Visible-light-driven NHC and organophotoredox dual catalysis for the synthesis of carbonyl compounds

• Vasudevan Dhayalan

Beilstein J. Org. Chem. 2025, 21, 2584–2603, doi:10.3762/bjoc.21.200

• -rich and electron-poor substituents. This reaction was carried out between arylcyclopropanes 5 and acyl fluoride 4 in the presence of NHC (10 mol %) and 4CzIPN (5 mol %). Mechanistic studies showed that the cascade proceeds via nucleophilic ring-opening of a cyclopropyl radical cation D with subsequent

• radical-/radical cross-coupling performed between intermediates C and E. The reaction of acyl fluoride 4 in the presence of Cs2CO3 and NHC to produce benzoate A and the formation of some reactive intermediates are shown in Scheme 2. These methods will find suitable application in medicinal chemistry and

• production of ketone scaffolds, including drug moieties. The organocatalyzed acylation proceeds with excellent site selectivity and broad functional group tolerance of alkanes such as F, Cl, Br, I, CN, CF3, Me, and OMe. The reaction was achieved between acyl fluoride 4 and highly substituted alkane 7 in 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

• compound 54 was proposed by the authors [38]. It involves deprotection of the TES group in 54 using tetrabutylammonium fluoride (TBAF) to give 55. In the presence of O2 and TBAF, 55 spontaneously oxidized to 56. Intramolecular hemiketalization of 56 resulted in the formation of hemiketal 57, followed by

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 MeI in presence of benzyltrimethylammonium fluoride (BTAF). At this stage, to prepare optically active natural product, the racemic mixture of 51 was separated using chiral HPLC to afford (+)-51 and (−)-51, which were used to prepare both enantiomers of complanadine A for biological evaluations

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

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

• additional photocatalyst. Moreover, under the same photocatalyst-free conditions, UV-A-light-mediated reduction could be achieved using triethylsilane as the only reductant with subsequent desilylation and NHC elimination with fluoride delivering the corresponding aldehyde product. Keywords: carbenes

• research has demonstrated that NHCs are also capable of stabilizing radical or excited-state species [12][13]. In 2020, our group reported the concept of photo-NHC catalysis where direct excitation of acylazolium intermediates generated from o-toluoyl fluoride substrates with UV-A light resulted in a novel

• 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

Rhodium-catalysed connective synthesis of diverse reactive probes bearing S(VI) electrophilic warheads

• Scott Rice,
• Julian Chesti,
• William R. T. Mosedale,
• Megan H. Wright,
• Stephen P. Marsden,
• Terry K. Smith and
• Adam Nelson

Beilstein J. Org. Chem. 2025, 21, 1924–1931, doi:10.3762/bjoc.21.150

• intermolecular reaction was generally dominant. We have previously discovered sulfonyl fluoride probes with promising activity against T. brucei, a parasitic kinetoplastid that causes vector-borne African trypanosomiasis (sleeping sickness) [24]. We therefore screened the 23 sulfonyl fluoride probes (derived

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

• state, and in the presence of glutathione, opening the possibility for applications in a biological environment. Some interesting isatin-based arylhydrazones were reported [115][116][117]. Compound 122H is a P-type hydrazone photoswitch. The addition of tetrabutylammonium fluoride (TBAF) deprotonates

[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

• fluoride, is used for the synthesis of spirocyclic derivatives from arylidene-azolones. Four types of the corresponding heterocycles have been studied. A series of 7-thia-3-azaspiro[4.4]nonan-4-ones was obtained with yields varying from 17 to 99%. The stereochemical study revealed selective formation of

• provided by both methods (with cesium fluoride being preferred), while for rhodanine 3e this method was able to produce almost quantitative yield of cycloadduct 8e. In contrast, for hydantoin 2e and imidazolone 4e the use of TBAF was preferable. It is interesting to note that in all cases, we obtained only

