Rotaxanes with integrated photoswitches: design principles, functional behavior, and emerging applications

• Jullyane Emi Matsushima,
• Khushbu,
• Zuliah Abdulsalam,
• Udyogi Navodya Kulathilaka Conthagamage and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2345–2366, doi:10.3762/bjoc.21.179

• ring appended to it, capable of capturing K+ ions (Figure 6) [51]. The authors demonstrated that this rotaxane can be incorporated into model lipid bilayers and mediate K+ ion transport across membranes through the shuttling motion of the macrocycle. In its trans configuration, the azobenzene allows

• pyridinium bisamide that forms a complex with the isophthalamide unit of the macrocycle and a chloride anion when the stiff-stilbene is in the cis configuration (Figure 17). Upon switching to the trans isomer, the expanded geometry of the macrocycle disrupts the complex, resulting in the dethreading of the

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

• enantiomers of 51 allowed Tsukano and co-workers to prepare both enantiomers of complanadine A. Their further biological evaluation of the complanadines and several synthetic intermediates revealed that the pseudo-dimeric structure, absolute configuration, and oxidation level are important for the observed

Recent advances in Norrish–Yang cyclization and dicarbonyl photoredox reactions for natural product synthesis

• Peng-Xi Luo,
• Jin-Xuan Yang,
• Shao-Min Fu and
• Bo Liu

Beilstein J. Org. Chem. 2025, 21, 2315–2333, doi:10.3762/bjoc.21.177

• room temperature, delivering spiroacetal (S)-114 with complete retention of configuration (>99% ee). The subsequent one-pot acetylation generated (S)-115 in 83% overall yield over three steps from (S)-112. The following functional group manipulations of (S)-115 – including debenzylation/debromination

Halogenated butyrolactones from the biomass-derived synthon levoglucosenone

• Johannes Puschnig,
• Martyn Jevric and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2025, 21, 2297–2301, doi:10.3762/bjoc.21.175

• epoxidations of 5 are highly stereoselective [44]. Unambiguous assignment of configuration for the diastereomers was not possible on the basis of the selective 1D NOE spectra due to the lack of informative crosspeaks. Limiting the amount of oxidant (H2O2 or peracetic acid) resulted in mixtures, suggesting that

Enantioselective radical chemistry: a bright future ahead

• Anna C. Renner,
• Sagar S. Thorat,
• Hariharaputhiran Subramanian and
• Mukund P. Sibi

Beilstein J. Org. Chem. 2025, 21, 2283–2296, doi:10.3762/bjoc.21.174

• -alkenylated products 43 with excellent enantioselectivities. Alkenyl trifluoroborates with (Z) configuration gave higher product yields than the analogous (E)-alkenyl trifluoroborates, but the corresponding alkenyl group in the product had (E) configuration in all cases. A key enabling aspect of the method

Pathway economy in cyclization of 1,n-enynes

• Hezhen Han,
• Wenjie Mao,
• Bin Lin,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2025, 21, 2260–2282, doi:10.3762/bjoc.21.173

• copper-catalyzed tandem process initiated by endo-cyclization of indolyl homopropargyl amides, enabling atom-economical synthesis of therapeutically significant bridged aza[n.2.1] skeletons. Angle strain and configuration-controlled cyclization of 1,n-enynes In cyclization reactions, angle strain and

• configuration exert pronounced effects on reaction pathways. These substrate-specific geometric parameters directly dictate transition state formation during ring closure. Recent advances demonstrated that deliberate manipulation of angle strain and configuration enabled divergent skeletal outcomes under

• the regio- and stereoselective 5-exo-dig alkoxycyclization of 1,5-enynes via gold(I) catalysis. The cyclization mode was controlled by the configuration of the double bond in the substrate. In Z-configured substrates, steric constraints promoted 5-endo-dig cyclization, generating bicyclo[3.1.0]hexane

A chiral LC–MS strategy for stereochemical assignment of natural products sharing a 3-methylpent-4-en-2-ol moiety in their terminal structures

• Rei Suo,
• Raku Irie,
• Hinako Nakayama,
• Yuta Ishimaru,
• Yuya Akama,
• Masato Oikawa and
• Shiro Itoi

