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

• reagent [20], the key intermediate 8 bearing a butenolide motif was obtained in 76% yield. Next, with the aid of the strong Lewis acid Bi(OTf)3, the regioselective elimination of 8 was achieved to produce the Δ14 olefin intermediate 9 in 86% yield. Afterwards, we evaluated the reactivity of 9 towards

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

• ][2][3][4][5][6]. Recently developed photocatalysis affords sustainable, regioselective green methods for producing a wide range of functionalized carbonyl compounds and their related bioactive chiral intermediates under mild conditions, employing dual organic photoredox catalysis [7][8][9][10][11

• Studer et al., which belongs to the class of aryl and heteroaryl electrophilic substitutions and is a highly versatile synthetic transformation in traditional organic chemistry. A highly regioselective dual catalytic approach for the novel acylation of electron-rich benzo-fused arenes or heterocycles 15

• regioselective acylation products, but heteroarene substrates produced a mixture of products, for example, furan, thiophene, and benzothiophene. Compared to the traditional LAs-mediated Friedel–Crafts acylation, the described radical method offers a regiodivergent result with good functional group tolerance. The

Total syntheses of highly oxidative Ryania diterpenoids facilitated by innovations in synthetic strategies

• Zhi-Qi Cao,
• Jin-Bao Qiao and
• Yu-Ming Zhao

Beilstein J. Org. Chem. 2025, 21, 2553–2570, doi:10.3762/bjoc.21.198

• is as follows: Starting from the chiral compound (S)-carvone, four simple transformations yield the enone intermediate 11. This intermediate undergoes an intermolecular [4 + 2] cycloaddition with diene 12, generating two sets of regioselective products in an approximate ratio of 1:1. The product with

• overall synthetic efficiency. A further highlight of this work was the development of a selenium dioxide-mediated regioselective oxidation. Leveraging the existing chiral centers in the molecular framework, this strategy allowed for the simultaneous installation of the desired oxidation states at three

• . Leveraging this regioselective oxidation, the authors achieved the total synthesis of (+)-20-deoxyspiganthine (2) from compound 71. Thus, 71 was converted to 79 via selective SeO2 oxidation (with H2O), triflation, and isopropenyl installation. After protecting the C12 tertiary alcohol and performing a

Pentacyclic aromatic heterocycles from Pd-catalyzed annulation of 1,5-diaryl-1,2,3-triazoles

• Kaylen D. Lathrum,
• Emily M. Hanneken,
• Katelyn R. Grzelak and
• James T. Fletcher

Beilstein J. Org. Chem. 2025, 21, 2524–2534, doi:10.3762/bjoc.21.194

• Information File 1). Reaction of each TMS-protected alkyne with ortho-bromoazidobenzene produced 1,5-diaryl-1,2,3-triazole products 7–12, each possessing an ortho-bromoaryl reactive site necessary for the annulation step. Regioselective formation of 1,5-diaryl-1,2,3-triazoles 7–12 was achieved using a

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

• are ubiquitous and privileged heterocyclic scaffolds in various functional organic materials and naturally occurring products. Although extensive efforts have focused on developing synthetic strategies toward carbazole derivatives, direct regioselective functionalization of the carbazole core remains

• challenging due to the inherently higher reactivity at the C3/C6 positions. In this study, we report a palladium-catalyzed, directing group-assisted, regioselective C1–H nitration of carbazoles. The protocol features a removable directing group and is amenable to gram-scale synthesis. This strategy provides a

• -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

Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds

• Natalya Akhmetdinova,
• Ilgiz Biktagirov and
• Liliya Kh. Faizullina

Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185

• ) (Scheme 11). The technique of regioselective oxidative contraction of a six-membered ring was described in the work by Luo, Zhang and co-workers [43] during their synthesis of the natural alkaloids, dactylicapnosines A (63) and B (64), which contain a 9,10-seco-7-dehydroaporphinoid skeleton with an

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

• with an Ir-catalyzed regioselective C–H borylation developed simultaneously by Ishiyama, Miyaura, Hartwig, and co-workers and Smith and co-workers [26][27]. First, the triflate group of 33 was removed by a Pd-catalyzed reduction with ammonium formate as the reducing reagent. The resulting Boc-protected

Recent advances in Norrish–Yang cyclization and dicarbonyl photoredox reactions for natural product synthesis

• Peng-Xi Luo,
• Jin-Xuan Yang,
• Shao-Min Fu and
• Bo Liu

Beilstein J. Org. Chem. 2025, 21, 2315–2333, doi:10.3762/bjoc.21.177

• -chloroperoxybenzoic acid) induced epoxidation, which was then followed by a Meinwald rearrangement to accomplish aldehyde 7. From 7, a sequence involving silyl enol ether formation, Simmons−Smith cyclopropanation, and acid-mediated regioselective ring-opening installed the C8 quaternary methyl group in 10. Subsequent

