Asymmetric synthesis of fluorinated derivatives of aromatic and γ-branched amino acids via a chiral Ni(II) complex

• Maurizio Iannuzzi,
• Thomas Hohmann,
• Michael Dyrks,
• Kilian Haoues,
• Katarzyna Salamon-Krokosz and
• Beate Koksch

Beilstein J. Org. Chem. 2025, 21, 659–669, doi:10.3762/bjoc.21.52

• , base, solvent, and reagent equivalents to optimize the alkylation reaction for both bromides 4 and 5 (Table 1 and Table 2). For Ni(II) complex of [2.3.5.6F]TfMePhe (6), firstly we screened different inorganic and organic bases (Table 1, entries 1–3) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) was

Recent advances in allylation of chiral secondary alkylcopper species

• Minjae Kim,
• Gwanggyun Kim,
• Doyoon Kim,
• Jun Hee Lee and
• Seung Hwan Cho

Beilstein J. Org. Chem. 2025, 21, 639–658, doi:10.3762/bjoc.21.51

• electrophiles While the direct formation of chiral copper species from organolithium compounds provides an efficient route to stereospecific allylic alkylation products, the requirement of stoichiometric amounts of the copper reagent limits its practical application [46]. An alternative approach utilizing more

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

• %), but when DMSO is used as solvent and reagent, the yield was greatly improved. The proposed mechanism involves the activation of the disulfide component by CuBr2 as the Lewis acid (Scheme 14). The copper(II) center coordinates the sulfur atom of the disulfide allowing for the electrophilic addition to

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

• with diverse N-nucleophiles was investigated. It was shown that the direction of the process depends on the type of employed nitrogen-containing reagent. For example, condensation with aliphatic amines leads to 2H-furo[3,2-b]pyran-2,7(3H)-diones bearing an exocyclic enamine moiety. At the same time

• target product was not obtained (Table 1, entries 3–5). Apparently, the presence of acid reagent is necessary for implementation of considered recyclization. In this regard we tried to perform the process under study using phenylhydrazine in salt form. Indeed, reflux of furanone 1a with the corresponding

• the best result was achieved in the case of EtOH (Table 1, entry 7). Then, we optimized the process time for the reaction with reagent 7a. It was shown that 8 h reflux is enough for the considered recyclization (Table 1, entry 10). Wherein, further shortening of the duration decreased the yield of

Deep-blue emitting 9,10-bis(perfluorobenzyl)anthracene

• Long K. San,
• Sebastian Balser,
• Brian J. Reeves,
• Tyler T. Clikeman,
• Yu-Sheng Chen,
• Steven H. Strauss and
• Olga V. Boltalina

Beilstein J. Org. Chem. 2025, 21, 515–525, doi:10.3762/bjoc.21.39

• crystals, addition of a drop of 1,2-dibromoethane). Only the addition of 1,2-dibromoethane enabled the generation of the Grignard reagent which was observed by bubbles and an instant increase of the reaction mixture’s temperature. CF2C6F5I (97.5 µL, 625 µmol) dissolved in dry THF (20 mL) was added with a

Synthesis of the aggregation pheromone of Tribolium castaneum

• Biyu An,
• Xueyang Wang,
• Ao Jiao,
• Qinghua Bian and
• Jiangchun Zhong

Beilstein J. Org. Chem. 2025, 21, 510–514, doi:10.3762/bjoc.21.38

• with Grignard reagent, and oxidation with RuCl3/NaIO4. Keywords: aggregation pheromone; chiral 2-methyloxirane; red flour beetle; total synthesis; Introduction The red flour beetle, Tribolium castaneum Herbst (Coleoptera: Tenebrionidae), is a cosmopolitan, destructive stored product pest [1], which

• olefine (5R,9R)-12, which could be obtained through Li2CuCl4-catalyzed coupling of chiral tosylate (S)-10 with a Grignard reagent derived from (R)-1-bromo-2-methylbutane ((R)-11). The key chiral building block (S)-10 was envisaged to be prepared through a sequence of hydrolyzation, decarboxylation, borane

• prepared the target aggregation pheromone (4R,8R)-1, (4R,8S)-1, (4S,8R)-1, and (4S,8S)-1 (Scheme 4). Li2CuCl4-catalyzed coupling of chiral tosylate (S)-10 with the Grignard reagent derived from (R)-1-bromo-2-methylbutane ((R)-11) and Mg afforded (5R,9R)-5,9-dimethylundec-1-ene ((5R,9R)-12) in 80% yield [35

