Pd-catalyzed dehydrogenative arylation of arylhydrazines to access non-symmetric azobenzenes, including tetra-ortho derivatives

• Loris Geminiani,
• Kathrin Junge,
• Matthias Beller and
• Jean-François Soulé

Beilstein J. Org. Chem. 2025, 21, 2234–2242, doi:10.3762/bjoc.21.170

• , most synthetic methods have focused on the preparation of symmetric derivatives [12][13]. Traditional approaches, such as oxidative coupling of anilines [14][15][16][17][18][19], reductive coupling of nitroarenes [20][21][22][23], or cross-coupling between anilines and nitroarenes have proven

• proved to be a suitable coupling partner, enabling the preparation of azoarene 3p in 70% yield. Moreover, starting from 1,4-dibromobenzene and 2 equivalents of 1a, a double reaction occurred, enabling the one-step synthesis of 1,4-bis[(E)-2-phenyldiazenyl]benzene (3q) in high yield. We next investigated

• -products. The presence of oxidants such as O2 mitigates this pathway by promoting oxidative dehydrogenation as the dominant pathway. Conclusion In summary, we have developed robust and efficient conditions for the preparation of azobenzenes via C–N coupling and dehydrogenation, employing [PdCl(C3H5)]2 with

Thiadiazino-indole, thiadiazino-carbazole and benzothiadiazino-carbazole dioxides: synthesis, physicochemical and early ADME characterization of representatives of new tri-, tetra- and pentacyclic ring systems and their intermediates

• Gyöngyvér Pusztai,
• László Poszávácz,
• Anna Vincze,
• András Marton,
• Ahmed Qasim Abdulhussein,
• Judit Halász,
• András Dancsó,
• Gyula Simig,
• György Tibor Balogh and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2220–2233, doi:10.3762/bjoc.21.169

• -dioxides, we aimed at elaborating a synthetic procedure for the preparation of their pyrrole-fused counterparts, 2,9-dihydro[1,2,3]thiadiazino[5,6-g]indole 1,1-dioxide derivatives. The simple and versatile process led, via Fischer indole cyclization of the corresponding hydrazones, to a wide structural

• KGaA, Darmstadt, Germany), adjusting the pH with HCl. Water for buffer and eluent preparation were provided by a Millipore Milli-Q water purification system. Kinetic aqueous solubility assay. All compounds were dissolved in DMSO to make stock solutions at 10 mM concentration. In the case of 7i, 7j, and

• water (5 mL) was added. The mixture was extracted with EtOAc (3 × 5 mL), washed with water (5 mL) and brine (5 mL), dried over MgSO4 and evaporated to give crude products 3 or 10, which were purified by recrystallization from isopropyl alcohol or by flash chromatography. Method B for the preparation of

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

• sustainable strategy for the preparation of 3-selenylindoles. In 2023, Satyanarayana also described a similar electrochemical cascade approach towards 3-selenylindoles from 2-alkynylanilines (Scheme 6) [202]. When graphite was used as anode, platinum as cathode and LiClO4 as electrolyte, the electrochemical

• ][254], this approach exhibited the following advantages like without metal catalysts and external oxidants, atom economy, facile access of starting materials, etc. In 2024, Cho succeeded in the preparation of trifluoromethylated oxazoles through in-situ aminotrifluoromethylation/cyclization of alkynes

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 atom economical preparation of dihydroxyacetone (DHA) in good yield from aqueous glyceraldehyde (Scheme 16) [78]. Transformation of 1,3-dihydroxy-2-propanone (dihydroxyacetone, DHA) has been a very popular topic for many years, using a variety of reactions like isomerizations and dehydrations [79

• intermediate furan-derived enones. Subsequent reductive amination was performed in the presence of ammonia or amines and Pd/Al2O3 under H2 pressure, providing the tetrahydrofuran-derived amines [184]. The same catalytic system could allow the one-pot preparation of tetrahydrofuran-derived secondary and

• , pharmaceuticals or high added value chemicals [215][216][217][218][219][220][221][222][223]. Its first commercial production began in the 1940s. Its preparation from biomass involves several different possible pathways. One is the C5 sugar route starting from xylose as an example, relying on acid hydrolysis of

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

• , unlike conventional linear synthesis strategies, they enable the preparation of libraries of organic compounds in higher yields and with significantly less time, resources, and chemical waste [1][2][3][4][5]. The Ugi reaction, discovered in 1959 by Ivar Karl Ugi [6], is one of the classic multicomponent