• generated diverse biradical intermediates via regioselective hydrogen transfer (δ-H or ε-H), further constructing various C–C bonds. This enabled efficient synthesis of the core skeletons of five natural products. The divergent strategy significantly reduces redundant synthetic steps, embodies synthetic

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

• preparation of chiral β-aminoalcohols [63]. Chiral copper(I) complexes convert imidate radicals, formed transiently through energy-transfer catalysis, to oxazolines. The transformation includes a regioselective and enantioselective HAT process. Upon blue LED irradiation, oxime imidates (derived from alcohols

• products with a new all-carbon quaternary stereocenter (Scheme 11) [86]. With a Ni(II)–bisoxazoline complex as the catalyst, various substrates underwent the transformation with good to high yields and high enantioselectivities. The reactions were regioselective, resulting in the selective

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

• dual roles as solvent and nucleophile, the gold-catalyzed intermolecular Markovnikov addition of methanol to the gold-activated alkyne proceeded to afford dienol intermediate 4. The intermediate 4 subsequently underwent a regioselective 6-endo-trig cyclization, generating the naphthalene core 7 (Scheme

• regioselective syntheses of indene, indenone, and naphthalene derivatives from simple aromatic 1,5-enyne substrates. In 2020, a solvent-controlled strategy for Au(I)-catalyzed divergent syntheses of phenanthrene and dihydrophenanthrene derivatives was developed by the Rodríguez group (Scheme 3) [10]. In

• -substituted internal alkynes underwent exclusive 8-endo-dig cyclization, efficiently delivering the strained dibenzo[b,d]azocine 56 (Scheme 12, path b). Distinct activation modes governed the selectivity, where regioselective terminal gold coordination triggered 7-exo-dig cyclization in terminal alkynes

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

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

• , protection of the resultant primary alcohol, and hydrogenation afforded ketone 65. The LaCl3·LiCl-promoted addition of 65 with Grignard reagent followed by TES protection of the resulting secondary alcohol, regioselective deprotection of the TES group and in situ oxidation provided aldehyde 66. Next, 66

• underwent dehydration with Martin′s sulfurane to afford the known intermediate 115 [83] and terminal alkene 116 (C12–C13 bond-cleaved byproduct). Thus, the formal total synthesis of (−)-platencin (24) was achieved. On the other hand, epoxidation of 113 followed by acid-mediated regioselective ring-opening

Bioinspired total syntheses of natural products: a personal adventure

• Zhengyi Qin,
• Yuting Yang,
• Nuran Yan,
• Xinyu Liang,
• Zhiyu Zhang,
• Yaxuan Duan,
• Huilin Li and
• Xuegong She

Beilstein J. Org. Chem. 2025, 21, 2048–2061, doi:10.3762/bjoc.21.160

• terpenes. There is no doubt that bioinspired total synthesis is currently a powerful and critical approach for complex natural product total synthesis. However, there still exist great challenges in the field, which would stimulate the discovery of new breakthroughs. Chemo- and regioselective employment of

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

• stabilized allyl cation intermediates that undergo regioselective trapping by internal O- and N-nucleophiles furnishing functionalized heterocycles. This method provides access to tetrahydrofuran or pyrrolidine frameworks, each bearing a trifunctionalized (E)-configured vinyl side chain. The use of a shorter

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

• 226. Regioselective hydrolysis of 226 with TFA yielded a dihydropyran intermediate, which was benzylated to deliver 227. Desilylation of 227 gave diol 228, which underwent intramolecular Michael reaction to form bicyclic compound 230 as a single stereoisomer (87% yield over two steps). This scaffold

• , featuring a stereospecific cyclization as the key step (Scheme 29a) [73][74]. To obtain the cyclization precursor 238, the prochiral diol 237 was prepared from (+)-Na-methylvellosimine (236) via a Tollens reaction. Subsequently, regioselective Ley–Griffith oxidation of 237 selectively targeted the C17

• -epigardneral (241) (Scheme 29b). The synthesis of 244 was achieved through a similar sequence of steps: Tollens reaction of 241, regioselective oxidation of diol 242, and acidic cyclization of aldehyde 243. Compound 244 was then converted into 245 in five additional steps. The benzylic oxidative cyclization of

Synthesis of N-doped chiral macrocycles by regioselective palladium-catalyzed arylation

• Shuhai Qiu and
• Junzhi Liu

Beilstein J. Org. Chem. 2025, 21, 1917–1923, doi:10.3762/bjoc.21.149

• ; inherent chirality; N-doped macrocycle; nonplanarity; regioselective cyclization; Introduction Chiral macrocycles have attracted significant research interest owing to their diverse applications in enantioselective recognition [1][2], catalysis [3][4], and circularly polarized luminescence [5][6

