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

• , protection of the resultant primary alcohol, and hydrogenation afforded ketone 65. The LaCl3·LiCl-promoted addition of 65 with Grignard reagent followed by TES protection of the resulting secondary alcohol, regioselective deprotection of the TES group and in situ oxidation provided aldehyde 66. Next, 66

• underwent the 1,2-addition of isopropenyllithium reagent (prepared from n-BuLi/tetraisopropenyltin (67) [55]) and DMP oxidation to afford ketone 68. A three-step transformation including RCM, Mukaiyama hydration, and esterification, 68 was converted to methyl oxalate 69. Irradiation of the reaction mixture

• hydroxyketone 86 in 60% yield with 92% ee and 8.4:1 dr. A secondary hydroxy-directed Grignard reagent addition of 86 followed by selective protection, generated alcohol ester 87. After one recrystallization, the ee value of 87 could be increased to 99%. Subsequently, TMSOTf-promoted transacetalation and in situ

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

• -dithiane linchpin coupling (Scheme 3b). To our delight, using DDQ as the optimal oxidizing reagent, the expected THF-containing product 23 was generated as a sole diastereoisomer, suggesting the pQM 22 underwent oxa-Michael addition only with the C10 alcohol. The free C12 alcohol did not affect this

• proposed key transformations (Scheme 6). Starting from the diaryl-THF-type precursor 36 with a phenol moiety, oxidation of the phenol with hypervalent iodine reagent PIDA generated the putative oxa-carbenium intermediate 37, which successfully underwent the Friedel–Crafts cyclization to provide

Measuring the stereogenic remoteness in non-central chirality: a stereocontrol connectivity index for asymmetric reactions

• Ivan Keng Wee On,
• Yu Kun Choo,
• Sambhav Baid and
• Ye Zhu

Beilstein J. Org. Chem. 2025, 21, 1995–2006, doi:10.3762/bjoc.21.155

• substituents. Intuitively, the intrinsic spatial separation among prochiral stereogenic elements, the reactive sites, and the stereochemical-defining substituents makes stereoinduction for non-central chirality using a chiral catalyst or reagent particularly challenging. However, a quantitative

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

• the maximum of 50% achievable using DIPEA. This study also led to the development of a novel silane-mediated photoreduction method where triethylsilane serves as both as terminal reductant and alkoxide trapping reagent, with subsequent treatment with fluoride providing the corresponding aldehyde

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

• norlignans hyperione A and ent-hyperione B was reported by the Deska group (Scheme 4) [33]. The synthesis commenced with a two-step conversion of ketone 22 to alkyne 23. Pd-catalyzed Tsuji-type reaction with zinc reagent 24, followed by acetonide hydrolysis, furnished allenic diol 25. Treating allenic diol

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

• , 1,000 μM, 2,500 μM, and 5,000 μM. Each concentration was tested in triplicate. Control wells received an equivalent volume of culture medium without compounds and served as untreated negative controls. Cytotoxicity analysis of compounds. After 48 hours of treatment, MTT reagent was added to each well at

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

• the hydrogen transfer reagent (Scheme 11). Notably, when starting from macrocyclic substrates featuring relatively shorter ansa chains (11–14 members, see 38a–c), highly efficient kinetic resolution was achieved, resulting in both recovered (Rp)-38 and reductive amination products (Sp)-39 with high

• high enantioselectivity (Scheme 16). Notably, with the use of acyclic azodicarboxylate as amination reagent, the products exhibited both inherent chirality and intriguing C–N axial chirality (see 57a). This method demonstrates excellent substrate compatibility, accommodating various calix[4]arenes with

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

• a diazonium salt 113 and a nucleophile 114 (Scheme 35B) [113] or a Grignard/aryllithium reagent 115 and a diazo compound 116 (Scheme 35C) [108]. Acylhydrazones 110 can be synthesised by reaction of hydrazine with 118 and subsequent acid-catalysed condensation of 119 with carbonyl 120 (Scheme 36

[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

• tetrahydrothiophenes are known to exhibit different biological activities [8]. However, to date the use of this reagent in the synthesis of spirocyclic derivatives to our knowledge is underinvestigated [26][27]. Results and Discussion In this work we present a systematic study of [3 + 2] cycloaddition of thioformylium

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

• , condensation of N-sulfonylated 1,2-diphenylethane-1,2-diamines and cyclohexane-1,2-dicarboxylic acid, and the final cyclization with the in situ generated Hendrickson reagent. Keywords: bisimidazoline; cyclohexane; cyclohexane-1,2-dicarboxylic acid; 1,2-diphenylethane-1,2-diamine; Introduction Chiral

