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

• into (−)-talaromycin B (232) in six steps. For (+)-talaromycin A (235) (Scheme 28b), a three-step transformation of 230 gave 233, and subsequent isomerization at the C6 spirocenter with TFA produced compound 234, which was converted into 235 in three additional steps. The introduction of an inducing

Synthesis of N-doped chiral macrocycles by regioselective palladium-catalyzed arylation

• Shuhai Qiu and
• Junzhi Liu

Beilstein J. Org. Chem. 2025, 21, 1917–1923, doi:10.3762/bjoc.21.149

• rings. In the molecular arrangement, a pair of enantiomers exists in each cell for MC3 (Figure 2d). Considering the C–C single bonds between the π-subunits, isomerization among different molecular configurations might occur via rotations. To further investigate the conformational stability of MC3

• , theoretical calculations were performed to evaluate the energy barriers of isomerization. As shown in Figure S3 (Supporting Information File 1), the configuration observed in the crystal structure has the lower energy by 24.0 kcal mol−1 than that of the isomeric structure with two pyrene units at the same

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

• removing the less soluble racemic products. Detailed studies were conducted to explore the reaction mechanism, focusing specifically on the role of the 2-acylanilines 73 as co-catalysts. Based on the experimental results and previous research, a plausible mechanism was proposed. Isomerization of substrates

Research progress on calixarene/pillararene-based controlled drug release systems

• Liu-Huan Yi,
• Jian Qin,
• Si-Ran Lu,
• Liu-Pan Yang,
• Li-Li Wang and
• Huan Yao

Beilstein J. Org. Chem. 2025, 21, 1757–1785, doi:10.3762/bjoc.21.139

• -affinity host–guest interactions between PA5 and these groups (mainly through phosphonate-quaternary ammonium ion pairing) [90]. Azobenzene guest molecules can achieve dual functions (on and off) as ligands through photo-induced cis-trans isomerization. Using pillar[6]arene as the ion channel, the host

• employed as an external trigger for supramolecular systems. Azobenzene can regulate geometry, shape, and interfacial curvature under ultraviolet or visible light irradiation. It undergoes cis–trans isomerization, which can trigger alterations in bioactivity or assembly configurations. Methods for creating

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

• methoxymethyl group cleavage, O-to-N rearrangement, and isomerization of the double bond. An oxazoline ring formation in the resulting unsaturated amides provided the corresponding enantioenriched vinyloxazoline. The reactivity of the electron-deficient double bond in the vinyloxazoline was explored in several

• electrolysis conditions and its removal was compatible with the double bond and acetal functions in ester 3d (see Supporting Information File 1 for attempts of other protecting groups such as Boc, Troc, and tfa). However, Pd-catalyzed N-Alloc deprotection induced isomerization of the double bond leading to 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

• traceless hydrolysis of β-GlcN-derived allyl glycosides with retention of the anomeric configuration [102]. Anomeric deallylation was achieved through an initial double-bond isomerization to the propenyl moiety, followed by oxidation of the glycosidic prop-1-enyl group to a formyl group, as in 111, with

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

• of this second reaction was calculated to be of 28 kcal/mol, slightly lower than the aromatic stabilization energy (ASE) and isomerization stabilization energy (ISE) calculated for benzene [20] (see reaction D in Scheme 1). Most likely this lowering stems from the strain imposed to the ortho

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

• diastereomer and characterized by NMR and HRMS data. Compound 13 is likely formed from aziridine 14 via the N→N acetyl group transfer and subsequent isomerization of the acetylaziridinyl substituent. The constitutional isomer of indole 9a, indole 15, having a nucleophilic reaction center in the β-position of

pH-Controlled isomerization kinetics of ortho-disubstituted benzamidines: E/Z isomerism and axial chirality

• Ryota Kimura,
• Satoshi Ichikawa and
• Akira Katsuyama

Beilstein J. Org. Chem. 2025, 21, 1568–1576, doi:10.3762/bjoc.21.120

• barriers by protonation, providing a novel approach to control the kinetics of isomerization via pH adjustment. The results showed that protonation of the amidine moiety significantly suppresses both C–N bond rotation and C–N/C–C concerted rotation, demonstrating the potential of ortho-disubstituted

• benzamidine derivatives as a novel pH-responsive molecular switch. Keywords: atropisomer; conformation; isomerization; molecular switch; organobase; Introduction pH-Responsive molecular motors and switches are a class of functional organic molecules capable of reversible structural and electronic changes