• be determined. Conclusion A study on [3 + 2]-cycloaddition reaction of various arylidene-azolones, with thioformylium methylide was performed. We have shown that cesium fluoride or TBAF can be an effective source of fluoride iones for activation of chloromethyl(trimethylsilyl)methyl sulfide. The

Thermodynamics and polarity-driven properties of fluorinated cyclopropanes

• Matheus P. Freitas

Beilstein J. Org. Chem. 2025, 21, 1742–1747, doi:10.3762/bjoc.21.137

• conversion of cyclopropane and methyl fluoride into mono-, di-, tri-, tetra-, penta-, and hexafluorinated cyclopropanes is exothermic, except for the all-cis-1,2,3-trifluorocyclopropane (1.2.3-c.c.). Compounds featuring geminal fluorines are particularly stabilized due to anomeric-like nF → σ*CF interactions

• dispersion corrections to improve the modeling of nonbonding interactions [23]. The same computational protocol was applied to cyclopropane, methane, and methyl fluoride, used as reference molecules in the isodesmic reactions. This methodology has proven reliable for predicting the energetics and properties

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

• led to the stereoselective formation of β,α-1,1'-dimannoside 26 in 66% yield [57]. The procedure also demonstrated excellent stereoselectivity with the fluoride donor 27, resulting in the formation of β-mannosyl-α-glucoside 28. Furthermore, the use of acetyl and temporary 4,6-O-benzylidene protecting

• , respectively [64]. The use of TMS-stabilized lactol acceptors also found application in the synthesis of an E-selectin inhibitor. The tribenzylated TMS-β-galactose acceptor 56 was reacted with the tetrabenzylated mannosyl fluoride donor 55, ensuring high stereoselectivity in the formation of the α,β-1,1

Advances in nitrogen-containing helicenes: synthesis, chiroptical properties, and optoelectronic applications

• Meng Qiu,
• Jing Du,
• Nai-Te Yao,
• Xin-Yue Wang and
• Han-Yuan Gong

Beilstein J. Org. Chem. 2025, 21, 1422–1453, doi:10.3762/bjoc.21.106

• −1 (Table 3). Importantly, both dimers displayed selective fluoride ion recognition through hydrogen bonding, with (M,M)-12c exhibiting a high binding constant (Ka = 2 × 105 M−1). The resulting [12c·F−] and [12d·F−] complexes exhibited red-shifted circular dichroism (CD), fluorescence, and CPL

• -width (FWHM values as 24 nm and 22 nm). Stepwise titration experiments with fluoride ions induced a change in the coordination number of the boron centers from three to four, forming corresponding anionic species. This coordination triggered red-shifted absorption and CPL responses while maintaining

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

• years later, the group extended the scope of nucleophiles to azoles, sulphoximines (and other HN=S species), phosphites, phosphonites or secondary phosphine oxides, and developed selective reaction conditions for the alternative sulphur–fluoride exchange (SuFEx) pathway by employing hard anionic

Recent advances and future challenges in the bottom-up synthesis of azulene-embedded nanographenes

• Bartłomiej Pigulski

Beilstein J. Org. Chem. 2025, 21, 1272–1305, doi:10.3762/bjoc.21.99

• and co-workers demonstrated that also BN heterocycles can be obtained using similar types of precursors (Scheme 23) [107]. Compound 179 was reacted with PhBCl2 to yield BN heterocycle 180 in 78% yield. Compound 180 exhibits high sensitivity for the visual detection of fluoride ions and undergoes an

Synthetic approach to borrelidin fragments: focus on key intermediates

• Yudhi Dwi Kurniawan,
• Zetryana Puteri Tachrim,
• Teni Ernawati,
• Faris Hermawan,
• Ima Nurasiyah and
• Muhammad Alfin Sulmantara

