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

• (CN ≈ COR >> NO2) reacted poorly. Iodanes, containing electron-withdrawing groups with low nucleophilicity (CF3), however, gave fair yields. We also found that ortho-substituted iodanes did not provide arylation products, which can be attributed to the unfavorable steric hindrance [30]. Iodanes

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

• , compounds 14 and 20 were evaluated for the cross-metathesis of the olefin moiety in 14. No reaction occurred and the desired product was not detected (not shown), presumably because of the steric hindrance from the TBS group. Following the removal of the silyl group, cyclopentanol 19 underwent the cross

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

• . Interestingly, for the cyclization of 3b, only compound MC3 was obtained in 85% yield, which is probably attributed to larger steric hindrance deriving from bis(trifluoromethyl)phenyl groups. These macrocycles show good solubility in common solvents, and their chemical structures have been unambiguously

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

• reaction mechanisms and applications of the chiral products for selected examples. Review Helical chirality Helicenes are a group of rigid polycyclic aromatic compounds composed of ortho-fused aromatic (hetero)cyclic rings, with their helically twisted conformation enforced by steric hindrance between

• enantioselectivity, with an s-factor up to >259 (Scheme 7). Notably, this reaction did not produce the typical arene C–H amination products but instead the dearomative amination products 26, which is believed to be due to the significant steric hindrance surrounding the amination site that impeded the subsequent

• demonstrated the successful construction of planarly chiral macrocycles with 12- to 14-membered ansa chains with high enantioselectivity when using NH2 as the directing group (see 33a,b). However, extending the ansa chain to 15 members led to the loss of planar chirality due to insufficient steric hindrance to

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

• , bottom), the thermal lifetimes drop significantly [38]. It is thus crucial to take into account the asymmetric nature of the imine bond and the steric hindrance of the substituents in the design of these photoswitches. For a detailed analysis of the structure–property relationship of these compounds we

• with bulky N-substitution suggest that the conformation is twisted, with reduced conjugation. Steric hindrance at the indoxyl nitrogen also provides higher thermal stability of the E-isomer, with mixtures of E and Z found at thermal equilibrium [77]. Heteroaromatic substitution in hemiindigo generates

• , which, combined with additional steric hindrance to the stilbene moiety and on the double bond, induces a helical twisting around the double bond in 71, thus generating a molecular motor, capable of unidirectional movement upon photoswitching (Figure 16, right) [84][85]. Sulphone hemithioindigos 70 have

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

• consistently high combined yields, ranging from 92% to 95%. Probably due to steric hindrance, when the phenyl group was attached to the para-position of the aniline (1e), the corresponding products 3e along with 3e′ could be obtained in 75% yields. Electron-deficient groups at the para-position, such as -Cl

• steric hindrance, leading to a moderate combined yield. Moreover, when the meta-substituted arylamine 1k was reacted under standard conditions, regioisomeric forms of quinolines were observed during GC and GC–MS analysis. Nearly identical results were obtained when 3,4-dimethylaniline (1l) was used. An

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

• )-N1,N2-bis((1R,2R)-2-(tert-butoxycarbonyl)-1,2-diphenylethyl)cyclohexane-1,2-dicarboxamide (4h) in 65% yield through the reaction with (1S,2S)-cyclohexane-1,2-dicarboxylic acid (3). However, compound 4h did not undergo cyclization possibly due to weak nucleophilicity and steric hindrance of the Boc

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

• formation of an α-glycoside on the donor side [54]. On the acceptor side, the β-configuration was favored due to steric hindrance from the C-2 phthalimido group in the triacetylated GalN-lactol acceptors 6 or 3,4-di-O-benzylated acceptors 8, resulting in kinetically controlled formation of β,α-1,1

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

• substrate scope of the developed synthetic approach was investigated. Aromatic and aliphatic carbonyl compounds reacted with primary and secondary amines. The reductive amination efficiently proceeded with both cyclic and acyclic secondary amines. Steric hindrance in ortho-position in carbonyl compound 13

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

• two NH sites remained uncoordinated due to steric hindrance. Non-covalent interaction (NCI) plot analysis revealed distinct intramolecular π–π dispersion interactions between the two aza[5]helicene moieties (green surface in Figure 4b) [29][30][31]. Optical properties The electronic absorption and

General method for the synthesis of enaminones via photocatalysis

• Paula Pérez-Ramos,
• Raquel G. Soengas and
• Humberto Rodríguez-Solla

Beilstein J. Org. Chem. 2025, 21, 1535–1543, doi:10.3762/bjoc.21.116

• moieties, respectively, since they could enable further chemical transformations. Unfortunately, when 2-methyl-3-bromochromone was employed as the substrate, the process failed to afford the desired enaminone product, which was possibly caused by a combination of increased steric hindrance and decreased

