Asymmetric synthesis of β-amino cyanoesters with contiguous tetrasubstituted carbon centers by halogen-bonding catalysis with chiral halonium salt

• Yasushi Yoshida,
• Maho Aono,
• Takashi Mino and
• Masami Sakamoto

Beilstein J. Org. Chem. 2025, 21, 547–555, doi:10.3762/bjoc.21.43

• of its unique interaction in organic synthesis. Chiral halonium salts have been found to have strong halogen-bonding-donor abilities and work as powerful asymmetric catalysts. Recently, we have developed binaphthyl-based chiral halonium salts and applied them in several enantioselective reactions

• ]. Hypervalent halogen compounds have been utilized as highly reactive substrates [21][22][23][24][25][26][27] and have recently been reported to work as halogen-bonding catalysts [28][29][30][31]. Previously, chiral halonium salts have been utilized in asymmetric catalysis [32][33][34][35], and we have

• alcohols [38]. In this context, their asymmetric syntheses are important and have also been researched mainly using chiral catalysts [39][40]. Previously, the Mannich reaction has been applied in the construction of contiguous stereogenic centers (Figure 2). In 2005, Jørgensen and co-workers reported the

Organocatalytic kinetic resolution of 1,5-dicarbonyl compounds through a retro-Michael reaction

• James Guevara-Pulido,
• Fernando González-Pérez,
• José M. Andrés and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2025, 21, 473–482, doi:10.3762/bjoc.21.34

• processes with low catalyst loading. It involves the kinetic resolution of alcohols, amines, and esters using chiral phosphoric acids [6][7][8][9][10][11][12][13] and sulfoximines with enals using chiral N-heterocyclic carbene (NHC) catalysts [14]. Additionally, these processes have been conducted using

• yields [27]. These reactions have been utilized in the enantioselective synthesis of aryl sulfoxides through the arylation of sulfonate anions in the presence of palladium catalysts [28][29]. They have also been used in the synthesis of the neuraminidase inhibitor (−)-oseltamivir [30] and the

Beyond symmetric self-assembly and effective molarity: unlocking functional enzyme mimics with robust organic cages

• Keith G. Andrews

Beilstein J. Org. Chem. 2025, 21, 421–443, doi:10.3762/bjoc.21.30

• demonstrating enzyme-like rate accelerations remain rare. This perspective will briefly highlight some of the key advances in traditional cavity catalysis, by cavity type, in order to contextualize the recent development of robust organic cage catalysts, which can exploit stability, functionality, and reduced

• enzyme dynamics. The wider history of supramolecular and cavity catalysis [3][13][15][16][17][18][19][21][48][49], and catalysis using confined transition-metal catalysts [50][51][52], dendrimers [53] or synzymes [54], micelles [55] or vesicles [56], catalytic antibodies [57][58][59] or molecularly

• proximal electrostatic potential, even when the charges are flexibly arranged, remote, and solvated in water. Metal-organic cages The exploration of metal-organic cages (MOCs), also known as supramolecular coordination cages (SCCs), as catalysts is thriving [22][36][138][139][140][141]. The reversible bond

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

• , making it particularly suited for large-scale applications. Recent advances highlight the unique advantages of both metal-based and metal-free catalysts under red-light irradiation, broadening the range of possible reactions, from selective oxidations to complex polymerizations. In biological contexts

• organic photocatalysts. Unlike metal-based systems, organic photocatalysts such as phthalocyanins, squaraines and cyanins, offer effective electron and energy transfer under red-light irradiation without relying on transition metals. This shift towards organic catalysts opens new possibilities for

• sustainable photocatalysis, with applications ranging from selective oxidation to cross-dehydrogenative coupling. These organic systems are valued for their reduced environmental impact, their wide availability, and tunability, making them viable alternatives to traditional metal-based catalysts for red-light

Synthesis of disulfides and 3-sulfenylchromones from sodium sulfinates catalyzed by TBAI

• Zhenlei Zhang,
• Ying Wang,
• Xingxing Pan,
• Manqi Zhang,
• Wei Zhao,
• Meng Li and
• Hao Zhang

Beilstein J. Org. Chem. 2025, 21, 253–261, doi:10.3762/bjoc.21.17

• catalysts in conjunction with oxygen [17][18][19][20][21][22], electrochemical oxidation [23][24], and photochemical oxidation techniques [25] have emerged as alternative methods. However, these approaches have a significant limitation: the substrates must be thiols, which have unpleasant odors. This has

