Efficient solid-phase synthesis and structural characterization of segetalins A–H, J and K

• Liangyu Liu,
• Wanqiu Lu,
• Quanping Guo and
• Zhaoqing Xu

Beilstein J. Org. Chem. 2025, 21, 2612–2617, doi:10.3762/bjoc.21.202

• synthetic approaches have encountered significant challenges. Sonnet et al. reported the first total synthesis of segetalin A (1) via Sasrin resin-based SPPS, followed by cyclization under highly dilute conditions (10−4 M) with diphenylphosphoryl azide (DPPA) [17]. While successful, this approach suffers

Pentacyclic aromatic heterocycles from Pd-catalyzed annulation of 1,5-diaryl-1,2,3-triazoles

• Kaylen D. Lathrum,
• Emily M. Hanneken,
• Katelyn R. Grzelak and
• James T. Fletcher

Beilstein J. Org. Chem. 2025, 21, 2524–2534, doi:10.3762/bjoc.21.194

• where the attachment of alkyne and azide functional groups was reversed, as summarized in Table 2. The azide analogs 19–24 [25][28][31][43] used in this study were prepared from commercially available amines using the Sandmeyer reaction (Table S2, Supporting Information File 1). Reaction of each azide

• prepared using non-brominated azide and alkyne reactants (Figure 4). Although 1,4-disubstituted-1,2,3-triazoles possessing quinoline and isoquinoline subunits are known [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40][41][42][43][44], no prior examples of analogous 1,5-regioisomers have

• been reported. 1,5-Diaryl-1,2,3-triazole control compounds 37–42 were prepared via tandem deprotection/click reactions of TMS-protected alkynes with phenyl azide in yields similar to bromophenyl annulation precursors 7–12 and 25–30. Compounds 43–48, inverting the diaryltriazole connectivity, were

Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds

• Natalya Akhmetdinova,
• Ilgiz Biktagirov and
• Liliya Kh. Faizullina

Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185

• in two steps [70]. The intermediate tricyclic ketone 137 was converted to the corresponding α-diazoketone through treatment with 2,4,6-triisopropylbenzenesulfonyl azide (trisylN3), KOH, tetrabutylammonium bromide (TBAB), and 18-crown-6. Concurrent cleavage of the benzoyl group under basic conditions

Comparative analysis of complanadine A total syntheses

• Reem Al-Ahmad and
• Mingji Dai

Beilstein J. Org. Chem. 2025, 21, 2334–2344, doi:10.3762/bjoc.21.178

• Barton–McCombie deoxygenation. The extra ethyl carboxylate was removed via a sequence of LiOH hydrolysis and a Curtius rearrangement using DPPA to form the corresponding acyl azide. Ketone 50 was produced in 98% yield over two steps. The newly formed ketone functionality enabled the introduction of the

• Scheme 5, the Dai synthesis starts with compound 58 which can be prepared from (+)-pulegone in three steps or via an organocatalyzed tandem sequence in one step. The terminal olefin of 58 was then converted to a primary azide via an anti-Markovnikov hydroazidation reaction with a combination of 59 and

• Paal–Knorr pyrrole synthesis delivered 63, which was unstable and spontaneously cyclized to provide 64. Compound 64 was then advanced to tetracyclic intermediate 67 in a one-pot tandem process, which initiated with Staudinger azide reduction with PPh3 to form a primary amine. After reversible

Research towards selective inhibition of the CLK3 kinase

• Vinay Kumar Singh,
• Frédéric Justaud,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Blandine Baratte,
• Thomas Robert,
• Stéphane Bach,
• Chada Raji Reddy,
• Nicolas Levoin and
• René L. Grée

Beilstein J. Org. Chem. 2025, 21, 2250–2259, doi:10.3762/bjoc.21.172

• anilinoquinazoline 3a. Deprotection of the methoxy group by BBr3 gave phenol 4a which was propargylated to intermediate 5a. A final click-type reaction [27][28][29][30][31] with azide 6 gave the first target intermediate 7a. The second key intermediate 7b was prepared in a very similar manner, but starting from 3

