α-Ketoglutaric acid in Ugi reactions and Ugi/aza-Wittig tandem reactions

• Vladyslav O. Honcharov,
• Yana I. Sakhno,
• Olena H. Shvets,
• Vyacheslav E. Saraev,
• Svitlana V. Shishkina,
• Tetyana V. Shcherbakova and
• Valentyn A. Chebanov

Beilstein J. Org. Chem. 2025, 21, 2021–2029, doi:10.3762/bjoc.21.157

• library of bis- and tetraamides was synthesized by the Ugi reaction with α-ketoglutaric acid, tert-butyl isocyanide, aromatic aldehydes, and aromatic amines. When o-azidoanilines were used, azidated peptidomimetics were obtained, the post-cyclization of which by the aza-Wittig reaction yielded a series of

• for the preparation of benzodiazepinone derivatives, which showed promising psychotropic effects [20][21][22][23][24], using a tandem combination of Ugi/azide–alkyne cycloaddition reactions. From this point of view, azido amines are promising reagents for use in the Ugi reaction, opening up the

• possibility of synthesizing various heterocyclic systems such as quinazolines [25], diazepinones [25][26], quinoxalinones [27], diazocinones [28], and imidazolines [29] due to the exceptional reactivity of the azido group. However, the use of azido amines in the Ugi reaction together with oxoacids, which have

Rhodium-catalysed connective synthesis of diverse reactive probes bearing S(VI) electrophilic warheads

• Scott Rice,
• Julian Chesti,
• William R. T. Mosedale,
• Megan H. Wright,
• Stephen P. Marsden,
• Terry K. Smith and
• Adam Nelson

Beilstein J. Org. Chem. 2025, 21, 1924–1931, doi:10.3762/bjoc.21.150

• successful execution of this approach and the demonstration of biological function of the resulting reactive probes. Results and Discussion We prepared five α-diazoamide substrates bearing S(VI) electrophiles (Scheme 1 and Table 1) [15]. Initially, three amines – morpholine, 4-phenylpiperidine and

Stereoselective electrochemical intramolecular imino-pinacol reaction: a straightforward entry to enantiopure piperazines

• Margherita Gazzotti,
• Fabrizio Medici,
• Valerio Chiroli,
• Laura Raimondi,
• Sergio Rossi and
• Maurizio Benaglia

Beilstein J. Org. Chem. 2025, 21, 1897–1908, doi:10.3762/bjoc.21.147

• described a new electrochemical procedure to provide vicinal diamines involving the use of Sn electrodes as both anode and cathode in a divided cell, Mn(OAc)3·2H2O as additive and n-Bu4NOAc as electrolyte. Under these conditions, using aldehydes and amines as starting materials to form the imines in situ

Systematic pore lipophilization to enhance the efficiency of an amine-based MOF catalyst in the solvent-free Knoevenagel reaction

• Pricilla Matseketsa,
• Margret Kumbirayi Ruwimbo Pagare and
• Tendai Gadzikwa

Beilstein J. Org. Chem. 2025, 21, 1854–1863, doi:10.3762/bjoc.21.144

• groups. This selective functionalization yielded MOFs in which the catalytically active amines are confined within highly lipophilic pores, reminiscent of many enzyme active sites. We determined that systematically increasing the lipophilicity of the pores results in a commensurate increase of catalyst

• pharmaceutical and agrochemical industries [38][39]. Various types of catalysts are used to enhance the efficiency and selectivity of the Knoevenagel reaction, including Lewis acids, ureas/ thioureas, amino acids, and bases such as alkali metal hydroxides, alkali metal alkoxide, amines, etc. [37][40][41][42][43

• determined that, when incubated with secondary or tertiary isocyanates, KSU-1 reacts exclusively at the hydroxy groups of the DPG linker before proceeding to react at the amines of BDC-NH2 (Table 1, entries 1 and 2). Thus, we had a method to generate, from a single framework, a series of amine-based MOFs

