Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

Gold extraction at the molecular level using α- and β-cyclodextrins

• Susana Santos Braga

Beilstein J. Org. Chem. 2025, 21, 1116–1125, doi:10.3762/bjoc.21.89

• spontaneous complex formation between α-CD and tetrabromoaurate and its current status of use in a few mining sites in the United States. Keywords: bromoaurate; cyanoaurate; cyclodextrin inclusion; self-assembly; supramolecular interactions; Introduction Gold has allured and captivated humankind ever since

Asymmetric synthesis of fluorinated derivatives of aromatic and γ-branched amino acids via a chiral Ni(II) complex

• Maurizio Iannuzzi,
• Thomas Hohmann,
• Michael Dyrks,
• Kilian Haoues,
• Katarzyna Salamon-Krokosz and
• Beate Koksch

Beilstein J. Org. Chem. 2025, 21, 659–669, doi:10.3762/bjoc.21.52

• final yield of 94%. At these conditions (DBU, MeCN and 0 °C) the base and bromide equivalents were further modified but no further increase in yield could be achieved. Thus, 1.5 equiv DBU with 1.05 equiv alkyl bromide in MeCN at 0 °C have been identified as optimal conditions for the Ni complex

• formation (Table 1, entry 12). By employing these conditions, the reaction was carried out on a decagram-scale, and the respective alkylated Ni(II) complex 6 was isolated with an excellent yield of 95% and high diastereomeric purity of 90% de (Scheme 2). In contrast, the optimal conditions to obtain the Ni

Recent advances in allylation of chiral secondary alkylcopper species

• Minjae Kim,
• Gwanggyun Kim,
• Doyoon Kim,
• Jun Hee Lee and
• Seung Hwan Cho

Beilstein J. Org. Chem. 2025, 21, 639–658, doi:10.3762/bjoc.21.51

• copper complex formation and subsequent selective olefin insertion results in the high levels of enantioselectivity (98:2 er) observed experimentally. DFT calculations further elucidated the origin of the high diastereoselectivity (up to 96:4 dr) in the allylic substitution step (Scheme 13b). Analysis of

Binding of tryptophan and tryptophan-containing peptides in water by a glucose naphtho crown ether

• Gianpaolo Gallo and
• Bartosz Lewandowski

Beilstein J. Org. Chem. 2025, 21, 541–546, doi:10.3762/bjoc.21.42

• naphthalene fluorescence during the titration. 1H NMR (D2O) stacked plot: top – H-Trp-OH; middle – H-Trp-OH + receptor 1 (1:1); bottom – receptor 1; the dotted black lines indicate shifts of the proton signals upon complex formation. 1H NMR (D2O) stacked plot: top – H-TrpAlaAla-NH2 (2); middle – 2 + receptor

• 1 (1:1); bottom – receptor 1; the dotted black lines indicate shifts of the proton signals upon complex formation and dotted red lines indicate lack of signal shift. Proposed binding mode of receptor 1 to tripeptide 2. Binding affinities of receptor 1 to amino acids determined by ITC experiments and

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

Quantifying the ability of the CF₂H group as a hydrogen bond donor

• Matthew E. Paolella,
• Daniel S. Honeycutt,
• Bradley M. Lipka,
• Jacob M. Goldberg and
• Fang Wang

Beilstein J. Org. Chem. 2025, 21, 189–199, doi:10.3762/bjoc.21.11

• donation ability of the CF2H group by 1H NMR titration with tri-n-butylphosphine oxide (n-Bu3PO) as a reference HB acceptor (Figure 4A and Figures S20–S40 in Supporting Information File 1). Unlike a previous method that relied on 31P NMR spectroscopy [52], our titration monitors the HB complex formation by

• species, the counteranion is BF4−. C) Possible interactions that interfere with the titration outcomes. A) HB complex formation between a donor and tri-n-butylphosphine oxide. B) 1H NMR spectra of 2b (5.0 mM) in the presence of different concentrations of tri-n-butylphosphine oxide in anhydrous CD3CN at