• 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

• dedicated to the synthesis of novel peptidomimetics using the four-component Ugi reaction and the study of a tandem Ugi/aza-Wittig combination based on α-ketoglutaric acid for the preparation of earlier unavailable quinoxalinone derivatives. Results and Discussion We began by studying the behavior of α

Asymmetric total synthesis of tricyclic prostaglandin D2 metabolite methyl ester via oxidative radical cyclization

• Miao Xiao,
• Liuyang Pu,
• Qiaoli Shang,
• Lei Zhu and
• Jun Huang

Beilstein J. Org. Chem. 2025, 21, 1964–1972, doi:10.3762/bjoc.21.152

• -keto ester 15 [24]. The β-keto ester 15 was expected to be derived from compounds 16 and 17 via an asymmetric aldol reaction [25]. The first phase of the synthesis required the efficient preparation of compound 14, for which a transition-metal-mediated oxidative radical cyclization of β-keto ester 15

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

• -worker described the asymmetric synthesis of (−)-rasfonin, harnessing an enantioselective enzymatic desymmetrization with lipase AK and an enzymatic oxidative kinetic resolution to install stereocenters [47]. The synthesis commenced with the preparation of fragment 100 from ethylene glycol (97) (Scheme

• leustroducsin B (96). Nanda’s synthesis of a) fragment 100, b) fragment 106 and c) (−)-rasfonin (109). Davies’ synthesis of (+)-pilocarpine (115) and (+)-isopilocarpine (116). Ōmura’s synthesis of salinosporamide A (125). Kang’s synthesis of ʟ-cladinose (124) and its derivative. Kang’s preparation of fragment

Synthesis, biological and electrochemical evaluation of glycidyl esters of phosphorus acids as potential anticancer drugs

• Almaz A. Zagidullin,
• Emil R. Bulatov,
• Mikhail N. Khrizanforov,
• Damir R. Davletshin,
• Elvina M. Gilyazova,
• Ivan A. Strelkov and
• Vasily A. Miluykov

Beilstein J. Org. Chem. 2025, 21, 1909–1916, doi:10.3762/bjoc.21.148

• -well flat-bottom plates at a density of 5 × 103 cells per well and allowed to adhere for 24 hours under standard culture conditions. Preparation of compound solutions. Stock solutions of diglycidyl methylphosphonate (1), diglycidyl methylphosphate (2), and triglycidyl phosphate (3) were prepared by

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

• applications in the preparation of chiral ligands. Keywords: chiral piperazines; electrosynthesis; flow chemistry; green chemistry; imino-pinacol coupling; Introduction Vicinal diamines represent a highly valuable class of compounds that, over the past decades, have found widespread application in natural

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

• ; nitrogen – blue; carbon – grey; hydrogen – pale green). Proposed synthetic approach. Preparation of the aldehyde 4. Cycloaddition with N-methylmaleimide. Cycloaddition with N-phenylmaleimide. Cycloaddition with dimethyl fumarate and dimethyl maleate. Supporting Information Supporting Information File 30

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

• preparation. Before introducing the different photoswitch classes in this review, we familiarise ourselves with different photophysical properties. A photochromic molecule can switch reversibly between a stable and a metastable state, which are shown in an energetic profile as two local minima (Figure 1

Unique halogen–π association detected in single crystals of C–N atropisomeric N-(2-halophenyl)quinolin-2-one derivatives and the thione analogue

• Mai Uchibori,
• Nanami Murate,
• Kanako Shima,
• Tatsunori Sakagami,
• Ko Kanehisa,
• Gary James Richards,
• Akiko Hori and
• Osamu Kitagawa

Beilstein J. Org. Chem. 2025, 21, 1748–1756, doi:10.3762/bjoc.21.138

• electron pair on the bromine atom and a π* orbital of the quinoline-thione ring, rather than a π-type halogen bonding. Although we attempted the preparation of single crystals of the optically pure form of 2a, unfortunately, crystals suitable for X-ray measurement could not be obtained (2a is chemically

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

• competent substrate for the aza-Diels–Alder reaction in with TsNCO to give oxazolo[3,2-c]pyrimidine derivative 7 as a single diastereomer. Proposed approach for the preparation of vinyloxazoline 6. Synthesis of furfuryl amino alcohols S-2d and R-2d and their electrochemical oxidation to esters S-3d and R-3d

