Recent advances in total synthesis of illisimonin A

• Juan Huang and
• Ming Yang

Beilstein J. Org. Chem. 2025, 21, 2571–2583, doi:10.3762/bjoc.21.199

• product. They resolved racemic intermediate 27 by derivatization with (S)-1-(1-naphthyl)ethyl isocyanate, followed by separation of the resulting diastereomers via silica gel chromatography (Scheme 3). By converting diastereomer 32 to (−)-illisimonin A, the absolute configuration of the natural product

• , illisimonin A was obtained only as a minor product. When O2 was replaced with the nitroaromatic compound 66 [38], the diastereoselectivity was reversed, thereby providing illisimonin A in 57% yield as a single diastereomer. The authors proposed that a hydrogen bond between the nitro group of 66 and the C8

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

• platform for synthesizing other family members and their structural analogues. The synthetic sequence commenced with common intermediate 103 as the starting material. Stereoselective reduction of 103 yielded compound 111 as a single diastereomer. Systematic optimization of reaction conditions revealed that

Ni-promoted reductive cyclization cascade enables a total synthesis of (+)-aglacin B

• Si-Chen Yao,
• Jing-Si Cao,
• Jian Xiao,
• Ya-Wen Wang and
• Yu Peng

Beilstein J. Org. Chem. 2025, 21, 2548–2552, doi:10.3762/bjoc.21.197

• (Scheme 3). By slightly modifying the reaction conditions of our previous studies [11][12], the expected bicyclization of 5 occurred smoothly, resulting in an efficient construction of the trans-tetrahydronaphtho[2,3-c]furan skeleton embedded in 13, which could be separated from the other diastereomer [14

Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds

• Natalya Akhmetdinova,
• Ilgiz Biktagirov and
• Liliya Kh. Faizullina

Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185

• 111 led to (±)-preterrenoid (107) with 68% yield, which was subjected to stereoselective oxidation with magnesium monoperoxyphthalate (MMPP) to give (±)-terrenoid (108) as a single diastereomer. Subsequent treatment of the key precursor 108 with catalytic amounts of NaOMe in MeOH resulted in

• . Irritation of a solution of 124 in CH3OH using a medium-pressure Hg lamp resulted in the formation of methyl ester 125 as a single diastereomer with a yield of 30%. Due to the decrease in the efficiency of this reaction at higher loads (>50 mg), the thermal conditions for the Wolff rearrangement were tested

• (BnOH, 2,4,6-collidine, 160 °C). The desired benzyl ester 126 was isolated as single diastereomer with a yield of 56% yield. Reduction of 126 with LiAlH4 followed by oxidation with Dess–Martin periodinane (DMP) led to the synthesis of a key aldehyde 127, with a yield of 75% in two steps. The target

The high potential of methyl laurate as a recyclable competitor to conventional toxic solvents in [3 + 2] cycloaddition reactions

• Ayhan Yıldırım and
• Mustafa Göker

Beilstein J. Org. Chem. 2025, 21, 2389–2415, doi:10.3762/bjoc.21.184

• purification techniques [62][63][64]. Synthesis of pyrrolo-isoxazolidines utilizing nitrosoarenes via the multicomponent strategy is indeed feasible [65][66]. In a similar manner, Chakraborty obtained diastereomer products, primarily in cis configuration, from the cycloaddition reaction of a fluoro or a furyl

• transition state (Scheme 2). Meanwhile, the diastereomeric ratio of interest can be determined by integrating the 1H NMR spectra, in particular by selecting the appropriate signal pairs (one from each diastereomer) belonging to the respective cycloaddition product. An example of these selected protons (trans

• ) between the phenyl rings substituted on the nitrogen atoms of both maleimide and nitrone [109]. The most significant evidence confirming the interactions that determine the diastereoselectivity observed here is that the cis diastereomer is the major addition product in the dipolar cycloaddition reaction

