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

• (75 °C) are needed. The selectivity of the reaction shown in Scheme 27 could be explained according to the proposed mechanism (Scheme 28a). The first step is the generation of the trialkyl(chloromethyl)ammonium chloride species 36 from the amine compound and CH2Cl2. Then, 36 decomposes by a cleavage

• product 35b was obtained, confirming that the dihaloalkane compound is the source of the methylene unit (Scheme 28c). Depending on the stability of the leaving carbocation, the selectivity of the R–N cleavage follows the decreasing order for the R groups: H, t-Bu, allyl, benzyl > methyl > primary

• amine with two methyl groups and a benzyl or allyl group, the cleavage of the N–CH2Ph and N–allyl bond takes place more selective (by 85% and 67%, respectively), instead of the cleavage of an N–Me bond. This explains the high selectivity observed for some examples in Scheme 27. Finally, this methodology

Binding of tryptophan and tryptophan-containing peptides in water by a glucose naphtho crown ether

• Gianpaolo Gallo and
• Bartosz Lewandowski

Beilstein J. Org. Chem. 2025, 21, 541–546, doi:10.3762/bjoc.21.42

• chain is the second highest among the tested amino acids and approximately 30% lower than towards Trp (entry 5, Table 1). Thus, the glucose-derived naphtho crown ether 1 displays selectivity towards the binding of tryptophan over other amino acids in water. Additionally, 1 displays a slight preference

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

• higher selectivity with milder reaction temperatures. The weaker C(sp2)–Br bond is easier to cleave than a C(sp2)–H bond, resulting in a higher likelihood of radical substitution at those positions. To the best of our knowledge, there are no previous examples of perfluorobenzyl substitution of any PAH(Br

• , and poor selectivity. The latter approach was shown to be more promising due to a faster rate, use of an inexpensive, low-boiling solvent, and easier work-up. This method will continue to be investigated in our laboratory. The emission spectrum of 9,10-ANTH(BnF)2 revealed its deeper blue fluorescence

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

• promotes the Michael reaction, leading to the formation of the enantiomer (3R,4S) and consequently returning to the racemate. Then, we decided to investigate how concentration affects the rate and selectivity of the reaction at room temperature (Table 4). The retro-Michael reaction mainly occurs at a

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

• adhesion on the vial walls. Thus, the reactor was operated at 17.7 Hz for 20 h and the dimerization to 9.2 occurred in 96% 1H NMR yield with a 6:94 anti/syn selectivity. A different selectivity was observed when crystals were first ground, and then irradiated under argon without applying forces (65% yield

• , 70:30 anti/syn). This indicates a unique divergent photomechanochemical reaction pathway with respect to the simple irradiation in solid state. Remarkably, no selectivity was observed in solution state (DMSO as solvent), while a completely reversed selectivity (99%, anti/syn 91:9) was obtained when

• insoluble reagents and/or photocatalysts. Additionally, as discussed, the use of impact forces can lead to unique selectivity profiles compared to solution-based methods, further enhancing its utility. Thirdly, dissolved oxygen must be often meticulously removed in solution-based methods via tedious

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

• -accelerations (1019) [1], tolerance of contaminants, and selectivity associated with the power of enzymes. It is for this reason that I have sought to introduce supramolecular approaches into my organocatalysis [2]. From thermodynamics, there are two components to catalysis: organization (entropic) and

• hydrophobic [160] products have been popular, including hydrolyses, ring openings, and rearrangements [22]. These reaction classes have been discussed [24][25][140]. Cavity-directed changes in ion-localization [161][162] and pKa are effective [37][107][163][164], and size-selectivity [36][165][166][167] and

• conspicuously rare [340]. One reason is the requirement for structural directional bonding in self-assembly strategies, which limits available bonding vectors for precise internally directed functionality [340]. Indeed, a recent perspective [21] identified two approaches to site-selectivity in supramolecular

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

• phenol 16 and acceptor 19 to the anomeric position, thereby, making it suitable for glycoconjugate formation. They also reported the glycosylations leading to disaccharide 20 formation in solvent free conditions in significant 1,2-trans selectivity. This study holds the potential in improving the various