• switches [19]. For example, hydrazone-based molecular switches undergo reversible E/Z isomerization around the C=N bond [1][2][3][4][5][6][7], with protonation significantly shifting the equilibrium. Beyond double-bond isomerization, pH stimuli have also been employed to modulate rotational barriers in

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

• carbethoxyformonitrile oxide (CEFNO) precursor. The nitrile oxides were generated in situ by the action of a base (Et3N) to compounds 4a–d in the dipolarophile-containing solution to prevent high concentrations of dipole molecules and to minimize the inevitable competition between the 32CA reaction and the isomerization

• of nitrile oxides to isocyanates or their dimerization [26][27]. Since isomerization is believed to be the primary direction of molecule degradation only for bulky o,o'-disubstituted aromatic dipoles [28][29][30], the main efforts in developing a methodology were focused on suppressing dimerization

Azobenzene protonation as a tool for temperature sensing

• Antti Siiskonen,
• Sami Vesamäki and
• Arri Priimagi

Beilstein J. Org. Chem. 2025, 21, 1528–1534, doi:10.3762/bjoc.21.115

• their widespread use in biomedicine [5][6], energy storage [7][8], soft robotics [9][10], and sensing [11]. The key factors for their success are the efficient photochemical isomerization, causing large spatial, spectral, and electronic changes, as well as the relative ease of modification of the

• azobenzene core by introducing different functional groups to the phenyl rings. For these reasons, azobenzenes can be sensitized to various stimuli and easily integrated into different types of materials. While cis–trans isomerization is the most prominent property of interest for azobenzenes, there are also

• they all typically result in significant changes in the absorption spectrum and/or alter the stability of the metastable isomer. In sensing, azobenzenes have been utilized, e.g., through changes in isomerization kinetics [17][18] or colorimetric properties. The colorimetric sensors are effective for

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

• towards 5-mercapto-1H-tetrazoles was compared with well-known analogues derived from adamantanethione and 2,2,4,4-tetramethyl-3-thioxocyclobutanone. Some of the isolated thioaminals were observed to undergo thermal isomerization in CDCl3 solution yielding the corresponding dithioacetals. Structural

• chemoselectivity was observed. A detailed study on the mechanism of these reactions showed that the initially formed S–H insertion products (type 5) underwent thermal isomerization leading to thermodynamically more stable N–H insertion ones (type 6) (Scheme 2) and the isomerization process was clearly dependent on

• contained thioaminals 9, which underwent a slow isomerization in CDCl3 solution. Notably, in the case of products 9k and 10k, bearing a Ph group at N(1), after a successful chromatographic separation, the less stable 9k underwent isomerization in CDCl3 solution (at rt) and no registration of NMR spectra of

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

• atomically precise write and read tool like an STM tip. Keywords: azo compounds; electron/hole-induced isomerization; isomerization; molecular switches; switching; Introduction Molecular electronic devices have been predicted to outperform silicon-based devices [1][2]. Reprogrammable arrays of molecular

• details). Next, we show the electron/hole-induced E–Z isomerization of a single FNAAP within the assembly. By placing the STM tip on selected molecules, the sample voltage is ramped, and the corresponding change in current is measured. These measurements are tagged as current–voltage (I–V) characteristics

• . Electrons and holes are injected into molecules at negative and positive sample voltages, respectively. It is known that upon injection of electrons or holes, molecules get transiently charged on the graphite surface and undergo isomerization (switch) [11][37][38]. Figure 4a shows two independent I–V

Tautomerism and switching in 7-hydroxy-8-(azophenyl)quinoline and similar compounds

• Lidia Zaharieva,
• Vera Deneva,
• Fadhil S. Kamounah,
• Nikolay Vassilev,
• Ivan Angelov,
• Michael Pittelkow and
• Liudmil Antonov

Beilstein J. Org. Chem. 2025, 21, 1404–1421, doi:10.3762/bjoc.21.105

• stabilization of the azo tautomer and making possible long range proton transfer to the quinolyl nitrogen atom. Keywords: azo dyes; E/Z isomerization; DFT; NMR; photochemistry; proton transfer; tautomerism; UV–vis; Introduction Azo compounds have long been utilized as dyes in industries such as textiles

• resistance [1][2][3][4]. In addition to their conventional use, azodyes have unique optical properties, defined by the E/Z isomerization [5][6] and by the tautomeric proton exchange [3][7][8][9][10][11], when a OH or NH group is present on a suitable position in the molecule. Both processes are strongly