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

• chromatography [1]. Sometime later, kinetic resolution (KR) emerged. This method is based on the different reaction rates of each enantiomer in a racemic mixture when they are reacted with a reagent, a chiral catalyst, or an enzyme. This process results in obtaining the less reactive enantioenriched enantiomer

Photomechanochemistry: harnessing mechanical forces to enhance photochemical reactions

• Francesco Mele,
• Ana M. Constantin,
• Andrea Porcheddu,
• Raimondo Maggi,
• Giovanni Maestri,
• Nicola Della Ca’ and
• Luca Capaldo

Beilstein J. Org. Chem. 2025, 21, 458–472, doi:10.3762/bjoc.21.33

• (9.1) (Scheme 9) [75]. In this case the authors used a ball-mill reactor equipped with a blue LED, and the reaction was run in a glass vial with two transparent PMMA balls. The authors noted that fluorination of the vial and the use of silica gel to adjust texture were needed to prevent reagent

• using a mixture of 12.1 (0.2 mmol), NaI (1 equiv), Koser’s reagent, and Na2CO3 (each 4 equiv), in the presence of 100 wt % of SAOED, pyrrolidine 12.2 was isolated in 90% yield. As far as the mechanochemical setup is concerned, the authors milled the reaction mixture at 30 Hz in a 5 mL stainless-steel

Beyond symmetric self-assembly and effective molarity: unlocking functional enzyme mimics with robust organic cages

• Keith G. Andrews

Beilstein J. Org. Chem. 2025, 21, 421–443, doi:10.3762/bjoc.21.30

• predominantly achieved organization and polarization independently [26]. As we shall see, there has been a bias towards organization (controlling reagent distributions), often leaving any catalysis to chance. This even appears to be a strategy: “the search for supramolecular reactors that contain no

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

• emerged as potent catalysts for red-light-mediated photoreactions. Furuyama et al. demonstrated that a ruthenium phthalocyanin complex could catalyze trifluoromethylation reactions of styrene derivatives 18 with either CF3SO2Cl or Umemoto’s reagent 19 under red-light irradiation without the need for

Three-component reactions of conjugated dienes, CH acids and formaldehyde under diffusion mixing conditions

• Dmitry E. Shybanov,
• Maxim E. Kukushkin,
• Eugene V. Babaev,
• Nikolai V. Zyk and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 262–269, doi:10.3762/bjoc.21.18

• Dmitry E. Shybanov Maxim E. Kukushkin Eugene V. Babaev Nikolai V. Zyk Elena K. Beloglazkina Department of Chemistry, M. V. Lomonosov Moscow State University, 119991 Moscow, Russian Federation 10.3762/bjoc.21.18 Abstract A diffusion mixing technique with a volatile reagent was successfully used to

• main reaction products. Keywords: aldol condensation; [4 + 2]-cycloaddition; diffusion mixing; formaldehyde; Knoevenagel condensation; three-component reactions; Introduction Formaldehyde is a reactive electrophilic reagent widely used as a C1 building block in multicomponent reactions [1][2][3]. Its

• reactions that proceed through the formation of formaldehyde condensation products (Scheme 1). Previously, we have proposed a convenient diffusion mixing technique for multicomponent reactions based on the absorption of volatile reagent vapors by a mixture containing the remaining reaction components. This

Visible-light-promoted radical cyclisation of unactivated alkenes in benzimidazoles: synthesis of difluoromethyl- and aryldifluoromethyl-substituted polycyclic imidazoles

• Yujun Pang,
• Jinglan Yan,
• Nawaf Al-Maharik,
• Qian Zhang,
• Zeguo Fang and
• Dong Li

Beilstein J. Org. Chem. 2025, 21, 234–241, doi:10.3762/bjoc.21.15

• reaction (Table 1). Employing PIDA as the promoter, THF as the solvent, and 72 W white LED as the light source, the desired product 3a formed in 85% isolated yield at room temperature (Table 1, entry 1). We found that the hypervalent iodine reagent was of significant importance for the present

Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• dioxazolone bearing a linear alkyl group was efficiently converted to the N-vinylamide 26a in good yield. The observed regioselectivity followed the anti-Markovnikov fashion stemming from the regioselective hydrozirconation of the alkyne using Schwartz’s reagent [100]. Aryl substituents on the dioxazolone

Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• stoichiometric quantities of a copper reagent [3]. This pioneering work, known as the “classical Ullmann reaction”, was extended by Ullmann and Goldberg to enable the C–N and C–O bond formation [4][5][6]. Subsequently, key developments in Cu-catalyzed cross-coupling reactions were achieved, including the

