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

• 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

• , resulting in the formation of a racemic product (Table 2, entry 4). Similar trends with catalyst E were observed: the amidic proton is essential to achieve high reactivity and selectivity and changing the halogen atom with other groups slightly decreases the stereoselectivity of the reaction. Steric effects

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

• building blocks used in natural product syntheses are often difficult to prepare or scale-up, constrained by subtle chemical reactivity, functional group compatibility, and control of stereoselectivity. Together, these factors continue to shape the pursuit of concise and practical synthetic routes to

• complex natural products [16][17]. Arenes and heteroarenes have long been readily accessible, as many can be obtained through industrial synthesis or microbial fermentation. The diverse reactivity of aromatic compounds has made them indispensable starting materials in synthetic and medicinal chemistry [18

• substrate electronic environments [29]. Reactivity is governed by the electron density of arenes, which directly influences kinetics and product distributions [30][31]. The inability to generically modulate this interaction has confined most catalytic systems to narrow substrate scopes. Addressing this

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

• experiments, coordination of thiourea 26 to the Zr center was suggested. This effect is considered to have tuned the reactivity of the Zr-catalyst, thereby having a positive effect on the reaction process. Finally, the regioselectivity of epoxide ring opening was compared between low-valent titanocene and

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

• , Russian Federation 10.3762/bjoc.22.2 Abstract A reactivity umpolung approach for the derivatization of cycloheptatrienes was extended to hexa(methoxycarbonyl)cycloheptatriene, which forms the corresponding anion reactive towards electrophiles. Despite the presence of four potential reactive sites, the

• , include the formation of norcaradienes, dihydroindazoles, a tetracyclodecene and a hydrazonocycloheptatriene derivative. Keywords: azo shift; cascade reactions; cycloheptatriene; relief of antiaromaticity; umpolung; Introduction Reactivity umpolung [1] is a synthetic concept in organic chemistry that

• ; these equivalents can be transformed after the desired connection has taken place. For instance, nitroalkanes [1] and nitroalkenes [5][6] are regarded as equivalents of unavailable acyl anions and vinyloxenium cations, respectively. Reversed reactivity patterns also emerge due to non-uniform structures

Synthesis and applications of alkenyl chlorides (vinyl chlorides): a review

• Daniel S. Müller

Beilstein J. Org. Chem. 2026, 22, 1–63, doi:10.3762/bjoc.22.1

• prepared in 1868 by Charles Friedel – best known for the Friedel–Crafts reaction – via the reaction of ketones with phosphorus pentachloride, these compounds have steadily gained attention over the decades. In recent years, their distinct reactivity and potential in organic synthesis have been increasingly

• important and versatile functional group. Keywords: alkenyl chloride; chloroalkenes; chloro olefins; vinyl chlorides; Introduction Alkenyl chlorides, while less extensively investigated than their brominated analogues, constitute a synthetically valuable class of organohalides with distinct reactivity

• review, and the reader is referred to the recent comprehensive accounts by Li [89] and Mitchenko [90] for further details. Hydrochlorination of terminal alkynes frequently results in complex product mixtures due to the greater reactivity of the initially formed alkenyl chloride intermediate (e.g., 150

Total synthesis of asperdinones B, C, D, E and terezine D

• Ravi Devarajappa and
• Stephen Hanessian

Beilstein J. Org. Chem. 2025, 21, 2730–2738, doi:10.3762/bjoc.21.210

• . Asperidinones 1–4 were obtained in 7% average yields via the direct prenylation route, and 14% from the allylation/cross-metathesis route, whereas terezine D (6) was isolated in 44% overall yield. Insights into the reactivity and stability of the iodozinc N-Fmoc-ᴅ-alanyl anthranilamide reagent derived from 29

Competitive cyclization of ethyl trifluoroacetoacetate and methyl ketones with 1,3-diamino-2-propanol into hydrogenated oxazolo- and pyrimido-condensed pyridones

• Svetlana O. Kushch,
• Marina V. Goryaeva,
• Yanina V. Burgart,
• Marina A. Ezhikova,
• Mikhail I. Kodess,
• Pavel A. Slepukhin,
• Alexandrina S. Volobueva,
• Vladimir V. Zarubaev and
• Victor I. Saloutin

