Chemoenzymatic synthesis of the cardenolide rhodexin A and its aglycone sarmentogenin

• Fuzhen Song,
• Mengmeng Zheng,
• Dongkai Wang,
• Xudong Qu and
• Qianghui Zhou

Beilstein J. Org. Chem. 2025, 21, 2637–2644, doi:10.3762/bjoc.21.204

• typical Mukaiyama hydration conditions [30][31][32] to install the C14 β-hydroxy group. However, only a trace amount of the undesired C14α-hydroxylated product 10 was obtained. Additional optimizations regarding the transition-metal catalyst, hydrogen source and solvent all failed to improve the results

Visible-light-driven NHC and organophotoredox dual catalysis for the synthesis of carbonyl compounds

• Vasudevan Dhayalan

Beilstein J. Org. Chem. 2025, 21, 2584–2603, doi:10.3762/bjoc.21.200

• carbenes (NHCs) with photocatalysts. The review encompasses transition-metal-based photocatalytic reactions for C–C and C–HA cross-coupling reactions involving various acyl fluorides, amides, aldehydes, carboxylic acids, and esters, highlighting their broad applications in organic synthesis and medicinal

• groups of MacMillan, Studer, Chi, Plunkett, Rovis, Hopkinson, and others developed NHC-involved radical reactions via visible light-promoted dual or triple photocatalysis, including NHC and transition metal-based photocatalytic reactions and their application in organic synthesis [41][42][43][44][45][46

• , generating an N-centered radical species C. This species subsequently undergoes a rapid C–N cross-coupling with ketyl radical B. This cross-coupling method offers a transition-metal free route to highly substituted amides 3 from aldehydes 1 and imines 2, without the need for any external reductants or

Palladium-catalyzed regioselective C1-selective nitration of carbazoles

• Vikash Kumar,
• Jyothis Dharaniyedath,
• Aiswarya T P,
• Sk Ariyan,
• Chitrothu Venkatesh and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2025, 21, 2479–2488, doi:10.3762/bjoc.21.190

• methodologies are greatly limited due to harsh reaction conditions that impact the scope of the reaction, poor yield, and regioselectivity issues. In sharp contrast, transition metal-catalyzed cross-coupling reactions promisingly improve the regioselectivity issues and substrate scope [25][26][27][28]. In

• addition to cross-coupling reactions, transition metal-catalyzed cyclization involving C–H activation approaches have also been reported [29][30][31][32][33][34][35][36]. Despite the significant advances in carbazole core constructions, the established protocols significantly lack access to selectively C1

• -decorated carbazoles. Consequently, functionalizing carbazoles via transition metal-catalyzed directed C–H activation becomes more attractive to introduce the desired functionality in a regioselective fashion. The C–H activation strategy is elegant in many ways since it utilizes nonfunctionalized or lesser

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

Catalytic enantioselective synthesis of selenium-containing atropisomers via C–Se bond formations

• Qi-Sen Gao,
• Zheng-Wei Wei and
• Zhi-Min Chen

Beilstein J. Org. Chem. 2025, 21, 2447–2455, doi:10.3762/bjoc.21.186

• axially chiral selenium-containing compounds by the formation of C–Se bonds is reviewed from three aspects. Review 1. Catalytic atroposelective synthesis of selenium-containing atropisomers by transition-metal-catalyzed C–H selenylation reactions Transition-metal-catalyzed enantioselective C–H activation

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

• total synthesis – 2010 In 2010, Siegel and co-workers reported their total synthesis of complanadine A (Scheme 2). Their synthesis centres on two transition metal-catalyzed alkyne–alkyne–nitrile [2 + 2 + 2] cycloadditions to forge the two pyridine rings encoded by complanadine A [21]. Notably, the C2–C3

• 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

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

• radical reaction and can occur either intermolecularly or as an intramolecular cyclization reaction. Radical coupling or combination is a possible transformation that is more feasible when one of the radicals is relatively stabilized (a persistent radical). Trapping a radical with a transition metal is

Pathway economy in cyclization of 1,n-enynes

• Hezhen Han,
• Wenjie Mao,
• Bin Lin,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2025, 21, 2260–2282, doi:10.3762/bjoc.21.173

• could be further derivatized (e.g., via borylation, epoxidation), establishing a versatile platform for accessing fused-ring natural products. Substituent-controlled cyclization of 1,n-enynes In transition metal-catalyzed cyclization reactions, the electronic properties and steric hindrance of

