Electrochemical reduction of unsaturated carbon–carbon bonds via 3d transition-metal catalysis

• Geon Kang,
• Minki Jeon,
• Pooja Kumari Jat,
• Cheoljae Kim and
• Isaac Choi

Beilstein J. Org. Chem. 2026, 22, 955–981, doi:10.3762/bjoc.22.75

• storage for controlling regioselective C–C bond formation beyond semihydrogenation chemistry [125]. In 2025, the Wang group reported a nickel electrocatalytic system featuring a bifunctional ligand equipped with a pendant amine, specifically designed to promote Ni–H formation while simultaneously

• hydride transfer to the α-carbon is reversible, while hydride transfer to the β-carbon proceeds with an effectively irreversible character (Scheme 18C). This divergence in reversibility depending on the insertion site provides experimental evidence that Ni–H insertion operates with distinct regioselective

Recent advances in copper-catalyzed direct hydroamination of alkenes with (hetero)aromatic amines

• Hyejeong Lee and
• Yunmi Lee

Beilstein J. Org. Chem. 2026, 22, 925–947, doi:10.3762/bjoc.22.73

• SIMesCuCl), highly β-regioselective amination reactions of arylamines with terminal and γ-substituted allylic sulfones 10 were achieved, affording diverse β-substituted β-amino sulfones 11 in high yields. The reaction was proposed to proceed via a copper–amido catalytic cycle, analogous to the Gunnoe-type

• vinylarene. The amido ligand then underwent regioselective intermolecular nucleophilic attack at the less substituted β-carbon of the alkene, generating zwitterionic intermediate II. Subsequent proton transfer from aniline released the anti-Markovnikov β-amino product 36 and regenerated the copper–amido

Total synthesis of the capsular polysaccharide repeating unit towards the development of a glycoconjugate vaccine against Klebsiella pneumoniae ST512

• Shuo Zhang,
• Ondřej Daněk and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2026, 22, 821–827, doi:10.3762/bjoc.22.64

• successfully cleaved the silylidene group, producing pentasaccharide diol 17 in 81% yield. The final stages involved the regioselective installation of an Fmoc group at the C6-hydroxy group, followed by glycosylation with building block 4 to provide hexasaccharide 19 with complete α-selectivity. Global

Synthesis of heterocycles based on azomethine ylides from α-amino acids (or amines) and carbonyl compounds

• Ekaterina V. Berezhnaya,
• Alexander I. Ponyaev,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2026, 22, 705–741, doi:10.3762/bjoc.22.55

• such as nitroalkenes and enones were completely regioselective, yielding regioisomers in which the activating group is located adjacent to the pyridyl moiety (86–96% ee). The work of Carretero's scientific group has developed effective methodologies for the enantioselective synthesis of complex

• configuration and the structure of the transition state [88]. In [1], we developed an efficient protocol for the diastereo- and regioselective synthesis of spiro[cyclopropa[a]pyrrolizine-2,2'-indenes] 128–131 using 1,3-dipolar cycloaddition reactions of stable azomethine ylide 123, obtained in situ by

• been created based on azomethine ylides obtained from isatin via the decarboxylative route. In 2025, an article [101] was published in which we studied in detail the diastereo- and regioselective three-component (3 + 2) cycloaddition reactions of azomethine ylides, obtained in situ from isatins 140 and

Regioselective approach to 5-arylsulfonylisoxazoles and their antimicrobial activity

• Artem S. Sazonov,
• Dmitry A. Vasilenko,
• Denis V. Porfiriev,
• Yuri K. Grishin,
• Rimma A. Gazzaeva,
• Alisa P. Chernyshova,
• Maxim A. Kryakvin,
• Anna A. Baranova,
• Vera A. Alferova and
• Elena B. Averina

Beilstein J. Org. Chem. 2026, 22, 592–602, doi:10.3762/bjoc.22.45

• Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119991 Moscow, Russian Federation 10.3762/bjoc.22.45 Abstract This study presents a novel regioselective synthesis of 3-electron-withdrawing-group-(EWG)-substituted 5-sulfonyl- and 5-sulfinylisoxazoles from 3-EWG-5-nitroisoxazoles via

• oxides are generally limited to aryl-substituted derivatives, making the abovementioned approaches inapplicable for the synthesis of 5-sulfoisoxazoles with an additional functional group. To circumvent these limitations, we proposed a novel chemo- and regioselective synthetic approach to 5

• significant difference compared to the control lane (Figure 7B), indicating that they did not inhibit DNA Topo IV decatenation activity. Conclusion In conclusion, we have developed a novel regioselective approach to the synthesis of 3-EWG-5-sulfonylisoxazoles or 3-EWG-5-sulfinylisoxazoles from readily

Experimental and DFT studies on the regioselective methanolysis of 5-azido-9-oxabicyclo[6.1.0]nonan-4-yl 4-nitrobenzoate isomers

• İlknur Polat,
• Selçuk Eşsiz and
• Emine Salamci

Beilstein J. Org. Chem. 2026, 22, 547–556, doi:10.3762/bjoc.22.40

• regioselective methanolysis of new azido-4-nitrobenzoate epoxycyclooctane isomers and the characterization of the resulting products are described herein. Firstly, treatment of key compound 8-azidocyclooct-4-en-1-ol with 4-nitrobenzoyl chloride followed by an epoxidation reaction and then methanolysis of the