Beilstein J. Org. Chem. 2025, 21, 1135–1160, doi:10.3762/bjoc.21.91

• . Reduction of the product to remove the Evans auxiliary furnished primary alcohol 72 in 84% yield. This alcohol was then protected as a THP ether, and the TBDMS group was removed using a fluoride source, yielding another primary alcohol 65 in 85% yield, thus completing the synthesis of the left-hand portion

• %), followed by protection of the secondary alcohol as TBDMS ether 81 (98%). The primary alcohol was then liberated using ammonium fluoride in hot methanol (60 °C). Oxidation of this alcohol to a carboxylic acid was achieved using TEMPO and (diacetoxyiodo)benzene (BAIB), completing the synthesis of the target

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

• pentafluoropyridine (PFP) via in situ formation of an active acid fluoride 48 to afford the corresponding amides 13 and 47 in moderate yields (Scheme 15) [47]. In addition, the amidation process could be scaled up to a gram scale to give 47 in 90% yield. Maruoka and co-workers (2021) converted cinnamic esters into

• active acid fluorides 48 by utilizing hypervalent iodine(III) of PhI(OPiv)2 and py·HF as the fluoride source to afford the corresponding amides 49 and 50 in excellent yields (Scheme 16) [48]. Herein, the hypervalent iodine(III) reagent reacted with the phenol group to give intermediates 51 and 52

• followed by the fluoride attack. Shibata and co-workers (2024) developed an amidation process by utilizing 1,1,2,2-tetrafluoroethyl-N,N-dimethylamine (TFEDMA) proceeding via an active acid fluoride in a mechanochemical fashion [49]. In this method, cinnamic acid was reacted with TFEDMA under solvent-free

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

• , oxidative addition of the C–I bond to palladium formed the four-membered aryl–palladium complex Int-5. Steric hindrance from the bulky dppm ligand, combined with slower aryne release (using KF as the fluoride source), attenuated aryne coordination. Under these electron-deficient conditions, CO

• to substrate 11, followed by oxidative addition and release of carbon dioxide to form the zwitterionic π-allylpalladium intermediate Int-21. Under the reaction conditions, silyl triflate 12 undergoes a fluoride-mediated 1,2-elimination to generate the cyclic allene intermediate Int-22. Through a

• double methylene insertions into nitrogen–boron bonds [53]. Copper-catalyzed substrate-controlled carbonylative synthesis of α-keto amides and amides [54]. Divergent sulfur(VI) fluoride exchange linkage of sulfonimidoyl fluorides and alkynes [55]. Modular and divergent syntheses of protoberberine and

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

• ) complex 1 was synthesized according the procedure described by Romoff et al. [16]. Sodium hydride was used as a 60% dispersion in mineral oil. Triethylamine was dried over CaH2 and distilled freshly before use. Perfluorobutanesulfonyl fluoride was dried over CaCl2 and freshly distilled before use. Other

Identification and removal of a cryptic impurity in pomalidomide-PEG based PROTAC

• Bingnan Wang,
• Yong Lu and
• Chuo Chen

Beilstein J. Org. Chem. 2025, 21, 407–411, doi:10.3762/bjoc.21.28

• pomalidomide or its close analogs, indicating that a side reaction unrelated to the SNAr of the fluoride has occurred. 1H NMR and MS analyses suggested that phthalimide 5 was the byproduct formed through this series of transformations. Supporting this hypothesis, analysis of the reaction intermediates

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

• -butyldimethylsilyloxy)-2,2-dimethylbutanoyl protecting group 33 [102] possessing the steric advantage of the pivaloyl group with the added advantage of it being cleaved with the help of fluoride anions implementing the affinity of the fluoride ion towards the Si atom [103]. Considering the versatility of the pivaloyl

Synthesis, structure, ionochromic and cytotoxic properties of new 2-(indolin-2-yl)-1,3-tropolones

