Palladium-catalyzed regioselective C1-selective nitration of carbazoles

• Vikash Kumar,
• Jyothis Dharaniyedath,
• Aiswarya T P,
• Sk Ariyan,
• Chitrothu Venkatesh and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2025, 21, 2479–2488, doi:10.3762/bjoc.21.190

• reagent resulted in complete loss of reactivity (Table 1, entry 12). Further, extending the reaction time had no significant effect on the yield (Table 1, entry 13). Finally, our investigation using various 3d transition metal catalysts such as Ni(OAc)2, Cu(OAc)2, and Co(OAc)2 in place of Pd₂(dba)3 did

Ex-situ generation of gaseous nitriles in two-chamber glassware for facile haloacetimidate synthesis

• Nikolai B. Akselvoll,
• Jonas T. Larsen and
• Christian M. Pedersen

Beilstein J. Org. Chem. 2025, 21, 2465–2469, doi:10.3762/bjoc.21.188

• donor; haloacetimidates; haloacetonitrile; two-chamber reactor; Introduction Trifluoroacetonitrile is an electrophilic reagent that has seen a variety of uses, mostly for incorporating trifluoromethyl groups into organic compounds [1]. As an example it has been successfully utilized for the synthesis

• [14][15][16][17]. Recently, 2,2,2-trifluoroacetaldehyde O-(aryl)oxime has been introduced as a precursor for trifluoroacetonitrile allowing to work under mild conditions at room temperature (Figure 1) [18]. Whether one prepares a precursor or the actual reagent, a separate setup is needed and hence

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

• reagent 118 using trifluoromethanesulfonic acid (TfOH) or TMSOTf as Lewis acids. The authors suggested that the reaction proceeded via the formation of an intermediate 119 followed by reaction with an alcohol nucleophile and a 1,2-carbon migration to produce a cyclopentane derivative 120 with a yield of

• 50% yield. Banerjee et al. [95] demonstrated an alternative method for the synthesis of cyclopentane derivatives. The method included the cleavage of epoxides using Grignard reagents followed by ring contraction. Treatment of epoxide 212 with Grignard reagent through intermediates 213 and 214

• produced aldehyde 215, and further reaction of 215 with the Grignard reagent gave alcohol 216 (Scheme 38). A promising method for the contraction of cyclohexane rings is the semipinacol rearrangement. For the enantioselective total synthesis of (−)-citrinadin A (217) and (+)-citrinadin B (218), the authors

Comparative analysis of complanadine A total syntheses

• Reem Al-Ahmad and
• Mingji Dai

Beilstein J. Org. Chem. 2025, 21, 2334–2344, doi:10.3762/bjoc.21.178

• with an Ir-catalyzed regioselective C–H borylation developed simultaneously by Ishiyama, Miyaura, Hartwig, and co-workers and Smith and co-workers [26][27]. First, the triflate group of 33 was removed by a Pd-catalyzed reduction with ammonium formate as the reducing reagent. The resulting Boc-protected

Halogenated butyrolactones from the biomass-derived synthon levoglucosenone

• Johannes Puschnig,
• Martyn Jevric and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2025, 21, 2297–2301, doi:10.3762/bjoc.21.175

• reduced form 6, which is sold as a solvent, is an inexpensive commercially available reagent (Scheme 1) [21]. Monohalogenation of LGO giving chloride 7a [22] and bromide 7b [23] is readily achieved in a single step, however, fluorinated 7c, which is a potent inflammasone inhibitor (0.8 ± 0.5 µM), has only

• monochlorination and bromination of ketone 6 via enamine 9a [31], and it was envisaged that 9a would be a suitable substrate to achieve the double halogenation using an excess of electrophilic halogen. When enamine 9a was treated with 1.0 mol equivalent of trichloroisocyanouric acid (TCCA), a reagent which can

• using CF3 donors in copper-catalyzed [34], base- and Lewis acid-mediated reactions [35][36][37]. The reaction of enamine 9a with Togni’s reagent (18) and subsequent hydrolysis gave the substituted derivative 19 in 35% yield (qNMR) (Scheme 4). The yield was improved using the N-methylpiperazine-derived

Enantioselective radical chemistry: a bright future ahead

• Anna C. Renner,
• Sagar S. Thorat,
• Hariharaputhiran Subramanian and
• Mukund P. Sibi

Beilstein J. Org. Chem. 2025, 21, 2283–2296, doi:10.3762/bjoc.21.174

• phosphoric acid catalytic system [31]. Aminoalkenes react with Togni’s reagent in the presence of a catalytic amount of CuCl and a chiral phosphoric acid to yield pyrrolidines. Using this methodology, chiral α-quaternary substituted pyrrolidines were synthesized in good yields and excellent

Pathway economy in cyclization of 1,n-enynes

• Hezhen Han,
• Wenjie Mao,
• Bin Lin,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2025, 21, 2260–2282, doi:10.3762/bjoc.21.173

• components such as solvents, catalysts, ligands and so on. Unlike traditional “one-to-one” reactions, pathway-controlled “one-to-many” transformations synthesize multiple products from single intermediates, dramatically reducing preparation time and reagent requirements (Scheme 1b). As an exceptionally

Research towards selective inhibition of the CLK3 kinase

• Vinay Kumar Singh,
• Frédéric Justaud,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Blandine Baratte,
• Thomas Robert,
• Stéphane Bach,
• Chada Raji Reddy,
• Nicolas Levoin and
• René L. Grée

Beilstein J. Org. Chem. 2025, 21, 2250–2259, doi:10.3762/bjoc.21.172

• reagent the 3-(methoxycarbonyl)phenylboronic acid ester 11. All derivatives have spectral and analytical data in agreement with the proposed structures (see experimental section and Supporting Information File 1). Kinase inhibition studies Our molecules have been submitted first to a primary screening

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

• efficacious but face significant challenges when applied to non-symmetric systems [24], particularly in achieving regioselectivity. These methods frequently require a particular reagent pair or an excess of one reactant, which limits their efficiency and versatility. In contrast, Baeyer–Mills reactions, which

• avoiding excess reagent, and simplifies purification and scale-up. With the most suitable reaction conditions in hand, the substrate scope was examined. First, the reactivity of different aryl bromides with phenylhydrazine (1a) to form non-symmetric azobenzene was explored (Scheme 1). Most of 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

• 50% yield and 99% ee after kinetic resolution using Escherichia coli (Scheme 57) [189]. Other reactions: Yamamoto synthesized 6-hydroxy-2-(trifluoromethyl)-2H-pyran-3(6H)-ones from furfural via trifluoromethylation using the Ruppert–Prakash reagent (TMSCF3), followed by a photo-Achmatowicz reaction

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