Synthesis and optical resolution of 4,5-diaminohomoadamantane: a promising scaffold for chiral ligands and bioactive compounds

• Polina A. Man’kova,
• Vadim A. Shiryaev,
• Olga S. Podlipnova,
• Marat M. Khisyamov,
• Dmitry S. Nikerov,
• Alexander N. Reznikov and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2026, 22, 1013–1022, doi:10.3762/bjoc.22.80

• , homoadamantan-4-ene (2) was obtained from homoadamantan-4-ol (1). In 1969, a method for the preparation of alkene 2 from homoadamant-4-yl tosylate was proposed [85]. However, the formation of methyl tosylate and the need for purification of the product reduces its usefulness. We herein report an improved method

• for the synthesis of compound 2 from alcohol 1 using phosphoric acid, affording the target compound in high yield and purity. In the next step, chloronitrosation of alkene 2 led to α-chloroxime 3 in moderate yield. Substitution of chlorine in 3 with azido and benzylamino groups was then carried out to

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

• several limitations – including batch variability, alkene isomerization, and over-reduction to alkanes, which are particularly problematic for terminal and polar substrates [7][8][9][10]. Recent review articles have comprehensively summarized advances in this research field. For instance, Gregori et al

• the generated alkene products under the relatively high reaction temperature of 150 °C, which partially consumes the target olefin products and reduces the final isolated yields. In a preliminary experiment, we tested 1-phenyl-1-propyne (5a) and 5-decyne (7a) as substrates under the established

• intermediate C. Following decarboxylation, the resulting dihydrido vinyl-nickel species D undergoes reductive elimination to release the (Z)-alkene product and regenerates the Ni(0) catalyst A, thereby closing the catalytic cycle. Conclusion In summary, we have developed a highly Z-selective semihydrogenation

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

• through inner-sphere substrate organization. From this perspective, alkene reduction is relatively more challenging because of the lower π-basicity of alkenes. Alternatively, outer-sphere electron transfer, mediated by electrolysis, or the strategic use of redox mediators and co-catalysts could also

• provide effective approaches for promoting selective alkene hydrogenation. Electrochemical and 3d transition-metal catalysis Owing to the straightforwardness of the reductive chemical transformation, a plethora of synthetic approaches has been utilized, with recent efforts increasingly converging on 3d

• , 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

• bonds afforded the corresponding saturated derivatives 8a–d. Specifically, alkynyl derivatives 7a–c were hydrogenated with H2 over a palladium catalyst, while the allyl derivative 7d was reduced with hydrazine over Raney nickel (Scheme 4). The absence of signals corresponding to alkene protons in the 1H

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

• , including copper–amido-mediated nucleophilic addition or aminocupration, Lewis acid-type alkene activation, and radical-mediated pathways. These complementary mechanisms provide access to diverse alkene classes with control over regioselectivity (Markovnikov vs anti-Markovnikov addition), stereoselectivity

• is because the direct interaction between an electron-rich nitrogen lone pair and a relatively inert alkene π-system is often kinetically disfavored in the absence of activation [19]. Furthermore, the hydroamination of unsymmetrical alkenes introduces additional complexity in controlling the

• valuable in hydroamination chemistry. Several distinct yet interrelated activation modes have been identified for copper-catalyzed alkene amination [27]. Copper frequently participates directly in amine activation via the formation of Cu–N species (Scheme 1a) [30][31]. In the presence of a base and

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

• values correlate well with the corresponding C–H bond dissociation energies [25], not unexpectedly perhaps given the similarity of electronegativities (Au, 2.54; C, 2.55; H, 2.20). Toste et al. selected the ratio of [4 + 3] vs [4 + 2] alkene–allene cycloadditions as a probe for ligand effects, employing

• 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

• system. Here the metal centre is subject to the effect of two good donors of about equal strength. This is the only system reported so far where gold(III) displays palladium-like reactivity, such as alkene insertions into Au–alkyl bonds and β-H elimination. The influence of C(−) and/or -PiPr2 donors

