Z-Selective semihydrogenation of alkynes via Ni/Lewis acid synergistic catalyzed system using DMF as hydrogen source and solvent

• Lei Kang,
• Haifeng Gao and
• Luo Yang

Beilstein J. Org. Chem. 2026, 22, 1004–1012, doi:10.3762/bjoc.22.79

• intermediates, yet their combination with nickel catalysts has been little explored in alkyne semihydrogenation. We envisioned that merging nickel’s competence in alkyne activation and hydrogen transfer with a Lewis acid’s capacity to modulate reaction pathways could enhance both selectivity and efficiency

• Z-olefins. Beyond expanding the toolbox for stereocontrolled alkyne semihydrogenation, this study offers fresh perspectives on the design of Lewis acid–metal synergistic catalytic systems. Results and Discussion We began by developing a base metal catalytic system for the semihydrogenation of

• , entry 21) durations resulted in incomplete conversion. Finally, the role of DMF was confirmed. Replacing DMF with formamide afforded markedly reduced yields (Table 3, entry 22), primarily because severe competitive alkyne hydrocyanation consumes substrates, which was comprehensively explored in our

Electrochemical reduction of unsaturated carbon–carbon bonds via 3d transition-metal catalysis

• Geon Kang,
• Minki Jeon,
• Pooja Kumari Jat,
• Cheoljae Kim and
• Isaac Choi

Beilstein J. Org. Chem. 2026, 22, 955–981, doi:10.3762/bjoc.22.75

• stereoselective hydrogenation of alkynes under electrochemical and transition-metal-catalyzed conditions. The alkyne semihydrogenation generally benefits from the stronger coordination ability of the C–C triple bonds and the greater accessibility of metal-bound intermediates, thereby often enabling stereocontrol

• -based systems [38][39]. In sharp contrast, electroorganic synthesis provides a fundamentally distinct mode of reactivity compared to conventional thermochemical approaches, in which electric current serves as the terminal reductant, thereby enabling unconventional mechanistic pathways for alkyne

• , or PCET-enabled hydride generation provide catalytically relevant M–H species, which subsequently engage with unsaturated substrates through distinct reaction modes. One prominent mode is migratory insertion, in which the coordinated alkene or alkyne inserts into the M–H bond to form a metal–alkyl or

Synthesis of sterically shielded piperidine nitroxides via acid-catalyzed heterocyclization of β-aminoketone derivatives with ketones

• Mark M. Gulman,
• Yurii I. Glazachev and
• Sergey A. Dobrynin

Beilstein J. Org. Chem. 2026, 22, 948–954, doi:10.3762/bjoc.22.74

• consistent with a single nitroxide species with a g-factor in the range of 2.0055–2.0057 (aN = 15–16 G) (Table 1); no additional hyperfine splitting was resolved. The slightly higher aN values in the alkynyl-substituted compounds likely stem from the electron-withdrawing influence of the alkyne group and/or

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

• addition of 2-arylethynylaniline 29 to form β-amino ketone intermediate II, which existed in equilibrium with its enol form. Subsequent coordination of the alkyne to the copper center promoted intramolecular 5-endo-dig hydroamination, yielding indole product 32 after proton transfer. Overall, the copper

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

• native glycans for chemical attachment through bioorthogonal chemistry (e.g. strain-promoted azide–alkyne cycloaddition/SPAAC) [114][115][116][117][118][119]. While this strategy enables visualisation and derivatisation of native glycoproteins in their natural environment, metabolic labelling rarely

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

• (II) congener, K[PtCl3(ethylene)] [28], as well as the first examples of gold(III) alkyne [29], CO [30], hydride [31] and σ-complexes [32] (Scheme 3). The olefin complexes were isolated as microcrystalline powders which as dry solids are fairly stable in air at room temperature. The olefin bonding is

