Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

• excellent yield (Scheme 2) [32]. The formed anhydride 3 was smoothly converted to the amide at room temperature. This method provides a green approach by allowing cinnamic acid derivatization in water as a benign solvent. Similarly, Rajendran and Rajan (2023) reported a one-pot transamidation of cinnamamide

• reagent (Scheme 7) [38]. By mimicking the electrophilic sp-carbon center of common coupling reagents (e.g., DCC, EDC), Zhao and co-workers (2021) employed allenone 22 as a coupling reagent for amidation [39]. Herein, cinnamic acid was smoothly converted to its corresponding amide 10 in a one-pot two-step

• amidation in 5 min reaction time via the formation of the isolable enol ester intermediate 23 (Scheme 8A). Similarly, Feng and co-workers (2019) studied one-pot two-step esterification of cinnamic acid (7) by applying electrophilic sp carbon center of methyl propiolate (25) as the coupling reagent via in

Synthesis of pyrrolo[3,2-d]pyrimidine-2,4(3H)-diones by domino C–N coupling/hydroamination reactions

• Ruben Manuel Figueira de Abreu,
• Robin Tiedemann,
• Peter Ehlers and
• Peter Langer

Beilstein J. Org. Chem. 2025, 21, 1010–1017, doi:10.3762/bjoc.21.82

• pyrrolopyrimidine derivatives. The envisioned methodology combines a Sonogashira–Hagihara reaction and a one-pot process comprising a Buchwald–Hartwig coupling reaction followed by a hydroamination [23][24]. Results and Discussion The bromination of 6-chloro-1,3-dimethyluracil (1) afforded, following a known

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

• a regioselective manner. From tetracyclic compound 11, a one-pot facial and regioselective hydroboration/amide reduction followed by oxidation produced (+)-lycoposerramine Q, which was then converted to (+)-fawcettidine by Ley oxidation. Alternatively, hydroboration of 11 in mild conditions without

• a fragmentation process for the total synthesis of (−)-phlegmariurine B. A one-pot epoxidation/nucleophilic epoxide opening introduced both a hydroxy group and a chloride across the cyclopentene, producing 14 in 57% yield. After oxidation of alcohol 14 to ketone 15, the Mukaiyama hydration then

• divergent total synthesis of several Cephalotaxus alkaloids. The α-hydroxylation of cyclopentanone, followed by amide reduction and methanol elimination in one-pot, produced (−)-cephalotaxine in 9 steps. Alternatively, Riley SeO2 oxidation of 31, benzylic bromination/hydrolyzation, facial selective ketone

Studies on the syntheses of β-carboline alkaloids brevicarine and brevicolline

• Benedek Batizi,
• Patrik Pollák,
• András Dancsó,
• Péter Keglevich,
• Gyula Simig,
• Balázs Volk and
• Mátyás Milen

Beilstein J. Org. Chem. 2025, 21, 955–963, doi:10.3762/bjoc.21.79

• described in the literature for trifluoroacetylation of aromatic ring systems with TFA [44][45]. Nevertheless, in our case, trifluoroacetylation of the pyrrole moiety of 30 by TFA and reduction of the carbonyl group of 33 with NaCNBH3 took place in one pot, which is unprecedented in the literature. It is

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

• synthesized in one pot with good yields and excellent diastereoselectivities (Table 4, entries 5 and 9). Surprisingly, carbamate substrates derived from di-substituted allylic alcohols (Figure 1) invariably failed to give the desired amino-sulfonoxylated products. With these substrates, 1H NMR analysis of the

A convergent synthetic approach to the tetracyclic core framework of khayanolide-type limonoids

• Zhiyang Zhang,
• Jialei Hu,
• Hanfeng Ding,
• Li Zhang and
• Peirong Rao

Beilstein J. Org. Chem. 2025, 21, 926–934, doi:10.3762/bjoc.21.75

• oxidative cleavage [47] was applied to deliver aldehyde 29. Finally, a one-pot acetalization and desilylation effectively afforded the acetal alcohol, which was then oxidized with the aid of TPAP, furnishing acetal aldehyde 14 in 67% yield over two steps. With the two fragments 13 and 14 in hand, the next

Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• solvent-mediated electronic and steric modulations frequently dictate reaction stereoselectivity, with even subtle solvent permutations potentially inducing complete stereochemical inversion in sensitive systems [33][34][35][36][37][38]. In 2023, He and Sessler disclosed a versatile one-pot synthesis of

• cycloaddition reactions with substituted furans as diene component to produce the corresponding epoxy-cycloaddition adducts. The authors developed an Ir/Sc tandem catalytic reaction to convert these adducts into polysubstituted 3-haloisoquinolines 99 in one pot. After obtaining isoquinoline compounds 99 with

Dicarboxylate recognition based on ultracycle hosts through cooperative hydrogen bonding and anion–π interactions

• Wen-Hui Mi,
• Teng-Yu Huang,
• Xu-Dong Wang,
• Yu-Fei Ao,
• Qi-Qiang Wang and
• De-Xian Wang

Beilstein J. Org. Chem. 2025, 21, 884–889, doi:10.3762/bjoc.21.72

• were synthesized via a one-pot strategy starting from macrocyclic precursors. Host–dicarboxylate binding was investigated using 1H NMR titrations, revealing that B4aH exhibits strong binding affinities toward a series of dicarboxylates, with association constants reaching up to 6896 M−1. The

• [29][31]. A one-pot reaction of submacrocycle 1a and 2-(benzyloxy)benzene-1,3-diol (2a) in the presence of 8.0 equivalents of CsF yielded the ultracycle precursor compounds. Three reorganized products B4a, B5a, and B6a with different ring sizes were isolated. As previously observed, the structural

• B4aH for C72− likely arise from cooperative noncovalent interactions and a size-matching effect. Conclusion In conclusion, we synthesized a series of hydroxy-substituted ultracycles of varying sizes on the lower-rim using a one-pot cyclization strategy. 1H NMR titration experiments indicate that the

Recent advances in the electrochemical synthesis of organophosphorus compounds

• Babak Kaboudin,
• Milad Behroozi,
• Sepideh Sadighi and
• Fatemeh Asgharzadeh

Beilstein J. Org. Chem. 2025, 21, 770–797, doi:10.3762/bjoc.21.61

• corresponding thiophosphorylated product (Scheme 27). Recently, a novel and one-pot electrochemical oxidation method was reported for synthesizing S-(hetero)aryl phosphorothioates without using any oxidants or transition metals at room temperature [68]. The reaction was carried out in an undivided cell. The

Sequential two-step, one-pot microwave-assisted Urech synthesis of 5-monosubstituted hydantoins from L-amino acids in water

• Wei-Jin Chang,
• Sook Yee Liew,
• Thomas Kurz and
• Siow-Ping Tan

Beilstein J. Org. Chem. 2025, 21, 596–600, doi:10.3762/bjoc.21.46

• this study, we present an innovative, sustainable approach to synthesizing hydantoins (H2a–j) directly from amino acids. This method employs a column chromatography-free, two-step, one-pot microwave-assisted synthesis that delivers hydantoins in yields ranging from 34% to 89%. The protocol demonstrates

• accessibility of these bioactive compounds for pharmaceutical applications. Keywords: amino acids; hydantoin; microwave-assisted; one-pot reaction; Urech synthesis; Introduction The hydantoin moiety is a scaffold found in many biologically active compounds exhibiting a diverse range of properties, including

• second step was attempted as part of a one-pot synthesis of hydantoins by the addition of concentrated hydrochloric acid followed by microwave irradiation of the reaction mixture at 80 °C for 15 min (Scheme 2). Gratifyingly, the acid-induced intra-cyclization of the urea derivative H1a proceeded smoothly

Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• temperatures, no specifically prepared solvents), one-pot, batch processes leading to tandem or cascade reactions, resource efficiency through the application of the 12 principles of Green Chemistry, and readily available starting materials such as waste materials from food production processes [1][2][3]. In

