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

• 22, 14195 Berlin, Germany School of Natural and Environmental Sciences, Newcastle University, Bedson Building, Newcastle upon Tyne, NE1 7RU, UK 10.3762/bjoc.21.153 Abstract Light-mediated methodologies for the reduction of acylazolium species generated during N-heterocyclic carbene (NHC)-catalyzed

• reactions have been developed. Employing the simple amine, DIPEA, as the terminal reductant, products resulting from overall 2-electron or 4-electron-reduction processes could be obtained using either a photocatalytic approach under blue light irradiation or directly under UV-A light irradiation without an

• additional photocatalyst. Moreover, under the same photocatalyst-free conditions, UV-A-light-mediated reduction could be achieved using triethylsilane as the only reductant with subsequent desilylation and NHC elimination with fluoride delivering the corresponding aldehyde product. Keywords: carbenes

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

• as a single diastereomer. Subsequently, one-pot transesterification and palladium-catalyzed decarboxylative allylation delivered compound 25 in 72% yield. Next, we expected that we could perform a chemo- and diastereoselective reduction of the ketone to introduce the hydroxy group at C9 in a single

• 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

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

• triflate 46, alkylation with sulfone 47 via treatment with butyllithium and hexamethylphosphoramide (HMPA) yielded the coupling product 48 as a mixture of diastereoisomers in 60% yield. Ultimately, single-electron reduction removed both the sulfone and benzyl groups of 48, furnishing (S)-α-tocotrienol (49

• bromide 71 in two steps. Lipase PS-mediated desymmetrization of 72 with vinyl butanoate provided monoester 73 in 90% yield with 97% ee. To obtain (S)-Rosaphen (74), monoester 73 was converted via mesylation followed by hydride reduction. In contrast, the synthesis of (R)-Rosaphen (75) required a four-step

• sequence comprising TBS protection, ester hydrolysis, mesylation, and hydride reduction. In 2014, Tokuyama and co-workers accomplished the total synthesis of (−)-petrosin and (+)-petrosin, two marine-derived bisquinolizidine alkaloids [45]. They first completed the synthesis of (−)-petrosin (84) (Scheme

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

• sufficient ionic conductivity is crucial to achieve efficient conversion (Table 1, entry 10). Lastly, replacing tetraethylammonium tetrafluoroborate with tetrabutylammonium tetrafluoroborate resulted in a negligible reduction of the chemical efficiency (Table 1, entry 9 vs 11). As demonstrated by Shono and

• 1a shows one distinct reductive peak at −1.75 V. Upon addition of one equivalent of MsOH, monoprotonated species 3a is formed, and a shift of the reduction peak to −1.92 V was observed. Subsequent addition of a second equivalent of acid leads to the formation of the bisprotonated species 4a, and as

• consequence, a shift of the reduction peak to −1.82 V was observed. However, the addition of three equivalents of methanesulfonic acid (corresponding to the typical reaction conditions) results in a decrease in the intensity of the reduction peak at −1.81 V. This observation is presumably associated with the

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

• extent of alkyl grafting, the –CH2– content in the pores of KSU-1n-Hex and KSU-1C14 is still greater than for KSU-1iPr and KSU-1t-Bu, assuming a uniform distribution of alkyl chains. Additionally, although the introduction of large alkyl substituents in a MOF is associated with a reduction in pore

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

• be synthesised through oxidation of aminoheteroarenes 12 (Scheme 4A) or reduction of nitroheteroarenes 13 (B). Bayer–Mills coupling (Scheme 4C) is suitable for both symmetric and asymmetric targets, usually in acidic conditions. Basic conditions [14] are more effective with very electron-poor

• (37) followed by reduction with Zn/Ba(OH)2 and partial re-oxidation (Scheme 12A) [52]. They can also be obtained from o-halogenated benzyl bromides 40 by lithium–halogen exchange followed by nucleophilic substitution and a second lithium–halogen exchange with iodine (Scheme 12B) or by nickel-catalysed

