A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Structural effects of meso-halogenation on porphyrins

• Keith J. Flanagan,
• Maximilian Paradiz Dominguez,
• Zoi Melissari,
• Hans-Georg Eckhardt,
• René M. Williams,
• Dáire Gibbons,
• Caroline Prior,
• Gemma M. Locke,
• Alina Meindl,
• Aoife A. Ryan and
• Mathias O. Senge

Beilstein J. Org. Chem. 2021, 17, 1149–1170, doi:10.3762/bjoc.17.88

• arrangement (Supporting Information File 1, Figure S60) which is propagated through the crystal packing (Supporting Information File 1, Figure S61). Finally, the structure of 24 is included due to the presence of 2A and 16A (Supporting Information File 1, Figures S62–S63). As a series of TMS-ethynyl

• -visible absorption measurements were performed using a Shimadzu MultiSpec-1501. Synthetic procedures The synthesis of 5-bromo-10,20-diphenylporphyrin (1) [46], [5-ethynyl-10,20-diphenylporphyrinato]nickel(II) (2A) [47], 5-bromo-10,20-dihexyl-15-phenylporphyrin (5) [48], [5-bromo-10,20-dihexyl-15

• -dibromo-10-hexyl-20-(3,4,5-trimethoxyphenyl)porphyrin (13) [24], 5,10-bis(4-methylphenyl)-15,20-bis((trimethylsilyl)ethynyl)porphyrin (16A) [53], and 10,15,20-trihexyl-5-((trimethylsilyl)ethynyl) porphyrin (24) [54] have previously been reported. Synthesis of 5-chloro-10,20-bis(4-methylphenyl)-15

Asymmetric Mannich reactions of (S)-N-tert-butylsulfinyl-3,3,3-trifluoroacetaldimines with yne nucleophiles

• Ziyi Li,
• Li Wang,
• Yunqi Huang,
• Haibo Mei,
• Hiroyuki Konno,
• Hiroki Moriwaki,
• Vadim A. Soloshonok and
• Jianlin Han

Beilstein J. Org. Chem. 2020, 16, 2671–2678, doi:10.3762/bjoc.16.217

• [41][42][43][44][45][46][47][48][49][50][51][52][53][54], the initial reaction conditions focused on the use of 1.3 equiv of 1-ethynyl-4-methoxybenzene (2a) in the presence of n-BuLi with CH2Cl2 as a solvent at −78 °C. The desired product 3a was obtained after 2.5 hours in 46% yield as a mixture of

• diastereoselectivity (69:31 dr, Table 1, entry 3). On the other hand, the solvent was found to show a significant effect on this transformation (Table 1, entries 4–6) and the results indicated dichloromethane was the best choice. Variation of the loading amount of 1-ethynyl-4-methoxybenzene (2a) did not provide any

When metal-catalyzed C–H functionalization meets visible-light photocatalysis

• Lucas Guillemard and
• Joanna Wencel-Delord

Beilstein J. Org. Chem. 2020, 16, 1754–1804, doi:10.3762/bjoc.16.147

• an aromatic unit in α-position to the nitrogen atom. Sensitive functional groups such as hydroxy, silyl, and ethynyl were tolerated by this protocol. Furthermore, this methodology was also extended towards the C–H annulation with dienes. The proposed mechanism of this reaction requiring only oxygen

Heterogeneous photocatalysis in flow chemical reactors

• Christopher G. Thomson,
• Ai-Lan Lee and
• Filipe Vilela

Beilstein J. Org. Chem. 2020, 16, 1495–1549, doi:10.3762/bjoc.16.125

• bipyridyl units have been designed to immobilise transition metal complexes through coordinate bonding for the oxidative coupling of amines [138]. [Ru(bpy)3]2+ units were synthesised with ethynyl groups para-substituted to the nitrogen heteroatom on four of the six pyridine rings. The ethynyl groups were

Diversity-oriented synthesis of 17-spirosteroids

• Benjamin Laroche,
• Thomas Bouvarel,
• Martin Louis-Sylvestre and
• Bastien Nay

Beilstein J. Org. Chem. 2020, 16, 880–887, doi:10.3762/bjoc.16.79

• Paris, Palaiseau Cedex, France 10.3762/bjoc.16.79 Abstract A diversity-oriented synthesis (DOS) approach has been used to functionalize 17-ethynyl-17-hydroxysteroids through a one-pot procedure involving a ring-closing enyne metathesis (RCEYM) and a Diels–Alder reaction on the resulting diene, under

