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

• final products 26k and 26l in 73% and 53% yield, respectively. Radical-trapping experiments with TEMPO (2,2,6,6-tetramethylpiperidine-1-oxyl) and BHT (butylated hydroxytoluene) additives confirmed the involvement of α-aminoalkyl radicals in this transformation, as shown in Scheme 14. A single-electron

• particularly noteworthy for its use at room temperature, requiring no transition metals, photocatalysts, or additives. Notably, Umemoto's reagent served as the trifluoromethyl source, and the reaction was facilitated under blue LED irradiation, achieving good to excellent yields. Moreover, this approach

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

• the gold-precipitating properties of a more affordable cyclodextrin, β-CD, is, on the other hand, still taking its first steps. In the case of the bromoaurate ion, the method implies the use of a precipitate co-former. There are, nonetheless, advantages to the use of additives, namely the possibility

• . C skyblue, O red, Br brown, Au yellow. (c) Schematic illustration of the mechanism leading to precipitation (named “supramolecular polymerisation” by the authors) after adding various additives to the solution of β-CD and [AuBr4]− anions. Reproduced from [51] (© 2023 H. Wu et al., published by

Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• features of the starting material. By exploiting preorganization, steric effects, or directing groups within the substrate, chemists can achieve high levels of regioselectivity, diastereoselectivity, and enantioselectivity without relying on external catalysts or additives. This approach has been

Dicarboxylate recognition based on ultracycle hosts through cooperative hydrogen bonding and anion–π interactions

• Wen-Hui Mi,
• Teng-Yu Huang,
• Xu-Dong Wang,
• Yu-Fei Ao,
• Qi-Qiang Wang and
• De-Xian Wang

Beilstein J. Org. Chem. 2025, 21, 884–889, doi:10.3762/bjoc.21.72

• ]. Additionally, dicarboxylates like tartrate, adipate or citrate are widely used as food additives [23][24]. Furthermore, functional materials based on dicarboxylates are expected to play a significant role in future technologies [25]. Therefore, the recognition and detection of dicarboxylates are of great

Chitosan-supported CuI-catalyzed cascade reaction of 2-halobenzoic acids and amidines for the synthesis of quinazolinones

• Xuhong Zhao,
• Weishuang Li,
• Mengli Yang,
• Bojie Li,
• Yaoyao Zhang,
• Lizhen Huang and
• Lei Zhu

Beilstein J. Org. Chem. 2025, 21, 839–844, doi:10.3762/bjoc.21.67

• promote this cascade reaction for the synthesis of quinazolinones without the need for additional ligands or additives (Scheme 1a) [7][10]. Since then, various copper-based catalysts, both homogeneous and heterogeneous, have been explored (Scheme 1b) [11][12][13][14][15][16]. For example, Wang’s group

Development and mechanistic studies of calcium–BINOL phosphate-catalyzed hydrocyanation of hydrazones

• Carola Tortora,
• Christian A. Fischer,
• Sascha Kohlbauer,
• Alexandru Zamfir,
• Gerd M. Ballmann,
• Jürgen Pahl,
• Sjoerd Harder and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2025, 21, 755–765, doi:10.3762/bjoc.21.59

• industrial production (Table 2, entries 4, 8, and 9). All these experiments gave only low ee values (4–19% ee, Table 2, entries 4–9), with a preference for the S-enantiomer. Use of aromatic alcohol or (R)-1-phenylethanol as additives did not improve either yields or enantioselectivities (Table 2, entries 5

• and 6 vs entry 4). Accordingly, experiments without additive performed better in terms of yield and enantioselectivity than those with additives but the ee values remain low (Table 2, entries 7–9 vs entries 4–6). Surprisingly, in all experiments with the pre-formed catalyst 6 (Table 2, entries 4–9), a

• of alcohols as additives has a negative effect on both yield and enantioselectivity. The enantioselectivity was generally low (Table 2, entries 4–9) and with preference for the S-configured hydrocyanide employing the pre-formed Ca complex 6. In addition, product 2 was obtained with absolute

Visible-light-promoted radical cyclisation of unactivated alkenes in benzimidazoles: synthesis of difluoromethyl- and aryldifluoromethyl-substituted polycyclic imidazoles

• Yujun Pang,
• Jinglan Yan,
• Nawaf Al-Maharik,
• Qian Zhang,
• Zeguo Fang and
• Dong Li

Beilstein J. Org. Chem. 2025, 21, 234–241, doi:10.3762/bjoc.21.15

• −), respectively (Scheme 1a). Despite these advances, the above methods still suffer from several limitations, including a narrow substrate scope, the reliance on expensive metal catalysts and excess additives, and the need for multistep synthesis of difluoromethylating reagents. These drawbacks restrict their

