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

• pyrrolones such interaction can lead to pyridazinone systems [10][11]. Despite on the plenty of reactions with nitrogen-containing nucleophiles there is only one example of recyclization using furanone with a carbonyl group at position 3 (Scheme 1a, previous work) [6]. However, no work on this type of

• communication we investigated the interaction of substituted 2H-furo[3,2-b]pyran-2-ones 1 with nitrogen-containing nucleophiles (Scheme 1b, this work). As a result, the general approach to preparation of pyrazolones with a 3-hydroxy-4-pyranone unit was developed. It’s important to underline that both pyrazolone

Vinylogous functionalization of 4-alkylidene-5-aminopyrazoles with methyl trifluoropyruvates

• Judit Hostalet-Romero,
• Laura Carceller-Ferrer,
• Gonzalo Blay,
• Amparo Sanz-Marco,
• José R. Pedro and
• Carlos Vila

Beilstein J. Org. Chem. 2025, 21, 533–540, doi:10.3762/bjoc.21.41

• properties along a C=C double bond [1]. This effect has been established to be very advantageous to expand the range of reactions of different functional groups that can be coupled efficiently through a conjugated π-system. In this context, the addition reaction of vinylogous nucleophiles to carbonyl

• compounds is a significant and important reaction for the selective synthesis of homoallylic alcohols in an efficient and sustainable way [2][3]. As carbonyl compounds, alkyl trifluoropyruvates [4][5] are an interesting class of compounds that have been used in addition reactions of different nucleophiles

• functionalization of 5-aminopyrazoles [26], we decided to study 4-alkenyl-5-aminopyrazoles as nucleophiles in the vinylogous addition reaction to electrophiles. Herein, we report the regioselective and diastereoselective functionalization of 4-cyclohexenyl-5-aminopyrazoles using alkyl trifluoropyruvates [27][28][29

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

• olefins with a wide range of nucleophiles, with many organocatalyzed asymmetric examples highlighted in the literature [23][24]. We have observed that the enantioenriched 1,5-dicarbonyl Michael adducts, synthesized via organocatalyzed reaction of cinnamaldehyde with benzyl phenyl ketone, undergo

Electrochemical synthesis of cyclic biaryl λ³-bromanes from 2,2’-dibromobiphenyls

• Andrejs Savkins and
• Igors Sokolovs

Beilstein J. Org. Chem. 2025, 21, 451–457, doi:10.3762/bjoc.21.32

• diaryl λ3-bromanes under remarkably mild conditions with subsequent applications of the in situ-generated arynes in cycloaddition reactions [3], meta-selective reactions with oxygen and nitrogen nucleophiles [4][5], regiodivergent meta or ortho-alkynylations [6], and regioselective (di)halogenation [7

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

• require rethinking cavity design, but will be achieved predominantly by synthetic advances, for instance by the internal functionalization of cavities with bifunctionality – chemical groups that simultaneously activate nucleophiles and electrophiles or otherwise stabilize charged pairs. Herein, I argue

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

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

• study found that by using [Os(phen)3]2+ as the photocatalyst and 660 nm red light, the reaction exhibited greater functional group tolerance, handling a variety of electron-deficient, neutral and rich (hetero)aryl bromides 9 and primary and secondary amine-based nucleophiles 10 with minimal degradation

• molecular orbital (HOMO), thereby shifting the absorption of the complexes into the NIR region (around 810 nm). The authors have demonstrated the efficiency of their photocatalyst in cross-dehydrogenative coupling reactions with N-phenyltetrahydroisoquinoline 21 and diverse nucleophiles (Scheme 7). Their

• this review hitherto. This singlet oxygen is generated by the energy transfer from the excited state of the phthalocyanin zinc complexes to molecular oxygen, allowing the oxidation of the N-phenyltetrahydroisoquinoline 21 into a reactive iminium intermediate that subsequently couples with nucleophiles