• reductive cross-coupling of benzyl halides when substituents prone to reduction (CN, esters) are present (Scheme 12C). The Ullman–Goldberg coupling of 41b with Boc-hydrazine followed by deprotection and oxidation then affords 35 [55]. Asymmetric diazocines can be synthesised by Sonogashira cross-coupling

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

• , FeCl3·6H2O provided the best results (Table 1, entry 2). A further reduction in catalyst loading from 25 mol % to 20 mol % and 10 mol % resulted in a noticeable decrease in both selectivity and conversion efficiency (Table 1, entries 7 and 8). This is likely due to insufficient C(sp2)–C(sp2) bond

Research progress on calixarene/pillararene-based controlled drug release systems

• Liu-Huan Yi,
• Jian Qin,
• Si-Ran Lu,
• Liu-Pan Yang,
• Li-Li Wang and
• Huan Yao

Beilstein J. Org. Chem. 2025, 21, 1757–1785, doi:10.3762/bjoc.21.139

• destruction of aromatic macrocycles and their components. The external triggers include: pH [93], oxidation–reduction states [94], enzymatic actions [95], and light [96]. Specifically, within host–guest frameworks, the capability to meticulously regulate the assembly of complexes and synchronize them with

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

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

• halogen atom transfer (XAT) agent [17][18]. Standard reduction potentials illustrate that hypophosphite is a powerful four-electron reductant [19]. Our previous studies have proved that NaH2PO2 can be a selective reducing agent in the catalyst-free reductive amination process [20][21][22] that can impart

• reaction medium, thereby preventing their reduction. This fact and the result of the control experiment where Schiff base was used as a starting material (Scheme 3a) demonstrated that Schiff base was not an intermediate in the developed reaction. The reactions between carbonyl compounds and secondary

• check the reduction pathway D-labeling experiments were carried out. The experiments with D3PO2 illustrated that D-atoms were distributed between α- and β-positions to nitrogen in the product in case of both reduction of enamine and reductive amination of cyclohexanone with morpholine (Scheme 4a

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

• . Moreover, an axially chiral tertiary alcohol-phosphine 42 was prepared from 39a through a three-step procedure including N-methylation, reduction of phosphine oxide, and Grignard addition to ester. Subsequently, 42 was applied as a bifunctional Lewis base organocatalyst in the formal [4 + 2] cyclization

• functionality in 63 allowed for versatile derivatizations, such as reduction, reductive amination, condensation, and olefination, which further expanded the structural diversity of the resulting products. Summary and Outlook The past few years have witnessed exciting progress in developing catalytic asymmetric

Transition-state aromaticity and its relationship with reactivity in pericyclic reactions

• Israel Fernández

Beilstein J. Org. Chem. 2025, 21, 1613–1626, doi:10.3762/bjoc.21.125

• Diels–Alder reactions. We then explored whether the aromaticity of the involved transition states plays a role in the observed reduction of the barriers. To this end, we computed the nuclear independent chemical shift (NICS) [44] values at the (3, +1) ring critical point of the electron density of the

• repulsion between the deformed reactants (Figure 2b). The less destabilizing Pauli repulsion computed for the catalyzed cycloaddition directly originates from the reduction of the electron density at the reactive C–C double bond of the dienophile, which translates into a lower <π(diene)|π(dienophile

• LAs [66] (Table 2). As expected, we found that the reduction of the activation barrier (up to ca. 25 kcal/mol) directly correlates with the relative Lewis acidity of the catalyst. In addition, the process becomes more and more asynchronous as the acidity of the catalyst increases, which strongly

Chemical synthesis of glycan motifs from the antitumor agent PI-88 through an orthogonal one-pot glycosylation strategy

• Shaokang Yang,
• Xingchun Sun,
• Hanyingzi Fan and
• Guozhi Xiao

Beilstein J. Org. Chem. 2025, 21, 1587–1594, doi:10.3762/bjoc.21.122

• comparison with previous, traditional, and time-consuming synthesis of PI-88 glycan components, the one-pot glycan assembly strategy has some advantages, including: 1) acceleration of glycan synthesis, 2) avoidance of purification of intermediates during glycosylation intervals, and 3) reduction of chemical

