Synthesis and uranyl(VI) extraction performance of a calix[4]pyrrole–tetrahydroxamic acid receptor

• Sara Karnib,
• Rana Baydoun,
• Wissam Zaidan,
• Nancy AlHaddad,
• Omar El Samad,
• Bilal Nsouli,
• Francine Cazier-Dennin and
• Pierre-Edouard Danjou

Beilstein J. Org. Chem. 2026, 22, 486–494, doi:10.3762/bjoc.22.36

• , particularly when the starting compounds are sterically hindered [50]. In this regard, a methanolic solution of PCP ester was allowed to react with a large excess of methanolic hydroxylamine in the presence of DBU for one night. At this stage, the formation of precipitated PCP hydroxamic acids was verified

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

• conditions. In line with this, compounds 8–10 having less sterically hindered narrow-rim substitution patterns were found to be more resistant to side reactions during wide-rim nitration as well as to the target exhaustive nitration itself. These reactions required a higher nitric acid concentration of ≈2.5

• -temperature preparation of the tetrapropargyl ether 24 from its silylated precursor 21. Surprisingly, attempts to apply these conditions to a complete removal of TBS groups in the less sterically hindered propargyl ethers 22 and 23 failed, and large amounts of the starting materials (as well as the partially

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

• in good to high yields, and the results were highly dependent on the steric congestion of the substrate. With increased lengths of the alkyl substituent on the nitrogen, the yield was slightly decreased. Sterically hindered N-methyl-N-tert-butylamide 22 produced the corresponding anilide in only 53

• , and secondary amines all furnished the corresponding amides 135–143 in high yields, though the sterically hindered 1-adamantylamine afforded the corresponding amide 142 in a moderate 56% yield. Notably, the tertiary amide moiety was cleaved with excellent chemoselectivity even in the presence of other

• unactivated tertiary amides under transition-metal-free conditions [73]. Lithium hexamethyldisilazide (LiHMDS) was used to activate the amide, enabling smooth cleavage of the C–N bond even in sterically hindered substrates (Scheme 22a). Using p-methylaniline as a nucleophile in the presence of three

Synthesis of tricyclic fused pyrrolidine nitroxides from 2-alkynylpyrrolidine-1-oxyls

• Mark M. Gulman,
• Yuliya F. Polienko,
• Sofia Yu. Trakhininа,
• Yuri V. Gatilov,
• Tatyana V. Rybalova,
• Sergey A. Dobrynin and
• Igor A. Kirilyuk

Beilstein J. Org. Chem. 2026, 22, 344–351, doi:10.3762/bjoc.22.22

• rotation of the radical separately from the framework is impossible could be particularly promising. Rigid polycyclic fused systems with incorporated nitroxide moieties could be one of the possible ways to achieve the above feature. We recently found that the reaction of sterically hindered 3-hydroxymethyl

A mild and atom-efficient four-component cascade strategy for the construction of biologically relevant 4-hydroxyquinolin-2(1H)-one derivatives

• Dmitrii A. Grishin,
• Kseniia I. Sharkovskaia,
• Ilya G. Kolmakov,
• Daria A. Ipatova,
• Rostislav A. Petrov,
• Nikolai D. Dagaev,
• Dmitry A. Skvortsov,
• Maria G. Khrenova,
• Valeriy V. Andreychev,
• Sergei A. Evteev,
• Yan A. Ivanenkov,
• Roman L. Antipin,
• Olga А. Dontsova and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2026, 22, 244–256, doi:10.3762/bjoc.22.18

• cyclohexanol in refluxing dichloromethane. Moreover, Steglich esterification (using DCC and DMAP in dichloromethane), known for its mild conditions and compatibility with sterically hindered substrates, also produced the cyclic pyranoquinoline 14 rather than the expected ester. During preparative

Conformational analysis of difluoromethylornithine: factors influencing its gas-phase and bioactive conformations

• Matheus P. Freitas

Beilstein J. Org. Chem. 2026, 22, 237–243, doi:10.3762/bjoc.22.17

• hyperconjugation, but the former experiences weaker steric repulsion. Conversely, conformer 18 is both the least stabilized by hyperconjugation and one of the most sterically hindered. The gas-phase preferences can be contrasted with the bioconformation of (S)-DFMO. Although PDB entry 9FOS is reported as ornithine

Circumventing Mukaiyama oxidation: selective S–O bond formation via sulfenamide–alcohol coupling

• Guoling Huang,
• Huarui Zhu,
• Shuting Zhou,
• Wanlin Zheng,
• Fangpeng Liang,
• Zhibo Zhao,
• Yifei Chen and
• Xunbo Lu

Beilstein J. Org. Chem. 2026, 22, 158–166, doi:10.3762/bjoc.22.9

• good to excellent yields (up to 99%), suggesting broad functional group compatibility. The protocol also demonstrated excellent compatibility with structurally and electronically distinct amide substrates. The sterically hindered 2-naphthylamide-derived sulfenamide afforded the desired product 3h’ in

