Synthesis and structural elucidation of a novel bis-spirooxindole from isatin and ethylenediamine

• Irene Moreno-Gutiérrez,
• Josefa L. López-Martínez,
• Sonia Berenguel-Gómez,
• Irene Torres-García,
• Duane Choquesillo-Lazarte,
• Manuel Muñoz-Dorado,
• Miriam Álvarez-Corral and
• Ignacio Rodríguez-García

Beilstein J. Org. Chem. 2026, 22, 813–820, doi:10.3762/bjoc.22.63

• NaBH4 or by the ethylenediamine acting as a hydride donor. In addition, if the formation of 28 by addition of the enol of 27 to the imine were reversible (and the reduction step irreversible), then the more stable, dipole-opposed C2-symmetric structure for 28 should be dominant, thus explaining the

• ). Reduction of 24 with NaBH4. NaBH₄ (95 mg, 2.52 mmol, 2 equiv) was added in portions to a stirred solution of 24 (0.40 g, 1.26 mmol, 1 equiv) in MeOH (15 mL) at room temperature. The mixture was stirred for 2 h, poured onto ice, and the resulting yellow precipitate of 25 was collected by filtration (295 mg

• ), MeOH, reflux, 5 h, 66%; (b) ethylenediamine (2 equiv), EtOH, reflux, 6 h, 67%; (c) 2 equiv NaBH4 (58%) or NaBH3CN (76%), reflux, MeOH. Proposed mechanism for the formation of 25. Synthesis of 30 from 5-methylisatin (29). Supporting Information Supporting Information File 32: Copies of IR, NMR and MS

Towards the targeted protein degradation of CK2: design and synthesis of CAM4066-based PROTACs

• Sophie Day-Riley,
• Sona Krajcovicova,
• Aryaman Raj Sokhal,
• Jan L. Venne,
• Paul Brear,
• Marko Hyvönen,
• Benjamin C. Whitehurst,
• Jason S. Carroll and
• David R. Spring

Beilstein J. Org. Chem. 2026, 22, 611–619, doi:10.3762/bjoc.22.47

• synthesis of the ligand–linker analogue 17 using intermediate 11, however, use of intermediates 12–14 were consistently giving low yields. Therefore, for those, methanolic reductive amination with NaBH4 was pursued. Successful optimisation of reductive amination conditions yielded the key ligand–linker

Continuous-flow carbonyl hydrogenation under subatmospheric to atmospheric hydrogen pressure enabled by robust heterogeneous Pt–Fe catalysts

• Hiroyuki Miyamura,
• Ryosuke Kajiyama,
• Shun-ya Onozawa,
• Yoshihiro Kon and
• Shū Kobayashi

Beilstein J. Org. Chem. 2026, 22, 575–582, doi:10.3762/bjoc.22.43

• catalysts. Results and Discussion Catalyst preparation First, we prepared Pt‒Fe/DMPSi‒Al2O3 with different Fe/Pt ratios by the simultaneous reduction of Pt and Fe salts in a solution containing dissolved sodium borohydride (NaBH4) and suspended DMPSi [15][30][31][32]. After DMPSi stabilized the resulting

• might be reduced by NaBH4 faster than FeCl2 in the solution phase, and the generated Pt(0) nanoparticles are stabilized by DMPSi surface. The reduction of FeCl2, which is usually more difficult to achieve can be catalyzed on the surface of Pt(0) nanoparticles and the formed Fe species are deposited and

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

• 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

• using acetic anhydride. Oxidative cleavage of olefin 73, followed by treatment with ʟ-proline led to an intermediate β-aldehyde with inverted stereochemistry at the β-C (4:1 dr). Subsequent reduction with NaBH4 yielded alcohol 74. Piv-protection of the primary alcohol, reductive deprotection of the Bn

• route shown in Scheme 18 was intercepted at 176. Instead of the previous radical cyclization, here, a reductive Ni(II)-induced cyclization afforded 188 (Scheme 20). Oxidation and ozonolysis with subsequent addition of NaBH4 yielded diol 190, whose TBDPS-group was cleaved under acidic conditions, before

Synthesis and anti-cancer activity of naphthalimide–organylselanyl conjugates

• Rajkumar Ravi and
• Selvakumar Karuthapandi

Beilstein J. Org. Chem. 2026, 22, 416–435, doi:10.3762/bjoc.22.29

• ): 2951, 2859, 1695, 1660, 1575, 1509, 1354, 1240, 1177, 1072, 828 cm−1. Synthetic procedure of compound 8 Dioctyl diselenide (289 mg, 0.75 mmol), NaBH4 (100 mg, 2.6 mmol), and 7.5 mL of DMSO were taken in a two-neck round-bottom flask at room temperature under a nitrogen-rich atmosphere. The mixture was

