Pd-Catalyzed asymmetric allylic amination with isatin using a P,olefin-type chiral ligand with C–N bond axial chirality

• Natsume Akimoto,
• Kaho Takaya,
• Yoshio Kasashima,
• Kohei Watanabe,
• Yasushi Yoshida and
• Takashi Mino

Beilstein J. Org. Chem. 2025, 21, 1018–1023, doi:10.3762/bjoc.21.83

• asymmetric allylic amination of allylic esters with isatin derivatives 11 as nucleophiles. The reaction proceeds efficiently, yielding the products (S)-13 with good-to-high enantioselectivity. A scale-up reaction was also successfully conducted at a 1 mmol scale. Additionally, when malononitrile was added to

• palladium catalysts with amines as nucleophiles have been reported [14][15][16][17][18][19][20][21][22][23][24][25], there have been only a few reports on the N-substitution of isatin using asymmetric methods. Recently, Wolf’s group reported a transition-metal-catalyzed (Pd-catalyzed) asymmetric allylic

• enantioselectivity as the 0.1 mmol scale reaction (entry 14). Next, we investigated the substrate scope of the palladium-catalyzed asymmetric allylic amination of 1,3-diphenyl-2-propenyl acetate (12) with isatin derivatives 11 as nucleophiles under the optimized conditions using (aR)-(−)-6 as the ligand and Na3PO4

Recent total synthesis of natural products leveraging a strategy of enamide cyclization

• Chun-Yu Mi,
• Jia-Yuan Zhai and
• Xiao-Ming Zhang

Beilstein J. Org. Chem. 2025, 21, 999–1009, doi:10.3762/bjoc.21.81

• enamides as nucleophiles, rendering them more stable than enamines. This stability is reflected in their frequent occurrence in natural products [4]. As a result, research on the synthetic applications of enamides has historically lagged behind that of enamines [5][6]. Beyond their use in hydrogenation

• cephalotaxine, cephalezomine H, (−)-cephalotaxine, (−)-cephalotine B, (−)-fortuneicyclidin A, (−)-fortuneicyclidin B, and (−)-cephalocyclidin A. Unlike enamines, tertiary enamides can participate in cyclization reactions initial as nucleophiles, and upon protonation, alkenylation, or alkylation, the resultant

• resulting iminium ion can be readily captured by a wide variety of nucleophiles, including alkenes and alkynes. These aza-Prins cyclizations have potential applications in the synthesis of natural alkaloids, as exemplified by She’s total synthesis of (−)-dihydrolycopodine and (−)-lycopodine [17]. These

Harnessing tethered nitreniums for diastereoselective amino-sulfonoxylation of alkenes

• Shyam Sathyamoorthi,
• Appasaheb K. Nirpal,
• Dnyaneshwar A. Gorve and
• Steven P. Kelley

Beilstein J. Org. Chem. 2025, 21, 947–954, doi:10.3762/bjoc.21.78

• regioselective, diastereoselective, and metal-free protocol for alkene amino-hydroxylation, which compared favorably to prior art in this area [25][26][27][28][29][30][31][32]. Naturally, we wondered if other O-nucleophiles were competent in the ring-opening of the aziridinium intermediate. Indeed, almost all

Silver(I) triflate-catalyzed post-Ugi synthesis of pyrazolodiazepines

• Muhammad Hasan,
• Anatoly A. Peshkov,
• Syed Anis Ali Shah,
• Andrey Belyaev,
• Chang-Keun Lim,
• Shunyi Wang and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2025, 21, 915–925, doi:10.3762/bjoc.21.74

• by nitrogen nucleophiles [59][60]. When the reaction was conducted with 5 mol % of AgOTf in toluene at 80 °C for 20 hours, pyrazolo[1,5-a][1,4]diazepine 16a was obtained in 46% yield, while complete conversion of the starting material 15a was not achieved (Table 1, entry 1). Increasing the

4-(1-Methylamino)ethylidene-1,5-disubstituted pyrrolidine-2,3-diones: synthesis, anti-inflammatory effect and in silico approaches

• Nguyen Tran Nguyen,
• Vo Viet Dai,
• Luc Van Meervelt,
• Do Thi Thao and
• Nguyen Minh Thong

