Recent advances in copper-catalyzed direct hydroamination of alkenes with (hetero)aromatic amines

• Hyejeong Lee and
• Yunmi Lee

Beilstein J. Org. Chem. 2026, 22, 925–947, doi:10.3762/bjoc.22.73

• –amido intermediate or aminocupration-type pathways, enabling efficient C–N bond formation under relatively mild conditions. Copper species may also operate in a Lewis acid-type capacity, where coordination to the alkene or copper-derived Brønsted acidity generated in situ increases alkene

• ester substituents. Notably, the reaction outcome was highly dependent on the reaction conditions. Although mild conditions favored C–N bond formation, high temperatures promoted alternative pathways, such as aromatic substitution, indicating that the C–N bond formation was reversible under Lewis acidic

• of heterogeneous copper nanomaterials used in aza-Michael addition reactions. In these systems, copper nanomaterials function as efficient heterogeneous catalysts that activate electron-deficient alkenes for the nucleophilic addition of amines under relatively mild conditions. Rashid et al. reported

A practical CO₂-mediated synthesis of 5,6-carboxylated silicon-rhodamines for targeted probe development

• Dongjie Hou,
• Shaowei Wu,
• Ning Xu,
• Pengjun Bao,
• Wenhao Jia,
• Qinglong Qiao and
• Zhaochao Xu

Beilstein J. Org. Chem. 2026, 22, 915–924, doi:10.3762/bjoc.22.72

• relatively mild conditions. Compared with previous approaches, this strategy avoids the need for specialized apparatus for in situ CO generation as well as expensive palladium catalysts, thereby significantly reducing experimental complexity and synthetic cost. Importantly, the resulting carboxylated SiR

• -carboxylated silicon-rhodamine (SiR) derivatives from brominated SiR precursors via lithium–halogen exchange and direct carboxylation. This method enables efficient access to carboxylated SiRs under mild conditions while avoiding the use of t-BuLi, toxic CO, and expensive palladium catalysts. The crude

Chiral cyclopropenimine-catalyzed enantioselective Michael reactions of phenol and benzofuran-derived α,β-unsaturated pyrazolamides with benzophenone-imine of glycine esters

• Ya Bai,
• Xue-Ying Wang,
• Si-Kai Zhu,
• Yan-Ting Shen,
• Sheng-Yong Zhang and
• Ping-An Wang

Beilstein J. Org. Chem. 2026, 22, 888–896, doi:10.3762/bjoc.22.69

• (Lambert catalyst, CSB-1) as an organocatalyst. In the presence of 20 mol % CSB-1, the Michael adducts were obtained in up to 85% yield and 98% ee under mild conditions. The configurations of these Michael products were deduced by X-ray single crystal diffraction of a pyroglutamic acid ester containing two

• series of 3-substitued glutamic acid esters in high yields and diastereoselectivities through DBU-catalyzed Michael additions of benzophenone-imine of glycine ester and α,β-unsaturated esters which derived from phenols and benzofurans under mild conditions [5][6]. The chiral 3-aryl-substituted glutamic

• deduced to be 2S and 3S either (Figure 6). Conclusion In conclusion, we have developed facile routes to chiral 3-substituted glutamic and pyroglutamic acid esters from phenols and benzofuran-derived α,β-unsaturated pyrazolamides in the presence of Lambert catalyst CSB-1 under mild conditions in good

Site-specific labelling of native peptides and proteins: chemical and enzymatic strategies

• Antonio Angelastro,
• Jonathan Bargh,
• Subhajit Guria,
• Victor Laserna and
• Louis Luk

Beilstein J. Org. Chem. 2026, 22, 857–881, doi:10.3762/bjoc.22.67

• (19) was later adapted for modification of an asparagine (Asn) residue in the Fc domain of trastuzumab [61]. Rhodium has also been used in visible-light-triggered single-electron transfer (SET) reactions, enabling labelling under mild conditions with spatiotemporal control. Another strategy employs a

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

• strategy is that the synthesis is often carried out under mild conditions without the use of a catalyst, and despite this, the resulting cycloadducts exhibit pronounced regio- and stereoselectivity [9][10][11]. In the second case, the generation of azomethine ylides from iminoesters is often realized using

• reaction of analogous azomethine ylides with 2-arylacrylates was catalyzed by chiral binol-based phosphoric acids [65]. In 2023, Retamosa and Sansano carried out a diastereoselective synthesis of polysubstituted pyrrolidines 59 under mild conditions via 1,3-dipolar cycloaddition between tert

