[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

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

• determined by the configuration of the spiro-core, while still allowing for the possibility of relative rotation to facilitate better binding to the targets. Furthermore, it appears to be as exceedingly advantageous from a synthesis perspective, as it enables the application of methods that have been

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

• conformational switching of a tripodal azopyrazole derivative (FNAAP) in its ultra-thin films on a HOPG surface at ambient conditions. Most of the molecules (>98%) in the film are in the EEE configuration and form a hexagonal close-packed assembly. Molecules within the condensed phase of EEE isomeric states were

Wittig reaction of cyclobisbiphenylenecarbonyl

• Taito Moribe,
• Junichiro Hirano,
• Hideaki Takano,
• Hiroshi Shinokubo and
• Norihito Fukui

Beilstein J. Org. Chem. 2025, 21, 1454–1461, doi:10.3762/bjoc.21.107

• (P,P)-1, whose configuration was previously confirmed [17]. The (P,P)-figure-eight conformation of CBBC 1 corresponds to the (Ra,Ra)-bathtub conformation, whose configuration is based on the axial chirality of the biaryl segment. Consequently, the 1st fractions of 3 and 5 were determined to be (Sa,Sa

• circle and red triangle mean selected signals due to figure-eight and bathtub conformations, respectively. Simulated dynamics of bis-olefin 5 at the B3LYP/6-31G(d) level of theory. The description for the configuration of A and B are based on the helical chirality of the 1,1-diphenylethylene units and

Advances in nitrogen-containing helicenes: synthesis, chiroptical properties, and optoelectronic applications

• Meng Qiu,
• Jing Du,
• Nai-Te Yao,
• Xin-Yue Wang and
• Han-Yuan Gong

Beilstein J. Org. Chem. 2025, 21, 1422–1453, doi:10.3762/bjoc.21.106

• units, as well as extending π-conjugated frameworks, are widely employed strategies for achieving longer-wavelength emission in optoelectronic materials. Inspired by the electronic configuration of borazine, boron has emerged as a valuable electron-accepting counterpart to electron-donating nitrogen in

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

• constructed by us [92]. The configuration allows to use two light sources whose beams path orthogonally through a cuvette. The absorbance spectra were measured using a fiber-optic micro-spectrometer QE 65000 (Ocean Optics, Inc., Dunedin, FL, USA) with approximately 0.7 nm spectral resolution in the range 250

Reactions of acryl thioamides with iminoiodinanes as a one-step synthesis of N-sulfonyl-2,3-dihydro-1,2-thiazoles

• Vladimir G. Ilkin,
• Pavel S. Silaichev,
• Valeriy O. Filimonov,
• Tetyana V. Beryozkina,
• Margarita D. Likhacheva,
• Pavel A. Slepukhin,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2025, 21, 1397–1403, doi:10.3762/bjoc.21.104

• , the atom N(2) deviates from the RMS plane S(1)C(3)C(4)C(5) by 0.461 Å. The atom of the N(1) morpholine fragment has a planar configuration with significant asymmetry in the lengths of C–N bonds. Due to the electron-acceptor effects of substituents, the C(3)‒H bond exhibits significant polarity and is

N-Salicyl-amino acid derivatives with antiparasitic activity from Pseudomonas sp. UIAU-6B

• Joy E. Rajakulendran,
• Emmanuel Tope Oluwabusola,
• Michela Cerone,
• Terry K. Smith,
• Olusoji O. Adebisi,
• Adefolalu Adedotun,
• Gagan Preet,
• Sylvia Soldatou,
• Hai Deng,
• Rainer Ebel and
• Marcel Jaspars

Beilstein J. Org. Chem. 2025, 21, 1388–1396, doi:10.3762/bjoc.21.103

• the biogenesis of this heterocyclisation leading to the pseudomonine biosynthesis [23]. The absolute configuration of the threonine residue in compounds 1 and 2 was assigned as ʟ, based on the derivatization of 1 and 2 hydrolysates with ʟ-FDAA, a Marfey’s reagent, followed by chromatographic profiling