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

• moderate diastereoselectivity; this was followed by Mn(III)-catalyzed metal-hydride hydrogen atom (MHAT) transfer to reduce the endocyclic olefin, forming 41 as a single diastereomer. Subsequent transformations – including a Wittig reaction, demethylation, and oxidation of the resulting phenol to a p

• stereoretentive coupling at C2 with aryl bromide 86, yielding 88 as a single diastereomer. Manipulation of the protecting group of 88 arrived at lycoplatyrine A (89). Notably, 87 and related α-hydroxy-β-lactams were obtained via Norrish–Yang cyclization of the corresponding neat α-keto amides in the solid state

Further elaboration of the stereodivergent approach to chaetominine-type alkaloids: synthesis of the reported structures of aspera chaetominines A and B and revised structure of aspera chaetominine B

• Jin-Fang Lü,
• Jiang-Feng Wu,
• Jian-Liang Ye and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2025, 21, 2072–2081, doi:10.3762/bjoc.21.162

• reported structures of alkaloids aspera chaetominines A and B have been synthesized. Moreover, the four-step synthesis of the reported structure of aspera chaetominine B generated another diastereomer that was converted in one-pot to (–)-isochaetominine C, which turned out to be the revised structure of

• synthesis of natural products [10][55][56], in early 2009, our group disclosed a highly efficient four-step, enantioselective and diastereodivergent synthesis of (–)-chaetominine (1) and with one more step, of another diastereomer [57][58]. The strategy features a DMDO oxidation-triggered [59] double

• (–)-isochaetominine A (4) and a diastereomer; 2) the diastereo- or enantiodivergent syntheses of chaetominine-family alkaloids and stereoisomers, and 3) the reported structures of aspera chaetominines A and B (12 and 13) and revised structure of aspera chaetominine B: 6 [(–)-isochaetominine C]. Results and Discussion

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

• divergent coupling approaches, and the stereocontrol with Evans oxazolidinone was always reliable to obtain an sole diastereomer (Scheme 6d). Bioinspired concise and scalable total synthesis sarglamides In 2023, Yue and co-workers investigated the ingredients of the Chinese folk medicine Sarcandra glabra

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

• a single diastereomer (Table 1, entry 4). To explain this diastereoselectivity, we hypothesize that the C–O bond, which occupies an axial position in the proposed transition state TS-1, could avert an additional hyperconjugative interaction (σ*C-O/π) that renders the reacting C=C bond electron

• was treated with p-toluenesulfonic acid (p-TSA) in EtOH at room temperature to afford ketal 24 in 83% yield as a single diastereomer. Subsequently, palladium-catalyzed decarboxylative allylation delivered compound 25 in 89% yield. The efficiency of our first-generation strategy for asymmetric

• 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

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

• monobenzoate 142 in 94% yield along with 4% yield of its diastereomer (dr = 24:1). Following a four-step conversion of 142 to epoxide 143, reductive cleavage produced a diol intermediate, which was subjected to chemoselective glycosylation with compound 144 to provide compound 145. After a four-step

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

[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

• a single diastereomer with traces or no of the other one (dr >19:1). For the derivative 5e with an oxygen-containing heterocycle, we failed to obtain the corresponding products under any of the proposed conditions. In all cases, we observed only very complex mixtures with traces of the target

• were formed, and the transformation rate was extremely low. This outcome may be attributed to the electron-acceptor properties of the oxygen atom, which likely disrupt the cycloaddition process. NMR analysis confirmed that each heterocyclic ring formed products exclusively as a single diastereomer

• reaction is shown to proceed with exclusive formation of a single diastereomer of the spirocyclic product, the exact configuration of which is dependent on the nature of heterocycle employed. Key stereo- and electronic factors for successful realization of the cycliaddition reaction were discovered, which

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

• -6 is a good substrate for an aza-Diels–Alder reaction with tosylisocyanate (TsNCO) providing the oxazolo[3,2-c]pyrimidine derivative 7 as the only detectable diastereomer (Scheme 6) [22][23][24]. Oxazolo[3,2-c]pyrimidines are substructures in several pharmaceutically relevant compounds such as

