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

• ) to obtain triazolobenzodiazepine which in turn can serve as a cyclic imine for a modified Joullié–Ugi 3-CR with isocyanide and trimethylsilyl azide (TMSN₃) in the synthesis of tetrazole-tethered triazolobenzodiazepines (Scheme 3B). We envisioned that the reaction conditions may need to be modified to

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

• and sustainability [95][96][97][98][99][100]. Numerous electrochemical constructions of cyclic compounds from alkynes have been developed. For examples, 2-aryl-3-sulfonyl-functionalized quinoline was formed by an electrochemical annulation of benzoxazinanone and p-arylsulfonyl hydrazide [101]. The

• synthesis of cyclic compounds have emerged. The electrochemical functionalization of alkynes was highlighted by Ahmed in 2019 [109], Zhang described radical annulation of 1,n-enynes under photo/electrochemical reaction conditions in 2023 [110], the electrochemical formation of heterocycles was summarized by

• -exo-dig N-radical addition into the C≡C bond to generate the cyclic species C. The radical anion D was then obtained via single electron reduction of C at the cathode. The subsequent protonation of D gave α-aminyl radical E [215][216][217], which was converted into the anion F by further cathodic

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

• a C1 building block for the N-formylation of secondary amines to formamides under catalyst-free conditions and air as oxidant. This method was applied to different aromatic and aliphatic (both cyclic and acyclic) amines (Scheme 3) [31]. Already in 1955, Parham and Reiff reported the synthesis and

• evolves towards cyclic acetals (Scheme 4) [32]. Exploring methods for the conversion of glycolaldehyde (GCA) to 3-(indol-3-yl)-2,3-dihydrofurans in organic solvents, Gu et al. reported a three-component reaction combining GCA, ethyl acetoacetate as 1,3-dicarbonyl component and indole. Using glycolaldehyde

• yield [83]. In their synthesis the cyclic acetal (2,5-diethoxy-1,4-dioxane-2,5-diyl)dimethanol or its dimethoxy analog was esterified with diphenyl phosphorochloridate in pyridine to give (2,5-diethoxy-1,4-dioxane-2,5-diyl)bis(methylene) tetraphenyl bis(phosphate). Subsequent removal of the phenyl

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

• The desymmetric enantioselective reduction of cyclic 1,3-dicarbonyl compounds is a powerful tool for the construction of ring systems bearing multiple stereocenters including all-carbon quaternary stereocenters, which are widely useful chiral building blocks for the total synthesis of structurally

• synthesized utilizing a desymmetric enantioselective reduction strategy of cyclic 1,3-dicarbonyl compounds as a key transformation. This review will summarize the application of this strategy in the total synthesis of terpenoid and alkaloid natural products from the year 2016 to 2025. We first focus on the

• synthesis of several terpenoids and alkaloids through the desymmetric enantioselective reduction of five-membered cyclic 1,3-dicarbonyl compounds. Subsequently, the utilization of six-membered cyclic 1,3-dicarbonyl compounds for the synthesis of some terpenoids natural products is described. Keywords

Discovery of cytotoxic indolo[1,2-c]quinazoline derivatives through scaffold-based design

• Daniil V. Khabarov,
• Valeria A. Litvinova,
• Lyubov G. Dezhenkova,
• Dmitry N. Kaluzhny,
• Alexander S. Tikhomirov and
• Andrey E. Shchekotikhin

Beilstein J. Org. Chem. 2025, 21, 2062–2071, doi:10.3762/bjoc.21.161

• substitution of the terminal chloride in 11 with various cyclic amines, including pyrrolidine, piperidine, and mono-tert-butoxycarbonyl (Boc)-protected piperazine, provided a set of aminoalkyl derivatives 12а–с (Scheme 4). This strategy enables the expansion of structural diversity within this scaffold and

• towards all tested cancer cell lines. However, no clear correlation between structure and activity was observed. For example, elongation of the alkyl substituents (N,N-diethylamino derivative 9b) led to a complete loss of antiproliferative activity, while its cyclic analog 9c showed the lowest IC50 value

• in the series for the HCT116 cell line. Incorporation of an additional aminoalkyl moiety in the structure of cyclic amine (compounds 9e, 9f) does not result in any meaningful changes of potency. The same modification of 6-methylindolo[1,2-c]quinazoline scaffold yielding derivatives 10a–c also gave

Bioinspired total syntheses of natural products: a personal adventure

• Zhengyi Qin,
• Yuting Yang,
• Nuran Yan,
• Xinyu Liang,
• Zhiyu Zhang,
• Yaxuan Duan,
• Huilin Li and
• Xuegong She

