Rongalite addition to dienones: diastereoselectivity in cyclic sulfone synthesis; stereochemical rationalization and prospects as a general conjugate nucleophile

• Melina Goga,
• Hao Zong,
• James Franco,
• Jazmine Prana,
• Rudolph Michel,
• Antonia Muro,
• Elana Rubin,
• Janet Brenya,
• Henk Eshuis and
• Magnus W. P. Bebbington

Beilstein J. Org. Chem. 2026, 22, 742–752, doi:10.3762/bjoc.22.56

• Information File 1 for a graphical representation of this and TS images directly generated from the computational data). The analogous calculations for 1a and 1b showed a much smaller difference in activation barrier, 1.0 kcal/mol, which is consistent with the lower selectivity observed for that substrate

• selectivity for formation of 26 at room temperature suggests a profile that is more reflective of kinetic control, such that we can argue that 26 forms between 1 and 2 orders of magnitude more rapidly than cyclic products 1a and 1b, such that they are not detectable in the 1H NMR spectra. Further anecdotal

Synthesis of heterocycles based on azomethine ylides from α-amino acids (or amines) and carbonyl compounds

• Ekaterina V. Berezhnaya,
• Alexander I. Ponyaev,
• Vitali M. Boitsov and
• Alexander V. Stepakov

Beilstein J. Org. Chem. 2026, 22, 705–741, doi:10.3762/bjoc.22.55

• enantioselectivity was observed. In a similar study, Wang et al. reported the CuI/TF-BiphamPhos (L3) complex, a new and highly efficient catalyst for the asymmetric 1,3-dipolar cycloaddition reaction [38]. The authors noted excellent reactivity, selectivity, and a wide range of structural variants for various

• /bisoxazoline L19 as a chiral catalyst system, high enantioselectivity (up to 97% ee) and moderate to high exo-selectivity were achieved in the reactions with N-methylmaleimide. The high efficiency of iminoesters as azomethine precursors is due to the high acidity at the enolizable Cα position and the formation

• . Further studies revealed that reactions of deactivated symmetrical dipolarophiles such as dimethyl fumarate, dibenzoylethylene, and fumarodinitrile proceeded with moderate exo-selectivity and good enantioselectivity (72–91% ee) (Scheme 32). Importantly, reactions with unsymmetrically substituted alkenes

Advantages of PROTACs in achieving selective degradation of homologous protein families

• Luxi Yang,
• Xinfei Mao,
• Jingyi Zhang,
• Jing Shu,
• Wenhai Huang,
• Xiaowu Dong,
• Yinqiao Chen and
• Mingfei Wu

Beilstein J. Org. Chem. 2026, 22, 628–661, doi:10.3762/bjoc.22.49

• . Compared with conventional small-molecule inhibitors, PROTACs exhibit notable advantages, particularly in achieving selectivity within highly homologous proteins. The ability to discriminate among members of such families holds broad implications for future disease treatment. In this review, we primarily

• summarize the advantages of PROTACs in conferring selectivity toward highly homologous proteins. This focus will provide a feasible strategy for developing PROTACs that selectively target highly homologous proteins and will ultimately support future therapeutic applications. Keywords: homologous protein

• ; PROTAC; protein–protein interaction; selectivity; ubiquitination; Introduction The cell is the fundamental unit of structure and function in the human body [1][2]. More than 20,000 proteins act in concert to regulate the entire cellular life process [1]. To date, dysregulated protein function has been

Towards the targeted protein degradation of CK2: design and synthesis of CAM4066-based PROTACs

• Sophie Day-Riley,
• Sona Krajcovicova,
• Aryaman Raj Sokhal,
• Jan L. Venne,
• Paul Brear,
• Marko Hyvönen,
• Benjamin C. Whitehurst,
• Jason S. Carroll and
• David R. Spring

Beilstein J. Org. Chem. 2026, 22, 611–619, doi:10.3762/bjoc.22.47

• off-target effects and incomplete or transient CK2 suppression. PROTACs offer an alternative strategy by inducing proteasome-mediated degradation, with potential advantages in potency, selectivity, and duration of action. Herein, a series of CK2-targeting PROTACs has been designed and synthesised. By