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

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

• and further treated with Lindlar catalyst and DIBAL-H to afford the alkene and aldehyde motifs of 195, respectively. Oxime formation and oxidation yielded an intermediate nitrile oxide, which underwent an intramolecular [3 + 2]-cycloaddition with the adjacent ethene substituent towards isoxazoline 196

• assemble 226 as an E/Z mixture. Hydrogenation of alkene 226 and treatment with allyltrimethylsilane were used to form 228. The ester moiety of 228 was reduced and the Bz-group was cleaved simultaneously to afford the respective diol (229), then TIPS-protection of the primary alcohol unit enabled the

• the secondary alcohol, hydroboration–oxidation of the terminal alkene and treatment with DMP produced aldehyde 261. The second building block (265) was synthesized via stereoselective Noyori reduction of 262 [105], followed by TMS cleavage and Bz-protection of the free alcohol unit (Scheme 30). Both

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

• ][3][4][5][6][7][8][9][10], we previously synthesized hetera[7]orthocyclophenes 1 having a heteroatom-embedded ansa-chain (X = O or NR) and an (E)-alkene moiety (Figure 1) [6][9], and found that the orthocyclophenes exhibit dynamic planar chirality in a wide range of stereochemical stability depending

• on the differences of the heteroatom and substituents on the (E)-alkene moiety [11][12]. The half-lives of the optical activity optt1/2 of 1aa (X = O, Y = H) and 1ba (X = NTs, Y = H) were 380 h and 56.7 h at 25 °C, respectively, indicating that the stereochemical stability of the oxygen-containing

• -substituted oxacyclophene 1ad We planned to construct the nine-membered cyclic ether skeleton of 1ad in the final step by an intramolecular Williamson etherification of haloalcohol 2 (Scheme 1). The iodine-substituted Z-alkene moiety of 2 was planned to be introduced through a trans-selective hydroiodination

Dialkylaminoalkylation of β-ketosulfones via ring-opening of 3-sulfonylpyrrolidines

• Evgeny M. Buev,
• Alexander V. Pavlushin,
• Vladimir S. Moshkin and
• Vyacheslav Y. Sosnovskikh

Beilstein J. Org. Chem. 2026, 22, 383–389, doi:10.3762/bjoc.22.26

• consists in the simultaneous generation of two reactive intermediates: terminal alkene A and N-methylazomethine ylide B, and final [3 + 2] cycloaddition. It was found that the latter approach depends on CH-acidity of the active methylene compounds and performs well with the acidic substrates in the range

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

• ring expansion, and additional 5-ring cyclisation by the pendant alkene a new tricyclic carbocation 14c is formed. From here a 1,2-alkyl shift delivers the 7,6,6-ring system of lydicene (15) [66]. Alternatively, a 1,5-hydride shift affords the secondary carbocation 14d which undergoes ring contraction

• ) and B (78) the tricyclic precursor 79 was invoked (see Scheme 22B) [129]. This compound could undergo oxidation at the alkene (and C-1) to give intermediate 80, which after oxidative cleavage affords the enolate of diketone 82 which can undergo transannular aldol addition to give either product 77 or

• liphagal (104) [150]. Oxidation of the alkene in 102 may give rise to an oxidised species, such as 105, which is able to undergo Meinwald rearrangement to the ring-expanded ketone 106. From here, epimerisation of the C-8 methyl group and acetalisation to 106a followed by elimination delivers the final

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

• springboards to three-dimensional molecular architectures largely untapped (Figure 2A) [13]. Enforcing localization of the arene π-system achieves precisely this: it activates the arene through induction of an alkene-like character, thereby presenting a twofold opportunity: (1) to advance dearomative chemistry

• aromaticity and unveiling the latent double-bond character within the aromatic ring. This dramatically increases reactivity, enabling alkene-like transformations with aromatic molecules that are inaccessible by conventional synthetic methods, thereby complementing traditional arene chemistry. Other modes of

• distortion enforces an alkene-like double-bond character at the junction, accompanied by enhanced reactivity unusual for aromatic systems [24][25]. In contrast to the breadth of structural and theoretical studies, synthetic utilization remains underexplored, despite the growing evidence that strain-induced