Hydrogen-bonded macrocycle-mediated dimerization for orthogonal supramolecular polymerization

• Wentao Yu,
• Zhiyao Yang,
• Chengkan Yu,
• Xiaowei Li and
• Lihua Yuan

Beilstein J. Org. Chem. 2025, 21, 179–188, doi:10.3762/bjoc.21.10

• macrocycle H1 and a metal ion via each of two end groups (pyridinium and terpyridyl). As such, host–guest complexation and zinc coordination of the AB-type monomer were investigated. To begin with, the complex formation between host H1 and G2 was explored by 1H NMR spectroscopic titrations in CDCl3/CD3CN 1:1

Tailored charge-neutral self-assembled L₂Zn₂ container for taming oxalate

• David Ocklenburg and
• David Van Craen

Beilstein J. Org. Chem. 2024, 20, 3007–3015, doi:10.3762/bjoc.20.250

• yellow solid from this process in quantitative yield and the complex is soluble in DMSO as intended. The signal of the methylene group (Hf) adjacent to the quinolate moiety shows splitting upon complex formation (Figures S3 and S4 in Supporting Information File 1). This observation is a known indication

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

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

• Sciences, 1113 Sofia, Bulgaria, University of Chemical Technology and Metallurgy, 8 St. Kliment Ohridski Blvd, 1756 Sofia, Bulgaria 10.3762/bjoc.20.221 Abstract Cyclodextrins (CDs) are host systems with inherent capability for inclusion complex formation with various molecular entities, mostly hydrophobic

• sides, unlike the internal cavity, are hydrophilic, decorated with primary (narrow rim) and secondary (wider rim) hydroxy groups. Van der Waals (vdW) and hydrophobic interactions have been identified as the main driving forces for CDs inclusion complex formation [2][3][4]. Electrostatic interactions and

• 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

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

• complex formation between biotin and streptavidin (Kd ≈ 1 × 10−14 M) in aqueous solution. Another advantage is that after the enrichment and proteolytic digestion of each of the enriched proteins likely releases several suitable peptides for LC–MS/MS analysis resulting in a reliable identification of

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

• developing novel inhibitors of integrin function, we identified a drug candidate (10n) through high throughput screening (HTS) that inhibits the integrin complex formation, which is an important step for integrin activation. The binding inhibitor 10n was effective as IC50 of 190 μM in AlphaScreen system, and

Enhanced host–guest interaction between [10]cycloparaphenylene ([10]CPP) and [5]CPP by cationic charges

• Eiichi Kayahara,
• Yoshiyuki Mizuhata and
• Shigeru Yamago

Beilstein J. Org. Chem. 2024, 20, 436–444, doi:10.3762/bjoc.20.38

• up new possibilities for the fabrication of supramolecular structures based on the non-covalent interactions using carbon nanorings [37][38]. Despite the unique structure of the host–guest complexes, however, their electronic structures are not very attractive. This is because the complex formation

• -complementary interaction between [5]CPP2+ and [10]CPP. The same size selectivity was observed for the complex formation between neutral CPPs [31]. As the protons in the 1H NMR of [10]CPP2+ and neutral [5]CPP resonate at 4.72 and 7.84 ppm, respectively [21], the observed chemical shifts of the complex indicate

• that the complex formation occurs between neutral [10]CPP and [5]CPP2+ forming [10]CPP⊃[5]CPP2+ (Figure 1c, path A) [21]. The absence of signals in the ESR measurements at room temperature also suggests the formation of complexes with a closed-shell electronic structure. The same complex was formed

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• -derived NHPI esters has found application in the total synthesis of natural products, including the plant metabolite denobilone A and the highly oxidized dibenzocyclooctadiene lignans heteroclitin J and kadsulignan E [55]. Activation via charge-transfer complex formation Under conditions where oxidative

• conditions, affording product 61 [60]. On the other hand, reaction with 1,7-enyne 62 affords dihydroquinolinone product 63 via a cascade radical addition/cyclization process [61]. In both transformations, HE serves a dual role by activating the NHPI ester through EDA complex formation and providing a