• about 35%. Steric factors also come into play; together these effects explain why stable mono-alkyne complexes [(C^C)Au(alkyne)L]+ 6 could be isolated but bis(alkyne) complexes are inaccessible (Scheme 4). Similarly, the formation of the dicarbonyl complex [(C^C)Au(CO)2]+ would be endothermic. Extending

• the reaction. The final product is then formed in a bimolecular reaction: LAuOO• + HAuL → LAuOOH + LAu• [53]. In both these cases the Au–H bond is activated by the presence of a strong C-donor in trans position. So far no O2 insertion has been reported for Au–H trans to N. Alkene and alkyne insertions

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

• with a dipolarophile, such as an alkene or alkyne, to form a five-membered heterocycle in one step. Currently, this type of reaction allows for the efficient preparation of bi- and polycyclic fused or spiro-linked structures with multiple chiral centers and high regio- and stereocontrol [1][2][3][4

• yields and excellent enantioselectivity (Scheme 48) [97]. A similar spirocyclic system was constructed via enantioselective (3 + 2) cycloaddition of isatin-derived azomethine ylides to 2,3-allenoates [98]. The authors consider allene in the cycloaddition reaction as a synthetic equivalent of alkyne for

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

• position of casbane diterpenes [14][15]. One total synthesis was reported that features a ring-closing alkyne metathesis (RCAM) reaction to forge the 14-membered macrocycle ring [16]. Besides depressin, only casbene (4) of the casbane family has been selected as a target for synthesis so far. The choice of

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

• synthesis see Supporting Information File 1, section 1.3). In parallel, PEG-based linkers bearing terminal alkyne handles were synthesised for modular CuAAC-based PROTAC assembly. The αD binder 16 had been synthesised via a two-step reaction. First, the phenolic group of 15 was converted into the

• CK2α further confirmed, that both the ATP-binding and αD-binding motifs retained their expected hydrogen-bonding and hydrophobic interactions, and the linker projected cleanly toward solvent-exposed region (Figure 1). Importantly, the absence of the terminal alkyne substituent in the electron density

•  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

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

• products were fused together by the nucleophilic attack of deprotonated alkyne 265 to aldehyde 261 (Scheme 31). The obtained diastereomers 266 were oxidized to the respective ketone 267, and again, Noyori reduction was performed to access 268 [105]. Treatment with AgBF4 at elevated temperature induced a

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

• carboxylic acid derivatives (Scheme 2b) [43]. They revealed that ortho-alkoxy substitution on the benzene-derived alkyne markedly enhanced both reactivity and enantioselectivity, while incorporation of a naphthyl substituent into the diyne enabled access to remote biaxially chiral molecules. Subsequent

• –C derivatives through reaction of 1-alkynylnaphthalenes with benzamides. In this context they observed that the stereoselectivity of the alkyne insertion could be tuned by solvent effects, particularly with hexafluoroisopropanol, which induced inversion of the C–C axial configuration (not shown). In

• yields, indicating potential utility in chiral fluorescent materials. In addition, Du’s group reported an N-heterocyclic carbene (NHC)-catalyzed (3 + 3) cycloaddition of 2,6-disubstituted alkyne esters 38 with 6-aminouracils 39, affording distal biaxial uracil frameworks with both C–C and C–N chiral axes

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

• of propargyl alcohol 3 and the alkyne moiety in 3 can be introduced by an alkynylation of the formyl group of aldehyde 4. Thus, we started this synthesis from O-protected 2-bromobenzyl alcohol derivative 5 for the introduction of the propanal moiety of 4 by a Heck reaction with allyl alcohol. The

• alkyne 6. Subsequent preparation of the lithium acetylide using n-BuLi, followed by treatment with formaldehyde, afforded propargyl alcohol 3a in 70% yield over three steps. The reaction of 3a with Red-Al generated a vinyl aluminum species, which was then treated with iodine to provide the iodinated Z

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

• different strategies were implemented to obtain propargylated and 2-azidoethylated p-aminocalixarenes. In the case of propargylated calixarenes, sterically crowding silyl protection was introduced into the alkyne groups of p-tert-butylcalix[4]arene (multiple) propargyl ethers, and the resulting compounds