Beilstein J. Org. Chem. 2025, 21, 817–829, doi:10.3762/bjoc.21.65

• nucleophiles [24]. Therefore, it is reasonable that the transimination reaction between 3a’–e’ and 4 preferentially takes place at the carbon atom of the imine (C=N) linkage instead of the carbonyl carbons at the 2- or 3-positions. Lastly, the covalent bond between the tetrahedral carbon atom and the

Recent advances in allylation of chiral secondary alkylcopper species

• Minjae Kim,
• Gwanggyun Kim,
• Doyoon Kim,
• Jun Hee Lee and
• Seung Hwan Cho

Beilstein J. Org. Chem. 2025, 21, 639–658, doi:10.3762/bjoc.21.51

• inception (Scheme 1). Early studies were mainly focused on palladium catalysts [5][6][7][8], as demonstrated by the independent pioneering works of Tsuji and Trost in the 1960s and 1970s, respectively. While palladium catalysts demonstrated excellent reactivity with soft stabilized nucleophiles in the

• phosphoramidite ligands significantly advanced this field, with contributions from numerous research groups including Hartwig, Helmchen, Carreira, Alexakis, and You [19]. In general, soft nucleophiles that typically possess conjugate acids with pKa values less than 25 have been utilized in most Pd and Ir

• nucleophiles 5 that have conjugate acids with pKa values greater than 25 such as organolithium, organomagnesium, organozinc, and organozirconium reagents. This crucial distinction effectively expanded the scope of allylic substitution reactions beyond traditional boundaries. The evolution of copper-catalyzed

Entry to 2-aminoprolines via electrochemical decarboxylative amidation of N‑acetylamino malonic acid monoesters

• Olesja Koleda,
• Janis Sadauskis,
• Darja Antonenko,
• Edvards Janis Treijs,
• Raivis Davis Steberis and
• Edgars Suna

Beilstein J. Org. Chem. 2025, 21, 630–638, doi:10.3762/bjoc.21.50

• also suitable as nucleophiles for the cyclization into 2-aminoproline and 2-aminopipecolic acid derivatives 6 (Figure 2, reaction 3). The starting disubstituted malonic esters are readily available by C-alkylation of inexpensive and readily available diethyl acetamidomalonate, followed by

• facilitated the cyclization, and the 6-membered heterocycles 6h,i could be obtained in 27% and 18% yield, respectively. In addition to sulfonamides, carbamates such as N-Boc and benzamide are also suitable as nucleophiles for the anodic decarboxylation/cyclization reaction. However, the corresponding 2

• tethered nitrogen nucleophiles such as sulfonamides, carbamates, and benzamide. The decarboxylative cyclization of a stereogenic center-containing sulfonamide proceeds with excellent diastereoselectivity (97:3 dr). The N-protected 2-aminoproline derivatives can be incorporated into dipeptides by an ester

Photocatalyzed elaboration of antibody-based bioconjugates

• Marine Le Stum,
• Eugénie Romero and
• Gary A. Molander

Beilstein J. Org. Chem. 2025, 21, 616–629, doi:10.3762/bjoc.21.49

• oxygen [42]. Through energy transfer (EnT) from the ruthenium-based photocatalyst to triplet oxygen, singlet oxygen is produced in a targeted manner, which oxidizes histidine to an endoperoxide, significantly increasing its reactivity toward nucleophiles (Figure 4A). This strategy employs a

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

• nucleophilic species present in the reaction medium, MMS can act as a methylene source. Under hydrolysis conditions, it can be a source of formaldehyde (Scheme 5a), but with other nucleophiles, after nucleophilic addition, the sulfide group can work as a leaving group, allowing for a sequential domino process

• phosphites can also undergo an addition to the C=O bond of the carbonyl component (Abramov reaction) giving α-hydroxy phosphonates 33 as byproducts (Scheme 26a) [72]. Competition between the two nucleophiles for the electrophilic carbonyl compound depends on their relative reactivity [74][77] and this lack

• difficult to separate [86][87][88]. Probably, the high reactivity of the imines generated by formaldehyde leads to their polymerization [84] or even to the incorporation of other nucleophiles present in the reaction mixture, such as the solvent or a second molecule of the amidine component (Scheme 32) [84

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