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

• five to seven-membered cyclic compounds [47]. Arylation reactions using diaryliodonium salts can occur through four distinct mechanisms. First, the arylation can occur under metal-free conditions, involving the formation of a three-membered ring transition state through ligand coupling, leading to the

• upon binding of the enolate molecule to iodine either through a carbon–iodine or an oxygen–iodine bond. Both intermediates, I and II, are in rapid equilibrium with each other and further undergo two different types of reactions: [1,2]-ligand coupling and [2,3]-rearrangement (Scheme 2). Either of these

• salt, subsequently leading to decarboxylative C–C coupling. Notably, this method achieves the incorporation of two fluorine atoms in the benzyl position without resorting to hazardous fluorination reagents, transition-metal catalysts, or organometallic compounds. The utility of this reaction is

Multicomponent synthesis of α-branched amines using organozinc reagents generated from alkyl bromides

• Baptiste Leroux,
• Alexis Beaufils,
• Federico Banchini,
• Olivier Jackowski,
• Alejandro Perez-Luna,
• Fabrice Chemla,
• Marc Presset and
• Erwan Le Gall

Beilstein J. Org. Chem. 2024, 20, 2834–2839, doi:10.3762/bjoc.20.239

• stoichiometric amount of LiCl was essential for the efficiency of the subsequent three-component coupling with aldehydes and amines. A variety of primary, secondary, and tertiary organozinc reagents as well as secondary amines and aromatic aldehydes could be used for the straightforward preparation of α-branched

• ]. In this context, while significant contributions have highlighted the reliable use of diverse organometallic species in the three-component coupling, most examples of sp3-hybridized compounds have remained restricted to allyl [5] or benzyl [5][6] organometallic reagents. Conversely, examples of

• 16 h at 80 °C (Table 1, entry 2). However, its suitability in the multicomponent coupling with an amine and an aldehyde still had to be demonstrated as there was no precedent for such a Mannich multicomponent coupling involving nonstabilized organozinc halides using THF or 2-MeTHF as solvent. To our

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

• porphyrin architectures, which could be used in supramolecular assemblies, catalysis, or sensing. In this work a library of arm-extended dodecasubstituted porphyrins was synthesized through the optimization of the classic Suzuki–Miyaura coupling of peripheral haloaryl substituents with a range of boronic

• acids. We report on palladium-catalyzed coupling attempts on the ortho-, meta-, and para-meso-phenyl position of sterically demanding dodecasubstituted saddle-shaped porphyrins. While para- and meta-substitutions could be achieved, ortho-functionalization in these systems remains elusive. Furthermore

• , borylation of a dodecasubstituted porphyrin’s meso-phenyl position was explored and a subsequent C–C coupling showed the polarity of the reaction can be reversed resulting in higher yields. X-ray analysis of the target compounds revealed the formation of supramolecular assemblies, capable of accommodating

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 spiroindolenines through a one-pot multistep process mediated by visible light

• Francesco Gambuti,
• Jacopo Pizzorno,
• Chiara Lambruschini,
• Renata Riva and
• Lisa Moni

Beilstein J. Org. Chem. 2024, 20, 2722–2731, doi:10.3762/bjoc.20.230

• NMR: TMS = 0.00; (CD3)2SO = 2.50; and 13C NMR: CDCl3 = 77.16; (CD3)2SO = 39.52. Data for 1H NMR spectra are reported as follows: chemical shift (δ ppm), multiplicity, coupling constants (Hz) and integration. Data for 13C NMR spectra are reported in terms of chemical shift (δ ppm). Interpretation of

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

• was studied by UV–vis and fluorescence spectroscopy. Keywords: cross-coupling; cyclization; heterocycles; palladium; Introduction Nucleobases contain the coded information and give DNA and RNA their typical structure. As a nucleobase, uracil is involved in numerous vital processes and is therefore a

• 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

5th International Symposium on Synthesis and Catalysis (ISySyCat2023)

