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

• imination-alkynylation-aza-Michael cascade for the enantio- and diastereoselective synthesis of 1,3-disubstituted isoindolines and tetrahydroisoquinolines 24 via a three-component coupling reaction involving 2-formylphenyl acrylates or 2-formylphenylcrotonates 21, arylalkynes 22, and anilines [46]. In this

• catalyst, affording chiral cyclopropyl pyrazoles with high levels of regio-, diastereo-, and enantioselectivities (Scheme 15) [55]. In the presence of Cu(CH3CN)4PF6 (5 mol %) and the chiral bisphosphine ligand (R,R)-iPr-DuPhos, the coupling of pyrazoles with substituted cyclopropenes proceeded efficiently

• %) and LiOt-Bu in CH3CN under blue LED irradiation enabled the coupling of alkenes 49 with carbazoles, indoles, and aniline derivatives to afford the corresponding amination products 50 with Markovnikov regioselectivity. Various styrene derivatives bearing electron-donating or electron-withdrawing

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

• readily available CO2, this method delivers carboxylated SiR derivatives in 60–93% yields while avoiding the use of t-BuLi, toxic CO, and expensive palladium catalysts. In addition, the crude carboxylation mixtures can be directly subjected to amide coupling without chromatographic purification, enabling

• maturity of photophysical optimization, the broader expansion of SiR chemistry is increasingly constrained by the limited accessibility of 5,6-carboxylated SiR derivatives. The carboxy groups provide a general and efficient handle for amide coupling with targeting ligands and are therefore central to the

• . Importantly, these species lack a carboxy group and therefore cannot participate in subsequent amide coupling reactions. Moreover, although small amounts of these byproducts were formed, they did not significantly interfere with the subsequent reactions. Thus, the reaction mixtures could be extracted with

Palladium-catalyzed benzocyclization reactions of quinoline-2-carboxamides via sequential C–H/N–H functionalization

• Shoichi Sugita,
• Kentaro Okano and
• Atsunori Mori

Beilstein J. Org. Chem. 2026, 22, 905–914, doi:10.3762/bjoc.22.71

• corresponding heterocycle-fused compounds. The high chemoselectivity of the 1,2-dihaloarene functional groups is confirmed in this reaction, thus enabling divergent synthesis of various multifused heterocyclic systems. Keywords: C–H activation; chemodivergent synthesis; C–N coupling; fused-ring system

• metal affinity [9][10]. It is therefore expected that annulation of the amide moiety in quinoline-2-carboxamides would extend their functionality as biologically active structures, ligands, and extractants. Transition-metal-catalyzed coupling reactions are crucial for constructing carbon–carbon and

• carbon–heteroatom bonds. The classical coupling reactions, such as Kumada–Tamao–Corriu coupling [11][12][13], Sonogashira coupling [14][15], Negishi coupling [16][17], Migita–Kosugi–Stille coupling [18][19][20], Suzuki–Miyaura coupling [21][22], and Hiyama coupling [23][24] involve carbon–halogen and

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

• benzofuran-derived pyrazolamides 5m–q were synthesized through DBU-mediated cyclocondensation of 2-hydroxybenzaldehydes with 4-bromocrotonates to afford (E)-2-benzofuranyl-3-acrylates followed hydrolysis and coupling with 3,5-dimethyl-1H-pyrazole (Scheme 2b) [12]. Initially, the Michael reaction between α,β

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

• sortase. Optimisations using depsipeptides or coupling strategies have further improved conversion efficiency and reduced reagent consumption [144]. Due to its ease of preparation, large libraries of sortase variants have been generated and screened to expand substrate scope [143]. In one example, sortase

The trans-influence in gold chemistry from a catalytic perspective

• Manfred Bochmann

Beilstein J. Org. Chem. 2026, 22, 838–856, doi:10.3762/bjoc.22.66

• ^C)AuH(C6F5)]− 21 react slowly at room temperature with DMAD to give the corresponding Z-vinyl products 24 and 25, respectively. On treatment with acid 24 decomposes with reductive C–C coupling but without Au–vinyl protolysis, while irradiation of THF solutions of 24 or 25 at room temperature leads