Convenient alternative synthesis of the Malassezia-derived virulence factor malassezione and related compounds

• Karu Ramesh and
• Stephen L. Bearne

Beilstein J. Org. Chem. 2025, 21, 1730–1736, doi:10.3762/bjoc.21.135

• -protected malassezione, which upon deprotection yields malassezione in an overall yield of ca. 20%. This is an improvement over the preparation of the isonitrile followed by an Fe hydride initiated isonitrile–olefin intramolecular coupling reaction, which generated malassezione with an overall yield of ca

• [20], or, more recently, (iii) prepared via an Fe hydride initiated isonitrile–olefin intramolecular coupling reaction (Scheme 1A) [18]. The reported synthetic route relies on an initial 4-step preparation of the isonitrile precursor, which was accomplished in an overall yield of ca. 14%. The

• subsequent iron-catalyzed reaction afforded 1 in only 35% yield. To avoid the low-yielding preparation of the isonitrile, we elected to use commercially available indole-3-acetic acid as the starting material, and to utilize an approach similar to that described for the synthesis of dibenzylketones from the

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

• review includes only the most relevant and recent developments in the preparation of α,α-linked 1,1'-glycosides. The review places particular emphasis on the synthesis of unsymmetrical trehalose derivatives, both with respect to the nature of the monosaccharide components (Glc, Gal, Man, GlcN, GalN, etc

• approach for the preparation of TMS-protected α-lactol acceptors was employed in the synthesis of a series of partially desymmetrized 1,1'-α,α-linked disaccharides (Scheme 13). 6-O-TBDPS-protected TMS-α-glucoside 161 was coupled with thioglycoside donor 160, furnishing the α,α-1,1'-disaccharide 162 with

• groups, particularly with regard to their type and positioning on the monosaccharide units. Other protocols allow for the preparation of highly desymmetrized 1,1'-disaccharides, albeit sometimes at the expense of only moderate isolated yields. Achieving stereoselectivity on the lactol acceptor side

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

• ], insertion reactions [16][17][18], cycloaddition reactions (e.g., [4 + 1], [3 + 2]) [19][20], and others [21][22][23]. Particularly, isocyanides have been widely exploited toward the preparation of centrally chiral structures through transition-metal-catalyzed or organocatalytic asymmetric reactions [24][25

• substrates under the standard conditions (Scheme 4b). On one hand, such findings demonstrated that the second cyclization determines enantioselectivity; on the other hand, it provided a practical way to the preparation of unsymmetrical pyrido[6]helicenes 26. Isocyanide-based multicomponent reactions Except

• chiral catalyst. Central-to-axial chirality transfer In parallel with Zhu’s work, Du, Chen, and co-workers reported an alternative way for the preparation of axially chiral 3-arylpyrroles [41] through a catalytic asymmetric Barton–Zard reaction [42] via central-to-axial chirality transfer strategy [43

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

• to the preparation of triazaphospholes and triazaarsoles, π-conjugated species with potential applications in materials science due to their luminescent properties [98]. However, these heavier alkyne analogues are typically kinetically unstable, which limits their use as dipolarophiles. Despite that

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

• reagents for the preparation of 3-aryl-substituted benzo[4,5]thieno[3,2-b]pyrroles by the annulation of the 1H-pyrrole ring to the benzo[b]thiophene system (Scheme 1, reaction 6). The behavior of indoles as aza-analogs of the benzo[b]thiophenes under the identified catalytic annulation conditions is also

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

• examples of oxindole/1,2,4-oxadiazole [20] and hydantoin/1,2,4-triazoline [22] spiro-compounds. Synthesis of dipolarophiles (5-iminohydantoins 2a–i). Preparation of the dipole precursors 4a–d. 32CA reactions of nitrile oxides with 5-iminohydantoins (synthesis of spiro-compounds 5a–l). Isolated yields are

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

• further the applicability of the present synthetic method. Due to the excellent solvating power of CyreneTM, the “one-pot” synthesis of 1,2,3-triazoles could be proposed to eliminate the preparation and isolation steps of azide components. This could open an even greener and facile protocol for CuAAC

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

• act as both electrophiles and nucleophiles [7]. This makes enaminones very reactive, providing an excellent scaffold for organic synthesis. Thus, enaminones are valuable building blocks in the preparation of several carbocyclic [8][9][10][11], heterocyclic [12][13][14][15][16][17][18] as well as

