Synthesis of the tetracyclic skeleton of Aspidosperma alkaloids via PET-initiated cationic radical-derived interrupted [2 + 2]/retro-Mannich reaction

• Ru-Dong Liu,
• Jian-Yu Long,
• Zhi-Lin Song,
• Zhen Yang and
• Zhong-Chao Zhang

Beilstein J. Org. Chem. 2025, 21, 2470–2478, doi:10.3762/bjoc.21.189

• leads to ketene D, which can undergo cycloaddition with an alkene to yield E. This fragmentation pathway dominates under various conditions (e.g., transition-metal catalysis, nucleophilic addition) and is driven by ring-strain release [11]. PET, an alternative to direct excitation and EnT, enables the

Comparative analysis of complanadine A total syntheses

• Reem Al-Ahmad and
• Mingji Dai

Beilstein J. Org. Chem. 2025, 21, 2334–2344, doi:10.3762/bjoc.21.178

• strategies and creative tactics, reflecting how emerging synthetic capabilities and concepts can positively impact natural product total synthesis. Keywords: biomimetic synthesis; C–H functionalization; complanadine; lycopodium alkaloid; skeletal editing; total synthesis; transition metal catalysis

• approaches. Overall, their synthesis highlights the impact of enabling transition metal catalysis on natural product total synthesis. The Siegel synthesis starts with chiral pool molecule (+)-pulegone (14), which encodes the first stereocenter of the entire sequence. (+)-Pulegone was converted to compound 15

• pyridine via a single-atom skeletal editing using the 145-year-old Ciamician–Dennstedt rearrangement, completing its long overdue debut in total synthesis. Overall, each of these four total syntheses showcase innovative strategies and creative and enabling tactics including modern transition metal

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

• describes several important catalytic asymmetric strategies applied to enantioselective radical reactions, including chiral Lewis acid catalysis, organocatalysis, photoredox catalysis, chiral transition-metal catalysis and photoenzymatic catalysis. The application of electrochemistry to asymmetric radical

• catalysis is discussed initially. This is followed by the recently emerging areas of transition-metal catalysis, photoenzymatic catalysis, and electrochemistry. Perspective Radical generation and reactions Synthetic methods based on free radical chemistry are some of the most efficient and powerful tools

• , transition-metal catalysis, and enzyme catalysis. Progress in enantioselective reactions using these approaches is discussed with the help of one or two examples in each category to highlight the outstanding achievements in the past three decades. Other modes of catalysis relying on hydrogen-bonding [13][14

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

• substituted amines under metal catalysis or catalyst-free conditions, using hydrosilane, formic acid, hydrogen, MeOH or HCOOH/Et3N as reducing sources [245]. The type and recyclability of catalysts, the nature of supports, reaction conditions, and reactors play important roles in the sustainability of the

Multicomponent reactions IV

• Thomas J. J. Müller and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2082–2084, doi:10.3762/bjoc.21.163

• a strong emphasis on heterocycle synthesis. Beyond traditional condensation-based approaches, mechanistically innovative crossovers – linking metal catalysis with radical chemistry and, more recently, with photo(redox) catalysis – are opening entirely new avenues for MCR development. Finally, seven

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

• activation; C–H annulation; iron metal catalysis; quinolines; styrene; Introduction Quinolines are one of the essential heteroaromatic motifs that play a crucial role across diverse scientific fields due to their wide range of applications. In contemporary medicine, quinoline derivatives frequently appear

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

• , and inherent chirality, remain largely underdeveloped. To date, only a single example has been reported for each case, all of which are restricted to palladium-catalyzed isocyanide insertion reactions. Second, the catalytic systems employed thus far are relatively limited. Although transition metal

• catalysis, particularly with palladium and silver, has proven to be highly effective, expanding the scope as well as the activation mode of chiral catalysts could greatly enrich reaction types and accessible structural diversity. Third, further investigation into the potential applications of the resulting

