Understanding the origin of stereoselectivity in the photochemical denitrogenation of 2,3-diazabicyclo[2.2.1]heptene and its derivatives with non-adiabatic molecular dynamics

• Leticia A. Gomes and
• Steven A. Lopez

Beilstein J. Org. Chem. 2025, 21, 2007–2020, doi:10.3762/bjoc.21.156

• molecular dynamics (NAMD) simulations of a series of diazabicyclo[2.1.1]hexenes. The minimum energy path showed stepwise σCN bond breaking and led directly to a minimum energy crossing point, corresponding to the inversion product. We also performed NAMD simulations on halogenated derivatives to test the

Photochemical reduction of acylimidazolium salts

• Michael Jakob,
• Nick Bechler,
• Hassan Abdelwahab,
• Fabian Weber,
• Janos Wasternack,
• Leonardo Kleebauer,
• Jan P. Götze and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2025, 21, 1973–1983, doi:10.3762/bjoc.21.153

• substrate (Figure 1b). This led to the successful development of a novel dual NHC/light-mediated reduction process using either the simple tertiary amine, NEt(iPr)2 (DIPEA) or the widely available silane HSiEt3, as the only reductant. Moreover, interesting insights into the reaction mechanism supported by

• reactions were carried out. As expected, conducting the reaction in the absence of the terminal reductant, DIPEA, led to a complex reaction mixture (Table 1, entry 2), while performing the reaction in the dark resulted only in recovered starting material (Table 1, entry 3). To our surprise, however

• , switching from MeCN to the chlorinated solvents DCM, DCE and chlorobenzene led to a decline in the formation of the fully reduced product 2 with O-benzoylated species 3 being obtained as the major product (38% in DCM, 35% in DCE, 38% in PhCl cf. 6–8% of 2, Table 1, entries 10–12). Significant reduction of 1

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

• stereoselectively access the syn-anti-cyclopentanol ring system with three vicinal stereogenic centers at C11, C12, and C8 via the oxidative radical cyclization that led to the asymmetric total synthesis of compound 4. Results and Discussion First generation asymmetric total synthesis of tricyclic-PGDM methyl ester

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

• enhanced the reaction performance. However, excessively bulky substituents at C4 and substitutions at both C4 and C5 hindered the coordination between substrate and catalyst, and led to reduced enantioselectivity. As to the structure of 128, the electronic effect of the bromo-substituted pyridine moiety

• 212. Four subsequent steps, including oxidation of propargylic alcohol and cyclization between the hydroxy group and ynone, provided compound 213 with a pyranone ring. Treatment of 213 with Me3SnOH hydrolyzed the methyl ester, and intramolecular Yamaguchi esterification then led to lactone 214, which

Rhodium-catalysed connective synthesis of diverse reactive probes bearing S(VI) electrophilic warheads

• Scott Rice,
• Julian Chesti,
• William R. T. Mosedale,
• Megan H. Wright,
• Stephen P. Marsden,
• Terry K. Smith and
• Adam Nelson

Beilstein J. Org. Chem. 2025, 21, 1924–1931, doi:10.3762/bjoc.21.150

• exploited. A high-throughput synthetic approach was harnessed to identify substrate/co-substrate/catalyst combinations, which led to the productive formation of intermolecular reaction products. Overall, the approach enabled the synthesis of thirty diverse reactive probes. The probes were screened for

Synthesis, biological and electrochemical evaluation of glycidyl esters of phosphorus acids as potential anticancer drugs

• Almaz A. Zagidullin,
• Emil R. Bulatov,
• Mikhail N. Khrizanforov,
• Damir R. Davletshin,
• Elvina M. Gilyazova,
• Ivan A. Strelkov and
• Vasily A. Miluykov

Beilstein J. Org. Chem. 2025, 21, 1909–1916, doi:10.3762/bjoc.21.148

• , synthetic chemistry, and medicine. This surge in interest has led to the development of innovative synthetic routes aimed at producing new members of these compounds [22]. For instance, fosfomycin [23] stands out as a broad-spectrum antibiotic currently employed in clinical settings, while thiotepa has been

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

• sustainable alternative; however, unfortunately, the electrochemical application is limited to only a few examples (Scheme 3). The electroreductive coupling of imines was first reported in the early 20th century by Law [42]. However, this initial method led to the formation of vicinal diamines with low to

• times higher than the batch protocol. Moreover, the significantly shorter residence time in the flow setup led to an improved space-time yield (STY), a key metric for comparing reactors of different volumes. Under these conditions, the STY of the flow process was 112.2 times higher than that achieved in

