSO, atmospheric pressure, −5 to −7 °C) from aromatic and heteroaromatic aldehydes [9], appeared to be unsuccessful: the starting aldehyde was almost quantitatively recovered

The Shono-type electroorganic oxidation of unfunctionalised amides. Carbon–carbon bond formation via electrogenerated N-acyliminium ions

• Alan M. Jones and
• Craig E. Banks

Beilstein J. Org. Chem. 2014, 10, 3056–3072, doi:10.3762/bjoc.10.323

• -acyliminium ion cyclisation strategy in the presence of a disubstituted acetylene nucleophile. Anodic oxidation proceeded in high yield and a smooth cyclisation of the pendant acetylene nucleophile was triggered by treatment with titanium tetrachloride. Ozonolysis of the chloromethyl alkene intermediate

One-pot functionalisation of N-substituted tetrahydroisoquinolines by photooxidation and tunable organometallic trapping of iminium intermediates

• Joshua P. Barham,
• Matthew P. John and
• John A. Murphy

Beilstein J. Org. Chem. 2014, 10, 2981–2988, doi:10.3762/bjoc.10.316

• of methopholine (3, Scheme 2). Previous syntheses of 3 involving oxidative functionalisation of 16a have used (4-chlorophenyl)acetylene as a pronucleophile [13][46]. However, isolation and hydrogenation of the resulting THIQ intermediate are required to access 3. Photoactivation of 16a and trapping

Mono- and multilayers of molecular spoked carbazole wheels on graphite

• Stefan-S. Jester,
• A. Vikas Aggarwal,
• Daniel Kalle and
• Sigurd Höger

Beilstein J. Org. Chem. 2014, 10, 2783–2788, doi:10.3762/bjoc.10.295

• curved (or bent; as seen in the molecular model in Figure 2c and d where one of the six carbazole units is marked by a white arrow). They are still not directly connected, but terminated with acetylene units. However, a gap can rarely be estimated from the brightness modulation (cf. circle in Figure 2c

Self-assembled monolayers of shape-persistent macrocycles on graphite: interior design and conformational polymorphism

• Joscha Vollmeyer,
• Friederike Eberhagen,
• Sigurd Höger and
• Stefan-S. Jester

Beilstein J. Org. Chem. 2014, 10, 2774–2782, doi:10.3762/bjoc.10.294

• Joscha Vollmeyer Friederike Eberhagen Sigurd Hoger Stefan-S. Jester Kekulé-Institut für Organische Chemie und Biochemie, Rheinische Friedrich-Wilhelms-Universität Bonn, Gerhard-Domagk-Str. 1, 53121 Bonn, Germany 10.3762/bjoc.10.294 Abstract Three shape-persistent naphthylene–phenylene–acetylene

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

• forming an oxonium ion intermediate, which is attacked by trimethylsilylacetylene to give the corresponding product (Scheme 3, reaction 2). The stereochemistry of the reaction products is possibly determined by the coordination between two π-electron orbitals of the oxocarbonium ion and the acetylene

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

• Analytical Chemistry, Technical University of Braunschweig, Hagenring 30, D-38106 Braunschweig, Germany 10.3762/bjoc.10.266 Abstract An addition/elimination sequence of selenium halides to pseudo-geminally bis(acetylene) substituted [2.2]paracyclophanes leads to new bridges with an endo-exo-diene

• intramolecular photocyclization, yielding the corresponding ladderane isomers [9][10][11]. The ethynyl group is well known for its ability to undergo coupling reactions, making the pseudo-geminal bis(acetylene) 1 and its derivatives good candidates for building molecular scaffolding [12][13]. The reaction

• between bis(acetylene) 1 and other acetylene derivatives has been reported to provide new π-bridges in [2.2]paracyclophane [14]. Furthermore, a new way for bridging [2.2]paracyclophanes has been accomplished by the addition of selenium monochloride to pseudo-geminally substituted bis(propargylic) alcohols

Building complex carbon skeletons with ethynyl[2.2]paracyclophanes

• Ina Dix,
• Lidija Bondarenko,
• Peter G. Jones,
• Thomas Oeser and
• Henning Hopf

Beilstein J. Org. Chem. 2014, 10, 2013–2020, doi:10.3762/bjoc.10.209

• yield (67%; for the spectroscopic data see Supporting Information File 1). In this intermediate the three triple bonds to be converted into a benzene ring possess only one degree of freedom: the rotation of the non-phane benzene ring around its connecting acetylene group. The cyclotrimerization of three

