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

• Isatin is a well-known natural indole derivative. Due to the broad biological activities of its derivatives, extensive research has been conducted on their synthesis. Furthermore, the isatin framework is a versatile starting material for various transformations, including multicomponent reactions and the

Studies on the syntheses of β-carboline alkaloids brevicarine and brevicolline

• Benedek Batizi,
• Patrik Pollák,
• András Dancsó,
• Péter Keglevich,
• Gyula Simig,
• Balázs Volk and
• Mátyás Milen

Beilstein J. Org. Chem. 2025, 21, 955–963, doi:10.3762/bjoc.21.79

• hydrogenation of the C=C double bond in the side chain gave brevicarine (2). The first total synthesis of brevicarine is shown in Scheme 3 [2][20][21]. Condensation of indole (11) with 1-methylpiperidone (12) gave compound 13 [22]. N-Alkylation of 13 with benzyl bromide, followed by treatment of the quaternary

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

• nucleophilic addition, and subsequent release of one molecule of amide, reactivating the active ruthenium(II) catalyst. In contrast, for diazomalonates, intermediate Int-78 releases ammonia with the help of Ru(II) or acetic acid, ultimately yielding 3H-indole 80. This change in selectivity may be due to the

• (such as indole substrates), Int-79 is more stable at −78 °C, favoring the formation of the mono-insertion product 86. In 2022, Wu and colleagues reported a novel methodology for constructing α-ketoamides 90 or 92 and amides 91 through copper-catalyzed dicarbonylation and monocarbonylation reactions

Recent advances in the electrochemical synthesis of organophosphorus compounds

• Babak Kaboudin,
• Milad Behroozi,
• Sepideh Sadighi and
• Fatemeh Asgharzadeh

Beilstein J. Org. Chem. 2025, 21, 770–797, doi:10.3762/bjoc.21.61

• phosphine oxide radical. The coupling product was obtained via the reaction of a phosphine oxide radical with thiazole compound. In another study on heteroaromatic compounds' electrochemical C–P coupling reactions, Gao et al. [55] reported an electrochemical reaction of indole derivatives with trialkyl

• -phosphorylated indole was obtained with high selectivity when n-Bu4NClO4 was used as the electrolyte. Additionally, under certain conditions that reduced the reaction yield, the C3-phosphorylated product was also observed. Similar to previous heteroaromatic coupling reactions with phosphine oxides [53][54], this

• reaction proceeded via anodic indole oxidation, followed by a reaction with trialkyl phosphite to give the corresponding indole phosphonate (Scheme 11). Cyclic voltammetry experiments confirmed that free indole can oxidize at the anode and generate a radical-cation intermediate. Also, no product was

Origami with small molecules: exploiting the C–F bond as a conformational tool

• Patrick Ryan,
• Ramsha Iftikhar and
• Luke Hunter

Beilstein J. Org. Chem. 2025, 21, 680–716, doi:10.3762/bjoc.21.54

• (I, Figure 2). This has several implications. For example, if the C–C(F) bond rotates, the orientation of the terminal C–F bond dipole changes, and this can alter the overall dipole moment of the molecule. Indoles 1–3 illustrate this point (Figure 2) [9]. The non-fluorinated indole 1 has an unvarying

• or against the dipole of the indole moiety. A similar phenomenon occurs with the difluorinated analogue 3. The fluorinated molecules 2 and 3 can be said to have a “chameleonic” character [9][10][11][12][13][14]: they have the ability to change polarity to suit their environment. This is a potentially

Sequential two-step, one-pot microwave-assisted Urech synthesis of 5-monosubstituted hydantoins from L-amino acids in water

• Wei-Jin Chang,
• Sook Yee Liew,
• Thomas Kurz and
• Siow-Ping Tan

Beilstein J. Org. Chem. 2025, 21, 596–600, doi:10.3762/bjoc.21.46

• -donating protic group close to the reaction center. Good yields (70–71%) of hydantoins containing heterocyclic groups, such as indole (H2c) and imidazole (H2d) were also achieved. This demonstrates potential application of this protocol in the synthesis of pharmacologically active hydantoin compounds. The

