Enantioselective radical chemistry: a bright future ahead

• Anna C. Renner,
• Sagar S. Thorat,
• Hariharaputhiran Subramanian and
• Mukund P. Sibi

Beilstein J. Org. Chem. 2025, 21, 2283–2296, doi:10.3762/bjoc.21.174

• enantioenriched catalysts ranging from chiral organometallic complexes to organocatalysts (small organic molecules) have been designed, synthesized, and successfully used in several organic transformations [1][2][3]. Despite these advances, catalytic methods involving radical intermediates were very rare until

• occurred in an anti fashion. Products were obtained with up to 97% ee via catalysis by complexes of magnesium or copper(II) with ligand L1. The absolute stereochemistry of the product could be controlled by a simple change from copper(II) to magnesium Lewis acids while using the same chiral ligand, thus

• different transition-metal complexes have been employed in metalloradical catalysis, including porphyrin complexes of cobalt(II) [55][56] and iron(III) [57][58]. Both cobalt in oxidation state +2 and iron in oxidation state +3 can be viewed as persistent metalloradicals. Zhang and co-workers reported a

Pd-catalyzed dehydrogenative arylation of arylhydrazines to access non-symmetric azobenzenes, including tetra-ortho derivatives

• Loris Geminiani,
• Kathrin Junge,
• Matthias Beller and
• Jean-François Soulé

Beilstein J. Org. Chem. 2025, 21, 2234–2242, doi:10.3762/bjoc.21.170

• )–aryl intermediate (B). Subsequently, ligand exchange occurs, generating hydrazido complexes C and C'. When bulky substituents are present on the phosphine ligand and/or (both) coupling partner(s) has ortho-substituent(s), the hydrazido complex C, chelating on the terminal nitrogen, is preferentially

Solar thermal fuels: azobenzene as a cyclic photon–heat transduction platform

• Jie Yan,
• Shaodong Sun,
• Minghao Wang and
• Si Wu

Beilstein J. Org. Chem. 2025, 21, 2036–2047, doi:10.3762/bjoc.21.159

• ], norbornadiene–quadricyclane (NBD–QC) complexes [17][18][19][20][21][22][23], dihydroazulene–vinylheptadiene (DHA-VHF) systems [24][25][26][27][28][29][30], and azobenzene derivatives [31][32][33][34] (Figure 2). In addition, other reversible photoisomers exhibit potential for development as solar thermal fuels

Photochemical reduction of acylimidazolium salts

• Michael Jakob,
• Nick Bechler,
• Hassan Abdelwahab,
• Fabian Weber,
• Janos Wasternack,
• Leonardo Kleebauer,
• Jan P. Götze and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2025, 21, 1973–1983, doi:10.3762/bjoc.21.153

• transition-metal complexes such as the Grubbs’ second-generation metathesis catalyst, NHCs are now also well-established as organocatalysts. With the first application pre-dating the unambiguous characterization of a free NHC by nearly 50 years, NHCs can facilitate numerous synthetically attractive

• efficiency observed upon switching from blue to UV-A light irradiation. Nevertheless, alternative scenarios involving the potential formation of excited donor–acceptor (EDA) complexes between benzoylazolium species 1 and DIPEA were considered. Measurements of the UV–vis spectra in the presence of the amine

Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis

• Lihua Wei,
• Rui Yang,
• Zhifeng Shi and
• Zhiqiang Ma

Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151

• been developed, employing enzymes, metal complexes, or organocatalysts to convert prochiral or meso precursors into chiral motifs. Different from other strategies constructing chiral centers by formation of a new chemical bond at the central carbon, enantioselective desymmetrization is achieved through

• desymmetrization of 1,3-diols in 2003 [56]. Subsequent advances included Cu-based complexes developed by Kang and co-workers [57][58], first applied in total synthesis in 2008. In this section, examples of transition-metal-catalyzed acylations of prochiral 1,3-diols in total synthesis are discussed, including Cu

• -catalyzed acylation Zn-based complexes are another class of effective catalysts used in desymmetrization of 1,3-diols, as reported by Trost and co-worker in 2003 [56]. In 2013, Trost et al. developed the synthesis of (−)-18-epi-peloruside A (Scheme 26) [68], and converted diol 204 into enantioenriched

Stereoselective electrochemical intramolecular imino-pinacol reaction: a straightforward entry to enantiopure piperazines