• 9k was obtained, albeit in low yield. Regrettably, this transformation failed to provide the corresponding enaminone products by replacing alicyclic amines by diisopropylamine, probably due to steric hindrance. Steric factors could also explain the lack of reactivity of seven-membered azepane. In

Ambident reactivity of enolizable 5-mercapto-1H-tetrazoles in trapping reactions with in situ-generated thiocarbonyl S-methanides derived from sterically crowded cycloaliphatic thioketones

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Marcin Palusiak,
• Heinz Heimgartner,
• Marta Denel-Bobrowska and
• Agnieszka B. Olejniczak

Beilstein J. Org. Chem. 2025, 21, 1508–1519, doi:10.3762/bjoc.21.113

• depends on both steric factors in 11 and the electronic structure of the reactive anion 12. In general, growing steric hindrance prefers the S-attack and, very likely, hinders rearrangement leading to thioaminals 9. This hypothesis is supported by the fact that no formation of products 9 is observed with

• hindered) suggests that the steric hindrance can play an important role in the trapping process. It is worth of emphasizing that thioaminals [33] and dithioacetals [34] constitute important groups of building blocks, which are of interest not only for pharmaceutically oriented studies [35] but also for

Microwave-enhanced additive-free C–H amination of benzoxazoles catalysed by supported copper

• Andrei Paraschiv,
• Valentina Maruzzo,
• Filippo Pettazzi,
• Stefano Magliocco,
• Paolo Inaudi,
• Daria Brambilla,
• Gloria Berlier,
• Giancarlo Cravotto and
• Katia Martina

Beilstein J. Org. Chem. 2025, 21, 1462–1476, doi:10.3762/bjoc.21.108

• efficiently, affording good-to-excellent yields. The Boc-protecting group proved to be stable under the reaction conditions, underlining the importance of avoiding the addition of acidic additives. Steric hindrance exerted a moderate influence on the reaction, and branched aliphatic amines yielded the

Tautomerism and switching in 7-hydroxy-8-(azophenyl)quinoline and similar compounds

• Lidia Zaharieva,
• Vera Deneva,
• Fadhil S. Kamounah,
• Nikolay Vassilev,
• Ivan Angelov,
• Michael Pittelkow and
• Liudmil Antonov

Beilstein J. Org. Chem. 2025, 21, 1404–1421, doi:10.3762/bjoc.21.105

• acceptors is more pronounced. The effect of the amino group is stronger comparing to NMe2 due to the steric hindrance in the latter. Since in 1 the azo group, an acceptor, is placed on position 8, it is also expended to bring additional inherent stabilization of the 1K tautomer. The effect of the

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

• : aliphatic > allylic > benzylic. In case of trisubstituted C=C bonds, the cyclisation proceeded with retention of configuration, however, higher reaction temperatures were required due to the increased steric hindrance. Competition experiments revealed a preference for 4-exo ring closure over 5-exo, 6-exo

Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

• and alcohols. Substrates with different substituents, including both electron-donating and electron-withdrawing groups, provided satisfactory yields (7a–f). However, steric hindrance significantly influenced the outcome, as ortho-substituted substrates yielded lower amounts (7c). The study also

• -substituents induced steric hindrance effects that led to lower yields. To gain further insight into the mechanism, several control experiments were performed. The results indicated that an iminoxyl radical is generated as the initiator of the reaction (Scheme 6). Initially, TBHP undergoes homolytic cleavage

A versatile route towards 6-arylpipecolic acids

• Erich Gebel,
• Cornelia Göcke,
• Carolin Gruner and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 1104–1115, doi:10.3762/bjoc.21.88

• equatorial position for the phenylacetylene residue and an axial position for the methyl ester (Figure 4b). This arrangement is most likely the reason for neither (2R,6R)-13 nor (2R,6R)-9 displaying a second signal set. The steric hindrance by forcing both bulky residues into an axial position is no longer

Pd-Catalyzed asymmetric allylic amination with isatin using a P,olefin-type chiral ligand with C–N bond axial chirality

• Natsume Akimoto,
• Kaho Takaya,
• Yoshio Kasashima,
• Kohei Watanabe,
• Yasushi Yoshida and
• Takashi Mino

Beilstein J. Org. Chem. 2025, 21, 1018–1023, doi:10.3762/bjoc.21.83

• , compound 7 has a primary alkyl group (n-propyl). This difference reduces steric hindrance and lowers the rotational barrier around the carbon–nitrogen bond, increasing the likelihood of racemization. Results and Discussion N-Propyl-N-cinnamoylamide 7 was prepared from phosphine oxide 8 [32] via an SNAr

