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

• reacted with aminoarylaldehydes 5 to form axially chiral 2-arylquinoline derivatives 6 (Scheme 2). Using the pyrrolidine derivative C2 as the most efficient organocatalyst, a range of quinoline derivatives were obtained in high yields and enantiomeric purities. The postulated mechanism consists of iminium

• ) annulation of enals with ynamides 8 to afford axially chiral 7-arylindolines 9 was reported [20]. The reaction mechanism, rationalized by DFT calculations, is believed to occur through catalyst C3 activation of the substrate 8, dehydration, and deprotonation with tautomerization leading to the enamine

• [27]. This transformation led to a series of axially chiral cycl[3.2.2]azines 24 in good yields and high enantiomeric purities (Scheme 8). The proposed mechanism comprises enamine activation, condensation with nitroolefin 23, ring closure, and catalyst elimination to provide the axially chiral product

Hot shape transformation: the role of PSar dehydration in stomatocyte morphogenesis

• Remi Peters,
• Levy A. Charleston,
• Karinan van Eck,
• Teun van Berlo and
• Daniela A. Wilson

Beilstein J. Org. Chem. 2025, 21, 47–54, doi:10.3762/bjoc.21.5

• . However, when the membrane gets too stiff, the deformation is prevented regardless of the increased force that is applied. For further affirmation of the mechanism circular dichroism (CD) spectroscopy was employed to give more insight on the morphological changes in the polymers secondary structure

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

• . Proposed mechanism for the formation of the hydroxylamine side product b. N-Phenethylhydroxylamine (d), originated during the reduction process, reacts with the acetaldehyde e resulting from the hydrolysis of the aldoxime precursor c. The reduced β-nitrostyrene scaffolds with their corresponding products

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

• . A plausible mechanism is proposed, suggesting a possible radical pathway. Keywords: electrophilic amination; hypervalent iodine reagents; sulfinamide; sulfonamide; Introduction Iodine(III) compounds, known as λ3-iodanes, have been extensively applied in organic synthesis. Although initially used

• from the simultaneous formation of sulfinamide 6ea also isolated in this reaction for the first time (both in trace amounts). Reaction mechanism The inability to detect sulfinamide 6 and the isolation of sulfonamide 5, along with other byproducts (3, 4, and 7), stimulated us to propose a plausible

• reaction mechanism that would support both the obtained yields and the formation of unexpected species. As mentioned above, the presence of light influences the reaction outcome. When the reaction was carried out in the absence of light, only 4a, 3a, and 7a were isolated (under these conditions, there was

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

• Michael addition product was obtained with low diastereoselectivity. The mechanism is described in Scheme 4: the bifunctional squaramide activates the azadiene through hydrogen bonding while the malononitrile is deprotonated by the tertiary amine present in the backbone of the catalyst, establishing

• -azadienes bearing substituents at the ortho-position were tested, the enantioselectivities decreased, probably due to higher steric hindrance. The mechanism of the reaction is depicted in Scheme 7; firstly, the dual activation of the azadiene and the enol form of the azlactone through hydrogen bonding with

• azadiene in a stepwise mechanism: firstly, the vinylogous Michael addition of the dienolate to the double bond of the α,β-unsaturated N-sulfonylimine occurs in a stereoselective fashion. Subsequently, cyclization due to an intramolecular aza-Michael reaction and protonation leads to the enantioenriched

Synthesis of 2H-azirine-2,2-dicarboxylic acids and their derivatives

• Anastasiya V. Agafonova,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2024, 20, 3191–3197, doi:10.3762/bjoc.20.264

• not isomerize at room temperature, which is typical for highly sterically congested isoxazoles containing a 3-tert-butyl substituent [26]. The mechanism of such isomerizations of isoxazoles has been previously discussed using DFT calculations [25][26], which revealed the formation of an isoxazole–Fe

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

• reactants. Finally, DFT calculations provided insights about the mechanism of this transformation, which strongly suggest that an SN2 reaction is operative. Keywords: alkylation; DFT calculations; fluorine chemistry; hypervalent iodine; sulfoxonium ylide; sulphur ylides; Introduction Introducing fluorine

• in 87% yield (Scheme 3b). To gain insight into the mechanism, we modelled two reaction pathways commonly suggested for the 2,2,2-trifuoroethyl(mesityl)iodonium triflate salt, and for related diaryliodonium salts (Figure 2). The first mechanism explored was the associative pathway that terminates via

