Photoorganocatalytic trifluoromethylation of (het)arenes in green conditions

• Egor N. Boronin,
• Svetlana E. Kaurkina,
• Milena M. Svetlakova,
• Anton S. Bolshakov,
• Maxim V. Arsenyev,
• Vasilii F. Otvagin,
• Alexey Yu. Fedorov,
• Timothy Noël and
• Alexander V. Nyuchev

Beilstein J. Org. Chem. 2026, 22, 662–671, doi:10.3762/bjoc.22.50

• solvent. Results and Discussion To identify reaction conditions consistent with the principles of green chemistry, we carried out an optimization study using different organic photocatalysts and solvents. The reactions were performed under an argon atmosphere in anhydrous solvents, employing 1,3,5

• improved outcome, delivering the product in 41% yield at only 1 mol % catalyst loading (Table 1, entry 3). On this basis, subsequent optimization was performed using 3DPAFIPN as the photocatalyst. Metal-containing catalysts were not used due to their lower environmental compatibility; moreover, they are

• at 25 °C) [30]. These results established EtOAc as the most suitable solvent for the transformation. The effect of reaction time was also evaluated. Variation from 1 h to 12 h (Table 1, entry 8) demonstrated that 6 h (Table 1, entry 5) is optimal for achieving the highest yield. Optimization of the

Advantages of PROTACs in achieving selective degradation of homologous protein families

• Luxi Yang,
• Xinfei Mao,
• Jingyi Zhang,
• Jing Shu,
• Wenhai Huang,
• Xiaowu Dong,
• Yinqiao Chen and
• Mingfei Wu

Beilstein J. Org. Chem. 2026, 22, 628–661, doi:10.3762/bjoc.22.49

• optimization often prioritizes the linker fragment, as its length and composition are critical determinants of target selectivity [39]. Recent evidence underscores the pivotal role of the linker in promoting the assembly of "positive cooperative" ternary complexes [40], wherein the linker participates in

• the VH032 ligand. Through systematic optimization of linker lengths, it was found that the molecule achieved optimal activity when the linker a consisted of six methylene groups and linker b consisted of three methylene groups. The resulting products 37 exhibited DC50 values of 7.7 nM and 5.0 nM for

Hydrogen production from formic acid catalyzed by NHC–Cu complexes

• Orlando Santoro and
• Catherine S. J. Cazin

Beilstein J. Org. Chem. 2026, 22, 620–627, doi:10.3762/bjoc.22.48

• labeling experiments. Proposed catalytic cycle for the NHC–Cu-catalyzed FA dehydrogenation. Dehydrogenative coupling of phenylsilane. Catalyst optimization.a Optimization of the amine.a Influence of the size of the amine on the dehydrogenation of FA/amine mixtures. Supporting Information Supporting

Computational prediction of C–H hydricities and their use in predicting the regioselectivity of electron-rich C–H functionalisation reactions

• Rasmus M. Borup,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2026, 22, 603–610, doi:10.3762/bjoc.22.46

• optimization in dimethyl sulfoxide (DMSO, ε = 47.2) using the GFN-FF-xTB [13] force field and the analytical linearised Poisson–Boltzmann (ALPB) [14] as the implicit solvation model. We then remove conformers with relative energies above 3 kcal/mol and select unique conformers by taking the centroids of a

• solvation model. We then conduct re-optimization in ORCA (v.5.0.4) [17][18], using the composite electronic structure method r2SCAN-3c [19] and the conductor-like polarizable continuum model (CPCM) [20] as the implicit solvation model. r2SCAN-3c is chosen as the optimal functional based on a benchmark study

• that evaluates the accuracy of different levels of theory, ranging from semiempirical methods (xTB [16]), composite electronic structure methods (r2SCAN-3c [19]) to DFT methods (M06-2X[21], CAM-B3LYP [22][23]). All methods are evaluated either as single-point calculations or optimization and frequency

Regioselective approach to 5-arylsulfonylisoxazoles and their antimicrobial activity

• Artem S. Sazonov,
• Dmitry A. Vasilenko,
• Denis V. Porfiriev,
• Yuri K. Grishin,
• Rimma A. Gazzaeva,
• Alisa P. Chernyshova,
• Maxim A. Kryakvin,
• Anna A. Baranova,
• Vera A. Alferova and
• Elena B. Averina