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

• for interconversion. However, steric repulsion between the C-1 substitutions and the terminal arene moieties in the M-conformational diastereomer resulted in the P-conformational diastereomer being thermodynamically favored. This led to the formation of (P)-helicene products following DDQ-mediated

• reaction produced the imine 16a which, upon treatment with Pd(PPh3)2Cl2 and KHMDS, led to furan ring formation and the generation of hetero[7]helicene 17a while maintaining the stereochemical configuration. Through this methodology, a range of elongated [7]- and [8]heterohelicenes 17b–d incorporating both

• 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

Systematic pore lipophilization to enhance the efficiency of an amine-based MOF catalyst in the solvent-free Knoevenagel reaction

• Pricilla Matseketsa,
• Margret Kumbirayi Ruwimbo Pagare and
• Tendai Gadzikwa

Beilstein J. Org. Chem. 2025, 21, 1854–1863, doi:10.3762/bjoc.21.144

• internal standard to the catalysis reactions. Interestingly, performing the reaction without dodecane revealed significantly lower conversions (Table 2B). This led us to a modified hypothesis; namely that in a lipophilic environment, such as a lipophilicized pore or one containing a hydrophobic solvent

• substitution, to isopropyl, then tert-butyl, subsequent increases in lipophilicity with n-hexyl and tetradecyl resulted in decreased conversions; a trend that can be more clearly perceived in Figure 4A. The combined dodecane-free results led us to speculate that it would be better to remove solvent as a

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

• led to a strong decrease in the thermal half-life, suggesting water is also involved in the Z–E thermal isomerisation process [70]. Bridged indigos have also been reported for which the Z-isomers are unstable. By bridging the two nitrogen atoms, these compounds show planar chirality and can be

• the thermal stability from hundreds of years to a few days. The addition of a further hydrogen-bond acceptor on the stator led to the discovery of hydrazones with a thermal stability of thousands of years (Scheme 34, left) [111]. The extra H-bond in 106-E and 107-E raises the energy of the linear

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

• conditions, the reaction led to a complete suppression in the yield of 3a and 3a′. The above results reveal that O2 plays a remarkable role in this transformation. Subsequently, the reaction was performed using N-methylaniline (1a′) under the optimized conditions (reaction 2), which afforded product 3a′ in

[3 + 2] Cycloaddition of thioformylium methylide with various arylidene-azolones in the synthesis of 7-thia-3-azaspiro[4.4]nonan-4-ones

• Daniil I. Rudik,
• Irina V. Tiushina,
• Anatoly I. Sokolov,
• Alexander Yu. Smirnov,
• Alexander R. Romanenko,
• Alexander A. Korlyukov,
• Andrey A. Mikhaylov and
• Mikhail S. Baranov

Beilstein J. Org. Chem. 2025, 21, 1791–1798, doi:10.3762/bjoc.21.141

• , proved to be a more promising derivatization approach (Scheme 4). Thus, the short-term action of hydrogen peroxide successfully converted compounds 7e, 7c, and 9e to their corresponding sulfoxides 11e, 11c, and 13e. However, prolonged oxidation led not only to sulfone formation but also to deeper

Unique halogen–π association detected in single crystals of C–N atropisomeric N-(2-halophenyl)quinolin-2-one derivatives and the thione analogue

• Mai Uchibori,
• Nanami Murate,
• Kanako Shima,
• Tatsunori Sakagami,
• Ko Kanehisa,
• Gary James Richards,
• Akiko Hori and
• Osamu Kitagawa

Beilstein J. Org. Chem. 2025, 21, 1748–1756, doi:10.3762/bjoc.21.138

• racemic quinolinones rac-1 in Figure 2 (single crystals of rac-2a were obtained from slow evaporation of hexane/methanol (1:1) mixture at room temperature) [37]. That is, in contrast to rac-1, in which homochiral layered polymer chains were formed, crystallization of quinoline-2-thione rac-2a led to the

• unstable and standing for a long period in the solution state resulted in several decomposed products). Conclusion We found that crystallization of racemic and optically pure C–N atropisomeric N-(halophenyl)quinolin-2-one derivatives led to the formation of homochiral layered polymer chains, which consist

Preparation of a furfural-derived enantioenriched vinyloxazoline building block and exploring its reactivity

• Madara Darzina,
• Anna Lielpetere and
• Aigars Jirgensons

Beilstein J. Org. Chem. 2025, 21, 1737–1741, doi:10.3762/bjoc.21.136

• successful as the reaction was stopped at the spirocycle 4d formation stage (Table 1, entry 9). The removal of the N-Alloc group in unsaturated ester S-3d was performed using a Pd catalyst and pyrrolidine as a nucleophile. The use of Pd(PPh3)4 as the catalyst led to a fast consumption of the starting