• Yurii A. Sayapin,
• Eugeny A. Gusakov,
• Inna O. Tupaeva,
• Alexander D. Dubonosov,
• Igor V. Dorogan,
• Valery V. Tkachev,
• Anna S. Goncharova,
• Gennady V. Shilov,
• Natalia S. Kuznetsova,
• Svetlana Y. Filippova,
• Tatyana A. Krasnikova,
• Yanis A. Boumber,
• Alexey Y. Maksimov,
• Sergey M. Aldoshin and
• Vladimir I. Minkin

Beilstein J. Org. Chem. 2025, 21, 358–368, doi:10.3762/bjoc.21.26

• -n-butylammonium salts (TBAX: F, Cl, Br, I, CN). Exclusively cyanide and fluoride anions lead to a naked-eye effect due to a change of the solution’s colour from yellow-orange to pale yellow (Figure 5). At the same time, a new fluorescence band appears at 420–440 nm. The Stokes shifts of fluorescence

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

• desired N-arylamide 13 is yielded through protodemetalation. In this process, copper does not undergo further catalytic turnover, presumably due to the formation of inactive copper fluoride or copper hydroxide species. 1.5 N-Phosphorylation of dioxazolones Recently, Son and Kuniyil reported the N

Quantifying the ability of the CF₂H group as a hydrogen bond donor

• Matthew E. Paolella,
• Daniel S. Honeycutt,
• Bradley M. Lipka,
• Jacob M. Goldberg and
• Fang Wang

Beilstein J. Org. Chem. 2025, 21, 189–199, doi:10.3762/bjoc.21.11

• counterions, such as the bromide and fluoride anions [50], on HB interactions, all ionic compounds were synthesized with tetrafluoroborate, a classical weakly coordinating anion. Results and Discussion We first assessed the hydrogen bond acidity, A, of these CF2H-containing compounds using an established

Nickel-catalyzed cross-coupling of 2-fluorobenzofurans with arylboronic acids via aromatic C–F bond activation

• Takeshi Fujita,
• Haruna Yabuki,
• Ryutaro Morioka,
• Kohei Fuchibe and
• Junji Ichikawa

Beilstein J. Org. Chem. 2025, 21, 146–154, doi:10.3762/bjoc.21.8

• singlet peaks at 32.0–33.4 ppm and 38.6–40.5 ppm, appearing in a 1:1 ratio. These new peaks were attributed to nickelacyclopropane Eb, which was formed in 19% yield. No peaks corresponding to benzofuranylnickel(II) fluoride Fb, which would arise from the oxidative addition of 1b to nickel(0), were

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

• fluoride and BF3·OEt2 as activator. A range of unsaturated amines 5 were cyclised to racemic β-fluorinated piperidines 6. Good yields were reported for all compounds except those with substituents present on the alkene. Homologation of the carbon chain from 5 to 6 carbons gave both 6- and 7-membered rings

• fluoride ion to displace PhI. In pathway B (bottom), the nitrogen is oxidised by the iodane, generating an electrophilic intermediate B. Nucleophilic attack by the double bond subsequently forms the 6-membered ring intermediate C, which is either immediately attacked by fluoride to form both cis and trans

• proposed by the authors (Scheme 3). Activation of the HVI reagent by H-bonding leads to ligand exchange to give an aminofluoro iodonium intermediate A. Cyclisation occurs via nitrogen attack on the alkene to then give aziridinium intermediate B. Subsequent nucleophilic attack by fluoride on the more

Mechanochemical difluoromethylations of ketones

• Jinbo Ke,
• Pit van Bonn and
• Carsten Bolm

Beilstein J. Org. Chem. 2024, 20, 2799–2805, doi:10.3762/bjoc.20.235

• sodium fluoride catalyst, with simple ketones, which resulted in the formation of difluoromethyl 2,2-difluorocyclopropyl ethers (Scheme 1B). Although the reactions worked well, it is also noteworthy that the use of TFDA as reagent, liberated fluoro(trimethyl)silane (TMSF), carbon dioxide, and ozone