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

• for evaluating the influence of particular chemical compounds on cell lines. The most widely recognised method for assessing the impact of specific chemical compounds on specific cell types is the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The reduction of the

Highly distinguishable isomeric states of a tripodal arylazopyrazole derivative on graphite through electron/hole-induced switching at ambient conditions

• Himani Malik,
• Sudha Devi,
• Debapriya Gupta,
• Ankit Kumar Gaur,
• Sugumar Venkataramani and
• Thiruvancheril G. Gopakumar

Beilstein J. Org. Chem. 2025, 21, 1496–1507, doi:10.3762/bjoc.21.112

• electronic coupling between molecules and the metal. We are unable to predict the exact number of charges in the molecule while switching, but what we could demonstrate is that charging can lead to a reduction in the HOMO–LUMO gap, as observed in the experiment. Thus, we propose that the reduction in the

Heterologous biosynthesis of cotylenol and concise synthesis of fusicoccane diterpenoids

• Ye Yuan,
• Zhenhua Guan,
• Xue-Jie Zhang,
• Nanyu Yao,
• Wenling Yuan,
• Yonghui Zhang,
• Ying Ye and
• Zheng Xiang

Beilstein J. Org. Chem. 2025, 21, 1489–1495, doi:10.3762/bjoc.21.111

• (7) and R (8) (Scheme 1). The secondary hydroxy group of brassicicene I was selectively TBS-protected in the presence of TBSOTf and 2,6-lutidine to give compound 13 in 93% yield. Then, compound 13 underwent oxidative rearrangement with PCC to afford ketone 14 in 61% yield. Under Luche reduction

• conditions, compound 15 and its diastereomer were obtained in a total yield of 90% at a ratio of 1:0.7. To improve the diastereoselectivity, we examined other reduction conditions and found that ʟ-Selectride afforded compound 15 in 90% yield with a dr of 9:1. Upon desilylation with TBAF, compound 15 was

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

• conditions is due to a favorable formation of EWG-substituted aryl radicals from the iodonium cation, based on their reduction potentials and bond-dissociation energies calculated by Romanczyk and Kurek [45]. The reduction potential in SET reactions for iodonium salts with EWG-substituted aryls significantly

• resulting aryl radical is subsequently captured by an isonitrile molecule, forming an imidoyl radical intermediate X1. The intermediate X1 facilitates the reduction of the Ru(III) species back to Ru(II) thereby completing the photoredox cycle, with the formation of the cationic intermediate X2. We propose

Copper catalysis: a constantly evolving field

• Elena Fernández and
• Jaesook Yun

Beilstein J. Org. Chem. 2025, 21, 1477–1479, doi:10.3762/bjoc.21.109

• , who focus on the preparation of phenethylamines and phenylisopropylamines via reduction of substituted β-nitrostyrenes using a system of sodium borohydride and copper(II) chloride [9]. The transformations are performed in one pot and proceed under mild conditions. The β-nitrostyrene products could be

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

• under MW irradiation in less than a third of the time, with the product obtained in pure form without the need for chromatographic purification. A further reduction in reaction time to 1.5 hours was possible at 80 °C, while incomplete conversion was observed after 1 hour (Table 3, entries 17 and 18

Advances in nitrogen-containing helicenes: synthesis, chiroptical properties, and optoelectronic applications

• Meng Qiu,
• Jing Du,
• Nai-Te Yao,
• Xin-Yue Wang and
• Han-Yuan Gong

Beilstein J. Org. Chem. 2025, 21, 1422–1453, doi:10.3762/bjoc.21.106

• two π-extended hetero[6]helicenes – 61a and 61b – incorporating thiadiazole and selenadiazole moieties, respectively [76]. Substitution of sulfur with selenium enhanced intermolecular interactions and led to a notable reduction in the optical bandgap, highlighting the effectiveness of heteroatom

