Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• of allylic peroxidation 2, 4 and 5 were observed (Scheme 4) [24]. Similar transformations were reported later using CuCl as the catalyst [39]. Later, Gade with coauthors demonstrated the allylic peroxidation of cyclohexane with TBHP using the alkylperoxocobalt(III) complexes [Co(BPI)(OAc)(OO-t-Bu

• -t-Bu)2. Allylic peroxidation of 3-substituted prop-1-ene-1,3-diyldibenzenes 8 was performed with TBHP as the oxidant/peroxidation agent and with Cu2O as the catalyst [42] (Scheme 6). The proposed mechanism of peroxides 9 formation does not include peroxo–copper complexes and begins with the

• formation of peroxide 9. The enantioselective peroxidation of alkenes 10 with TBHP with the formation of the optically active products 11 was carried out in good yields and low ee by the use of in situ-generated chiral bisoxazoline–copper(I) complexes (Scheme 7) [43]. Studying the oxidation of α-pinene (12

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

• nucleophilic organozincate complexes (e.g., LiBuZnBrCl), which is a well-established process in THF [29][30]. Due to the hygroscopic character of LiCl and the necessity to determine the amount of organozinc by iodolysis [20] in order to adjust the stoichiometry of the reagents for the multicomponent coupling

Investigation of a bimetallic terbium(III)/copper(II) chemosensor for the detection of aqueous hydrogen sulfide

• Parvathy Mini,
• Michael R. Grace,
• Genevieve H. Dennison and
• Kellie L. Tuck

Beilstein J. Org. Chem. 2024, 20, 2818–2826, doi:10.3762/bjoc.20.237

• , highly sensitive chemosensors via a facile synthetic route/method, we have explored three chelates for lanthanide ions (DO3A, 2,6-pyridinedicarboxylic acid and DO2A), resulting in complexes with different overall charges. Additionally we have explored two copper(II) binding groups (di(2-picolyl)amine and

• aqueous hydrogen sulfide and 100 ppb for gaseous hydrogen sulfide [16]. However, due to the limited aqueous solubility and ligand dissociation of this chemosensor, and to the weakly luminescent bis species at usable concentrations, we extended this work to the lanthanide–macrocycle binary complexes [Ln

• not exhibit any discernible increase in luminescence. As far as we are aware, there are only three reports of lanthanide-based probes for the detection of gaseous hydrogen sulfide. Two are the europium(III) complexes from our group ([Eu(triazole-DPA)3·Cu]3+ and [Eu(DO2A)(triazole-DPA)·Cu]+), which are

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

• one, may have slowed down the protodeboronation process, as substrates with electron-withdrawing groups are postulated to increase the Lewis acidity of the boronic acid, which may allow an increased incidence of protodeboronation to occur. It is also known that aryl–B(Pin) complexes have a greater

• porphyrins Nonplanar porphyrins are known to form supramolecular assemblies [6], either through hydrogen-bonding networks or through π–π interactions. Examples of this can be seen in the trapping of Keggin-type heteropolyoxometalate (POM) through nonplanar Mo(V)–porphyrin complexes [58], or porphyrin

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

• considered were calculated using Equation 4 and Equation 5, respectively, where H(A) stands for the enthalpy of the FLP, H(H+) for the enthalpy of the proton, H(F−) for the enthalpy of the fluoride ion, and H([A-H+]) and H([A-F−]) for the enthalpies of the complexes formed between the FLP and a proton and a

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

• hydrogen bonding, although generally not dominant, can influence the complex formation as well [5]. Cyclodextrins form inclusion complexes with polar and non-polar substances of various aggregate states. This incredible versatility, combined with the enhanced stability against oxidation, as well as

• process. An occupancy of up to 7 hydration water molecules has been found and a comparison between α-CD, β-CD, and γ-CD hydration mechanisms is provided. Results and Discussion Nonhydrated γ-CD As with the other two cyclodextrins (α- and β-), before proceeding to the complexes with water, we considered