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

• protons of 1 shifted downfield and a marginal downfield shift of several crown ether protons as well as H-1 and H-3 of the glucopyranose was also observed. These observations suggest that the main interaction between 1 and H-Trp-OH is the π–π stacking between the naphthalene unit of 1 and the indole

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

• [16][17]. Indole derivatives, including those with conjugated aromatic and alicyclic rings, are of considerable interest because of their diverse biological activities (antibacterial, antimicrobial, anticancer, antidiabetic, etc.) [18][19][20][21][22]. For this reason, the synthetic goal of this work

• is to obtain heterocyclic indole compounds conjugated with a 1,3-tropolone moiety. The variability of the products of acid-catalyzed reactions in the series of 2,3,3-trimethylindolenine with 1,2-benzoquinone derivatives depends on the nature of the substituents in the 1,2-benzoquinone. Thus, the

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

• 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

Heteroannulations of cyanoacetamide-based MCR scaffolds utilizing formamide

• Marios Zingiridis,
• Danae Papachristodoulou,
• Despoina Menegaki,
• Konstantinos G. Froudas and
• Constantinos G. Neochoritis

Beilstein J. Org. Chem. 2025, 21, 217–225, doi:10.3762/bjoc.21.13

• of aliphatic and aromatic substituents (Scheme 4). Pyrimidines and pyrimidone-bearing indole derivatives are crucial in organic chemistry because of their extensive use as bioactive compounds with a wide array of significant biological activities (DB03074, DB03304, DB08131) [70][71][72]. In a similar

• obtained 15 diversely substituted heteroannulated pyrimidones, employing privileged thiophene, quinoline and indole scaffolds in a rapid fashion, without the need of column chromatography, in a parallel setup. Heteroannulated pyrimidones in drug discovery: blockbuster drugs that are based on the privileged

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

• (Scheme 23) [47]. These reactions were catalyzed by both BINOL-derived (TRIP) CPA (S)-C23 and SPINOL-derived CPA (S)-C24, providing axially chiral products 71 and 73, respectively. Control experiments showed the importance of the N–H group on the indole ring and the presence of both carboxylate groups in

• reported. However, the reaction did not tolerate a variety of substitutions on the amide group, probably because of its involvement in hydrogen bonding with the organocatalyst (R)-C23. Expanding on earlier methodologies of Chen et al. [60][61] and Wang et al. [62] utilizing indole derivatives instead of β

• -naphthols, new atroposelective reactions of quinones and iminoquinones were developed [63]. The reaction of quinones with an ester group 109 and indoles with alkyl substituents 110 catalyzed by CPA C29 provided products 112 with regioselectivity on the pyrrole ring of indole (Scheme 35). On the contrary

Synthesis of acenaphthylene-fused heteroarenes and polyoxygenated benzo[j]fluoranthenes via a Pd-catalyzed Suzuki–Miyaura/C–H arylation cascade

• Merve Yence,
• Dilgam Ahmadli,
• Damla Surmeli,
• Umut Mert Karacaoğlu,
• Sujit Pal and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2024, 20, 3290–3298, doi:10.3762/bjoc.20.273

• -catalyzed annulation reaction between bromo-chloronaphthalene dicarboximides 6 and heteroarylboronic esters that enabled the syntheses of acenaphthylene-fused thiophene and indole derivatives 7 having donor-acceptor units (Scheme 1a) [40]. In 2021, Jin and co-workers developed an elegant Pd-catalyzed

• reaction cascade starting from diarylalkynes 8, which involves indole formation/peri-C–H annulation and N-dealkylation reactions to afford acenaphthylene-fused indole products 9 (Scheme 1b) [41]. Recently, Takeuchi and co-workers reported an effective Ir-catalyzed [2 + 2 + 2] cycloaddition between 1,8

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

• authors proposed a possible mechanism for the reaction which is depicted in Scheme 20. The chiral phosphoric acid activates both the azoalkene acting as a Brønsted acid and the indole acting as a Lewis base promoting a Friedel–Crafts-type 1,4-addition of the indole to the azoalkene. In this manner, a