Convenient alternative synthesis of the Malassezia-derived virulence factor malassezione and related compounds

• Karu Ramesh and
• Stephen L. Bearne

Beilstein J. Org. Chem. 2025, 21, 1730–1736, doi:10.3762/bjoc.21.135

• intent of using the benzyl group to protect the indole nitrogen rather than the Boc group. However, Pd-catalyzed hydrogenation of 25d led to a mixture of products, of which some were consistent with reduction of the indole ring. With respect to the scalability of the synthesis, the reactions can be

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

• [50], and trichloroacetimidates [51][52]. However, the monosaccharide components were mostly fully benzylated or acetylated, so that the 1,1'-glycosylation reactions led to the formation of symmetric nonreducing products [53]. For instance, the tetrabenzylated chloride donor 1 was reacted with the

• presence of boron trifluoride etherate as promoter to afford the β,α-1,1'-linked disaccharide 12 in 52% yield (Scheme 2). The electron-withdrawing effect of the 2-azido group in the structurally similar donor 13 led to a significant drop in efficiency and the formation of the desired disaccharide 14 along

• -configuration on the glycosyl acceptor side was “retained” from the 1,2-orthoester progenitor. The nature of the protecting groups proved to be critical for the glycosylation outcome: the use of bulkier benzoyl esters, as in the phenyl 1,2-orthoester 19, led to a lower yield (36%) of the 1,1'-linked product 20

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

• signal shifted to 25.7 ppm, and the 1H signal shifted to 1.57 ppm. However, under these conditions, the pyruvylation proceeded sluggishly, with incomplete conversion even after 18.5 h, resulting in low yields of 17–22% (Table 1, entries 1 and 2). Additionally, extending the reaction time led to an

• β-selectivity due to the neighboring group effect [41][48][49][50]. Subsequently, treatment with triethylsilane (Et₃SiH) and trimethylsilyl trifluoromethanesulfonate (TMSOTf) led to the opening of the benzylidene ring and removal of the TMS group, yielding compound 14, which can serve as an acceptor

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

• water led to the drop of the yield while comparably low amounts (less than 0.7 equiv) were favorable (see Table S2 in Supporting Information File 1). This influence could be explained by hindering of the iminium ion formation in the presence of water. Thus, the optimization of the reaction conditions

• ). Insertion of D into β-position to nitrogen atom in the product was likely to be caused by fast exchange via keto–enol tautomeric equilibrium in the starting cyclohexanone or equilibrium between iminium cation and enamine (Scheme 4b). Reduction of the iminium cation led to insertion of D into α-position of

• protonation of an aldehyde (Step_2’). Due to the higher basicity of the secondary amine compared with the carbonyl group of benzaldehyde, protonation of dimethylamine was the main reaction pathway (30.9 vs −2.6 kcal/mol). However, it was found that the protonation of the carbonyl group led to a great

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

• is worth noting that the presence of a hydrogen bonding donor in 27 is crucial for achieving high enantioselectivity. As shown, while replacing the OH with NHMe led to a slight decrease of ee (28c versus 28b), the protection of the OH with methyl caused a severe drop (28d versus 28b). The application

• chiral INT-C, which, after imine-enamine tautomerization, led to the formation of final product 28. α-Acidic isocyanide-based transformations De novo arene formation In 2019, Zhu and co-workers developed the first example of catalytic enantioselective Yamamoto–de Meijere pyrrole synthesis [36][37

• substrates bearing strong electron-withdrawing groups resulted in almost no reactivity (e.g., 49d). Additionally, it was found that the N-substituent R3 in 48 has a significant effect on both reactivity and enantioselectivity. While replacing Ts with Bn led to no reaction at all (49e versus 49a

Thermodynamic equilibrium between locally excited and charge transfer states in perylene–phenothiazine dyads

• Issei Fukunaga,
• Shunsuke Kobashi,
• Yuki Nagai,
• Hiroki Horita,
• Hiromitsu Maeda and
• Yoichi Kobayashi

Beilstein J. Org. Chem. 2025, 21, 1577–1586, doi:10.3762/bjoc.21.121

• driven by the enhanced electron-donating ability of the TPA units, but rather by the stabilization of the PTZ 1LE state, which is facilitated by planarization of the PTZ moiety in the excited state and the resulting increase in π-conjugation. This behavior led to the persistent presence of 1LE-state

Facile synthesis of hydantoin/1,2,4-oxadiazoline spiro-compounds via 1,3-dipolar cycloaddition of nitrile oxides to 5-iminohydantoins