• configuration to that of 3, evidenced by a medium through space correlation between the amide proton, H-8 (δH 9.9) and the methyl, H3-12 (δH 1.76) in the NOESY spectrum (see Figure 2 and Supporting Information File 1, Figure S23). Based on HRESIMS, 1D and 2D NMR data, the structure of compound 4, was confirmed

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• : aliphatic > allylic > benzylic. In case of trisubstituted C=C bonds, the cyclisation proceeded with retention of configuration, however, higher reaction temperatures were required due to the increased steric hindrance. Competition experiments revealed a preference for 4-exo ring closure over 5-exo, 6-exo

• % yield. Interestingly, only the xylono-lactone showed complete inversion of the configuration at C-2 while the lyxono-lactone showed complete retention of the configuration. The ribono- and arabinono-lactone displayed predominant retention and inversion, respectively. Switching the triflyl group for the

Synthetic approach to borrelidin fragments: focus on key intermediates

• Yudhi Dwi Kurniawan,
• Zetryana Puteri Tachrim,
• Teni Ernawati,
• Faris Hermawan,
• Ima Nurasiyah and
• Muhammad Alfin Sulmantara

Beilstein J. Org. Chem. 2025, 21, 1135–1160, doi:10.3762/bjoc.21.91

• a cancer therapeutic, exhibiting anti-inflammatory, anti-angiogenic, antimicrobial, antifungal, and antimalarial activities. While Keller-Schierlein first determined its chemical structure, Anderson later confirmed its absolute configuration using X-ray crystallography [16]. During the screening of

• sediment in Yalongwan, China [22]. The C14–C15 olefin geometry of borrelidins G and H (Table 1, entries 10 and 11) exhibited a Z-configuration, as confirmed by NOESY correlations. Borrelidins J–L (Table 1, entries 13–15) were isolated from an endophytic Streptomyces sp. NA06554 from Aster tataricus in Aba

• borrelidin [38]. They highlighted a significant limitation in existing methods for constructing the deoxypropionate unit of borrelidin, which features four 1,3-alternating methyl groups with a syn,syn,anti-configuration. These methods typically required at least three synthetic steps to iteratively form each

A versatile route towards 6-arylpipecolic acids

• Erich Gebel,
• Cornelia Göcke,
• Carolin Gruner and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 1104–1115, doi:10.3762/bjoc.21.88

• to investigate how the configuration of the stereocenter in C2 position influences diastereoselectivity. In the first approach, NaBH3CN was used under acidic conditions to reduce the acyliminium intermediate formed from the N-acyl enamine upon protonation at C5, while in the second approach

• kinetically controlled diastereofacial selectivity. The resulting diastereomers are separable by chromatography. 1H NMR was used to assign the configuration of the 2 diastereomers [53][54][55]. Carbon C2 is R-configured, as ᴅ-2-aminoadipic acid (1) was employed as the starting material. The minor diastereomer

• adopts a chair with only gauche couplings for H2 [3J(H2,H3,pro-S) = 5.7 Hz and 3J(H2,H3,pro-R) = 3.6 Hz]. Similarly, the configuration at C6 becomes evident by gauche couplings only between H6 and H5 [3J(H6,H5,pro-S) = 3J(H6,H5,pro-R) = 5.1 Hz] with an axial position for the aryl substituent at C6 as

Supramolecular assembly of hypervalent iodine macrocycles and alkali metals

• Krishna Pandey,
• Lucas X. Orton,
• Grayson Venus,
• Waseem A. Hussain,
• Toby Woods,
• Lichang Wang and
• Kyle N. Plunkett

Beilstein J. Org. Chem. 2025, 21, 1095–1103, doi:10.3762/bjoc.21.87

• heteroatoms at axial positions resulting in a three-center four-electron bond [13][14]. In this unique “T” configuration, the bond length between iodine and one of the heteroatoms is influenced by the bond distance of the other heteroatom and is responsible for the stabilization of the hypervalent iodine

Pd-Catalyzed asymmetric allylic amination with isatin using a P,olefin-type chiral ligand with C–N bond axial chirality

• Natsume Akimoto,
• Kaho Takaya,
• Yoshio Kasashima,
• Kohei Watanabe,
• Yasushi Yoshida and
• Takashi Mino