Beilstein J. Org. Chem. 2025, 21, 2048–2061, doi:10.3762/bjoc.21.160

• reduction of ketone using SmI2 and propionaldehyde provided 15 diastereoselectively. Friedel–Crafts cyclization using trimethyl orthoformate and TMSOTf provided the cyclic acetal moiety to be oxidized with PDC, delivering the isocoumarin skeleton in 16. Chemoselective removal of the ester with the lactone

Solar thermal fuels: azobenzene as a cyclic photon–heat transduction platform

• Jie Yan,
• Shaodong Sun,
• Minghao Wang and
• Si Wu

Beilstein J. Org. Chem. 2025, 21, 2036–2047, doi:10.3762/bjoc.21.159

• challenges in large-scale fabrication are inherent limitations. Conjugated azobenzene polymers undergo photoisomerization and thermally triggered back-isomerization, enabling cyclic "charging–discharging" of energy. However, their solid-state phase transition behavior is inherently governed by molecular

Understanding the origin of stereoselectivity in the photochemical denitrogenation of 2,3-diazabicyclo[2.2.1]heptene and its derivatives with non-adiabatic molecular dynamics

• Leticia A. Gomes and
• Steven A. Lopez

Beilstein J. Org. Chem. 2025, 21, 2007–2020, doi:10.3762/bjoc.21.156

• ][68][69][70][71][72][73][74][75][76][77][78] mechanisms of cyclic azoalkenes have been studied with experimental and computational techniques for more than six decades, in solution [51][55][59][60][61][64][67][69][70][73][74][75][76][78][79], gas phase [50][55][62][64][65], and solid state [60][63

• calculations have provided valuable insights into the photochemical stereoselectivities of cyclic azoalkenes. In 1998, Yamamoto and co-workers investigated the reaction paths for α-C–N and β-C–C bond cleavage during the direct and sensitized photolysis of DBH [81]. The minimum energy geometries in S0, S1, T1

Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis

• Lihua Wei,
• Rui Yang,
• Zhifeng Shi and
• Zhiqiang Ma

Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151

• in intramolecular [7-exo] and [8-endo] cyclization, furnishing the 7-membered cyclic ether 40 and 8-membered cyclic ether 41, respectively. Finally, MOM deprotection produced (−)-heliannuol D (42) and (+)-heliannuol A (43). In 2002, Chênevert and co-workers completed the total synthesis of (S)-α

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

• methodology, the trans-1,2-diaminocyclohexane was replaced with (S)-1,1′-binaphthyl-2,2′-diamine. Under the optimized conditions, the corresponding cyclic product 2k was obtained in 34% yield, consistent with previous observations reporting reduced efficiency as the ring size increases [44]. To confirm the

• precedents involving electroreduction of activated imines and diiminium species [19]. Furthermore, control experiments conducted in the absence of methanesulfonic acid (Table 1, entry 3) resulted in no observable product formation, highlighting the acid activation in driving this transformation. Cyclic

• voltammetry measurements were also carried out in order to evaluate the electrochemical redox properties of the species involved in the process and to provide evidence for the behavior of the monoprotonated and the bisprotonated diimines, 3a and 4a (Scheme 8). The cyclic voltammogram of the starting diimine

Preparation of spirocyclic oxindoles by cyclisation of an oxime to a nitrone and dipolar cycloaddition

• Beth L. Ritchie,
• Alexandra Longcake and
• Iain Coldham

Beilstein J. Org. Chem. 2025, 21, 1890–1896, doi:10.3762/bjoc.21.146

• ][10][11][12][13]. Of note, Cook and co-workers described an elegant approach using tryptophan as a starting material and an oxidative rearrangement of an indole that allows access to a variety of spirooxindole alkaloids from the Alstonia genus [14]. An efficient way to construct cyclic nitrogen

Chiral phosphoric acid-catalyzed asymmetric synthesis of helically chiral, planarly chiral and inherently chiral molecules

• Wei Liu and
• Xiaoyu Yang

Beilstein J. Org. Chem. 2025, 21, 1864–1889, doi:10.3762/bjoc.21.145

• chirality originating from the rigid conformation of molecules lacking symmetry, which do not fit into the aforementioned four categories, are termed inherent chirality. Notable examples include inherently chiral calix[4]arenes and saddle-shaped medium-sized cyclic compounds. Catalytic asymmetric synthesis

• reaction mechanisms and applications of the chiral products for selected examples. Review Helical chirality Helicenes are a group of rigid polycyclic aromatic compounds composed of ortho-fused aromatic (hetero)cyclic rings, with their helically twisted conformation enforced by steric hindrance between