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

• aromatic amines. Another strategy for both symmetric and asymmetric targets is the azo coupling of a diazonium salt 15 (Scheme 5A) with a nucleophile, which can be a (hetero)aromatic 16 [29] (B), a lithiated ring 19 [39] (C), or a precursor 20a,b [29][32][40] (D). In case of more than one reactive position

Continuous-flow-enabled intensification in nitration processes: a review of technological developments and practical applications over the past decade

• Feng Zhou,
• Chuansong Duanmu,
• Yanxing Li,
• Jin Li,
• Haiqing Xu,
• Pan Wang and
• Kai Zhu

Beilstein J. Org. Chem. 2025, 21, 1678–1699, doi:10.3762/bjoc.21.132

• classifications necessitate tailored nitrating reagent selections, giving rise to fundamentally distinct mechanistic pathways. This reactivity is exemplified by the comparative kinetic profiles: N-nitration of amines and O-nitration of alcohols – facilitated by accessible lone electron pairs – exhibit markedly

Influence of the cation in hypophosphite-mediated catalyst-free reductive amination

• Natalia Lebedeva,
• Fedor Kliuev,
• Olesya Zvereva,
• Klim Biriukov,
• Evgeniya Podyacheva,
• Maria Godovikova,
• Oleg I. Afanasyev and
• Denis Chusov

Beilstein J. Org. Chem. 2025, 21, 1661–1670, doi:10.3762/bjoc.21.130

• issue is a fundamentally important factor. In the present work, the reactivity of the hypophosphites of alkali metals (Li, K, Rb, and Cs) in reductive amination was explored for the first time. A set of secondary and tertiary amines was synthesized from various types of carbonyl compounds and amines

• . The remedy for Parkinson’s disease, piribedil, was obtained in high yield. The plausible mechanism of the elaborated process was proposed and supported by DFT calculations. Keywords: amines; DFT; hypophosphites; reductive amination; role of cations; Introduction Sodium hypophosphite, NaH2PO2, is one

• has shown clear influence of the cation in the hypophosphite salt on the effectiveness of the reductive amination. The acidity of the reaction media was a key factor affecting the equilibrium in the interaction between carbonyl compounds and amines. Intermediately acidic media is the optimal for the

Catalytic asymmetric reactions of isocyanides for constructing non-central chirality

• Jia-Yu Liao

Beilstein J. Org. Chem. 2025, 21, 1648–1660, doi:10.3762/bjoc.21.129

• unsymmetrical diisocyanide was used, the initial isocyanide insertion was found to be non-regioselective, delivering a 1:1 mixture of regioisomers (17c and 17c’). Intriguingly, 17a could act as a chiral acylating reagent, applying in the kinetic resolution of racemic primary amines rac-18. Additionally, after

Azide–alkyne cycloaddition (click) reaction in biomass-derived solvent Cyrene^TM under one-pot conditions

• Zoltán Medgyesi and
• László T. Mika

Beilstein J. Org. Chem. 2025, 21, 1544–1551, doi:10.3762/bjoc.21.117

• successfully introduced into homogeneous [26][27][28][29] and heterogeneous [30][31] carbon–carbon and carbon–heteroatom bond-forming protocols. Although its reactive carbonyl group could limit its application when a strong base (aldol condensation [29]) or amines (potential Schiff-base formation) are present

General method for the synthesis of enaminones via photocatalysis

• Paula Pérez-Ramos,
• Raquel G. Soengas and
• Humberto Rodríguez-Solla

Beilstein J. Org. Chem. 2025, 21, 1535–1543, doi:10.3762/bjoc.21.116

• condensation of 1,3-dicarbonyl compounds with amines [30]. While this approach is simple and straightforward, it often leads to a mixture of constitutional isomers in which the two different α-positions of the ketone have been functionalized. Therefore, the development of novel methods for the synthesis of