• microwave irradiations. Taking advantage of the propargyl alcohol moiety present on commercially available steroids, this classical strategy was applied to mestranol and lynestrenol, giving a collection of new complex 17-spirosteroids. Keywords: diversity-oriented strategy; 17-ethynyl-17-hydroxysteroids

• targeted strategy, lies on the 17-ethynyl-17-hydroxysteroids (Figure 1). They are commonly used as contraceptive while their skeleton is structurally diversified, especially at ring A. They are thus synthetically relevant as starting materials in a DOS approach. Indeed, after installing an alkenyl ether on

Towards triptycene functionalization and triptycene-linked porphyrin arrays

• Gemma M. Locke,
• Keith J. Flanagan and
• Mathias O. Senge

Beilstein J. Org. Chem. 2020, 16, 763–777, doi:10.3762/bjoc.16.70

• porphyrin units have been connected in a number of different ways; from phenylene, ethynyl, ethenyl or alkane linkers [5][6][7][8], to meso–β- [9] or β–β-linkages [10] or alternatively by connecting two or more meso–meso-linked porphyrin units via oxidative fusing reactions [11][12][13][14][15]. However

• Information File 1 for full experimental data). Instead we focused on the synthesis of systems with ethynyl spacers between the triptycene bridgehead positions and chromophores. To allow for the generation of symmetric and unsymmetric dyads 9,10-diethynyltriptycene 5 and its anthracene precursor were

• synthesized as per a literature procedure [36] while, 9-[(triisopropylsilyl)ethynyl]-10-ethynyltriptycene (12) and its precursors were synthesized according to the procedure from Toyota et al. [37], respectively. Synthesis of triptycene-linked porphyrin dimers With the introduction of synthetic handles to the

Regioselectively α- and β-alkynylated BODIPY dyes via gold(I)-catalyzed direct C–H functionalization and their photophysical properties

• Takahide Shimada,
• Shigeki Mori,
• Masatoshi Ishida and
• Hiroyuki Furuta

Beilstein J. Org. Chem. 2020, 16, 587–595, doi:10.3762/bjoc.16.53

• , Japan 10.3762/bjoc.16.53 Abstract A series of α- and β-ethynyl-substituted BODIPY derivatives (3a, 4a, 5a, 5b, 6a, 6b) were synthesized by gold(I)-catalyzed direct C–H alkynylation reactions of dipyrromethane and BODIPY, respectively, with ethynylbenziodoxolone (EBX) in a regioselective manner

• . Depending on the position of the ethynyl substituent in the BODIPY skeleton, the photophysical properties of the resulting α- and β-substituted BODIPYs are notably altered. The lowest S0–S1 transition absorbance and fluorescence bands are both bathochromically shifted as the number of substituents increases

• ., bromination) of BODIPY derivatives often affords a mixture of multiply halogenated products, which is tedious to separate by column chromatography. The introduction of one or more alkynyl groups into the BODIPY skeleton indeed produces useful building blocks for functional π-materials. For example, ethynyl

Palladium-catalyzed Sonogashira coupling reactions in γ-valerolactone-based ionic liquids

• László Orha,
• József M. Tukacs,
• László Kollár and
• László T. Mika

Beilstein J. Org. Chem. 2019, 15, 2907–2913, doi:10.3762/bjoc.15.284

• various iodoaromatic compounds (1a, d, m) with propargyl alcohol (4).a Palladium-catalyzed Sonogashira coupling of various iodoaromatic compounds (1a, d, m) with 1-ethynyl-1-cyclohexanol (6).a Palladium-catalyzed Sonogashira coupling of various iodoaromatic compounds (1a, d, m) with 3-ethyl-1-pentyn-3-ol

Thermal stability of N-heterocycle-stabilized iodanes – a systematic investigation

• Andreas Boelke,
• Yulia A. Vlasenko,
• Mekhman S. Yusubov,
• Boris J. Nachtsheim and
• Pavel S. Postnikov

Beilstein J. Org. Chem. 2019, 15, 2311–2318, doi:10.3762/bjoc.15.223

• of group-transfer reactions. Prominent examples include ethynyl benziodoxolones (EBX, L1 = alkyne) [12], the Zhdankin reagent azidobenziodoxole (ABX, L1 = N3) [13], cyanobenziodoxole (CBX, L1 = CN) [14] or Togni’s reagent (L1 = CF3) [15]. Even though the transferable ligand (L1) has been varied