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

• of a dehydroalanine derivative using silane-mediated halogen atom transfer [28]. Dual catalytic approaches that merge photocatalysis with Lewis acid [29], organo- [30], or transition metal catalysis [31] have enabled access to bond formations that are otherwise challenging to achieve. In particular

• , the combination of nickel catalysis and photoredox catalysis has become one of the most studied strategies to forge carbon–carbon bonds. The groups of Soengas and Rodríguez-Solla used this strategy to develop a general method for the synthesis of enaminones [32]. Light-induced transition metal

• catalysis that does not require exogenous photocatalysts has emerged as a new paradigm in photochemical synthesis [33]. Here, a transition metal complex plays a dual role by harnessing photon energy to facilitate bond-breaking and bond-forming events. For example, Sipos and co-workers demonstrate in this

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

• reactions of intermolecular annulation of a variety of non-aromatic five- [4][5][6] and six-membered carbo- and heterocycles [7][8][9] with azirines, which occur under transition metal catalysis or photocatalysis. Annulation of the pyrrole ring to an aromatic system is limited to reactions of functionalized

Copper catalysis: a constantly evolving field

• Elena Fernández and
• Jaesook Yun

Beilstein J. Org. Chem. 2025, 21, 1477–1479, doi:10.3762/bjoc.21.109

• , decarboxylative functionalizations, and Chan–Lam coupling reactions. In doing so, the authors point out the combination of transition-metal catalysis and electrochemistry as an efficient, sustainable method for the oftentimes challenging formation of C–C and C–heteroatom bonds in complex molecules. Another Review

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

• ), pronounced chiroptical activity (|gabs| = 0.0054–0.0056), and substantial ΦF of 0.21–0.32 under both neutral and acidic conditions. This work exemplifies the power of transition-metal catalysis for constructing enantioenriched helicenes with tunable photophysical properties. These contributions from 2021

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

Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

• release (82). Numerous cinnamic acid derivatives with electron-withdrawing and -donating groups were converted to the corresponding amides 76–81 in moderate to excellent yields (Scheme 24B) [60]. 2.1.2 Transition-metal catalysis: Several transition metals have been exploited to catalyze O/N-acylations of

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

• , 13C, and 31P NMR as well as mass-spectrometric data of all synthesized compounds and selected crystal structures. Acknowledgements Portions of this work are included in the doctoral thesis of Christian Andreas Fischer, “Insights in Group 2 Metal Catalysis: New Ways and New Obstacles”, Friedrich

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

• will be crucial for advancing the field of asymmetric synthesis. Representative transition-metal catalysis for allylic substitution. Formation of stereogenic centers in copper-catalyzed allylic alkylation reactions. Copper-mediated, stereospecific SN2-selective allylic substitution through retentive

Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• traps the sulfonium ylide (Scheme 16). In an independent work, Mhaske et al. proposed an alternative methodology to furnish β-amino ketone 20a (Scheme 17), using DMSO as a formaldehyde surrogate but with activation via ammonium persulfate (APS), avoiding the use of transition-metal catalysis [51]. In

• medicinal chemistry [58]. One of the most effective strategies for their synthesis is the addition of alkynes to imines or enamines, which is typically carried out under metal catalysis and elevated temperatures. This process requires the use of high boiling point solvents such as toluene, dimethylformamide

• function as aldehyde equivalent in reactions where iminium species are involved. In this case, the C–X bond of the dihaloalkanes can be activated by metal catalysis, allowing the incorporation of the C1 building block by a mechanism that does not involve the preformation of an imine/enamine intermediate

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

• organic chemistry [2][3][4][5], organocatalysis [6][7], metal catalysis [8][9], biochemistry [10][11], materials science [12][13], and supramolecular chemistry [14][15], although its successful application to asymmetric catalysis has been limited (Figure 1) [16][17][18][19][20]. In 2018, Arai and co