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

• ) (Figure 8b) the needed reduction is observed in position 2 for CH3 group (weakly), substantially for NR2 in position 4 and strongly for all substituents in position 6. The value of ΔE(KE-E) (Figure 8c) has to be larger than 2, but it cannot be achieved. Almost all functional groups on position 2 and all

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

• mechanism was proposed to start with formation of a Fe(III)–H species which delivers a hydrogen radical to the less-substituted end of the alkene. The resulting tertiary C-centred radical 147 then couples with a Ni(0) complex (generated by a reduction of the Ni(II) pre-catalyst) and after an oxidative

• addition of the aryl halide, the disubstituted oxetane product is generated by a reductive elimination. Finally, the two catalytic cycles are closed by an oxidation/reduction process: the Fe(II) species is reoxidised by atmospheric oxygen and the Ni(I) complex is reduced by the added manganese powder. In

• reduction of the Ni(II) pre-catalyst) via oxidative addition, radical coupling and reductive elimination. The last step is a single-electron transfer between the resulting Ir(II) and Ni(I) complexes, regenerating the active catalysts and closing the two cycles. In 2021, Romanov-Michailidis and Knowles et al

Recent advances in amidyl radical-mediated photocatalytic direct intermolecular hydrogen atom transfer

• Hao-Sen Wang,
• Lin Li,
• Xin Chen,
• Jian-Li Wu,
• Kai Sun,
• Xiao-Lan Chen,
• Ling-Bo Qu and
• Bing Yu

Beilstein J. Org. Chem. 2025, 21, 1306–1323, doi:10.3762/bjoc.21.100

• amidyl radicals from HRP: (a) direct single-electron oxidation of amide HRP in the presence of photocatalyst and a base via a proton-coupled electron transfer (PCET) process by the cleavage of the N–H bond; (b) single-electron reduction of HRP catalyzed by photocatalyst via a single-electron transfer

• 29 in the presence of 4CzIPN and a base via a PCET process. Radical 29 subsequently engaged in a HAT process with substrate 26, generating either a Si radical or a Ge radical 28. Following this, radical 28 underwent Giese addition with activated alkenes. The reduction of species 31 was efficiently

• cleavage N-Amidopyridinium salts are known to undergo SET reduction, leading to the formation of amidyl radicals. Hong’s group has made significant advances in the cleavage of N–N bonds in recent years. Through SET reduction of N-amidopyridinium salts to generate amidyl radicals, Hong’s group has

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

• . Dehydrogenation played a pivotal role as a key step also in the synthesis of larger π-scaffolds. For example, Murata and co-workers reported the synthesis of an azulene containing isomer of benzo[a]pyrene 9 (Scheme 2) [33]. Reduction of ketone 7 using LiAlH4 resulted in alcohol 8 which was subsequently

• 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

• constructed by condensation of dialdehyde 160 with compounds 161–163 yielding diketones 164–166. Next, diketones 164–166 were subjected to nucleophilic addition reaction by lithiated triisopropylsilyl (TIPS) acetylene, followed by SnCl2-mediated reduction of the intermediate diols. Finally, azulene-embedded

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

• then reacts with sodium trifluoromethanesulfinate (36) to form a sulfonyl hypobromite intermediate 38 (Scheme 20). This intermediate undergoes reduction at the cathode, leading to the formation of oxygen-centered and sulfonyl-centered radicals, which subsequently form a trifluoromethyl radical. This

• (4CzIPN), leading to either the reduction of sulfoxonium ylides to hydrocarbons or their participation in radical coupling with alkenes for carboarylation reactions. The reactions were carried out under mild, room temperature conditions using a DCM/H2O 1:2 solvent system. Various reaction conditions were

• -methacryloylbenzamide derivatives (Scheme 44), both alkyl chlorides and bromides gave the expected six-membered annulated products 83a–c in satisfactory yields. A proposed mechanism, as shown in Scheme 45, involves the photoexcitation of Pd(0) to its excited state II, facilitating the single-electron reduction of the