Total synthesis of the capsular polysaccharide repeating unit towards the development of a glycoconjugate vaccine against Klebsiella pneumoniae ST512

• Shuo Zhang,
• Ondřej Daněk and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2026, 22, 821–827, doi:10.3762/bjoc.22.64

• ). Finally, protection of the hydroxy groups with benzyl ethers furnished building block 3 in 83% yield. With the building blocks in hand, the assembly of the hexasaccharide was pursued as outlined in Scheme 2. The synthesis commenced with the coupling of monosaccharides 1 and 2 promoted by NIS/TfOH followed

Synthesis and structural elucidation of a novel bis-spirooxindole from isatin and ethylenediamine

• Irene Moreno-Gutiérrez,
• Josefa L. López-Martínez,
• Sonia Berenguel-Gómez,
• Irene Torres-García,
• Duane Choquesillo-Lazarte,
• Manuel Muñoz-Dorado,
• Miriam Álvarez-Corral and
• Ignacio Rodríguez-García

Beilstein J. Org. Chem. 2026, 22, 813–820, doi:10.3762/bjoc.22.63

• and HMBC experiments were used for signal assignment. Chemical shifts (δ) are expressed in ppm and coupling constants (J) in hertz (Hz). Chemical shifts are reported using CD3OD or DMSO-d6 as internal reference. IR spectra were recorded with a Bruker Alpha spectrometer using a single reflection ATR

Knoevenagel condensation of 4,5- and 1,8-diazafluorenes

• Darya S. Cheshkina,
• Christina S. Becker,
• Alina A. Sonina and
• Maxim S. Kazantsev

Beilstein J. Org. Chem. 2026, 22, 803–812, doi:10.3762/bjoc.22.62

• for their synthesis involves coupling reactions of diazafluoren-9-one [4][6][7] or diazafluoren-9-diazomethane [17][18] with thiones yielding the products in moderate yields (20–70%). However, these routes require the preliminary synthesis of malodorous thiones and diazomethane derivatives from the

Halogenated azobenzene acrylates: from efficient solution photoswitching to stable solid-state photochromic materials

• Martina Vachtlová,
• Michaela Fecková,
• Vítězslav Zima,
• Jan Podlesný,
• Milan Klikar,
• Oldřich Pytela,
• Patrik Pařík,
• Jakub Opršal,
• Eliška Juhaňáková,
• Veronika Chrtová and
• Filip Bureš

Beilstein J. Org. Chem. 2026, 22, 782–794, doi:10.3762/bjoc.22.60

• halogenated azobenzene acrylate monomers bearing fluorine, chlorine or bromine substituents is reported. The monomers were prepared via a facile three-step synthetic route involving azo-coupling, O-alkylation and O-acylation. Apart from the steady electrochemical properties, halogen substitution proved to be

• polyacrylate or polystyrene materials. Results and Discussion Synthesis of azobenzene monomers The target azobenzene monomers 1a–f were obtained using a facile three-step synthetic route as shown in Scheme 1. The first step represents an azo-coupling reaction between phenol and the corresponding diazonium

Design, synthesis, and biological evaluation of FXR/ASK1 dual-target modulators

• Xi Zhang,
• Jingyan Wang,
• Ziqiang Zhao,
• Caiyi Wang,
• Zenghui Ye,
• Wei-Yuan Ma,
• Jian-Xing Xu and
• Fengzhi Zhang

Beilstein J. Org. Chem. 2026, 22, 771–781, doi:10.3762/bjoc.22.59

• LiOH or lithium aluminum hydride to obtain compounds Z4–7. The synthesis of compounds Z8–15 followed a similar preparation procedure as for Z1–7. The synthesis of target compounds Z16–29 is illustrated in Scheme 7. Intermediates 8 and 10 were synthesized by the Suzuki cross-coupling reaction using

• Z26–29. The synthesis of target compound Z30 is illustrated in Scheme 8. Treatment of intermediate 2 with N-Boc-4-hydroxypiperidine (11) in the presence of sodium hydride produced ether 12, followed by removal of the Boc-protecting group, provided intermediate 13. Coupling of intermediate 13 with IXa