• authors also carried out cycloaddition reactions of 1,2,3-triphenylcyclopropene and 2,3-diphenylcycloprop-2-enecarboxylic acid with azomethine ylides formed from ninhydrin and peptides 133, such as Gly–Gly and Gly–Gly–Gly. All reactions proceed under mild conditions to form spiro[3-azabicyclo[3.1.0

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

• was revived by a simple operation even if the catalyst became slightly deactivated. Interestingly, both the combination of metal species in the catalysts and the ratio of metals had a great impact on catalytic performance. The newly developed continuous-flow hydrogenation reaction under mild

• conditions is adaptable to sustainable chemical synthesis, minimizing energy consumption and enabling the use of green hydrogen. In addition, the newly obtained insights regarding the relationships among the Fe/Pt ratios in the catalysts, the bimetallic structure, and the resulting catalytic performance for

Get a better glimpse on sequential photoreactions of trisnorbornadienes with ¹⁹F NMR spectroscopy

• Julian Felix Maria Hebborn,
• Ben Eric Merten,
• Thomas Paululat and
• Heiko Ihmels

Beilstein J. Org. Chem. 2026, 22, 527–534, doi:10.3762/bjoc.22.38

• /quadricyclane system 1f/2f0,3 has some favorable MOST properties, namely a high energy density and a long half-life of the trisquadricyclane. In addition, the cycloaddition reaction can be initiated under mild conditions with visible light (λex = 405 or 420 nm) in the presence of Ir(ppy)3 or flavine 4 as

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

• (Scheme 13) [29]. The reactions were carried out under mild conditions and required only low catalyst loading. The key to achieving high enantioselectivity lies in the stereoselective synthesis of the starting compounds which relies on polar–π interactions between an aryl component containing a highly

Recent advances in the cleavage of non-activated amides

• Eun-Sol Choi and
• Hyo-Jun Lee

Beilstein J. Org. Chem. 2026, 22, 352–369, doi:10.3762/bjoc.22.23

• scope of the esterification was indeed broad under mild conditions, enabling late-stage functionalization. For example, esterification of a fenofibric acid-derived primary amide with menthone derivatives furnished the corresponding ester 50 in 98% yield. In 2024, Aisa et al. reported a facile and

• , enabling efficient direct transamidation under mild conditions. In 2019, Dash et al. reported a transition-metal-free transamidation of DMAc under mild conditions (Scheme 21) [71]. In the presence of 1.5 equivalents of potassium tert-butoxide (KOt-Bu) as a base, DMAc underwent smooth transamidation with

• coupled with cooperative alkali metal counter cations, have expanded the scope of amide C–N bond cleavage under mild conditions. In parallel, the installation of activating groups on the amide nitrogen has enabled chemoselective cleavage, opening the door to late-stage transformations of target amides

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

• renders the pyranoquinoline carbonyl more electrophilic than that of the acyclic ester, facilitating its alcoholysis at elevated temperature and extended reaction times. Consequently, pyranoquinolines may be regarded as kinetic products, formed rapidly under mild conditions, whereas the open-chain esters

• cyclohexanol in refluxing dichloromethane. Moreover, Steglich esterification (using DCC and DMAP in dichloromethane), known for its mild conditions and compatibility with sterically hindered substrates, also produced the cyclic pyranoquinoline 14 rather than the expected ester. During preparative

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

• and with excellent enantioselectivities. The catalytic system operated under mild conditions within a practical timeframe and demonstrated broad substrate tolerance, providing a range of chiral helicenes. Notably, unsymmetrical phosphine oxides also underwent smooth Michael addition, with excellent

Base-promoted deacylation of 2-acetyl-2,5-dihydrothiophenes and their oxygen-mediated hydroxylation

• Vladimir G. Ilkin,
• Margarita Likhacheva,
• Igor V. Trushkov,
• Tetyana V. Beryozkina,
• Vera S. Berseneva,
• Vladimir T. Abaev,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2026, 22, 192–204, doi:10.3762/bjoc.22.13

• S3 of Supporting Information File 1) we have studied their transformations in ethanolic or methanolic solutions in the presence of sodium ethoxide or methoxide, accordingly. As a result, catalyst-free oxidation under mild conditions of 2-acetyl-2,5-dihydrothiophenes into 2-hydroxy-substituted