• [48][49]. However, some of the previously reported methods have limitations such as the use of strong oxidants, expensive reagents/catalysts, and lengthy work-up procedures, so there is still a need for simpler and more environmentally friendly methods for the preparation of 3-sulfenylchromones. In

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

Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• catalysts have been gaining increasing attention owing to their abundance, cost-effectiveness, and sustainability. Recently, these catalytic systems have been applied to the chemical transformation of dioxazolones, conferring a convenient protocol towards amidated products. This review highlights recent

• electrophiles in various nucleophilic transformations due to their susceptibility to rapid decomposition into the corresponding isocyanates (Scheme 1a) [2][3]. They have attracted increasing interest as electrophilic amide sources in amidation using transition-metal catalysts such as ruthenium, rhodium, and

• iridium (Scheme 1b) [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]. Notably, dioxazolones have primarily been studied in directed carbon–hydrogen amidation processes, which can circumvent the need for tedious prefunctionalizations. Copper catalysts have gained recognition and attracted

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

• ], however, no comprehensive review focusing on Cu-catalyzed electrochemistry has been reported to date. Copper catalysts are potential candidates for pharmaceutical applications owing to their abundance, low cost, and lower toxicity compared with noble transition metals such as palladium [39]. In terms of

• the product are accessible by adjusting the two distinct chiral catalysts. C–N Bond formation In 2018, Mei et al. developed the electrochemical C–H amination of arenes with amine electrophiles using copper catalysis, which provided a step-economical approach for the synthesis of aromatic amines by

• reactions of copper catalysts without ligands face limitations owing to slow electron transfer kinetics, irreversible copper plating, and competing substrate oxidation. To overcome these challenges, Sevov et al. developed a ligand-free, Cu-catalyzed electrochemical Chan–Lam coupling using a ferrocenium salt

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

• emerged among copper catalysts because it can act as a precursor to triflic acid in addition to a powerful copper-catalytic effect. Indeed, Cu(OTf)2 has proven to be an excellent surrogate for triflic acid compared with other metal triflates because it is inexpensive and exhibits high activity with low

• transition-metal catalysts provides synthetic tools even more advantageously. Copper has also become very interesting in this field, mainly in processes aimed at synthesizing heterocyclic compounds. Among the various catalysts, Cu(OTf)2 stands out in heterocyclic synthesis and ring transformations due to its

• counteranion. The use of a carbamate among the substrates instead of the amine allowed the synthesis of propargylcarbamates 11. This reaction, effective only for the aromatic aldehydes, did not require other co-catalysts or ligands (Scheme 8) [21]. Three-component reactions of alkynes, alkyltrifluoroborates

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• becoming increasingly relevant also in medicine. Many axially chiral compounds are important as catalysts in asymmetric catalysis or have chiroptical properties. This review overviews recent progress in the synthesis of axially chiral compounds via asymmetric organocatalysis. Atroposelective

• acids feature as the most prolific catalytic structure. The last part of the article discusses hydrogen-bond-donating catalysts and other catalyst motifs such as phase-transfer catalysts. Keywords: asymmetric organocatalysis; atropoisomers; atroposelective synthesis; axial chirality; stereogenic axis

• to NHC-catalyzed reactions. The major part is devoted to chiral Brønsted acid catalysis as it seems so far the most widely used activation principle for the generation of axially chiral compounds. Hydrogen-bond-donating catalysts and various other activation modes complete the discussion of recent

Facile one-pot reduction of β-nitrostyrenes to phenethylamines using sodium borohydride and copper(II) chloride

• Laura D’Andrea and
• Simon Jademyr

Beilstein J. Org. Chem. 2025, 21, 39–46, doi:10.3762/bjoc.21.4

• aluminum hydride, sodium borohydride is a non-pyrophoric and easy-to-handle reducing agent. Since the first attempts in 1967, NaBH4 has been employed to reduce β-nitrostyrene scaffolds to the corresponding nitroalkanes [19][20][21]. Several catalysts have been combined with NaBH4 to facilitate full

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

• chemistry. Packed bed reactors are used when solid heterogeneous catalysts and reagents (e.g., inorganic bases) are handled. Specialized reactors for electro- [36][37] and photochemical [38][39][40] experiments have also been developed. Depending on the flow of the reaction mixture, flow reactions can be