• acetoxonium ion, facilitating the 1,2-trans glycoside formation in high selectivity. The special feature of this protecting group lies in its orthogonal deprotection in the presence of acetyl or benzoyl protecting groups. The chloroacetyl group was found to be particularly labile on the application of

• ] or hydrazine dithiocarbonate [116][117]. Owing to its versatile selectivity, it has been widely used in oligosaccharide synthesis [118][119][120][121][122] to implement the neighbouring group participation protocol, thereby producing 1,2-trans glycosides in high yield and selectivity without

Synthesis, characterization, antimicrobial, cytotoxic and carbonic anhydrase inhibition activities of multifunctional pyrazolo-1,2-benzothiazine acetamides

• Ayesha Saeed,
• Shahana Ehsan,
• Muhammad Zia-ur-Rehman,
• Erin M. Marshall,
• Sandra Loesgen,
• Abdus Saleem,
• Simone Giovannuzzi and
• Claudiu T. Supuran

Beilstein J. Org. Chem. 2025, 21, 348–357, doi:10.3762/bjoc.21.25

• evolves [3]. Complex chemical scaffolds with more than one protein-engaging functionality in a single molecule are advantageous for selectivity. This concept of synergistic compounds and complex chemical interactions helps to boost biological activity and prolongs the emergence of resistance in pathogens

• for four types of human CA isoforms: CA I, CA II, CA IX, and XII. The first two are cytosolic forms while the other two are transmembrane forms. Reason for the selection of these CA isoforms was to develop a comparative relationship for inhibition selectivity between CAs (IX, XII) attributed to tumour

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

• become a powerful approach for achieving sustainable chemical transformations, combining high efficiency with energy-saving, mild conditions. By harnessing the deeper penetration and selectivity of red and near-infrared light, this method minimizes the side reactions typical of higher-energy sources

• for red-light-mediated reactions. In particular, the versatility of these catalysts offers new avenues for facilitating red-light-driven chemical transformations with greater selectivity and efficiency. Recently, the squaraine family, a class of organic compounds characterized by a four-membered

Molecular diversity of the reactions of MBH carbonates of isatins and various nucleophiles

• Zi-Ying Xiao,
• Jing Sun and
• Chao-Guo Yan

Beilstein J. Org. Chem. 2025, 21, 286–295, doi:10.3762/bjoc.21.21

• biologically important 3-substituted and spirooxindole derivatives [5][6][7]. The unique molecular architecture and remarkable pharmacological activities have made spirooxindole one of the hottest synthetic targets with fruitful chemical and steric selectivity [8][9][10][11][12][13][14][15]. In recent years

• triene derivatives can be prepared under relative mild reaction conditions with good steric selectivity. The single crystal structures of compounds 7a and 8a were successfully determined by X-ray diffraction method (Figure 4 and Figure 5). From the crystal structures, it can be found that the compound 7a

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

• difluoromethylene (PhCF2) group, stand out as particularly valuable in drug design. The CF2H group can serve as a lipophilic isostere for hydroxy (OH), amino (NH2), and thiol (SH) groups, thereby enhancing the efficacy and selectivity of therapeutic agents [4][5][6]. Similarly, the PhCF2 group offers unique

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

• reactions, particularly in controlling the high reactivity and selectivity of radical intermediates [13][14]. Early studies on copper-mediated radical reactions, such as Julia’s work on radical cyclization reaction [15], along with advancements in dimerization [16][17], oxidative cleavage [18][19], and

• functionalization with directing groups, however, achieving similar results without the assistance of a directing group continues to be a significant challenge [53][54]. Radical-based approaches can facilitate C(sp³)–H functionalization without directing groups, however, controlling the selectivity is difficult. In

• limited, which can restrict both reactivity and selectivity. Significant progress has been achieved in C–H activation reactions, with the use of directing groups, which play a crucial role in selectivity and reactivity. However, the use of directing groups requires additional synthetic steps for their