• double bond, sulfur and amide group. The difference in the stability of these types of anions results in their distinct reactivity. Conclusion We have reported the solvent dependent transformation of dihydrothiophenes 1 under mild conditions. It was found that, in ethanolic solution in the presence of

Circumventing Mukaiyama oxidation: selective S–O bond formation via sulfenamide–alcohol coupling

• Guoling Huang,
• Huarui Zhu,
• Shuting Zhou,
• Wanlin Zheng,
• Fangpeng Liang,
• Zhibo Zhao,
• Yifei Chen and
• Xunbo Lu

Beilstein J. Org. Chem. 2026, 22, 158–166, doi:10.3762/bjoc.22.9

• /bjoc.22.9 Abstract A selective and efficient method for the synthesis of sulfinimidate esters via an NBS-promoted oxidative coupling of sulfenamides with alcohols has been developed. This operationally simple, metal-free protocol uses inexpensive and readily available reagents, operates under mild

• conditions, exhibits a broad substrate scope and high chemoselectivity, and clearly distinguishes itself from classical Mukaiyama-type oxidations. The reaction is readily scalable to gram quantities and is applicable to late-stage functionalization of complex alcohols, including bioactive molecules such as

Highly electrophilic, gem- and spiro-activated trichloromethylnitrocyclopropanes: synthesis and structure

• Ilia A. Pilipenko,
• Mikhail V. Grigoriev,
• Olga Yu. Ozerova,
• Igor A. Litvinov,
• Darya V. Spiridonova,
• Aleksander V. Vasilyev and
• Sergey V. Makarenko

Beilstein J. Org. Chem. 2026, 22, 123–130, doi:10.3762/bjoc.22.5

• cyanoacetate, ethyl cyanoacetate, benzoylacetonitrile), carbocyclic (1,3-indanedione), and heterocyclic (Meldrum’s acid, dimethylbarbituric acid, 3-methyl-1-phenyl-5-pyrazolone) CH-acids – allows the synthesis of both monocyclic and spirocyclic 1SR,2RS vic-trichloromethylnitrocyclopropanes under mild

• conditions. The reaction is carried out either in tetrahydrofuran in the presence of triethylamine or in methanol in the presence of fused potassium acetate. The structures of the isolated individual products were characterized by 1H and 13C NMR, IR spectroscopy, mass spectrometry, and confirmed by single

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

• catalytic hydrogenation are relatively rare. This is partly due to the high stability of six-membered aromatic heterocycles, such as pyridine, making it difficult to interrupt the aromaticity under mild conditions [34]. Furthermore, the heteroatoms (such as nitrogen and oxygen atoms) within the saturated

• stereoselectively. In 2023, Chen in collaboration with Zhang, reported a simple and efficient rhodium–thiourea-catalyzed asymmetric hydrogenation reaction for the synthesis of highly optically pure tetrahydroquinoxaline 48 and dihydroquinoxalinones 50 (Scheme 6) [57]. Due to the mild conditions and broad substrate

• electrochemical systems, have expanded the toolbox further by enabling reductive dearomatization under exceptionally mild conditions and with high functional-group compatibility. Collectively, these hydride- and electron-transfer approaches enrich the landscape of arene reduction by providing tunable control over

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

• conditions required. As an alternative, dithiane-based ketone synthesis has long been used, but it suffers from drawbacks in terms of step economy [10][11]. To address these limitations, the authors developed a radical-based one-pot ketone synthesis that proceeds under mild conditions. When thioester 11 and

• developed by the Kishi group thus offers significant advantages over traditional methods, proceeding under mild conditions with easily prepared starting materials. Its versatility highlights the potential for broad application in drug discovery and the development of new materials. In 2025, the Nakamura

• tryptophan. The resulting radical species underwent fast dimerization to furnish the desired dimer 61. This zirconocene-catalyzed dimerization proceeded smoothly under remarkably mild conditions at room temperature, suggesting broad applicability. Indeed, the reaction was shown to tolerate a wide substrate

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

One-pot synthesis of ethylmaltol from maltol

• Immanuel Plangger,
• Marcel Jenny,
• Gregor Plangger and
• Thomas Magauer

Beilstein J. Org. Chem. 2025, 21, 2755–2760, doi:10.3762/bjoc.21.212

• via methylation of a dianionic intermediate, proved unsuitable due to competing overalkylation and the necessity of sub-zero temperatures. In contrast, a transient protecting group approach enabled selective methylation under mild conditions. This culminated in a scalable, operationally simple one-pot