Synthesis of diaryl phosphates using phytic acid as a phosphorus source

• Kazuya Asao,
• Seika Matsumoto,
• Haruka Mori,
• Riku Yoshimura,
• Takeshi Sasaki,
• Naoya Hirata,
• Yasuyuki Hayakawa and
• Shin-ichi Kawaguchi

Beilstein J. Org. Chem. 2026, 22, 213–223, doi:10.3762/bjoc.22.15

• the other mechanism is based on an E2 reaction, which involves the elimination of phosphoric acid accompanied by alkene formation. The phosphoric acid ester of a secondary alcohol releases phosphoric acid and alkenes through thermal degradation, which has been previously observed using isosorbide

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

• chloride, and radical reduction. Subsequently, reduction of the cyanide group with DIBAL-H and a Wittig reaction afford alkene 114 in 82% yield. Sodium metal was then used as a single-electron reducing agent to provide the second cycloaddition precursor 115, which was converted to the enamine. The enamine

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

• compound loss or degradation at the purification step. 1.2 Exchange reactions This chapter deals with exchange reactions, meaning that a given substituent on the alkene is formally exchanged for chlorine. The reactions are very different from each other in terms of mechanism and for a full discussion the

• 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

• access cyclohexenyl chlorides via chloride trapping of alkenyl cation intermediates (Scheme 48B) [157]. Comparable yields were obtained when either alkene or alcohol precursors were employed, consistent with the formation of a common cationic intermediate. The method proved limited to six-membered ring

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

• ) compounds in polar nucleophilic or non-nucleophilic solvents [10][11][12][20][29][30][31][32][33][34][35][36]. Fujita discusses typical pathways of alkene oxidation with hypervalent iodine in great detail including the stereochemical course of reaction involving a cyclic iodonium ion [30]. In the literature

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

• the hydroxy moiety in C12 was performed, followed by Grignard addition of ethynylmagnesium bromide and then hydrocyanation to result in vinyl nitrile 57 over five steps. The key Wagner–Meerwein-type rearrangement occurred in 68% yield furnishing epoxide 58. Hydrogenation of the alkene moiety as well

• 63. The D-ring was saturated and the remaining alkene epoxidized – a strategy that we have observed in cyclopamine synthesis before. The sequence needed several protecting group manipulations. Therefore, epoxide 64 was synthesized in eleven steps from ketone 62. The key spirocyclization was performed

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

• of single-electron NHC catalysis by incorporating oxidatively generated aryloxymethyl radicals A as a key intermediate. A variety of γ-aryloxy ketones 12 were successfully prepared in the presence of NHC (15 mol %), photocatalyst (2 mol %), using 467 nm LED and a combination of alkene 11, amide 9

• for 18 h (Scheme 6) [56]. Gao, Ye, and co-workers reported the iminoacylation of alkenes 17 via photoredox NHC dual catalysis in the presence of NHC (20 mol %), photocatalyst (5 mol %), with Na2CO3 (1.2 equiv) using a 36 W blue LED. In this method, the alkene-attached iminyl radicals A and the NHC

• -attached ketyl radical B are generated under photoredox NHC catalysis under visible-light irradiation. The 5-exo-trig radical cyclization of the alkene-tethered iminyl radicals A furnished a dihydropyrrole-derived radical coupled with the NHC group attached ketyl radical B. This approach features readily

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

• [5.2.1.01,5]decane core with a cis-pentalene unit. The product was further processed into rearrangement precursor 46 (as an inseparable mixture, dr = 1:1.6) by TBS protection of the primary alcohol and epoxidation of the alkene with m-CPBA. Unlike Rychnovsky’s substrate, epoxy alcohol 46 underwent

• reaction of 87 was employed, generating both the kinetic product 88 and the desired thermodynamic product 89. Heating 88 promoted a retro-Diels–Alder/Diels–Alder equilibrium, favoring the more stable isomer 89. Palladium-catalyzed hydrogenation of the 1,2-disubstituted alkene in 89, followed by Mo(CO)6

