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

• arylcyclopropanes 5 by applying NHC/ photoredox cooperative organocatalysis under visible-light irradiation. This method allows sequential C–O and C–C bond formation, leading to access to various γ-aroyloxy keto-ester derivatives 6 in good yield up to 81% and excellent functional group tolerance, including electron

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

• , particularly iridoids. One of the promising methods for ring contraction in the absence of multiple bonds in the six-membered ring of terpenoids was proposed by Grishko et al. [26] (Scheme 6). The key step of 2,3-fragmentation was the cleavage of an enolized C–C bond at a keto group, followed by an

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

• hemiaminal opening and amine–ketone condensation, iminium ion 65 was produced for the next pyrrole nucleophilic addition to form a strategically important C–C bond and afford 66, which was protected as Boc carbamate in the same pot to give 67 in 96% yield from 64. In this tandem sequence, the nucleophilicity

• of the electron-rich pyrrole group is essential for the key C–C bond formation. In the next step, the pyrrole group was converted to the pyridine group encoded by the natural product. This single-atom skeletal editing step (67 → 68) was achieved using the Ciamician–Dennstedt rearrangement, a reaction

• synthesis, they used an electron-rich and nucleophilic pyrrole as the precursor of the electron-deficient pyridine to enable a tandem sequence involving an intramolecular nucleophilic addition of the pyrrole to an iminium ion to form a key C–C bond. The pyrrole group was then converted to the desired

Pathway economy in cyclization of 1,n-enynes

• Hezhen Han,
• Wenjie Mao,
• Bin Lin,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2025, 21, 2260–2282, doi:10.3762/bjoc.21.173

• 60 °C initiated nickel-mediated intramolecular [2 + 2] cycloaddition to form dihydrocyclobuta[c]quinolin-3-one framework 164. Conversely, when the temperature was elevated to 140 °C, thermal ring-expansion of the four-membered intermediate was induced through C–C bond cleavage/reorganization

Thiadiazino-indole, thiadiazino-carbazole and benzothiadiazino-carbazole dioxides: synthesis, physicochemical and early ADME characterization of representatives of new tri-, tetra- and pentacyclic ring systems and their intermediates

• Gyöngyvér Pusztai,
• László Poszávácz,
• Anna Vincze,
• András Marton,
• Ahmed Qasim Abdulhussein,
• Judit Halász,
• András Dancsó,
• Gyula Simig,
• György Tibor Balogh and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2220–2233, doi:10.3762/bjoc.21.169

• derivatives 10a,b exhibiting an extended aromatic ring system were isolated instead of the expected primarily formed congeners 11a,b, due to in situ oxidation of the C–C bond. Alternatively, when the one-pot method (method B, bismuth nitrate pentahydrate + PPA, MeOH, closed vial, 110 °C) was applied for the

Electrochemical cyclization of alkynes to construct five-membered nitrogen-heterocyclic rings

• Lifen Peng,
• Ting Wang,
• Zhiwen Yuan,
• Bin Li,
• Zilong Tang,
• Xirong Liu,
• Hui Li,
• Guofang Jiang,
• Chunling Zeng,
• Henry N. C. Wong and
• Xiao-Shui Peng

Beilstein J. Org. Chem. 2025, 21, 2173–2201, doi:10.3762/bjoc.21.166

• , A proceeded an intramolecular nucleophilic attack by N and deprotonation to finish 15a. The other possible pathway was radical route, in which PhSe• dimerized to reform 14a or added to C≡C bond in 13a to afford B. The subsequent anodic oxidation of B gave C, which underwent nucleophilic cyclization

• -exo-dig N-radical addition into the C≡C bond to generate the cyclic species C. The radical anion D was then obtained via single electron reduction of C at the cathode. The subsequent protonation of D gave α-aminyl radical E [215][216][217], which was converted into the anion F by further cathodic

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

• -proline as a catalyst (Scheme 25) [100]. The C–C-bond formation between biomass-based feedstock by aldol condensation reactions of furfural with 1-hydroxyacetone has been reported by Subrahmanyam and co-workers (Scheme 26) [101]. C4 biobased carbonyl platforms Acetoin Acetoin is a very important C4

Bioinspired total syntheses of natural products: a personal adventure

• Zhengyi Qin,
• Yuting Yang,
• Nuran Yan,
• Xinyu Liang,
• Zhiyu Zhang,
• Yaxuan Duan,
• Huilin Li and
• Xuegong She