• the other complexes only two options were modelled (Figure 2, n = 2–7, structures a and b). The first water molecule can bind to the narrow rim (n = 1; Figure 2, structures a–c) or the wide rim (n = 1; Figure 2, structures d and e). All attempts to position single water molecule in the cavity or near

Efficient modification of peroxydisulfate oxidation reactions of nitrogen-containing heterocycles 6-methyluracil and pyridine

• Alfiya R. Gimadieva,
• Yuliya Z. Khazimullina,
• Aigiza A. Gilimkhanova and
• Akhat G. Mustafin

Beilstein J. Org. Chem. 2024, 20, 2599–2607, doi:10.3762/bjoc.20.219

• in two different ways: with metallophthalocyanine catalysts present and by including hydrogen peroxide as a co-oxidant (Scheme 1). Metal–phthalocyanine complexes (PcM) are recognized as catalysts for gentle, particular oxidation reactions under aerobic [14] and H2O2-based conditions [15][16][17][18

Anion-dependent ion-pairing assemblies of triazatriangulenium cation that interferes with stacking structures

• Yohei Haketa,
• Takuma Matsuda and
• Hiromitsu Maeda

Beilstein J. Org. Chem. 2024, 20, 2567–2576, doi:10.3762/bjoc.20.215

• cations [21]. Moreover, ion-pairing assemblies of 1a+ and the π-electronic receptor–anion complexes as pseudo-π-electronic anions exhibited electric conductive properties [22][23][24][25]. The structures and electronic states of ions directly affect the arrangement of constituent ions in the assemblies

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

• benzylic position (Scheme 31). 1.3.2 Co-assisted anodic oxidation. In 2021, Xu and colleagues developed an electrocatalytic approach for the intramolecular oxidative allylic amination and C–H alkylation using cobalt–salen complexes as catalysts [43]. In this reaction, the cobalt catalyst [Co(II)] is first

• complex compounds (Scheme 35). In addition, Niu and coworkers reported a similar work on a cobalt-electrocatalyzed atroposelective C–H annulation of benzamides with acetylenes [48]. 1.3.3 Ni-assisted anodic oxidation: Apart from cobalt, nickel complexes have also been applied in anionic oxidations and

Evaluating the halogen bonding strength of a iodoloisoxazolium(III) salt

• Dominik L. Reinhard,
• Anna Schmidt,
• Marc Sons,
• Julian Wolf,
• Elric Engelage and
• Stefan M. Huber

Beilstein J. Org. Chem. 2024, 20, 2401–2407, doi:10.3762/bjoc.20.204

• abstractions, e.g. to activate gold chloride complexes [18][19]. Therefore, besides the development of new bidentate catalyst motifs, we were still interested in the optimization of these “simpler” derivatives. Thus, we designed a new catalyst motif [20] featuring an isoxazole ring, XB donor 7Z, and compared

• preactivation process between the XB donor, the gold complex, or the amide can be assumed. Such a sigmoidal curve for this reaction has also been observed in one of the previous studies on the XB activation of gold complexes [15]. The prototypic iodolium 1BArF showed significantly better results reaching ≈85

• ]. For all catalyst systems, decomposition of the −BArF24 anion was observed via 1H and 19F NMR spectroscopy, which is known to happen in the presence of activated gold complexes [29]. The stability of the DAI cations was checked with 1H NMR: the characteristic doublets belonging to the respective

Synthesis, electrochemical properties, and antioxidant activity of sterically hindered catechols with 1,3,4-oxadiazole, 1,2,4-triazole, thiazole or pyridine fragments

• Daria A. Burmistrova,
• Andrey Galustyan,
• Nadezhda P. Pomortseva,
• Kristina D. Pashaeva,
• Maxim V. Arsenyev,
• Oleg P. Demidov,
• Mikhail A. Kiskin,
• Andrey I. Poddel’sky,
• Nadezhda T. Berberova and
• Ivan V. Smolyaninov