Fluorinated azobenzenes as supramolecular halogen-bonding building blocks

• Esther Nieland,
• Oliver Weingart and
• Bernd M. Schmidt

Beilstein J. Org. Chem. 2019, 15, 2013–2019, doi:10.3762/bjoc.15.197

• photochemical properties upon introducing the heavy iodine to the azobenzene building block, as well as the effect of the ethynyl group in case of A3 (Figure 2). Vertical electronic absorption spectra of the different azobenzenes were calculated at the TD-B3LYP/def2-TZVP level of theory including Grimme D3

Norbornadiene-functionalized triazatriangulenium and trioxatriangulenium platforms

• Roland Löw,
• Talina Rusch,
• Tobias Moje,
• Fynn Röhricht,
• Olaf M. Magnussen and
• Rainer Herges

Beilstein J. Org. Chem. 2019, 15, 1815–1821, doi:10.3762/bjoc.15.175

• monolayers. A linear, π-conjugated spacer (e.g., an ethynyl unit) is attached to the central carbon atom and the functional molecule is mounted on top. This architecture allows investigating molecules on surfaces under controlled conditions. The size of the platforms determines the intermolecular distances

• parameter controlling the cis–trans rate acceleration of azobenzenes and not the length of the spacer [1]. A full conjugation path from the azobenzene on top through the ethynyl spacer and the platform to a bulk gold surface shortens the half-life of the metastable cis-isomer from days to seconds even

• of a triplet sensitizer, mediate the spin change (which otherwise is forbidden) and accelerate the cycloreversion. Substitution in the 2 and 3 positions shifts the bathochromic absorption to 375 nm which is in agreement with similar systems [8]. Furthermore, the cyano and ethynyl groups provide a

Synthesis, enantioseparation and photophysical properties of planar-chiral pillar[5]arene derivatives bearing fluorophore fragments

• Guojuan Li,
• Chunying Fan,
• Guo Cheng,
• Wanhua Wu and
• Cheng Yang

Beilstein J. Org. Chem. 2019, 15, 1601–1611, doi:10.3762/bjoc.15.164

• derivatives P5A-Py was synthesized by following our previously reported processes [34], and P5A-DPA was synthesized by the processes illustrated in Scheme 1. The ethynyl-bearing pillar[5]arene derivative P5A was obtained through the co-cyclization of 4.0 equiv of 1,4-dimethoxybenzene with 1.0 equiv of the

Diazocine-functionalized TATA platforms

• Roland Löw,
• Talina Rusch,
• Fynn Röhricht,
• Olaf Magnussen and
• Rainer Herges

Beilstein J. Org. Chem. 2019, 15, 1485–1490, doi:10.3762/bjoc.15.150

• ” (triazatriangulenium) platforms which adsorb on Au(111) surfaces. A spacer, such as an ethynyl group is connected to the central carbon atom like a post and the azobenzene is mounted on top of the spacer. After preparation of an ordered self-assembled monolayer on gold, the azobenzene units are freestanding upright on

• that are more stable in their trans-configurations [23]. To investigate the electronic coupling effects, we synthesized two diazocine derivatized TATA platforms with ethynyl spacers (diazocine-TATAs). In compound 1 the diazocine is connected to the platform with the ethynyl group in para-position to

• the azo group, providing a full π-conjugation path of the N=N unit through the ethynyl spacer into the platform. Diazocine-TATA 2 is connected in meta-position and thus interrupting conjugation [24][25]. Both diazocine-TATAs are equipped with methoxy groups, which serve as “reporter units” indicating

Borylation and rearrangement of alkynyloxiranes: a stereospecific route to substituted α-enynes

• Ruben Pomar Fuentespina,
• José Angel Garcia de la Cruz,
• Gabriel Durin,
• Victor Mamane,
• Jean-Marc Weibel and
• Patrick Pale

Beilstein J. Org. Chem. 2019, 15, 1416–1424, doi:10.3762/bjoc.15.141

• challenge in organic chemistry. Results and Discussion Reaction set up First we selected the simple 2-ethynyl-3-dimethyloxirane 1a to probe the feasibility of the reaction. In order to avoid unwanted reactions upon metalation [23], the ethynyl group was silylated and a bulky silyl group was installed to