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

• demands solutions that meet multiple targets, such as yield, selectivity, purity, cost, environmental impact, etc. In recent years, the advancement of artificial intelligence (AI), machine learning (ML), and automation has produced a paradigm shift for chemical synthesis optimization techniques. By

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

• approaches have also gained widespread attention for their unique advantages in these transformations [4]. Radical chemistry often exhibits complementary reactivity to two-electron pathways and can be performed with high selectivity, atom economy, and functional group tolerance [5]. A well-known radical

• derivatives, a tertiary amide was firstly used to exclude selectivity issues arising from the hydrogen atoms of the amide functionality, yielding compound 23 in synthetically useful yield (39%). Interestingly, a secondary amide was formed in a higher yield of compound 24 (62%) compared to a Dha with a

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

• to explain the stereochemistry of the product of the IEDADA reaction, the Si face of the azadiene should be attacked by the enecarbamate with endo selectivity, thus leading to the (4S,5R,6R)-cycloadduct 46. In 2019, as a follow-up work of their previous work, Masson and co-workers published a

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

• Jon Atiba Buldt Wang-Yeuk Kong Yannick Kraemer Masiel M. Belsuzarri Ansh Hiten Patel James C. Fettinger Dean J. Tantillo Cody Ross Pitts Department of Chemistry, University of California, Davis, 1 Shields Avenue, Davis, CA 95616, U.S.A. 10.3762/bjoc.20.259 Abstract Selectivity in radical chain

• a single oligomer across a panoply of different transformations typically range from <1% to ≈30% when n > 1 is desired [35]. To the best of our knowledge, the assembly of functionalized [n]staffanes from 1 in high yield/selectivity and in one step via controlled radical oligomerization remains a

• chloropentafluorosulfanylated [2]staffane (SF5-BCP-BCP-Cl, 2), based on alternating radical polarity matching in the chain-propagation steps (Figure 1, bottom) [45][46][47]. Density functional theory (DFT) calculations provide insight into our observed selectivity, and our hypothesis is bolstered by computation of relative

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

• , we have collected and described the HVI-mediated halocyclisation reactions reported in the literature for each halide. We have organised the examples firstly by the halide nucleophile, and then secondly by the internal heteroatom nucleophile involved in the cyclisation. The selectivity (chemo-, regio

• cyclisation of alkenyl N-tosylamides using BF3-activated aryl iodane(III) carboxylates to create 3-fluoropiperidines [35]. The challenges faced relate to selectivity due to competing carboxyaminations (18, 18’), rather than fluoroamination (17, 17’), and difficulties in controlling the diastereoselectivity

• (Scheme 10). The selectivity of the reaction was also found to be influenced by the presence of electrolytes like TBABF4, and the ligand attached to I(III). Carboxyfluorination was observed, in which a ligand from the iodane, e.g., OAc, OPiv or o-I-OBz, adds and was found to compete with fluoroamination

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• solutions [18]. Similarly, Burns and co-workers reported di- and tetra-urea picket porphyrins highlighting, the impact of buried solvent molecules, such as DMSO, on the selectivity, affinity, and stoichiometry of anion binding [19]. Iron complexes of tetra-urea picket porphyrins further demonstrate how

• second-sphere interactions with a multipoint hydrogen-bonding pattern enhance CO2 reduction in organic solvents, improving stability, facilitating proton transfer, reducing energy barriers, and increasing selectivity [20]. Apart from advances in synthetic methodologies [2][21][22][23], the exploration of

• 100 °C for 6 hours in dichloroethane (DCE). All catalysts demonstrated regioselectivities of 95:5 (70b:71b) with 100% selectivity and good conversions (60% for 18a, 84% for 18b, 100% for 18c, 8% for 18d, 27% for 18e, and 8% for 18f), irrespective of the nature of anion. Additionally, they performed

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

• with greater efficacy and selectivity against targets related to BC. Thus, the 1,5-disubstituted tetrazole-indole hybrids, presented different effects on cell proliferation inhibition in MCF-7 cells (Figure 1) that could be attributable to the molecular background of cells [46][47][48][49]. The

