Deep-blue emitting 9,10-bis(perfluorobenzyl)anthracene

• Long K. San,
• Sebastian Balser,
• Brian J. Reeves,
• Tyler T. Clikeman,
• Yu-Sheng Chen,
• Steven H. Strauss and
• Olga V. Boltalina

Beilstein J. Org. Chem. 2025, 21, 515–525, doi:10.3762/bjoc.21.39

• -step reactions with anthraquinone starting materials [24], or by Ullman coupling reactions of acene bromides with perfluoroalkyl iodides [25]. Notably, direct UV photoinduced reactions between anthracene and perfluoroalkyl iodides in the presence of a reducing agent, Na2S2O3, yielded perfluoroalkylated

Synthesis of N-acetyl diazocine derivatives via cross-coupling reaction

• Thomas Brandt,
• Pascal Lentes,
• Jeremy Rudtke,
• Michael Hösgen,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2025, 21, 490–499, doi:10.3762/bjoc.21.36

• switching efficiency in aqueous solutions. In order to investigate the chemistry of this promising photoswitch and to unlock further applications, we now investigate strategies for the synthesis of derivatives, which are based on cross-coupling reactions. Fourteen vinyl-, aryl-, cyano-, and amino

• substitution. Substituents such as halogen atoms must be introduced into the N-acetyl diazocine structure during the synthesis of the building blocks. In the present work we start from mono- and dihalogenated N-acetyl diazocine 2–4 (Figure 2) and focus on the further derivatization via cross-coupling reactions

• except the preparation of the aminoaniline building block tert-butyl (2-amino-5-bromophenyl)carbamate (5), which was prepared by Boc-protection of the 5-bromo-2-nitroaniline (6) and subsequent reduction of the nitro group (see Supporting Information File 1, section II.1). Cross-coupling reactions Stille

The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

• glycosylation reaction between the two extremes of substitution reactions enables the synthetic chemists to manoeuvre and design the coupling reactions according to the regio- and stereochemical demand. In chemical glycosylation, the role of protecting groups in directing the attack of the incoming nucleophile

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

• . While transition metals such as copper, palladium, cobalt, and nickel are well-established in catalyzed cross-coupling reactions, J. Cornella et al. have highlighted the reactivity of main-group elements like bismuth, which can mimic transition-metal behavior through oxidative addition. In their recent

• 9,10-dicyanoanthracene radical anion (DCA•−) [29]. This system effectively drives photoredox-mediated reduction and C–C cross-coupling reactions under mild red-light conditions with various aryl halides, an aliphatic iodide, and O- and N-tosylated substrates (Scheme 4a). The authors discuss two

• molecular orbital (HOMO), thereby shifting the absorption of the complexes into the NIR region (around 810 nm). The authors have demonstrated the efficiency of their photocatalyst in cross-dehydrogenative coupling reactions with N-phenyltetrahydroisoquinoline 21 and diverse nucleophiles (Scheme 7). Their

Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• stoichiometric quantities of a copper reagent [3]. This pioneering work, known as the “classical Ullmann reaction”, was extended by Ullmann and Goldberg to enable the C–N and C–O bond formation [4][5][6]. Subsequently, key developments in Cu-catalyzed cross-coupling reactions were achieved, including the

• amounts of copper reagents. Consequently, investigation into more practical and sustainable reactions remains an area of ongoing research [10]. Conventional cross-coupling reactions typically require C(sp2)-based electrophiles and nucleophiles as coupling partners. Generally, the reaction is initiated

• through oxidative addition, followed by transmetalation and reductive elimination, to obtain the desired product. Throughout the catalytic cycle, the catalyst undergoes conversion between [M]n and [M]n+2 (Figure 1) [11]. However, using alkyl electrophiles as coupling partners in cross-coupling reactions

Nickel-catalyzed cross-coupling of 2-fluorobenzofurans with arylboronic acids via aromatic C–F bond activation

