Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning

• Pablo Quijano Velasco,
• Kedar Hippalgaonkar and
• Balamurugan Ramalingam

Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3

Synthesis of fluoroalkenes and fluoroenynes via cross-coupling reactions using novel multihalogenated vinyl ethers

• Yukiko Karuo,
• Keita Hirata,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 2691–2703, doi:10.3762/bjoc.20.226

• fluoroenynes via Suzuki–Miyaura and Sonogashira cross-coupling reactions using novel multihalogenated fluorovinyl ethers, which are easily prepared from the reaction between phenols and 2-bromo-2-chloro-1,1,1-trifluoroethane (halothane). These reactions make use of the unique structure of multihalogenated

• fluorovinyl ethers, which contains a reactive bromine atom, to afford a series of fluoroalkenes and fluoroenynes in moderate to high yields. Keywords: fluoroalkenes; fluoroenynes; multihalogenated vinyl ethers; Suzuki–Miyaura cross-coupling reactions; Sonogashira cross-coupling reactions; Introduction

• % yield (Table 1, entry 13). Thus, it was concluded that triphenylphosphine is necessary for Suzuki–Miyaura cross-coupling of 1 with 4 and that it is involved in the production of palladium(0). Next, the reaction conditions for the Sonogashira cross-coupling were optimized (Table 2). On the basis of a

Biphenylene-containing polycyclic conjugated compounds

• Cagatay Dengiz

Beilstein J. Org. Chem. 2023, 19, 1895–1911, doi:10.3762/bjoc.19.141

• through Sonogashira cross-coupling reactions with alkynes featuring different protecting groups such as TIPS, TES, and TIBS. Scheme 7 illustrates the derivatization process using one of the chosen examples, specifically the TIPS group. Accordingly, the cross-coupling products 33a–c were obtained in yields

• selectively synthesize compound 87 through a hybrid approach involving the integration of both solution and surface chemistry techniques [53]. The key compound 96 to be used in the synthesis of POA 87 was synthesized in two steps. In the first step, 94 was obtained using a double Sonogashira cross-coupling

Construction of hexabenzocoronene-based chiral nanographenes

• Ranran Li,
• Di Wang,
• Shengtao Li and
• Peng An

Beilstein J. Org. Chem. 2023, 19, 736–751, doi:10.3762/bjoc.19.54

• Sonogashira cross-coupling reaction of phenylacetylene 50 and 1,4-dibromotetrafluorobenzene. The resulting bis[aryl(ethynyl)]tetrafluorobenzene 59 was able to undergo a 2-fold [4 + 2] cycloaddition reaction with cyclopentadienone 2, affording polyaromatic 60 in a 70% yield. The final step was the Scholl

• , diiodide NG 71 reacted with phenylacetylene 50 through Sonogashira cross-coupling, followed by Diels–Alder reaction with tetracyclone 2 to afford precursor 72 in an overall 22% yield. Then the final helical NG 73, which contains different conformations was obtained through Scholl reaction in the presence

• , following the similar synthetic procedure from the dibromo 74 only gave achiral meso isomers (P,P,M,M) [52]. Wang and co-workers synthesized the triangular NG 82 by oxidative cyclodehydrogenation of the hexaphenylbenzene-trimer 81 [53]. As shown in Scheme 9, two-fold Sonogashira cross-coupling reaction of

Total synthesis of insect sex pheromones: recent improvements based on iron-mediated cross-coupling chemistry

• Eric Gayon,
• Guillaume Lefèvre,
• Olivier Guerret,
• Adrien Tintar and
• Pablo Chourreu

Beilstein J. Org. Chem. 2023, 19, 158–166, doi:10.3762/bjoc.19.15

• ]) are linear syntheses involving a great number of steps and purifications as well as cryogenic temperatures. Moreover, the introduction of the C=C unsaturation is achieved via a Wittig reaction or a Pd-catalyzed Sonogashira cross-coupling followed by a reduction by a borane reagent, methods which lead

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• -membered triflate 71 was synthesized from diketone 26 in 5 steps and 37% overall yield. Both fragments were assembled by a Sonogashira cross-coupling, affording 72 in 72% yield. In a first attempt, TBS protection was considered on the bicylo[3.2.1]octane. However, later in the strategy, the deprotection

Simple synthesis of multi-halogenated alkenes from 2-bromo-2-chloro-1,1,1-trifluoroethane (halothane)

• Yukiko Karuo,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1567–1574, doi:10.3762/bjoc.18.167

• HF from 1 provides 2 as an E/Z mixuture (E/Z = 1:1). We speculated that the stability of the E isomer was equal to that of the Z isomer under these conditions. To expand the scope of this reaction, we subjected product 2 to a Sonogashira cross-coupling reaction (Scheme 3). This gave a highly

• functionalized enyne structure that will be useful in various molecular transformations [27][28][29]. On the basis of a previous report, Sonogashira cross-coupling of 2 with trimethylsilylacetylene was performed with a bis(triphenylphosphine)palladium(II) dichloride. The reaction proceeded smoothly to give