• Anthony J. Burke and
• Elisabete P. Carreiro

Beilstein J. Org. Chem. 2024, 20, 2704–2707, doi:10.3762/bjoc.20.227

• performance. In their contribution “Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs”, Moutayakine and Burke described a new synthetic route for the synthesis of 10,11-dihydro-5H-dibenzo[b,e][1,4]diazepinone (DBDAP

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

• fluorine-containing building blocks have been developed [21][22][23][24][25]. Jubault and Poisson et al. reported SN2’ reactions of hydride or alcohols to electrophilic fluorine-containing alkenes gave the corresponding fluoroalkenes (Scheme 1B) [21]. In recent years, many fluorine-containing coupling

Computational design for enantioselective CO₂ capture: asymmetric frustrated Lewis pairs in epoxide transformations

• Maxime Ferrer,
• Iñigo Iribarren,
• Tim Renningholtz,
• Ibon Alkorta and
• Cristina Trujillo

Beilstein J. Org. Chem. 2024, 20, 2668–2681, doi:10.3762/bjoc.20.224

• fluoride ion, respectively. Volcanic 1.3.3, a Python package for the NaviCat platform, was used to generate 3D volcano plots, facilitating the identification of the most appropriate catalyst for the coupling reaction being considered [27]. Volcano plots Volcano plots are a visualisation of the Sabatier

• ), S1 is the substituent on the LB, and S2 is the substituent on the LA. Capture of CO2 and PO by an FLP Chemoselectivity Our investigations began by examining the uncatalysed coupling reaction between CO2 and PO (Scheme 1), which exhibits a calculated activation barrier (ΔG‡) greater than 55 kcal·mol−1

• (Figure S6, Supporting Information File 1). Therefore, in order to observe the coupling between these two moieties under standard conditions, the presence of a catalyst is necessary. In the literature, metal-based and organocatalysts have been reported as efficient catalysts for this reaction [24][25]. As

Transition-metal-free decarbonylation–oxidation of 3-arylbenzofuran-2(3H)-ones: access to 2-hydroxybenzophenones

• Bhaskar B. Dhotare,
• Seema V. Kanojia,
• Chahna K. Sakhiya,
• Amey Wadawale and
• Dibakar Goswami

Beilstein J. Org. Chem. 2024, 20, 2655–2667, doi:10.3762/bjoc.20.223

• oxidative coupling of salicylaldehyde with arylboronic acids to successfully produce 2-hydroxybenzophenones [14]. Recently, a Ni-catalyzed decarbonylation–oxidation of 3-arylbenzofuran-2(3H)-ones emerged as an innovative route to access 2-hydroxybenzophenones [2]. The use of transition metals poses

The scent gland composition of the Mangshan pit viper, Protobothrops mangshanensis

• Jonas Holste,
• Paul Weldon,
• Donald Boyer and
• Stefan Schulz

Beilstein J. Org. Chem. 2024, 20, 2644–2654, doi:10.3762/bjoc.20.222

• diastereomers were then subjected to silver nitrate column chromatography to separate the geometric isomers. This separation was only partially achieved (Supporting Information File 1, Figure S10), but one diastereomer was enriched and the sample was subjected to NOESY NMR experiments. Coupling was observed

• between H-5 (4.82 ppm) and C-6-methyl (1.66 ppm) (Supporting Information File 1, Figure S11) for the minor compound eluting earlier in GC, indicating that both hydrogen atoms are close together and that the double bond has a Z-configuration. The other diastereomer showed no coupling between H-5 (4.84 ppm

Deciphering the mechanism of γ-cyclodextrin’s hydrophobic cavity hydration: an integrated experimental and theoretical study

• Stiliyana Pereva,
• Stefan Dobrev,
• Tsveta Sarafska,
• Valya Nikolova,
• Silvia Angelova,
• Tony Spassov and
• Todor Dudev

Beilstein J. Org. Chem. 2024, 20, 2635–2643, doi:10.3762/bjoc.20.221

• properties of γ-CD (the largest of the three most abundant native CDs), the main experimental methods applied in this study were differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). By coupling these techniques with density functional theory (DFT) calculations we try to shed some

Applications of microscopy and small angle scattering techniques for the characterisation of supramolecular gels