• selectivity and well-characterised bivalent binding mode across the ATP and αD pockets. Because a successful degrader must first engage the protein of interest with sufficient affinity, a PROTAC derived from CAM4066 was expected to retain CK2 specificity and achieve kinase-directed degradation rather than

Computational prediction of C–H hydricities and their use in predicting the regioselectivity of electron-rich C–H functionalisation reactions

• Rasmus M. Borup,
• Nicolai Ree and
• Jan H. Jensen

Beilstein J. Org. Chem. 2026, 22, 603–610, doi:10.3762/bjoc.22.46

• . However, nitrene insertion into compound 3 [40] is better predicted by BDE, although the two lowest BDEs are within 0.1 kcal/mol of each other. As noted by Cernak et al. [6], reaction selectivity of this reaction “has a strong dependence on the structure of the nitrene precursor, highlighting the caution

• that must be used when applying simple measures of selectivity prediction in a complex setting.” Compound 4 Vermeulen et al. [41] reported the Fe(DPD)-catalysed oxidation of (+)-artemisinin (compound 4). Similarly to nitrene insertion into cycloheximide (compound 2), the reactive site does not

Design and synthesis of an erdafitinib-based selective FGFR2 degrader

• Yumeng Jin,
• Shidong Wang,
• Sihan Pan,
• Shuqi Huang,
• Weichen Zhou,
• Xiaohao Huang,
• Lei Zheng and
• Lingfeng Chen

Beilstein J. Org. Chem. 2026, 22, 583–591, doi:10.3762/bjoc.22.44

• . Selectivity analysis revealed that LC-JD-6 specifically degraded FGFR2 with minimal impact on other FGFR subtypes. Further studies confirmed that LC-JD-6 also efficiently reduced the expression of FGFR2 on the cell membrane surface. In conclusion, this study successfully developed LC-JD-6, a novel FGFR2

• positioned in the solvent-exposed region of the molecule. Given this observation, we selected the aliphatic amine group as a suitable conjugation site (Figure 2a). Previous studies have shown that different linkers exhibit distinct selectivity profiles [31]. Therefore, in this study, novel FGFR2 degraders

• effectively degrade FGFR2 via the proteasomal pathway, while the VHL E3 ligase-based degrader DGY-09-192 is capable of degrading both FGFR1 and FGFR2 simultaneously [40]. These findings suggest that different E3 ligase ligands may influence the selectivity and efficiency of degradation [41]. Nevertheless, due

Continuous-flow carbonyl hydrogenation under subatmospheric to atmospheric hydrogen pressure enabled by robust heterogeneous Pt–Fe catalysts

• Hiroyuki Miyamura,
• Ryosuke Kajiyama,
• Shun-ya Onozawa,
• Yoshihiro Kon and
• Shū Kobayashi

Beilstein J. Org. Chem. 2026, 22, 575–582, doi:10.3762/bjoc.22.43

• activity and selectivity. The binding energies of Pt 4d in Pt–Fe/DMPSi‒Al2O3 (332, 315 eV) are lower than those of Pt/DMPSi‒Al2O3 (333, 316 eV) and Pt–Ni/DMPSi‒Al2O3 (334, 317 eV) [30]. Thus, the Pt species in Pt–Fe/DMPSi‒Al2O3 is the most electronically negative among the catalysts, which leads to a

Kinetic resolution of racemic planar-chiral vinylcymantrenes by molybdenum-catalyzed asymmetric metathesis dimerization

• Haruna Imazu,
• Hitoshi Izu,
• Yasuhiro Ohki and
• Masamichi Ogasawara

Beilstein J. Org. Chem. 2026, 22, 568–574, doi:10.3762/bjoc.22.42

• chiral-2a/meso-2a = 96:4 molar ratio, and the selectivity factor (krel) was calculated to be 754 based on a second-order equation. In all the three substrates examined, the dimerized products, chiral-2, were obtained in >98% ee thanks to the outstanding enantioselectivity. Keywords: cymantrene; kinetic