Beilstein J. Org. Chem. 2025, 21, 2716–2729, doi:10.3762/bjoc.21.209

• starting substrates in multicomponent syntheses [17][18][19]; at the same time, they often show extraordinary reactivity. For example, the introduction of polyfluoroalkyl-3-oxo esters into the aforementioned Hantzsch and Biginelli reactions leads to the hydrated heterocycles, which can provide insight into

Mechanistic insights into hydroxy(tosyloxy)iodobenzene-mediated ditosyloxylation of chalcones: a DFT study

• Jai Parkash,
• Sangeeta Saini,
• Vaishali Saini,
• Omkar Bains and
• Raj Kamal

Beilstein J. Org. Chem. 2025, 21, 2703–2715, doi:10.3762/bjoc.21.208

• . The reactivity characteristics of these compounds are similar to transition metal reagents, as a result these hypervalent compounds can be used as an alternative. For example, iodobenzene diacetate (PhI(OAc)2), can be used to selectively oxidize alcohols to aldehydes or ketones over toxic chromium(VI

Recent advancements in the synthesis of Veratrum alkaloids

• Morwenna Mögel,
• David Berger and
• Philipp Heretsch

Beilstein J. Org. Chem. 2025, 21, 2657–2693, doi:10.3762/bjoc.21.206

• group in the sequence to temporarily mask that specific group and its reactivity. The latter are considered undesirable transformations, since they do not contribute to advancing the complexity of the synthetic intermediate toward the target and should therefore be avoided, or at least minimized in use

• trifluoroethanol enabled the desired [4 + 2]-addition. Some aromatization as well as ketal deprotection was observed, so by optimization, AgSbF6 and diethyl fumarate enhanced this reactivity, while this modification also significantly improved the yield to 59% of this step. It was noted that the silver salt helped

Chemoenzymatic synthesis of the cardenolide rhodexin A and its aglycone sarmentogenin

• Fuzhen Song,
• Mengmeng Zheng,
• Dongkai Wang,
• Xudong Qu and
• Qianghui Zhou

Beilstein J. Org. Chem. 2025, 21, 2637–2644, doi:10.3762/bjoc.21.204

• reagent [20], the key intermediate 8 bearing a butenolide motif was obtained in 76% yield. Next, with the aid of the strong Lewis acid Bi(OTf)3, the regioselective elimination of 8 was achieved to produce the Δ14 olefin intermediate 9 in 86% yield. Afterwards, we evaluated the reactivity of 9 towards

Thiazolidinones: novel insights from microwave synthesis, computational studies, and potentially bioactive hybrids

• Luan A. Martinho,
• Victor H. J. G. Praciano,
• Guilherme D. R. Matos,
• Claudia C. Gatto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2025, 21, 2618–2636, doi:10.3762/bjoc.21.203

• forms of compounds 3n and 4n exhibited smaller HOMO–LUMO gaps compared to their protonated and deprotonated counterparts, suggesting higher reactivity (Table 5). Conclusion In summary, we have developed a straightforward approach to a Knoevenagel condensation-type reaction using ethylenediamine (EDA) as

Total syntheses of highly oxidative Ryania diterpenoids facilitated by innovations in synthetic strategies

• Zhi-Qi Cao,
• Jin-Bao Qiao and
• Yu-Ming Zhao

Beilstein J. Org. Chem. 2025, 21, 2553–2570, doi:10.3762/bjoc.21.198

• , the bis-epoxy ketone exhibited distinct reactivity under ring-opening conditions compared to mono-epoxy substrates, presumably due to steric constraints. Leveraging the directing ability of the C10 hydroxy group, stereospecific Mukaiyama hydration of the C6–C7 double bond was achieved, furnishing

Rapid access to the core of malayamycin A by intramolecular dipolar cycloaddition

• Yilin Liu,
• Yuchen Yang,
• Chen Yang,
• Sha-Hua Huang,
• Jian Jin and
• Ran Hong

Beilstein J. Org. Chem. 2025, 21, 2542–2547, doi:10.3762/bjoc.21.196

• inaccessible (Scheme 5) [41]. We assumed the steric hinderance of the Boc protecting group might have a great impact to the reactivity of ketone. Investigation along this line is currently on the way. Conclusion In summary, we have streamlined the rapid construction of the core perhydrofuropyran skeleton of