• strategy employed transition metal-catalyzed carbene intermediates to mediate stereoselective cyclization, affording bicyclo[4.3.0]nonane derivatives with configurations distinct from Diels–Alder adducts. In 2013, Alami and co-workers demonstrated catalyst-dependent cycloisomerization of aromatic enynes

• aromatic enyne precursors, where product selectivity was controlled by the catalytic system employed. In 2014, Ma and co-workers disclosed a regioselective synthetic strategy for carbazole derivatives, where the directionality of alkyl migration was modulated by the choice of transition metal catalysts

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

• intricate and inefficient using these standard synthetic protocols. The transition-metal-catalyzed C–N bond formation has emerged as a viable route to access non-symmetric azobenzenes, owing to the broad functional group tolerance of Buchwald–Hartwig amination reactions [34][35][36][37][38][39][40]. Kong

Electrochemical cyclization of alkynes to construct five-membered nitrogen-heterocyclic rings

• Lifen Peng,
• Ting Wang,
• Zhiwen Yuan,
• Bin Li,
• Zilong Tang,
• Xirong Liu,
• Hui Li,
• Guofang Jiang,
• Chunling Zeng,
• Henry N. C. Wong and
• Xiao-Shui Peng

Beilstein J. Org. Chem. 2025, 21, 2173–2201, doi:10.3762/bjoc.21.166

• transformations far from thermodynamic equilibria have emerged abundantly with the consideration of green chemistry [89][90][91][92]. Redox-active organic compounds, transition metal coordinating compounds and even an electrode surface were commonly employed as catalysts in the electrochemical transformations [93

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

• MPa NH3 and 2 MPa H2. The reaction could be carried for 10 catalytic cycles without deactivation. Zhang developed a transition-metal copper-catalyzed chemoselective asymmetric hydrogenation of the carbonyl group in exocyclic α,β-unsaturated cyclopentanones. Chiral exocyclic allylic pentanols (a

The application of desymmetric enantioselective reduction of cyclic 1,3-dicarbonyl compounds in the total synthesis of terpenoid and alkaloid natural products

• Dong-Xing Tan and
• Fu-She Han

Beilstein J. Org. Chem. 2025, 21, 2085–2102, doi:10.3762/bjoc.21.164

• cyclic prochiral dicarbonyl substrates. In addition, various approaches could be used for the desymmetrization reactions such as enzyme catalytic-, organocatalyst-, and transition-metal-catalyzed reductions [5][6][7]. Advance about the synthesis of several terpenoid and alkaloid natural products (1–5

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

Asymmetric total synthesis of tricyclic prostaglandin D2 metabolite methyl ester via oxidative radical cyclization

• Miao Xiao,
• Liuyang Pu,
• Qiaoli Shang,
• Lei Zhu and
• Jun Huang

Beilstein J. Org. Chem. 2025, 21, 1964–1972, doi:10.3762/bjoc.21.152

• by the anomeric effect [23] in the tricyclic scaffold. Compound 13 could be produced from olefin 14 via cross-metathesis. The regio- and diastereoselective connection of C8 and C12 in compound 14 could be realized through a transition-metal-mediated oxidative radical cyclization through TS-1 from β

• -keto ester 15 [24]. The β-keto ester 15 was expected to be derived from compounds 16 and 17 via an asymmetric aldol reaction [25]. The first phase of the synthesis required the efficient preparation of compound 14, for which a transition-metal-mediated oxidative radical cyclization of β-keto ester 15

• transition-metal-mediated oxidative radical cyclization for constructing cyclopentanone 14. First, we used Mn(OAc)3·2H2O/Cu(OAc)2·H2O [21] as the oxidant system to perform oxidative annulation of β-keto ester 15 in MeCN as solvent. However, only 9% of the desired product 14 was obtained after conducting the

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

• biologically active molecules. Based on the reaction types, three strategies are discussed: enzymatic acylation, transition-metal-catalyzed acylation, and local desymmetrization. Keywords: asymmetric synthesis; desymmetrization; 1,3-diols; natural product; total synthesis; Introduction Natural products

• emphasis on the desymmetrization of diols. Prochiral 1,3-diols, as simple and practical substrates, have been widely used in developed desymmetrization methodologies with applications in the total synthesis of natural products and bioactive molecules, including enzymatic acylation, transition-metal

• (125) was obtained through a 12-step sequence from 124. Desymmetrization via transition-metal-catalyzed acylation Although enzymatic acylation reactions are widely employed in total synthesis, certain substrates are incompatible with acylation catalyzed by existing lipases. Inspired by enzymatic