• Margherita Gazzotti,
• Fabrizio Medici,
• Valerio Chiroli,
• Laura Raimondi,
• Sergio Rossi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2025, 21, 1897–1908, doi:10.3762/bjoc.21.147

• products, agrochemicals, and pharmacologically active compounds. Enantiomerically pure 1,2-diamines and their derivatives are also increasingly used in stereoselective synthesis, particularly as chiral auxiliaries or as ligands for metal complexes in asymmetric catalysis [1]. Metal-based reductants

• photochemical and electrochemical methods, have been explored. Over the past two decades a variety of light-promoted imino-pinacol coupling reactions have been developed, involving the use of catalytic transition-metal complexes [35][36], organic dyes [37][38][39], and polyaromatic compounds [40][41] as

Fe-catalyzed efficient synthesis of 2,4- and 4-substituted quinolines via C(sp²)–C(sp²) bond scission of styrenes

• Prafull A. Jagtap,
• Manish M. Petkar,
• Vaishnavi R. Sawant and
• Bhalchandra M. Bhanage

Beilstein J. Org. Chem. 2025, 21, 1799–1807, doi:10.3762/bjoc.21.142

• probes for sensing and bioimaging applications (Figure 1) [16][17]. Quinoline-derived metal complexes have also demonstrated broad utility, functioning as effective catalysts in organic synthesis and finding applications across medicinal chemistry, materials science, photovoltaics, and chemical sensing

Research progress on calixarene/pillararene-based controlled drug release systems

• Liu-Huan Yi,
• Jian Qin,
• Si-Ran Lu,
• Liu-Pan Yang,
• Li-Li Wang and
• Huan Yao

Beilstein J. Org. Chem. 2025, 21, 1757–1785, doi:10.3762/bjoc.21.139

• nanoparticles [73]. Calixarene-based amphiphiles are characterized by their low cytotoxicity and ability to load drugs. The structure of calixarene-drug complexes can respond to external stimuli, causing the self-assembled complex to disassemble, which enables sustained drug release. Based on these

• -assembly after separately modifying hydrophobic and hydrophilic segments; the other is the formation of host–guest complexes between water-soluble PAs and guest molecules containing hydrophobic chains, followed by self-assembly into bilayer vesicles through host–guest interactions, hydrophobic effects, and

• destruction of aromatic macrocycles and their components. The external triggers include: pH [93], oxidation–reduction states [94], enzymatic actions [95], and light [96]. Specifically, within host–guest frameworks, the capability to meticulously regulate the assembly of complexes and synchronize them with

Thermodynamics and polarity-driven properties of fluorinated cyclopropanes

• Matheus P. Freitas

Beilstein J. Org. Chem. 2025, 21, 1742–1747, doi:10.3762/bjoc.21.137

• its ability to form ion complexes and self-assemble into a stacking arrangement [12][13][14]. Therefore, understanding the energetics and polarity of fluorinated cyclopropanes is crucial for elucidating the intramolecular forces that govern the stability of molecular structures. Moreover, these

• 1.2.3-c.c., it is capable of interacting with ions and potentially acting as both an anion and a cation carrier. To evaluate this property, Na+ and Cl− ions were simulated in interaction with one and two molecules of 1.2.3-c.c., forming complexes akin to a "sandwich," as illustrated in Figure 3. In

• these complexes, the cation coordinates with the fluorine atoms, while the anion interacts with the positively charged hydrogen atoms. The complexation is thermodynamically favorable when compared to the isolated species (ions and 1.2.3-c.c.), as indicated by the ΔH0 of formation: −32.5 kcal mol−1 for

Approaches to stereoselective 1,1'-glycosylation

• Daniele Zucchetta and
• Alla Zamyatina

Beilstein J. Org. Chem. 2025, 21, 1700–1718, doi:10.3762/bjoc.21.133

• 3,4,6-tri-O-benzylated 1,2-anhydroglucose 129 using an organoboron catalyst (Scheme 11). In situ-generated tricyclic borinate complexes (formed between 1,2-glycosyl diols and diarylborinic acids) effectively promoted the glycosylation with glycosyl anhydro sugars, yielding the 1,1'-α,α-trehalose

Catalytic asymmetric reactions of isocyanides for constructing non-central chirality