• -aminocalix[4]arenes enriched with alkyne or azide functionalities can be readily used as multifunctional platforms to obtain even higher functionalized macrocycles. As an example, they can be used for the preparation of sophisticated supramolecular assemblies with homo- or heterodimeric calixarene cores and

• calixarene-based multi(macrocycles) and multi(catenanes) having impressive topology [61][62][63][64][65][66][67][68][69]. Over the past two decades, azide and alkyne groups have also appeared among the most synthetically valuable functionalities introduced into calixarene cores due to the ease of their

Synthesis of tricyclic fused pyrrolidine nitroxides from 2-alkynylpyrrolidine-1-oxyls

• Mark M. Gulman,
• Yuliya F. Polienko,
• Sofia Yu. Trakhininа,
• Yuri V. Gatilov,
• Tatyana V. Rybalova,
• Sergey A. Dobrynin and
• Igor A. Kirilyuk

Beilstein J. Org. Chem. 2026, 22, 344–351, doi:10.3762/bjoc.22.22

• pyrroline series (0.1–0.3 M−1s−1). These rates are more than two orders of magnitude higher than those of tetraethyl nitroxides of the pyrrolidine series (0.001–0.0001 M−1s−1) [28][29]. This could result from the electron-withdrawing effect of alkyne or heteroaromatic substituent. Moreover, it can be noted

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

• η2-arene complexes and alkenes are well-established (Scheme 4A) [65][66], analogous transformations with alkyne dienophiles had remained elusive. Oxidative liberation of the resulting complexes furnished several unprecedented free barrelenes (Scheme 4B). Intriguingly, η2-coordination of barrelenes 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

• (±)-LSD by Vollhardt and co-workers, the pyridine part was constructed by a Co-catalyzed [2 + 2 + 2] cycloaddition between alkyne 84 and nitrile 85, constructing the ergoline core 86. Methylation with MeOTf provided pyridinium 87, and subsequent NaBH4-mediated hydrogenation selectively generated the

• rearrangement and Lewis acid-promoted acetal–ene reaction provided the tetracyclic skeleton 101. With 101 in hands, a 6 step transformation afforded the alkyne 102 in an overall yield of 45%. After obtaining 102, the authors used a free radical reaction to initiate a one-step 6-exo-trig cyclization

• excellent enantioselectivity (96% ee). Subsequent transformations over six steps (overall yield: 71%) provided the piperidine building block 200. Coupling of the key fragments 197 and 200 was achieved in two steps (77% yield), affording alkyne intermediate 201. This was followed by a sequence of strategic

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

• authors justified the low yield by the high volatility of 19 and loss thereof during work-up (Scheme 5). It should be noted that the two-step procedure for converting a ketone into the corresponding alkyne can be accomplished in a single step, as recently reported by Ghaffarzadeh and co-workers) [50

• corresponding alkyne 50 by elimination with LDA were achieved in superb yields (Scheme 10). Gross and Gloede introduced catechol–PCl3 as an effective reagent for the conversion of ketones to the corresponding alkenyl chlorides [62] (Scheme 11A). Hudrlik later demonstrated that, in the case of 2

• alkenyl chloride 156 was isolated only in trace amounts, alongside isomerized alkene 157 and dichloride 158. Notably, only the sterically hindered tert-butyl-substituted alkyne afforded the desired product 155 in high yields, whereas hydrochlorination of 4-octyne proved inefficient to deliver compound 159

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

• different cyclizations due to the conjugated imine and alkyne bonds [27], and the hydroxyalkyl moiety linked to the triple bond can also act as a nucleophilic site. Another attractive feature of these compounds is the presence of the trifluoromethyl group (CF3). The latter serves as a valuable structural