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

• , entry 3). Reducing the catalyst loading to 5 mol % slightly affected the yield of 3bb, which was 90% (Table 1, entry 4). Next, we evaluated various additives with 5 mol % of Ni(cod)2 to stabilize regenerated zero-valent nickel species (Table 1, entries 5–8). While phosphine ligands such as triphenyl

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

• the coupling with copper triflate as catalyst, without ligand, co-catalyst or other additives. The reaction involved the formation of the imine XVII followed by alkynylation to propargylamine XVIII, cyclization, and oxidation to quinoline 23 (Scheme 17) [34]. Three component oxidative annulation to

Hot shape transformation: the role of PSar dehydration in stomatocyte morphogenesis

• Remi Peters,
• Levy A. Charleston,
• Karinan van Eck,
• Teun van Berlo and
• Daniela A. Wilson

Beilstein J. Org. Chem. 2025, 21, 47–54, doi:10.3762/bjoc.21.5

• , solutions of PSar homopolymer and saccharose were employed, initiating the shape transformation as well (Supporting Information File 1, Figures S33 and S35). This suggests that various hydrophilic biocompatible additives could be viable for inducing osmotic shock in shape transformation. Both PEG and PSar

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

Intramolecular C–H arylation of pyridine derivatives with a palladium catalyst for the synthesis of multiply fused heteroaromatic compounds

• Yuki Nakanishi,
• Shoichi Sugita,
• Kentaro Okano and
• Atsunori Mori

Beilstein J. Org. Chem. 2024, 20, 3256–3262, doi:10.3762/bjoc.20.269

• %, respectively. The highest yield of 2b was obtained in the presence of CyJohnPhos (L3) as ligand, while tricyclohexylphosphine (L2) gave the best yield in the reaction of 1c. Concerning the reaction of 1c, the use of tetra-n-butylammonium bromide and pivalic acid as additives and PCy3 (L2) as a ligand further

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• -alkyloxazolidinones, eliminating the need for any Lewis base or additives [74]. This represented a significant advancement over their previously reported work. They used six different protonated porphyrins as catalysts: TPPH4X2 (18a, X = Cl; 18b, X = Br; 18c, X = I), and TPPH4(RCOO)2 (18d, R = CF3; 18e, R = ClCH2

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

• investigated (Scheme 63b) [132]. Vicinal bis-tert-butylperoxides 204 were isolated in low yields among various oxidation products. Xu and Liu with colleagues demonstrated the influence of the solvent and additives on the chemoselectivity of iodine-catalyzed oxidation of styrenes 206 with TBHP (Scheme 64) [133

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

• intermediate I. Furthermore, intermediate I subsequently undergoes another SET reaction, resulting in intermediate II and the regeneration of the photocatalyst. Intermediate II undergoes deprotonation, facilitated by the presence of Cs2CO3 as base, to yield the final products 27 or 29. Additives like BQ likely

• additives. An efficient conversion was detected when the substrate contains electron-rich functionalities. In contrast, the yield dropped notably when the amines were substituted with electron-deficient functionalities. In addition, asymmetric diaryliodonium salts were examined, and the transfer of the aryl

Synthesis and antimycotic activity of new derivatives of imidazo[1,2-a]pyrimidines

• Dmitriy Yu. Vandyshev,
• Daria A. Mangusheva,
• Khidmet S. Shikhaliev,
• Kirill A. Scherbakov,
• Oleg N. Burov,
• Alexander D. Zagrebaev,
• Tatiana N. Khmelevskaya,
• Alexey S. Trenin and
• Fedor I. Zubkov

Beilstein J. Org. Chem. 2024, 20, 2806–2817, doi:10.3762/bjoc.20.236

• ]pyrimidines thus formed did not show significant bioactivity, they found applications as additives in electrochemical copper plating processes [21][22] (Figure 2). Based on the above, the main goal of this work was to develop a convenient method for the construction of potentially pharmacophoric imidazo[1,2-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

• back to [Co(II)] at the anode (Scheme 32). Recently, two additional studies on cobalt–salen complex-induced (cyclo)additions were reported by the Kim [44] and Findlater groups [45]. By employing cobalt–salen as a catalyst, along with PhMeSiH2 and dimethoxypyridine as additives, n-Bu4NPF6 as the

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

• , such as substrate concentrations, bases, and additives, are considered in local models. The development of these models usually involves using HTE [22][23][24] for efficient data collection, coupled with Bayesian optimization (BO) [25] for searching the best reaction conditions to achieve the desired