Beilstein J. Org. Chem. 2026, 22, 592–602, doi:10.3762/bjoc.22.45

• inhibited DNA Topo IV decatenation activity. Reactions for preparing 5-sulfonylisoxazoles. Scope of 5-nitroisoxazoles 1a–g in the reaction with thiophenols. Scope of 5-thioisoxazoles 2a-p in the reaction with mCPBA. Oxidation of 5-thioisoxazoles into 5-sulfinylisoxazoles. Optimization of oxidizing

Kinetic resolution of racemic planar-chiral vinylcymantrenes by molybdenum-catalyzed asymmetric metathesis dimerization

• Haruna Imazu,
• Hitoshi Izu,
• Yasuhiro Ohki and
• Masamichi Ogasawara

Beilstein J. Org. Chem. 2026, 22, 568–574, doi:10.3762/bjoc.22.42

• examined in the AMD/KR studies, and the results are summarized in Table 1. At the outset, the optimization of the reaction conditions, including a proper choice of chiral molybdenum-alkylidene precatalysts, was examined using rac-1a as a prototypical substrate. The AMD/KR reactions were conducted in

Experimental and DFT studies on the regioselective methanolysis of 5-azido-9-oxabicyclo[6.1.0]nonan-4-yl 4-nitrobenzoate isomers

• İlknur Polat,
• Selçuk Eşsiz and
• Emine Salamci

Beilstein J. Org. Chem. 2026, 22, 547–556, doi:10.3762/bjoc.22.40

• ++(d,p) [29][30][31], and SMD [32] model (methanol (ε = 32.613)) were employed. Initial geometries were pre-optimized using MM2 (ChemDraw 3D) prior to DFT optimization to account for conformational flexibility. The 3D molecular structures were visualized using the open-source software cheMVP.exe. DFT

Get a better glimpse on sequential photoreactions of trisnorbornadienes with ¹⁹F NMR spectroscopy

• Julian Felix Maria Hebborn,
• Ben Eric Merten,
• Thomas Paululat and
• Heiko Ihmels

Beilstein J. Org. Chem. 2026, 22, 527–534, doi:10.3762/bjoc.22.38

• 19F NMR spectroscopy, further structural optimization is necessary for application purposes. Experimental Synthesis 1,3,5-Tris(bicyclo[2.2.1]hepta-2,5-dien-2-yl)-2,4,6-trifluorobenzene (1f) A mixture of 1,3,5-tribromo-2,4,6-trifluorobenzene (212 mg, 575 µmol), 4,4,5,5-tetramethyl-2-(bicyclo[2.2.1

Modern synthetic pathways towards eribulin and its subunits

• Sebastian Dominik Graf

Beilstein J. Org. Chem. 2026, 22, 495–526, doi:10.3762/bjoc.22.37

• aldehyde 200. Another optimization was achieved during the formation of the central ketal motif of 186 (Scheme 22). Here, the diastereomeric mixture of 183 (see Scheme 19) was exposed to light-mediated DDQ-oxidation within a continuous flow setup, which yielded epimers (R)-184 and (S)-184. This mixture was

A facile and practical method for the synthesis of trans-(±)-taxifolin and its derivatives via Darzens reaction

• Bo Peng,
• Panpan Yang,
• Maaz Khan,
• Xiaotong Lin,
• Jiang Wu,
• Peng Fu and
• Qingqing Wu

Beilstein J. Org. Chem. 2026, 22, 443–450, doi:10.3762/bjoc.22.31

• synthesis of trans-(±)-taxifolin, some representative derivatives, such as (±)-TD-1, (±)-TD-2, (±)-TD-3, (±)-TD-4 (Scheme 3), could also be synthesized readily by this method, highlighting the potential applicability of this method to structural optimization of the taxifolin skeleton. It is worth noting

• developed in this work. Yields are isolated yields; asynthesis on 10 gram scale; bsynthesis on 1 gram scale. Reaction conditions optimization for the Darzens reaction of 2 with 3a.a Acid screening for the deprotection and cyclization of (±)-4a to trans-(±)-taxifolin.a Supporting Information Supporting