• appropriate chiral Mo-alkylidene precatalyst, the highly diastereo- and enantioselective kinetic resolution (KR) of the racemic substrates was attained with the krel values ([reaction rate of the fast-reacting enantiomer]/[reaction rate of the slow-reacting enantiomer]; selectivity factor) of up to 96 for the

Molecular tweezer–peptide conjugates disrupt the protein–protein interaction between survivin and histone H3 essential in mitosis

• Catherine Gsell,
• Philipp Rebmann,
• Karina Opara,
• Christine Beuck,
• Peter Bayer,
• David Bier,
• Ingrid R. Vetter and
• Thomas Schrader

Beilstein J. Org. Chem. 2026, 22, 557–567, doi:10.3762/bjoc.22.41

• attached phosph(on)ate anions as powerful new hosts for the amino acids lysine and arginine. In the recent past, we demonstrated that the affinity and selectivity of our lysine-selective molecular tweezers could be improved by attaching natural peptide recognition elements. This could be documented in

• and precisely the natural binding site in the wide 14-3-3-cleft [10]. These examples for designed protein–protein interaction (PPI) inhibitors demonstrated that short but highly flexible linkers are imperative to increase selectivity and minimize entropical penalty. The design was strongly supported

Synthesis and uranyl(VI) extraction performance of a calix[4]pyrrole–tetrahydroxamic acid receptor

• Sara Karnib,
• Rana Baydoun,
• Wissam Zaidan,
• Nancy AlHaddad,
• Omar El Samad,
• Bilal Nsouli,
• Francine Cazier-Dennin and
• Pierre-Edouard Danjou

Beilstein J. Org. Chem. 2026, 22, 486–494, doi:10.3762/bjoc.22.36

• [4]resorcinarene hydroxamic acid has also shown a pronounced binding tendency and selectivity for uranyl and proved to be applicable for the determination of uranium in standard and environmental samples [34]. Importantly, more recent studies have demonstrated that pre-organized or cyclic hydroxamate

Recent advances in the stereoselective synthesis of distal biaxially chiral molecules

• Fanxing Zhou,
• Chen Zhang,
• Lingyu Sun,
• Yiyun Fang,
• Siming Zheng,
• Lina Hu,
• Mengyang Shen,
• Zhen Zhao,
• Wei Xu,
• Yunqiang Sun and
• Zi-Qiang Rong

Beilstein J. Org. Chem. 2026, 22, 461–479, doi:10.3762/bjoc.22.34

• atropisomeric (hetero)biaryls (Scheme 17) [56]. This highly enantioselective C–H arylation of heteroarenes employs a Pd(0) complex with H8-BINAPO L8 as the chiral ligand, enabling the arylation of 1,2,3-triazoles and pyrazoles in excellent yields with great selectivity. This method also facilitates

Cone p-aminocalix[4]arenes enriched with ‘clickable’ alkyne or azide functionalities

• Ilia Korniltsev,
• Vasily Bazhenov,
• Alexander Gorbunov,
• Dmitry Cheshkov,
• Stanislav Bezzubov,
• Vladimir Kovalev and
• Ivan Vatsouro

Beilstein J. Org. Chem. 2026, 22, 399–415, doi:10.3762/bjoc.22.28

• carbamoylmethylphosphine oxides along with enrichment of the extraction selectivity [36][37][38][39][40][41][42][43][44][45]. Even more impressive is the effect from grafting of four urea groups at the wide rims of calix[4]arene macrocycles achieved by reacting p-aminocalix[4]arenes with aryl- or arylsulfonyl isocyanates

• their structures, in which the nitrated aromatic units experience an additional shielding. This may be also responsible for the selectivity of the two-fold nitration of compounds 8 and 9 leading to calixarenes 12 and 13 rather than to their isomers containing nitro groups in the propargylated aromatic