• with them being viable electrophilic sites for halogen bond formation with 1a, supporting the mechanism in path 1. We also expressed the LUMO and LUMO+1 molecular orbitals of 2a’ (Figure 3, middle and right, respectively), which showed lobes centered on the I–C bonds to both the trifluoroethyl and

Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies

• Lucía Campos-Prieto,
• Aitor García-Rey,
• Eddy Sotelo and
• Ana Mallo-Abreu

Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261

• ). Finally, recent research has implicated melatonin in modulating the Nrf2/ARE pathway, a crucial defense mechanism against OS and inflammation. In this study, FATMHs and LATMHs were synthesized through Ugi reaction and evaluated for their therapeutic potential in AD. Among these compounds, FATMH 6a emerged

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

• formation [35][48]. For instance, in 2022, we reported a method for chloropentafluorosulfanylation of [1.1.1]propellane, i.e., to make SF5-BCP-Cl (4), that ostensibly proceeds through a radical chain propagation mechanism [36]. Under optimized conditions, we obtained product 4 in 86% yield, and the

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

• 4 [9][10] (Figure 1). Halogenated cyclised structures have also been found to exhibit medicinal and pharmaceutical properties, including antibacterial [11], antibiotic [12], and enzyme inhibition [13] among others. The general mechanism for the HVI-mediated halocyclisation of alkenes proceeds

• -, 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

• good yields, demonstrating the scope of the reaction. The authors proposed an alternative reaction mechanism to those already described, in which trans-aminopalladation of the alkene, mediated by Pd(II), occurs with intramolecular attack of the nitrogen on the terminal carbon, generating a 6-membered

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

• active groups for a variety of substrates, making their use as supramolecular organocatalysts based on bifunctional activation mechanism (hydrogen-bonding/Lewis basicity) highly promising. At the same time, additional functional groups that are required for the catalysis can be easily installed on the

• ]pyrrole α,β-isomer 4 was found to be catalytically active providing a 57% conversion to 10, suggesting a concerted cycloaddition mechanism. Calix[4]pyrrole α,α-isomer 3 and dipyrromethane 5 were catalytically inactive. The authors concluded that the catalytic inactivity of 3 is caused by the parallel

• , with TBAI as a co-catalyst, up to 74% yields (Table 1). The inactivity of porphyrin 18 was attributed to the inaccessibility of the inner core imine due to its planar structure. The mechanism of the epoxide ring-opening reaction was elucidated by DFT calculations, which suggested that the macrocycle

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

• chemistry and optical science. A plausible reaction mechanism for the formation of the target molecules 18a–n via a high-order multicomponent reaction is shown in Scheme 3 and consists of two processes: an Ugi-azide reaction and a Pd/Cu-catalyzed heteroannulation reaction. The Ugi-azide reaction mechanism

• cytotoxic compounds. For example, a cytotoxic effect was found in CAL 27 cells, presumably through a mechanism of TNF-α inhibition in vitro, which could be related to the anti-inflammatory effect identified in several studies of NSAIDs that inhibit cancer cell viability in vitro [37][38]. In another study

• aimed at inhibiting tubulin assembly, N-mesyl-2-(1-phenylvinyl)indoles were active against HCT-116 cells on the order of a GI50 of 10 mM, although the mechanism originally sought was not demonstrated [39]. Therefore, in this work, the cytotoxic activity of methanesulfonylindoles 18a–j was explored

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

• ][34]. In sharp contrast, propargyltrichlorosilane is configurationally stable and only reacts through the SE2’ mechanism under Lewis base-catalyzed conditions [43][44][45], although it was reported that distillation of propargyltrichlorosilane substantially isomerizes it to the thermodynamically more

• structure–enantioselectivity relationship is exactly opposite to that for the analogous allylation reaction reported by Nakajima [47], thus it raises a possibility that the asymmetric induction mechanism could be fundamentally different between the present allenylation with propargyltrichlorosilane and the

• study, Hoveyda and co-workers proposed a similar mechanism for the isomerization of alkynes to allenes catalyzed by 1,8-diazabicyclo[5.4.0]undec-7-ene [61]. Conclusion In this study, we prepared distilled propargyltrichlorosilane with >99% isomeric purity for the first time, developed its asymmetric

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

• molecules were screened for various bioactivities and led to the discovery of new antibiotics, antifungals, as well as anticancer compounds (Figure 4). Importantly, the underlying mechanism of bacterial growth suppression has been identified for several Syn-BNP antibiotics, which includes both general mode