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

• Zi-Ying Xiao Jing Sun Chao-Guo Yan College of Chemistry & Chemical Engineering, Yangzhou University, Yangzhou 225002, China 10.3762/bjoc.21.21 Abstract In this paper, the nucleophilic substitution reactions of various N- and P-containing nucleophiles to MBH carbonates of isatins were investigated

• an indole motif with a ketone and a γ-lactam moiety occur in numerous natural substances [1][2][3][4]. Isatins have many interesting aspects in organic reactions and potential applications. The versatile reactivity of isatins used both as an electrophiles and nucleophiles and their easy availability

• - and P-containing nucleophiles to MBH carbonates of isatins and convenient synthesis of diverse functionalized 3-substituted oxindole derivatives. Results and Discussion Initially, the reaction conditions were briefly examined by using MBH nitrile of isatin 1a and p-toluidine (2a) as model reaction. It

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

• ][58][59][60][61], and photoinduced alkylations of various nucleophiles [22][62][63][64][65][66][67][68]. Recently, these sustainable catalytic systems have gradually been applied to amidations employing dioxazolones as amide sources. To the best of our knowledge, no review article has yet covered the

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

• amounts of copper reagents. Consequently, investigation into more practical and sustainable reactions remains an area of ongoing research [10]. Conventional cross-coupling reactions typically require C(sp2)-based electrophiles and nucleophiles as coupling partners. Generally, the reaction is initiated

• identical racemic carbonyl nucleophiles to generate Cu-enolate 44 and Ni-enolate 43 simultaneously (Figure 10). The Ni-enolate 43 undergoes anodic oxidation through single-electron transfer, releasing nickel-bound α-carbonyl radical 45, whereas the copper complex 44 remains electrochemically inert under

• reactions are essential synthetic methodologies. The discovery of Chan–Lam coupling reactions, which use arylboronic acids and N-nucleophiles, provided a C–N bond-forming protocol using copper catalysis, offering a complementary method to noble transition-metal catalysis [78]. Recently, dual-catalytic

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

• directly to the alkene, then reacts with the nucleophile to afford product 7. The regioselective 1,2-difunctionalization of allyl alcohol has been developed as a three-component cascade reaction using arenes and sulfonamides as nucleophiles to achieve arylation/hydroamination processes. The reaction

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

Synthesis, characterization, and photophysical properties of novel 9‑phenyl-9-phosphafluorene oxide derivatives

• Shuxian Qiu,
• Duan Dong,
• Jiahui Li,
• Huiting Wen,
• Jinpeng Li,
• Yu Yang,
• Shengxian Zhai and
• Xingyuan Gao

Beilstein J. Org. Chem. 2024, 20, 3299–3305, doi:10.3762/bjoc.20.274

• hand, we turned our attention to the synthesis of PhFlOP-based compounds through a Cs2CO3-facilitated nucleophilic substitution with substituted carbazoles as the nucleophiles (Scheme 2). For example, tert-butyl, bromo, carbazolyl, or phenyl substituents were introduced into the carbazoles. To our

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

• nucleophiles is more effective when a pre-formed nucleophile is used [4]. Thus, HIR 2 was added to the reaction mixture after the in situ formation of the sulfenate anion (by retro-Michael addition). First experiments were carried out under the previously described conditions for BBX electrophilic amination

• conducted at room temperature for 20 hours, which resulted in a reduction of the yield for 5aa to 9% (Table 1, entry 5). This result might be due to the reactivity of this hypervalent iodine reagent. Indeed, we have previously observed that the transfer of the benzylamine moiety to carbon-based nucleophiles

Efficient synthesis of fluorinated triphenylenes with enhanced arene–perfluoroarene interactions in columnar mesophases

• Yang Chen,
• Jiao He,
• Hang Lin,
• Hai-Feng Wang,
• Ping Hu,
• Bi-Qin Wang,
• Ke-Qing Zhao and
• Bertrand Donnio

Beilstein J. Org. Chem. 2024, 20, 3263–3273, doi:10.3762/bjoc.20.270

• perfluorobenzene, perfluoropyridine, perfluoronaphthalene, decafluorobiphenyl, and many other synthesized perfluoroarenes, and the nucleophiles are also abundant and contain aryllithium, conjugated organic dilithium reagents, phenols and benzenethiols, etc. [35][36][37][38][39][40][41][42][43]. We recently