• , Huang, and Mei et al. explored Cu-catalyzed electrochemical C(sp2)–H bromination of 8-aminoquinoline amide at the C5 site of quinoline using NH4Br as a brominating reagent under anoxic oxidation conditions (Figure 13) [64]. This catalytic reaction has a broad substrate scope, and further investigation

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

• -difunctionalization of alkenes carried out with carbazates (N-aminocarbamates) and (hetero)arene nucleophiles or amines exploiting N-(tert-butyl)-N-fluoro-3,5-bis(trifluoromethyl)benzenesulfonamide (NFBS) as intermolecular hydrogen-atom-transfer reagent results in alkylarylation processes (Scheme 5) [19]. The

• was crucial for the formation of the organozinc reagent (Scheme 19) [36]. Spiro-2,3-dihydroquinazolinones 26 were formed exploiting a one-pot multicomponent reaction, using isatoic anhydride, ketones and primary amines. The isolation of the amide intermediate XXIII obtained by the copper-catalyzed

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

• -axial chirality conversion and formation of axially chiral products 21a–e (Scheme 7). This critical aromatization was later studied in more detail, and the team was able to achieve enantiodivergent aromatization, which led to different atropoisomers based on the oxidation reagent used [26]. The use of

Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning

• Pablo Quijano Velasco,
• Kedar Hippalgaonkar and
• Balamurugan Ramalingam

Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3

• an AI model that recommends the sequence of operations needed to perform the corresponding chemical reactions, including the order of reagent addition [35]. This model facilitates that the synthesis tasks are sent to a robotic research lab from anywhere in the world, allowing the robot to execute the

• system comprised of a flow chemistry synthesis platform, a reagent delivery system, a packed bed reactor, process-analytical tools, and an integrated software control system that automates end-to-end process operations and monitoring. The system has been used to demonstrate the synthesis of at least ten

• . Using this configuration, the platform can perform a calibration of the reagent and product concentration through a standard addition method. Once the PAT is calibrated, the platform performs dynamic experiments where the concentration of the reagents is ramped to explore the parametric space. Finally

Synthesis, structure and π-expansion of tris(4,5-dehydro-2,3:6,7-dibenzotropone)

• Yongming Xiong,
• Xue Lin Ma,
• Shilong Su and
• Qian Miao

Beilstein J. Org. Chem. 2025, 21, 1–7, doi:10.3762/bjoc.21.1

• the carbonyl groups in 1, it was treated with three equivalents Lawesson's reagent, affording dithioketone 8a in a 40% yield together with trithioketone 8b in a yield of 10%. To expand the π-skeleton of 1, compound 8a was subjected to the Barton–Kellogg reaction with diazo compound 9, which was

Reactivity of hypervalent iodine(III) reagents bearing a benzylamine with sulfenate salts

• Beatriz Dedeiras,
• Catarina S. Caldeira,
• José C. Cunha,
• Clara S. B. Gomes and
• M. Manuel B. Marques

Beilstein J. Org. Chem. 2024, 20, 3281–3289, doi:10.3762/bjoc.20.272

• first report from Zhdankin and co-workers in 1994, described the preparation of azidobenziodoxolone, ABX (I), a reagent widely used in oxidative azide transfer reactions [21]. Years later, Zhdankin’s group also reported the synthesis of amidobenziodoxolone (II) [14]. Other examples of N-containing

• groups (V), which proved to be useful in the transfer of imine radicals [17]. Bolm et al. contributed also to this topic by introducing a sulfoximidoyl-containing benziodoxolone (VI) [18]. Recently, our group disclosed the first HIRs bearing a primary amine moiety, the benzylamine benziodoxolone reagent

• reagent 2a in most organic solvents, an alternative solvent was tested; nevertheless, BBX 2a showed to be insoluble when using toluene (Table 1, entry 3). To have further insights on the formation of sulfonamide 5aa, an experiment was conducted under the same stoichiometric conditions that yielded product

Giese-type alkylation of dehydroalanine derivatives via silane-mediated alkyl bromide activation

• Perry van der Heide,
• Michele Retini,
• Fabiola Fanini,
• Giovanni Piersanti,
• Francesco Secci,
• Daniele Mazzarella,
• Timothy Noël and
• Alberto Luridiana