• chiral macrocycles, have been reported [17][25], highlighting a critical gap in the design of chiral macrocycles with tailored electronic landscapes. Herein, we reported the synthesis, characterizations and photophysical properties of inherent chiral N-doped macrocycles (Figure 1b) via regioselective

Preparation of spirocyclic oxindoles by cyclisation of an oxime to a nitrone and dipolar cycloaddition

• Beth L. Ritchie,
• Alexandra Longcake and
• Iain Coldham

Beilstein J. Org. Chem. 2025, 21, 1890–1896, doi:10.3762/bjoc.21.146

• that can be explored for its ability to undergo dipolar cycloaddition chemistry. Results and Discussion The oxindole core was prepared from isatin following known chemistry to give the spirocyclic epoxide 1 (Scheme 2) [28]. This was subjected to regioselective ring-opening with allyltrimethylsilane in

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

• ]. Diarylborinic acids have been shown to provide exclusive catalytic performance in the site-selective monofunctionalization of various 1,2- and 1,3-diols [60], as well as in the regioselective glycosylation of polyhydroxyglycosyl acceptors via base-promoted deprotonation of a specific hydroxy group involved in

Continuous-flow-enabled intensification in nitration processes: a review of technological developments and practical applications over the past decade

• Feng Zhou,
• Chuansong Duanmu,
• Yanxing Li,
• Jin Li,
• Haiqing Xu,
• Pan Wang and
• Kai Zhu

Beilstein J. Org. Chem. 2025, 21, 1678–1699, doi:10.3762/bjoc.21.132

• technologies including ultrasonication, microwave irradiation, and microreaction technology into conventional nitration frameworks. Nikseresht et al. developed a novel heterogeneous heteropoly acid catalyst (PMA@MIL-53(Fe)), enabled efficient regioselective nitration of phenols under ultrasonic irradiation

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

• unsymmetrical diisocyanide was used, the initial isocyanide insertion was found to be non-regioselective, delivering a 1:1 mixture of regioisomers (17c and 17c’). Intriguingly, 17a could act as a chiral acylating reagent, applying in the kinetic resolution of racemic primary amines rac-18. Additionally, after

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

• cross-coupling reactions of bifunctional boryl- and germyl-containing compounds. On the other hand, a Full Research Paper presented by Lee and co-workers introduces a highly regioselective formal hydrocyanation method of allenes [7]. The strategy is based on a copper-catalyzed hydroalumination of

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

• 6 exhibiting enhanced chiroptical performance and protonation-induced CPL amplification [19]. Meanwhile, Audisio’s team developed heterohelicenes via regioselective [3 + 2]-cycloadditions, with compound 7 displaying pH-responsive CPL sign inversion (|glum| = +1.1 × 10−3 at 430 nm, −1.2 × 10−3 at 585

• for high-efficiency chiral optoelectronic and quantum materials. In 2024, Kivala’s group selectively synthesized highly distorted [6]helicenes 29a and 29b incorporating azocine units via a regioselective Beckmann rearrangement from oxime precursor 29c [43] (Table 8). For comparative evaluation, the

• 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

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

• , vinyl, ethynyl or sulphide are sufficient if a superbase such as LIDAKOR or LICKOR is used (Scheme 16) [54][55]. The reaction tends to be remarkably regioselective (in terms of the epoxide opening) and stereoselective, however, it should be treated with caution in case of allyl ethers as they can also

• still runs smoothly, if the aryl is substituted for cyclohexyl. The proposed mechanism, supported by control experiments, deuterium exchange studies and energy calculations, consists of the following steps: conjugate addition of the carbene to the allenoate, regioselective addition of the resulting

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

• 59%. In an effort to evaluate the practicality of visible light-promoted xanthylation, Alexanian’s group conducted a regioselective C–H xanthylation of polyolefins (Scheme 10) [96]. Building on previous findings, the HRP-9 undergoes homolytic N–S cleavage, yielding amidyl radical 45. This radical

• abstracts a hydrogen atom from substrate 1 through HAT, producing an α-amido-acridinyl radical intermediate 92 and a substrate-derived carbon-centered radical 4. Radical 4 undergoes regioselective addition to the acceptor, forming transient radical adduct 93. A concomitant SET from 92 to 93 generates a

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

• regioselective functionalization at the periphery of the PAHs. Besides triflyloxylation (42, 43), the introduction of one or two dichlorovinylene groups (43, 44) was observed. As in previous cases, the exact ratio of the products depended on the amount of DDQ and concentration of the precursor. Analysis of NICS