• influenced by the structural variations and the environment (temperature, solvent properties, acidity and presence of other molecules). The E/Z isomerization of the azodyes, caused by light irradiation [12][13][14] or electrochemically [15][16], has paved the way for the development of innovative materials

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

• construction, alkyne hydrogenation, ylide and carbene reaction, metathesis, E/Z isomerization, and other methods, including Cα and Cβ functionalizations. Preparing various functional group-tethered aromatic groups can be achieved by directly installing an aromatic group via cross-coupling reactions and other

• using flow conditions, Kim and co-workers (2021) reported the cis–trans isomerization of α-functionalized stilbenes in a flow microreactor (Scheme 65B) [112]. The isomerization could be regioselectively controlled in an incredibly short time within milliseconds (247, 248) to give either the E-isomeric

Recent total synthesis of natural products leveraging a strategy of enamide cyclization

• Chun-Yu Mi,
• Jia-Yuan Zhai and
• Xiao-Ming Zhang

Beilstein J. Org. Chem. 2025, 21, 999–1009, doi:10.3762/bjoc.21.81

• incorporated into cyclization reactions. The iminium species generated from enamides via nucleophilic addition or substitution are capable of engaging in further electrophilic additions or isomerization processes. Exploiting the multiple reactivities of enamides facilitates the development of diverse

• iminium intermediates can serve as electrophiles. Due to the presence of an amide, the resulting iminiums from the enamides can be stabilized to take part in the second nucleophilic addition, though direct isomerization of the iminiums to the enamides is also possible (Figure 1). Guided by these

• . Cyclization/isomerization – collective total synthesis of fawcettimine-type alkaloids The bicyclic decahydroquinoline enamide motif can serve as a versatile precursor to access different types of tricyclic N-heterocycles. As demonstrated in the above work from She’s group, the aza-Prins cyclization renders

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

• C(sp3)–C(sp3) coupling via distal stereocontrol, efficiently producing C3-alkylated pyrrolidines, while the nickel catalytic system afforded C2-alkylated pyrrolidines through a tandem alkene isomerization/hydroalkylation process. This method utilized readily accessible catalysts, chiral BOX ligands

• insertion to achieve C3 selectivity, whereas nickel catalysis involved alkene isomerization to generate a (2,3-dihydropyrrolyl) intermediate Int-35, followed by C2-selective coupling. In 2024, the Zheng group reported a catalyst-controlled cyclization reaction of bicyclo[1.1.0]butanes (BCBs) 32 with α

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

• summary, we have discovered an unanticipated Cu–Bpin-promoted diastereoselective dimerization of 4,4-dichloro-2-butenoic acid derivatives. The reaction occurs via initial Cu–Bpin insertion followed by keto–enol isomerization and salt metathesis to generate a lithium enolate which is then trapped by a

Light-enabled intramolecular [2 + 2] cycloaddition via photoactivation of simple alkenylboronic esters

• Lewis McGhie,
• Hannah M. Kortman,
• Jenna Rumpf,
• Peter H. Seeberger and
• John J. Molloy

Beilstein J. Org. Chem. 2025, 21, 854–863, doi:10.3762/bjoc.21.69

• isomerization of alkenes [18][19], [2 + 2] cycloadditions [20][21][22][23][24], and dearomative [4 + 2] cycloadditions [25][26][27]. When considering conjugated alkenes, the triplet excited state energy and excited state lifetime are intrinsically linked to the degree of conjugation and substitution of a

• reactivity in EnT catalysis has also been intensively pursued (Figure 1B). The controlled geometric isomerization of boron-containing conjugated dienes [42], styrenes [43][44][45] and β-boryl acrylates [46][47] has been established with great effect, while elegant [2 + 2] cycloaddition strategies to readily

• . Herein, we demonstrate the sensitization of alkenylboronates to enable efficient intramolecular [2 + 2] cycloaddition using high energy photosensitizers (Figure 1C). Sensitization was quickly established and explored through the use of alkene scrambling (geometrical isomerization) reaction probes, to

Substituent effects in N-acetylated phenylazopyrazole photoswitches

• Radek Tovtik,
• Dennis Marzin,
• Pia Weigel,
• Stefano Crespi and
• Nadja A. Simeth

Beilstein J. Org. Chem. 2025, 21, 830–838, doi:10.3762/bjoc.21.66

• discovered that simple acylation of the pyrazole moiety leads to increased quantum yields of isomerization, long Z-isomer life-times, good spectral separation, and high photostability. Keywords: azobenzenes; azopyrazoles; photochromism; photoswitches; substituent effects; Introduction Organic photoswitches