• presence of amines and CuI as catalyst, as reported by Zhang and co-workers (Scheme 1B) [32]. On the other hand, Li et al. disclosed a silver-catalyzed amination of propargyl alcohols to afford enaminones (Scheme 1C) [33]. Although these new methods provide a wide variety of enaminones, there are

• 9k was obtained, albeit in low yield. Regrettably, this transformation failed to provide the corresponding enaminone products by replacing alicyclic amines by diisopropylamine, probably due to steric hindrance. Steric factors could also explain the lack of reactivity of seven-membered azepane. In

Photoredox-catalyzed arylation of isonitriles by diaryliodonium salts towards benzamides

• Nadezhda M. Metalnikova,
• Nikita S. Antonkin,
• Tuan K. Nguyen,
• Natalia S. Soldatova,
• Alexander V. Nyuchev,
• Mikhail A. Kinzhalov and
• Pavel S. Postnikov

Beilstein J. Org. Chem. 2025, 21, 1480–1488, doi:10.3762/bjoc.21.110

• significant attention within organic and medicinal chemistry. Commonly, amide bonds are formed via the reaction of carboxylic acids or their derivatives with appropriate amines (Scheme 1A) [4]. Although this conventional approach is effective and straightforward, it usually suffers from harsh conditions and

Copper catalysis: a constantly evolving field

• Elena Fernández and
• Jaesook Yun

Beilstein J. Org. Chem. 2025, 21, 1477–1479, doi:10.3762/bjoc.21.109

• yield of up to 99%, with excellent regio- and E-selectivities. The method could be used for functional-group transformations of amines, amides, and lactams, as well as for gram-scale syntheses, demonstrating synthetic usefulness and versatility. A complementary Full Research Paper by Martina and co

Microwave-enhanced additive-free C–H amination of benzoxazoles catalysed by supported copper

• Andrei Paraschiv,
• Valentina Maruzzo,
• Filippo Pettazzi,
• Stefano Magliocco,
• Paolo Inaudi,
• Daria Brambilla,
• Gloria Berlier,
• Giancarlo Cravotto and
• Katia Martina

Beilstein J. Org. Chem. 2025, 21, 1462–1476, doi:10.3762/bjoc.21.108

• environmental abundance, low cost and low overall toxicity. A wide range of aminating reagents have been utilised, including nitrogen electrophiles and amines in the presence of external or internal oxidants [27], in many types of copper-catalysed synthetic protocols. The direct copper-catalysed C–H amination

• of azolic substrates, but here the amines and the ligands are still used in excess and auxiliary oxidants are occasionally employed [33][34][35]. Although electrophilic amines, such as chloroamines [36][37], hydroxylamine [38][39][40], acylated hydroxylamine (with a wider reaction scope) [41][42][43

• , that still required high temperatures, but the excess of amine (2 equiv) was lowered and only a catalytic amount of acid was utilised. Similar acidic protocols were subsequently developed by Li et al. [46], in which benzoxazoles were reacted with secondary amines and amides, with higher temperature

Advances in nitrogen-containing helicenes: synthesis, chiroptical properties, and optoelectronic applications

• Meng Qiu,
• Jing Du,
• Nai-Te Yao,
• Xin-Yue Wang and
• Han-Yuan Gong

Beilstein J. Org. Chem. 2025, 21, 1422–1453, doi:10.3762/bjoc.21.106

• corresponding lactams 29d and 29e and amines 29f and 29g were also obtained. Compounds 29a and 29b exhibit λabs centered at 513 nm, while the amines 29f and 29g display high ФF values of 0.48 and 0.56, respectively. Notably, azocine derivative 29b exhibits the highest CPL activity among the series, with a |glum

High-pressure activation for the solvent- and catalyst-free syntheses of heterocycles, pharmaceuticals and esters

• Kelsey Plasse,
• Valerie Wright,
• Guoshu Xie,
• R. Bernadett Vlocskó,
• Alexander Lazarev and
• Béla Török