Enantioselective regiospecific addition of propargyltrichlorosilane to aldehydes catalyzed by biisoquinoline N,N’-dioxide

• Noble Brako,
• Sreerag Moorkkannur Narayanan,
• Amber Burns,
• Layla Auter,
• Valentino Cesiliano,
• Rajeev Prabhakar and
• Norito Takenaka

Beilstein J. Org. Chem. 2024, 20, 3069–3076, doi:10.3762/bjoc.20.255

• systematic catalyst structure–reactivity and selectivity relationship study. The observed catalyst structure–enantioselectivity relationship of the present allenylation reaction was found exactly opposite to that of the analogous allylation reaction. The method provided eleven α-allenic alcohols in 22–99

• stable allenyltrichlorosilane that affords undesired homopropargylic alcohols [35][36] (Scheme 2b). Furthermore, Iseki [35] and Nakajima [36] evaluated only one chiral catalyst in their independent studies (i.e., no catalyst structure–reactivity and selectivity relationship study). In this context, we

• selectivity. Although both protocols reported the same result with respect to the selectivity, we decided to test whether the combination of propargyl bromide and CuF2 could afford isomerically pure propargyltrichlorosilane on a preparative scale. To our delight, we were able to generate

Chemical structure metagenomics of microbial natural products: surveying nonribosomal peptides and beyond

• Thomas Ma and
• John Chu

Beilstein J. Org. Chem. 2024, 20, 3050–3060, doi:10.3762/bjoc.20.253

• biased towards (or against) certain amino acids; while these trends are statistically valid, whether there is an underlying chemical principle that governs the observed selectivity remains unclear [52]. For example, tailoring enzymes for β-hydroxylation most often act on aspartate and asparagine. In

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• photoredox catalysis [26][27][28]. These methods allow selectivity to be controlled despite the presence of the complex cocktail of radical species generated by hydroperoxides under redox or homolysis conditions. The main challenge in selective radical peroxidation is the wide range of possible pathways

gem-Difluorovinyl and trifluorovinyl Michael acceptors in the synthesis of α,β-unsaturated fluorinated and nonfluorinated amides

• Monika Bilska-Markowska,
• Marcin Kaźmierczak,
• Wojciech Jankowski and
• Marcin Hoffmann

Beilstein J. Org. Chem. 2024, 20, 2946–2953, doi:10.3762/bjoc.20.247

• , we observed a striking illustration of this phenomenon. A Michael addition involving gem-difluorovinyl and trifluorovinyl acceptors was successfully achieved, demonstrating high stereoselectivity. This selectivity was further elucidated through theoretical calculations. Using this methodology, a

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• ]. They offer several advantages over traditional reagents, including low toxicity, high reactivity, and excellent selectivity [43] under simple reaction conditions. The distinctive reactivity of DIAS enables the smooth arylation of various carbon and heteroatom nucleophiles under gentle conditions, with

• -donating groups. The reaction exhibited high selectivity, with substitution at the C3 position not impeding the reaction. Different substituted diaryliodonium tetrafluoroborates were also investigated, yielding good product yields. The above protocol for the arylation of pyridine N-oxides 28, resulted in

• the reaction efficiency and selectivity was explored. A high selectivity was found for electron-withdrawing moieties, resulting in high yields of the N2-substituted products. Also, tetrazole 50 was arylated using the same hypervalent iodonium salts as a follow-up, but less than 14% of the targeted

C–H Trifluoromethylthiolation of aldehyde hydrazones

• Victor Levet,
• Balu Ramesh,
• Congyang Wang and
• Tatiana Besset

Beilstein J. Org. Chem. 2024, 20, 2883–2890, doi:10.3762/bjoc.20.242

• mixture. When the reaction was conducted in the presence of NBS in acetonitrile for 10 min, followed by the addition of AgSCF3, the desired product was isolated in 91% yield. A total selectivity for the formation of the Z isomer was observed as ascertained by 2D NMR (for more details, see Supporting