• hyperchromic effects compared for NH- and NMe-PAP-H. Photochemical isomerization Upon irradiation with a 365 nm LED (exemplarily displayed for NMe-PAP-CN in Figure 2), we observed a decrease of the π→π* band for the E isomers. Simultaneously the π→π* bands around 253–369 nm and the n→π* bands around 426–457

• spectral separation of the isomers. Since we encountered fast back isomerization only for NAc-PAP-OH (vide infra), the PSDs could only be determined from the UV–vis spectra. NAc-PAPs showed high to quantitative formation of the Z-configurated isomers. For example, NAc-PAP-Br showed an isomerization

Synthesis and photoinduced switching properties of C₇-heteroatom containing push–pull norbornadiene derivatives

• Daniel Krappmann and
• Andreas Hirsch

Beilstein J. Org. Chem. 2025, 21, 807–816, doi:10.3762/bjoc.21.64

• heat, catalysis, or an electrochemical input [4][5][6], the stored energy can be released converting the molecule back in the parent form (Figure 1). Typical MOST systems are azobenzenes (E/Z-isomerization) [7][8][9][10], the isomerization of dihydroazulenes/vinylheptafulvenes [11][12][13], conversion

• , it is essential not only to achieve a high storage density and good quantum efficiency for the isomerization process but also to ensure large half-lifes and durability in switching reliability [20]. By making structural adjustments to the parent carbon scaffold, it is possible to target specific

• products alongside the formation of the desired QCs [32][34][35][36][37][38]. Despite this, the focus has largely been on symmetrical 2,3-substituted derivatives, with reports primarily on the reversible isomerization of oxa-NBD to oxa-QC derivatives [39]. Asymmetrical push–pull derivatives have received

Development and mechanistic studies of calcium–BINOL phosphate-catalyzed hydrocyanation of hydrazones

• Carola Tortora,
• Christian A. Fischer,
• Sascha Kohlbauer,
• Alexandru Zamfir,
• Gerd M. Ballmann,
• Jürgen Pahl,
• Sjoerd Harder and
• Svetlana B. Tsogoeva

Beilstein J. Org. Chem. 2025, 21, 755–765, doi:10.3762/bjoc.21.59

• the R-product from E-hydrazone is slightly lower in energy (Table 3). However, the activation barrier for the rate-limiting step is 0.4 kcal·mol−1 lower for the pathway shown in Figure 2 and that yields the S-product from the Z-hydrazone. As the activation barrier to thermal E/Z-isomerization is more

Copper-catalyzed domino cyclization of anilines and cyclobutanone oxime: a scalable and versatile route to spirotetrahydroquinoline derivatives

• Qingqing Jiang,
• Xinyi Lei,
• Pan Gao and
• Yu Yuan

Beilstein J. Org. Chem. 2025, 21, 749–754, doi:10.3762/bjoc.21.58

• , we conducted a 5.0 mmol scale reaction and obtained the target product 3aa in 82% yield (Scheme 3). Based on previous reports, a plausible mechanism was proposed. In the presence of a copper catalyst, aniline reacts with cyclobutanone oxime to form an imine intermediate, which undergoes isomerization

Orthogonal photoswitching of heterobivalent azobenzene glycoclusters: the effect of glycoligand orientation in bacterial adhesion

• Leon M. Friedrich and
• Thisbe K. Lindhorst

Beilstein J. Org. Chem. 2025, 21, 736–748, doi:10.3762/bjoc.21.57

• ]. Specifically, the reversible E/Z isomerization of the azo group in azobenzene glycosides is suited to control the spatial presentation of glycoligands and, for example, switch carbohydrate-specific bacterial adhesion on and off [20][21][22][23]. Indeed, glycoazobenzene derivatives are excellent tools to

• other hand, leads to a PSS with more E isomer, namely an E/Z ratio of 85:15. Irradiation of 3 and 4 with light of 520 nm effects an E to Z isomerization with an E/Z ratio of 23:77 in both cases, since 520 nm light addresses the bathochromically shifted n–π* band of the E isomers due to the ortho-fluoro

• hypothesize that isomerization of the azo group in the tested azobenzene glycoconjugates controls the orientation of the attached glycoligand and therefore, different glycoazobenzene isomers show various affinities for the bacterial lectin FimH as reflected by the measured RIP values. This is clearly seen

Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45