• synthesis of diorganyl monoselenides 7 and 8: (a) N-(3-bromopropyl) phthalimide, K2CO3, CH3CN, reflux 48 h, yield 53%; (b) hydrazine hydrate, ethanol, reflux 8 h, yield 48%; (c) 4-bromo-1,8-naphthalic anhydride, ethanol, reflux 2 h, yield 66%; (d) diphenyl diselenide, NaBH4, DMSO and THF, rt, 1.5 h, yield

Improved synthesis and physicochemical characterization of the selective serotonin 2A receptor agonist 25CN-NBOH

• Adrian G. Rossebø,
• Hannah G. Kolberg,
• Anders E. Tønder,
• Louise Kjaerulff,
• Poul Erik Hansen,
• Karla A. Frydenvang,
• Jesper Østergaard and
• Jesper L. Kristensen

Beilstein J. Org. Chem. 2026, 22, 175–184, doi:10.3762/bjoc.22.11

• %), molecular sieves (4 Å, powder, 325 mesh), and hydrogen chloride solution (3 M in methanol, LiChropur™) were purchased from Sigma-Aldrich (St. Louis, MO, USA). 1-Octanol was purchased from Ferak Berlin (Berlin, Germany), triethylamine (99%) from Thermo Fisher Scientific (Fair Lawn, NJ, USA), NaBH4

• for 1.5 hours at room temperature. Subsequently, the reaction was cooled in an ice bath before NaBH4 (192 mg, 5.08 mmol, 2.03 equiv) was added in four portions over 15 minutes. The reaction was left to stir at that temperature for an additional 20 minutes before leaving it at room temperature for 35

• 1.0 Hz before Fourier transformation. Spectra were processed with MestReNova. Synthesis of 25CN-NBOH·HCl (1·HCl). a) 2C-CN is available in 4 steps from 2C-H [12]: 1) TFAA, TEA, DCM; 2) TiCl4, dichloromethyl methyl ether, DCM; 3) NH2OH, HCl, EtOH, then Ac2O; 4) NaBH4, EtOH, then HCl. b) Salicylaldehyde

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

• (±)-LSD by Vollhardt and co-workers, the pyridine part was constructed by a Co-catalyzed [2 + 2 + 2] cycloaddition between alkyne 84 and nitrile 85, constructing the ergoline core 86. Methylation with MeOTf provided pyridinium 87, and subsequent NaBH4-mediated hydrogenation selectively generated the

• , which perfomed as a key substrate for the aerobic oxidation. The formation of the tetracyclic 3-spirooxindole structure 137 was achieved through a transition-metal-free intramolecular cross-dehydrogenative coupling. With 137 in hand, a sequence of transformations including ketone reduction with NaBH4

Recent advancements in the synthesis of Veratrum alkaloids

• Morwenna Mögel,
• David Berger and
• Philipp Heretsch

Beilstein J. Org. Chem. 2025, 21, 2657–2693, doi:10.3762/bjoc.21.206

Synthesis of new tetra- and pentacyclic, methylenedioxy- and ethylenedioxy-substituted derivatives of the dibenzo[c,f][1,2]thiazepine ring system

• Gábor Berecz,
• András Dancsó,
• Mária Tóthné Lauritz,
• Loránd Kiss,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2645–2656, doi:10.3762/bjoc.21.205

• substitution reactions of benzo-1,3-dioxoles and benzo-1,4-dioxanes [20]. Reduction of ketones 6 and 7 with NaBH4 gave alcohols 16 and 17, which were chlorinated with SOCl2 to result in compounds 18 and 19. Treatment of the latter with the appropriate amines gave amino derivatives 20a, 20c–e, and 21a, 21c–p

• of compound 28 with 1,2-dibromoethane (29), reduction with NaBH4 (30), chlorination with SOCl2 (31) and subsequent treatment with methylamine afforded pentacyclic product 25. Reaction of bromoalkyl derivative 30 with potassium thioacetate gave acetylthio derivative 32, which was cyclized after

• removal of the acetyl group by intramolecular dehydrative thioetherification [3] to the bridged molecule 26. As regards the synthesis of compound 27, reduction of ketone 28 with NaBH4 (33), chlorination with SOCl2 (34) and treatment with 2-bromoethanol afforded 2-bromoethoxy derivative 35, which was

Ni-promoted reductive cyclization cascade enables a total synthesis of (+)-aglacin B

• Si-Chen Yao,
• Jing-Si Cao,
• Jian Xiao,
• Ya-Wen Wang and
• Yu Peng

Beilstein J. Org. Chem. 2025, 21, 2548–2552, doi:10.3762/bjoc.21.197

• diastereocontrol for 12 (dr = 20:1), and could easily proceed on a scale of ten grams (Supporting Information File 1). For the reduction of the chiral auxiliary in 12, NaBH4 in THF/H2O proved to be the optimal conditions, giving the primary alcohol 6 in 80% yield. Subsequently, oxidation of this alcohol by IBX