Beilstein J. Org. Chem. 2024, 20, 3274–3280, doi:10.3762/bjoc.20.271

• photocatalytic activation (Figure 1b) [17][18][19][20][21]. A photocatalytic HAT or SET generates the corresponding boryl, α-amino or silyl radical, which can abstract a halogen atom from alkyl halides to form the corresponding alkyl radical. However, the use of TTMS as a XAT reagent had already been established

Germanyl triazoles as a platform for CuAAC diversification and chemoselective orthogonal cross-coupling

• John M. Halford-McGuff,
• Thomas M. Richardson,
• Aidan P. McKay,
• Frederik Peschke,
• Glenn A. Burley and
• Allan J. B. Watson

Beilstein J. Org. Chem. 2024, 20, 3198–3204, doi:10.3762/bjoc.20.265

• . studentship. G.A.B., F.P., and A.J.B.W. thank the Leverhulme Trust (RPG-2020-380). A.J.B.W. thanks the Leverhulme Trust for a Research Fellowship (RF-2022-014) and the EPSRC Programme Grant ‘‘Boron: Beyond the Reagent’’ (EP/W007517/1) for support.

Direct trifluoroethylation of carbonyl sulfoxonium ylides using hypervalent iodine compounds

• Radell Echemendía,
• Carlee A. Montgomery,
• Fabio Cuzzucoli,
• Antonio C. B. Burtoloso and
• Graham K. Murphy

Beilstein J. Org. Chem. 2024, 20, 3182–3190, doi:10.3762/bjoc.20.263

• discovered by Umemoto has proven an effective electrophilic trifluoroethyl transfer reagent [34][35], and to further explore the potential of fluoroalkyliodonium salts we evaluated the reactivity of such compounds in the context of sulfoxonium ylide derivatization. As depicted in Table 1, we began our

• easily available 2,2,2-trifluoroethyl(mesityl)iodonium triflate reagent enabled the straightforward trifluoroethylation of diverse sulfoxonium ylides under mild conditions and short reaction times. Various computational strategies were also employed to differentiate between competing halogen bond

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

• point of comparison, we examined the reactivity of 1 with CF3SF4Cl. This reagent is known to behave comparably to SF5Cl in radical chain reactions [17][59][60][61] and can also be prepared conveniently in house [62]. In an analogous equivalents screen, we found that the 5:3 product ratio shifts from 7.7

• phenomenon is quite sensitive to changes in the fluorinated sulfur reagent scaffold (see Supporting Information File 1 for more details). This second instance of controlled oligomerization of 1 using CF3SF4Cl was also studied at the PWPB95-D4/def2-QZVPP//PCM(Et2O)-ωB97X-D/def2-TZVP level of theory (Figure 3

• , e.g., a radical or cation) on the transannular carbon atom of a bicyclopentyl moiety can interact through space [35][63][64]. The consequence is ostensibly that more "nucleophilic" INT2 and INT5 are better matched for Cl atom abstraction from the "electrophilic" reagent (SF5Cl or CF3SF4Cl). To test

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

• firstly through the coordination of an alkene by the HVI reagent, which activates it toward intramolecular attack by an internal nucleophile. Following this, substitution of the iodane(III) can occur from the nucleophilic halide in solution to reveal the halo-cyclised product (Figure 2). In this review

• -, stereo-) of the reaction, which is influenced by the type of HVI reagent, the nature of the substrates employed and the proposed mechanism from the authors are all described. The halocyclisation of alkenes to make halogenated carbo or heterocycles is yet to be covered by a review, which is the vacancy

• C‒F bond to give predominantly the trans product, but this pathway competes with a less favourable SN2 nucleophilic attack by fluorine to form the cis product. However, a mechanism entirely mediated by the I(III) HVI reagent, with the Pd(OAc)2 only acting as a Lewis acid to activate the HVI reagent

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

• trifluoroethanol as the solvent and at room temperature [23][24][25][26]. In the initial reaction, propargylamine served as a bifunctional reagent, with the primary amine group participating in the first step and the terminal alkyne promoting the subsequent heteroannulation. (Scheme 2). As observed in our previous

• trifluoroethanol to Et3N for the subsequent catalysis). Thus, this protocol enabled a straightforward and rapid synthesis of highly 2-substituted indoles under mild reaction conditions, highlighting the versatility of propargylamine as a bifunctional reagent in post-Ugi-azide transformations. Our group pioneered

• the application of this reagent as a central building block in the synthesis of hybrid systems via Ugi-azide reactions, including structures based on triazoles-tetrazoles [24][26][27], benzofuran-tetrazoles [23] and indolizines-tetrazoles [25], all of which have significant relevance in medicinal