• )-2-amino-1,2-diphenylethyl]sulfonamides 2 in 61–74% yields. The sulfonamides 2 were then further reacted with (1S,2S)-cyclohexane-1,2-dicarboxylic acid (3) in the presence of EDCI (3-ethyl-1-(3-dimethylaminopropyl)carbodiimide hydrochloride) as a coupling reagent under the catalysis of DMAP (4

• in the formation of cyclohexane-1,2-dicarboxamides 4 due to their poor nucleophilicity. Finally, (1S,2S)-N1,N2-bis((1R,2R)-2-(sulfonamido)-1,2-diphenylethyl)cyclohexane-1,2-dicarboxamides 4 were cyclized with the Hendrickson reagent (triphenylphosphonium anhydride triflate in situ generated from

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

• this new molecular recognition motif to create a supramolecular amphiphilic reagent using WP7 and an amphiphilic paraquat derivative G2. This pH-responsive drug delivery system has considerable potential for future medical applications. Hydrophilic supramolecular polymers that respond to stimuli

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

• be isolated because of the low rotational stability [32]. Quinolinone rac-1a was converted to quinoline-thione rac-2a by reaction with Lawesson’s reagent, and subsequently, the enantiomers [(P)-2a and (M)-2a] were separated by MPLC using a chiral IH column. Unfortunately, the barrier value of

Continuous-flow-enabled intensification in nitration processes: a review of technological developments and practical applications over the past decade

• Feng Zhou,
• Chuansong Duanmu,
• Yanxing Li,
• Jin Li,
• Haiqing Xu,
• Pan Wang and
• Kai Zhu

Beilstein J. Org. Chem. 2025, 21, 1678–1699, doi:10.3762/bjoc.21.132

• compound production, fundamentally involving the interaction between organic substrates and nitrating reagents. The intrinsic kinetics of nitration processes are governed by the synergistic interplay between the substrate’s molecular architecture and nitrating reagent reactivity. Distinct substrate

• classifications necessitate tailored nitrating reagent selections, giving rise to fundamentally distinct mechanistic pathways. This reactivity is exemplified by the comparative kinetic profiles: N-nitration of amines and O-nitration of alcohols – facilitated by accessible lone electron pairs – exhibit markedly

• reagent, demonstrating broad functional group tolerance while revealing that only the N-nitro unit on N1 participates in nitroarene formation [8]. According to Yao et al., SO3H-functionalized imidazole ionic liquids (e.g., [MIMBs]HSO4, 98.1% yield) enabled efficient m-xylene nitration with mitigated

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

• undesired anomeric epimerization, leading to the production of two stereoisomers in a ratio of α/β = 1:1.6 [28][29]. To increase the yield and minimize anomeric epimerization, we employed the more reactive reagent, methyl 2,2-dimethoxypropanoate, which contains a hemiketal moiety. As expected, the reaction

• was significantly faster, and the starting material was completely consumed within 2 h, followed by deacetylation to yield the desired product 6 in 51% (Table 1, entry 3). The use of this more reactive reagent maintained high R-diastereoselectivity. It is hypothesized that this reaction will yield a

• same reaction mixture, in situ activation of disaccharide donor 8 and acceptor 9 using TolSCl/AgOTf reagent combination was introduced. This two-step, one-pot glycosylation gave a 42% yield of disaccharide 10, maintaining good β-stereoselectivity at the galactosyl linkage (α/β = 1:5.8). The 2

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

• unsymmetrical diisocyanide was used, the initial isocyanide insertion was found to be non-regioselective, delivering a 1:1 mixture of regioisomers (17c and 17c’). Intriguingly, 17a could act as a chiral acylating reagent, applying in the kinetic resolution of racemic primary amines rac-18. Additionally, after

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

• reaction, in which 2H-azirines act as the annulation reagent. Keywords: annulation; azirines; benzothiophenes; indoles; nickel catalysis; Introduction 2H-Azirines represent a valuable class of nitrogen heterocycles that are widely used as versatile building blocks in organic synthesis. In particular, the

• modified at the positions 1 and 2. The N-methylaza analog of the benzo[b]thiophene (N-methylindole) reacts similarly to provide the annulation product in moderate yield. The described reaction is the first example of a dealkoxycarbonylative annulation reaction using 2H-azirines as annulation reagent

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

• components of drug derivative formulations, present in more than 7,000 active pharmaceutical compounds [43], the possibility of introducing a pyridine ring into the enaminone structure could be useful for the development of new drug candidates. When pyrrolidine was used as amine reagent, the target enaminone

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

• the transesterification of 4a with methanol (2a). The detailed procedure and reagent loading are given in Supporting Information File 1 (section 2.7). After each reaction cycle, the catalyst was separated by centrifugation, then washed with methanol and hexane to remove organic impurities, dried at 80

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

• thiocarbonyl S-methanides 1a and 1b, respectively, in situ generated at 45 °C in absence of any trapping reagent, were described in earlier publications [6][10][11][12][13][14][28]. In the present study, the thermal stability of the new dispiro-1,3,4-thiadiazolines 2c and 2d was tested in THF solution at a

