Recent advances in the stereoselective synthesis of distal biaxially chiral molecules

• Fanxing Zhou,
• Chen Zhang,
• Lingyu Sun,
• Yiyun Fang,
• Siming Zheng,
• Lina Hu,
• Mengyang Shen,
• Zhen Zhao,
• Wei Xu,
• Yunqiang Sun and
• Zi-Qiang Rong

Beilstein J. Org. Chem. 2026, 22, 461–479, doi:10.3762/bjoc.22.34

• in catalysis, drug discovery, and functional materials. Review One-step construction of remote biaxial chiral molecules In recent years, the development of asymmetric catalytic methods, including both transition-metal catalysis and organocatalysis, has provided powerful tools for the one-step

• , transition-metal-catalyzed approach for the synthesis of helically chiral polyaryl compounds with well-defined sequences of axial chirality. Using this method, they successfully obtained pentaaryl 6 (Scheme 1b) and nonaryl derivatives (not shown) bearing four and eight consecutive chiral axes, respectively

• alkylation for dynamic kinetic resolution. Moreover, additional alkylation at a sterically congested second rotational axis enabled the construction of remote, double axially chiral molecules 26. Further advances have come from transition-metal catalysis. Li’s group established a rhodium-catalyzed protocol

Cone p-aminocalix[4]arenes enriched with ‘clickable’ alkyne or azide functionalities

• Ilia Korniltsev,
• Vasily Bazhenov,
• Alexander Gorbunov,
• Dmitry Cheshkov,
• Stanislav Bezzubov,
• Vladimir Kovalev and
• Ivan Vatsouro

Beilstein J. Org. Chem. 2026, 22, 399–415, doi:10.3762/bjoc.22.28

• derived from propargylated and 2-azidoethylated precursors possess drastically different complexation abilities towards transition-metal cations [81][82][83][84] including the formation of unique inherently dinuclear iridium(III) complexes with cone calix[4]arenes having pairs of 2-(4-aryltriazol-1-yl

• apparently not sufficient to provide any significant selectivity for the formation of homo/heterocapsules. Finally, since the triazole groups arranged at the narrow rim of the calix[4]arene macrocycle are capable of complexation with transition-metal cations, showing different complexation preferences

Recent advances in the cleavage of non-activated amides

• Eun-Sol Choi and
• Hyo-Jun Lee

Beilstein J. Org. Chem. 2026, 22, 352–369, doi:10.3762/bjoc.22.23

• of conventional, non-activated amides remains far more difficult. This review summarizes recent advances over the past decade in the activation and cleavage of non-activated amide C–N bonds for their conversion into diverse carboxylic acid derivatives. Key strategies covered include transition-metal

• ]. Such activation has enabled a wide array of transformations, including metal-catalyzed cross-couplings via oxidative addition into the amide C–N bond (Scheme 1c) [32][33][34][35][36], and transition-metal-free acyl substitutions facilitated by improved leaving-group ability [37][38][39][40]. Although

• remains a significant and persistent challenge in synthetic chemistry [41][42][43][44]. Classical approaches for activating non-activated amides typically rely on transition-metal catalysts acting as Lewis acids, which coordinate to the carbonyl oxygen and enhance electrophilicity (Scheme 1d). However

Arene activation via π-bond localization: concepts and opportunities

• Paul Meiners,
• Julian J. Melder and
• Tobias Morack

Beilstein J. Org. Chem. 2026, 22, 257–273, doi:10.3762/bjoc.22.19

• as well as transition metal coordination to aromatic fragments in an η2-, η3-, and η4-fashion. The structural and reactivity consequences of these perturbations are analyzed in detail, and representative examples of stoichiometric and, where available, catalytic applications in synthesis are

• disrupting the aromatic core, such as electrophilic and nucleophilic aromatic substitutions, transition metal-catalyzed cross-couplings [11], and C–H functionalizations [12]. Taken together with their natural abundance, these transformations have established arenes and heteroarenes as versatile synthetic