• Connor R. M. MacDonald and
• Emily R. Draper

Beilstein J. Org. Chem. 2024, 20, 2608–2634, doi:10.3762/bjoc.20.220

• , cells that allow for the coupling of SAS with non-X-ray techniques continue to be developed; these include spectroscopy, rheology, and electrochemistry [62][63][64]. Ascribing changes in properties of interest directly to changes in the structure further elucidates the interesting properties of self

• structural characteristics that give material properties of interest. However, care must be taken to sure a truly representative environment is probed. Coupling rheology with SAS (rheo-SAS) is of particular interest for soft matter applications due to its ability to identify and rationalise how changes in

Synthesis and cytotoxicity studies of novel N-arylbenzo[h]quinazolin-2-amines

• Battini Veeraiah,
• Kishore Ramineni,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Hélène Solhi,
• Rémy Le Guevel,
• Chada Raji Reddy,
• Frédéric Justaud and
• René Grée

Beilstein J. Org. Chem. 2024, 20, 2592–2598, doi:10.3762/bjoc.20.218

• attractive results in this area. Keywords: Buchwald–Hartwig coupling; cytotoxicity; heterocycles; Pd catalysis; quinazolines; Introduction Nitrogen-containing heterocyclic molecules are ubiquitous in living systems. Among them, quinazolines, and especially the 4-aminoquinazolines (type A molecules, Figure

• afforded the known aldehyde 2 in 65% yield [13]. Then, reaction with guanidinium carbonate in DMA at high temperature [12], gave the desired intermediate 2-aminobenzo[h]quinazoline (3). In a final step, classical Buchwald–Hartwig coupling [14][15][16][17] with bromobenzene under the conditions described

• better accuracy on small coupling constants, resolution in 1H NMR was enhanced using Traficante. All compounds were purified by flash column chromatography on silca gel unless otherwise noted. Melting points were obtained using an Electrothermal IA9200 series digital apparatus with thin-wall glass tube

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

• amination: Direct and selective CH-aminations and amidations are challenging reactions. In this context, the regioselective sulfonamidation of (hetero)aromatic groups was achieved by the Lei group via dehydrogenative aryl C–H/N–H cross-coupling [9]. A crucial step in this transformation is the generation of

• )–H functionalization C–N coupling reaction by developing an electrochemical method for the bioconjugation of tyrosine in proteins/polypeptides with phenothiazine residues, achieving excellent site- and chemoselectivity (Scheme 4a). This method was inspired by an earlier work from the Gouin group

• 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

• simply memorize the most frequently reported solvents and reagents in the literature. Beker et al. [178] showed that some machine learning models could not outperform simple statistical analyses based on the popularity of reported conditions in the literature, using the Suzuki–Miyaura coupling as an

• ML and automated robotic experimentation to accelerate the exploration of general reaction conditions for heteroaryl Suzuki–Miyaura cross-coupling. They achieved an average yield that was twice as high as that of previous human-guided experiments. Recently, Wang et al. [65] formulated the

Synthesis and conformational analysis of pyran inter-halide analogues of ᴅ-talose

• Olivier Lessard,
• Mathilde Grosset-Magagne,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2024, 20, 2442–2454, doi:10.3762/bjoc.20.208

• order to decipher the key physical properties of complex pyran inter-halides, we performed 19F NMR analysis of halogenated talose analogues 12–15 (Figure 2). First, all analogues adopt standard 4C1-like conformations. Comparison of the vicinal and geminal coupling constants for each organohalogen

• Kohn–Sham orbitals produced from DFT are localized to describe the system as one dominant resonance structure. As the Fock matrix is not diagonal in terms of the NBOs, coupling between orbitals can be quantified with second order perturbation theory. These couplings represent donation from an occupied

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• organocatalytic enantioselective Hosomi–Sakurai reaction of imines using allyltrimethylsilane was reported by List and co-worker [32]. In this approach, the direct synthesis of Fmoc-protected homoallylic amines 47 was achieved by a three-component coupling of allyltrimethylsilane (46) with the in situ-formed N