• calixarene core. This correlates well with the above selectivity of nitration observed for calixarenes 8 and 9 and may be tentatively explained by an electron-withdrawing effect of the propargyl groups. However, in the molecular structures of calixarenes 15 and 16, another feature was observed: in both cases

Design, synthesis and biological evaluation of 2,5-diaryloxazolo[4,5-d]pyrimidin-7-ylamines as selective cytotoxic agents against HeLa cells

• Maryna V. Kachaeva,
• Agnieszka B. Olejniczak,
• Marta Denel-Bobrowska,
• Victor V. Zhirnov,
• Yevheniia S. Velihina,
• Stepan G. Pilyo and
• Volodymyr S. Brovarets

Beilstein J. Org. Chem. 2026, 22, 390–398, doi:10.3762/bjoc.22.27

• carcinoma cells), and T98G (Human glioblastoma multiforme cells). Cytotoxicity was determined by measurement of 50% inhibition of cell growth by the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The selectivity index (SI) was calculated for the investigated compounds. The

• cytotoxicity results (CC50, µM) for the investigated compounds and the calculated selectivity index values are presented in Table 1. The compounds 2, 6, and 8 were found to be non-toxic towards all the cancer and non-cancer cell lines investigated (CC50 > 1000 µM). In general, cancer cells form the following

• rows in the order of decreasing sensitivity to the active compounds: HeLa: 1 > 3 > 9 > 5 > 7 > 4 A549: 1 > 3 > 4 > 5 > 7 = 9 HepG2: 3 > 1 > 4 T98G: 3 > 1 It was observed that compounds 1 and 3 showed the highest cytotoxicity against all cancer cells. Compound 1 exhibited the highest selectivity towards

Electrosynthetic access to unsymmetrical oxaza[8]helicenes with high chiral stability and strong circularly polarized luminescence (CPL)

• Tin Zar Aye,
• Rubal Sharma,
• Muthu Karuppasamy,
• Daiya Suzuki,
• Haruka Nakajima,
• Yoshitane Imai,
• Mitsuhiro Arisawa,
• Mohamed S. H. Salem and
• Shinobu Takizawa

Beilstein J. Org. Chem. 2026, 22, 372–382, doi:10.3762/bjoc.22.25

• ]helicenes. Inspired by the superior selectivity and sustainability of organic electrosynthesis as an eco-friendly alternative to conventional oxidative methods [43][44][45][46][47], we leveraged our electrochemical approaches [48][49][50][51][52], and redesigned the synthons to access a new unsymmetrical

Ring contraction and ring expansion reactions in terpenoid biosynthesis and their application to total synthesis

• Nicolas Kratena,
• Nicolas Heinzig and
• Peter Gärtner

Beilstein J. Org. Chem. 2026, 22, 289–343, doi:10.3762/bjoc.22.21

Arene activation via π-bond localization: concepts and opportunities

• Paul Meiners,
• Julian J. Melder and
• Tobias Morack

Beilstein J. Org. Chem. 2026, 22, 257–273, doi:10.3762/bjoc.22.19

• introduced by Cheong and Altman in 2020 (Figure 10A) [83]. In this study, the authors explored an intramolecular, decarboxylative C–H functionalization of benzylic electrophiles, uncovering a decisive role of the base in governing site selectivity. Computational and mechanistic analyses revealed that only

• [80]. Computational investigations of this latter transformation identified an η3-allylnaphthalene–η1-allenyl palladium complex as the key to achieving ortho-selectivity (Figure 10B) [85][86]. Building on these insights, the Bao group employed malonates as alkylating agents in reactions with

• of this protocol, in which sterically demanding ligands promoted para-selectivity, while less encumbered systems channeled the reaction toward ortho-functionalization [88]. Following a conceptually related strategy, Yamaguchi and co-workers leveraged a three-component strategy that accesses the key

A mild and atom-efficient four-component cascade strategy for the construction of biologically relevant 4-hydroxyquinolin-2(1H)-one derivatives