• efficiently even with secondary hydroxy groups. The method also accommodated sterically hindered and functionalized alcohols. tert-Butylmethanol in which the hydroxy group is attached to a methylene adjacent to a bulky tert-butyl group, gave the desired product 3v’ in 91% yield, while a halogenated alcohol

• with alcohols to access sulfinimidate esters. The method uses inexpensive and readily available reagents and features a broad substrate scope, high chemoselectivity, and excellent tolerance toward sterically hindered and functionalized alcohols. It avoids typical Mukaiyama-type oxidation pathways and

Highly electrophilic, gem- and spiro-activated trichloromethylnitrocyclopropanes: synthesis and structure

• Ilia A. Pilipenko,
• Mikhail V. Grigoriev,
• Olga Yu. Ozerova,
• Igor A. Litvinov,
• Darya V. Spiridonova,
• Aleksander V. Vasilyev and
• Sergey V. Makarenko

Beilstein J. Org. Chem. 2026, 22, 123–130, doi:10.3762/bjoc.22.5

• cyclopropane ring is probably a consequence of the formation of a sterically hindered carbanion II in a conformation with an anti-periplanar position of the bulky substituents – bromine and a trichloromethyl group (Scheme 6). Due to the steric reasons, the anion in this conformation is selectively protonated

Reactivity umpolung of the cycloheptatriene core in hexa(methoxycarbonyl)cycloheptatriene

• Dmitry N. Platonov,
• Alexander Yu. Belyy,
• Rinat F. Salikov,
• Kirill S. Erokhin and
• Yury V. Tomilov

Beilstein J. Org. Chem. 2026, 22, 64–70, doi:10.3762/bjoc.22.2

• (methoxycarbonyl)cycloheptatriene 3 (pKa(DMSO) = 8.65) [20][21] with potassium tert-butoxide and subjected to reactions with electrophilic reagents. The reactions gave two primary products 4 and 5 (Scheme 1) through an attack to either the most available i-position or the most nucleophilic but sterically hindered

• sterically hindered 2-(methoxycarbonyl)phenyldiazonium ion afforded only one isomer of dihydroindazole 8k which indicates the influence of the steric factor on the azocyclopropane rearrangement. However, the reaction additionally gave the product of an i-substitution with subsequent proton migration to form

• with the formation of 4a,b, as well as the formation of hydrazone product 10k exclusively in the case of the most sterically hindered diazonium electrophile leads to the conclusion that the direct electrophilic attack onto the i-position could take place in all these cases. To clarify this, we analyzed

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

• products 28–35, 38 and 39 [56]). The yields varied considerably depending on the substrate, leading to the following conclusions: (a) unhindered ketones lacking functional groups generally react in high yields; (b) sterically hindered ketones provide products 33, 36, and 39 with low yields; (c) electron

• alkenyl chloride 156 was isolated only in trace amounts, alongside isomerized alkene 157 and dichloride 158. Notably, only the sterically hindered tert-butyl-substituted alkyne afforded the desired product 155 in high yields, whereas hydrochlorination of 4-octyne proved inefficient to deliver compound 159

Tandem hydrothiocyanation/cyclization of CF₃-iminopropargyl alcohols with NaSCN in the presence of AcOH

• Ruslan S. Shulgin,
• Ol’ga G. Volostnykh,
• Anton V. Stepanov,
• Igor’ A. Ushakov,
• Alexander V. Vashchenko and
• Olesya A. Shemyakina

Beilstein J. Org. Chem. 2025, 21, 2694–2702, doi:10.3762/bjoc.21.207

• , providing products 2b,c and 3b,c with similar yields (Table 2, entries 1 and 2). The slightly decreased yield observed for product 3c obtained from iminopropargyl alcohol having a cyclohexyl substituent, is probably due to the steric effect (Table 2, entry 2). The more sterically hindered CF3-iminopropargyl

Efficient solid-phase synthesis and structural characterization of segetalins A–H, J and K

• Liangyu Liu,
• Wanqiu Lu,
• Quanping Guo and
• Zhaoqing Xu

Beilstein J. Org. Chem. 2025, 21, 2612–2617, doi:10.3762/bjoc.21.202

• from the high cost of the specialized resin and large solvent volumes required for dilution, coupled with DPPA's poor efficiency in forming sterically hindered peptide bonds involving residues like Val or Ile. Dahiya and Kaur synthesized segetalin C (3) via a solution-phase fragment coupling strategy

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

• the simultaneous construction of four quaternary carbon centers (C1, C4, C5, and C12) and the core AB bicyclic skeleton, markedly improving synthetic efficiency. Subsequent oxidative desymmetrization of the C14–C15 olefin in (±)-33 established the sterically hindered C11 quaternary carbon center. An α