Dialkylaminoalkylation of β-ketosulfones via ring-opening of 3-sulfonylpyrrolidines

• Evgeny M. Buev,
• Alexander V. Pavlushin,
• Vladimir S. Moshkin and
• Vyacheslav Y. Sosnovskikh

Beilstein J. Org. Chem. 2026, 22, 383–389, doi:10.3762/bjoc.22.26

• optimization of the reaction conditions.a Supporting Information Supporting Information File 12: Experimental section, characterization data and copies of spectra. Funding This work was financially supported by the Russian Science Foundation (Grant 22-73-10008-П).

Electrosynthetic access to unsymmetrical oxaza[8]helicenes with high chiral stability and strong circularly polarized luminescence (CPL)

• Tin Zar Aye,
• Rubal Sharma,
• Muthu Karuppasamy,
• Daiya Suzuki,
• Haruka Nakajima,
• Yoshitane Imai,
• Mitsuhiro Arisawa,
• Mohamed S. H. Salem and
• Shinobu Takizawa

Beilstein J. Org. Chem. 2026, 22, 372–382, doi:10.3762/bjoc.22.25

• -bromophenanthrene (1) via Buchwald–Hartwig amination with p-toluidine under Pd catalysis [55] – was subjected to phosphoric acid-mediated annulation with p-benzoquinone to give the hydroxycarbazole derivative 3 through a tandem Michael addition/ring-closure sequence. After rapid optimization of key parameters (see

• insight into the electronic transitions, we performed time-dependent DFT (TD-DFT) calculations for all oxaza[7]helicenes 6 and oxaza[8]helicenes 5 after geometry optimization at the S1 minimum (see Supporting Information File 1 and Supporting Information File 2) [62][63]. The convergence of these

A mild and atom-efficient four-component cascade strategy for the construction of biologically relevant 4-hydroxyquinolin-2(1H)-one derivatives

• Dmitrii A. Grishin,
• Kseniia I. Sharkovskaia,
• Ilya G. Kolmakov,
• Daria A. Ipatova,
• Rostislav A. Petrov,
• Nikolai D. Dagaev,
• Dmitry A. Skvortsov,
• Maria G. Khrenova,
• Valeriy V. Andreychev,
• Sergei A. Evteev,
• Yan A. Ivanenkov,
• Roman L. Antipin,
• Olga А. Dontsova and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2026, 22, 244–256, doi:10.3762/bjoc.22.18

• (Scheme 3) involved the optimization of a two-step procedure reported previously for their preparation from corresponding anilines and malonic ester [40][41][42][43]. The intermediate N1,N3-bis(4-halogenophenyl)malonamides 1a–c were synthesized from 4-halogen-substituted anilines and diethyl malonate in

Conformational analysis of difluoromethylornithine: factors influencing its gas-phase and bioactive conformations

• Matheus P. Freitas

Beilstein J. Org. Chem. 2026, 22, 237–243, doi:10.3762/bjoc.22.17

• minimize gauche C–F interactions [13][14][15][16][17][18]. It is also noteworthy that the zwitterionic form of DFMO dissociates upon gas-phase optimization, whereas the non-zwitterionic form in implicit water, modeled using the solvation model density (SMD), remains stable in a type-I conformation, with

Base-promoted deacylation of 2-acetyl-2,5-dihydrothiophenes and their oxygen-mediated hydroxylation

• Vladimir G. Ilkin,
• Margarita Likhacheva,
• Igor V. Trushkov,
• Tetyana V. Beryozkina,
• Vera S. Berseneva,
• Vladimir T. Abaev,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2026, 22, 192–204, doi:10.3762/bjoc.22.13

• products (Scheme 1D) or the deacetylated products (Scheme 1E) have been developed. Results and Discussion Dihydrothiophene 1a was selected as a model substrate for our optimization study (Table 1). Initially, this compound was treated in ethanolic solution (2 mL) at room temperature in air for 1 h in the