Beilstein J. Org. Chem. 2025, 21, 2048–2061, doi:10.3762/bjoc.21.160

• propose the biosynthetic pathway, which has not yet been reported in Duh’s isolation report (Scheme 1a). In our proposal, the linear sesquiterpenoid trans-nerolidol (1) with a chiral tertiary alcohol undergoes dihydroxylation to generate triol 2, which further proceeds a C–C bond cleavage to afford

• evidences of chemical transformations. Thus, a bioinspired total synthesis was investigated (Scheme 1b). Synthetically, we did not start from trans-nerolidol (1) to construct a C–C bond cleavage. Instead, a convergent coupling approach was selected to quickly access the aldehyde precursor. Phenyl sulfide 5

• as a single isomer, which further underwent a migratory rearrangement and afforded iboluteine. On the other hand, oxidation of ibogaine with molecular iodine achieved both indole and amine oxidations, delivering lactam 35. Intermediate 35 could be oxidized with H2O2 through C–C bond cleavage to give

Understanding the origin of stereoselectivity in the photochemical denitrogenation of 2,3-diazabicyclo[2.2.1]heptene and its derivatives with non-adiabatic molecular dynamics

• Leticia A. Gomes and
• Steven A. Lopez

Beilstein J. Org. Chem. 2025, 21, 2007–2020, doi:10.3762/bjoc.21.156

• calculations have provided valuable insights into the photochemical stereoselectivities of cyclic azoalkenes. In 1998, Yamamoto and co-workers investigated the reaction paths for α-C–N and β-C–C bond cleavage during the direct and sensitized photolysis of DBH [81]. The minimum energy geometries in S0, S1, T1

• with the experimentally observed preferred product. Notably, all trajectories leading to retained housane passed through a region characterized by dihedral angles exceeding 110°, corresponding to the inverted housane if the C–C bond is formed and to the inverted diradical if it is not. This observation

• with CASSCF (8,9)/ANO-S-VDZP, monitoring C–C-bond formation, H–C–C–C dihedral angle, and relative energy for 1 (b), 3 (c), and 5 (d). The energy is relative to the lowest total energy of each trajectory. The red trajectories return to reactant, the green trajectories form retained housane, the blue

Aryl iodane-induced cascade arylation–1,2-silyl shift–heterocyclization of propargylsilanes under copper catalysis

• Rasma Kroņkalne,
• Rūdolfs Beļaunieks,
• Armands Sebris,
• Anatoly Mishnev and
• Māris Turks

Beilstein J. Org. Chem. 2025, 21, 1984–1994, doi:10.3762/bjoc.21.154

• derivatives 9a–c. We observed a distinct preference for (E)-geometry formation in the resulting C=C bond. Internal alcohol, ester, and acylamide functional groups were found to be compatible with the reaction conditions, whereas for external nucleophiles N- or O-arylation precedes that of the alkyne. In the

Asymmetric total synthesis of tricyclic prostaglandin D2 metabolite methyl ester via oxidative radical cyclization

• Miao Xiao,
• Liuyang Pu,
• Qiaoli Shang,
• Lei Zhu and
• Jun Huang

Beilstein J. Org. Chem. 2025, 21, 1964–1972, doi:10.3762/bjoc.21.152

• a single diastereomer (Table 1, entry 4). To explain this diastereoselectivity, we hypothesize that the C–O bond, which occupies an axial position in the proposed transition state TS-1, could avert an additional hyperconjugative interaction (σ*C-O/π) that renders the reacting C=C bond electron

Synthesis of N-doped chiral macrocycles by regioselective palladium-catalyzed arylation

• Shuhai Qiu and
• Junzhi Liu

Beilstein J. Org. Chem. 2025, 21, 1917–1923, doi:10.3762/bjoc.21.149

• % and 90%, respectively. For MC2, four C–C bonds are formed between the dichlorobenzene units and tert-butylphenyl groups, generating two dihydroindolo[2,3-b]carbazole subunits. In contrast, there is only one newly formed C–C bond between the dichlorobenzene unit and one pyrene moiety for MC1

Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

• already known as dye [89] have only been studied very recently. Exchanging the C=C bond for a C=N bond gives a new subclass of extremely short-lived T-type photoswitches with visible light activation, thermal half-lives in the µs range, and very large spectral separation. The study of iminothioindoxyl

• . Strongly electron-withdrawing groups can weaken the photogenerated C–C bond, thus making the diarylethene thermally unstable, as in the case of c-126b and c-126c (Figure 22) [128][129]. Moreover, electron-withdrawing groups were also found to improve the fatigue resistance by avoiding the irreversible

Fe-catalyzed efficient synthesis of 2,4- and 4-substituted quinolines via C(sp²)–C(sp²) bond scission of styrenes

• Prafull A. Jagtap,
• Manish M. Petkar,
• Vaishnavi R. Sawant and
• Bhalchandra M. Bhanage