• Juliana V. Petrova,
• Varvara T. Tkachenko,
• Victor A. Tafeenko,
• Anna S. Pestretsova,
• Vadim S. Pokrovsky,
• Maxim E. Kukushkin and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 1552–1560, doi:10.3762/bjoc.21.118

• triethylamine hydrochloride. This method has proven to be simple and effective in most cases, with the exception of compound 5g. The moderate solubility of this compound in diethyl ether led to partial precipitation from the reaction mixture. It is worth noting that chromatographic purification is also possible

• N1 nitrogen atom (2i) led to a sharp decrease in the yield of the cycloaddition product 5j, whereas the presence of the N3-CH2COOEt (2h) fragment slightly enhanced the yield of 5i compared to the bis-phenyl substituted dipolarophile 2g. The low yield observed for product 5j may be accounted for by a

• -CH3 to -OCH3 led to a decrease in IC50 by at least 20 µM and turned out to be comparable to that obtained for 5d. Conclusion In this study, we firstly investigated the 1,3-dipolar cycloaddition reactions of nitrile oxides to 5-iminohydantoins at their exocyclic C=N bond. A convenient preparative

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

• -dimethylformamide (DMF) at 20 °C afforded the best results, giving the desired product 9a in 70% isolated yield (Table 1, entry 1). Changing NiBr2·diglyme to other nickel salts, such as Ni(OTf)2 and NiCl2·diglyme led to lower yields (Table 1, entries 2 and 3). Similarly, changing the ligand for dtbbpy or

• resulted in a complex reaction mixture in which only traces of the desired enaminone 9a were detected (Table 1, entry 12). Longer reaction times also led to significant degradation, isolating the desired enaminone in only 18% yield (Table 1, entry 13). The reaction with 3-chlorochromone gives lower yield

Calcium waste as a catalyst in the transesterification for demanding esters: scalability perspective

• Anton N. Potorochenko and
• Konstantin S. Rodygin

Beilstein J. Org. Chem. 2025, 21, 1520–1527, doi:10.3762/bjoc.21.114

• of δ-valerolactone (4e) successfully led to the opening of the ring structure of the lactone and the formation of methyl 5-hydroxypentanoate (5e) in 91% yield at a catalyst loading of 1 wt % and for 3 h. The transesterification of triglycerides obtained from the esterification of linear saturated C5

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

• CH2Cl2 led to isolation of a colorless, crystalline material with a narrow melting point of 107‒109 °C (yield 66%). The 1H NMR spectrum registered for the purified product perfectly fitted with that one of the crude mixture and thereby confirmed formation of a single product with a single set of the Me‒S

• observed in reactions with 1b. For example, thermal decomposition of 2b performed in THF solution at 45 °C in the presence of 4a (molar ratio 1.1:1.0) led to the exclusive formation of the S-insertion product, i.e., dithioacetal 10c, which was isolated after chromatographic workup as a crystalline compound

• , trapping reactions (toluene, 60 °C) performed with 2d, functionalized with two spiro-cyclohexyl rings, and 5-mercaptotetrazoles 4a‒e led selectively to dithioacetals 10m‒q, which could be separated chromatographically as crystalline materials in good yields (46‒89%). Isomeric thioaminals of type 9 were not

Photoredox-catalyzed arylation of isonitriles by diaryliodonium salts towards benzamides

• Nadezhda M. Metalnikova,
• Nikita S. Antonkin,
• Tuan K. Nguyen,
• Natalia S. Soldatova,
• Alexander V. Nyuchev,
• Mikhail A. Kinzhalov and
• Pavel S. Postnikov

Beilstein J. Org. Chem. 2025, 21, 1480–1488, doi:10.3762/bjoc.21.110

• as Cs2CO3 (Table 1, entry 10) and KOH (Table 1, entry 11) led to diminished yields, reducing the product formation to 30% and 11%, respectively. In both cases we observed substantial decomposition of the iodonium salt affecting the yield of the desired product. We also performed the reaction with

• photochemical reactions such as the reagents concentrations and ratio. Surprisingly, both dilution of the reaction mixture to 0.05 M and concentration to 0.2 M led to reduced yields (Table 1, entries 12 and 13) compared to the optimal concentration of 0.1 M. Furthermore, the yield of 2aa exhibited minimal

• [Ru(bpy)3](PF6)2 as the photocatalyst, under an Ar atmosphere with irradiation by blue LED light (Table 1, entry 2). With the optimized conditions in hands, a series of benzamides 2aa–je were synthesized using various symmetrical diaryliodonium salts 1a–k and isonitriles (Scheme 2). The analysis of