Synthesis of triazolo- and tetrazolo-fused 1,4-benzodiazepines via one-pot Ugi–azide and Cu-free click reactions

• Xiaoming Ma,
• Zijie Gao,
• Jiawei Niu,
• Wentao Shao,
• Shenghu Yan,
• Sai Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 2202–2210, doi:10.3762/bjoc.21.167

• /bjoc.21.167 Abstract A one-pot Ugi–azide reaction followed by intramolecular Cu-free azide–alkyne cycloaddition generates a polycyclic scaffold 7 bearing polycyclic triazole, tetrazole, and benzodiazepine rings. This method could be extended for obtaining a more complicated scaffold 8 containing a

• piperazinone ring. Keywords: benzodiazepine; click reaction; multicomponent reaction; one-pot; piperazinone; polycyclic; triazole; tetrazole; Ugi–azide reaction; Introduction Triazole, tetrazole, and benzodiazepine are privileged heterocyclic rings commonly found in drug molecules and functional materials [1

• methods for the synthesis of tetrazoles [25][26][27][28], the Ugi–azide reaction is a good approach for constructing 1,5-disubstituted-tetrazoles (1,5-DS-T) [29][30][31]. This scaffold can be subsequently linked to 1,2,3-triazole [32], 4H-chromen-4-one [33], pyrrolo[3,4-b]indolizine [34], and other

Electrochemical cyclization of alkynes to construct five-membered nitrogen-heterocyclic rings

• Lifen Peng,
• Ting Wang,
• Zhiwen Yuan,
• Bin Li,
• Zilong Tang,
• Xirong Liu,
• Hui Li,
• Guofang Jiang,
• Chunling Zeng,
• Henry N. C. Wong and
• Xiao-Shui Peng

Beilstein J. Org. Chem. 2025, 21, 2173–2201, doi:10.3762/bjoc.21.166

• of carbamates as well [271]. Notably, the above approach provided imidazopyridines in high yields under aqueous solution without any metal catalysts. Early in 2008, an electrochemical copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) to access 1,2,3-triazole was realized by Finn [272]. But the

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

The application of desymmetric enantioselective reduction of cyclic 1,3-dicarbonyl compounds in the total synthesis of terpenoid and alkaloid natural products

• Dong-Xing Tan and
• Fu-She Han

Beilstein J. Org. Chem. 2025, 21, 2085–2102, doi:10.3762/bjoc.21.164

• 77 and subsequent deprotection produced tertiary alcohol 78. Starting from this common intermediate, on the one hand, through successive manipulations by diazotization and in situ azide substitution, AgNO3-mediated aza-Cope/Mannich [62] reaction delivered ketone 79. Subsequently, a three-step

• operation including azide–alkene dipolar cycloaddition, irradiation of the resulting triazoline to aziridine 80 and in situ ring opening followed by deacetylation achieved the first total synthesis of (−)-hunterine A (14). On the other hand, aza-Cope/Mannich reaction of 78 produced imine intermediate 81

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

• 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

• further purification after filtration. The use of starting components containing highly reactive groups, for example, an azide group, in the Ugi reaction provides opportunities for various post-cyclizations to obtain nitrogen-containing heterocyclic systems with potential biological activity [18]. To

• this case a carboxyl proton. In order to avoid the step of isolation of the intermediate azide derivatives 8, we also studied a one-pot method for the synthesis of compounds 9. For this KGA 1, aldehydes 2a,b, azidoanilines 7b,c, and tert-butyl isocyanide (4) were stirred in methanol at 45 °C for 24

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

• isoindoline – were reacted with 2,2,6-trimethyl-4H-1,3-dioxin-4-one to give the corresponding β-ketoamides 4. Treatment of the β-ketoamides 4 with 4-acetamidobenzenesulfonyl azide (p-ABSA) and triethylamine gave the α-diazo-β-ketoamides 5. Subsequent KOH-mediated deacetylation yielded the corresponding α