Beilstein J. Org. Chem. 2025, 21, 1018–1023, doi:10.3762/bjoc.21.83

• -catalyzed asymmetric allylic amination of allyl esters with isatin using (aR)-(−)-6 possesses an S-configuration. This stereochemical outcome follows the same reaction mechanism as the Pd-catalyzed asymmetric allylic substitution of allyl esters with indoles using (aR)-(−)-6 [31]. To explore further

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

• the reduction of amide-generated ketone 12 after a subsequent Dess–Martin oxidation. Upon treatment of 12 with Co(acac)2 and PhSiH3 in iPrOH at 80 °C, the Mukaiyama hydration of enamide delivered hemiaminal 13. Despite the incorrect configuration of the newly formed hydroxy group, it is considered

• inconsequential due to the reversibility of hemiaminal. Consequently, further reduction of the amide could complete the total synthesis of (+)-fawcettimine with in situ adjustment of the hemiaminal configuration. The incorrect configuration observed in the Mukaiyama hydration also inspired the authors to develop

• cyclization to form products in high yields and excellent enantioselectivities. Notably, only a single diastereomer was produced in each case. The single-crystal X-ray crystallography revealed a cis-configuration for both the alkene and ketone substituents on the enamide, indicating that the intramolecular

On the photoluminescence in triarylmethyl-centered mono-, di-, and multiradicals

• Daniel Straub,
• Markus Gross,
• Mona E. Arnold,
• Julia Zolg and
• Alexander J. C. Kuehne

Beilstein J. Org. Chem. 2025, 21, 964–998, doi:10.3762/bjoc.21.80

• quinodal electronic structure, diradicals with broken Kekulé-conjugation exhibit much stronger diradical character. In accordance with the above-described nomenclature, these diradicals are termed non-Kekulé diradicals. This tendency of diradicals to form a closed-shell electronic configuration can be

• described using the diradical index y0, which corresponds to a closed-shell system for y0 = 0 and a purely open-shell diradical for y0 = 1. In the open-shell electron configuration, the diradicals can acquire a singlet state with open-shell but antiparallel spins (total electronic spin, S = 0) or a triplet

A convergent synthetic approach to the tetracyclic core framework of khayanolide-type limonoids

• Zhiyang Zhang,
• Jialei Hu,
• Hanfeng Ding,
• Li Zhang and
• Peirong Rao

Beilstein J. Org. Chem. 2025, 21, 926–934, doi:10.3762/bjoc.21.75

• simultaneously installing the hydroxy group at C30. The latter intermediate could in turn be derived from dienone 11 by an AcOH-interrupted Nazarov cyclization [32][33][34], thereby establishing the B ring with the desired all-cis stereochemical configuration, including the quaternary carbon at C10 and the

• % brsm). Since the newly created configuration at C30 was inconsequential, an intramolecular aldol reaction was directly carried out by treatment with LiHMDS to furnish β-hydroxylactone, which could be converted to dienone 11 through TPAP oxidation. Having secured 11, we proceeded to evaluate the pivotal

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

• , obtaining a separable mixture of the major cis and minor trans diastereomers of the sp3-enriched pyrazolodiazepine 17. The relative configuration of the stereocenters in the major cis isomer of 17 was established via scXRD analysis. Both diastereomers of 17 were found to be amenable to chemoselective amide

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

• cases, with SIPr providing the best result (Table 1, entry 11). Under these optimized conditions, product 2 was isolated in 60% yield as a single diastereomer. The relative configuration of 2 was determined by two-dimensional NMR analysis (see Supporting Information File 1 for details). This

Regioselective formal hydrocyanation of allenes: synthesis of β,γ-unsaturated nitriles with α-all-carbon quaternary centers

• Seeun Lim,
• Teresa Kim and
• Yunmi Lee

Beilstein J. Org. Chem. 2025, 21, 800–806, doi:10.3762/bjoc.21.63

• -system configuration promotes selective functionalization, enabling the synthesis of various complex products through a single transformation [17][18][19]. Therefore, allenes have become versatile intermediates in numerous transition-metal-catalyzed reactions [20][21]. Despite extensive studies on the