Beilstein J. Org. Chem. 2025, 21, 2243–2249, doi:10.3762/bjoc.21.171

• all compounds. In this study, we developed a method to determine the absolute configuration of the terminal MPO moiety with high accuracy and sensitivity by a combination of chemical degradation, chemical synthesis, and chiral LC–MS analysis. The applicability of this method was demonstrated through

• typically determined using NMR-based techniques, such as coupling constant analysis and NOE experiments, sometimes with the aid of computational chemistry [3][4][5][6][7]. In contrast, absolute configuration remains more challenging to determine, as it frequently requires chemical degradation or

• groups. Total synthesis is a powerful approach for determining absolute configuration through the comparison of specific rotation or chromatographic behavior; however, it requires considerable time and effort. In this context, we have been working on developing effective approaches to determine the

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

• (according to LC–MS) was always the (E) isomer. However, in the case of compounds 7c and 7h, the (Z) isomers were present in relatively high quantities and could also be successfully isolated and characterized after flash chromatography. The configuration of the C=N double bond was determined on the basis of

• both Figures, beside the selective 1D NOESY spectrum (upper part in Figure 2 and Figure 3), the 1H NMR spectrum (lower part) is also presented. The spatial proximity of NH with N=CH (marked with a red arrow in Figure 2) or with CH2 (red arrow in Figure 3) proves the (E) or (Z) configuration of the N=C

A m-quaterphenyl probe for absolute configurational assignments of primary and secondary amines

• Yuka Takeuchi,
• Mutsumi Kobayashi,
• Yuuka Gotoh,
• Mari Ikeda,
• Yoichi Habata,
• Tomohiko Shirai and
• Shunsuke Kuwahara

Beilstein J. Org. Chem. 2025, 21, 2211–2219, doi:10.3762/bjoc.21.168

• conformers, obtained via DFT calculations, show a correlation with both the sign and intensity of the experimentally observed CD spectra. Keywords: absolute configuration; chiral amine; chiral quaternary ammonium salt; circular dichroism; DFT calculation; Introduction Determining the absolute

• effect in CD, the direction of twist can be estimated. The absolute configuration of amines can be determined by comparing the direction of the twist determined by CD with that obtained by conformational analysis using theoretical calculations. However, this method has only been applied to simple primary

• amines. In this work, we report that the method was applied to chiral amino alcohols and amino acid esters. We also applied the method to chiral secondary amines, for which it is generally difficult to determine the absolute configuration due to the conformational complexity of their derivatives [33]. By

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

• . Additionally, there is a lack of corresponding pharmacological activity studies. In 2021, the group of Han completed the first enantioselective total synthesis of (+)-toxicodenane A (16) and determined its absolute configuration by employing an early-stage desymmetric enantioselective reduction of a 1,3

• Prins cyclization produced the oxa-bridged product 88. Finally, ozonolysis of 88 followed by Wittig reaction of the resultant ketone and subsequent reduction accomplished the total synthesis of (+)-toxicodenane A (16). The authors eventually confirmed that the absolute configuration of (+)-16 was 4S,5S

Further elaboration of the stereodivergent approach to chaetominine-type alkaloids: synthesis of the reported structures of aspera chaetominines A and B and revised structure of aspera chaetominine B

• Jin-Fang Lü,
• Jiang-Feng Wu,
• Jian-Liang Ye and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2025, 21, 2072–2081, doi:10.3762/bjoc.21.162

• absolute configuration was unambiguously determined by the comparison with the reported compound chaetominine (1)” [32]. The only information regarding the absolute configuration mentioned in the text is as follows: “aspera chaetominine A (1) was presumably biosynthesized from ʟ-isoleucine, ʟ-valine

• (–)-isochaetominine C (6), whose absolute configuration is tentatively assigned as 2R,3R,11S,14R. It is worth noting that compound 13 has been obtained in our previous investigation [63]. However, the 1H and 13C NMR spectra were recorded in DMSO-d6 which prevent a direct comparison with the data of aspera

Measuring the stereogenic remoteness in non-central chirality: a stereocontrol connectivity index for asymmetric reactions

• Ivan Keng Wee On,
• Yu Kun Choo,
• Sambhav Baid and
• Ye Zhu

Beilstein J. Org. Chem. 2025, 21, 1995–2006, doi:10.3762/bjoc.21.155

• formed in the product. 2.2 Determine, according to the Cahn–Ingold–Prelog (CIP) rules, the atoms that distinguish the newly created stereogenic element's configuration. These are the atoms whose identities represent the first point of difference between the set of substituents in assigning the