• ). Firstly, hydrogenation with palladium on carbon led to the formation of 55 in a good yield. Secondly, an alkylation of the NH of the indole followed by intramolecular cyclization led to tetracyclic derivative 56 in an 80% yield. Next, a deprotection of the azo nitrogen atom led to derivative 57 in a 92

• [44]. The mechanism of the reaction is taking place in an analogous manner as per the previous article, and the chiral phosphoric acid is activating both the azoalkene and the indole through hydrogen bonding. The newly synthesized chiral pyrroloindolines were subjected to biological assays confirming

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

• with subsequent nucleophilic attack by chloride to form the product. A metal-free chlorocyclisation of indole derivatives was reported by Yu and co-workers in 2019 (Scheme 25) [45]. The authors reported the use of 1-chloro-1,2-benziodoxol-3-one (45) as a single reagent to form 6- or 7-membered rings

• PhI(OAc)2, which formed a range of 5- and 6-membered bromomethyl cyclic imines 56 in good yields from unsaturated imines 57. Xia and co-workers reported the bromocyclisation of indole derivatives 58 (Scheme 31) using PIDA and CuBr2 as the oxidant and bromide source, respectively [52]. Racemic pyrrolo

• [2,3-b]indoles 59 were synthesised in up to quantitative yields under mild reaction conditions at room temperature. A range of other indole derivatives were cyclised in similarly good yields demonstrating the scope of the reaction. Li and Liu reported the bromoamidation of alkenes in 2014 (Scheme 32

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

• , 98160, México 10.3762/bjoc.20.256 Abstract A series of 1,5-disubstituted tetrazole-indole hybrids were synthesized via a high-order multicomponent reaction consisting of an Ugi-azide/Pd/Cu-catalyzed hetero-annulation cascade sequence. This operationally simple one-pot protocol allowed high bond-forming

• structural diversity and complexity compared to classical 3- or 4-CRs [17][18][19]. In the same context, the hybridization of 1,5-disubstituted tetrazoles with an indole moiety using I-MCRs such as the Ugi-azide reaction as a key step, is very limited. To our knowledge, only three reactions have been

• -indole system 10, in a two-step reaction: Ugi-azide followed by a cyclization reaction catalyzed by AuCl3, in good to high yields [21]. In 2019, Salahi et al. synthesized the series of tetrazole-indoles 15 via an Ugi-azide reaction in moderate to high yields [22]. It is noteworthy that none of the

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

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

• material in Europe (Scheme 1). It is obtained by extraction and isolation of the colorless indole-O-glycoside indicane which is then hydrolyzed to give indoxyl. The latter undergoes oxidative dimerization to provide indigo. In the 19th century, syntheses of indigo were developed which made the pigment

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

• were found to be suitable for the reaction, delivering 1,3-enynes with medium to high yields and excellent regioselectivities (Scheme 3, 3a–e, 3n–p). Interestingly, when the 3-position of indole was blocked by a methyl group, the 2-position of indole underwent nucleophilic attack with an E/Z ratio of 2

Synthesis of spiroindolenines through a one-pot multistep process mediated by visible light

• Francesco Gambuti,
• Jacopo Pizzorno,
• Chiara Lambruschini,
• Renata Riva and
• Lisa Moni

Beilstein J. Org. Chem. 2024, 20, 2722–2731, doi:10.3762/bjoc.20.230

• indole alkaloids. Here, we develop a novel approach for the one-pot multistep synthesis of different spiro[indole-isoquinolines]. The protocol proposed involves the visible light mediated oxidation of N-aryl tertiary amines using bromochloroform with the generation of a reactive iminium species, which

• cyclization of the indole derivatives is the most popular (Scheme 1a). For instance, the efficient synthesis of spiro[indoline-3,2′-pyrrolidines] [8][9][10] or spiro-isoxazoles [11] through different dearomatization processes has been reported. Recently, Ramana and Dothe have proposed an elegant gold

• , our plan provides: the oxidation of N-aryltetrahydroisoquinolines (N-Ar-THIQs) generating in situ the iminium ions 1, the 3C Ugi-type reaction of an electron-rich aniline, an isocyanide and 1; the subsequent oxidation of the Ugi-type product 2; and the final cyclization to give the spiro[indole-THIQs