• chiral molecules that do not fit into conventional categories of central, axial, planar or helical chirality, such as saddle-shaped, medium-sized cyclic compounds [45] and others [46]. These structurally distinct chiral molecules have received considerable research attention due to their broad range of

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

• coefficient of the closed form [131]. Regarding the ethene bridge, several cyclic and acyclic solutions have been extensively reported and reviewed [132][133]. Some of the most common bridges are pentene, perfluoropentene, maleic anhydride, and maleimide. An interesting study correlated the ring size of the

• bridge to the photophysical properties of four different perfluoroalkenylated diarylethene derivatives [134]. Unsurprisingly, the acyclic 128a turned out to be the worst-performing in terms of fatigue resistance due to the competing E–Z photoisomerisation reaction. The fatigue resistance of the cyclic

[3 + 2] Cycloaddition of thioformylium methylide with various arylidene-azolones in the synthesis of 7-thia-3-azaspiro[4.4]nonan-4-ones

• Daniil I. Rudik,
• Irina V. Tiushina,
• Anatoly I. Sokolov,
• Alexander Yu. Smirnov,
• Alexander R. Romanenko,
• Alexander A. Korlyukov,
• Andrey A. Mikhaylov and
• Mikhail S. Baranov

Beilstein J. Org. Chem. 2025, 21, 1791–1798, doi:10.3762/bjoc.21.141

• authors have shown that arylidene-azolones are very promising substrates for these transformations, since their exo-cyclic double bond easily reacts with various 1,3-dipoles [16][17][18][19][20]. Thioformylium methylide is a well known 1,3-dipole, which is readily generated from chloromethyl

Preparation of a furfural-derived enantioenriched vinyloxazoline building block and exploring its reactivity

• Madara Darzina,
• Anna Lielpetere and
• Aigars Jirgensons

Beilstein J. Org. Chem. 2025, 21, 1737–1741, doi:10.3762/bjoc.21.136

• -wise process [22]. The first step involves addition of the oxazoline nitrogen to TsNCO leading to a zwitterionic intermediate A, which undergoes 1,4-conjugate addition forming a cyclic intermediate B. Subsequently, the electron-rich double bond in intermediate B reacts with a second equivalent of TsNCO

Approaches to stereoselective 1,1'-glycosylation

• Daniele Zucchetta and
• Alla Zamyatina

Beilstein J. Org. Chem. 2025, 21, 1700–1718, doi:10.3762/bjoc.21.133

• anomeric configuration of the lactol acceptor is particularly challenging when the desired form is not thermodynamically favored, as is the case with β-mannose derivatives. A refined strategy employing cyclic stannanes to lock the anomeric hydroxy group of a mannose-derived lactol in the equatorial

• -benzylidene acetal group. The 4,6-O-benzylidene acetal exerts both torsional and electronic disarming effects, influencing the reactivity of glycosyl donors and the nucleophilicity of glycosyl acceptors, thereby improving the stereoselectivity of glycosylation [92][93][94]. In general, 4,6-O-cyclic protecting

• achieve a full desymmetrization of both pyranose moieties by additionally differentiating the protecting groups at C6–OH and C4–OH of each monosaccharide component, the cyclic 4,6-O-di-tert-butylsilylene (DTBS) group was installed as seen in the orthogonally protected lactol acceptor 94 (Scheme 8) [95

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

• substrate scope of the developed synthetic approach was investigated. Aromatic and aliphatic carbonyl compounds reacted with primary and secondary amines. The reductive amination efficiently proceeded with both cyclic and acyclic secondary amines. Steric hindrance in ortho-position in carbonyl compound 13

On the aromaticity and photophysics of 1-arylbenzo[a]imidazo[5,1,2-cd]indolizines as bicolor fluorescent molecules for barium tagging in the study of double-beta decay of ¹³⁶Xe

• Eric Iván Velazco-Cabral,
• Fernando Auria-Luna,
• Juan Molina-Canteras,
• Miguel A. Vázquez,
• Iván Rivilla and
• Fernando P. Cossío

Beilstein J. Org. Chem. 2025, 21, 1627–1638, doi:10.3762/bjoc.21.126

• values. Our calculations show that, as expected, 12-crown-4 16a and 15-crown-5 16b are too small and consequently the barium cation lies outside the average molecular plane determined by the macrocycle. In the case of 18-crown-6 16c, the cyclic ligand accommodates very well the cation, which is now

• within the average molecular plane. In addition, the corresponding ΔGiso values increase with the n-values (Figure 4A). Ligand 21-crown-7 15d suggests that this size of the cyclic ligand is less than optimal, since the calculated structure shown a concave-convex topology, in which one oxygen atom

