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

• synthetic bottlenecks. Since Nobel laureate E. J. Corey proposed the revolutionary concept of “retrosynthetic analysis” [1], the design of synthetic strategies has built upon this core intellectual framework: starting from the target molecule, a stepwise deconstruction guided by reverse logic leads to a

• of established Deslongchamps and Reisman protocols then enabled the formal synthesis of ryanodol (4) in 22 steps. Zhao’s total synthesis of garajonone (8) and formal syntheses of ryanodol (4) and ryanodine (1) Traditional total synthesis strategies often follow a linear, stepwise approach – analogous

Effect of a photoswitchable rotaxane on membrane permeabilization across lipid compositions

• Udyogi N. K. Conthagamage,
• Lilia Lopez,
• Zuliah A. Abdulsalam and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2498–2512, doi:10.3762/bjoc.21.192

• the axle occurs in rotaxane 1, the dominant absorption of the azobenzene units ensures that most of the light energy is directed toward azobenzene photoisomerization. Additionally, their different release kinetics provide more insights: rotaxane 1 causes gradual, stepwise release beginning from the

Assembly strategy for thieno[3,2-b]thiophenes via a disulfide intermediate derived from 3-nitrothiophene-2,5-dicarboxylate

• Roman A. Irgashev

Beilstein J. Org. Chem. 2025, 21, 2489–2497, doi:10.3762/bjoc.21.191

• ). Herein, we wish to report a modified strategy based on route IV involving the stepwise construction of the TT framework. This approach is accomplished via the nucleophilic substitution of the nitro group with a S-nucleophile to obtain the thiophene-3-thiolate or its equivalent, followed by further S

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

• that the rate-determining step of the key PET reaction involved C19–C12 bond formation and C19–C3 bond cleavage. Investigation of the bond length changes along the IRC path, spin density, and NBO analysis indicated that this process is neither strictly concerted nor stepwise, but falls in between, and

• process IN2 → IN3 is neither strictly concerted nor stepwise [37][38]. This can be attributed to the inherent ring-strain release in the transient structure located on the PES and the hyperconjugative interaction between the N9 nonbonding p orbital and σ(C19–C3)* during geometrical distortions. This

• concerted nor stepwise. These findings shed light on the mechanistic innovation of a PET-initiated radical-derived reaction that was driven by the ring-strain release. Synthetic plan. a) General model of cyclobutenone bond cleavage; b) our previously reported method; c) plan for indole Aspidosperma alkaloid

An Fe(II)-catalyzed synthesis of spiro[indoline-3,2'-pyrrolidine] derivatives

• Elizaveta V. Gradova,
• Nikita A. Ozhegov,
• Roman O. Shcherbakov,
• Alexander G. Tkachenko,
• Larisa Y. Nesterova,
• Elena Y. Mendogralo and
• Maxim G. Uchuskin

Beilstein J. Org. Chem. 2025, 21, 2383–2388, doi:10.3762/bjoc.21.183

• e) [12]. The second category of synthetic methods relies on more accessible, non-pre-functionalized starting materials and stepwise assembly of the spirocyclic core. This strategy enables the synthesis of functionalized 3H-indoles, which can be further elaborated into structurally diverse products

Synthesis of triazolo- and tetrazolo-fused 1,4-benzodiazepines via one-pot Ugi–azide and Cu-free click reactions

• Xiaoming Ma,
• Zijie Gao,
• Jiawei Niu,
• Wentao Shao,
• Shenghu Yan,
• Sai Zhang and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 2202–2210, doi:10.3762/bjoc.21.167

• of compounds 6a (red) and 8a (blue). Ugi–azide reaction for the synthesis of 1,5-DS-T-containing heterocycles. Proposed Ugi–azide-initiated synthesis of polyheterocyclic scaffolds 7 and 8. 4-CR vs stepwise Ugi–azide reactions for the synthesis of 7a. Synthesis of benzodiazepines 7a–k. Reaction

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

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

• preference for inversion across several derivatives of 1 [77][78]. These studies suggest that the thermal denitrogenation of diazabicyclo[2.1.1]hep-2-ene undergoes a concerted mechanism of elimination of nitrogen, while the photochemical reaction proceeds via a stepwise mechanism. Quantum mechanical

• , and T2, conical intersections, transition structures, and singlet–triplet crossing were computed using CASSCF(10,8)/6-31G(d)//MP2/6-31G(d) [81]. The results suggested a stepwise C–N bond breaking with the formation of the diazenyl diradical intermediate [81]. In 2003, Olivucci and his co-workers

• the denitrogenation mechanism of 7,7‐diethoxy‐2,3‐diazabicyclo[2.2.1]hept‐2‐ene, showing that a stepwise C–N-bond cleavage is energetically favored using broken‐symmetry (BS)‐(U)CCSD/6‐31G(d) and suggested that an equatorial conformation of the diazinyl diradical leads to the formation of the inverted

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

• internal nucleophiles (Scheme 4), that could be used instead of the alcohol. The carboxylic acid-containing silane 7 (R = COOH), which was obtained by stepwise oxidation of the alcohol 7d, failed to give the desired lactone 8t product due to O-arylation of the carboxylic acid, leading to phenyl alkyl ester