• Takeshi Fujita,
• Haruna Yabuki,
• Ryutaro Morioka,
• Kohei Fuchibe and
• Junji Ichikawa

Beilstein J. Org. Chem. 2025, 21, 146–154, doi:10.3762/bjoc.21.8

• coupling reactions of aromatic C–F and C–Br bonds with arylboronic acids. Keywords: arylboronic acid; benzofuran; C–F bond activation; cross-coupling; nickel; Introduction The metal-catalyzed activation of aromatic carbon–fluorine (C–F) bonds is widely recognized as a challenging task in synthetic

• distinct aryl groups onto a benzofuran ring through orthogonal coupling reactions, exploiting the reactivity difference between C–F and C–Br bonds (Scheme 4). Using a palladium catalyst, 5-bromo-2-fluorobenzofuran (1e) was coupled with [4-(trifluoromethyl)phenyl]boronic acid (2g). In this reaction, only

• ]benzofuran (3fa) in 81% yield. Next, we explored the mechanism of the coupling reactions between 2-fluorobenzofurans 1 and arylboronic acids 2. Because these reactions proceed under mild conditions despite involving aromatic C–F bond activation [19], direct oxidative addition of C–F bonds is unlikely (Scheme

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• Pd-catalyzed cross-coupling reactions, allowing the formation of C–C and C–N bonds in the o-position of the aryl chalcogen compounds. α-Aminophosphonates 14 were the result of a one-pot condensation of an aldehyde, a primary amine and phosphite P(OMe)3 with copper triflate acting as Lewis acid

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

• different conditions. This parallel reactor setup was successfully utilized for the multistep synthesis of 18 compounds of an anticonvulsant drug, employing various reaction pathways to perform photoredox carbon–nitrogen cross-coupling reactions. A parallel droplet flow system was developed by Eyke et al

• stirred tank reactor (CSTR) cascade. The platform allowed to showcase the autonomous optimization to find the ideal reaction conditions for Suzuki–Miyaura and photoredox-catalyzed coupling reactions. A plug-and-play, continuous-flow chemical synthesis system (Figure 6a) was intelligently designed by

Efficient synthesis of fluorinated triphenylenes with enhanced arene–perfluoroarene interactions in columnar mesophases

• Yang Chen,
• Jiao He,
• Hang Lin,
• Hai-Feng Wang,
• Ping Hu,
• Bi-Qin Wang,
• Ke-Qing Zhao and
• Bertrand Donnio

Beilstein J. Org. Chem. 2024, 20, 3263–3273, doi:10.3762/bjoc.20.270

• commercial perfluoroarene chemical blocks and reagents, involving catalyzed C–F-bond activation and cross-coupling reactions, usually requiring precious transition-metal catalysts and tedious synthetic routes [28][29][30][31][32][33][34]. Therefore, low-cost and facile synthetic strategies are desired to

Germanyl triazoles as a platform for CuAAC diversification and chemoselective orthogonal cross-coupling

• John M. Halford-McGuff,
• Thomas M. Richardson,
• Aidan P. McKay,
• Frederik Peschke,
• Glenn A. Burley and
• Allan J. B. Watson

Beilstein J. Org. Chem. 2024, 20, 3198–3204, doi:10.3762/bjoc.20.265

• further diversification of the triazole products, including chemoselective transition metal-catalysed cross-coupling reactions using bifunctional boryl/germyl species. Keywords: chemoselectivity; click chemistry; copper; germanium; triazole; Introduction Since its inception, click chemistry has been

• functionalisation strategies [76]. The germanyl group installed in the triazole products can be used as a reactive handle for further diversification including cross-coupling reactions. The CuAAC reaction and installation of functional groups for product diversification. Scope of germanyl acetylene CuAAC. Alkyne

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• strategic approach allows precise control of the stereogenic centers at the C3-position during cyclization (Scheme 16). Ugi-4CR/metal-catalyzed reaction: The fusion of MCRs with cross-coupling reactions represents an attractive approach as a result of the increased intricacy and effectiveness [62]. Moreover