Pentacyclic aromatic heterocycles from Pd-catalyzed annulation of 1,5-diaryl-1,2,3-triazoles

• Kaylen D. Lathrum,
• Emily M. Hanneken,
• Katelyn R. Grzelak and
• James T. Fletcher

Beilstein J. Org. Chem. 2025, 21, 2524–2534, doi:10.3762/bjoc.21.194

• reactivity of this family of pentacyclic aromatic heterocycles towards N-benzylation and the antimicrobial properties of such resulting quaternary ammonium compounds are ongoing. Examples of polycyclic aromatic heterocycle structures: phenanthridine (left), 1,5-naphthyridine (center), and 1,9-phenanthroline

Assembly strategy for thieno[3,2-b]thiophenes via a disulfide intermediate derived from 3-nitrothiophene-2,5-dicarboxylate

• Roman A. Irgashev

Beilstein J. Org. Chem. 2025, 21, 2489–2497, doi:10.3762/bjoc.21.191

• addition to potassium thioacetate, the reactivity of ester 1 was investigated with other related S-nucleophiles, such as potassium ethyl xanthate (KSC(S)OEt), sodium diethyldithiocarbamate (NaSC(S)NEt2) as well as thioacetamide in the presence of K2CO3 and Na2S2 (Table 1, entries 2–5). In each case, the

• . Conclusion In summary, this study reveals an unusual and previously poorly understood reactivity of 3-nitrothiophene-2,5-dicarboxylate toward sulfur-containing nucleophiles such as potassium thioacetate or thioacetamide, which resulted in the efficient formation of both bis(thiophen-3-yl) sulfide and

Palladium-catalyzed regioselective C1-selective nitration of carbazoles

• Vikash Kumar,
• Jyothis Dharaniyedath,
• Aiswarya T P,
• Sk Ariyan,
• Chitrothu Venkatesh and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2025, 21, 2479–2488, doi:10.3762/bjoc.21.190

• challenging due to the inherently higher reactivity at the C3/C6 positions. In this study, we report a palladium-catalyzed, directing group-assisted, regioselective C1–H nitration of carbazoles. The protocol features a removable directing group and is amenable to gram-scale synthesis. This strategy provides a

• reagent resulted in complete loss of reactivity (Table 1, entry 12). Further, extending the reaction time had no significant effect on the yield (Table 1, entry 13). Finally, our investigation using various 3d transition metal catalysts such as Ni(OAc)2, Cu(OAc)2, and Co(OAc)2 in place of Pd₂(dba)3 did

Synthesis of the tetracyclic skeleton of Aspidosperma alkaloids via PET-initiated cationic radical-derived interrupted [2 + 2]/retro-Mannich reaction

• Ru-Dong Liu,
• Jian-Yu Long,
• Zhi-Lin Song,
• Zhen Yang and
• Zhong-Chao Zhang

Beilstein J. Org. Chem. 2025, 21, 2470–2478, doi:10.3762/bjoc.21.189

• , which indicates that steric hindrance at C2 has a limited effect on the reactivity. However, when the steric hindrance of the protecting group was increased by replacing –Cbz with –Boc, the activity of the PET reaction decreased, which resulted in a lower yield of 10f (45%). In the case of substrate 9g

Ex-situ generation of gaseous nitriles in two-chamber glassware for facile haloacetimidate synthesis

• Nikolai B. Akselvoll,
• Jonas T. Larsen and
• Christian M. Pedersen

Beilstein J. Org. Chem. 2025, 21, 2465–2469, doi:10.3762/bjoc.21.188

• turned out to be unsuccessful as the reaction seemed to achieve an equilibrium, with some amount of hemiacetal left. Generally, it was observed that the trifluoroacetimidates were somewhat more sensitive to flash column chromatography, suggesting a higher reactivity compared to the trichloroacetimidates

The intramolecular stabilizing effects of O-benzoyl substituents as a driving force of the acid-promoted pyranoside-into-furanoside rearrangement

• Alexey G. Gerbst,
• Sofya P. Nikogosova,
• Darya A. Rastrepaeva,
• Dmitry A. Argunov,
• Vadim B. Krylov and
• Nikolay E. Nifantiev