Recent total synthesis of natural products leveraging a strategy of enamide cyclization

• Chun-Yu Mi,
• Jia-Yuan Zhai and
• Xiao-Ming Zhang

Beilstein J. Org. Chem. 2025, 21, 999–1009, doi:10.3762/bjoc.21.81

• diastereo- and enantioselectivities. The substituent on the enamide could be varied from aryl to tert-butyl groups, though the terminating aryl group still necessitates an electron-rich arene. As was found in their previous work, the steric hindrance of the phenyl or tert-butyl group was supposed to be

A convergent synthetic approach to the tetracyclic core framework of khayanolide-type limonoids

• Zhiyang Zhang,
• Jialei Hu,
• Hanfeng Ding,
• Li Zhang and
• Peirong Rao

Beilstein J. Org. Chem. 2025, 21, 926–934, doi:10.3762/bjoc.21.75

• 4.4:1 mixture of regioisomeric alcohols with the desired isomer being the major component, presumably due to the considerable steric hindrance from the quaternary carbon at C4. However, decagram-scale separation of these two isomers by chromatography proved troublesome. Fortunately, the distinct

Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• , oxidative addition of the C–I bond to palladium formed the four-membered aryl–palladium complex Int-5. Steric hindrance from the bulky dppm ligand, combined with slower aryne release (using KF as the fluoride source), attenuated aryne coordination. Under these electron-deficient conditions, CO

Recent advances in the electrochemical synthesis of organophosphorus compounds

• Babak Kaboudin,
• Milad Behroozi,
• Sepideh Sadighi and
• Fatemeh Asgharzadeh

Beilstein J. Org. Chem. 2025, 21, 770–797, doi:10.3762/bjoc.21.61

• the gram-scale preparation of some samples. An electrochemical flow system was used in this method, in which carbon and platinum electrodes were used as the anode and cathode, respectively, at a constant current of 55 mA (Scheme 8). Due to the steric hindrance caused by the tert-butyl group, the

• solvent. The results showed that potassium iodide is critical in this reaction, and the reaction failed to give a corresponding product without using KI. This reaction was quickly extended to a wide range of substituted indoles. Moreover, despite significant steric hindrance or the presence of a long

Copper-catalyzed domino cyclization of anilines and cyclobutanone oxime: a scalable and versatile route to spirotetrahydroquinoline derivatives

• Qingqing Jiang,
• Xinyi Lei,
• Pan Gao and
• Yu Yuan

Beilstein J. Org. Chem. 2025, 21, 749–754, doi:10.3762/bjoc.21.58

• substrates for this transformation. However, due to steric hindrance, ortho-substituted aniline 1s exhibited significantly lower reactivity, resulting in diminished yields of product 3sa. Notably, disubstituted anilines were also compatible with the protocol, furnishing the desired products 3ta–ya in

Vinylogous functionalization of 4-alkylidene-5-aminopyrazoles with methyl trifluoropyruvates

• Judit Hostalet-Romero,
• Laura Carceller-Ferrer,
• Gonzalo Blay,
• Amparo Sanz-Marco,
• José R. Pedro and
• Carlos Vila

Beilstein J. Org. Chem. 2025, 21, 533–540, doi:10.3762/bjoc.21.41

• -butyl group is present in the C-3 position of the pyrazole as in the case of substrate 2e, the reaction did not take place, likely due to a considerable increase in steric hindrance. We also attempted to synthesize 4-(alkenyl)-5-aminopyrazoles using an acyclic ketone, such as acetone, but unfortunately

• the starting material 3ea, prepared from 2-indanone, the corresponding product was not observed, probably due to an increase in steric hindrance. Finally, 4-cyclohexenyl-5-aminopyrazoles bearing different substituents at the N-1 or C-3 position afforded the corresponding trifluoromethyl carbinols 5aba

Deep-blue emitting 9,10-bis(perfluorobenzyl)anthracene

• Long K. San,
• Sebastian Balser,
• Brian J. Reeves,
• Tyler T. Clikeman,
• Yu-Sheng Chen,
• Steven H. Strauss and
• Olga V. Boltalina

Beilstein J. Org. Chem. 2025, 21, 515–525, doi:10.3762/bjoc.21.39

• irradiation [37]. Notably, the apparent absence of the photodimer in the case of 9,10-ANTH(BnF)2 is likely due to the steric hindrance of the bulky perfluorobenzyl groups in the 9- and 10-positions on the ANTH core. Conclusion The perfluorobenzylation of ANTH and ANTH(Br)2 was performed for the first time