• enaminones has attracted much attention over the past decades. Kuwano’s group described the synthesis of enaminones from ethyl ketones via a nickel-catalyzed selective β-amination (Scheme 1A) [31]. The preparation of enaminones can also be achieved by the reaction of aldehydes and calcium carbide in the

Ambident reactivity of enolizable 5-mercapto-1H-tetrazoles in trapping reactions with in situ-generated thiocarbonyl S-methanides derived from sterically crowded cycloaliphatic thioketones

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Marcin Palusiak,
• Heinz Heimgartner,
• Marta Denel-Bobrowska and
• Agnieszka B. Olejniczak

Beilstein J. Org. Chem. 2025, 21, 1508–1519, doi:10.3762/bjoc.21.113

• ]-cycloaddition of respective thiocarbonyl dipolarophiles (preferably non-enolizable thioketones) with diazomethane, was demonstrated as a favorable method for their generation [5][6]. In the past three decades, 1,3-dipoles 1 have extensively been studied as useful building blocks for the preparation of various

• (for synthesis of 4b,c, and 4e, see ref. [15]). The solution of diazomethane (CH2N2) in pentane was prepared without distillation and determination of the concentration following a procedure described in an earlier publication [28]. Preparation of 2c as a new precursor of thiocarbonyl S-methanide 1c

• . Witczak (Wilkes University) for stimulating discussions in the course of preparation of the manuscript. Funding Financial support by the University of Łódź within the IDUB grant (2023-2024) is acknowledged (G.M.). The authors (A. O. and M. D.-B.) thank the Polish Ministry of Science and Higher Education

Highly distinguishable isomeric states of a tripodal arylazopyrazole derivative on graphite through electron/hole-induced switching at ambient conditions

• Himani Malik,
• Sudha Devi,
• Debapriya Gupta,
• Ankit Kumar Gaur,
• Sugumar Venkataramani and
• Thiruvancheril G. Gopakumar

Beilstein J. Org. Chem. 2025, 21, 1496–1507, doi:10.3762/bjoc.21.112

• experimental conditions. The choice of molecules that can be studied under ultra-high vacuum (UHV) is limited due to the requirement of their thermal stability and UHV compatible sublimation temperature. Therefore, the solution-based preparation method and solid-state measurements at ambient conditions hold

• accommodate ≈200 Tbits in a 1 cm2 area. Experimental Preparation of adlayer The FNAAP molecule is synthesized as per our previous report [29]. Ultra-thin films were prepared by drop casting from ethanolic solutions of molecules (concentration between 10−5 to 10−6 M) on freshly cleaved highly oriented

Heterologous biosynthesis of cotylenol and concise synthesis of fusicoccane diterpenoids

• Ye Yuan,
• Zhenhua Guan,
• Xue-Jie Zhang,
• Nanyu Yao,
• Wenling Yuan,
• Yonghui Zhang,
• Ying Ye and
• Zheng Xiang

Beilstein J. Org. Chem. 2025, 21, 1489–1495, doi:10.3762/bjoc.21.111

• diterpenoids, including alterbrassicicene E and brassicicenes A and R in 4 or 5 chemical steps from brassicicene I. This strategy lays the foundation for the preparation of fusicoccane diterpenoids and their analogues for biological studies. Keywords: cotylenol; fusicoccane diterpenoids; heterologous

• chemical steps. This work lays the foundation for the preparation of fusicoccane natural products and exploration of their biological activities. Selected fusicoccane diterpenoids and overview of this study. (a) Representative members of the fusicoccane diterpenoid family. (b) This work: heterologous

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

• bioactive compounds. According to the DrugBank there are more than 250 approved drugs classified as amides [2]. Just recently, between February 2021 and June 2022, sixteen anticancer drugs containing an amide bond have been approved by the U.S. FDA [3]. Consequently, the preparation of amides has garnered

• low tolerance to sensitive functional groups. Due to these reasons, alternative routes toward the preparation of amides are still in great demand in modern synthetic chemistry [5]. The arylation of isonitriles was introduced nearly a decade ago as an alternative synthetic pathway for the preparation

• . Control experiments, Figure S20). Conclusion In conclusion, a novel synthetic methodology for the preparation of benzamides from isonitriles and diaryliodonium salts has been proposed utilizing visible-light photoredox ruthenium-based catalysis. Both symmetrical and unsymmetrical diaryliodonium salts were