• herein are hits from various bioactivity screens. For each Syn-BNP, its name is in bold, the microorganism that harbors the corresponding BGC is italicized, followed by its bioactivity and the target/mechanism of action (if known). a) “Offloading” is the final step of NRP biosynthesis, wherein the mature

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

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

• colleagues firstly demonstrated that the decomposition of tert-butyl hydroperoxide (TBHP) by Co(II) naphthenate proceeds via a chain mechanism, leading to the formation of tert-butoxy and tert-butylperoxy radicals (Scheme 4) [24]. When cyclohexene (1) and oct-1-ene (3) were added, the corresponding products

• -t-Bu)2. Allylic peroxidation of 3-substituted prop-1-ene-1,3-diyldibenzenes 8 was performed with TBHP as the oxidant/peroxidation agent and with Cu2O as the catalyst [42] (Scheme 6). The proposed mechanism of peroxides 9 formation does not include peroxo–copper complexes and begins with the

• peroxidation of 31 with the formation of products 32 can be achieved as both using Cu-catalysis and in metal-free conditions (Scheme 13). The metal-free peroxidation with TBHP was also demonstrated using 3,4-dihydro-1,4-benzoxazin-2-ones 33 as substrates (Scheme 13) [54]. The assumed mechanism of the target

Structure and thermal stability of phosphorus-iodonium ylids

• Andrew Greener,
• Stephen P. Argent,
• Coby J. Clarke and
• Miriam L. O’Duill

Beilstein J. Org. Chem. 2024, 20, 2931–2939, doi:10.3762/bjoc.20.245

• correspond to a geometric rearrangement, e.g., Berry pseudorotation, which occurs prior to decomposition [31]. A large dihedral angle φ is thought to facilitate this rearrangement, thus accelerating decomposition [38][39]. Decomposition mechanism Further analysis was carried out to gain a better

• understanding of the decomposition mechanism. Despite large differences in Tonset, most samples showed relatively consistent second decomposition steps at ca. 225 °C (Figure 3b), which is indicative of a common decomposition intermediate for all compounds. To investigate this common intermediate, ex-situ mass

• heated to temperature T2 (136–205 °C, see Supporting Information File 1) until 20–40% mass loss of original weight. Based on this data, the following decomposition mechanism is proposed (Figure 4a): MS, 1H and 31P NMR analysis after heating to T1 showed the presence of (methyloxycarbonylmethyl

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

• presence of fluorine and a newly installed electron-deficient aryl group on α-carbon which increases electrophilicity of the α-carbon center [55]. The proposed reaction mechanism (Scheme 2) begins with the formation of one of two potential iodine intermediates, labeled as I or II. These intermediates arise

• absence of a base. Additionally, the presence of 40 equivalents of water proved to be crucial for the reaction, as altering the amount of water significantly impacted the product yield, indicating the importance of water in the reaction mechanism. A diverse range of functionalized diaryliodonium salts

• mechanism by adding 2 equivalents of TEMPO to the reaction mixture. The absence of the desired product indicated the involvement of a radical pathway in the process. The proposed reaction mechanism begins with the activation of eosin Y by visible light from 5 W blue LEDs, transitioning it to its excited

Synthesis of pyrrole-fused dibenzoxazepine/dibenzothiazepine/triazolobenzodiazepine derivatives via isocyanide-based multicomponent reactions

• Marzieh Norouzi,
• Mohammad Taghi Nazeri,
• Ahmad Shaabani and
• Behrouz Notash

Beilstein J. Org. Chem. 2024, 20, 2870–2882, doi:10.3762/bjoc.20.241

• analysis, mass spectrum, and IR are consistent with the structure (for details see Supporting Information File 1). Finally, a single crystal X-ray analysis of compound 6a was performed, confirming the structure (Figure 4). The proposed mechanism for an isocyanide-based multicomponent domino reaction for

• mmol) under solvent-free conditions, stirring in an oil bath at 80 °C for 2 h (monitored by TLC). A suggested mechanism for compounds 4. Synthesis of pyrrole-fused dibenzoxazepine/triazolobenzodiazepine through a 4-CR. Gram-scale synthesis of pyrrole-fused dibenzoxazepine/triazolobenzodiazepine 4a and

N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240

Synthesis of tricarbonylated propargylamine and conversion to 2,5-disubstituted oxazole-4-carboxylates