Beilstein J. Org. Chem. 2025, 21, 1374–1387, doi:10.3762/bjoc.21.102

• that achieving these reactions at even higher scales is reasonable. The reactions occurred in a similar fashion as they did at the mg scale [36] and all reactions produced higher than 96% isolated yield of the product. Where the two alkyl amines were used, the reactions were complete within 30 s of

• alcohols with acetic acid. Molecular volumes of the reactants and products and the reaction volume (ΔV) for the Paal–Knorr reaction of amines with 2,5-hexanedione. Supporting Information Supporting Information File 6: Materials and methods, spectral data of new compounds, and HRMS spectra of known

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• challenging amines. The combination of simple reaction conditions and excellent chemoselectivity makes this protocol very robust and suitable for both the academia and industry. Kinetic and computational experiments support an SN1 mechanism via loss of sulphur dioxide and oxetane carbocation formation. Two

• benzotriazole-adduct formation proceeds poorly with sterically demanding secondary amines and fails with primary amines. However, the latter may be overcome by adding a temporary benzyl group on the amine which can be subsequently cleaved by hydrogenolysis as demonstrated by the authors. Finally, it was shown

• access to a large library of functionalised oxetanes in moderate to excellent yields and under very simple reaction conditions, which are compatible with a wide range of nucleophiles including alcohols (primary, secondary and tertiary), phenols, aliphatic and aromatic amines or heteroaryls (e.g., furan

Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

Investigations of amination reactions on an antimalarial 1,2,4-triazolo[4,3-a]pyrazine scaffold

• Henry S. T. Smith,
• Ben Giuliani,
• Kanchana Wijesekera,
• Kah Yean Lum,
• Sandra Duffy,
• Aaron Lock,
• Jonathan M. White,
• Vicky M. Avery and
• Rohan A. Davis

Beilstein J. Org. Chem. 2025, 21, 1126–1134, doi:10.3762/bjoc.21.90

• vitro and in vivo antimalarial drug leads. With a view to generating a library of unique antimalarial 1,2,4-triazolo[4,3-a]pyrazines and exploring regiochemical preference for nucleophilic amines, we utilised the known synthetic 5-chloro-3-(4-chlorophenyl)-[1,2,4]triazolo[4,3-a]pyrazine (1) as a

• scaffold for aminations with 14 commercially available primary amines. Reacting scaffold 1 with excess primary amine at room temperature for 16 h generated the desired amine analogues in respectable yields (18–87%) and high purity (≥95%) following chromatography workup. The structures of the 14 previously

• -position of the pyrazine ring [10][11]. During small-scale late-stage functionalisation of natural products, we have observed that amination or amidation with primary amines often involves less of a kinetic barrier than might otherwise be expected [12][13][14]. The use of readily available liquid amines in

Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

• cinnamic acid. For example, Chen and co-workers (2020) reported the Pd-catalyzed N-acylation of cinnamic acids using tertiary amines to generate the corresponding amides 83 and 84 in good yields via C–N cleavage (Scheme 25) [61]. The active Pd0 species was inserted into the carboxylate group to afford the

• cyclopropenone 333 followed by the second cyclopropenone ring-opening (335) (Scheme 75B) [128]. Leyva-Pérez and co-workers (2022) reported the esterification and amidation of diphenylcyclopropenone (309) with alcohols and amines, respectively, catalyzed by Cu(II) (Scheme 76A) [129]. In addition, they prepared a

• , Suryavanshi and co-workers (2020) utilized PhI(OAc)2 to mediate the oxidative olefination of amines and Wittig reagents 415 to give the corresponding cinnamate esters 416–419 via formation of imines 421 (Scheme 87B) [148]. In addition, a gram scale operation has been conducted smoothly. 3.1.3 Carbene

Biobased carbon dots as photoreductants – an investigation by using triarylsulfonium salts