• structure and reactivity. The following chapters introduce the broader mechanistic framework of transition metal coordination to a subset of the aromatic system, specifically η2-, η3-, and η4-coordination. These partial coordination modes effectively clamp the otherwise delocalized π-system, disrupting

Total synthesis of natural products based on hydrogenation of aromatic rings

• Haoxiang Wu and
• Xiangbing Qi

Beilstein J. Org. Chem. 2026, 22, 88–122, doi:10.3762/bjoc.22.4

• ][19][20]. In recent years, promoted by the rapid development of asymmetric catalysis, a wealth of reactions applicable to aromatic systems – including substitution reactions, transition-metal-coupling reactions, and even dearomatization [21][22][23] – have been reported, further extending their

• both homogeneous and heterogeneous systems, the hydrogenation of (hetero)arenes has become a cornerstone of modern synthesis for constructing saturated carbocycles and heterocycles [37]. When an appropriate ligand is paired with a transition-metal catalyst, stereoselective hydrogenation of aromatic

• range, the reaction was scaled up to the gram scale with high yield and high enantioselectivity. Recently, Du and co-workers reported a transition-metal-free asymmetric transfer hydrogenation reaction (Scheme 6) [58]. Under a hydrogen atmosphere, using chiral phosphoric acid and achiral borane as

Advances in Zr-mediated radical transformations and applications to total synthesis

• Hiroshige Ogawa and
• Hugh Nakamura

Beilstein J. Org. Chem. 2026, 22, 71–87, doi:10.3762/bjoc.22.3

• for future development. Keywords: halogen atom transfer; photoredox; radical; total synthesis; zirconium; Introduction Zirconium, a transition metal in the same group as titanium, has been employed across research fields and in medical applications owing to its distinctive physical and chemical

• bond dissociation energy (BDE). Although zirconium shares many characteristics with titanium as a group-congener transition metal, it is known to form stronger bonds in several cases. For example, the Ti–O BDE is reported as 115 kcal·mol−1, whereas the Zr–O BDE is 132 kcal·mol−1 [4]; likewise, Ti–Br

Synthesis and applications of alkenyl chlorides (vinyl chlorides): a review

• Daniel S. Müller

Beilstein J. Org. Chem. 2026, 22, 1–63, doi:10.3762/bjoc.22.1

• Synthesis of Acetylenes” [29] which discusses the preparation of alkenyl chlorides via ketone chlorination using PCl5 (Figure 3A). The synthesis of β-chlorovinyl ketones was later reviewed by Poland and Benson in 1966 (Figure 3B) [30]. More recently, Morandi and co-workers summarized transition-metal

• contribution to the field, particularly via chromium-mediated olefinations, is covered in a Comprehensive Organic Synthesis chapter (Figure 3D) [34][35]. Carbochlorination and carbonylchlorination reactions were reviewed by Petrone, Ye, and Lautens in their Chemical Reviews article on transition-metal

• . Thus, the hydrochlorination of terminal aliphatic alkynes serves as a valuable benchmark reaction to differentiate between purely ionic and transition-metal-catalyzed hydrochlorination processes which often show highly monoselective reactions [95]. Somewhat surprisingly, a recent study by Dai

Mechanistic insights into hydroxy(tosyloxy)iodobenzene-mediated ditosyloxylation of chalcones: a DFT study

• Jai Parkash,
• Sangeeta Saini,
• Vaishali Saini,
• Omkar Bains and
• Raj Kamal

Beilstein J. Org. Chem. 2025, 21, 2703–2715, doi:10.3762/bjoc.21.208

• . The reactivity characteristics of these compounds are similar to transition metal reagents, as a result these hypervalent compounds can be used as an alternative. For example, iodobenzene diacetate (PhI(OAc)2), can be used to selectively oxidize alcohols to aldehydes or ketones over toxic chromium(VI

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