• presence of KOH. In this reaction, halothane plays a key role in the construction of highly halogenated and structurally intriguing products. The tri-halogenated alkenyl ether has potential applications in organic chemistry, e.g., in Suzuki–Miyaura or Sonogashira cross-coupling reactions. Further

Recent developments and trends in the iron- and cobalt-catalyzed Sonogashira reactions

• Surendran Amrutha,
• Sankaran Radhika and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 262–285, doi:10.3762/bjoc.18.31

• exceptional versatility [13][14][15]. Therefore, the low cost first series transition metals such as iron and cobalt show higher significance than other transition metals. Naturally, Sonogashira cross-coupling reactions using cobalt or iron catalysts were reported as more cost-effective alternatives to the

• /hydroalkoxylation of alkynes was also reported (Scheme 8). Vogel and co-workers demonstrated the Sonogashira cross-coupling reaction of aryl iodides with terminal alkynes by utilizing cheap, non-toxic iron salts and copper iodide (Scheme 9) [26]. The reaction of 4-iodotoluene with phenylacetylene was chosen as the

• synthesized 2-arylbenzo[b]furans by intramolecular arylation and Sonogashira cross-coupling of o-iodophenol with phenylacetylene/1-substituted-2-trimethylsilylacetylene under iron(III) catalysis in the presence of 5 mol % 1,10-phenanthroline as ligand and Cs2CO3 as base (Scheme 14) [31]. The use of 1,10

Visible-light-mediated copper photocatalysis for organic syntheses

• Yajing Zhang,
• Qian Wang,
• Zongsheng Yan,
• Donglai Ma and
• Yuguang Zheng

Beilstein J. Org. Chem. 2021, 17, 2520–2542, doi:10.3762/bjoc.17.169

• promising, scalable green process that can be used as an alternative to the conventional Sonogashira cross-coupling reactions. In 2018, Lalic and co-workers [66] extended this approach to alkyl halides and reported the photoinduced copper-catalyzed Sonogashira coupling of alkynes and alkyl iodide 21. The

Chemical syntheses and salient features of azulene-containing homo- and copolymers

• Vijayendra S. Shetti

Beilstein J. Org. Chem. 2021, 17, 2164–2185, doi:10.3762/bjoc.17.139

• -(n-dodecyl)azulene (16) is shown in Scheme 5A. The Sonogashira cross-coupling reaction between 4,7-dibromo-6-(n-dodecyl)azulene (13) and 4,7-diethynyl-6-(n-dodecyl)azulene (16) yielded 4,7-polyazulene 17 linked through ethynyl bridges (Scheme 5B). Similarly, the Yamamoto cross-coupling reaction

Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides

• Mathias B. Danielsen and
• Jesper Wengel

Beilstein J. Org. Chem. 2021, 17, 1828–1848, doi:10.3762/bjoc.17.125

• containing a stretch of four DNA nucleotides in the middle, flanked by the modifications in a ´mixmer´ design, which is important for designing gapmer ASOs [31]. Another well-established method for C-5 pyrimidine modification involves the Sonogashira cross-coupling reaction between an alkyne group and a 5

2,4-Bis(arylethynyl)-9-chloro-5,6,7,8-tetrahydroacridines: synthesis and photophysical properties

• Najeh Tka,
• Mohamed Adnene Hadj Ayed,
• Mourad Ben Braiek,
• Mahjoub Jabli,
• Noureddine Chaaben,
• Kamel Alimi,
• Stefan Jopp and
• Peter Langer

Beilstein J. Org. Chem. 2021, 17, 1629–1640, doi:10.3762/bjoc.17.115

• properties. Herein, starting from readily available anthranilic acid, an efficient synthesis of 2,4-bis(arylethynyl)-9-chloro-5,6,7,8-tetrahydroacridine derivatives was accomplished via a one-pot double Sonogashira cross-coupling method. The UV-visible absorption and emission properties of the synthesized

• )-9-chloro-5,6,7,8-tetrahydroacridine derivatives via a double Sonogashira cross-coupling method. The arylethynyl groups expand the π-conjugation of the tetrahydroacridine core. The substituents located at the aryl group influenced the photophysical properties of the prepared molecules. In particular

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• ) and 5′-O-DMTr-protected N4-(dimethylaminomethylene)-2′-deoxycytidine (134a–d) by using Sonogashira cross coupling reaction between the propargylated nucleobases, i.e., 1-propargylthymine, N4-acetyl-1-propargylcytosine, N6-benzoyl-9-propargyladenine, and N2-isobutyryl-9-propargylguanine (13a–d) and 5

• -dimethoxytrityl-5-(4-(thymin-1-yl)phenyl)ethynyl-2′-deoxyuridine (141) were synthesized via a Sonogashira cross coupling reaction between the N1-(3/4-iodophenyl)thymine derivatives 136c and 136d and 2′-deoxy-5-ethynyluridine derivative 139 (Scheme 35) [75]. All four nucleoside monomers were converted into

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• Hale and Hatakeyama [57]. Recently, Burton’s group developed some efficient and tin-free total syntheses of all three inthomycins A–C ((+)-1, (+)-2, and (−)-3) using a Suzuki or Sonogashira cross-coupling of the (E)- or (Z)-alkenyl iodides 130 with the dienylboronic ester 128 as key step (Schemes 18–22