Beilstein J. Org. Chem. 2024, 20, 2378–2391, doi:10.3762/bjoc.20.202

• derivatives are used as ligands in the synthesis of metal complexes (Ni(II), Pd(II), Pt(II), Cu(I), Ag(I) etc.) exhibiting antibacterial and antitumor activity [34]. In most cases, polyfunctional catechol thioethers were obtained by Michael reaction via the interaction of o-, p-benzoquinone and the

• of complexes 5 and 8 do not contain any solvent molecules, while the unit cell of crystals 6·0.5CH3CN contains one acetonitrile molecule per two catechol molecules. The nitro-substituted pyridine group in 5 is disordered in two positions. The X-ray structure of catechol 5 is shown in Figure 1, and

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

• and type II’ β-hairpin. Even though the latter was consistently lower in ground state energy (up to 6 kcal/mol for some catalysts), predictive models for enantioselectivity were found for both catalyst conformers in separate MLR models. For organophosphorous ligands of transition metal complexes, the

• the ML model by being considered as a nucleophile or electrophile, depending on the reaction mechanism. Descriptors allowed for the inclusion of a variety of co-catalysts, ranging from Fe-piano stool complexes to copper complexes. The consideration of co-catalysis into model development further

gem-Difluorination of carbon–carbon triple bonds using Brønsted acid/Bu₄NBF₄ or electrogenerated acid

• Mizuki Yamaguchi,
• Hiroki Shimao,
• Kengo Hamasaki,
• Keiji Nishiwaki,
• Shigenori Kashimura and
• Kouichi Matsumoto

Beilstein J. Org. Chem. 2024, 20, 2261–2269, doi:10.3762/bjoc.20.194

• the use of HF or its complexes as a reagent. These reactions seem to proceed via the formation of the vinyl fluoride as the intermediate [25][26][27][28]. In the first example, Olah and co-workers reported the reaction of terminal alkynes with HF/pyridine (Olah reagent) (Figure 1, reaction 1) [29][30

Efficacy of radical reactions of isocyanides with heteroatom radicals in organic synthesis

• Akiya Ogawa and
• Yuki Yamamoto

Beilstein J. Org. Chem. 2024, 20, 2114–2128, doi:10.3762/bjoc.20.182

• -covalent electron pair, making it impossible to generate boron radicals by homolysis via the n–σ* transition. In addition, since boron has an empty orbital, it forms ate complexes when Lewis base compounds coexist. As the result, the boryl groups of the ate complexes are bulky and often cause steric

• hindrance. However, several examples of isocyanide insertion reactions into B–H and B–B bonds are known. For example, isocyanides coordinate to diborane (B2H6) or trialkylboranes (BR'3) to form Lewis acid–base complexes (RNC→BH3 or RNC→BR'3), but these complexes are thermally labile, and hydrogen or alkyl

• Lewis acid–base complexes (t-BuNC→BH3) to generate the corresponding isocyanide–boryl radicals 17 (t-BuNC→BH2•), which can be observed by ESR (Scheme 10b) [47]. However, the synthetic application of this boryl radical has not been investigated. Among the cyclic diboron compounds, a series of five

Computational toolbox for the analysis of protein–glycan interactions

• Ferran Nieto-Fabregat,
• Maria Pia Lenza,
• Angela Marseglia,
• Cristina Di Carluccio,
• Antonio Molinaro,
• Alba Silipo and
• Roberta Marchetti

Beilstein J. Org. Chem. 2024, 20, 2084–2107, doi:10.3762/bjoc.20.180

• –ligand complexes, and analyse MD outcomes. Moreover, selected case studies have been reported to highlight the importance of computational tools in studying protein–glycan systems, revealing the capability of these tools to provide valuable insights into the binding kinetics, energetics, and structural

• using the doglycans.py tool. (https://bitbucket.org/biophys-uh/doglycans/). 2. Glycam-Web carbohydrate builder [50]: Free online web-service that gives the possibility to model the 3D structures of molecules and complexes containing carbohydrates starting from monosaccharide building blocks, being also

• study protein–ligand complexes Detailed investigations of protein–ligand interactions, combining experimental and computational methods, provide an indispensable basis to depict holistic pictures of molecular complexes allowing to modulate them at will. The computational approach involves i) predicting