• Dmitrii A. Grishin,
• Kseniia I. Sharkovskaia,
• Ilya G. Kolmakov,
• Daria A. Ipatova,
• Rostislav A. Petrov,
• Nikolai D. Dagaev,
• Dmitry A. Skvortsov,
• Maria G. Khrenova,
• Valeriy V. Andreychev,
• Sergei A. Evteev,
• Yan A. Ivanenkov,
• Roman L. Antipin,
• Olga А. Dontsova and
• Elena K. Beloglazkina

Beilstein J. Org. Chem. 2026, 22, 244–256, doi:10.3762/bjoc.22.18

• rapid access to these previously unreported compounds, offering a versatile platform for systematic structure–activity relationship exploration and paving the way for the development of next-generation antibacterial agents with optimized potency and selectivity. Results and Discussion Chemistry For

• (transesterification/alcoholysis) under the influence of alcohol, ultimately yielding the open-chain ester (Scheme 6). This mechanistic rationale explains both the observed selectivity and the intrinsic limitations of the reaction scope imposed by the dual role of the alcohol as nucleophile and solvent. Interestingly

• , replacing alcohols with secondary amines (e.g., pyrrolidine) as the reaction medium did not lead to the desired amides. Experimental trials resulted in the formation of complex mixtures (as confirmed by 1H NMR), suggesting that the high reactivity of amines interferes with the selectivity of the cascade

Configuration–packing synergy enabling integrated crystalline-state RTP and amorphous-state TADF

• Ruiyan Wang and
• Yunan Wu

Beilstein J. Org. Chem. 2026, 22, 224–236, doi:10.3762/bjoc.22.16

• , the triplet exciton management and channel selectivity in different phases of PI-Cz 1 were systematically studied, validating the feasibility of “configuration-packing synergy” for controllable RTP–TADF switching within the same molecule. Results and Discussion Single crystals of 1 were successfully

Screwing the helical chirality through terminal peri-functionalization

• Devesh Chandra,
• Sachin and
• Upendra Sharma

Beilstein J. Org. Chem. 2026, 22, 205–212, doi:10.3762/bjoc.22.14

• -induced spin selectivity. These functionalities have great potential to transform in key areas such as drug discovery and modern diagnostic tools, as well as in distinct emerging fields like spintronics and optoelectronics [14]. Helicenes have found applications in chiral optoelectronics, i.e., as

Improved synthesis and physicochemical characterization of the selective serotonin 2A receptor agonist 25CN-NBOH

• Adrian G. Rossebø,
• Hannah G. Kolberg,
• Anders E. Tønder,
• Louise Kjaerulff,
• Poul Erik Hansen,
• Karla A. Frydenvang,
• Jesper Østergaard and
• Jesper L. Kristensen

Beilstein J. Org. Chem. 2026, 22, 175–184, doi:10.3762/bjoc.22.11

• efficacy [2]. Activation of the 5-HT2AR is thought to induce altered states of consciousness and suppress the default-mode network, a process hypothesized to underlie their clinical benefits [3]. However, classic psychedelics lack receptor selectivity, prompting efforts to develop more selective 5-HT2AR

Asymmetric Mannich reaction of aromatic imines with malonates in the presence of multifunctional catalysts

• Kadri Kriis,
• Harry Martõnov,
• Annette Miller,
• Mia Peterson,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2026, 22, 151–157, doi:10.3762/bjoc.22.8

• adduct in 83% ee (Table 1, entry 9). Replacing the five-membered pyrrolidine ring in the catalyst structure with the more flexible six-membered piperidine ring (catalyst H, Table 1, entry 13) reduced its selectivity slightly (78% ee). However, the catalyst derived from phenylglycine (catalyst F) or

• product in a slightly less enantioselective way (71% ee). When comparing the halogen bond donor properties of tetrafluoroiodophenyl and iodophenyl moieties, the latter is weaker as it is less electron-withdrawing. However, there is a very small difference between reactivity and selectivity for catalysts E