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

• -triazoles 28 can be obtained by click chemistry (Scheme 6B) via one-pot deprotection of 26 and Cu(I)-catalysed reaction with an azide [43][44]. Heteroarylimines 31a,b can be easily obtained by condensation of a (hetero)aromatic aldehyde 30a,b with a (hetero)aromatic amine 29a,b [36][37][38] (Scheme 7). The

Transition-state aromaticity and its relationship with reactivity in pericyclic reactions

• Israel Fernández

Beilstein J. Org. Chem. 2025, 21, 1613–1626, doi:10.3762/bjoc.21.125

• triazaphospholes (Scheme 3) which can be further transformed into protio- and iodotriazaphospholes [101]. We first compared these metal cyaphide/azide cycloadditions with the analogous non-metallic process involving t-BuC≡P as dipolarophile [102][103]. Interestingly, we found that, although in all cases the

• electropositive magnesium atom whereas the stronger orbital interactions derive from a more stabilizing direct π(C≡P)→π*(azide) molecular orbital interaction coupled with a stronger reverse π(azide)→π*(C≡P) interaction. Conclusion Through selected representative examples, in this perspective article the interplay

Facile synthesis of hydantoin/1,2,4-oxadiazoline spiro-compounds via 1,3-dipolar cycloaddition of nitrile oxides to 5-iminohydantoins

• Juliana V. Petrova,
• Varvara T. Tkachenko,
• Victor A. Tafeenko,
• Anna S. Pestretsova,
• Vadim S. Pokrovsky,
• Maxim E. Kukushkin and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2025, 21, 1552–1560, doi:10.3762/bjoc.21.118

• '-disubstituted ureas were initially reacted with oxalyl chloride to form imidazolidinetriones 1a,b, which were then added to an iminophosphorane formed in situ from an aryl azide and triphenylphosphine. As a result of the aza-Wittig reaction, 5-iminohydantoins 2a–i were then used as dipolarophiles in the 32CA

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

• CyreneTM, as a biomass-originated polar aprotic solvent, could be utilized as an alternative reaction medium for one-pot copper(I)-catalyzed azide–alkyne cycloaddition (click or CuAAC) reactions, for the synthesis of various 1,2,3-triazoles under mild conditions. Nineteen products involving N-substituted-4

• methods, the copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) reaction, the so-called click reaction [7], has received substantial attention for the selective synthesis of various 1,2,3-triazoles that are of utmost importance in the synthesis of biologically active compounds such as active

• -triazoles in a less toxic and recyclable medium could further control and reduce the environmental impacts of this synthetically very important transformation. Herein, we report a study on the copper(I)-catalyzed azide–alkyne cycloaddition (CuAAC) reaction in CyreneTM under mild conditions. Results 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

• , Burley, Watson, and co-workers present a new synthesis of germyl triazoles from germyl alkynes through a copper-catalyzed azide–alkyne cycloaddition (CuAAC) reaction [6]. The resulting Ge-substituted triazoles could be further diversified. For example, through chemoselective transition-metal-catalyzed

Synthesis of β-ketophosphonates through aerobic copper(II)-mediated phosphorylation of enol acetates

• Alexander S. Budnikov,
• Igor B. Krylov,
• Fedor K. Monin,
• Valentina M. Merkulova,
• Alexey I. Ilovaisky,
• Liu Yan,
• Bing Yu and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2025, 21, 1192–1200, doi:10.3762/bjoc.21.96

• from diisopropyl H-phosphonate (2a) was confirmed by HRMS analysis of the crude reaction mixture. Finally, vinyl azide 4a and silyl enol ether 4b were introduced into standard reaction conditions (Scheme 4, reaction 3). However, no phosphorylation product 3a was observed. On the basis of the obtained