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

• their amides, esters, and azides by FeCl2-catalyzed isomerization of 3-aryl-5-chloroisoxazole-4-carbonyl chlorides into 3-aryl-2H-azirine-2,2-dicarbonyl dichlorides followed by their reaction with nucleophiles are reported. Two approaches to the preparation of 3-aryl-5-chloroisoxazole-4-carbonyl

• the reaction with nucleophiles (Scheme 1). Two approaches to the preparation of diacyl chlorides 2 without using noble metals have also been developed. Results and Discussion 5-Сhloroisoxazole-4-carbonyl chlorides 1, required for the preparation of 2H-azirine-2,2-dicarboxylic acids and their

• isomerization to 3-aryl-2H-azirine-2,2-dicarbonyl dichlorides followed by their fast reaction at the same temperature with O- and N-nucleophiles. 3-Aryl-2H-azirine-2,2-dicarboxylic acids were prepared in 64–98% yield, whereas 3-(tert-butyl)-2H-azirine-2,2-dicarboxylic acid could not be obtained by this method

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

• , the intramolecular HVI-mediated halocyclisation of alkenes using carbon, oxygen, nitrogen or sulfur nucleophiles. Herein, we describe the examples reported in the literature, which are organised by the different halogens involved and the internal nucleophiles. Keywords: cyclisation; halogenation

• carbocycles can be synthesized mildly and effectively using HVI reagents. Nitrogen nucleophiles A metal-free synthesis of β-fluorinated piperidines was reported in 2012 by Meng, Li and co-workers (Scheme 1) [26]. The authors describe a reaction using PhI(OPiv)2 as oxidant with HF·pyridine as the source of

• nucleophiles In 2000, Hara and co-workers reported the fluorocyclisation of unsaturated alcohols and carboxylic acids promoted by HVI reagents (Scheme 11) [36]. Using 4-tolyl difluoroiodane 10 as the reaction promoter, and pyridine·6HF as a source of fluoride, a range of unsaturated alcohols 23 to fluorinated

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

• nucleophiles to unsaturated compounds with electron-withdrawing groups, is a cornerstone in constructing carbon–carbon and carbon–heteroatom bonds [1]. It is instrumental in synthesizing natural products [2][3][4][5] and pharmaceuticals [6], underlining its significance in organic chemistry. Recent

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

• copper catalyst afforded nearly better results for the arylated products. In 2022, Linde et al., demonstrated a conventional approach for achieving arylations of nitrogen- and oxygen nucleophiles via SNAr reaction, using o-fluorinated diaryliodonium salts 40, which enabled access to a greater range of

• (Scheme 17) suggests that the reaction initiates with an SNAr at the ortho-carbon, forming a Meisenheimer complex I and a novel iodine(III) intermediate II. This type of reactivity is unprecedented, as past reactions between nucleophiles and diaryliodonium salts usually lead to a reduction of iodine(III

Multicomponent synthesis of α-branched amines using organozinc reagents generated from alkyl bromides

• Baptiste Leroux,
• Alexis Beaufils,
• Federico Banchini,
• Olivier Jackowski,
• Alejandro Perez-Luna,
• Fabrice Chemla,
• Marc Presset and
• Erwan Le Gall

Beilstein J. Org. Chem. 2024, 20, 2834–2839, doi:10.3762/bjoc.20.239

• ]. Since its discovery in 1912, the reaction has benefitted from regular improvements over the years and recent developments, such as the use of organometallic species as nucleophiles in the so-called “organometallic Mannich reaction”, which have helped to expand the boundaries of the original process [4

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

• ] because of their easily modifiable dipeptide frameworks. Several methods exist for accessing PCPAs, such as the amination of 1-halo-1-alkynes [16][17], tandem reactions of α-imino esters with nucleophiles and electrophiles [18], and the nucleophilic addition of an acetylide to α-carbonylated N-acylimines