Modern synthetic pathways towards eribulin and its subunits

• Sebastian Dominik Graf

Beilstein J. Org. Chem. 2026, 22, 495–526, doi:10.3762/bjoc.22.37

• using CrCl3 and NbCpCl4. The last steps towards 1 are known procedures [68]. By comparison to former methods, this technique does not require further desulfonylation after the macrocyclization [19][68]. Choi and co-workers used a previously reported protocol on stereo- and regioselective allene-Prins

• Liu and co-workers [81]. Regioselective deprotection, oxidative cleavage, reduction with NaBH4 and Bn-protection afforded 50, which was subsequently transformed to aldehyde 51 via ozonolysis and treatment with SMe2. Next, HWE reaction and acidic treatment triggered the cyclizations towards enone 53

• protected with TESCl, then regioselective oxidation of the primary TES ether and addition of vinyl grignard led to 87. Another oxidation afforded α,β-unsaturated carbonyl 88 and acidic treatment with BnOH triggered the oxa-Michael reaction and transketalization towards tetracyclic 90. Following Kishi

Electrosynthetic access to unsymmetrical oxaza[8]helicenes with high chiral stability and strong circularly polarized luminescence (CPL)

• Tin Zar Aye,
• Rubal Sharma,
• Muthu Karuppasamy,
• Daiya Suzuki,
• Haruka Nakajima,
• Yoshitane Imai,
• Mitsuhiro Arisawa,
• Mohamed S. H. Salem and
• Shinobu Takizawa

Beilstein J. Org. Chem. 2026, 22, 372–382, doi:10.3762/bjoc.22.25

• is often hindered by chemoselectivity and regioselective control. Here, we exploit the differential redox potentials of two coupling partners as a key player to achieve a chemo- and regioselective electrosynthetic access to a new family of unsymmetrical oxaza[8]helicenes. A controlled anodic sequence

• , enabling regioselective intermolecular coupling with 4. While a Scholl-type coupling-first scenario cannot be ruled out, the computed acidity of [3]·+ (pKa ≈ −5.2) together with the more spin-density localization in Int-I supports a deprotonation-first, neutral-radical pathway, consistent with related

Ring contraction and ring expansion reactions in terpenoid biosynthesis and their application to total synthesis

• Nicolas Kratena,
• Nicolas Heinzig and
• Peter Gärtner

Beilstein J. Org. Chem. 2026, 22, 289–343, doi:10.3762/bjoc.22.21

• . Regioselective, endocyclic elimination delivers the unoxidised terpene precursor 42 towards aridacins. In the rich family of Euphorbia diterpenoids various ring systems are conjectured to be biosynthetically related, such as the casbane, lathyrane, tigliane, and ingenane skeletal [89][90]. The transannular aldol

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

• sequential electron transfer and protonation, enabling regioselective partial dearomatization that is difficult to achieve under hydrogenation conditions. Likewise, hydride reagents – including NaBH3CN, DIBAL-H, and other aluminum or borohydride derivatives – have been widely employed for the selective

• heteroaromatic core, achieving regioselective catalytic hydrogenation that discriminates between the phenyl and heteroaromatic moieties remains a persistent challenge. A recent work by Qi and co-workers has substantially advanced the selective hydrogenation of indole-containing compounds. Systematic tuning of

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

• regioselectivity. In a related study, Ota and Yamaguchi et al. reported the regioselective ring-opening of oxetanes using zirconocene catalysis (Scheme 6) [21]. Treatment of oxetane 27 with zirconocene in the presence of an Ir-photoredox catalyst led to ring opening via the less substituted radical intermediate

• range of α-fluorocarbonyl substrates and olefins (Scheme 9B). In 2025, Ota and Yamaguchi et al. reported a zirconocene-mediated selective cleavage of C–O bonds (Scheme 10A) [35]. The authors had previously demonstrated regioselective ring-opening reactions of epoxides and oxetanes by exploiting the

Sustainable electrochemical synthesis of aliphatic nitro-NNO-azoxy compounds employing ammonium dinitramide and their in vitro evaluation as potential nitric oxide donors and fungicides

• Alexander S. Budnikov,
• Nikita E. Leonov,
• Michael S. Klenov,
• Andrey A. Kulikov,
• Igor B. Krylov,
• Timofey A. Kudryashev,
• Aleksandr M. Churakov,
• Alexander O. Terent’ev and
• Vladimir A. Tartakovsky

Beilstein J. Org. Chem. 2025, 21, 2739–2754, doi:10.3762/bjoc.21.211

• particular interest for the regioselective synthesis of azoxy compounds [5][71][72]. Unique and understudied representatives of the latter are nitro-NNO-azoxy compounds [R–N(O)=N–NO2], first synthesized at ZIOC RAS [73][74][75]. Nowadays, aromatic and heterocyclic compounds of this class have been studied in

Total synthesis of asperdinones B, C, D, E and terezine D

• Ravi Devarajappa and
• Stephen Hanessian

Beilstein J. Org. Chem. 2025, 21, 2730–2738, doi:10.3762/bjoc.21.210

• transferase AnaPT. A second, less evident approach, starts with a prenylindole, followed by introducing an (R)- or (S)-2-aminopropionate (alanine) unit at C-3 by a Negishi cross-coupling reaction (Figure 2, approach B, D–F). Although each approach has precedents in different contexts, achieving regioselective

• , the Pirrung group reported two practical syntheses of 7-prenylindole [48][49]. The regioselective C-7 prenylation of indole has been achieved by directing-group C–H activation as reported by Snieckus [50]. However, the deprotection of the preferred N-bis-tert-butylphosphinoyl directing group required

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