• chemical shifts of the Hb proton in 74 with the same signals in the free substrate 73 and protonated 75 at −40 °C. It was revealed that the aldimine proton Hb in the free imine appears as a singlet at 7.95 ppm, while in both 74 and 75 it becomes a doublet with a 15 Hz trans JH–H coupling constant. However

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

Improved deconvolution of natural products’ protein targets using diagnostic ions from chemical proteomics linkers

• Andreas Wiest and
• Pavel Kielkowski

Beilstein J. Org. Chem. 2024, 20, 2323–2341, doi:10.3762/bjoc.20.199

• proteomics protocols may have many steps and operations in common, there is a great variability in how these individual steps are arranged into a workflow (Figure 3). The important aspect of any chemical proteomics study is the efficient coupling between the probe–protein conjugate and the selected linker

• interrupted CuAAC mechanism [65]. The thiotriazole product of this reaction, which is indistinguishable in the protein-level downstream analysis, is formed by coupling between protein free thiol groups and the triazole–copper adduct (Figure 4). However, its formation can be avoided by eliminating the free

• attempted, in which the coupling of the probe–peptide conjugate with a suitable reporter tag may help to improve the detectability in an excess of probe-unmodified peptides [65][81][82]. The speed of acquisition of mass spectra of the current LC–MS/MS methods does not ultimately cover all unmodified and

Hydrogen-bond activation enables aziridination of unactivated olefins with simple iminoiodinanes

• Phong Thai,
• Lauv Patel,
• Diyasha Manna and
• David C. Powers

Beilstein J. Org. Chem. 2024, 20, 2305–2312, doi:10.3762/bjoc.20.197

• iminoiodinane reacts directly with the olefin to generate a short-lived alkyl-bound iodinane 7 or iodonium species 8 (Scheme 4f). Ligand coupling from 7 or extrusion of iodobenzene from 8 would furnish a carbocation intermediate 9 which could undergo C–C bond rotation prior to ring closure to form the aziridine

Catalysing (organo-)catalysis: Trends in the application of machine learning to enantioselective organocatalysis

• Stefan P. Schmid,
• Leon Schlosser,
• Frank Glorius and
• Kjell Jorner

Beilstein J. Org. Chem. 2024, 20, 2280–2304, doi:10.3762/bjoc.20.196

• physical organic chemistry with data-driven analysis techniques, in particular MLR, to gain a greater understanding of the enantioselectivity-determining steps for a C–N coupling catalysed by CPA derivatives (Figure 15A) [143]. Based on their findings that π–π interactions between the catalyst’s triazole

Synthesis and reactivity of the di(9-anthryl)methyl radical

• Tomohiko Nishiuchi,
• Kazuma Takahashi,
• Yuta Makihara and
• Takashi Kubo

Beilstein J. Org. Chem. 2024, 20, 2254–2260, doi:10.3762/bjoc.20.193

• structure of DAntM radical (left) and its spin delocalization on two anthryl units. (b) Plausible head-to-head σ-dimerization of the DAntM radical. (a) ESR spectrum of the DAntM radical (black line, Exp.) and its simulated pattern (red line, Sim.). (b) Hyperfine coupling constant of the DAntM radical. (a

• ) ESR spectrum of anthroxyl radical 5 (black line, Exp.) and its simulated pattern (red line, Sim.). (b) Hyperfine coupling constant of 5. (c) X-ray structure of 5. Hydrogen atoms are omitted for clarity. Cyclic voltammogram (CV) of DAntM cation. (a) CV measured with scan rate at 3.0 V s−1. (b) Scan

Cell-free protein synthesis with technical additives – expanding the parameter space of in vitro gene expression

• Tabea Bartsch,
• Stephan Lütz and
• Katrin Rosenthal

Beilstein J. Org. Chem. 2024, 20, 2242–2253, doi:10.3762/bjoc.20.192

• biocatalysts [1][2]. The open environment allows easy manipulation of the protein synthesis [3] and coupling to subsequent enzyme activity assays, e.g., for substrate screening [4][5]. The CFPS system is advantageous for proteins that are difficult to express in a viable host cell, e.g., due to toxic effects