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

• also be reduced through hydride-based or electron-transfer pathways, which provide complementary modes of reactivity that are often orthogonal to metal-catalyzed hydrogenation systems. Classical dissolving-metal reductions such as the Birch reduction convert arenes into 1,4-dihydro intermediates via

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

• . 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

• 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

• -catalyzed additions of alkynes to acyl chlorides to access β-chlorovinyl ketones (2024) [31]. A review by Sharma and Singh covers comprehensively the synthesis and application of β-halovinyl aldehydes [32]. It should be noted that the synthesis of β-chloroalkenes substituted with an electron-withdrawing

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

• existing metal-catalyzed C–H bond functionalization methods (Scheme 3) [53]. Recently, Scheidt et al. discovered an NHC/organic photoredox-catalyzed three-component coupling reaction for the efficient and novel preparation of γ-aryloxy ketone scaffolds 12. This transformation builds on the emerging field

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

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

• has emerged as a powerful strategy for the rapid synthesis of functionally enriched axially chiral diaryl compounds. However, due to the potential strong coordination between organoselenium compounds and transition metals, the direct construction of C–Se bonds via metal-catalyzed C–H bond

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

• 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

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

• single process that established five new carbon–carbon bonds and nine contiguous stereocenters, including four all-carbon quaternary centers (Scheme 3). Transition-metal-catalyzed radical reactions Recent advances in enantioselective radical reactions catalyzed by base metals (e.g., Fe, Co, Ni, Mn

• , organocatalysts, transition-metal complexes, and enzymes. In many cases, low catalyst loadings have been achieved, especially in transition-metal catalyzed, photoredox, and biocatalytic methods. Photoredox catalysis has had a tremendous impact on the field of organic radical chemistry. In many modern radical

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

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

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

• dehydration over mesoporous solid acids and the second one is a metal-catalyzed hydrogenation. HFO was obtained in 85% yield and its conversion rate to GBL was about 97%. Different bifunctional Pt-based solid acids were used. An overall GBL yield of 82.7% from furfural was obtained (Scheme 33). Gollnick and

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

Aryl iodane-induced cascade arylation–1,2-silyl shift–heterocyclization of propargylsilanes under copper catalysis

• Rasma Kroņkalne,
• Rūdolfs Beļaunieks,
• Armands Sebris,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2025, 21, 1984–1994, doi:10.3762/bjoc.21.154

• the reagents of choice for arylation reactions, where an umpolung of reactivity is required [1]. Arylations employing diaryl-λ3-iodanes can be performed under metal-free [2] or metal-catalyzed conditions. For alkyne arylations [Cu] [3] or [Pd] catalysis [4][5][6] is typically employed. Internal

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

• (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

• reactions, chemists have developed a series of catalysts composed of transition-metal cores and chiral ligands, which have been applied to various asymmetric reactions [50][51][52]. Compared to the enzymatic methods, the transition-metal-catalyzed approach may provide an advantage to access both enantiomers

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

Synthesis of chiral cyclohexane-linked bisimidazolines

• Changmeng Xi,
• Qingshan Sun and
• Jiaxi Xu

Beilstein J. Org. Chem. 2025, 21, 1786–1790, doi:10.3762/bjoc.21.140

• bisimidazolines are efficient chiral ligands in metal-catalyzed asymmetric organic transformations. Chiral cyclohexane-linked bisimidazolines were prepared from optically active cyclohexane-1,2-dicarboxylic acid and 1,2-diphenylethane-1,2-diamines via the monosulfonylation of 1,2-diphenylethane-1,2-diamines

• bisoxazolines [1][2][3][4][5][6][7][8][9] and bisimidazolines [10][11][12][13][14][15] are efficient chiral ligands and have been widely applied in various metal-catalyzed asymmetric organic transformations. Various chiral bisoxazoline ligands have been prepared from diacids and enantiopure vicinal amino

• alcohols and utilized in different metal-catalyzed asymmetric organic reactions [1][2][3][4][5][6][7][8][9]. In comparison with bisoxazoline ligands, relatively less attention has been paid to bisimidazoline ligands [10][11][12][13][14][15]. Some well investigated bisimidazoline ligands are pyridine-linked

Influence of the cation in hypophosphite-mediated catalyst-free reductive amination

• Natalia Lebedeva,
• Fedor Kliuev,
• Olesya Zvereva,
• Klim Biriukov,
• Evgeniya Podyacheva,
• Maria Godovikova,
• Oleg I. Afanasyev and
• Denis Chusov

Beilstein J. Org. Chem. 2025, 21, 1661–1670, doi:10.3762/bjoc.21.130

• Scientific) and readily available in bulk quantities compound. In organic synthesis, it is most commonly used in metal-catalyzed reductions where NaH2PO2 serves as a molecular hydrogen donor [6][7][8][9][10][11][12][13][14][15][16]. However, recent studies demonstrated application of hypophosphites as a

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

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

• , and flow chemistry are being harnessed to push the limits of light-driven reactions [36]. Terada and colleagues show in this thematic issue how flow chemistry is used to significantly improve the yield of a π-Lewis acidic metal-catalyzed cyclization–radical addition sequence [37]. Recently, chemists

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

• 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

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

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

• , 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

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

• stimuli-responsive chiral electrochromic materials. In the same year, You’s group developed a transition-metal-catalyzed C–H/C–H-type regioselective C3-arylation of benzothiophenes using molecular oxygen as the oxidant [79]. This strategy afforded the TADF-active compound 64a, which exhibits efficient

Recent advances in amidyl radical-mediated photocatalytic direct intermolecular hydrogen atom transfer

• Hao-Sen Wang,
• Lin Li,
• Xin Chen,
• Jian-Li Wu,
• Kai Sun,
• Xiao-Lan Chen,
• Ling-Bo Qu and
• Bing Yu

Beilstein J. Org. Chem. 2025, 21, 1306–1323, doi:10.3762/bjoc.21.100

• molecules. On the other hand, C–H bonds exhibit low reactivity due to their relatively high bond dissociation energy (BDE) (Figure 1a). Therefore, the direct functionalization of C–H bonds is extremely challenging [1][2][3][4][5]. In recent decades, transition-metal-catalyzed C–H bond functionalization

Recent advances and future challenges in the bottom-up synthesis of azulene-embedded nanographenes

• Bartłomiej Pigulski

Beilstein J. Org. Chem. 2025, 21, 1272–1305, doi:10.3762/bjoc.21.99

• unexpected deboronization reaction upon the addition of TFA. On-surface synthesis Recently, the field of on-surface chemistry has made significant progress, with the successful development of complex metal-catalyzed on-surface reactions that are not accessible through classical solution-based organic