• configuration of the new stereogenic element. One or two sets of atoms could be identified. a) These atoms labeled in step 1 are considered higher in priority than any other atoms. b) If the comparison is down to between an atom already labeled in step 1 and one other atom, such comparison and this set of atoms

• index (Scheme 2). A detailed process for assigning the index is shown in Scheme 2A for asymmetric hydrogenation of 2-butanone [1]. The atoms involved in bond cleavage and bond formation are highlighted in orange color. The atoms responsible for assignment of the stereochemical configuration of the

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

• -metathesis reaction smoothly in the presence of the Hoveyda–Grubbs second-generation catalyst to afford the enone 13 in 63% yield with the desired trans-configuration. Enone 13 was then subjected to the Pd/C-catalyzed hydrogenation to give the thermodynamically favored bicyclic hemiketal 21 in 92% yield as

• stereochemistry at C9. Therefore, alcohol 32 was subjected to a one-pot Mitsunobu reaction, hydrolyzation, and spirolactonization to give the corresponding alcohol 26 with inversed configuration at C9. Finally, terminal alkene 26 was transformed by Dai’s Ru-catalyzed Z-selective cross-metathesis with 33 [9][40

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

• , 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

• with a Daicel Chiralpak IF column (Figure S1, Supporting Information File 1). The absolute configuration of the separated enantiomers of MC1 was determined based on the calculated CD spectra (Figure S4, Supporting Information File 1). The first fraction was defined as the (+)-enantiomer, and the second

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

• absolute configuration of the piperazine formed, a pure sample of compound 2b derived from (1R,2R)-trans-diaminocyclohexane was crystallized from a chloroform solution resulting in the formation of white crystals suitable for single crystal X-ray diffraction studies. The absolute configuration of the

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

• reaction produced the imine 16a which, upon treatment with Pd(PPh3)2Cl2 and KHMDS, led to furan ring formation and the generation of hetero[7]helicene 17a while maintaining the stereochemical configuration. Through this methodology, a range of elongated [7]- and [8]heterohelicenes 17b–d incorporating both

• enantioselective synthesis of planarly chiral macrocycles through a dynamic kinetic resolution approach [15]. Despite bearing an amino group on the phenyl ring, the configuration of the macrocyclic paracyclophane 32 was found to be unstable at room temperature. Consequently, by employing a CPA-catalyzed asymmetric

• the efficient asymmetric synthesis of inherently chiral eight-membered N-heterocycle 6,7-diphenyldibenzo[e,g][1,4]diazocines (DDDs), which displayed a rigid saddle-shaped configuration [16]. Starting from readily available [1,1'-biphenyl]-2,2'-diamines 62 and benzyl compounds 63, the asymmetric

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

• stable isomer is not always intuitive, and several early studies focused on this aspect [96][105][106]. For small substituents (H, Me, CN) in aprotic solvents and in the absence of other external factors, the equilibrium is usually shifted towards the least hindered configuration, regardless of the

• irradiation [118] (Figure 20). The primary example of a diarylethene is stilbene: it was discovered that upon irradiation, stilbene would not only switch between the E- (I) and Z-configuration (II) but also, in its Z-configuration, it would undergo a 6π-electrocyclisation (III) (see Scheme 39) [119]. However

[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

• relative configuration (cis or trans) of the substituents. Therefore, the structures of the obtained compounds were determined by single crystal X-ray analysis (Figure 1). Thus, all the obtained derivatives of oxo-rhodanine 6, rhodanine 8 and imidazolone 9 had a cis configuration, while the derivatives of

• thiohydantoin 7, on the contrary, have a trans configuration of two vicinal stereocenters (Scheme 3 and Figure 1). Thus, in all cases we have obtained, probably, the most thermodynamically favorable isomers. This result allows us to assume a stepwise mechanism of the ylide addition to the double bond of

• thiohydantoin derivatives, since the initial compounds 2 had a predominant Z-configuration. At the same time, for cases 1, 3 and 4, both a synchronous and stepwise mechanism are possible. The discovered stereochemistry of the reaction correlates well with the previously obtained data, when the most