• (0.13–0.22 mmol, 1.0 equiv), sodium (0.66–1.11 mmol, 5 equiv), dry EtOH (2.5–3.0 mL). Control experiments. Proposed mechanism. Optimization of the transformation of dihydrothiophene 1a.a Optimization of the transformation of dihydrothiophene 4a.a Supporting Information Supporting Information File 17

A new synthesis of Tyrian purple (6,6’-dibromoindigo) and its corresponding sulfonate salts

• Holly Helmers,
• Mark Horton,
• Julie Concepcion,
• Jeffrey Bjorklund and
• Nicholas C. Boaz

Beilstein J. Org. Chem. 2026, 22, 167–174, doi:10.3762/bjoc.22.10

• to produce 4. This reaction sequence would mediate the oxidation of the tolyl methyl group of 3 to an aldehyde without the use of chromium(VI). Benzylic bromination of 3 was accomplished using a combination of a radical initiator and a bromine source. Initial optimization of the benzylic bromination

Circumventing Mukaiyama oxidation: selective S–O bond formation via sulfenamide–alcohol coupling

• Guoling Huang,
• Huarui Zhu,
• Shuting Zhou,
• Wanlin Zheng,
• Fangpeng Liang,
• Zhibo Zhao,
• Yifei Chen and
• Xunbo Lu

Beilstein J. Org. Chem. 2026, 22, 158–166, doi:10.3762/bjoc.22.9

• substitution to give enantioenriched sulfilimines with up to 93% ee, underscoring the potential of this platform for the streamlined construction of chiral sulfur(IV)–nitrogen frameworks. Further optimization to enhance stereocontrol is currently underway. Representative molecules containing a sulfilimine

• diastereomeric sulfinimidate esters. Reaction optimization for the synthesis of sulfinimidate esters.a Supporting Information Supporting Information File 4: Experimental procedures, characterization data and copies of spectra. Funding We are grateful to the National Natural Science Foundation of China

Highly electrophilic, gem- and spiro-activated trichloromethylnitrocyclopropanes: synthesis and structure

• Ilia A. Pilipenko,
• Mikhail V. Grigoriev,
• Olga Yu. Ozerova,
• Igor A. Litvinov,
• Darya V. Spiridonova,
• Aleksander V. Vasilyev and
• Sergey V. Makarenko

Beilstein J. Org. Chem. 2026, 22, 123–130, doi:10.3762/bjoc.22.5

• described earlier [39] results in its formation in 18% of yield (Table 1, method A). Optimization of the process by using various bases and solvents showed that the best yield of cyclopropane 2 (64%) was obtained in a tetrahydrofuran (THF) solution in the presence of triethylamine (Table 1, method E). The

Synthesis and applications of alkenyl chlorides (vinyl chlorides): a review

• Daniel S. Müller

Beilstein J. Org. Chem. 2026, 22, 1–63, doi:10.3762/bjoc.22.1

• in a combined yield of 44% (Scheme 4). Additional optimization reactions showed that when the reaction was carried out at −10 °C even in the absence of Hünig’s base dichloride 15 could be obtained in 92% yield. Treatment of 15 with KOt-Bu in toluene gave the desired compound 19 in 43% yield. The

• (Scheme 62B). Systematic optimization studies revealed that additives, such as magnesium bromide etherate or HMPA, had a pronounced impact on both reaction efficiency and stereoselectivity. In 2005, Yan reported that the direct oxidative addition of chloroform to a Mg–TiCl4 bimetallic system generates a

Sustainable electrochemical synthesis of aliphatic nitro-NNO-azoxy compounds employing ammonium dinitramide and their in vitro evaluation as potential nitric oxide donors and fungicides

• Alexander S. Budnikov,
• Nikita E. Leonov,
• Michael S. Klenov,
• Andrey A. Kulikov,
• Igor B. Krylov,
• Timofey A. Kudryashev,
• Aleksandr M. Churakov,
• Alexander O. Terent’ev and
• Vladimir A. Tartakovsky

Beilstein J. Org. Chem. 2025, 21, 2739–2754, doi:10.3762/bjoc.21.211

• Table 1. After extensive optimization, we found that a 77% yield (75% isolated yield) of 2a was achieved by performing the model reaction under CCE (constant current electrolysis) conditions in an undivided electrochemical cell, using a platinum plate as the anode and a platinum wire as the cathode