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• , 3,4,5-substituted pyrazoles 5 are formed (Scheme 2) [45]. The Lewis acid catalyst accelerates the reaction via participation in the formation of β-diketonate complexes. Other carbonyl compounds suitable for pyrazole synthesis are 2,4-diketoesters 13. These intermediates can be prepared from diethyl

• solution and in the solid state [127]. Furthermore, even sugar-functionalized pyrazoles have been accessed by this approach [128], and it was readily implemented in a continuous flow reactor [129]. Besides traditional Sonogashira catalyst systems, highly reactive and reusable immobilized Pd-complexes, such

• aliphatic alkynes, copper iodide is necessitated as a co-catalyst [141]. In addition to classic Sonogashira catalysts, phosphane-free palladium [Pd(NN)] chelate complexes can also be used, which promote excellent regioselectivity [142]. A variation of the reaction is possible with Mo(CO)6 as a carbon

1,2-Difluoroethylene (HFO-1132): synthesis and chemistry

• Liubov V. Sokolenko,
• Taras M. Sokolenko and
• Yurii L. Yagupolskii

Beilstein J. Org. Chem. 2024, 20, 1955–1966, doi:10.3762/bjoc.20.171

• meso form in high combined yield (90%, Scheme 16) [94]. The product was used as a ligand for the preparation of transitional metal carbonyl complexes. The addition reaction of trichlorofluoromethane (CFC-11) to 1,2-difluoroethylene in the presence of aluminum chloride under pressure was described [51

• transitional metal complexes with 1,2-difluoroethylene as a ligand should be mentioned [109][110][111]. Conclusion In conclusion, our literature analysis demonstrated that radical processes are most typical for 1,2-difluoroethylene, while examples of electrophilic reactions are scarce, and nucleophilic

Regioselective alkylation of a versatile indazole: Electrophile scope and mechanistic insights from density functional theory calculations

• Pengcheng Lu,
• Luis Juarez,
• Paul A. Wiget,
• Weihe Zhang,
• Krishnan Raman and
• Pravin L. Kotian

Beilstein J. Org. Chem. 2024, 20, 1940–1954, doi:10.3762/bjoc.20.170

• negligible. These data suggest that deprotonation occurs prior to alkylation and that deprotonation of either indazole tautomer leads to anions of identical or highly similar energy. Furthermore, as seen in Figure 4, a total, five coordinated complexes were found to be at least 4.5 kcal/mol more stable than

• the uncoordinated anion when calculated as isolated structures. When the calculation is performed as a reaction of E and Z-enolates with Cs+ ion, two coordinated complexes 6(N-H)NNCs-E and-6(N-H)NOCs-Z are exergonically formed by 9.7 and 10.9 kcal/mol, respectively. We then searched for transition

• identified as 6(N-H) (bottom). DFT-calculated Cs+-coordinated complexes with different enolate forms of 6(N-H) calculated as isolated compounds (top) and calculated intermediates of the reactions of 6(-N1H-Z) and 6(-N1H-E) with Cs+ (bottom). DFT-calculated reaction coordinate diagram for the reaction of 6

Methyltransferases from RiPP pathways: shaping the landscape of natural product chemistry

• Maria-Paula Schröder,
• Isabel P.-M. Pfeiffer and
• Silja Mordhorst

Beilstein J. Org. Chem. 2024, 20, 1652–1670, doi:10.3762/bjoc.20.147

• can also be employed to mimic non-ribosomal peptides [12][13], since it is substantially more challenging to engineer non-ribosomal peptide synthetase (NRPS) pathways. Non-ribosomal peptides are often produced by giant multi-modular enzyme complexes (type I NRPS) and they are most commonly involved in

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• in this section, radical-based approaches enable the fluorination of a diverse range of benzylic substrates, which rely on the use of FAT reagents, such as Selectfluor, NFSI or copper fluoride complexes. Nucleophilic benzylic C(sp3)–H fluorination Nucleophilic fluorine sources can be more economical