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

• furnish 79 in excellent yield. The key connection in this synthesis proceeded in a one-pot fashion in 67% yield. At first, tosylhydrazone 79 was subjected to a thermal Eschenmoser fragmentation at 150 °C under microwave conditions to obtain both, an alkyne and aldehyde moiety in intermediate 80. The crude

• material was concentrated and subjected to a Horner–Wadsworth–Emmons (HWE) reaction with phosphonate 77. In the same pot, the alkyne moiety was also methylated to furnish dienyne 72. Now, the key Diels–Alder step could be performed. Initial attempts failed, but a rhodium-catalyzed reaction in

• fragmentation, a Horner–Wadsworth–Emmons (HWE) reaction and an alkyne methylation, all proceeding in one-pot. This then set the stage for the key Diels–Alder/aromatization sequence. Although three entirely different approaches are displayed, all three pose a fast 13 or 15 step longest linear sequence access to

Recent advances in total synthesis of illisimonin A

• Juan Huang and
• Ming Yang

Beilstein J. Org. Chem. 2025, 21, 2571–2583, doi:10.3762/bjoc.21.199

• enantioenriched compound 33, a nickel-catalyzed hydrocyanation of the terminal alkyne was performed. Subsequent protection of the tertiary alcohol with TESOTf and reduction of the resulting cyanide to an aldehyde afforded compound 34 (Scheme 4). Addition of isopropenyllithium to aldehyde 34, followed by TES

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

• . This work not only demonstrates the efficacy of the titanium-mediated intramolecular alkyne-1,3-diketone coupling but also provides a novel strategic approach for synthesizing natural products within this structural class. The synthesis commenced from commercially available compound 83. Sequential

• alkyne difunctionalization, furyl group installation, Achmatowicz rearrangement, and subsequent functional group manipulations provided intermediates 84 and 85. C5-acylation and methylation under kinetically controlled conditions followed by Sonogashira coupling yielded cyclization precursor 89

• . Treatment of 89 with Ti(OiPr)4/iPrMgCl promoted the intramolecular stereoselective alkyne–1,3-dicarbonyl coupling, resulting in the construction of the AB ring system. This transformation afforded tricyclic compound 91 as the major product, accompanied by minor amounts of by-product 90. Subjecting 91 to

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

• cleavage of the N–O bond, oxidation and Baeyer–Villiger oxidation. The starting functional groups (including alkyne and nitrone) for the proposed oxazoline were established in literature precedents [29][30][31]. Moreover, the readily available intermediate 8 [32] bearing three defined stereogenic centers

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

• tandem deprotection/click chemistry followed by Pd-catalyzed annulation is summarized in Table 1. The alkyne-substituted analogs 1–6 [48][49][50][51][52] used in this study were prepared from commercially available aryl halides using microwave-promoted Sonogashira coupling (Table S1, Supporting

• Information File 1). Reaction of each TMS-protected alkyne with ortho-bromoazidobenzene produced 1,5-diaryl-1,2,3-triazole products 7–12, each possessing an ortho-bromoaryl reactive site necessary for the annulation step. Regioselective formation of 1,5-diaryl-1,2,3-triazoles 7–12 was achieved using a

• where the attachment of alkyne and azide functional groups was reversed, as summarized in Table 2. The azide analogs 19–24 [25][28][31][43] used in this study were prepared from commercially available amines using the Sandmeyer reaction (Table S2, Supporting Information File 1). Reaction of each azide

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

• alkyne insertion step may be rate-limiting, as it involves the participation of selenol, alkyne, and the rhodium catalyst. The Rh(III) mechanism appears to be more plausible than route B, which can be attributed to the enhanced ion-pairing effect resulting from the higher oxidation state of rhodium

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

• rearrangement of alkyne 230 into aldehyde 232, which contains two vicinal quaternary chiral centers at C8 and C10 (Scheme 41). (−)-Spirochensilide A belongs to an emerging and biologically important class of natural products with a unique spirocyclic core [99][100][101][102]. It is also a promising compound for