• /intramolecular Ullmann-type C–N coupling reactions. Azido-Ugi 4CR/cyclization (AU-4CR) strategy: The azido-Ugi four-component reaction (AU-4CR) is an elegant and atom economical approach for obtaining substituted tetrazoles, which are very relevant in medicinal chemistry [64]. When combined with suitable post

Extension of the π-system of monoaryl-substituted norbornadienes with acetylene bridges: influence on the photochemical conversion and storage of light energy

• Robin Schulte,
• Dustin Schade,
• Thomas Paululat,
• Till J. B. Zähringer,
• Christoph Kerzig and
• Heiko Ihmels

Beilstein J. Org. Chem. 2024, 20, 3061–3068, doi:10.3762/bjoc.20.254

• molecular system. Herein, we present the synthesis of mono-, bis-, and tris-norbornadiene derivatives with alkynylbenzene and alkynylnaphthalene core units, along with studies of their photochemical properties. The target compounds were synthesized by Sonogashira–Hagihara coupling reactions of 2

• made available in reasonable yields by Sonogashira–Hagihara coupling reactions and the potential of these compounds for MOST applications was assessed. In particular, the compounds showed red-shifted absorption of up to 420 nm. Upon direct irradiation, the norbornadienes are converted into the

• –cycloreversion cycle of norbornadiene (1a) and quadricyclane (2a). Synthesis of alkynyl-arene-linked norbornadienes 1h–n by Sonogashira–Hagihara coupling reactions. Photoisomerization of norbornadiene derivatives 1h–l,n (20 µM) to quadricyclanes 2h–l,n in cyclohexane, m = number of norbornadienylethynyl units, n

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• , transition metal-free conditions, and the presence of a C–I bond in the product, allowing for further functionalization through various coupling reactions, making the reaction method highly attractive. In 2022, Dohi and colleagues emphasized the high reactivity of TMP-iodonium acetates in the O-arylation of

C–C Coupling in sterically demanding porphyrin environments

• Liam Cribbin,
• Brendan Twamley,
• Nicolae Buga,
• John E. O’ Brien,
• Raphael Bühler,
• Roland A. Fischer and
• Mathias O. Senge

Beilstein J. Org. Chem. 2024, 20, 2784–2798, doi:10.3762/bjoc.20.234

• ][25], Negishi [26], and Kumada [27] coupling reactions, as well as modern iridium and rhodium-based coupling techniques [28], are just some examples of the C–C bond formations that have been implemented to achieve complex substitution patterns and functional arrangements on porphyrins. Of these named

• coupling reactions, Suzuki–Miyaura couplings are known to be a robust tool when functionalizing porphyrins [29][30]. Many complex porphyrinoid architectures have been synthesized in this manner, from functional porphyrin arrays [31][32][33] to sterically challenging meso-substituted aryl bis-pocket

• was synthesized through classic C–C coupling reactions at the meso-phenyl position. It was found varying temperature and the pH of the solution are effective mitigations to overcome unfavorable reaction electronics or demanding sterics presented at the meso-phenyls’ meta- or para-position

Access to optically active tetrafluoroethylenated amines based on [1,3]-proton shift reaction

• Yuta Kabumoto,
• Eiichiro Yoshimoto,
• Bing Xiaohuan,
• Masato Morita,
• Motohiro Yasui,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2024, 20, 2776–2783, doi:10.3762/bjoc.20.233

• ]. As a diastereoselective synthesis, reductive coupling reactions of commercially available 4-bromo-3,3,4,4-tetrafluoro-1-butene and glyceraldehyde 10a, its imine derivative 11, or Garner's aldehyde 10b have been reported [23][24]. Although the diastereoselectivities were low in some cases, the

Synthesis of benzo[f]quinazoline-1,3(2H,4H)-diones

• Ruben Manuel Figueira de Abreu,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2708–2719, doi:10.3762/bjoc.20.228