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

• , provided compound 78. Finally, a sequence comprising terminal alkene reduction, epoxidation of the tetrasubstituted alkene, and LiDBB-promoted intramolecular reductive cyclization and deprotection completed the asymmetric total synthesis of (+)-ryanodine (1) in 17 steps. Notably, the additive used in the

• , terminal alkene reduction, and intramolecular reductive cyclization culminated in the completion of the first asymmetric total synthesis of (+)-20-deoxyspiganthine (2) in 19 steps. Micalizio’s formal total synthesis of ryanodol (4) In 2020, the Micalizio group at the University of California, San Diego

• epoxidation of the tetrasubstituted alkene followed by Grieco elimination yielded diene 92. Subsequent oxidation of the hemiacetal, saponification of the lactone, intramolecular epoxide opening, and Hoveyda–Grubbs (II)-catalyzed RCM afforded tetracyclic compounds 94 and its transesterification product 93

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

• functionality strategy employing oxazoline to unmask the 1,2-hydroxyamine moiety proves feasible, eliminating the need for alkene functionalization required in previous endeavours. This current strategy provides a reliable platform for accessing diverse uracil nucleosides and their derivatives, facilitating the

• three contiguous stereogenic centers (Scheme 1A). The pyran ring was constructed by a RCM reaction [16]. Subsequent functionalization of the alkene to install the 1,2-cis-hydroxy amine required 6 steps from the sterically more demanding side. In continuing our recent interest in accessing unusual

• position. Therefore, dihydroxylation [37] readily converted alkene 11 to diol 12 as a mixture of inseparable isomers. Without purification, oxidative cleavage with NaIO4 resulted in a compound with strong UV absorption, which was eventually identified as enone 14 (Scheme 3). It is assumed that the

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

• leads to ketene D, which can undergo cycloaddition with an alkene to yield E. This fragmentation pathway dominates under various conditions (e.g., transition-metal catalysis, nucleophilic addition) and is driven by ring-strain release [11]. PET, an alternative to direct excitation and EnT, enables the

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

• , followed by diastereoselective α-alkylation, produced 38. A Wittig reaction and subsequent deketalization converted the ketone in 38 to the terminal alkene 39, allowing for subsequent sequential chemoselective hydrogenations: first, hydrogenation of the exo-olefin using Wilkinson’s catalyst proceeded with

• known two-step sequence to 61, followed by Mitsunobu reaction, ester reduction, thioether oxidation, and silylation of the primary alcohol to furnish sulfone 64. The two key fragments – aldehyde 60 and sulfone 64 – were merged via Julia–Kocienski olefination to construct alkene 65. Treatment of 65 with

• (C6F5)3B triggered a Meinwald rearrangement, generating aldehyde 66. Nucleophilic addition, oxidation of the resulting alcohol, and base-promoted epimerization at C6 of 67' delivered 67. Subsequent dihydroxylation of the alkene in 67 and protection of the resulting 1,2-diol as a cyclic carbonate

Halogenated butyrolactones from the biomass-derived synthon levoglucosenone

• Johannes Puschnig,
• Martyn Jevric and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2025, 21, 2297–2301, doi:10.3762/bjoc.21.175

• low, the synthesis of 7c via this method represents a substantial improvement on previous approaches to this material [24]. The Baeyer–Villiger oxidation of 7c was uneventful and the fluorinated alkene 17 was isolated in 50% yield. The α-trifluoromethylation of ketones and aldehydes can be performed

• cascade to give enone 21 in 42% yield. Baeyer–Villiger oxidation of this highly activated alkene promoted an epoxidation/Baeyer–Villiger oxidation cascade to yield lactone 22 in 67% yield (dr 2:1). The low diastereoselectivity suggested that the epoxidation happened subsequent to the ring contraction, as

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

• -trig cyclization and HAT furnished the enantioenriched products with up to 97:3 er. In addition to intramolecular radical reactions, intermolecular radical transformations have also been achieved using photoenzymatic catalysis, such as the addition of fluoroalkyl radicals to alkene substrates [36] and