Microwave-assisted Cu(I)-catalyzed, three-component synthesis of 2-(4-((1-phenyl-1H-1,2,3-triazol-4-yl)methoxy)phenyl)-1H-benzo[d]imidazoles

• Yogesh Kumar,
• Vijay Bahadur,
• Anil K. Singh,
• Virinder S. Parmar,
• Erik V. Van der Eycken and
• Brajendra K. Singh

Beilstein J. Org. Chem. 2014, 10, 1413–1420, doi:10.3762/bjoc.10.145

• , when path A and path B were explored, the desired product was afforded in different yields (Scheme 1). The treatment of acetylene 2a with phenylazide (1a) in the presence of copper sulfate and D-glucose as a reductant [32][33] in THF/H2O (2:1) as a solvent under stirring at rt as well as under

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

• polymerization of functional lactide monomers, post-polymerization modification, or a combination of these two approaches. The appending hydroxy [9], carboxyl [10], poly(ethylene glycol) (PEG) [11][12][13][14], allyl [15], azido [16] and acetylene [17] functionalities on PLA backbones have been reported and

• offered great opportunities for covalent post-polymerization modification of PLAs. Among various functional groups, acetylene functionalized PLA has attracted much attention [17][18][19]. By having a single functional lactide monomer, it allows for facile placement of a broad range of pendant functional

• because of its high selectivity and excellent tolerance to different functional groups and reaction conditions. Our group has prepared the first ‘clickable’ PLA using 2-hydroxy-4-pentynoic acid (1) as a precursor (Scheme 1) and studied ‘click’ modification of acetylene functionalized PLA [17]. One new

Synthesis, characterization and DNA interaction studies of new triptycene derivatives

• Sourav Chakraborty,
• Snehasish Mondal,
• Rina Kumari,
• Sourav Bhowmick,
• Prolay Das and
• Neeladri Das

Beilstein J. Org. Chem. 2014, 10, 1290–1298, doi:10.3762/bjoc.10.130

• tribromotriptycenes as synthons [36], syntheses of triethynyltriptycenes (TETs) 1 and 2 were efficiently realized in two steps (Scheme 1). In the presence of Pd(0) catalyst and cuprous iodide (cocatalyst), Sonogashira cross-coupling reaction of 2,6,14-tribromotriptycene with 3.0 equiv of (trimethylsilyl)acetylene in

Tandem Cu-catalyzed ketenimine formation and intramolecular nucleophile capture: Synthesis of 1,2-dihydro-2-iminoquinolines from 1-(o-acetamidophenyl)propargyl alcohols

• Gadi Ranjith Kumar,
• Yalla Kiran Kumar,
• Ruchir Kant and
• Maddi Sridhar Reddy

Beilstein J. Org. Chem. 2014, 10, 1255–1260, doi:10.3762/bjoc.10.125

• , the reaction is not possible with acetylene as the alkyne partner to produce 3,4-unsubstituted adducts. We herein report the intramolecular version of Wang's protocol for the synthesis of differently substituted products. To explore the practicality of the above reaction, a series of starting

A new building block for DNA network formation by self-assembly and polymerase chain reaction

• Holger Bußkamp,
• Sascha Keller,
• Marta Robotta,
• Malte Drescher and
• Andreas Marx

Beilstein J. Org. Chem. 2014, 10, 1037–1046, doi:10.3762/bjoc.10.104

• 1,3,5-triethynylbenzene scaffold. The oligonucleotides should be directly fused to the benzene ring via the three acetylene modifications resulting in a Y-shape topology. Thereby a rigid core with reduced degrees of rotation will be generated in contrast to other approaches that used more flexible

The influence of intraannular templates on the liquid crystallinity of shape-persistent macrocycles

• Joscha Vollmeyer,
• Ute Baumeister and
• Sigurd Höger

Beilstein J. Org. Chem. 2014, 10, 910–920, doi:10.3762/bjoc.10.89

• Supporting Information File 1). Then 6 is attached to 5 in a fourfold Sonogashira–Hagihara reaction. To compensate the acetylene dimerization side reaction, the acetylene is added in 25% excess. Fluoride-induced removal of the silyl protecting groups yields the precursor 7. With Pd(PPh3)2Cl2 and CuI as