• were explored, using a total volume of 4.5 mL reaction mixture, and the screening results can be readily translated to continuous flow synthesis. The application of segmented flow or microslug reactors was demonstrated in the decarboxylative arylation cross-coupling reaction promoted by catalysts and

• reaction steps. Nandiwale et al. [61] reported the autonomous optimization of three multiphase catalytic reactions involving the handling of solid substrates, operating the photoreactor, and feeding of the slurries, catalysts, and inorganic bases in an automated flow platform comprising a continuous

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

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• -heterocycles using various catalytic systems such as chiral metal catalysts, chiral Lewis acids or chiral organocatalysts. This review presents an overview of the recent advances in enantioselective cyclization reactions of 1-azadienes catalyzed by non-covalent organocatalysts. Keywords: α,β-unsaturated

• reviews [17][18]. Review Hydrogen bond donors: bifunctional thioureas and squaramides The use of bifunctional catalysts is commonplace in organocatalyzed transformations [19][20][21][22][23]. These catalysts are able to activate an electrophile and a nucleophile simultaneously and in IEDADA reactions they

• catalysts are synthesized by joining together two fragments of cinchona alkaloids. In this manner, it is possible to obtain a symmetric catalyst, which can engage in hydrogen bonding interactions and deprotonation processes. Although they were originally used for Sharpless dihydroxylation, they have been

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

• extensive scope across a range of benign solvent conditions [7][8][9][10]. In addition, the CuAAC reaction uses inexpensive Cu catalysts [11], is insensitive towards oxygen and water [12][13], and consistently delivers high yields and (where relevant) enantioselectivities [8][9][10][14][15][16][17][18][19

Synthesis of extended fluorinated tripeptides based on the tetrahydropyridazine scaffold

• Thierry Milcent,
• Pascal Retailleau,
• Benoit Crousse and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2024, 20, 3174–3181, doi:10.3762/bjoc.20.262

• strategy, the control of the stereoselectivity of the intramolecular aza-Michael addition could be envisaged with various chiral catalysts in further studies. These heterocyclic hydrazino acids, when incorporated into the peptidic structure, appear to confer an extended conformation. These interesting

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• the fluoride source did not yield the desired fluorooxazines, highlighting the role of BF3·Et2O as both a fluoride reagent and an activating reagent of iodosylbenzene. Different chiral iodide catalysts were studied, revealing that the substituents of the catalysts significantly influenced the

• stereochemistry of the reaction. Linear chiral catalysts were found to offer higher stereoselectivity compared to spiro-catalysts. Under optimized conditions, the asymmetric aminofluorination of N-cinnamylbenzamides 37 using BF3·Et2O as the fluorine reagent demonstrated good yields and high stereoselectivity

• is then attacked by a nucleophile. The use of chiral iodine catalysts is essential for controlling the stereochemistry of the reaction. The specific arrangement of the catalyst influences the orientation of this nucleophilic attack as supported by density functional theory (DFT) calculations. In 2022

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

• two macrocycles as metal-free catalysts. Keywords: calix[4]pyrroles; electrocatalysis; free-base porphyrins; organocatalysis; photocatalysis; tetrapyrrolic macrocycles; Introduction Tetrapyrrolic macrocycles are a class of cyclic compounds that contain four pyrrolic units in their ring. Examples of

• recognition, and supramolecular assemblies [9][10][11][12][13]. There are numerous examples of using metalloporphyrins as artificial photosynthesis models, enzyme mimics, and catalysts for various organic transformations, where a metal center acts as an active site [14][15][16][17]. However, metal-free (or

• free-base) macrocycles have not been explored as much in terms of catalysis, even though they are starting compounds for the preparation of their metallated analogues that are commonly used as catalysts. In contrast with a calix[4]pyrrole macrocycle with four NHs (from four pyrrole units), a metal-free

Enantioselective regiospecific addition of propargyltrichlorosilane to aldehydes catalyzed by biisoquinoline N,N’-dioxide

• Noble Brako,
• Sreerag Moorkkannur Narayanan,
• Amber Burns,
• Layla Auter,
• Valentino Cesiliano,
• Rajeev Prabhakar and
• Norito Takenaka

Beilstein J. Org. Chem. 2024, 20, 3069–3076, doi:10.3762/bjoc.20.255

• catalyst is (i.e., less degree of conformational freedom for a bound substrate), the better is the enantioselectivity for analogous chlorosilane-mediated reactionss [47][48][49][51][54]. Therefore, we gradually narrowed the chiral pocket of catalysts from 3 to 4, 5 [53], and 6 [56][57]. To our surprise