• -type additions. However, an alternative radical chain mechanism has been discussed in the literature [62] (Scheme 14). In this instance, chain initiation takes place through photoinduced SET, enabled by EDA complex formation between the reductant N-(n-butyl)-1,4-dihydronicotinamide (BuNAH) and an NHPI

Tying a knot between crown ethers and porphyrins

• Maksym Matviyishyn and
• Bartosz Szyszko

Beilstein J. Org. Chem. 2023, 19, 1630–1650, doi:10.3762/bjoc.19.120

• such as K+, NH4+, and Ba2+ required two crown ether cavities attached to the porphyrin to form the coordination complexes through the dimerisation of the macrocycle. The dimensions of the crown ether pocket determined the complex formation; for example, if there was a mismatch in the sizes of the

• ]. The CsF binding led to a supramolecular self-assembly process, inducing a sandwich host–guest complex formation in the solid state (Scheme 2). It was established that fluoride is preferred over any other halide anions. The binding of the ion pairs was observed in highly polar solvent media, but in the

• . The addition of CsF showed an ion-pair host–guest complex formation. β-Crowned porphyrins The β-crowned porphyrins can be considered a particular case of annulated tetrapyrroles [105]. This class of macrocycles incorporating β-substituted pyrrole rings can also be considered porphyrinocrown ethers, in

Cyclodextrins permeabilize DPPC liposome membranes: a focus on cholesterol content, cyclodextrin type, and concentration

• Ghenwa Nasr,
• Hélène Greige-Gerges,
• Sophie Fourmentin,
• Abdelhamid Elaissari and
• Nathalie Khreich

Beilstein J. Org. Chem. 2023, 19, 1570–1579, doi:10.3762/bjoc.19.115

• CD concentration. The main reason behind these observations is the preferential lipid membrane extraction exhibited by the CDs. As a matter of fact, α-CD can remove phospholipids from membranes. A previous work reported that α-CD can extract DPPC through a special complex formation between the acyl

Complexes of resorcin[4]arene with secondary amines: synthesis, solvent influence on “in-out” structure, and theoretical calculations of non-covalent interactions

• Waldemar Iwanek

Beilstein J. Org. Chem. 2023, 19, 1525–1536, doi:10.3762/bjoc.19.109

• . This final geometry was used to calculate the contributions of non-covalent interactions in complex formation using the HFLD method with the recommended def2-TZVP(-f) base set and the universal solvation model (SMD) [26]. The procedure outlined above for determining the most energetically stable R[4]A

• . The yields of complex formation ranged from 45 to 78%. 1:1 Complex of R[4]A with dimethylamine: 45% yield; white solid; 1H NMR (400 MHz, DMSO-d6, T = 298 K) δ 7.15 (s, 4H, PhCH), 6.75–4.67 (br s, 8H, OH), 6.10 (s, 4H, PhCH), 4.34 (t, J = 7.70 Hz, 4H, CH), 2.30 (s, 6H, N(CH3)2), 1.94 (t, J = 6.97 Hz

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• had occurred, which was attributed to halogen bond complex formation. In 2019, the Murphy group reported the first transformation induced by blue LED irradiation of cyclic and acyclic iodonium ylides (e.g., 6) and alkenes, which generated cyclopropanes 40 in yields up to 96% (Scheme 8) [125]. UV–vis

• direct cycloaddition between the ylide and alkene. Murphy’s report of formal X–H insertions with iodonium ylides was similarly proposed to initiate upon complex formation with a Lewis base. Adduct formation was believed to both increase the acidity of halogen bond acceptor’s attached protons, as well as

• Radiofluorination of iodonium ylides In the preceding sections, the halogen-bonded complexes between iodonium ylides and Lewis basic reactants all decomposed to furnish functionalized β-dicarbonyl motifs. This is despite there being two available σ-holes for complex formation, and two pathways by which reductive

Direct C2–H alkylation of indoles driven by the photochemical activity of halogen-bonded complexes

• Martina Mamone,
• Giuseppe Gentile,
• Jacopo Dosso,
• Maurizio Prato and
• Giacomo Filippini