Assembly strategy for thieno[3,2-b]thiophenes via a disulfide intermediate derived from 3-nitrothiophene-2,5-dicarboxylate

• Roman A. Irgashev

Beilstein J. Org. Chem. 2025, 21, 2489–2497, doi:10.3762/bjoc.21.191

• -dicarboxylates by its one-pot reduction–alkylation using NaBH4 in DMF followed by an alkylating agent. Base-promoted cyclization of electron-deficient 3-alkylthio derivatives furnished 2-aryl-, 2-aroyl-, and 2-cyano-substituted thieno[3,2-b]thiophenes, bearing a 3-hydroxy group. This protocol broadens access to

• (Table 2). Thus, 4-(chloromethyl)benzonitrile was used as a model alkylating agent, NaBH4 and Na2S2O4 were used as mild and accessible reducing agents, and K2CO3 was originally considered as a base for the alkylation step. In our first experiment, NaBH4 in methanol was used to reduce disulfide 3 (Table 2

• , entry 1). However, methanol proved to be an ineffective solvent due to the rapid decomposition of NaBH4 and poor solubility of substrate 3. Most of the starting material was recovered unchanged after complete decomposing NaBH4. In contrast, when ethanol (Table 2, entry 2) or isopropanol (Table 2, entry

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

• NiCl2/NaBH4 in methanol at room temperature, affording the corresponding amine 4 in 93% yield. To align with green chemistry principles, we employed a recently reported mechanochemical protocol by Ito and co-workers for the reduction of nitro compounds to amines [72]. Using this solvent-free method

• , compound 2a was successfully reduced to the corresponding amine 4 in 85% yield. Similarly, the nitro group of compound 3 was also reduced under the NiCl2/NaBH4-promoted conditions, affording 9H-carbazol-1-amine (5) in 90% yield. Mechanistic studies Next, we sought to gain mechanistic insights into the

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

• step. However, the diastereoselective reduction of the ketone in 25 was challenging because the ketone was embedded in the concave face, which was more sterically hindered than the convex face. Common reductants, such as NaBH4, DIBAL-H, and LiAlH(Ot-Bu)3, provided product 32 with the opposite

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

• -nitrobenzyl bromide (47) with 50 or with 52, after its reduction with NaBH4. The intermediate products are then treated with lead in a buffered basic environment to get the final product in low yield accompanied by two by-products, 54a,b. For the O-heterodiazocine, reduction with triphenylphosphine and a

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

• , usage of classical reducing agents – H2 on Pd/C or NaBH4 did not show similar chemoselectivity [26]. Additionally, the NaH2PO2 usability is engaging due to fine green chemistry metrics, e.g., an E-factor less than 1 was reached, moreover the main wastes of this process were safe and useful as

Synthesis of an aza[5]helicene-incorporated macrocyclic heteroarene via oxidation of an o-phenylene-pyrrole-thiophene icosamer

• Yusuke Matsuo,
• Aoi Nakagawa,
• Shu Seki and
• Takayuki Tanaka

Beilstein J. Org. Chem. 2025, 21, 1561–1567, doi:10.3762/bjoc.21.119

• acyclic heteroaromatics [26][27]. Thus, to a solution of 4 in CH2Cl2 was added 15 equivalents of PIFA at −78 °C and stirred for 3 h. The mixture was then allowed to warm to room temperature to give a dark solution. The system was worked-up with NaBH4/MeOH for 10 minutes followed by extraction with CH2Cl2

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

• azulene-embedded dione 59 in 39% yield. Finally, NaBH4 reduction followed by SnCl2/AcOH dehydration gave target non-alternant isomer of hexacene 60 in 43% yield. Interestingly, for the same number of rings, azulene-embedded acene isomers isomers exhibit greater stability than their fully benzenoid acene

Selective monoformylation of naphthalene-fused propellanes for methylene-alternating copolymers

• Kenichi Kato,
• Tatsuki Hiroi,
• Seina Okada,
• Shunsuke Ohtani and
• Tomoki Ogoshi

Beilstein J. Org. Chem. 2025, 21, 1183–1191, doi:10.3762/bjoc.21.95

• -fused propellanes simply by reduction into the corresponding alcohols followed by acid-mediated Friedel–Crafts-type reactions (Figure 2a and Figure S201 in Supporting Information File 1) [67][68]. Reduction by NaBH4 proceeded well for both monoaldehydes [4.3.3]_CHO and [3.3.3]_CHO resulting in over 90