Preparation of 3-(alkylamino)imidazo[1,2-a]pyridine-2-carbaldehydes via Kornblum oxidation and unexpected ring-opening reactions of the corresponding alcohols under oxidative conditions

• Sandile J. Mkhize,
• Memory Zimuwandeyi,
• Manuel A. Fernandes,
• Amanda L. Rousseau and
• Moira L. Bode

Beilstein J. Org. Chem. 2026, 22, 763–770, doi:10.3762/bjoc.22.58

• ester. In this paper, we describe the synthesis of a library of derivatives of 8, whose imidazo[1,2-a]pyridine core could be accessed via the Groebke–Blackburn–Bienayme (GBB) multicomponent coupling reaction [20][21][22][23]. Results and Discussion In order to access our initial target compounds 7, the

• -chloroaniline, followed by reduction; ii) reaction of the corresponding carboxylic acid with 2-chloroaniline under peptide-coupling conditions followed by reduction; and iii) reduction of the ester to the aldehyde, followed by reductive amination to give compounds 8. Initial attempts at direct conversion of

• ]. The very small number of compounds of this type reported is suggestive of their inherent instability and their tendency to readily decarboxylate. Having ruled out using a peptide-coupling approach we moved to investigate the preparation of the 2-substituted aldehyde derivative, with subsequent

Synthesis and biological evaluation of new brassinosteroid analogs with C-22 benzoate function

• María Núñez,
• Camila Escobar,
• Mario Párraga,
• Mauricio Soto,
• Luis Espinoza-Catalán,
• Katy Díaz and
• Andrés F. Olea

Beilstein J. Org. Chem. 2026, 22, 753–762, doi:10.3762/bjoc.22.57

• these signals show direct correlation (1JHC coupling) in the 2D HSQC and 2JHC or 3JHC on the 2D HMBC spectra (Figures S1–S5, Supporting Information File 1). The structural determination of compounds 24–28 has been performed in a similar manner to that used for compound 23. Next, Sharpless

• . From a comparison of binding energy and relative accumulation in dBES1 overexpression it might be expected that there is an acceptable correlation between both parameters. For example, compound 19, possessing a chlorine substituent on the phenyl ring, has an outstanding molecular coupling in BRI1, and

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

• sulfide oxidation. In that early work, the stereochemical analysis was dependent on conformational analysis and comparison of coupling constants in the 1H NMR spectra. Experiments discussed in our inital report confirmed that the reaction proceeded under kinetic control [21]. Closer examination of the

Synthesis of depressin, cryptomeridiol and 4-epi-cryptomeridiol enabled by a terpenoid chiral pool-producing platform

• Yao Kong,
• Tao Wang,
• Chen Wang,
• Pengcheng Zhang,
• Yuanning Liu,
• Kaibiao Wang,
• Fen Liu,
• Hongli Jia and
• Zhengren Xu

Beilstein J. Org. Chem. 2026, 22, 683–690, doi:10.3762/bjoc.22.53

• efficient macrocyclization methods, including tetracarbonylnickel-promoted cyclization of allylic dibromide [17][18], copper-mediated intramolecular carbene–olefin cyclization [19], titanium-induced intramolecular carbonyl coupling [20], and organozinc carbenoid-mediated intramolecular cyclopropanation [21

Hydrogen production from formic acid catalyzed by NHC–Cu complexes

• Orlando Santoro and
• Catherine S. J. Cazin

Beilstein J. Org. Chem. 2026, 22, 620–627, doi:10.3762/bjoc.22.48

• formate products. Excess H2 can be generated by dehydrogenative coupling of those species in the presence of the copper catalyst. Indeed, metal hydride systems have shown high catalytic activity in such a reaction [59][60]. In addition, the formation of products compatible with the polymerization of

• silicon compounds was observed in all reactions (see Supporting Information File 1, Figure S3). Noteworthy, by replacing formic acid with acetic acid only 1 equivalent of hydrogen was released. The different reactivity towards the dehydrogenative coupling of the silyl carboxylate species can be due to