• pure propargyltrichlorosilane, it clearly demonstrated that this class of chiral Lewis bases regiospecifically catalyzed the addition of propargyltrichlorosilane to aldehydes, and that these catalysts did not induce the propargyl–allenyl metallotropic rearrangement albeit activating the C–Si bond. Thus

• the two transformations. Studies directed toward a better understanding of possible transition-state structures and the design of new catalysts to improve the results are currently underway in our laboratories. A potential energy surface (PES) for the proposed mechanism for (a) isomerization of

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

• carried out as part of the investigation of the enzymatic function of cytochrome P-450 with low valent ruthenium complex catalysts. Various phenols 86 bearing para-substituents were transformed into the corresponding tert-butyldioxy dienones 87 smoothly using RuCl2(PPh3)3 as the catalyst (Scheme 31) [83

Synthesis of fluorinated acid-functionalized, electron-rich nickel porphyrins

• Mike Brockmann,
• Jonas Lobbel,
• Lara Unterriker and
• Rainer Herges

Beilstein J. Org. Chem. 2024, 20, 2954–2958, doi:10.3762/bjoc.20.248

• ]. Beyond their essential biological roles, porphyrins and their derivatives are employed in a number of applications, acting as catalysts in numerous reactions, including oxidation, reduction, and cycloaddition [6][7][8][9][10]. Particularly when electron-rich porphyrins act as reducing agents, e.g. in

gem-Difluorovinyl and trifluorovinyl Michael acceptors in the synthesis of α,β-unsaturated fluorinated and nonfluorinated amides

• Monika Bilska-Markowska,
• Marcin Kaźmierczak,
• Wojciech Jankowski and
• Marcin Hoffmann

Beilstein J. Org. Chem. 2024, 20, 2946–2953, doi:10.3762/bjoc.20.247

• , serve as effective motifs for designing stable gem-difluorovinyl and trifluorovinyl Michael acceptors. To our knowledge, this represents the inaugural instance of employing potent bases such as n-BuLi and tert-BuLi to fulfill dual roles as both base catalysts and Michael donors. The reactions exhibited

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

• or without the use of transition metals [44]. Thus, they address both the financial and environmental challenges associated with organic synthesis by acting as environmentally benign substitutes for costly organometallic catalysts and heavy-metal-based oxidants. Diaryl iodide salts consist of two

• 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

• reactions occurred under mild conditions and without any need of transition-metal catalysts. In 2023, Wu and colleagues successfully synthesized a range of meta-substituted biaryl ethers. The reaction involves phenols 61 and cyclic diaryliodonium salts 73, dissolved in tert-butyl alcohol, in the presence 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

• literature. In light of the promise of appropriately designed nonplanar porphyrins as receptors and catalysts we report here on our efforts to use the Suzuki–Miyaura reaction for the modification of the o,m,p-phenyl positions in 5,10,15,20-tetraryl-2,3,7,8,12,13,17,18-octaethylporphyrins. Results and

• -workers for the synthesis of meso-substituted aryl bis-pocket porphyrins [34]. Therein catalysts Pd(dppf)Cl2 and Pd(PPh3)3 were identified to be the most effective for accomplishing the Suzuki–Miyaura coupling at the ortho-position of the meso-phenyl position in sterically hindered planar porphyrins

Copper-catalyzed yne-allylic substitutions: concept and recent developments

• Shuang Yang and
• Xinqiang Fang

Beilstein J. Org. Chem. 2024, 20, 2739–2775, doi:10.3762/bjoc.20.232

• substitutions of 5-ethynylthiophene esters. A series of C-, N-, O-, and S-nucleophiles could react smoothly to obtain various thiophene derivatives with different functional groups (Scheme 29, 28a–t). Control experiments showed that terminal alkyne and copper catalysts are crucial for the smooth progress of the

• ethynylethylene carbonates and copper catalysts (Scheme 37). He et al. [77] completed formal [4 + 1] and [4 + 2] annulations and obtained two types of seldomly studied heterocycles of thieno[2,3-c]pyrrole (Scheme 38, 36a–j) and thieno[2,3-d]pyridazine (Scheme 39, 38a–h) in high yields. It is worth noting that the