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

• other hand, Fan and co-workers (2020) prepared α-amidoketone 71 by employing vinyl azide and cinnamic acid (7) in good yield via cascade reaction (Scheme 23B) [58]. The thermal decomposition of the azide led to the generation of the reactive azirine intermediate 72. Moreover, Li and co-workers (2020

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

• (Scheme 3A). The mesylate could be cleanly substituted with azide by heating substrate with excess NaN3 in DMSO (Scheme 3B). With an excess of Schwartz’s reagent, the carbonyl was cleanly reduced to give 1,3-oxazine 62. Contrary to what we had initially predicted from literature precedent, there was no

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

• involving the Ugi reaction between arylglyoxals 1, benzylamines 2, o-azidobenzoic acid (3), and cyclohexyl isocyanide (4a), followed by a triphenylphosphine-promoted tandem Staudinger/aza-Wittig cyclization (Scheme 1a) [33]. The overall strategy was enabled by the presence of an azide group in the

• 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

Synthesis of N-acetyl diazocine derivatives via cross-coupling reaction

• Thomas Brandt,
• Pascal Lentes,
• Jeremy Rudtke,
• Michael Hösgen,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2025, 21, 490–499, doi:10.3762/bjoc.21.36

• provided the corresponding amino-substituted N-acetyl diazocine 21 (Scheme 1). Another option for carbon–heteroatom bond formation reactions are copper-catalyzed Ullmann-type reactions, which have already been applied to the parent diazocine [36][37]. The attempted synthesis of azide-functionalized N

• of amino-N-acetyl diazocine by deprotection of the carbamate. Reaction conditions for the attempted Ullmann-type reaction with sodium azide. Reaction conditions for the palladium-catalyzed introduction of a nitrile functionality. Quantum yields of N-acetyl diazocine 1 in organic and aqueous media

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

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

• . According to the reaction mechanism outlined in Figure 12, the copper catalyst reacts with an azide ion to generate a Cu(II)–N3 complex 60, which is then anodically oxidized to the Cu(III)–N3 complex 61. The Cu(III)–N3 complex 61 releases the azidyl radical 62 from the azide ion 58, returning it to the Cu

• (II)–N3 complex 60. The azidyl radical 62 then reacts with N-arylenamine 57 via radical addition. Thereafter, it undergoes oxidation to form a kinetically labile vinyl azide intermediate 64. This vinyl azide intermediate 64 dissociates, yielding Cu(II) iminyl complex 65 via denitrogenation

• in Figure 16. Cu(II)(N3)2 (102) is generated from TMSN3 (98) and Cu(acac)2 in the presence of K3PO4; this is followed by anodic oxidation to form a Cu(III)(N3)3 complex 101. The resulting Cu(III)(N3)3 complex 101 releases an azide radical (103), and Cu(II)(N3)2 (102). The azide radical (103) then

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

• cascade reaction for the preparation of α-alkoxy-N-alkyltriazoles 44 that was developed starting from aliphatic aldehydes, alcohols, TMSN3 as azide source and alkynes (Scheme 33) [52]. The reaction occurs under mild conditions in acetonitrile at room temperature but is inhibited when using aromatic

• aldehydes and phenols. The mechanism involves the reaction of the azide with the hemiacetal XLII generated in situ from the aldehydes and alcohols, followed by coupling with the alkynes to form the triazole ring. Both, copper triflate and copper metal are essential for the success of the reaction. On the

• , followed by silyl deprotection and azide cycloaddition resulting in the triazole product. The presence of Cu(OTf)2 as the catalyst, sodium ascorbate as a mild reductant and TBAF to deprotect the alkyne moiety are crucial in the cycloaddition step. Conclusion In this review the developments on the

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

• first report from Zhdankin and co-workers in 1994, described the preparation of azidobenziodoxolone, ABX (I), a reagent widely used in oxidative azide transfer reactions [21]. Years later, Zhdankin’s group also reported the synthesis of amidobenziodoxolone (II) [14]. Other examples of N-containing