Beilstein J. Org. Chem. 2025, 21, 1799–1807, doi:10.3762/bjoc.21.142

• employed an I2/DMSO-facilitated C–C bond-scission strategy of styrenes, followed by C–N bond formation and subsequent [4 + 2] annulation. Jiang and co-workers developed a method for synthesizing 4-substituted quinolines using vinyl azides as dual synthons, facilitating both the C–C and C–N bond cleavage

• during GC–MS analysis) and formaldehyde (2a′′) via C–C bond scission of styrene in the presence of FeIII/O2, possibly through a 1,2-addition of O2 to styrene [49][58][59][60]. This in-situ generated aldehyde species then undergoes condensation with the amine 1a, leading to the formation of the

• the FeIII species. An alternative mechanism involving a concerted [4 + 2] cycloaddition between the aza-butadiene moiety in II and the alkene, leading to intermediate IV, cannot be ruled out. Conclusion In summary, we have successfully developed a highly efficient method for the oxidative C–C bond

Formal synthesis of a selective estrogen receptor modulator with tetrahydrofluorenone structure using [3 + 2 + 1] cycloaddition of yne-vinylcyclopropanes and CO

• Jing Zhang,
• Guanyu Zhang,
• Hongxi Bai and
• Zhi-Xiang Yu

Beilstein J. Org. Chem. 2025, 21, 1639–1644, doi:10.3762/bjoc.21.127

• not known). A hydrogenation reaction to reduce the C=C bond in 11 was then successfully applied, delivering product 12 in 80% yield (5 mol % RhCl(PPh3)3 catalyst and 1 atm hydrogen atmosphere were used). Next, we tested whether Krapcho decarboxylation reaction can convert 12 into 1 in one step

Transition-state aromaticity and its relationship with reactivity in pericyclic reactions

• Israel Fernández

Beilstein J. Org. Chem. 2025, 21, 1613–1626, doi:10.3762/bjoc.21.125

• deformed reactants along the reaction coordinate, defined in this case by the shortest C···C bond-forming distance. From the data in Figure 2a, which shows the computed activation strain diagrams (ASDs) for the uncatalyzed and AlCl3-catalyzed reactions from the beginning of the process up to the respective

• between isoprene and methyl acrylate (black lines) and the analogous process catalyzed by AlCl3 (red lines) and projected onto the C···C bond-forming distance. (a) Evolution of the NICS(3, +1) values along a z-axis perpendicular to the molecular plane of the TS involved in the 1-butene and acetaldehyde

• acetaldehyde (black lines) and the analogous process catalyzed by AlCl3 (red lines) and projected onto the C···C bond-forming distance. AICD (a) and EDDB (b) plots for the transition state involved in the DGRT between ethene and ethane. Comparative activation strain analyses (a) and energy decomposition

3-Aryl-2H-azirines as annulation reagents in the Ni(II)-catalyzed synthesis of 1H-benzo[4,5]thieno[3,2-b]pyrroles

• Julia I. Pavlenko,
• Pavel A. Sakharov,
• Anastasiya V. Agafonova,
• Derenik A. Isadzhanyan,
• Alexander F. Khlebnikov and
• Mikhail S. Novikov

Beilstein J. Org. Chem. 2025, 21, 1595–1602, doi:10.3762/bjoc.21.123

• formation of the C–C bond between the rings of the reacting molecules occurs in the coordination metal sphere as an intra-, rather than intermolecular, process. The formation of compound 17, the product of oxidative dimerization of indole-based enol 15, in the second reaction also points to different

pH-Controlled isomerization kinetics of ortho-disubstituted benzamidines: E/Z isomerism and axial chirality

• Ryota Kimura,
• Satoshi Ichikawa and
• Akira Katsuyama

Beilstein J. Org. Chem. 2025, 21, 1568–1576, doi:10.3762/bjoc.21.120

• rotational barrier (132 kJ·mol−1), suggesting that the protonation suppresses the C–N bond rotation via the increased double-bond nature of the C–N axis. A similar trend was found for the C–N/C–C concerted rotation (Figure 2). Compared with the C–N bond rotation, the C–N/C–C bond rotation requires a higher

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• categorised into 6 synthetic strategies as depicted in Scheme 1: a) C–O bond-forming cyclisations, b) C–C bond-forming cyclisations, c) [2 + 2] cycloadditions between carbonyls and alkenes, d) ring expansions, e) ring contractions and f) O–H insertions. In the following subchapters, these strategies will be

