A chiral LC–MS strategy for stereochemical assignment of natural products sharing a 3-methylpent-4-en-2-ol moiety in their terminal structures

• Rei Suo,
• Raku Irie,
• Hinako Nakayama,
• Yuta Ishimaru,
• Yuya Akama,
• Masato Oikawa and
• Shiro Itoi

Beilstein J. Org. Chem. 2025, 21, 2243–2249, doi:10.3762/bjoc.21.171

• –MS detection of the MPO-derived fragment and to achieve a separation of four candidate stereoisomers. To this end, methylation of commercially available methyl acetoacetate (2) and subsequent reduction of the ketone carbonyl group was carried out to prepare a mixture of four stereoisomers of methyl 3

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

• photoswitching event involves a molecular size reduction between the E- and Z isomers, thereby driving structural changes that enable applications in molecular machines, biological allosteric modulators, and advanced functional materials (Figure 1a) [9][10][11]. Despite the widespread interest in azobenzenes

• batch of Cs2CO3 showed a dramatic reduction in product yield (Table 1, entry 12). Control experiments with varying amounts of water (0–10 equiv) demonstrated that a small amount of water is crucial for the reaction (Supporting Information File 1, Table S7 and Table 1, entry 11). This effect, previously

• reported in Buchwald–Hartwig reactions, enhances yield by facilitating the reduction of Pd(II) to Pd(0) and improving the solubility of the base [56]. To ensure the generality of the conditions, 1-bromo-2-(trifluoromethoxy)benzene was also tested, yielding the desired azobenzene 3c in 69% yield with the

Electrochemical cyclization of alkynes to construct five-membered nitrogen-heterocyclic rings

• Lifen Peng,
• Ting Wang,
• Zhiwen Yuan,
• Bin Li,
• Zilong Tang,
• Xirong Liu,
• Hui Li,
• Guofang Jiang,
• Chunling Zeng,
• Henry N. C. Wong and
• Xiao-Shui Peng

Beilstein J. Org. Chem. 2025, 21, 2173–2201, doi:10.3762/bjoc.21.166

• ] generated [Cp2Fe]+ along with cathodic reduction of MeOH to H2 and MeO− acting as a base. Deprotonation of 1a using MeO− produced the anion A, which underwent single-electron transfer (SET) with [Cp2Fe]+ to give the nitrogen-centered radical B with regeneration of [Cp2Fe] [164][165][166][167][168][169][170

• ][194][195][196][197][198][199][200], the authors proposed a possible reaction mechanism. For the synthesis of 11a in Pt plate electrodes, two-electron anodic oxidation of I− formed I+. Addition of I+ to C≡C in 10 resulted in the production of A. Meanwhile, continuous reduction of H2O at the cathode

• formed H2 and HO−. The anti-nucleophilic attack of the N atom in A and the following HO− facilitated deprotonation and formed the corresponding 3-iodoindole 11a. Excessive-reduction (a minor side-reaction) of 11a took place as well in certain instances, resulting in the formation of 12a. And for the

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

• -Hydroxypropanal (3-HPO) and 2,3-dihydroxypropanal (2,3-HPO) Xu et al. reported the cross-aldol reaction of formaldehyde and acetaldehyde for the synthesis of 3-hydroxypropanal and further reduction to 1,3-propanediol (PDO). The reaction was promoted by X-5Mg/SiO2 and Mg/SiO2 (X = Mn, Co, Ni, Fe) catalysts

• biomass-based molecule and widely used building block in the food industry as flavoring compound. It can be synthesized from diacetyl by reduction using enzymes such as Aerobacter aerogenes [102] or thiamine diphosphate-dependent lyase (ThdP-lyase) [103]. The biotechnological production of chiral acetoin

• high reactivity of HFO permitted that a limited loading of catalyst could be employed. The reduction of the Friedel–Crafts adduct gave the targeted indoyl lactones with good yield (Scheme 38) [123]. Bos and Riguet reported the one pot synthesis of α,γ-substituted chiral γ-lactones from HFO. The

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 desymmetric enantioselective reduction of cyclic 1,3-dicarbonyl compounds is a powerful tool for the construction of ring systems bearing multiple stereocenters including all-carbon quaternary stereocenters, which are widely useful chiral building blocks for the total synthesis of structurally

• synthesis of complex terpenoid and alkaloid natural products by strategically applying desymmetric enantioselective reduction. Advance before 2016 in this area has been overviewed in an elegant review article. Since then, a series of more challenging terpenoid and alkaloid natural products have been

• synthesized utilizing a desymmetric enantioselective reduction strategy of cyclic 1,3-dicarbonyl compounds as a key transformation. This review will summarize the application of this strategy in the total synthesis of terpenoid and alkaloid natural products from the year 2016 to 2025. We first focus on the

Bioinspired total syntheses of natural products: a personal adventure

• Zhengyi Qin,
• Yuting Yang,
• Nuran Yan,
• Xinyu Liang,
• Zhiyu Zhang,
• Yaxuan Duan,
• Huilin Li and
• Xuegong She

Beilstein J. Org. Chem. 2025, 21, 2048–2061, doi:10.3762/bjoc.21.160

• reduction of ketone using SmI2 and propionaldehyde provided 15 diastereoselectively. Friedel–Crafts cyclization using trimethyl orthoformate and TMSOTf provided the cyclic acetal moiety to be oxidized with PDC, delivering the isocoumarin skeleton in 16. Chemoselective removal of the ester with the lactone

• underwent dehydroxylation protocol involving base-promoted mesylate elimination and catalytic hydrogenation reactions, providing 31a. Reduction of lactam and ester in one pot with LiAlH4 and acid-promoted hydrolysis of ketal protection to ketone furnished 32a. Finally, oxidation of the primary alcohol to

• , we treated it to Zn powder in AcOH to facilitate the N-walking transformation, and generated keto-ibogamine product 33 as a mixture of diastereomers (Scheme 4c). Then, reduction of ketone to methylene under Wolff–Kishner–Huang conditions provided ibogamine and its epimer in a 1:1.3 ratio. This result

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