Asymmetric Mannich reaction of aromatic imines with malonates in the presence of multifunctional catalysts

• Kadri Kriis,
• Harry Martõnov,
• Annette Miller,
• Mia Peterson,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2026, 22, 151–157, doi:10.3762/bjoc.22.8

• adduct in 83% ee (Table 1, entry 9). Replacing the five-membered pyrrolidine ring in the catalyst structure with the more flexible six-membered piperidine ring (catalyst H, Table 1, entry 13) reduced its selectivity slightly (78% ee). However, the catalyst derived from phenylglycine (catalyst F) or

• ]. Although basic conditions caused partial racemization during the protection or deprotection step, the Boc-protected amine was obtained in low enantiomeric purity. Chiral HPLC analysis and comparison with an authentic sample revealed the S-configuration of the Mannich adduct [29]. Absolute configurations of

Total synthesis of asperdinones B, C, D, E and terezine D

• Ravi Devarajappa and
• Stephen Hanessian

Beilstein J. Org. Chem. 2025, 21, 2730–2738, doi:10.3762/bjoc.21.210

• ]. For example, using 1 equivalent of reagent 29, the cross-coupling of 3-iodo-6-prenyl-N-acetylindole (27) led to the adduct 32 in 52% yield accompanied by the reduced product 37 in 30% and the dehydro product 38 in 10% yield. Control experiments revealed that the iodozinc reagent from 29 was unaffected

Tandem hydrothiocyanation/cyclization of CF₃-iminopropargyl alcohols with NaSCN in the presence of AcOH

• Ruslan S. Shulgin,
• Ol’ga G. Volostnykh,
• Anton V. Stepanov,
• Igor’ A. Ushakov,
• Alexander V. Vashchenko and
• Olesya A. Shemyakina

Beilstein J. Org. Chem. 2025, 21, 2694–2702, doi:10.3762/bjoc.21.207

• ), 5.56 s (CH2) ppm, 19F NMR: δ 60.3 ppm), that disappeared by the end of the reaction (Figure 1c and d). Probably, the salts 2f,g are unstable and decompose under the reaction conditions. The formation of products 2 and 3 can be explained by different directions of cyclization of the primary adduct of

• imino group in the E-isomer of adduct A leads to 4-thiocyano-2,5-dihydrofuran 3. Taking into account the NMR monitoring data, it can be assumed that the yield and ratio of products are influenced by the stereoselectivity of the reaction and the stability of salts 2 under reaction conditions. We also

Recent advancements in the synthesis of Veratrum alkaloids

• Morwenna Mögel,
• David Berger and
• Philipp Heretsch

Beilstein J. Org. Chem. 2025, 21, 2657–2693, doi:10.3762/bjoc.21.206

• TBSO-substituent on the dienophile and the diene. As a result of such endo-addition, the benzyloxy group in the diene and the acylpyridine of the dienophile are oriented cis to each other in adduct 99. Next up was the formation of the C20–OH by addition of MeMgBr to the ketone 99, which initially gave

• [53]. This delivered the desired exo-adduct with good ee on a decagram-scale and installed three stereocenters with the correct configuration. The aldehyde moiety was converted to the terminal alkyne 110 via Seyferth–Gilbert homologation using the Ohira–Bestmann reagent. Reduction of the ethyl ester

Thiazolidinones: novel insights from microwave synthesis, computational studies, and potentially bioactive hybrids

• Luan A. Martinho,
• Victor H. J. G. Praciano,
• Guilherme D. R. Matos,
• Claudia C. Gatto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2025, 21, 2618–2636, doi:10.3762/bjoc.21.203

• reaction with these substrates is not commonly reported in the literature [37][39]. The reaction of EDA in EtOH as solvent was investigated; however, a complex mixture of products was observed, with no evidence of formation of the Knoevenagel adduct. This outcome appears to result from both mono- and

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

• rearrangement. Finally, a White–Chen C–H oxidation [33][34][35] was employed to install the lactone ring, thereby completing the synthesis. The synthesis began with commercially available compound 19 and known compound 20 (Scheme 2). These were joined via an intermolecular aldol reaction to give adduct 21

• into the pentacyclic diene intermediate 93 via a two-step sequence. Subsequent [4 + 2] cycloaddition of 93 with singlet oxygen yielded an unstable endoperoxide adduct 94, which rearranged to diketone 95. A five-step sequence, featuring an intramolecular aldol reaction to assemble the pentacyclic core

• adduct and ultimately enabled the completion of the synthesis. This strategic pivot offers a key lesson for handling fragile cycloaddition adducts. Suzuki’s synthetic effort towards illisimonin A A synthetic study aimed at constructing the tricyclo[5.2.1.01,5]decane core of illisimonin A was reported by

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

• adduct was subjected to AgOTf-catalyzed lactonization to successfully construct the D ring of target molecular framework. Next, a 1,4-addition reaction introduced a vinyl group to compound 68, affording compound 70. A Pauson–Khand cyclization of 70 under [RhCl(CO)2]2/CO conditions smoothly furnished the