• simultaneous occurrence of two dehydrogenative mechanisms can explain the results of the isotopic labeling experiments. Indeed, while HD arises from the coupling of HCO2D with phenylsilane, the formation of H2 takes place by dehydrogenative coupling of the hydrosilanes present in the reaction mixture. To

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

• native framework while serving as a more accessible synthetic handle for downstream coupling chemistry. As 1 itself was known not to have any effect on cell viability while its uncharged methyl ester analogue did, the neutralised pro-drug analogue of the ATP-site binder was employed to prevent such

• corresponding triflate using triflic anhydride, followed by Suzuki–Miyaura cross-coupling with phenylboronic acid to give 16 in 59% yield (Scheme 1). Boc removal from intermediates 11–14 enabled attachment of the αD binder aldehyde 16 via reductive amination. Interestingly, NaBH(OAc)3 had performed well in the

•  1, section 1.4) was prepared according to literature and functionalised with 2-azidoacetic acid to introduce an azido-handle suitable for CuAAC-mediated triazole formation. CuAAC coupling of these alkyne precursors 17–20 with the azido-VHL ligand 22 afforded four final VHL-based PROTACs 23–26 in

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

• tweezers. Importantly, the H3 N-terminus had to be fully conserved (vide infra), so that covalent attachment of the tweezer moiety had to occur at the peptide C-terminus. A first prototype 1 could be realized with a C3-spacer and click coupling between azidopropylamide on Lys-4 at the peptide's C-terminus

• -terminus (peptide ordered from Genscript), which was subjected to click reaction with the butynyl tweezer (Scheme 1). The coupling protocol was identical to the published version [9][10]. Reaction progress was monitored by analytical HPLC and the product could be purified by preparative HPLC. After

• threonine, complementary to the cationic surface patch on survivin. B) Click coupling (i) between the H3-T3ph peptide with C-terminal 5-azidoornithine 3 and butynyl tweezer 4a with subsequent deprotonation (ii) to the sodium salt of peptide tweezer 2a. Binding peptide yellow, ornithine grey, butynyl group

Melifoliox B, a novel phloroglucin derivative isolated from Melicope barbigera (Rutaceae) and synthesis of new oxidation products from melifoliones A and B

• Horst Weber,
• Kim-Thao Tran-Cong,
• Bernhard Mayer,
• Guido J. Reiss,
• Iryna S. Konovalova,
• Marc S. Appelhans,
• Kenneth R. Wood and
• Claus M. Passreiter

Beilstein J. Org. Chem. 2026, 22, 535–546, doi:10.3762/bjoc.22.39

• , the aromatic protons of the added phenyl ring appear as a typical coupling pattern in the expected range for phenyl ethers. The acetyl-methyl group is shifted by 0.3 ppm to a higher field and the methyl group in position 9 resonates at the same field strength as in the case of 2-iodomelifolione A (8

• group and the center of the multiplet for the axial H-5 lie exactly on the top of each other at 1.61 ppm. The same applies to the signals of both axial H-7 and H-8 at 1.57 ppm. The signal for H-8a appears as a nearly symmetrical quintet, resulting from the trans diaxial coupling with H-8ax (about 10 Hz

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

• storage. The target compound was readily synthesized by a Suzuki–Miyaura coupling reaction and examined with respect to the key properties for MOST applications. Upon direct or photosensitized irradiation, the trisnorbornadiene was transformed stepwise and almost quantitatively into the corresponding

• trisnorbornadiene 1f was synthesized in 36% yield through a Suzuki–Miyaura coupling reaction of tribromotrifluorobenzene 3 with the 2-borononorbornadiene 1e (Scheme 2) [43]. The product 1f was identified and fully characterized by NMR spectroscopy (1H, 13C, 19F, COSY, HSQC, HMBC), mass spectrometry, melting point

• Information File 1, Figure S16). Contrary to the 1H NMR spectra, the 19F NMR spectra showed significantly fewer signals (one or two per molecule) during the photoreaction because of the symmetry of norbornadiene 1f and its photoproducts and the less complex coupling pattern. Thus, the 19F NMR spectra of the