• transition-metal complexes to generate metal–fluorine bonds capable of FAT to benzylic substrates. In a follow-up to their work using electrophilic fluorine sources for palladium-catalysed benzylic C–H fluorination (Figure 5), the Sanford group demonstrated in 2012 the same transformation could be achieved

Electrophotochemical metal-catalyzed synthesis of alkylnitriles from simple aliphatic carboxylic acids

• Yukang Wang,
• Yan Yao and
• Niankai Fu

Beilstein J. Org. Chem. 2024, 20, 1497–1503, doi:10.3762/bjoc.20.133

• invention of cooperative catalysis with electrochemical transition metal catalysis, which generally has mild oxidation potential for the generation of persistent radicals in the form of nucleophile-bound metal complexes. We and other groups have successfully applied this reaction design to enantioselective

Photoswitchable glycoligands targeting Pseudomonas aeruginosa LecA

• Yu Fan,
• Ahmed El Rhaz,
• Stéphane Maisonneuve,
• Emilie Gillon,
• Maha Fatthalla,
• Franck Le Bideau,
• Guillaume Laurent,
• Samir Messaoudi,
• Anne Imberty and
• Juan Xie

Beilstein J. Org. Chem. 2024, 20, 1486–1496, doi:10.3762/bjoc.20.132

• crystalline complexes. The protein is represented by orange ribbon, His53 by lines, and calcium by green sphere. Synthesis of photoswitchable LecA inhibitors. Reagents and conditions: (i) DMC, Et3N, H2O, −10 °C to rt, 8 h, 50% for 7, 40% for 10; (ii) BrCH2CH2NHBoc, K2CO3, DMF, 60 °C, 15 h, 91% for 8, 80% for

Bioinformatic prediction of the stereoselectivity of modular polyketide synthase: an update of the sequence motifs in ketoreductase domain

• Changjun Xiang,
• Shunyu Yao,
• Ruoyu Wang and
• Lihan Zhang

Beilstein J. Org. Chem. 2024, 20, 1476–1485, doi:10.3762/bjoc.20.131

• : bioinformatics; conserved motifs; ketoreductase; polyketide synthase; stereocontrol; Introduction Type I modular polyketide synthases (PKSs) are large enzyme complexes that play a crucial role in the biosynthesis of bacterial polyketides, including many important clinical drugs such as erythromycin (antibiotic

Rapid construction of tricyclic tetrahydrocyclopenta[4,5]pyrrolo[2,3-b]pyridine via isocyanide-based multicomponent reaction

• Xiu-Yu Chen,
• Ying Han,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2024, 20, 1436–1443, doi:10.3762/bjoc.20.126

• carbon atom of isocyanide has both a lone electron pair and empty orbitals, so it has outstanding electrophilic and nucleophilic reactivity. At the same time, isocyanide also has good coordination ability to coordinate with metals to form diverse metal complexes [1][2][3]. Therefore, isocyanides have

A comparison of structure, bonding and non-covalent interactions of aryl halide and diarylhalonium halogen-bond donors

• Nicole Javaly,
• Theresa M. McCormick and
• David R. Stuart

Beilstein J. Org. Chem. 2024, 20, 1428–1435, doi:10.3762/bjoc.20.125

• engage in halogen-bonding interactions [29][30]. In this work, a series of halogen-bond donor molecules and their halogen bond complexes with chloride anion were optimized at the M062x/6-311+G(d) level of theory [31] with def2-tzvpp used for iodine and astatine, and with SMD solvation in tetrahydrofuran

• kcal/mol). The X---Cl distance calculated for the halogen-bonding complexes 41 and 45 of phenyl chloride (25) and mesityl chloride (29) with chloride anion were 3.85 and 3.71 Å, respectively. These values are larger than the sum of the van der Waals radii (3.5 Å) for two chlorine atoms [36] and

• ---Cl distance for halogen-bond complexes 9–24, 42–44, and 46–56; representative examples are shown in Scheme 4. As a reference we considered the trend in X–Cl covalent bond distance with respect to the van der Waals radii of X [36], and we observed a linear trend with a positive slope (Scheme 4b, grey