• competent substrate for the aza-Diels–Alder reaction in with TsNCO to give oxazolo[3,2-c]pyrimidine derivative 7 as a single diastereomer. Proposed approach for the preparation of vinyloxazoline 6. Synthesis of furfuryl amino alcohols S-2d and R-2d and their electrochemical oxidation to esters S-3d and R-3d

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

• (4) was treated with methyl pyruvate in acetonitrile (Table 1, entry 1) to produce pyruvylated galactose 5. The use of polar solvents such as acetonitrile promotes the formation of the more thermodynamically favorable diastereomer [21][28][29]. For the property of the R-isomer of 5, the 13C NMR

3-Aryl-2H-azirines as annulation reagents in the Ni(II)-catalyzed synthesis of 1H-benzo[4,5]thieno[3,2-b]pyrroles

• Julia I. Pavlenko,
• Pavel A. Sakharov,
• Anastasiya V. Agafonova,
• Derenik A. Isadzhanyan,
• Alexander F. Khlebnikov and
• Mikhail S. Novikov

Beilstein J. Org. Chem. 2025, 21, 1595–1602, doi:10.3762/bjoc.21.123

• diastereomer and characterized by NMR and HRMS data. Compound 13 is likely formed from aziridine 14 via the N→N acetyl group transfer and subsequent isomerization of the acetylaziridinyl substituent. The constitutional isomer of indole 9a, indole 15, having a nucleophilic reaction center in the β-position of

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

• 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

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

• extended enolate 96 to the ketone, cyclisation via addition/elimination and base-catalysed epimerisation towards the thermodynamically more stable diastereomer. In 2019, Nair and co-workers showed that this formal cycloaddition can also be performed with 1,2-dicarbonyls as electrophiles and under an

• epimerisation to obtain diastereoenriched spirocycles, utilising t-BuOK/t-BuOH for the anti-diastereomer 163 and LDA/PivOH at −78 °C for the syn-diastereomer 162 (dr >10:1 in both protocols). Mechanistic and computational studies suggested the following series of steps: excitation of 159 via energy transfer

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

• , heterogeneous catalytic hydrogenation of the enamine with palladium on carbon was chosen. While the hydride reduction of the acyliminium intermediate gave a nearly 1:1 diastereomer ratio, a 9:1 ratio was obtained for the catalytic hydrogenation (Scheme 4). While the hydride reduction of the N-acyliminium

• kinetically controlled diastereofacial selectivity. The resulting diastereomers are separable by chromatography. 1H NMR was used to assign the configuration of the 2 diastereomers [53][54][55]. Carbon C2 is R-configured, as ᴅ-2-aminoadipic acid (1) was employed as the starting material. The minor diastereomer

• evident by an antiperiplanar coupling of the axially positioned H6 with 3J(H6,H5,pro-S) = 11.7 Hz and a gauche coupling with 3J(H6,H5,pro-R) = 3.3 Hz. The major diastereomer, assigned as (2R,6S)-9 was found as a mixture of conformers in solution (Figure 2a). Like for (2R,6R)-9, one conformer of (2R,6S)-9

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

• cyclization to form products in high yields and excellent enantioselectivities. Notably, only a single diastereomer was produced in each case. The single-crystal X-ray crystallography revealed a cis-configuration for both the alkene and ketone substituents on the enamide, indicating that the intramolecular

Harnessing tethered nitreniums for diastereoselective amino-sulfonoxylation of alkenes

• Shyam Sathyamoorthi,
• Appasaheb K. Nirpal,
• Dnyaneshwar A. Gorve and
• Steven P. Kelley

Beilstein J. Org. Chem. 2025, 21, 947–954, doi:10.3762/bjoc.21.78

• single regioisomer and diastereomer of B was formed (within the limits of 1H NMR detection), attesting to very selective reactivity. Here and in related projects, we found that many I(III) sources could generate a nitrenium ion, including iodosobenzene (PhIO) and iodomesitylene diacetate. However, unless