• and Suzuki–Miyaura cross-coupling reactions followed by Brønsted acid-mediated cycloisomerisation. The developed methodology tolerates various functional groups and leads to moderate up to quantitative yields of the final products. The impact of different functional groups on the optical properties

• of palladium-catalysed Sonogashira–Hagihara and Suzuki–Miyaura cross-coupling reactions (Scheme 1). The final cyclisation step is accomplished by an acid-mediated cycloisomerisation. The synthesis of starting materials 4 was carried out by our previously reported protocol [65]. While compounds 4a–f

• known which allow for an individual introduction of substituents at both positions [37][38][51][52][53][54][55][56][57][58][59][60][61]. In our previous work, we developed a new method which enables both positions to be independently functionalised by Sonogashira- and Suzuki–Miyaura cross-coupling

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

• chlorine atoms as reported by Hosoya and Niwa et al. In this study, we investigated the synthesis of fluoroalkenes 2 or fluoroenynes 3 by Suzuki–Miyaura or Sonogashira cross-couplings with a key building block 1 (Scheme 1D). Results and Discussion Optimization of the conditions of cross-coupling reactions

Transition-metal-free synthesis of arylboronates via thermal generation of aryl radicals from triarylbismuthines in air

• Yuki Yamamoto,
• Yuki Konakazawa,
• Kohsuke Fujiwara and
• Akiya Ogawa

Beilstein J. Org. Chem. 2024, 20, 2577–2584, doi:10.3762/bjoc.20.216

• are one of the fundamental aryl compounds in organic synthesis, especially in cross-coupling reactions [1][2][3][4][5][6][7][8][9], and their applications are widespread, including dye synthesis, pharmaceutical and agrochemical synthesis, and industrial manufacturing [10][11]. In recent years, a

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• cathodic reduction and to prevent the reoxidation of the reduced SO2 at the anode, a divided cell setup is required (Scheme 12). C–H bond halogenation: Aryl and alkyl halides are important synthetic building blocks for cross-coupling reactions as well as bioactive molecules with applications in

Machine learning-guided strategies for reaction conditions design and optimization

• Lung-Yi Chen and
• Yi-Pei Li

Beilstein J. Org. Chem. 2024, 20, 2476–2492, doi:10.3762/bjoc.20.212

• of SMILES without affecting their molecular structures or modifying specific functional groups in coupling reactions with chemistry-informed reaction templates. Despite the need for large amounts of data to train base models, the main advantage of text-based reaction representation is that it can be

Tandem diazotization/cyclization approach for the synthesis of a fused 1,2,3-triazinone-furazan/furoxan heterocyclic system

• Yuri A. Sidunets,
• Valeriya G. Melekhina and
• Leonid L. Fershtat

Beilstein J. Org. Chem. 2024, 20, 2342–2348, doi:10.3762/bjoc.20.200

• Federation 10.3762/bjoc.20.200 Abstract A straightforward protocol for the synthesis of a previously unknown [1,2,5]oxadiazolo[3,4-d][1,2,3]triazin-7(6H)-one heterocyclic system was developed. The described approach is based on tandem diazotization/azo coupling reactions of (1,2,5-oxadiazolyl)carboxamide

• a 1,2,3-triazin-4-one core. The proposed method is based on tandem diazotization/azo coupling reactions of the corresponding amides (Scheme 1). In addition, application perspectives of thus prepared heterocyclic entities as thermally stable components of functional organic materials or NO-donor drug

• coupling reactions of the obtained compounds 2. It should be emphasized that amino-1,2,5-oxadiazoles correspond to very weak nucleophiles due to the highly electron-withdrawing effect of the heterocycle. Our previous efforts achieved a certain result indicating that (1,2,5-oxadiazolyl)diazonium salts