• these examples, even if the whole process is performed in one-pot, the reaction needs two steps: the generation of the Ugi (or Passerini) adduct and then the post-cyclization reaction. Interestingly, Peshkov et al. showed that when phenyl glyoxal is used instead of ethyl glyoxylate, a pyrrolone

Study of the interaction of 2H-furo[3,2-b]pyran-2-ones with nitrogen-containing nucleophiles

• Constantine V. Milyutin,
• Andrey N. Komogortsev and
• Boris V. Lichitsky

Beilstein J. Org. Chem. 2025, 21, 556–563, doi:10.3762/bjoc.21.44

• intramolecular hydrogen bond between the NH-unit and the carbonyl group. The presented results indicate that the reaction of the aliphatic amine doesn’t lead to recyclization of the studied heterocyclic system. Further, we hypothesized that synthesis of the enamine 4a can be realized in one-pot variant without

New tandem Ugi/intramolecular Diels–Alder reaction based on vinylfuran and 1,3-butadienylfuran derivatives

• Yuriy I. Horak,
• Roman Z. Lytvyn,
• Andrii R. Vakhula,
• Yuriy V. Homza,
• Nazariy T. Pokhodylo and
• Mykola D. Obushak

Beilstein J. Org. Chem. 2025, 21, 444–450, doi:10.3762/bjoc.21.31

• reaction and Diels–Alder [4 + 2] cycloaddition based on vinylfuran and 1,3-butadienylfuran derivatives was designed and studied. It was found that in the case of 3-(furan-2-yl)acrylaldehyde, a one-pot Ugi reaction and intramolecular Diels–Alder vinylarene (IMDAV) reaction leads to the formation of the

• yields. The studied tandem Ugi and intramolecular Diels–Alder reactions allow high substituent variation in the named isoindoles. Keywords: 1,3-butadienylfuran; furo[2,3-f]isoindole; intramolecular Diels–Alder reaction; isoindole; one-pot; Ugi reaction; vinylfuran; Introduction Energy-saving and

• environmentally friendly synthetic strategies, especially one-pot multicomponent and tandem reactions, are key to modern organic and medicinal chemistry [1][2][3][4][5][6][7] and have proven to be successful in generating diverse heterocyclic scaffolds, as highlighted in a recent book [8]. Multicomponent

Unraveling aromaticity: the dual worlds of pyrazole, pyrazoline, and 3D carborane

• Zahra Noori,
• Miquel Solà,
• Clara Viñas,
• Francesc Teixidor and
• Jordi Poater

Beilstein J. Org. Chem. 2025, 21, 412–420, doi:10.3762/bjoc.21.29

• -1,3-dimethylimidazolinium hexafluorophosphate (ADMP) in the presence of DBU in acetonitrile. This one-pot process enables sequential diazotization and cyclization, leading to the formation of two or three C–N bonds under extremely mild conditions, with excellent tolerance for various functional groups

The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

• in attaining the required stereospecific glycosylation outputs. Apart from the widely convenient stepwise synthesis, recently one-pot glycosylations have also made an important mark which minimise the tedious purification of the intermediate molecules in each step [53][54][55][56][57][58]. In the

• rigorous planning of one-pot glycosylation the role of a neighbouring group and possible effect of remote participating groups comes into play. One-pot glycosylations have also opened the door of the automated oligosaccharide synthesis which applies the principle of solid-phase synthesis [59][60][61][62

Synthesis of disulfides and 3-sulfenylchromones from sodium sulfinates catalyzed by TBAI

• Zhenlei Zhang,
• Ying Wang,
• Xingxing Pan,
• Manqi Zhang,
• Wei Zhao,
• Meng Li and
• Hao Zhang

Beilstein J. Org. Chem. 2025, 21, 253–261, doi:10.3762/bjoc.21.17

• -tolyldisulfane (2a, 1.87 g) in a yield of 76% (Scheme 4). A similar yield of 90% was obtained for compound 4a. To make the synthesis of 3-sulfenylchromones more convenient, the product was synthesized by a one-pot method using 2-hydroxyacetophenone as the starting material (Scheme 4). First, 2