• Jia-Yu Liao

Beilstein J. Org. Chem. 2025, 21, 1648–1660, doi:10.3762/bjoc.21.129

• thionolactones, getting rid of the pre-formation of stoichiometric Ru-complexes [52][53]. Mechanistic investigations indicated that this transformation proceeds through a two-step sequence promoted by the same catalyst: 1) the diastereo- and enantioselective [3 + 2] cycloaddition to generate spiro-S,O-ketal 52

Photocatalysis and photochemistry in organic synthesis

• Timothy Noël and
• Bartholomäus Pieber

Beilstein J. Org. Chem. 2025, 21, 1645–1647, doi:10.3762/bjoc.21.128

• ; photochemistry; Soon after its first reported synthesis in 1936 [1], [Ru(bpy)3]Cl2 (bpy = 2,2'-bipyridine) and its derivatives attracted significant attention due to their photophysical properties [2][3][4]. These complexes can efficiently absorb visible light through a metal-to-ligand charge transfer (MLCT

• Review article discussing photocatalysts capable of harnessing low-energy red light to trigger chemical reactions [19]. In addition to photoredox catalysis, several mechanistic platforms that leverage light – such as the use of electron donor–acceptor complexes [20], proton-coupled electron transfer [21

On the aromaticity and photophysics of 1-arylbenzo[a]imidazo[5,1,2-cd]indolizines as bicolor fluorescent molecules for barium tagging in the study of double-beta decay of ¹³⁶Xe

• Eric Iván Velazco-Cabral,
• Fernando Auria-Luna,
• Juan Molina-Canteras,
• Miguel A. Vázquez,
• Iván Rivilla and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2025, 21, 1627–1638, doi:10.3762/bjoc.21.126

• energies computed at 298.17 K. We also extended this study to the interaction between complexes 15a–d and benzene (14) and computed the corresponding complexation energies as In addition, Figure 4 includes the chief geometric parameters of the different complexes, as well as the corresponding free energy

• analysis of the effect of the aromatic ring represented by the benzene ring shown in Scheme 2 and in Figure 4B was also performed. We observed that for complexes 17a (n = 1) and 17b (n = 2) the low size of the crown ethers generates a poor coordination to Ba2+, which results in more charge available for

• -311+G** (S0) and using TDDFT (S1). Hydrogen atoms have been omitted for clarity. Fully optimized geometries (B3LYP-D3BJ/6ccrow-311++G**&DefTZVPP(Ba) level of theory) of Ba2+·crown ethers 15a–d (A) and phenyl·Ba2+·crown ether complexes 17a–d (B). Barium cations are represented in dark blue. Descriptors

Transition-state aromaticity and its relationship with reactivity in pericyclic reactions

• Israel Fernández

Beilstein J. Org. Chem. 2025, 21, 1613–1626, doi:10.3762/bjoc.21.125

• this end, selected representative examples ranging from fundamental processes such as Diels–Alder or Alder–ene reactions to double-group transfer reactions or 1,3-dipolar cycloadditions involving metal complexes are presented. It is found that while more synchronous processes tend to exhibit greater

• computed lower strain energy and ultimately into the lower barrier. 1,3-Dipolar cycloaddition reactions between azides and metal cyaphide complexes Similar to the Diels–Alder cycloaddition reaction, the 1,3-dipolar cycloaddition between a 1,3-dipole (acting as 4π system) and a 2π dipolarophile is a widely

• , very recently it was found that the C≡P moiety, in particular, can be stabilized in the form of a cyaphide ligand bonded to a metal fragment [99][100]. These cyaphide complexes are proven to readily undergo 1,3-dipolar cycloaddition reactions with organic azides [99][100][101], affording novel metal

3-Aryl-2H-azirines as annulation reagents in the Ni(II)-catalyzed synthesis of 1H-benzo[4,5]thieno[3,2-b]pyrroles

• Julia I. Pavlenko,
• Pavel A. Sakharov,
• Anastasiya V. Agafonova,
• Derenik A. Isadzhanyan,
• Alexander F. Khlebnikov and
• Mikhail S. Novikov

Beilstein J. Org. Chem. 2025, 21, 1595–1602, doi:10.3762/bjoc.21.123

• mechanisms of the formation of azirindine 16 under Ni(II)- and Cu(I)-catalysis. Oxidative dimerization of non-aromatic cyclic enols has been previously observed in their reactions with 3-arylazirines catalyzed by Cu(I) and Cu(II) complexes and was attributed to the recombination of intermediate free radicals