Changed reactivity of secondary hydroxy groups in C8-modified adenosine – lessons learned from silylation

• Jennifer Frommer and
• Sabine Müller

Beilstein J. Org. Chem. 2020, 16, 2854–2861, doi:10.3762/bjoc.16.234

• phosphoramidite building block 9 (Scheme 2). Results and Discussion Typically, the synthesis of C8-alkynyl derivatives relies on C8-bromoadenosine as reactant for the Sonogashira cross-coupling reaction to introduce the amino linker N-(propyn-2-yl)-6-(trifluoroacetamido)hexanamide (L) bearing an alkynyl moiety

• , which allows its selective removal with simultaneous preservation of the 2’-O-TBDMS group. This advantage on the one hand, might cause problems on the other. It was not for sure, if the cyclic silyl ether would be sufficiently stable under the conditions of iodination and Sonogashira cross coupling, and

Regiodivergent synthesis of functionalized pyrimidines and imidazoles through phenacyl azides in deep eutectic solvents

• Paola Vitale,
• Luciana Cicco,
• Ilaria Cellamare,
• Filippo M. Perna,
• Antonio Salomone and
• Vito Capriati

Beilstein J. Org. Chem. 2020, 16, 1915–1923, doi:10.3762/bjoc.16.158

• ], (c) carbon–sulfur bond-forming reactions [9], (d) directed ortho-metalation and nucleophilic acyl substitution strategies [10], (e) Pd-catalyzed aminocarbonylation of aryl iodides, Suzuki–Miyaura and Sonogashira cross-coupling reactions [11][12][13], (f) Cu-catalyzed C–N coupling reactions [14], and

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

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

• investigated for its use as a rigid isolating unit in the synthesis of multichromophoric arrays. Sonogashira cross-coupling conditions are utilized to attach various porphyrins and boron dipyrromethenes (BODIPYs) to the triptycene scaffold. While there are previous examples of triptycene porphyrin complexes

• evident linearity in these systems. Moreover, initial UV–vis and fluorescence studies show the promise of triptycene as a linker for electron transfer studies, showcasing its isolating nature. Keywords: BODIPY; Pd-catalyzed cross-coupling; porphyrins; Sonogashira cross-coupling; triptycene; Introduction

• complexes such as 2 were synthesized by us with the purpose of conducting electron transfer studies [25]. Both Suzuki and Sonogashira cross-coupling reactions were employed to realize this new class of triptycene-linked trimeric porphyrins. The three porphyrins, or three BODIPYs in 2 were either linked

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

• Glaser-coupling reactions [37]. Conventionally, an alkynylation of the BODIPY core has been achieved by palladium-catalyzed Sonogashira cross-coupling with halogenated BODIPYs (Figure 1b) [35][37]. However, due to the coexistence of multiple C–H bonds, a regioselective direct C–H alkynylation of the

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

• Sonogashira coupling of iodobenzene (1a) and phenylacetylene (2a). Reaction conditions: 0.8 mL [TBP][4EtOV], 0.5 mol % catalyst, T = 55 °C, t = 3 h. Palladium-catalyzed Sonogashira cross-coupling of iodobenzene (1a) and phenylacetylene (2a) in ionic liquids. Sonogashira coupling reaction of iodobenzene (1a

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

• decomposition, which is a necessary precondition for ultra-high vacuum STM investigations. The 3-bromo-2-cyano-substituted norbornadiene 4 was synthesized as described in the literature (Scheme 1) [10][11][12]. 4 was converted to 5 with trimethylsilylacetylene (72%) in a Sonogashira cross-coupling reaction. The

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

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

• a function of electronic coupling (conjugation) of the azo unit to gold. The para-diazocine-TATA 1 was synthesized in a 5-step synthesis route (Scheme 1). Bromotoluene 3 was synthesized as described [26]. In a Sonogashira cross-coupling reaction acetylene-substituted toluene 5 was prepared from

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

• procedures 7 is obtained over two mono-iodination steps, we report here the di-iodination in a single step. Subsequently, 7 was reacted in a Sonogashira cross coupling with trimethylsilylacetylene to give 1,4-bis(2-trimethylsilylethynyl)-2,3-difluorobenzene (8). Finally, 8 was converted to the dicarboxylic

Nucleoside macrocycles formed by intramolecular click reaction: efficient cyclization of pyrimidine nucleosides decorated with 5'-azido residues and 5-octadiynyl side chains

• Jiang Liu,
• Peter Leonard,
• Sebastian L. Müller,
• Constantin Daniliuc and
• Frank Seela

Beilstein J. Org. Chem. 2018, 14, 2404–2410, doi:10.3762/bjoc.14.217

• %) together with the dimeric side product 3 (4.5%, Scheme 1) [37]. The moderate yield of the 5’azido-dC derivative results from incomplete conversion. Possibly, traces of copper used for the Sonogashira cross coupling and high substrate concentration were initiating dimerization of azide 2. Nevertheless, an