• regioselectivity in high yields. Upon heating to 65 °C in toluene solution, in analogy to the well-known compounds 2a and 2b, they extruded N2 and the in situ-generated reactive thiocarbonyl S-methanides 1c and 1d, in absence of any trapping reagent, underwent 1,3-dipolar electrocyclization yielding the

• crowded thioketones 7b [28], as well as 7c,d derived from cyclobutanedione. The in situ generation of sterically crowded thiocarbonyl S-methanides 1c,d (via a 1,3-dipolar cycloreversion) in absence of any trapping reagent and their electrocyclization (ring closure) leading to thiiranes 8a,b. Reactions 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

• cotylenin A and cotylenol (Figure 3a). Oxidation of brassicicene I with Dess–Martin reagent afforded intermediate 9 in 92% yield. The tertiary hydroxy group of compound 9 was further protected with a TMS group to provide compound 10 in 90% yield, a key intermediate in the synthesis of cotylenol and

N-Salicyl-amino acid derivatives with antiparasitic activity from Pseudomonas sp. UIAU-6B

• Joy E. Rajakulendran,
• Emmanuel Tope Oluwabusola,
• Michela Cerone,
• Terry K. Smith,
• Olusoji O. Adebisi,
• Adefolalu Adedotun,
• Gagan Preet,
• Sylvia Soldatou,
• Hai Deng,
• Rainer Ebel and
• Marcel Jaspars

Beilstein J. Org. Chem. 2025, 21, 1388–1396, doi:10.3762/bjoc.21.103

• the biogenesis of this heterocyclisation leading to the pseudomonine biosynthesis [23]. The absolute configuration of the threonine residue in compounds 1 and 2 was assigned as ʟ, based on the derivatization of 1 and 2 hydrolysates with ʟ-FDAA, a Marfey’s reagent, followed by chromatographic profiling

High-pressure activation for the solvent- and catalyst-free syntheses of heterocycles, pharmaceuticals and esters

• Kelsey Plasse,
• Valerie Wright,
• Guoshu Xie,
• R. Bernadett Vlocskó,
• Alexander Lazarev and
• Béla Török

Beilstein J. Org. Chem. 2025, 21, 1374–1387, doi:10.3762/bjoc.21.102

• still offered a reasonable increase in rates and thus, in yields. In addition to the synthetic advantages, the benefits HHP offers can also translate to green chemistry. The use of HHP extends the scope of solvent-, reagent- and catalyst-free reactions that significantly reduce workup and waste

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

• , the synthesis starts with the preparation of a reactive amine species 170 which is then reacted with a Grignard or, in case of ester-containing substrates, with an organozinc reagent. Because this method involves only two simple steps and is not limited to aryl groups, it provides a more rapid access

• that it likely proceeds through a p-quinone methide intermediate 213. The authors also demonstrated on two selected examples (214) that the products could be further derivatised to 3-substituted benzofurans 215 and benzindoles 216 with a hypervalent iodine reagent. In 2022, Bull et al. disclosed a

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

• (Figure 1c) [19][20][21][22][23][24][25][26][27], serve as key species for the HAT process. These HR were generated from different HAT reagent precursors (HRP) in a variety of strategies. Among these, amidyl radical HRPs have gained significant attention in recent years due to their ease of HRP synthesis

• /mol (Figure 2a) [28][29][30]. Almost 5 kcal/mol difference between two species could spontaneously undergo a HAT process. That also justifies the selectivity and efficiency of amidyl radical serving as HAT reagent. 2) Recent research indicated a critical correlation between electronic effects and

• radical anion 15 was reduced by the photocatalyst Ir(Fppy)3 from the reagent 11. The resulting anion 14 underwent aromatization to release a nitrile anion, subsequently yielding product 12. This strategy also successfully produced products 16 and 17 with yields of 85% and 56%, respectively, from

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

• radical then reacts with acrylamide to yield the desired product 37. As shown in Scheme 21, a visible light-induced trifluoromethylation/arylation using Umemoto’s reagent for the synthesis of trifluoromethylated oxindole derivatives was reported by Huang and Zhang’s group in 2021 [13]. This method is

• particularly noteworthy for its use at room temperature, requiring no transition metals, photocatalysts, or additives. Notably, Umemoto's reagent served as the trifluoromethyl source, and the reaction was facilitated under blue LED irradiation, achieving good to excellent yields. Moreover, this approach

• ), the process involves the homolytic cleavage of Umemoto's reagent 39 under visible light irradiation, releasing a trifluoromethyl radical 42. The radical then adds to the double bond of N-arylacrylamide, forming intermediate radical 43. Subsequently, this intermediate undergoes intramolecular