Beilstein J. Org. Chem. 2025, 21, 2456–2464, doi:10.3762/bjoc.21.187

• equilibrium lie outside the carbohydrate ring system. Consideration of such effects is essential to rationalize the reactivity of structurally complex and densely protected carbohydrate compounds. Keywords: benzoylated galactofuranosides; DFT; DLPNO-CCSD(T); pyranoside-into-furanoside rearrangement

Catalytic enantioselective synthesis of selenium-containing atropisomers via C–Se bond formations

• Qi-Sen Gao,
• Zheng-Wei Wei and
• Zhi-Min Chen

Beilstein J. Org. Chem. 2025, 21, 2447–2455, doi:10.3762/bjoc.21.186

• excellent conversion rates (up to 95% yield) and high enantioselectivity (up to 96% ee). Notably, isoquinoline derivatives containing polycyclic naphthalene moieties or ortho-substituted phenyl groups also demonstrated good reactivity and compatibility. DFT calculations indicated that the C–Se bond

Transformation of the cyclohexane ring to the cyclopentane fragment of biologically active compounds

• Natalya Akhmetdinova,
• Ilgiz Biktagirov and
• Liliya Kh. Faizullina

Beilstein J. Org. Chem. 2025, 21, 2416–2446, doi:10.3762/bjoc.21.185

• of reactivity, they are environmentally sustainable alternatives to heavy metals. The advantage of hypervalent catalytic systems based on iodine lies in their reusability [63]. The oxidative contraction of the tetralone cycle 117 depended on the stoichiometric amounts of iodine(III)-based chiral

• simple building blocks [72]. The main feature of light-induced transformations is the involvement of electronically excited states that occur during photon absorption, leading to the formation of reactive intermediates causing significant changes in chemical compound reactivity. As a result, light energy

• compounds [78][79][80][81][82]. The work of Davis, Derksen and co-workers [83] presents interesting results on the use of UV light to study the reactivity of bicyclic divinyl ketones and the dependence of photochemical reaction products on wavelength. Under anhydrous conditions, irradiation of divinyl

The high potential of methyl laurate as a recyclable competitor to conventional toxic solvents in [3 + 2] cycloaddition reactions

• Ayhan Yıldırım and
• Mustafa Göker

Beilstein J. Org. Chem. 2025, 21, 2389–2415, doi:10.3762/bjoc.21.184

• reactivity of this double bond can pose significant challenges, particularly in cycloadditions or other organic transformations that necessitate extended cycloaddition processes and elevated temperatures. With a boiling point in excess of 260 °C, methyl laurate has the potential to function as a green

Synthetic study toward vibralactone

• Liang Shi,
• Jiayi Song,
• Yiqing Li,
• Jia-Chen Li,
• Shuqi Li,
• Li Ren,
• Zhi-Yun Liu and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2025, 21, 2376–2382, doi:10.3762/bjoc.21.182

• developed an approach to assemble the bicyclic skeleton of vibralactone (6) utilizing an intramolecular alkylidene carbene C–H insertion as key step. The insights gained from this study illustrate how diverse reactivity patterns and electrophilic characteristics of alkylidene carbenes influence ring closure

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

• synthesis, the 3-chloropyridine 68 used in the Dai synthesis exhibited much lower reactivity compared to the 3-bromopyridine 55 used in the Tsukano synthesis. Thus, a set of new reaction conditions was needed. To solve this reactivity issue, a protocol developed by Stoltz et al. in their jorunnamycin

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

• , 108d) underwent the desired photochemical reaction (Scheme 13b), yielding spiroacetals 109a, 109b, and 109d following CAN (cerium(IV) ammonium nitrate) oxidation. In contrast, C7-methoxy-substituted analogs (108c, 108e) remained unreactive. Reactivity correlated with UV–vis absorption profiles

• : reactive substrates exhibited λmax < 460 nm (yellow-orange), whereas unreactive ones showed λmax > 460 nm (dark red-purple). This suggests insufficient excitation energy for Norrish type-II hydrogen abstraction in the latter. Such chromophore-dependent reactivity provides critical insights for designing

• less favorable pathway compared to the previously employed 1,5-HAT. Initial feasibility studies revealed that the non-brominated substrate exhibited poor reactivity in the photochemical 1,6-HAT reaction (Scheme 14), as its unreactive conformer J dominated the equilibrium. In contrast, the brominated