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

• cycloadditions involving metal cyaphides should be in-plane aromatic species due to the cyclic delocalization of 6-electrons in the molecular plane. Indeed, the evolution of the NICS(3, +1) values along a z-axis perpendicular to the molecular plane shows the expected bell shape with a maximum value at z = 0 Å

Synthesis of optically active folded cyclic dimers and trimers

• Ena Kumamoto,
• Kana Ogawa,
• Kazunori Okamoto and
• Yasuhiro Morisaki

Beilstein J. Org. Chem. 2025, 21, 1603–1612, doi:10.3762/bjoc.21.124

• structures, such as one-handed helical and propeller-shaped structures, can be constructed by folding the π-conjugated system using [2.2]paracyclophane as the chiral crossing unit, leading to circularly polarized luminescence (CPL) properties. Chiral cyclic dimers and trimers were synthesized using planar

• term for cyclic compounds with at least one aromatic ring in the main chain backbone [1]. Cyclophane compounds have long been known; [2.2]paracyclophane was first reported as a cyclic dimer of paraxylylene by Brown et al. in 1949 [2]. In 1951, Cram et al. reported the practical synthesis of [2.2

• , enantiopure [2.2]paracyclophane was used as a chiral monomer to prepare optically active conjugated polymers and cyclic trimers [21], in which π-electron systems were stacked to form zigzag and triangular structures, respectively. The conjugated polymers and cyclic trimers exhibited circularly polarized

3-Aryl-2H-azirines as annulation reagents in the Ni(II)-catalyzed synthesis of 1H-benzo[4,5]thieno[3,2-b]pyrroles

• Julia I. Pavlenko,
• Pavel A. Sakharov,
• Anastasiya V. Agafonova,
• Derenik A. Isadzhanyan,
• Alexander F. Khlebnikov and
• Mikhail S. Novikov

Beilstein J. Org. Chem. 2025, 21, 1595–1602, doi:10.3762/bjoc.21.123

• , differing in the nature and number of heteroatoms and their mutual arrangement. These also include ortho-fused heterocycles, which are obtained from functionalized cyclic systems and azirines as annulation reagents. Significant progress has been achieved in the synthesis of pyrrolo-fused systems by the

• , while changing the solvent gave completely unsatisfactory results. The absence of the methoxycarbonyl group in the obtained product 3a was unexpected, since there are no examples in the literature of the annulation reactions of cyclic substrates with azirines which are accompanied by the loss of an

• mechanisms of the formation of azirindine 16 under Ni(II)- and Cu(I)-catalysis. Oxidative dimerization of non-aromatic cyclic enols has been previously observed in their reactions with 3-arylazirines catalyzed by Cu(I) and Cu(II) complexes and was attributed to the recombination of intermediate free radicals

Synthesis of an aza[5]helicene-incorporated macrocyclic heteroarene via oxidation of an o-phenylene-pyrrole-thiophene icosamer

• Yusuke Matsuo,
• Aoi Nakagawa,
• Shu Seki and
• Takayuki Tanaka

Beilstein J. Org. Chem. 2025, 21, 1561–1567, doi:10.3762/bjoc.21.119

• largest cyclic array in the series. The oxidative fusion reaction with [bis(trifluoroacetoxy)iodo]benzene (PIFA) afforded a cyclophane-type aza[5]helicene-incorporated macrocycle, the structure of which was unambiguously revealed by X-ray diffraction analysis. Its optical properties have been investigated

• ][2][3][4][5]. In addition to these promising functionalities, their cyclic polyaromatic frameworks can be further transformed into fused structures. To this end, belt-like polyaromatic architectures can be developed, inspiring ongoing efforts toward the construction of carbon nanotube analogs (Figure

•  1) [6][7][8][9][10][11][12]. Nevertheless, partially fused macrocyclic intermediates are also important as they exhibit structural strain associated with both the polycyclic segments and the inherent strain stemming from the macrocyclic structure. For instance, cyclic chrysenylenes [13][14][15][16

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

• another cycle via the single quaternary carbon atom C5 demonstrated significant biological activity, greater than analogs with non-spiro-bonded cyclic fragments [3][4]. Hydantoin derivatives also exhibit a wide range of biological activities. Compounds containing the hydantoin pharmacophore group, are

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

• view of these results, it seems evident that six-membered cyclic amines have the optimal ring size for the photocatalyzed enaminone formation process. For enaminones 9b–k the remaining mass balance comprised mainly unreacted starting materials. The scalability of the process was demonstrated in

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

• substitution pattern on the regioselectivity and stereoselectivity of the reactions. A Review article by Papis and co-workers discusses various copper(II) triflate-catalyzed multicomponent reaction types [2]. Therein, the synthesis of cyclic and acyclic compounds, as well as three-component and four-component