General method for the synthesis of enaminones via photocatalysis

• Paula Pérez-Ramos,
• Raquel G. Soengas and
• Humberto Rodríguez-Solla

Beilstein J. Org. Chem. 2025, 21, 1535–1543, doi:10.3762/bjoc.21.116

• the reactivity of unsaturated esters towards an aza-Michael addition is the use of transition metal complexes as catalysts/promoters [40][41][42]. Considering this background, we reasoned that Ni(II) could be a suitable catalyst for the amination of unsaturated systems. Initial investigations were

Azobenzene protonation as a tool for temperature sensing

• Antti Siiskonen,
• Sami Vesamäki and
• Arri Priimagi

Beilstein J. Org. Chem. 2025, 21, 1528–1534, doi:10.3762/bjoc.21.115

• +MSA−. Because the azo group contains two nitrogens with lone pairs and an excess of MSA was used in the experiments, geometry optimizations were also performed for complexes with two MSA molecules (1H+MSA−MSA, 2H+MSA−MSA and 3H+MSA−MSA). In addition to protonation, we also considered hydrogen-bonded

• complexes between 1–3 and MSA (X-MSA and X-(MSA)2, X = 1, 2 or 3). The geometry-optimized structure of 3H+MSA−MSA is shown in Figure 3. In this structure, the second MSA molecule does not bind directly to the azo group but forms a hydrogen bond with the mesylate anion, and one of its oxygen atoms interacts

• with the 3H+ ion. All geometry-optimized structures for compounds 1–3 are shown in Supporting Information File 1, Figures S19–S28). Table 1 presents the calculated Gibbs free energy changes (∆G°) for the complexes. Among the XH+MSA−MSA (X = 1, 2 or 3) complexes, 3 shows the highest protonation

Microwave-enhanced additive-free C–H amination of benzoxazoles catalysed by supported copper

• Andrei Paraschiv,
• Valentina Maruzzo,
• Filippo Pettazzi,
• Stefano Magliocco,
• Paolo Inaudi,
• Daria Brambilla,
• Gloria Berlier,
• Giancarlo Cravotto and
• Katia Martina

Beilstein J. Org. Chem. 2025, 21, 1462–1476, doi:10.3762/bjoc.21.108

• selectivity for the desired product. Despite the advantages of the developed protocol, the homogeneously catalysed procedure negatively impacted the purification and recovery of the products because of the presence of copper salts and complexes. We observed that multiple aqueous washes of the reaction crude

• also required to obtain a pure final product. To overcome this problem, a heterogeneous catalytic approach has been developed in which copper is anchored on an aminated silica support. Given that ammonia, amino derivatives and other nitrogen-containing compounds form strong coordination complexes with

Advances in nitrogen-containing helicenes: synthesis, chiroptical properties, and optoelectronic applications

• Meng Qiu,
• Jing Du,
• Nai-Te Yao,
• Xin-Yue Wang and
• Han-Yuan Gong

Beilstein J. Org. Chem. 2025, 21, 1422–1453, doi:10.3762/bjoc.21.106

• with Ru(II) to form NIR-emissive complexes that exhibit redox-responsive chiroptical switching, notably with complex 8 showing reversible electronic circular dichroism (ECD) upon oxidation [21]. Liao and co-workers introduced a narrowband CP-TADF emitter 9, characterized by a narrow emission bandwidth

• −1 (Table 3). Importantly, both dimers displayed selective fluoride ion recognition through hydrogen bonding, with (M,M)-12c exhibiting a high binding constant (Ka = 2 × 105 M−1). The resulting [12c·F−] and [12d·F−] complexes exhibited red-shifted circular dichroism (CD), fluorescence, and CPL

• , the team achieved the enantioselective synthesis of heterodehydrospiroenes on a gram scale using chiral vanadium(V) complexes – marking a significant advancement in asymmetric electrochemical catalysis. In a complementary study that same year, they reported a two-step electrochemical synthesis of a

High-pressure activation for the solvent- and catalyst-free syntheses of heterocycles, pharmaceuticals and esters

• Kelsey Plasse,
• Valerie Wright,
• Guoshu Xie,
• R. Bernadett Vlocskó,
• Alexander Lazarev and
• Béla Török