• Kento Iwai,
• Akari Hikasa,
• Kotaro Yoshioka,
• Shinki Tani,
• Kazuto Umezu and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2024, 20, 2827–2833, doi:10.3762/bjoc.20.238

• results, a plausible mechanism was proposed, as shown in Scheme 3a. The 5-exo-dig ring closure is induced by O-attack of the amide moiety on the ethynyl group to form 6, during which a stoichiometric proton source (water in the solvent) is necessary. Subsequently, one of the ethoxycarbonyl groups at the 4

• mechanism, as illustrated in Scheme 3b [13][14], we cannot negate this mechanism because the reaction media and bases were different. PCPA 4a was heated in the presence of methanesulfonic acid to undergo 6-endo-dig cyclization. However, hydration predominantly occurred, converting the ethynyl group to a

Investigation of a bimetallic terbium(III)/copper(II) chemosensor for the detection of aqueous hydrogen sulfide

• Parvathy Mini,
• Michael R. Grace,
• Genevieve H. Dennison and
• Kellie L. Tuck

Beilstein J. Org. Chem. 2024, 20, 2818–2826, doi:10.3762/bjoc.20.237

• for the detection of both gaseous and/or aqueous H2S are shown in Figure 1 [12][16][17]. These sensors all function via the copper sequestration mechanism, where upon addition of hydrogen sulfide to the quenched bimetallic species, luminescence modulation occurs. In our quest for highly selective

Synthesis and antimycotic activity of new derivatives of imidazo[1,2-a]pyrimidines

• Dmitriy Yu. Vandyshev,
• Daria A. Mangusheva,
• Khidmet S. Shikhaliev,
• Kirill A. Scherbakov,
• Oleg N. Burov,
• Alexander D. Zagrebaev,
• Tatiana N. Khmelevskaya,
• Alexey S. Trenin and
• Fedor I. Zubkov

Beilstein J. Org. Chem. 2024, 20, 2806–2817, doi:10.3762/bjoc.20.236

• maleimides or N-arylitaconimides. The mechanism of the studied processes was postulated basing on experimental data, HPLC–MS analysis of reaction mixtures, and quantum chemical calculations. Molecular docking results of the obtained imidazo[1,2-a]pyrimidines, when compared with voriconazole, a drug already

• -spectrum antifungal agents. Among the many drugs and hits, the azole-based systems (including triazoles and imidazoles) are of particular importance in this context. Their mechanism of action is the inhibition of the activity of the enzyme lanosterol 14α-demethylase (CYP51), which is encoded by the CYP51

• method of controlling fungal infections. The mechanism of inhibition of azoles and their derivatives is based on the formation of a coordination bond between their heterocyclic nitrogen atom, which carries an unshared electron pair, and the haem iron atom. The formation of this bond leads to inhibition

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

• , proceeding through a five-membered transition state. To clarify the mechanism, two experiments were conducted. In the first one, 2-acetonaphthone with a trideuteromethyl group (1i-d3) was subjected to the standard reaction conditions. Two products were obtained: First, 3i-d2 containing a CF2H group, and

• yields were determined by 1H NMR spectroscopy using 1,2-dichloroethane as the internal standard. In parentheses: yields after column chromatography (with product purities of ca. 90%). aWith CsCl. bWith KCl. Proposed mechanism (A) and mechanistic investigations (B and C). The yields were determined by 1H

Access to optically active tetrafluoroethylenated amines based on [1,3]-proton shift reaction

• Yuta Kabumoto,
• Eiichiro Yoshimoto,
• Bing Xiaohuan,
• Masato Morita,
• Motohiro Yasui,
• Shigeyuki Yamada and
• Tsutomu Konno

Beilstein J. Org. Chem. 2024, 20, 2776–2783, doi:10.3762/bjoc.20.233

• ]-proton shift reaction in this study is expected to proceed via the reaction mechanism reported by Soloshonok [25][26][27][28][29][30][31][32], as shown in Scheme 6. First, DBU interacts with the benzylic hydrogen of the imine (R)-16, and this hydrogen is about to be abstracted as a proton. This hydrogen

• reaction mechanism. Investigation of the reaction conditions. Supporting Information Supporting Information File 3: Full experimental details, 1H, 13C, 19F NMR spectra of 16a–g and 23a–g, and HPLC charts of racemic as well as chiral compounds 23a–g. Supporting Information File 4: Crystallographic