• 1c, the length of the template seems to be similar to the alkyl template in 1a. However, the tendency of oligoethylene oxides to obtain a helical conformation [55] may fold the arylene–acetylene backbone into a boat conformation which is no longer a discotic mesogen. For the macrocycles 2a–d, the

• arylene–acetylene macrocycles. The fact that 1d has a low melting point similar to 1a although the interior is empty, is remarkable and prompted us to investigate 1a and 1d in more detail by X-ray diffraction to gain deeper insight into the structure of their liquid crystalline phases. X-ray diffraction 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

• ) metallacycle 6 (via tin(IV) precursors) active at low catalyst loadings (1–3%) in acetonitrile at 60 °C under a nitrogen atmosphere. The catalyst was effective with aromatic and aliphatic aldehydes, cyclic secondary amines, and phenyl- or TMS-acetylene providing the corresponding propargylamines 1 in excellent

• partners, but imines bearing hindered ortho substituents or too electron-rich imines were not allowed. The reaction with alkylacetylenes( i.e., 1-hexyne), resulted in low yields and selectivity (Scheme 13). The proposed mechanism is shown in Scheme 14. The coordination of acetylene to gold produces the

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

• bromides rather than expensive iodides and using 4 or propiolic acid rather than TMS-acetylene as inexpensive alkyne sources are described. Keywords: alkynes; decarboxylative couplings; Erlotinib; palladium; propiolic acid; Introduction The Sonogashira coupling reaction of aryl or alkenyl halides with

• 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

• the acetylenic proton of 5 was necessary. Analogously to acetylene [80][81], the protection of propiolic acid with acetone was carried out in presence of an excess of KOH (6.0 equiv) at room temperature (Scheme 2). The screening of the optimal palladium catalyst for the Pd-catalyzed coupling reaction

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 acetylene 3 (0.5 mmol) in 5 mL of CH2Cl2 was added the peptide 5 (0.5 mmol), 0.012 g (0.05 mmol) of CuSO4·5H2O in 0.25 mL of H2O and 0.04 g (0.2 mmol) of sodium ascorbate in 0.25 mL of H2O. The reaction mixture was stirred at 40 °С for 1 h. After the reaction was completed 10 mL of CH2Cl2 was

Organobase-catalyzed three-component reactions for the synthesis of 4H-2-aminopyrans, condensed pyrans and polysubstituted benzenes

• Moustafa Sherief Moustafa,
• Saleh Mohammed Al-Mousawi,
• Maghraby Ali Selim,
• Ahmed Mohamed Mosallam and
• Mohamed Hilmy Elnagdi

Beilstein J. Org. Chem. 2014, 10, 141–149, doi:10.3762/bjoc.10.11

• -3,5-dicyanophthalic acid ester derivatives 37a–c were developed. The synthetic methods utilize one-pot reactions of acetylene carboxylic acid esters, α,β-unsaturated nitriles and/or active methylenenitriles in the presence of L-proline or DABCO. Plausible mechanisms are suggested for the formation of

The difluoromethylene (CF₂) group in aliphatic chains: Synthesis and conformational preference of palmitic acids and nonadecane containing CF₂ groups

• Yi Wang,
• Ricardo Callejo,
• Alexandra M. Z. Slawin and
• David O’Hagan

Beilstein J. Org. Chem. 2014, 10, 18–25, doi:10.3762/bjoc.10.4

• ][16][17] for introduction of the CF2 groups. Thus treatment of ketone 21 with DAST resulted in an efficient conversion to difluoromethyleneacetylene 22. This terminal acetylene is amenable to acetylide formation on treatment with BuLi [19][20] and condensation with hexaldehyde gave propargylic alcohol

• synthetic route to 27 is illustrated in Scheme 3. The strategy for incorporating the two CF2 groups followed that used for the preparation of palmitic acid 6c. In this case propargylic ketone 30 was treated with DAST to generate difluoroacetylene 31. The resultant acetylene could then be deprotonated for

• conjugation to aldehyde 32. Oxidation and then fluorination of ketone 34 with DAST, introduced the second CF2 group and generated tetrafluoroacetylene 35. Finally hydrogenation of the central acetylene group gave the saturated tetrafluorononadecane 27. This compound proved to be a crystalline solid (mp 35–37