• -mediated intramolecular cross-couplings, 2-alkylideneoxetanes can also be accessed by formal [2 + 2] cycloadditions, which are discussed in chapter 1.3.2. 1.2 C–C Bond-forming cyclisations This relatively uncommon strategy is usually based on an ionic mechanism in which an SN2 substitution takes place

• comprehensive work by Volochnyuk and Ryabukhin et al. who analysed the oxetane core tolerance towards various reaction conditions such as oxidations, reductions, alkylations or C–C bond formations [83]. Since the general recognition of 3-oxetanone as the principal building block, a large number of new

Recent advances and future challenges in the bottom-up synthesis of azulene-embedded nanographenes

• Bartłomiej Pigulski

Beilstein J. Org. Chem. 2025, 21, 1272–1305, doi:10.3762/bjoc.21.99

• construction of the azulene moiety in the final step by creation of new C–C bond(s) or oxidation of a partially saturated precursor (Figure 3a); 2) The use of precursors that already contain the azulene moiety or moieties, which are then annulated into fully fused PAHs in the final step (Figure 3b). Obviously

• does not exhibit biradical character. Instead, heptagons and pentagons are primarily non-aromatic, with a localized double C=C bond in the seven-membered ring, giving compound 29 predominantly benzenoid properties. Interestingly, PAH 29 undergoes single or double bromination with NBS in a mixture of

Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

• radical A. This is followed by the conversion of a substrate containing C(sp3)–H bonds adjacent to an oxygen atom into an alkyl radical intermediate B. The alkyl radical intermediate then adds to the C=C bond of N-arylacrylamide, generating a second alkyl radical intermediate C, which undergoes

• -transfer (SET) process occurred efficiently under blue LED irradiation in the presence of Ir[dF(CF3)ppy]2(dtbbpy)PF6 as the photocatalyst. This was followed by deprotonation and radical migration, yielding α-aminoalkyl radical A, which added to the intramolecular C=C bond of N,N-dimethylaniline to produce

• the starting material 28 to yield an alkyl radical intermediate 31. This radical undergoes C=C-bond addition, cyclization, and deprotonation, ultimately leading to the formation of the desired products. Simultaneously, MeOH is reduced at the cathode to release H2, maintaining the electronic balance of

Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

• based on C–C bond activations have been explored. For instance, Ravikumar and co-workers (2021) employed diphenylcyclopropenone (309) to synthesize the corresponding esters 310–313 and amides 314 and 315. The reaction was catalyzed by Pd/N-heterocyclic carbene via oxidative Pd insertion into the C–C

• bond of cyclopropenone to give a cyclic intermediate 316 (Scheme 74A) [125]. On the other hand, Wu and co-workers (2022) developed a Pd-catalyzed selective ring-opening of cyclopropenones and vinyl epoxide 318 to give the corresponding esters 319–321 in good yields via a π–allyl palladium intermediate

Pd-Catalyzed asymmetric allylic amination with isatin using a P,olefin-type chiral ligand with C–N bond axial chirality

• Natsume Akimoto,
• Kaho Takaya,
• Yoshio Kasashima,
• Kohei Watanabe,
• Yasushi Yoshida and
• Takashi Mino

Beilstein J. Org. Chem. 2025, 21, 1018–1023, doi:10.3762/bjoc.21.83

• ligands with axial chirality for Pd-catalyzed asymmetric allylic substitution reactions. For example, the Zhou group reported a P,olefin-type chiral ligand 3 with C–C bond axial chirality for this reaction (Figure 2) [27]. Additionally, we have recently reported chiral ligands with C–N bond axial

Studies on the syntheses of β-carboline alkaloids brevicarine and brevicolline

• Benedek Batizi,
• Patrik Pollák,
• András Dancsó,
• Péter Keglevich,
• Gyula Simig,
• Balázs Volk and
• Mátyás Milen

Beilstein J. Org. Chem. 2025, 21, 955–963, doi:10.3762/bjoc.21.79

• , versatile key triflate intermediate 3, which allowed the introduction of substituents attached by a C–C bond to position 4 of the β-carboline scaffold by cross-coupling reactions. Sonogashira reaction of compound 3 with N-(3-butynyl)phthalimide (4) led to coupled compound 5. Cleavage of the phthalimide

Origami with small molecules: exploiting the C–F bond as a conformational tool

• Patrick Ryan,
• Ramsha Iftikhar and
• Luke Hunter

Beilstein J. Org. Chem. 2025, 21, 680–716, doi:10.3762/bjoc.21.54

• concepts to their own scaffolds of interest. Review 1 Alkanes The simplest organic scaffolds are the alkanes. In such molecules, C–C bond rotations often have low energy barriers, and they often deliver conformers that are similar in energy, and this means that many alkanes have considerable conformational