Synthetic approach to borrelidin fragments: focus on key intermediates

• Yudhi Dwi Kurniawan,
• Zetryana Puteri Tachrim,
• Teni Ernawati,
• Faris Hermawan,
• Ima Nurasiyah and
• Muhammad Alfin Sulmantara

Beilstein J. Org. Chem. 2025, 21, 1135–1160, doi:10.3762/bjoc.21.91

• CuBr·SMe2, facilitating the formation of deoxypropionate 125 in 80% yield with excellent regioselectivity (>99:1) and stereoselectivity (99:1 dr). Ozonolysis of 125 followed by reductive work up with NaBH4 afforded alcohol 126 in 92% yield. At this stage, the authors explored an alternative procedure for

Studies on the syntheses of β-carboline alkaloids brevicarine and brevicolline

• Benedek Batizi,
• Patrik Pollák,
• András Dancsó,
• Péter Keglevich,
• Gyula Simig,
• Balázs Volk and
• Mátyás Milen

Beilstein J. Org. Chem. 2025, 21, 955–963, doi:10.3762/bjoc.21.79

• worth mentioning that in a similar reaction of 30 with NaCNBH3 in acetic acid (instead of TFA) we did not observe any reaction, however, with NaBH4 (instead of NaCNBH3) in TFA, the formation of 32 was detected. Conclusion In conclusion, a new method for the synthesis of β-carboline alkaloid brevicarine

Photochemically assisted synthesis of phenacenes fluorinated at the terminal benzene rings and their electronic spectra

• Yuuki Ishii,
• Minoru Yamaji,
• Fumito Tani,
• Kenta Goto,
• Yoshihiro Kubozono and
• Hideki Okamoto

Beilstein J. Org. Chem. 2025, 21, 670–679, doi:10.3762/bjoc.21.53

• state. The orange and blue sites, respectively, indicate negative and positive regions (−0.02 ≈ 0.02 hartree). Synthesis of building blocks 10, 13, and 15. Reagents and conditions: a) NaBH4, MeOH, THF, reflux; b) PBr3, reflux; c) N-methylmorpholine-N-oxide, THF, reflux; d) ethylene glycol, p-TsOH

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• activation, atroposelective aza-Michael addition, and intramolecular aldol reaction to form the cationic intermediate Int-6. Release of the catalyst C2, reduction with NaBH4, and dehydration with acetic acid leads to the desired product 6. Recently, an organocatalytic atroposelective intramolecular (4 + 2

Facile one-pot reduction of β-nitrostyrenes to phenethylamines using sodium borohydride and copper(II) chloride

• Laura D’Andrea and
• Simon Jademyr

Beilstein J. Org. Chem. 2025, 21, 39–46, doi:10.3762/bjoc.21.4

• Aalborg, Denmark current address: Centre for Analysis and Synthesis, Lund University, Naturvetarvägen 14, 223 62 Lund, Sweden 10.3762/bjoc.21.4 Abstract Phenethylamines and phenylisopropylamines of scientific relevance can be prepared with a NaBH4/CuCl2 system in 10 to 30 minutes via reduction of

• substituted β-nitrostyrenes. This one-pot procedure allows the quick isolation of substituted β-nitrostyrene scaffolds with 62–83% yield under mild conditions, without the need for special precautions, inert atmosphere, and time-consuming purification techniques. Keywords: 2C-X; CuCl2; NaBH4; β-nitrostyrene

• aluminum hydride, sodium borohydride is a non-pyrophoric and easy-to-handle reducing agent. Since the first attempts in 1967, NaBH4 has been employed to reduce β-nitrostyrene scaffolds to the corresponding nitroalkanes [19][20][21]. Several catalysts have been combined with NaBH4 to facilitate full

Efficient one-step synthesis of diarylacetic acids by electrochemical direct carboxylation of diarylmethanol compounds in DMSO

• Hisanori Senboku and
• Mizuki Hayama

Beilstein J. Org. Chem. 2024, 20, 2392–2400, doi:10.3762/bjoc.20.203

• ) [21] are known compounds and were prepared from the corresponding commercially available ketones by reaction with NaBH4 in EtOH or EtOH/THF 1:1. 1,1-Diphenylethanol (1i) is also a known compound and was prepared according to the reported procedure [29]. 9H-Fluoren-9-ol (1m) and triphenylmethanol (1n

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• -morpholinyl amido and benzophenone imino groups with LiAlH4 and NaBH4 afforded the corresponding syn-2-benzyl-1,3-amino alcohol 134 in 83% yield. In the case of the dimethylamide derivative, deprotection of benzophenone imine 128 with NH2OH·HCl followed by the LiAlH4 reduction gave rise to chiral syn-2-benzyl