3,3'-Linked BINOL macrocycles: optimized synthesis of crown ethers featuring one or two BINOL units

• Somayyeh Kheirjou,
• Jan Riebe,
• Maike Thiele,
• Christoph Wölper and
• Jochen Niemeyer

Beilstein J. Org. Chem. 2025, 21, 1719–1729, doi:10.3762/bjoc.21.134

• macrocycles Me/H/iPr-M22 in good yields of 59/78/77%. Again, we applied this protocol for the synthesis of the unsymmetric derivative HiPr-M22, this time in two diastereomeric forms. In the unsymmetric case, the introduction of two BINOL units with opposite configuration does not furnish a meso-compound, so

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

• traditionally presents challenges such as modest stereoselectivity, the formation of various diastereomeric by-products and moderate yields. The configuration of the glycosidic linkage (ββ, αα or βα) is the most important factor in choosing an appropriate glycosylation approach, alongside the specific

• exploiting the participation effect of the neighboring protecting group [43][44], employing anomeric lactols as acceptors is more complex as lactols with the desired configuration are frequently difficult to obtain (e.g., through anomerization). In addition to the nature of the leaving group and promoter

• formation of an α-glycoside on the donor side [54]. On the acceptor side, the β-configuration was favored due to steric hindrance from the C-2 phthalimido group in the triacetylated GalN-lactol acceptors 6 or 3,4-di-O-benzylated acceptors 8, resulting in kinetically controlled formation of β,α-1,1

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

• system configuration strategies, critical process parameters and operating ranges, performance evaluation metrics, universal methodologies for kinetics analysis, safety assessment protocols, and scale-up approaches. The presented content aims to offer actionable guidance for researchers and engineers

Structural analysis of stereoselective galactose pyruvylation toward the synthesis of bacterial capsular polysaccharides

• Tsun-Yi Chiang,
• Mei-Huei Lin,
• Chun-Wei Chang,
• Jinq-Chyi Lee and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2025, 21, 1671–1677, doi:10.3762/bjoc.21.131

• , and the immunological properties may base on R/S-configuration. However, precisely controlling the formation of R- and S-isomers and identifying the correct conformer can be challenging due to the structural similarities between these two isomers. Researchers have recently developed strategies to

• define the stereochemistry of pyruvate ketals as either R- or S-configurations. Typically, S-configuration exhibits 13C NMR shifts between δ 17–24 ppm and 1H NMR shifts δ 1.60–2.10 ppm, whereas the R-configuration shows 13C shifts downfield at δ 24-27 ppm and 1H shifts at δ 1.40–2.00 ppm [19][20][21][22

• produce solid compound 6. A single crystal of compound 6 was obtained through recrystallization using ethyl acetate and n-hexane. The X-ray structural data provided direct evidence supporting the R-configuration (Figure 2a). The material crystallized in the monoclinic space group P21, with cell dimensions

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

• observed between the dimer and trimer, despite the same absolute configuration of the planar chiral [2.2]paracyclophane units, which was reproduced by theoretical studies. Keywords: circularly polarized luminescence; oligomer; [2.2]paracyclophane; planar chirality; Introduction Cyclophane is a general

• same absolute configuration. The |glum| value of 7 was 0.4 × 10−3 (Figure S18A, Supporting Information File 1), which was lower than that of 6. In the case of the film states of 6 and 7, low PL brightness and intermolecular random orientation of fluorophores resulted in noisy CPL signals. The CD

• | values of the ordered of 10–4–10–3. The chiroptical properties of dimers and trimers showed opposite Cotton effects and CPL signals, despite the same absolute configuration of the planar chiral [2.2]paracyclophane crossing points. The π-conjugation system of the dimer that exhibited CPL was highly curved

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

• states (TSs) were found depending on the configuration of the amidine N–H and the rotational direction. The C–N bond rotation of the molecular form of amidine was calculated to be 68 kJ·mol−1 for Z-amidine and 71 kJ·mol−1 for E-amidine. Protonation of the amidine moiety drastically increases the

• separation of the two peaks, HPLC analysis of each separated component showed single peaks, suggesting that the E and Z isomers of amidine 2 trifluoroacetate salt could be separated by standard RP-HPLC. The configuration of the amidine moiety of each component was characterized by NOE experiments (for