Tandem hydrothiocyanation/cyclization of CF₃-iminopropargyl alcohols with NaSCN in the presence of AcOH

• Ruslan S. Shulgin,
• Ol’ga G. Volostnykh,
• Anton V. Stepanov,
• Igor’ A. Ushakov,
• Alexander V. Vashchenko and
• Olesya A. Shemyakina

Beilstein J. Org. Chem. 2025, 21, 2694–2702, doi:10.3762/bjoc.21.207

• acid at the triple bond – vinyl thiocyanates. This protocol features simple operating, readily prepared starting materials and occurs under relatively mild conditions. Keywords: CF3-alkynyl imines; hydrothiocyanation; isothiazolium thiocyanates; propargyl alcohols; sodium thiocyanate; Introduction

• operational simplicity, relatively mild conditions and readily prepared starting materials. Experimental General information. 1Н, 13С {1H}, and 19F NMR spectra were recorded on a Bruker DPX-400 spectrometer (400.1, 100.6, and 376 MHz, respectively) in CDCl3 and (CD3)2CO using hexamethyldisiloxane (HMDS) as

Visible-light-driven NHC and organophotoredox dual catalysis for the synthesis of carbonyl compounds

• Vasudevan Dhayalan

Beilstein J. Org. Chem. 2025, 21, 2584–2603, doi:10.3762/bjoc.21.200

• ][2][3][4][5][6]. Recently developed photocatalysis affords sustainable, regioselective green methods for producing a wide range of functionalized carbonyl compounds and their related bioactive chiral intermediates under mild conditions, employing dual organic photoredox catalysis [7][8][9][10][11

• , and advanced optical and energy materials. Review Visible-light-driven NHC/4CzIPN-catalyzed reactions Recently, Shu and co-workers developed a direct and innovative preparation of highly functionalized aryl amide derivatives 3 from aryl aldehydes 1 and substituted imines 2 under mild conditions in the

• presence of NHC (20 mol %), 4CzIPN (2 mol %) under mild conditions, producing corresponding unsymmetrical ketone derivatives 8 in up to 95% yield. An Ir-based photocatalyst was initially selected because its excited state is a strong oxidant (E1/2[Ir*III/II] = +1.21 V). Although 4-ethylanisole exhibits a

Ni-promoted reductive cyclization cascade enables a total synthesis of (+)-aglacin B

• Si-Chen Yao,
• Jing-Si Cao,
• Jian Xiao,
• Ya-Wen Wang and
• Yu Peng

Beilstein J. Org. Chem. 2025, 21, 2548–2552, doi:10.3762/bjoc.21.197

• the formation of inter- or intramolecular carbon–carbon bonds under mild conditions [9][10][11][12], and strategically applied this method for the divergent syntheses of some natural products [13][14][15][16][17]. Herein, we report our recent advance to a total synthesis of (+)-aglacin B (2), which

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

• their subsequent reaction with O-nucleophiles in the second chamber. The method is easy to setup, control and gives access to new haloacetimidates under mild conditions, similar to the ones used for the synthesis of the more commonly used trichloroacetimidates. Keywords: gaseous reagents; glycosyl

• [14][15][16][17]. Recently, 2,2,2-trifluoroacetaldehyde O-(aryl)oxime has been introduced as a precursor for trifluoroacetonitrile allowing to work under mild conditions at room temperature (Figure 1) [18]. Whether one prepares a precursor or the actual reagent, a separate setup is needed and hence

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

• aldehyde 53 [39] (Scheme 10). The key steps in this synthesis are based on an asymmetric rhodium-catalyzed [4 + 2] cycloaddition reaction [40], followed by a unique benzilic acid-type rearrangement under very mild conditions [41]. A step-by-step mechanism for the benzilic acid-type rearrangement of

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

• –Yang cyclization and related photoredox reactions, owing to their ability to undergo selective activation under mild conditions (e.g., long-wavelength irradiation) – a feature that minimizes competing fragmentation pathways. Notably, different dicarbonyl substrates exhibit distinct reactivity patterns

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

• substrates or organometallic complexes upon photoexcitation has enabled the synthetic community to access reactive open-shell species under very mild conditions. The ability of excited photocatalysts to induce other reagents, substrates, or other catalysts to participate in new activation modes makes them a