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• –halogen bond formation, as well as C–H functionalization [27]. Some notable examples include C–H arylation, various cross-coupling reactions, oxidative coupling, and photocatalytic radical reactions. The advantages of visible-light-induced photoredox catalysis are due to the ability to utilize visible

• photocatalysis. The generated alkyl radicals then undergo the desired addition with alkyne to produce alkenyl radicals that via Ni-catalysed coupling reactions with aryl bromides form trisubstituted alkenes Z-selectively. Internal alkynes are not suitable for this transformation due to the steric reason, but

• nickel-catalyzed cross-coupling reactions with aryl halides to deliver the desired cross-coupled products. Interestingly, in absence of any xanthate, sec-butyl radicals underwent cross-coupling reactions with aryl halides to form sec-butyl arenes, whereas in the presence of xanthate, no undesired sec

Rhodium-catalyzed homo-coupling reaction of aryl Grignard reagents and its application for the synthesis of an integrin inhibitor

• Kazuyuki Sato,
• Satoki Teranishi,
• Atsushi Sakaue,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai,
• Hiroyuki Takeda,
• Tatsuo Kinashi and
• Masaaki Omote

Beilstein J. Org. Chem. 2024, 20, 1341–1347, doi:10.3762/bjoc.20.118

• alloy, and has been used as one of the methods for obtaining homo-coupling biaryl compounds (Scheme 1) [1][2]. Starting from these works, various modified Ullmann-type coupling reactions have been developed [3][4]. However, the reaction usually required high temperatures and the yield was not very high

• . Therefore, alternative procedures for homo-coupling reactions using other transition-metal catalysts such as palladium, nickel, manganese, and iron have been developed [5][6][7][8][9][10][11][12][13]. In recent years, transition-metal-free coupling reactions have also been developed for environmentally

• and Discussion Methodology development In our work towards Rh-catalyzed homo-coupling reactions of benzyl halides, we observed that a similar rhodium–bis(benzyl) complex can also be formed from benzyl halide by using a Grignard reagent instead R2Zn in the presence of RhCl(PPh3)3 to subsequently give

Phenotellurazine redox catalysts: elements of design for radical cross-dehydrogenative coupling reactions

• Alina Paffen,
• Christopher Cremer and
• Frederic W. Patureau

Beilstein J. Org. Chem. 2024, 20, 1292–1297, doi:10.3762/bjoc.20.112

• . Our future research efforts in the area of Te(II) catalysis will likely focus on milder coupling reactions on the one hand, and/or on novel more robust and more active ligand designs on the other. In particular, more investigations will likely be needed regarding the optimization of the possible Te

• Alina Paffen Christopher Cremer Frederic W. Patureau Institute of Organic Chemistry, RWTH Aachen University, Landoltweg 1, 52074 Aachen, Germany 10.3762/bjoc.20.112 Abstract Redox active phenotellurazine catalysts have been recently utilized in two different cross-dehydrogenative coupling

• reactions. In this study, we revisit the design of the phenotellurazine redox catalysts. In particular, we investigate the level of cooperativity between the Te- and N-centers, the effect of secondary versus tertiary N-centers, the effect of heterocyclic versus non-heterocyclic structures, and the effect of

Synthesis and optical properties of bis- and tris-alkynyl-2-trifluoromethylquinolines

• Stefan Jopp,
• Franziska Spruner von Mertz,
• Peter Ehlers,
• Alexander Villinger and
• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 1246–1255, doi:10.3762/bjoc.20.107

• ][23], dyes, preservatives and as ligands in complex chemistry [24][25][26][27]. In the context of our interest in the application of cross-coupling reactions to polyhalogenated heterocycles [28][29][30][31], we studied Sonogashira reactions of brominated 2-trifluoromethylquinolines. The optical

• cross-coupling reactions of various acetylenes containing electron-rich and electron-withdrawing functional groups, like methoxy or cyano, as well as thienyl and cyclopropyl groups. In general, all products were achieved in very good yields, ranging from 71 to 99%. Only product 6h, containing a TMS