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

• 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

Chiral phosphoric acid-catalyzed asymmetric synthesis of helically chiral, planarly chiral and inherently chiral molecules

• Wei Liu and
• Xiaoyu Yang

Beilstein J. Org. Chem. 2025, 21, 1864–1889, doi:10.3762/bjoc.21.145

• molecular platforms in various applications, such as circularly polarized luminescence (CPL) materials, chiral liquid crystals and asymmetric catalysis. Currently, the asymmetric catalytic synthesis of helicenes predominantly revolves around transition metal-catalyzed asymmetric annulation reactions

• , including the asymmetric [2 + 2 + 2] cycloaddition of aryl-substituted polyynes and hydroarylation of alkynes [18][19]. In contrast, the application of asymmetric organocatalysis for enantioselective synthesis of chiral helicenes remains relatively underdeveloped compared to transition metal-catalyzed

• enantioselectivity. Overall, with the recent rapid advancements of CPA catalysis, along with the utilization of CPA catalysts in asymmetric radical chemistry, transition metal-catalyzed reactions and photoredox chemistry, we envision that CPA catalysts will continue to play a central role in the future asymmetric

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

• strategies have been explored in recent decades for the synthesis of structurally diverse quinolines. Among them, transition-metal-catalyzed multicomponent reactions (MCRs) have emerged as particularly effective for constructing complex quinoline-based heterocycles [26][27][28]. Catalytic pathways such as

• -metal catalysts. One of the key transformations in organic synthesis is the selective oxidative cleavage of alkenes to yield ketones or aldehydes [43][44][45][46][47]. Traditionally, such transformations have been achieved using various oxidizing agents, transition-metal-based systems, organo- and

• promising industrial relevance. Oxidative cleavage of alkenes to yield carbonyl compounds is one of the key transformations in synthetic organic chemistry [41][42]. Over the past two decades, this field has witnessed significant advancements, primarily through the use of organic oxidants and transition

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

• ], insertion reactions [16][17][18], cycloaddition reactions (e.g., [4 + 1], [3 + 2]) [19][20], and others [21][22][23]. Particularly, isocyanides have been widely exploited toward the preparation of centrally chiral structures through transition-metal-catalyzed or organocatalytic asymmetric reactions [24][25

• , 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

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

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

• the aromaticity of the transition state and the activation barriers of different pericyclic reactions spanning from the parent Diels–Alder reactions to higher-order cycloadditions or even transition-metal-mediated transformations [22][23][24][25][26][27][28][29]. By selecting illustrative examples, in

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

• heteroaromatic system have been reported to date. The formation of dihydrobenzofuro[3,2-b]pyrrole cycloadducts as by-products has been observed in the synthesis of aziridines by the transition metal-catalyzed reaction of benzofurans with 3-arylazirines [16]. This paper presents the use of azirines as annulation

• discussed. Results and Discussion Guided by the known fact that 3-arylazirines in the presence of transition metal compounds are sensitive to the enol form of 1,3-dicarbonyls [5][17][18][19], we chose for our study methyl 3-hydroxybenzo[b]thiophene-2-carboxylate (1) as an aromatic substrate having a 1,3

Azide–alkyne cycloaddition (click) reaction in biomass-derived solvent Cyrene^TM under one-pot conditions

• Zoltán Medgyesi and
• László T. Mika

Beilstein J. Org. Chem. 2025, 21, 1544–1551, doi:10.3762/bjoc.21.117

• important transformation exhibiting higher chemical and environmental safety. Keywords: alternative solvent; click chemistry; cycloaddition; CyreneTM; 1,2,3-triazoles; Introduction In the past few decades, transition-metal-catalyzed coupling and addition reactions have represented one of the most powerful

• it is negative in the Ames test [25]. Recently, we determined key physicochemical properties of CyreneTM and showed that it has a negligible vapor pressure (<9.6 kPa) and low viscosity (<6.8 mPa·s) at typical transition-metal-catalyzed reaction temperatures (30–140 °C) [26]. CyreneTM has been

• obtained for Cu sources in different solvent systems [40][41]. Although CuAAC reactions can be efficiently performed in water, the moisture content of the organic reaction environment could have a significant effect on the efficiency of a transition-metal-catalyzed reaction. Because CyreneTM is fully

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

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

• , Burley, Watson, and co-workers present a new synthesis of germyl triazoles from germyl alkynes through a copper-catalyzed azide–alkyne cycloaddition (CuAAC) reaction [6]. The resulting Ge-substituted triazoles could be further diversified. For example, through chemoselective transition-metal-catalyzed