• ) [112], ethyl 2-nitro-2-nitrosopropanoate (1h) [112], 1-nitrosocyclohexane-1-carbonitrile (1i) [113], were prepared according to the reported procedures. General procedure for the optimization of the reaction conditions for the synthesis of 2-nitro-2-(nitro-NNO-azoxy)propane (2a) from 2-nitro-2

• length constraints were used for the generation of conformer ensembles of transition states in order to avoid optimization to starting reagent(s) or product(s). On the next step, most stable conformers were identified by re-optimization of generated conformers and vibrational analysis on ωB97X-3c [94

Competitive cyclization of ethyl trifluoroacetoacetate and methyl ketones with 1,3-diamino-2-propanol into hydrogenated oxazolo- and pyrimido-condensed pyridones

• Svetlana O. Kushch,
• Marina V. Goryaeva,
• Yanina V. Burgart,
• Marina A. Ezhikova,
• Mikhail I. Kodess,
• Pavel A. Slepukhin,
• Alexandrina S. Volobueva,
• Vladimir V. Zarubaev and
• Victor I. Saloutin

Beilstein J. Org. Chem. 2025, 21, 2716–2729, doi:10.3762/bjoc.21.209

• three nucleophilic centers in 1,3-diaminopropan-2-ol (3), and because there is a need to increase diastereoselectivity of the cyclization process. Table 1 presents the optimization steps for the reaction conditions at various solvents and temperature. The reaction course was monitored by TLC and 19F NMR

• , AcOH, Et3N, 60 °C. The proposed mechanism of three-component cyclization of 3-oxo ester 1, methyl ketones 2a–d and 1,3-diaminopropan-2-ol (3). Optimization of the reaction conditions for ethyl trifluoroacetoacetate (1), acetone (2a) and 1,3-diaminopropan-2-ol (3). The conversion and the preparative

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

• transformation compared to KSCN and NH4SCN (Table 1, entry 12 vs entries 18 and 19). The optimization of the reaction conditions showed that the best yields were obtained when the reaction was carried out in AcOH/MeCN 1:3 using 2 equiv of NaSCN (Table 1, entry 12). Isothiazolium salt 2a and 2,5-dihydrofuran 3a

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

• trifluoroethanol enabled the desired [4 + 2]-addition. Some aromatization as well as ketal deprotection was observed, so by optimization, AgSbF6 and diethyl fumarate enhanced this reactivity, while this modification also significantly improved the yield to 59% of this step. It was noted that the silver salt helped

Chemoenzymatic synthesis of the cardenolide rhodexin A and its aglycone sarmentogenin

• Fuzhen Song,
• Mengmeng Zheng,
• Dongkai Wang,
• Xudong Qu and
• Qianghui Zhou

Beilstein J. Org. Chem. 2025, 21, 2637–2644, doi:10.3762/bjoc.21.204

• . Based on the above preliminary results, we subsequently performed extensive optimization of fermentation conditions for a scalable synthesis of 4. As shown in Table 1, when the substrate loading was increased to 0.25 g/L, a much longer reaction time (2 days) was required to allow complete conversion

• natural products. Representative CGs with promising biological activities. Retrosynthetic analysis of rhodexin A and sarmentogenin. Chemoenzymatic synthesis of sarmentogenin (2). Synthesis of rhodexin A. Optimization of the fermentation conditions of the biocatalytic C14–H α-hydroxylation. Supporting

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

• -membered and the five-membered rings. A relaxed dihedral scan – which allows a geometry optimization at every step – indicated that torsion barriers exceed 25 kJ/mol (Figure 5), indicating that the torsion angle is about twice as rigid as the torsion of a regular sigma bond in ethane (≈12 kJ/mol) [77][78

• solutions, adapted from ref. [92][93]. Optimization of reaction conditions for the synthesis of (Z)-5-benzylidene-2-thioxothiazolidin-4-one under microwave heating.a Experimental and Boltzmann-weighted B97-D/def2-TZVPP chemical shifts (ppm) of molecules 3n and 4n. Boltzmann-weighted B97-D/def2-TZVPP