• represent the prediction targets, as some additives, such as molecular sieves and zeolites, cannot be represented by SMILES notation. However, the labels in the datasets may have some inconsistencies, such as different names for the same chemical, which may affect the learning and performance of the models

Facile preparation of fluorine-containing 2,3-epoxypropanoates and their epoxy ring-opening reactions with various nucleophiles

• Yutaro Miyashita,
• Sae Someya,
• Tomoko Kawasaki-Takasuka,
• Tomohiro Agou and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2024, 20, 2421–2433, doi:10.3762/bjoc.20.206

• its convenient handling and availability at a low cost. Following to the reported protocol [41], although a catalytic amount of Al2O3 and MgO worked nicely (entries 1 and 2 in Table 1), it was clarified that these additives were not necessary for the attainment of the same level of chemical yields

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

• heterocycle substitute at the sulfur atom [49][50][54]. Non-enzymatic process of the rat (Wistar) liver homogenate lipid peroxidation (LP) in the presence of additives of target compounds 1–9 was studied in vitro. The concentration of the carbonyl compounds forming in the reaction of the lipid peroxidation

• ). The CV curves of 7 at the potential ranges from –0.5 to 1.3 V (curve 1); from –0.5 to 1.8 V (curve 2) (CH3CN, GC electrode, Ag/AgCl/KCl(sat.), 0.15 M n-Bu4NClO4, c = 3 mmol·L−1). The level of TBARS in rat liver homogenates in vitro, in the presence of compounds 1–9, Trolox, and without additives

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

• additions to imines, comprising alcohols, thiols, phosphonates, diazoacetamides, peroxides, benzothiazolines and more as nucleophiles. Apart from reactant classes, the reactions also vary in additives, and solvent among others. Since these reactions all adhere to the same mechanism of enantioinduction, the

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

• osmolarity using ten different technical additives including organic solvents, polymers, and salts. It is shown that the synthesis of two model proteins, namely superfolder GFP (sfGFP) and the enzyme truncated human cyclic GMP-AMP synthase fused to sfGFP (thscGAS-sfGFP), is very robust against most of the

• tested additives. Keywords: cell-free protein synthesis; cGAS; Escherichia coli cell-free extract; sfGFP; TX-TL; Introduction In addition to other applications such as biomanufacturing or biosensing, cell-free protein synthesis (CFPS) of enzymes has established itself as a tool for rapid screening of

• encoding for the target protein, amino acids and nucleoside triphosphates as substrates, an energy regeneration system and other additives such as polyethylene glycol (PEG) [9]. Although CFPS has been used and improved since the 1960s, there are challenges in its application such as low production volumes

Factors influencing the performance of organocatalysts immobilised on solid supports: A review

• Zsuzsanna Fehér,
• Dóra Richter,
• Gyula Dargó and
• József Kupai

Beilstein J. Org. Chem. 2024, 20, 2129–2142, doi:10.3762/bjoc.20.183

• generated by altering the reaction conditions during synthesis [52][53][54][55][56][57] or by using potassium chloride or ammonium fluoride salts as additives [58][59][60]. In a comprehensive study [61], the catalytic properties of three types (rope, rod and fibre) of mesoporous silica Santa Barbara

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

• -membered cyclic diboron compounds 18 undergo an insertion reaction of isocyanides into the boron–boron single bond of 18 under mild conditions without the addition of any additives (Scheme 11a) [48]. The reaction is thought to proceed by an ionic mechanism. Recently, several insertion-type reactions of

Novel oxidative routes to N-arylpyridoindazolium salts

• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2024, 20, 1906–1913, doi:10.3762/bjoc.20.166

• . Our experiments with the acid additives (see above) showed that protonation of the pyridyl group suppresses the pyridoindazolium salt formation. Voltammetry testing also showed that 2,6-lutidine addition facilitates oxidation of the amine (Figure 2); the peak potential was of 100 mV shifted toward

• into the reaction mixture (Figure 4a,b). Notably, the effect was more pronounced in the presence of lutidine, especially in the case of TEMPO. The difference between the oxidation potential of A3 and the potential of the TEMPO/TEMPO+ redox couple is rather significant (ca. 0.35 V); the base additives

• useful compounds with multiple functionalities that were poorly available previously. CV curves for salt S2 and corresponding amine A2 (left, Figure 1a) and salt S3 with and without diethyl malonate additives (right, Figure 1b). (Pt, MeCN, 0.1 M Bu4NBF4, 0.1 V/s, vs Ag/AgCl, KCl(sat.). CV curves for