• Valentina Benazzi,
• Arianna Bini,
• Ilaria Bertuol,
• Mariangela Novello,
• Federica Baldi,
• Matteo Hoch,
• Alvise Perosa and
• Stefano Protti

Beilstein J. Org. Chem. 2025, 21, 1024–1030, doi:10.3762/bjoc.21.84

• ); triarylsulfonium salts; visible light; Introduction Carbon dots (CDs) are a class of zero-dimensional carbon-based semiconducting nanoparticles bearing on the surface a wide range of functional groups, such as carboxylic acids, alcohols, and amines, that garnered significant attention in the last decade among the

• + species, a process where transition-metal-based complexes are employed [29], often (in the case of Ru(II)-based derivatives) in the presence of tertiary amines as sacrificial reductants [27][28]. Nonetheless, while this work serves primarily as a preliminary study comparing the reducing power of various

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

• 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

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

• ) triflate-catalyzed post-Ugi assembly of novel pyrazolo[1,5-a][1,4]diazepine scaffolds is reported offering high yields (up to 98%) under mild conditions. The synthetic sequence involves the Ugi four-component reaction (U4CR) of pyrazole-3-carbaldehydes, primary amines, 3-substituted propiolic acids, and

• employed the U4CR of ortho-halogenated benzaldehydes 7, primary amines 2, 3-substituted propiolic acids 8, and isocyanides 4 to synthesize propargylamides 9. These propargylic Ugi adducts 9 were subsequently subjected to a Cu-catalyzed tandem azide–alkyne cycloaddition/Ullmann coupling resulting in the

• account chemical and pharmacological importance of fused pyrazole derivatives [48][49][50][51][52][53], we herein report the post-Ugi assembly of novel pyrazolo[1,5-a][1,4]diazepine scaffolds 16 (Scheme 1d). The synthetic sequence involves an Ugi reaction of pyrazole-3-carbaldehydes 14, primary amines 2

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

• bromides) and the Lewis acid activator, a selective mono- or di-methylene insertion reaction can be carried out, generating α-/β-boryl-substituted tertiary organic amines 83 from simple secondary organic amines. Using N-alkyl-N-arylaminoboranes as the reactant, the reaction proceeds at −78 °C with CH2Br2

Cu–Bpin-mediated dimerization of 4,4-dichloro-2-butenoic acid derivatives enables the synthesis of densely functionalized cyclopropanes

• Patricia Gómez-Roibás,
• Andrea Chaves-Pouso and
• Martín Fañanás-Mastral

Beilstein J. Org. Chem. 2025, 21, 877–883, doi:10.3762/bjoc.21.71

• aliphatic gem-dichloride, we explored the feasibility of a base-mediated formation of chlorocyclopropanes (Table 2). Evaluation of bases such as metal tert-butoxides, phosphates, acetates, and organic amines resulted in either low conversion or decomposition of 2 (see Supporting Information File 1 for

Regioselective formal hydrocyanation of allenes: synthesis of β,γ-unsaturated nitriles with α-all-carbon quaternary centers

• Seeun Lim,
• Teresa Kim and
• Yunmi Lee

Beilstein J. Org. Chem. 2025, 21, 800–806, doi:10.3762/bjoc.21.63

• conditions and shows broad applicability to di- and trisubstituted allenes. Its practicality is demonstrated through the gram-scale synthesis and functional group transformations of amines, amides, and lactams, emphasizing its versatility and synthetic significance. Keywords: α-quaternary nitrile; Cu

• are important intermediates in organic syntheses because of the versatility of the cyano group, which can be readily transformed into a wide range of functional groups, including amides, carboxylic acids, amines, aldehydes, ketones, and N-heterocycles [6][7][8]. However, the synthesis of all-carbon

• synthesis and the successful transformation of nitrile products into amines, amides, and lactams. Further studies are underway to broaden the scope and application of the proposed method. Synthesis of acyclic nitrile-substituted quaternary carbon centers from allenes. Hydrocyanation of allene 1a with tosyl