The scent gland composition of the Mangshan pit viper, Protobothrops mangshanensis

• Jonas Holste,
• Paul Weldon,
• Donald Boyer and
• Stefan Schulz

Beilstein J. Org. Chem. 2024, 20, 2644–2654, doi:10.3762/bjoc.20.222

• components, carboxylic acids, alcohols, glycerol ethers, amides, and volatile compounds such as phenol, benzaldehyde, or indole were present (Figure 1 and Table 1). While some of these compounds were easily identified, a group of diketopiperazines (DKPs) and a series of unknown putative carboxylic acids (A–F

Applications of microscopy and small angle scattering techniques for the characterisation of supramolecular gels

• Connor R. M. MacDonald and
• Emily R. Draper

Beilstein J. Org. Chem. 2024, 20, 2608–2634, doi:10.3762/bjoc.20.220

• -assembly across length scales using a combination of SANS and cryo-TEM, as well as other characterisation techniques. To investigate how the change in capping group changed the self-assembly of diphenylalanine, indole-FF, and carbazole-FF (F = phenylalanine) were characterised by SAXS. While both indole-FF

• and carbazole-FF were shown to have fibre radii that were quantifiable by SAXS, the model fit to the indole-FF showed the length to exceed the q range measured. Cryo-TEM was used to corroborate the presence of such fibres, and though they cannot prove the modelled length’s accuracy, they were able to

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

• involves building a ring onto a preexisting system, whether cyclic or non-cyclic. The Lei group developed an electrooxidative annulation reaction that facilitates LSF [28]. A regio- and stereoselective protocol was established for the [4 + 2] annulation of indole derivatives, allowing access to highly

• functionalized pyrimido[5,4-b]indoles due to its high functional group tolerance. Multiple examples were demonstrated with indole 1H-carboxamides linked to drug molecules or natural products at the R2 position. Additionally, an alkyl azide at the R2 position and an iodide at the R1 position were tolerated

• , enabling further functionalization. The proposed mechanism involves radical–radical cross-coupling. The indole 1H-carboxamide generates a nitrogen-centered radical during anodic oxidation in the presence of a base, while the 1,3-dimethylindole derivative forms an indole radical cation. The radical–radical

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• -diaminonaphthalene derivatives 42, which after hydrolysis and extraction into toluene, were reacted with indole, 3-methylindole, 3,4-dihydroisoquinoline, and benzoyl hydrazone ethyl glyoxylate ester to afford terminal (E)-trifluoromethyl homoallylic amines 44 with up to 3 adjacent stereocentres with high to

Efficacy of radical reactions of isocyanides with heteroatom radicals in organic synthesis

• Akiya Ogawa and
• Yuki Yamamoto

Beilstein J. Org. Chem. 2024, 20, 2114–2128, doi:10.3762/bjoc.20.182

• generates a stannylated imidoyl radical 20. The subsequent 5-exo cyclization, hydrogen abstraction from n-Bu3SnH, and aromatization successfully afforded the stannylated indole derivative 21 (Scheme 13) [8][54][55][56]. The stannyl group of 21 could be transferred to aryl or vinyl group by cross-coupling

• reaction of o-ethenylaryl isocyanides with disulfides in the presence of diphenyl ditelluride yields the corresponding dithiolated indole derivatives 23 (Scheme 16) [60]. Initially, the thiotelluration products via 5-exo cyclization are formed in situ. The subsequent aromatization followed by photoinduced

• isocyanides with diphosphines. Radical reaction of tin hydride and hydrosilane toward isocyanide. Isocyanide insertion into boron compounds. Isocyanide insertion into cyclic compounds containing boron units. Photoinduced hydrodefunctionalization of isocyanides. Tin hydride-mediated indole synthesis and cross

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

• compounds 38 are also interesting building blocks in pyrazole synthesis. Through the reaction of 1,5-diaryl-1,3,5-pentanetriones 38 with hydrazines, Knorr synthesis of pyrazoles and Fischer indole synthesis can be combined in a pseudo-three-component fashion to give 5-(indol-3-yl)pyrazoles 39 (Scheme 11