Synthesis of dipolar molecular rotors as linkers for metal-organic frameworks

• Sebastian Hamer,
• Fynn Röhricht,
• Marius Jakoby,
• Ian A. Howard,
• Xianghui Zhang,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2019, 15, 1331–1338, doi:10.3762/bjoc.15.132

• molecules. Four rotors are fluorescent in the visible region. The linker designs are based on push–pull-substituted phenylene cores with ethynyl spacers as rotational axes, functionalized with carboxylic acid groups for implementation in MOFs. The substituents at the phenylene core are chosen to be small to

• is provided by ethynyl units as rotary joints. Carboxylate groups are terminating the axes on both sides because they are known to form the typical paddle wheel structures in MOFs [36]. Benzo-annelated 2,1,3-thiadiazoles were introduced (2 and 3) to shift absorption and fluorescence into the visible

• Müllen et al. [32] without compromising MOF compatibility by 4,5-diamino substitution. Synthesis of dipolar molecular rotor linkers The key step for the synthesis of all reported linkers is the coupling of a substituted aromatic core unit with two ethynyl substituents in para-orientation as spacer units

Remarkable effect of alkynyl substituents on the fluorescence properties of a BN-phenanthrene

• Alberto Abengózar,
• David Sucunza,
• Patricia García-García and
• Juan J. Vaquero

Beilstein J. Org. Chem. 2019, 15, 1257–1261, doi:10.3762/bjoc.15.122

• fluorescence quantum yield of BN-phenanthrene seems to be a general effect, irrespective of its position. It should be noted that the introduction of ethynyl groups into the all-carbon phenanthrene skeleton results in a slight increase in the fluorescence quantum yields compared to that of phenanthrene [27

Stereo- and regioselective hydroboration of 1-exo-methylene pyranoses: discovery of aryltriazolylmethyl C-galactopyranosides as selective galectin-1 inhibitors

• Alexander Dahlqvist,
• Axel Furevi,
• Niklas Warlin,
• Hakon Leffler and
• Ulf J. Nilsson

Beilstein J. Org. Chem. 2019, 15, 1046–1060, doi:10.3762/bjoc.15.102

• mesyl chloride in pyridine at 0 °C to give 2-deoxy-1-mesylgalactoheptulose 8 (91%), followed by a nucleophilic substitution reaction with sodium azide in dimethylformamide to give the azide 9 in good yield (90%) [26]. The azide 9 was reacted with a panel of substituted ethynyl arenes to give

• -Tetra-O-benzyl-1,2-dideoxy-1-[4-(4-fluorophenyl)-1H-1,2,3-triazol-1-yl]-β-D-galactoheptulose (10b): Compound 9 (113 mg, 0.198 mmol), 1-ethynyl-4-fluorobenzene (29 mg, 0.238 mmol), and copper(I) iodide (4 mg, 0.035 mmol) were dissolved in dry acetonitrile (3 mL) under nitrogen, triethylamine (55 μL,0.397

• -galactoheptulose (10c): Compound 9 (107 mg, 0.185 mmol) and copper(I) iodide (4 mg, 0.035 mmol) were dissolved in dry acetonitrile (3 mL) under nitrogen, triethylamine (51 μL (0.369 mmol) and 1-ethynyl-3-fluorobenzene (26 μL, 0.221 mmol) were added, and the reaction was left at room temperature overnight. Upon

Photochemical generation of the 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) radical from caged nitroxides by near-infrared two-photon irradiation and its cytocidal effect on lung cancer cells

• Ayato Yamada,
• Manabu Abe,
• Yoshinobu Nishimura,
• Shoji Ishizaka,
• Masashi Namba,
• Taku Nakashima,
• Kiyofumi Shimoji and
• Noboru Hattori

Beilstein J. Org. Chem. 2019, 15, 863–873, doi:10.3762/bjoc.15.84

• addition to the fundamental study. Results and Discussion The caged-TEMPOs 2a and 2b were synthesized as shown in Scheme 2. The new compounds, 5-ethyl- and 6-ethyl-2-(4-nitrophenyl)benzofuran (5a and 5b), were synthesized from 1-ethynyl-4-nitrobenzene (4) that was prepared from the commercially available 1

The LANCA three-component reaction to highly substituted β-ketoenamides – versatile intermediates for the synthesis of functionalized pyridine, pyrimidine, oxazole and quinoxaline derivatives