Modern synthetic pathways towards eribulin and its subunits

• Sebastian Dominik Graf

Beilstein J. Org. Chem. 2026, 22, 495–526, doi:10.3762/bjoc.22.37

• –Kishi (NHK) coupling and Pd-mediated cyclization. Fragment 31 was synthesized from known precursor 28 [74] in 9 steps via MMTr-protection, replacement of the Bn- with TBDMS-protecting groups, hydroxylation of sulfone 29 to alcohol 30, tosylation, bromide substitution, acidic MMTr-cleavage and DMP

• -oxidation (Scheme 4, above). For the assembly of 33, only the hydrolysis of previously reported 32 [75] with Me3SnOH and thioesterification using EtSH and DCC were necessary (Scheme 4, below). Both fragments (31 and 33) were fused together via NHK coupling to furnish 34 in 86% yield. The addition of SrCO3

• proved to be suitable for the cyclization towards 35 and the eventual macrocyclization was achieved via coupling of the alkyl bromide unit with the thioester. Mechanistically, this reaction is enabled by the formation of an intermediate alkylzinc halide, which is produced by single electron transfer

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

• carboxylic acid derivatives such as esters, acyl chlorides and anhydrides with hydroxylamine salts [41]. A variety of coupling or activating agents were also employed in case of simple addition of hydroxylamine to carboxylic acid compounds [42][43][44]. In addition, alternative methods starting from

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

• , Hayashizaki, and Ito reported a highly stereoselective asymmetric cross-coupling reaction of 2-methylnaphthylmagnesium bromide with bromonaphthalene, catalyzed by a nickel complex with ferrocenylphosphine as the ligand, successfully synthesizing biaxially chiral molecules, namely 1,1':5',1"- and 1,1':4',1

• [2 + 2 + 2] cycloaddition reaction between α,ω-diynes 1 and monoalkynes 2, providing an alternative to traditional asymmetric coupling strategies for the synthesis of C2-symmetric biaryl chiral compounds (Scheme 1a) [40]. They further demonstrated the feasibility of constructing N-, O-, and C

• studies have further broadened the synthetic toolbox for remote biaxial chirality. Du and co-workers designed a series of chiral phosphoric acid catalysts derived from protected axially chiral diols 13, employing a boronic acid-mediated coupling strategy to construct remote biaxially chiral phosphoric

Synthesis and stereochemical analysis of dynamic planar chiral oxa[7]orthocyclophene

• Yukiho Hashimoto,
• Yuuya Kawasaki,
• Kazunobu Igawa and
• Katsuhiko Tomooka

Beilstein J. Org. Chem. 2026, 22, 436–442, doi:10.3762/bjoc.22.30

• Advanced Science and Technology, Kumamoto University, Kurokami, Kumamoto 865-8555, Japan 10.3762/bjoc.22.30 Abstract Planar chiral C6-substituted oxa[7]orthocyclophenes were designed and synthesized, and their stereochemical behavior was analyzed. The Kumada–Tamao coupling of the C6-iodo-substituted

• -substituted oxacyclophenes 1ab (X = O, Y = Me), 1ac (X = O, Y = Ph), and 1ad (X = O, Y = I), in which 1ad was used as the key intermediate for the synthesis of 1ab and 1ac via Kumada–Tamao coupling with Grignard reagents (Figure 2). Results and Discussion Retrosynthesis and synthesis of the C6-iodo

• coupling of compound 1ad with MeMgBr and PhMgBr in the presence of a catalytic amount of NiCl2(PPh3)2 proceeded smoothly to provide the C6-methyl-substituted 1ab in 79% yield and the C6-phenyl-substituted 1ac in 99% yield (Scheme 3) [15][16]. Suitable single crystals were obtained from racemic 1ac, and its

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

• important functionalities which can be introduced into calix[4]arene structures either through a wide-rim exhaustive nitration followed by reduction of the nitro groups [5][6][7][8][9][10][11][12][13], or through azo coupling followed by cleavage of the calixarene azo compounds thus formed [14][15][16][17

• ]arene. Notably, the alternative strategy of utilizing an azo coupling/cleavage sequence has only been applied thus far for the wide-rim modification of narrow-rim unsubstituted calixarenes. Since the exhaustive nitration and reduction steps proceed under relatively drastic conditions, which are poorly