Rapid access to the core of malayamycin A by intramolecular dipolar cycloaddition

• Yilin Liu,
• Yuchen Yang,
• Chen Yang,
• Sha-Hua Huang,
• Jian Jin and
• Ran Hong

Beilstein J. Org. Chem. 2025, 21, 2542–2547, doi:10.3762/bjoc.21.196

• smoothly to deliver the aldehyde which was immediately subjected to the condensation reaction with benzylhydroxylamine. The corresponding nitrone 10 then underwent an intramolecular cycloaddition. Adduct 11 was isolated as the major product in 42% yield for 2 steps. Comprehensive NMR analysis revealed the

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

• explained to some extent by their structural diversity. Figure 1 shows the general formula of iridoids. The authors [16] have established regiocontrol of the effect of the 1,6-anhydro bridge on the Dieckmann condensation of dicarboxylic acid diester 16, obtained in four steps from 13, the Diels–Alder adduct

• compound was synthesized from the Diels–Alder adduct 14 between LG and 1,3-butadiene by two methods – vicinal hydroxylation of the double bond followed by periodate cleavage of the vic-diols and ozonolysis of the double bond. Alternatively, Wagner oxidation of the double bond in adduct 14 by treatment with

• in a stable aldehyde 23. This aldehyde is a product of intramolecular aldol–croton condensation and can be used in the synthesis of bartsioside (24) or its analogues [21][22] (Scheme 4). The authors [19] performed similar oxidative transformations with Diels–Alder adduct 25 obtained from LG and

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

• mechanism involving single-electron oxidation of an enamine intermediate, addition of the resulting radical to the olefin, single-electron oxidation of the adduct to form a carbocationic intermediate, and intramolecular nucleophilic attack on the carbocation to form the pyrrolidine ring. The reaction

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

• addition happened to generate the spiroindoleninium intermediate. This transient species was subsequently trapped by water physisorbed in the silica gel, forming hemiaminal adduct 132. A 1,5-hydride shift was then mediated by Al2O3, ultimately affording the spiro[indoline-3,3'-pyrrolidin]-2-one derivatives

Synthesis of triazolo- and tetrazolo-fused 1,4-benzodiazepines via one-pot Ugi–azide and Cu-free click reactions

• Xiaoming Ma,
• Zijie Gao,
• Jiawei Niu,
• Wentao Shao,
• Shenghu Yan,
• Sai Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 2202–2210, doi:10.3762/bjoc.21.167

• introduce reactants in a sequential manner. Thus, we changed the reaction conditions by first reacting 0.2 mmol each of 1a and 2a in 2 mL MeOH at 40 °C for 40 min to form the Schiff base Int-I followed by the addition of 0.2 mmol each of 3a and TMSN3 (4) to obtain the desired 1,5-DS-T 5a as Ugi–azide adduct

• conditions: 1) 0.2 mmol each of 2-azidobenzaldehyde (1a) and 2-yn-1-amines 2 in MeOH (2 mL), 40 °C for 40 min; then addition of 0.2 mmol each of 2-isocyanoacetate (9) and TMSN3 (4), 40 °C for 12 h; 2) changing solvent to MeCN (2 mL), 130 °C for 2 h. Control reactions to trap the Ugi–azide adduct. Gram-scale

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

• -(phenylethynyl)-N-tosylbenzamide (25a) to afford the amidyl radical B, which then proceeded intramolecular 5-exo-dig radical annulation to form the five-membered intermediate C. The oxidation of C followed by capturing an AcO− generated the intermediate E, which was converted into triacetate adduct F through

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

• 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

• [183]. 2-(Furan-2-yl)-1,3-dioxolane with higher reactivity was generated through the acetalization of furfural with ethylene glycol, and converted to Diels–Alder cycloadducts in the presence of acrylonitrile at 60 °C. Treatment of the Diels–Alder adduct in basic conditions allowed the rearomatization

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

• , including (−)-ψ-akuammigine (Scheme 33) [81]. The synthesis commenced with dibenzoate 274, which underwent a Pd-catalyzed Trost desymmetrization using sulfonamide 275 and ligand 276. Deprotection of the resulting adduct furnished alcohol 277, which was subsequently converted to silyl enol ether 278 in two

Preparation of spirocyclic oxindoles by cyclisation of an oxime to a nitrone and dipolar cycloaddition

• Beth L. Ritchie,
• Alexandra Longcake and
• Iain Coldham

Beilstein J. Org. Chem. 2025, 21, 1890–1896, doi:10.3762/bjoc.21.146

• to one another and cis to the ring junction NC–H. The relative stereochemistry of the oxindole quaternary stereocentre was less obvious from this method, but the coupling constants of the aliphatic ring protons in the 1H NMR spectrum had similar values to those in the adduct 5a, suggesting that the