• various nucleophiles. This is because the imino carbon atom of 2 is also highly electrophilic, similar to DEMO [23][24][25]. This method offers an advantage over conventional methods as the N-acyl group can be modified by altering the acid amide. In this study, lithium acetylides were employed as

• nucleophiles to synthesize PCPAs, and their ring closures were also investigated. Results and Discussion NAI 2 can be generated by treating N,O-acetal 1 with a base, such as triethylamine. However, the addition of an amine was omitted because lithium acetylide functions both as nucleophile and base. When 1a

Copper-catalyzed yne-allylic substitutions: concept and recent developments

• Shuang Yang and
• Xinqiang Fang

Beilstein J. Org. Chem. 2024, 20, 2739–2775, doi:10.3762/bjoc.20.232

• –heteroatom bonds vicinal to alkenyl or alkynyl groups, which are highly valuable for downstream synthesis. At present, unstabilized nucleophiles [33][34][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51] are commonly used in Cu-catalyzed allylic substitutions because of the inner-sphere

• mechanism and relatively harsh reaction conditions such as anhydrous, anaerobic, and low temperatures are usually required (Scheme 1a). Therefore, using stabilized nucleophiles in Cu-catalyzed allylic substitutions is a tremendous challenge. On the other hand, since the pioneering work of van Maarseveen [52

• ] and Nishibayashi [53] groups in 2008, Cu-catalyzed asymmetric propargylic substitutions have made significant progress [54][55][56][57][58][59][60]. The protocol allows the use of stabilized nucleophiles via the outer-sphere mechanism, and the copper allenylidene intermediate formed by copper and

Base-promoted cascade recyclization of allomaltol derivatives containing an amide fragment into substituted 3-(1-hydroxyethylidene)tetronic acids

• Andrey N. Komogortsev,
• Constantine V. Milyutin and
• Boris V. Lichitsky

Beilstein J. Org. Chem. 2024, 20, 2585–2591, doi:10.3762/bjoc.20.217

• nucleophiles and open access to a large array of substituted pyridin-4-ones. Various conditions and reagents employed for these transformations are presented in numerous papers [24][25][26][27][28][29]. Besides that, approaches to the synthesis of pyridazinones and pyrazoles based on the interaction of 3

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• was demonstrated by the LSF of primary natural and pharmaceutical amines carrying potential competing nucleophiles, such as tryptamine and primaquine (Scheme 16). In the context of electrochemical difunctionalizations the Lei group published a transition-metal-free electrochemical difunctionalization

• . Nucleophilic attack on the benzylic carbocation results in a 1,3-difunctionalized product (Scheme 18). The introduction of two heteroatoms was reported by Liu, Li, and Jin [27]. They developed a method demonstrating excellent tolerance for a wide range of readily available alkenes and O,N-centered nucleophiles

Facile preparation of fluorine-containing 2,3-epoxypropanoates and their epoxy ring-opening reactions with various nucleophiles

• Yutaro Miyashita,
• Sae Someya,
• Tomoko Kawasaki-Takasuka,
• Tomohiro Agou and
• Takashi Yamazaki

Beilstein J. Org. Chem. 2024, 20, 2421–2433, doi:10.3762/bjoc.20.206

• -to-handle reagent, NaOCl·5H2O. Because very little has been disclosed about the reactivity of such 2,3-epoxyesters, their epoxy ring opening by a variety of nucleophiles was carried out and we succeeded in clarifying these chemo- as well as regioselective processes proceeding via the SN2 mechanism to

• mainly afford 2-substituted 3-hydroxyesters usually in a highly anti selective manner. Keywords: α,β-unsaturated esters; epoxyesters; fluorine; Grignard-based cuprates; nucleophiles; Introduction Fluorine-containing compounds have been utilized in diverse fields due to their special character

• is the high regio- and stereoselectivities of its epoxy ring opening specifically occurring at the 2 position in an SN2 manner, when it is treated with appropriate nucleophiles (Nu), leading to the formation of the 2-substituted 3-hydroxyesters with 2,3-anti stereochemistry. These characteristic