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

• transition-metal catalysis. As the use of osmium catalysts has already demonstrated scalability in industrial applications [22], the introduction of bismuthinidene complexes presents another step forward in expanding the photoredox catalysis toolkit, potentially paving the way for more sustainable and

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

• chemistry. Combining electrochemistry with transition-metal catalysis is a promising and rapidly growing methodology for effectively forming challenging C–C and C–heteroatom bonds in complex molecules in a sustainable manner. In this review, we summarize the recent advances in the combination of

• remains a significant challenge owing to the high energy barrier required for oxidative addition and facile β-hydride elimination [12]. The development of radical approaches facilitated by transition-metal catalysis has provided a promising solution to overcome the limitations of conventional coupling

• achieved by precisely controlling the potential. Additionally, the merging of electrochemistry and transition-metal catalysis offers advantages in controlling substrate activation, intermediate reactivity, and bond formation, as well as facilitating asymmetric transformations. As a result, electrochemical

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

• the hydrosilane to generate a silyl radical. This silyl radical is then oxidized anodically to produce a silyl cation. The silyl cation subsequently abstracts a proton from water (H2O), forming the desired silanol product (Scheme 28). While many methods combining metal catalysis and electrochemistry

• product (Scheme 34). To date, only a few enantioselective reactions using metal catalysis and electrochemistry have been reported. Very recently, Ackermann and coworkers employed Co(OAc)2 as a catalyst and a salicyloxazoline derivative as a chiral ligand to achieve the electrochemical atroposelective C–H

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

• Research (NCCR) Catalysis, ETH Zurich, Zurich CH-8093, Switzerland 10.3762/bjoc.20.196 Abstract Organocatalysis has established itself as a third pillar of homogeneous catalysis, besides transition metal catalysis and biocatalysis, as its use for enantioselective reactions has gathered significant

• pitfall regarding computational data is its accuracy with respect to the ground truth, in particular for multiple factors relevant throughout catalysis, such as non-covalent interactions (NCIs) for organocatalysis or spin properties for transition metal catalysis [35][36]. While most quantities can in

• transition metal catalysis [46][47][48] and biocatalysis [49][50][51], they are however not common for organocatalysis. Therefore, much research has been devoted to develop models that perform well on the available small data sets [52][53]. 1.2 Representation In order to be processed by any ML model, the

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

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

• solubility issues of metal fluoride salts, safety issues with hydrogen fluoride, poor nucleophilicity [79], and side reactivity as a base [75][79], a few elegant examples of nucleophilic benzylic C(sp3)–H fluorination have been reported. Metal catalysis Fluoride sources have been used in combination with

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

• electrophotochemical transition metal catalysis [26][27][28][29][30][31] as a unique and powerful synthetic platform for radical decarboxylative functionalization of aliphatic carboxylic acids [32][33][34][35][36][37]. In particular, the commonly required high activation energy for radical decarboxylation was provided

• 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

• metal catalysis as a viable and potentially general approach for reaction discovery and would find broad application in new synthetic contexts. Decarboxylative cyanation: background and our working hypothesis. Scope of electrophotochemical decarboxylative cyanation of aliphatic carboxylic acids. All

Challenge N- versus O-six-membered annulation: FeCl₃-catalyzed synthesis of heterocyclic N,O-aminals

• Giacomo Mari,
• Lucia De Crescentini,
• Gianfranco Favi,
• Fabio Mantellini,
• Diego Olivieri and
• Stefania Santeusanio

Beilstein J. Org. Chem. 2024, 20, 1412–1420, doi:10.3762/bjoc.20.123

• remarkable advantages such as an environmentally benign alternative to traditional transition-metal catalysis, a low cost, nontoxicity, good stability, and easy handling [30][31]. Upon increasing the amount of FeCl3 to 20 mol %, the time of the reaction was reduced from 86 to 38 hours, and the yield of 5a