• Tilman Lechel,
• Roopender Kumar,
• Mrinal K. Bera,
• Reinhold Zimmer and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2019, 15, 655–678, doi:10.3762/bjoc.15.61

• the examples shown in Scheme 14 [33]. Nonaflate PM54 underwent a Suzuki–Miyaura reaction to PM55 or a Sonogashira coupling to PM56 under standard conditions. The ethynyl-substituted pyrimidine derivative PM12 could also be employed in C–C coupling reactions as shown by its connection to pyridyl

• polyphosphoric acid to undergo a Fischer indole reaction to 5-indolyl-substituted oxazole OX20. To demonstrate the versatility of the route to new oxazole derivatives, typical palladium-catalyzed processes are compiled in Scheme 27. First, the acetyl moiety was converted into a vinyl or an ethynyl substituent

• reagent. First, the corresponding nonaflate is generated from OX7 that immediately underwent elimination to the alkyne. Ethynyl-substituted oxazole OX23 was isolated in excellent yield and subsequently employed in Sonogashira couplings. Iodobenzene afforded compound OX24 in high yield and (β-ketoenamide

Design, synthesis and structure of novel G-2 melamine-based dendrimers incorporating 4-(n-octyloxy)aniline as a peripheral unit

• Cristina Morar,
• Pedro Lameiras,
• Attila Bende,
• Gabriel Katona,
• Emese Gál and
• Mircea Darabantu

Beilstein J. Org. Chem. 2018, 14, 1704–1722, doi:10.3762/bjoc.14.145

• (ethynyl)-s-triazine and various icosanyloxyphenylazides) with liquid crystalline and luminescent properties [22]. On the other hand, mesogenic supramolecular perylene bisimide assemblies with a number of 2-amino-4,6-bis[(4-alkoxy)phenylamino]-s-triazines [23], amphiphilic azobenzene-containing linear

[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

• -substituted ethynyl)-1,3,2-dioxaborolanes (R4–C≡C–BPin; Scheme 10) was recently developed by Harrity et al. [79][80][81][84][91][107]. In most cases this reaction proceeds with excellent regioselectivity (>98:2) to give the corresponding 1-(substituted phenyl)-3,5-disubstituted -4-BPin-pyrazole, whose BPin

• -tetramethyl-2-ethynyl-1,3,2-dioxaborolane (R4: H) reacts with alkyl/arylsydnones with completely opposite ratio (>7:1) of both regioisomers – i.e., for the BPin group the reaction preferentially occurs in position 3 of the final pyrazole (see entries 62, 64–66, 89, 109 and 110 in Table 4). In this case, using

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

• 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

• . Electrochemical synthesis of 9-ethyl-3-ethynyl-9H-carbazole (2b). Electrochemical synthesis of 1-ethynyl-4-methoxybenzene (2c). Electrochemical synthesis of 2-ethynylnaphthalene (2a). Electrolysis conditions optimization (Scheme 5).a Supporting Information Supporting Information File 58: Detailed experimental

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

• , phenylglycine and tyrosine) have been prepared using a large excess (4 equivalents) of [(trimethylsilyl)ethynyl]dimethylaluminum as the nucleophile [14][48][52]. The reaction of the sulfinylimines 5 with (trimethylsilyl)ethynyllithium provided the crude intermediates 6, which were converted into the N-sulfinyl

Synthesis and photophysical properties of novel benzophospholo[3,2-b]indole derivatives

• Mio Matsumura,
• Mizuki Yamada,
• Atsuya Muranaka,
• Misae Kanai,
• Naoki Kakusawa,
• Daisuke Hashizume,
• Masanobu Uchiyama and
• Shuji Yasuike

Beilstein J. Org. Chem. 2017, 13, 2304–2309, doi:10.3762/bjoc.13.226

• , Japan Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo 113-0033, Japan 10.3762/bjoc.13.226 Abstract The parent benzophospholo[3,2-b]indole was prepared by the reaction of dichlorophenylphosphine with a dilithium intermediate, which was prepared in two steps from 2-ethynyl-N,N

• Scheme 1. The key precursor 2 was synthesized by I2-mediated electrophilic cyclization of 2-ethynyl-N,N-dimethylaniline 1 [36][37]. Treatment of compound 2 with n-butyllithium in anhydrous THF at −78 °C and subsequently with PhPCl2 resulted in ring closure, affording the desired benzophospholo[3,2-b