• , (+)-ryanodol (4), indicates that the pyrrole-2-carboxylate unit at the C3 position is critical for receptor binding, as established by structure–activity relationship (SAR) studies [28]. However, the direct and selective modification of the highly sterically hindered C3 hydroxy group within this

Synthetic study toward vibralactone

• Liang Shi,
• Jiayi Song,
• Yiqing Li,
• Jia-Chen Li,
• Shuqi Li,
• Li Ren,
• Zhi-Yun Liu and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2025, 21, 2376–2382, doi:10.3762/bjoc.21.182

• not proceed to form the all-carbon quaternary center and only decomposition of 21 was observed. The failure is likely due to the sterically hindered environment of the substituted β-lactone ring which precludes the C–H insertion or deprotonation of the β-lactone and interrupted the generation of the

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

• natural product synthesis. This review summarizes the latest advancements in these reactions for constructing terpenoids, alkaloids, and antibiotics. Through Norrish–Yang cyclization, dicarbonyls (e.g., 1,2-diketones and α-keto amides) can efficiently construct sterically hindered ring structures, which

• , enabling the construction of diverse architectures including sterically hindered cyclobutanes, spiroketals, and fused polycycles. However, the potential of dicarbonyls in photoreactions warrants further exploration. Future research could investigate a broader range of dicarbonyl substrates to uncover new

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

• efficiency, as the reaction proceeds smoothly even when both coupling partners possess sterically hindered substituents at the 2,6-positions. For example, the coupling of 2,6-difluorophenylhydrazine with 1-bromo-2,6-dimethoxybenzene yielded tetra-ortho-substituted azobenzene 5a in a notable yield of 63

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

• ], the enzyme-catalyzed desymmetric enantioselective reduction of 28, afforded hydroxyketone 54 in 65% yield with >99% ee and 8–9:1 dr on multigram scale [34]. Functional group transformations of 54 in four steps produced sterically hindered allyl triflate 55. By employing the palladacycle catalyst 45

• -catalyzed Suzuki cross-coupling reaction of sterically hindered substrates developed by Han [35][36][37], the coupled product 57 was obtained in a satisfactory yield (72%) from 55 and pinacol boronate 56, along with trace amounts of the double bond migrated side product 58 (57:58 = ca. 15:1). Demethylation

α-Ketoglutaric acid in Ugi reactions and Ugi/aza-Wittig tandem reactions

• Vladyslav O. Honcharov,
• Yana I. Sakhno,
• Olena H. Shvets,
• Vyacheslav E. Saraev,
• Svitlana V. Shishkina,
• Tetyana V. Shcherbakova and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2021–2029, doi:10.3762/bjoc.21.157

• compared to compounds 5, which can be clearly seen in the spectrum of compound 8h with both substituted ortho-positions of the amine moiety. In our opinion, this indicates the presence of rotamerism [59][60] caused by the restricted rotation of the sterically hindered amide group. The 1H NMR spectra 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

• -catalyzed propargylsilane activation pathway [26]. Therefore, the presence of a base was imperative. The only applicable base was found to be the non-nucleophilic 2,6-di-tert-butylpyridine (B1, Table 1, entries 1–6, 9–18). We also considered the structurally similar, but less sterically hindered 2,6

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

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

• ), as well as electron-donating groups like methoxy (2f), aryl/alkyl (2h,i), and alkenyl substituents (2e), were well tolerated. Notably, the sterically hindered derivative 2h was isolated with the highest yield of 87% indicating that bulky ortho-substituents on the aromatic rings do not influence the

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

• photoisomerisation, making it an all-visible example of a molecular motor (Scheme 29) [85]. Irradiation at 470 nm of 98-A leads to the thermally unstable 98-B, which immediately converts to the less sterically hindered 98-C. Further irradiation leads to the thermally unstable 98-D, which again converts quickly to

Structural analysis of stereoselective galactose pyruvylation toward the synthesis of bacterial capsular polysaccharides

• Tsun-Yi Chiang,
• Mei-Huei Lin,
• Chun-Wei Chang,
• Jinq-Chyi Lee and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2025, 21, 1671–1677, doi:10.3762/bjoc.21.131

• 72% yield and excellent regio- and stereoselectivity. Regarding the acceptor, compound 6 harbored two free alcohol groups at the C3 and C2 positions. Since the C3 alcohol group is less sterically hindered and exhibits better nucleophilicity, the glycosidic bond formed regioselectively at the C3

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

• , pioneered by Bringmann and co-workers [45], has proven to be a powerful approach for synthesizing axially chiral biaryls, particularly in the challenging case of sterically hindered tetra-ortho-substituted scaffolds [46][47]. In this context, α-acidic isocyanides have been successfully employed as carbon