• the halogen bond is not essential for the stereoselectivity of the reaction, but the halogen atom has a beneficial effect on both reactivity and stereoselectivity. A comparative experiment using an imine with a para-toluenesulfonyl protecting group afforded the product in lower selectivity (Table 1

Symmetrical D–π–A–π–D indanone dyes: a new design for nonlinear optics and cyanide detection

• Ergin Keleş,
• Alberto Barsella,
• Nurgül Seferoğlu,
• Zeynel Seferoğlu and
• Burcu Aydıner

Beilstein J. Org. Chem. 2026, 22, 131–142, doi:10.3762/bjoc.22.6

• theory (DFT) methods. The dyes also exhibit chemosensor properties, showing selectivity for cyanide via a Michael addition mechanism that causes the disappearance of the ICT band, and a significant color change was observed in both organic and aqueous media. In addition, the interaction mechanism between

• photophysical properties of the dyes. The sensitivity/selectivity properties of the dyes to anions were investigated in DMSO and aqueous media, revealing that the dyes were selectively responsive only to cyanide anions. Changes after interactions were determined through absorption spectra and color changes

• also showed significant color changes with increasing polarity. Color changes of 2a; from purple to blue, 2b; blue to green, and 2c; pale orange to pale pink (Figure 2d). Dyes do not show any significant emission. Chemosensor properties Cyanide selectivity study The dyes 2a–c could have the ability to

Total synthesis of natural products based on hydrogenation of aromatic rings

• Haoxiang Wu and
• Xiangbing Qi

Beilstein J. Org. Chem. 2026, 22, 88–122, doi:10.3762/bjoc.22.4

• ]. Although oxidative dearomatization has been a widely studied and powerful approach in synthetic chemistry [21][26][27][28], researchers have gradually recognized its inherent limitations, including narrow substrate scope, poor selectivity, and low functional group compatibility. Under the circumstance of

• hydrogenation of aromatic rings The catalytic hydrogenation of arenes offers a powerful route to disrupt aromaticity and access synthetically valuable intermediates. However, its implementation in strategic synthesis has been hindered by the persistent challenge of controlling selectivity across diverse

• -art systems depend on expensive transition metals such as platinum, ruthenium, or palladium, inflating the cost of large-scale applications. In addition, precious-metal catalysts often display poor selectivity, while heteroatoms in heteroarenes – acting as Lewis bases – tend to coordinate to the metal

Advances in Zr-mediated radical transformations and applications to total synthesis

• Hiroshige Ogawa and
• Hugh Nakamura

Beilstein J. Org. Chem. 2026, 22, 71–87, doi:10.3762/bjoc.22.3

• benzylic position, giving the hydrogenated products with high site selectivity. Zr-catalyzed radical reaction in the total synthesis of complex natural products This section presents examples of zirconium-mediated reactions applied to the synthesis of complex molecules. For application in total synthesis

Reactivity umpolung of the cycloheptatriene core in hexa(methoxycarbonyl)cycloheptatriene

• Dmitry N. Platonov,
• Alexander Yu. Belyy,
• Rinat F. Salikov,
• Kirill S. Erokhin and
• Yury V. Tomilov

Beilstein J. Org. Chem. 2026, 22, 64–70, doi:10.3762/bjoc.22.2

• reactions mainly involve the initial electrophilic attack onto the α-position relative to the hydrogen atom. The selectivity is either due to the high stability of the α-nucleophilic conformer or due to the promotion by the adjacent ester group. Cascade reactions upon the target connection, if installed

• unavailability of other stable cycloheptatrienyl anions until recently, its derivatives were not expected to show high selectivity in reactions. Herein, we present the first examples of selective reactions of low-symmetry hexa(methoxycarbonyl)cycloheptatrienyl anion 2 [20] towards electrophiles. Additionally

• principle [38]. At least, the reaction times and conditions required for the alkylation reactions investigated, which proceed through an α-attack, indicate relatively high barriers. This in turn indicates that the selectivity observed in alkylation reactions (α-attack) is due to some stabilization of the