Beilstein J. Org. Chem. 2025, 21, 1374–1387, doi:10.3762/bjoc.21.102

• imidazole-based N-heterocyclic carbene (NHC)–CuCl complexes [40]. However, their synthesis is often tainted by the use of toxic reagents and solvents. In addition, when o-phenylenediamine reacts with ketones, the common catalytic methods yield benzodiazepine products [41]. In our case the reaction of o

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• reduction of the Ni(II) pre-catalyst) via oxidative addition, radical coupling and reductive elimination. The last step is a single-electron transfer between the resulting Ir(II) and Ni(I) complexes, regenerating the active catalysts and closing the two cycles. In 2021, Romanov-Michailidis and Knowles et al

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

• methods utilizing electron donor–acceptor (EDA) complexes and peroxide initiators have recently gained attention due to their operational simplicity and environmental friendliness. In 2024, Song’s group and co-workers presented a novel metal-free, visible-light-promoted method for synthesizing

• difluoroamidated oxindoles via electron donor–acceptor (EDA) complexes (Scheme 37) [23]. The method involved the use of N-phenylacrylamides and bromodifluoroacetamides as starting materials, with N,N,N’,N’-tetramethylethylenediamine (TMEDA) acting as the electron donor. The reaction proceeded efficiently under

• energy (327 kJ/mol) and is less reactive compared to alkyl bromides or iodides. Previous methodologies predominantly relied on alkyl bromides and iodides due to their lower bond dissociation energies. By leveraging the excited-state reactivity of Pd(0) complexes under blue LED irradiation, this method

Enhancing chemical synthesis planning: automated quantum mechanics-based regioselectivity prediction for C–H activation with directing groups

• Julius Seumer,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2025, 21, 1171–1182, doi:10.3762/bjoc.21.94

• activation, transforming these inert bonds into reactive carbon–transition metal (C–M) bonds. Subsequent transformations of these complexes enable the formation of an array of new functional groups, such as carbon–carbon and carbon–heteroatom bonds, underpinning a plethora of synthetic applications

• literature sample from Chen and colleagues [4]. 2. Next, we identify all relevant palladacycle complexes involved in the C–H activation facilitated by ortho-directing groups. For each match, a model complex is constructed containing the substrate and a Pd atom. In this complex, the Pd atom is bonded to the

• carbon at the reaction site and to the heteroatom of the directing group, as illustrated in Figure 5. To assess the geometry of these complexes, we generate a 2D structure using RDKit, where all atoms are constrained to lie in a single plane. Although this type of 2D embedding is typically used only for

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

• organic compounds, with the driving forces leading to inclusion being van der Waals and hydrophobic interactions for apolar guests, and/or hydrogen bonding when the guest features H-bond accepting groups that interact with the hydroxy groups of the cyclodextrins. Interactions with metal ions/complexes and

• coordination with inorganic and organometallic complexes involves hydrophobic interactions and van der Waals forces (mainly with the organic parts of these guests). Several forces are at play in the formation of supramolecular assemblies with gold in the form of haloaurate ions, as detailed in the forthcoming

• networks to optimize the chemical parameters of the extraction. An optimal value of gold removal, lying between 98 and 98.9%, was found to occur with a contact time of 40 minutes, a concentration of α-CD of 11.61 g/L and KOH was added in enough quantity to raise the solution pH to 5 [47][48]. Complexes of

Supramolecular assembly of hypervalent iodine macrocycles and alkali metals

• Krishna Pandey,
• Lucas X. Orton,
• Grayson Venus,
• Waseem A. Hussain,
• Toby Woods,
• Lichang Wang and
• Kyle N. Plunkett

Beilstein J. Org. Chem. 2025, 21, 1095–1103, doi:10.3762/bjoc.21.87

• and I. Without any metal coordination, DFT suggests conformer I is more stable than conformer II by ≈60 kJ/mol. However, upon complexation with Li+, both complexes 2 and 3 are remarkably similar in energy with the difference of less than 1 kJ/mol. This very small energy difference should be too small

• for marked differences in the arrangement of groups in space. The overlaid image of lithium complexes 2 and 3 (Figure 8) shows the similar arrangement of all groups on plane except for one benzyl ring (highlighted by a red asterisk) in complex 2 that faces outside the interior of the macrocycle. A