Cu–Bpin-mediated dimerization of 4,4-dichloro-2-butenoic acid derivatives enables the synthesis of densely functionalized cyclopropanes

• Patricia Gómez-Roibás,
• Andrea Chaves-Pouso and
• Martín Fañanás-Mastral

Beilstein J. Org. Chem. 2025, 21, 877–883, doi:10.3762/bjoc.21.71

• the base metal cation. Gratifyingly, we observed that the use of LiOt-Bu led to the formation of product 2 as a single diastereomer (Table 1, entry 5). A slightly lower diastereoselectivity was observed when KOt-Bu was used, which also gave rise to 2 in diminished yield (Table 1, entry 6). The nature

• cases, with SIPr providing the best result (Table 1, entry 11). Under these optimized conditions, product 2 was isolated in 60% yield as a single diastereomer. The relative configuration of 2 was determined by two-dimensional NMR analysis (see Supporting Information File 1 for details). This

• . However, when the reaction was carried out with KOt-Bu, we observed the selective conversion of 9 into product 20 featuring a different cyclopropane scaffold. Slight modification of the reaction conditions allowed us to obtain product 20 in 56% yield as a single diastereomer (Scheme 5a). Taking advantage

Asymmetric synthesis of β-amino cyanoesters with contiguous tetrasubstituted carbon centers by halogen-bonding catalysis with chiral halonium salt

• Yasushi Yoshida,
• Maho Aono,
• Takashi Mino and
• Masami Sakamoto

Beilstein J. Org. Chem. 2025, 21, 547–555, doi:10.3762/bjoc.21.43

• , the reaction catalyzed by only 1 mol % of iodonium salt 9b provided the opposite diastereomer of 17a as the major product compared with that without a catalyst, which revealed the high catalytic activity of our catalyst. Further reaction conditions optimization was conducted using 9a as a catalyst

• amide moiety and with almost no enantioselectivity. Although the addition of a catalytic amount of 9e accelerated the reaction, the same diastereomer of 17b as the major product was obtained as for the reaction without a catalyst, which shows the importance of halonium salt moieties in our catalysts

• % catalyst loading. Although the diastereoselectivity of the products were moderate in most cases, the opposite diastereomer was obtained as the major product compared with reactions without a catalyst. To the best of our knowledge, the present paper is the first to report the asymmetric construction of β

Organocatalytic kinetic resolution of 1,5-dicarbonyl compounds through a retro-Michael reaction

• James Guevara-Pulido,
• Fernando González-Pérez,
• José M. Andrés and
• Rafael Pedrosa

Beilstein J. Org. Chem. 2025, 21, 473–482, doi:10.3762/bjoc.21.34

• a greater or lesser extent, in all the solvents tested except in water (Table 1, entry 19), where the mixture remains unchanged after 100 hours. The enantiomeric ratio of the diastereomer anti-1 depends on the solvent used, with toluene (Table 1, entry 22) providing the best results. Finally

• initially promotes deracemization by rapidly reacting with the enantiomer (3R,4S) of the diastereomer anti-1. Over time, the initial equilibrium is established either because the catalyst begins to react with the syn-diastereomer or because, once the retro-Michael reaction has occurred, the catalyst

• other Michael adducts prepared by reacting with differently activated ketones, the enantiomeric ratio of the isolated anti-diastereomer was excellent (entries 1 and 10–13, Table 5). Interestingly, the method also provides good resolution for Michael adducts 8 and 9 synthesized by reacting keto sulfones

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• , and with bulky substituents, the reaction did not proceed. Further derivatizations of the products were carried out: firstly, the derivative 35e was reduced using NaBH3CN to obtain 36 as a single diastereomer in a good yield. Next, a hydrolysis of 36 using concentrated sulfuric acid led to the 1,2