Beilstein J. Org. Chem. 2023, 19, 575–581, doi:10.3762/bjoc.19.42

• ambient temperature and under visible-light irradiation. Interestingly, this method employs 1,4-diazabicyclo[2.2.2]octane (DABCO) as sacrificial donor in the EDA complex formation with 2. To test the feasibility of our design plan, we focused on the reaction between 3-methylindole (1a, 2 equiv) and α

Phenanthridine–pyrene conjugates as fluorescent probes for DNA/RNA and an inactive mutant of dipeptidyl peptidase enzyme

• Josipa Matić,
• Tana Tandarić,
• Marijana Radić Stojković,
• Filip Šupljika,
• Zrinka Karačić,
• Ana Tomašić Paić,
• Lucija Horvat,
• Robert Vianello and
• Lidija-Marija Tumir

Beilstein J. Org. Chem. 2023, 19, 550–565, doi:10.3762/bjoc.19.40

• signalize complex formation (interaction with a biomolecule, cyclodextrine, metal cation, etc.) or change of receptor conformation [5][6]. Employment of pyrene as a biosensor is complicated due to its large aromatic surface's hydrophobicity and fluorescence sensitivity to oxygen. Therefore, modifications of

CuAAC-inspired synthesis of 1,2,3-triazole-bridged porphyrin conjugates: an overview

• Dileep Kumar Singh

Beilstein J. Org. Chem. 2023, 19, 349–379, doi:10.3762/bjoc.19.29

• 126, it was used to form water-soluble porphyrin nanospheres by self-inclusion complex formation in water. Tritriazole-bridged porphyrin system This section contains the synthesis of porphyrin conjugates having three 1,2,3-triazole groups as linkers. In 2012, Beletskaya and co-workers [55] described

Inclusion complexes of the steroid hormones 17β-estradiol and progesterone with β- and γ-cyclodextrin hosts: syntheses, X-ray structures, thermal analyses and API solubility enhancements

• Alexios I. Vicatos,
• Zakiena Hoossen and
• Mino R. Caira

Beilstein J. Org. Chem. 2022, 18, 1749–1762, doi:10.3762/bjoc.18.184

• . Furthermore, no previous structure determinations via SCXRD analysis of CD complexes of BES and PRO have been reported. Many studies involved phase solubility analyses to determine CD complex formation and association constants. Our previous study of the complexation of the steroidal anticancer agent 2

• kneading experiments (co-grinding of the respective hosts and guests with water as a medium), the complex identities being subsequently determined unequivocally by powder X-ray diffraction (PXRD). Authentic CD complex formation was deduced from close correlation between the angular peak positions of the

• derivatised CDs containing BES and PRO, thus confirming the sustained interest in this approach and its significance in drug delivery. Previous studies of the complexation of BES, PRO and related compounds by CDs in the solution phase have typically reported the use of NMR spectroscopy to investigate complex

Automated grindstone chemistry: a simple and facile way for PEG-assisted stoichiometry-controlled halogenation of phenols and anilines using N-halosuccinimides

• Dharmendra Das,
• Akhil A. Bhosle,
• Amrita Chatterjee and
• Mainak Banerjee

Beilstein J. Org. Chem. 2022, 18, 999–1008, doi:10.3762/bjoc.18.100

• through p-position leading to the formation of the thermodynamically stable halo derivative via a σ-complex formation. The high concentration of substrates and reagents in the close proximity in this solvent-less process and grinding force could be the other reasons for the fast reaction kinetics. The

Heteroleptic metallosupramolecular aggregates/complexation for supramolecular catalysis

• Prodip Howlader and
• Michael Schmittel

Beilstein J. Org. Chem. 2022, 18, 597–630, doi:10.3762/bjoc.18.62

• procedure developed by Sauvage on the basis of topological control [33] has found ample use in the preparation of rotaxane-based machines and devices [34]. A key element is a macrocyclic phenanthroline with an endotopic binding site as it precludes homoleptic complex formation. A further principle