• 120 °C for 12 h; yield based on 3. Gram-scale synthesis of 2a and 4a and one-pot synthesis of 4a. Control experiments. Plausible reaction mechanism. Optimization of reaction conditions.a Supporting Information Supporting Information File 110: Experimental procedures, compound characterization data

Streamlined modular synthesis of saframycin substructure via copper-catalyzed three-component assembly and gold-promoted 6-endo cyclization

• Asahi Kanno,
• Ryo Tanifuji,
• Satoshi Yoshida,
• Sota Sato,
• Saori Maki-Yonekura,
• Kiyofumi Takaba,
• Jungmin Kang,
• Kensuke Tono,
• Koji Yonekura and
• Hiroki Oguri

Beilstein J. Org. Chem. 2025, 21, 226–233, doi:10.3762/bjoc.21.14

• , was obtained in one-pot, presumably via generation of the aminonitrile 17 and subsequent nucleophilic attack of the phenolic hydroxy group to form the five-membered ring. Our efforts to optimize this one-pot sequence led to the best results, affording 11 in 73% isolated yield, when acetone cyanohydrin

• a fluorescent intermediate 18, and subsequent ring opening allowed a streamlined one-pot access to the substructure of THIQ alkaloids 14 in a good yield of 60% from 11. The structure of the resulting 14 was elucidated through comprehensive two-dimensional NMR spectroscopy, complemented by NOE

• –Spengler-type reactions. (c) This work: streamlined modular assembly featuring copper(I)-catalyzed regiocontrolled three-component coupling (8 → 10), one-pot formation of the 2,3-diaminobenzofuran ring in the key intermediate 11, and subsequent gold(I)-mediated regiocontrolled 6-endo hydroamination

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• ; heteropolycycles; multicomponent reactions; one-pot reaction; Introduction Copper has gained a relevant role in organic synthesis as an alternative to precious metals due to its low toxicity, ease of handling, high catalytic activity, and cost-effectiveness [1][2]. In recent years, Cu(OTf)2 has significantly

• Pd-catalyzed cross-coupling reactions, allowing the formation of C–C and C–N bonds in the o-position of the aryl chalcogen compounds. α-Aminophosphonates 14 were the result of a one-pot condensation of an aldehyde, a primary amine and phosphite P(OMe)3 with copper triflate acting as Lewis acid

• orientation between the electron-rich nitrogen of the diene and the electron-poor carbon of the alkyne. A different one-pot procedure affording tetrahydropyridines was developed employing two molecules of aromatic aldehydes, ethyl acetoacetate and two molecules of aniline. The copper triflate catalyst acts in

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

• ]. Hayashi realized an organocatalytic domino sequence that afforded axially chiral biaryls [24]. The transformation relied on an organocatalytic Michael/Henry cascade. The enamine-type Michael addition was catalyzed by the Hayashi–Jørgensen organocatalyst C7 (Scheme 6). Then, a series of one-pot reactions

• was carried out to provide the final biaryl products 17. In a related strategy, Hayashi´s team realized an organocatalytic Michael/aldol cascade leading to chiral dihydronaphthalene derivatives 20a–e [25]. Through a series of one-pot reactions, aromatization was achieved with concomitant central-to

• be carried out in a one-pot fashion with comparable results and without significant variation from the two-step procedure. Utilization of the Povarov reaction and subsequent oxidation by DDQ was also done by Wang et al. in 2020 [54]. In situ-formed imines from anilines 91 and benzaldehydes 92 were

Facile one-pot reduction of β-nitrostyrenes to phenethylamines using sodium borohydride and copper(II) chloride

• Laura D’Andrea and
• Simon Jademyr

Beilstein J. Org. Chem. 2025, 21, 39–46, doi:10.3762/bjoc.21.4

• substituted β-nitrostyrenes. This one-pot procedure allows the quick isolation of substituted β-nitrostyrene scaffolds with 62–83% yield under mild conditions, without the need for special precautions, inert atmosphere, and time-consuming purification techniques. Keywords: 2C-X; CuCl2; NaBH4; β-nitrostyrene