Approaches to stereoselective 1,1'-glycosylation

• Daniele Zucchetta and
• Alla Zamyatina

Beilstein J. Org. Chem. 2025, 21, 1700–1718, doi:10.3762/bjoc.21.133

• configuration has been explained by the formation of a picolinium adduct, resulting from the trapping of the acidic by-product TMSOTf by the pyridine moiety of the picoloyl group during glycosylation [69]. The resulting intermediate, a picolinium-stabilized TMS-glycoside, exhibits high configurational stability

• dimethyl disulfide/triflic anhydride and use thioglycosyl donors, 4-O-picoloyl-protected 1-O-TMS-lactol acceptors have been shown to exhibit enhanced β-stereoselectivity, likely due to the formation of a transient picolinium adduct with the TMS-glycoside. Tribenzylated 4-O-picoloyl-1-O-TMS-β-glycoside 101

• -glycoside acceptors 156 and 158, respectively (Scheme 13). The picoloyl protecting group, when placed at the remote C4–OH position, has been shown to additionally stabilize the anomeric configuration in TMS-α-glycoside acceptors, which has been attributed to the formation of a picolinium adduct, formed via

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

• adduct 10 was identified using GC–MS (Figure S1, Supporting Information File 1). When the reaction was performed under air-equilibrated conditions, the intended product 9a was obtained in a 31% yield, indicating that air influenced the interaction between the Ni-catalyst and the α,β-unsaturated carbonyl

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

• benzotriazole-adduct formation proceeds poorly with sterically demanding secondary amines and fails with primary amines. However, the latter may be overcome by adding a temporary benzyl group on the amine which can be subsequently cleaved by hydrogenolysis as demonstrated by the authors. Finally, it was shown

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

• abstracts a hydrogen atom from substrate 1 through HAT, producing an α-amido-acridinyl radical intermediate 92 and a substrate-derived carbon-centered radical 4. Radical 4 undergoes regioselective addition to the acceptor, forming transient radical adduct 93. A concomitant SET from 92 to 93 generates a

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

Synthesis of β-ketophosphonates through aerobic copper(II)-mediated phosphorylation of enol acetates

• Alexander S. Budnikov,
• Igor B. Krylov,
• Fedor K. Monin,
• Valentina M. Merkulova,
• Alexey I. Ilovaisky,
• Liu Yan,
• Bing Yu and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2025, 21, 1192–1200, doi:10.3762/bjoc.21.96

• isolated in 77% yield (1.3 g, 4.61 mmol). In order to propose the reaction mechanism, control experiments were conducted (Scheme 4). The reaction is completely inhibited by the addition of (2,2,6,6-tetramethylpiperidin-1-yl)oxyl (TEMPO) or BHT (Scheme 4, reaction 1). A BHT-adduct derived from a P-centered

A multicomponent reaction-initiated synthesis of imidazopyridine-fused isoquinolinones

• Ashutosh Nath,
• John Mark Awad and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 1161–1169, doi:10.3762/bjoc.21.92

• tested, AlCl₃ gave the best result, while CuCl, ZnCl2, PdCl2 and Sc(OTf)3 showed moderate conversions (30–55%), and InCl3 had the lowest efficiency. Without any Lewis acid we observed no conversion by LC–MS (Table 1, entry 16). During the reaction, IMDA adduct 7a was detected by LC–MS (Figure S1

• calculated using the Gaussian 16 software (Figure 3) [21]. The N-acylated compound 6a has a baseline relative energy of 0 kJ/mol, while the transition state of the Diels–Alder (TS-DA) reaction presents the highest energy barrier at 1.221 kJ/mol. The DA adduct shows a little lower energy at 1.001 kJ/mol

Investigations of amination reactions on an antimalarial 1,2,4-triazolo[4,3-a]pyrazine scaffold

• Henry S. T. Smith,
• Ben Giuliani,
• Kanchana Wijesekera,
• Kah Yean Lum,
• Sandra Duffy,
• Aaron Lock,
• Jonathan M. White,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2025, 21, 1126–1134, doi:10.3762/bjoc.21.90

• previous reports [10]. A single and identical product was obtained from each reaction and the product, 2, was characterised following analysis of HRESIMS and 1D (1H, 13C) and 2D (COSY, HSQC, HMBC, ROESY) NMR data. The HRESIMS data of 2 showed a Na adduct ion at m/z 372.0991 [M + Na]+ (calcd for

Gold extraction at the molecular level using α- and β-cyclodextrins

• Susana Santos Braga

Beilstein J. Org. Chem. 2025, 21, 1116–1125, doi:10.3762/bjoc.21.89

• that a 2:1 ratio (α-CD to KAuBr4) was sufficient to ensure a co-precipitation yield of 78% and that this value remains relatively constant with increasing amounts of α-CD. It was, thus, concluded that adding extra amounts of α-CD do not help increasing the yield and that the co-precipitated adduct has