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

• ketones 42 [37]. With this transformation polysubstituted cyclohexanes 43 bearing four consecutive stereocenters are afforded through efficient one-pot cyclization with good yields (43–95%) and with high enantioselectivities (80–97% ee) (Scheme 15). In general, 1-azadienes 14 with different substitution

Controlled oligomerization of [1.1.1]propellane through radical polarity matching: selective synthesis of SF₅- and CF₃SF₄-containing [2]staffanes

• Jón Atiba Buldt,
• Wang-Yeuk Kong,
• Yannick Kraemer,
• Masiel M. Belsuzarri,
• Ansh Hiten Patel,
• James C. Fettinger,
• Dean J. Tantillo and
• Cody Ross Pitts

Beilstein J. Org. Chem. 2024, 20, 3134–3143, doi:10.3762/bjoc.20.259

• substituted BCPs [25][26][27] or photochemical appendage of 1 onto an extant BCP [28][29][30][31] are relatively effective tactics for the selective assembly of certain [n]staffanes; the main caveat is that multiple synthetic steps are required. On the other hand, while a one-pot radical chain oligomerization

• synthetic and computational study demonstrates that selective one-pot syntheses of [2]staffanes can be achieved when employing reagents that serve as radical sources of "extreme" electron-withdrawing groups (e.g., SF5 or CF3SF4), which impact relative philicities of the bicyclopentyl radical intermediates

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• cost effective and selective, one-pot transformation. Pharmaceutical uses for bio-active cyclic molecules accessible by I(III) reagents are plentiful; anticancer drugs can be formed from the basis of pyrrolo[2,3-b]indoles 1 [3][4], 2-oxazolines 2 [5][6], dihydrofuran 3 [7][8], and spirocyclic scaffolds

• the synthesis of cyclic imines using a one-pot protocol involving Grignard addition to a cyano group followed by PhI(OAc)2 (Scheme 30) [51]. The authors used p-tolylmagnesium bromide for both the arylation of the unsaturated carbonitriles 55 and as a bromide source. Bromocyclisation was achieved using

Synthesis of the 1,5-disubstituted tetrazole-methanesulfonylindole hybrid system via high-order multicomponent reaction

• Cesia M. Aguilar-Morales,
• América A. Frías-López,
• Nadia V. Emilio-Velázquez,
• Alejandro Islas-Jácome,
• Angelica Judith Granados-López,
• Jorge Gustavo Araujo-Huitrado,
• Yamilé López-Hernández,
• Hiram Hernández-López,
• Luis Chacón-García,
• Jesús Adrián López and
• Carlos J. Cortés-García

Beilstein J. Org. Chem. 2024, 20, 3077–3084, doi:10.3762/bjoc.20.256

• , 98160, México 10.3762/bjoc.20.256 Abstract A series of 1,5-disubstituted tetrazole-indole hybrids were synthesized via a high-order multicomponent reaction consisting of an Ugi-azide/Pd/Cu-catalyzed hetero-annulation cascade sequence. This operationally simple one-pot protocol allowed high bond-forming

• and resource optimization. In addition, all the target compounds were fully characterized using 1H and 13C NMR spectroscopy and HRMS. It is important to mention that this protocol cannot be considered a true one-pot synthesis, as it requires a solvent exchange between reaction steps (e.g., from

Cyclodextrin-based rotaxanes for polymer materials: challenge on simultaneous realization of inexpensive production and defined structures

• Yosuke Akae

Beilstein J. Org. Chem. 2024, 20, 3026–3049, doi:10.3762/bjoc.20.252

• produce simple structured rotaxane species (Scheme 3) [46][47][48]. In this method, dodecanediamine and α-CD are mixed in water to form a pseudo[3]rotaxane (1), and the subsequent one-pot end-capping reaction driven by the amino group on the axle ends and substituted phenyl isocyanate produced [3]rotaxane