[3 + 2] Cycloaddition of thioformylium methylide with various arylidene-azolones in the synthesis of 7-thia-3-azaspiro[4.4]nonan-4-ones

• Daniil I. Rudik,
• Irina V. Tiushina,
• Anatoly I. Sokolov,
• Alexander Yu. Smirnov,
• Alexander R. Romanenko,
• Alexander A. Korlyukov,
• Andrey A. Mikhaylov and
• Mikhail S. Baranov

Beilstein J. Org. Chem. 2025, 21, 1791–1798, doi:10.3762/bjoc.21.141

• thiohydantoin 7, on the contrary, have a trans configuration of two vicinal stereocenters (Scheme 3 and Figure 1). Thus, in all cases we have obtained, probably, the most thermodynamically favorable isomers. This result allows us to assume a stepwise mechanism of the ylide addition to the double bond of

• thiohydantoin derivatives, since the initial compounds 2 had a predominant Z-configuration. At the same time, for cases 1, 3 and 4, both a synchronous and stepwise mechanism are possible. The discovered stereochemistry of the reaction correlates well with the previously obtained data, when the most

Approaches to stereoselective 1,1'-glycosylation

• Daniele Zucchetta and
• Alla Zamyatina

Beilstein J. Org. Chem. 2025, 21, 1700–1718, doi:10.3762/bjoc.21.133

• thiol under UV irradiation using DPAP as a cleavable photoinitiator, which gave the thiodisaccharide 146 (Scheme 12) [116]. The success of these reactions was largely attributed to the use of acetic acid as a solvent in its frozen state (−80 °C), combined with stepwise UV exposure (3 × 60 min) at λmax

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

• ) of the butadiene + ethylene reaction proceeds with a lower barrier (up to 7 kcal/mol) than the corresponding stepwise pathway leading to a diradical intermediate (Scheme 1a) [19][20]. Similar preferences for concerted pathways over stepwise mechanisms were also found for dipolar cycloadditions and

• further support to the barrier-lowering effect induced by the aromaticity of the transition state. While the purported ‘‘aromatic stabilization’’ is mainly established based on comparisons to transition states of alternative stepwise reaction routes, its extension to highly related processes following

Ambident reactivity of enolizable 5-mercapto-1H-tetrazoles in trapping reactions with in situ-generated thiocarbonyl S-methanides derived from sterically crowded cycloaliphatic thioketones

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Marcin Palusiak,
• Heinz Heimgartner,
• Marta Denel-Bobrowska and
• Agnieszka B. Olejniczak

Beilstein J. Org. Chem. 2025, 21, 1508–1519, doi:10.3762/bjoc.21.113

• the in situ-generated thiocarbonyl S-methanides 1 (from 1,3,4-thiadiazolines 2) with enolizable 5-mercapto-1H-tetrazoles 4, leading to the N- or S-insertion products 9 and 10, respectively. Stepwise mechanism of the competitive N- and S-insertion reactions between the in situ-generated thiocarbonyl S

Highly distinguishable isomeric states of a tripodal arylazopyrazole derivative on graphite through electron/hole-induced switching at ambient conditions

• Himani Malik,
• Sudha Devi,
• Debapriya Gupta,
• Ankit Kumar Gaur,
• Sugumar Venkataramani and
• Thiruvancheril G. Gopakumar

Beilstein J. Org. Chem. 2025, 21, 1496–1507, doi:10.3762/bjoc.21.112

• ) A stepwise change in current is observed generally, indicating that the molecule can switch between any given state, or any order does not exist for the switching. (b) The molecule can be switched from the lowest current state to the highest current state (cf. time trace taken at 1.1 V) without any

Advances in nitrogen-containing helicenes: synthesis, chiroptical properties, and optoelectronic applications

• Meng Qiu,
• Jing Du,
• Nai-Te Yao,
• Xin-Yue Wang and
• Han-Yuan Gong

Beilstein J. Org. Chem. 2025, 21, 1422–1453, doi:10.3762/bjoc.21.106

• ), exceptionally high BCPL as 100.2 M−1 cm−1, and marked chiroptical activity (|gabs| = 2.50 × 10−3 at 435 nm; |glum| = 5.00 × 10−3 at 460 nm) (Table 6). Upon mild oxidation, neutral 22 undergoes stepwise conversion into highly charged, multispin open-shell species 222+2• and 224+4•, preserving strong chiroptical

• for NIR optoelectronic applications. Building on this work, in 2025 the same group reported the synthesis of a stable N-heterotriangulene dimer (compound 30) bridged by a rigid π-conjugated [5]helicene [44]. This chiral dimer undergoes reversible stepwise oxidation to 30•+ and 302+, accompanied by

• -width (FWHM values as 24 nm and 22 nm). Stepwise titration experiments with fluoride ions induced a change in the coordination number of the boron centers from three to four, forming corresponding anionic species. This coordination triggered red-shifted absorption and CPL responses while maintaining

Tautomerism and switching in 7-hydroxy-8-(azophenyl)quinoline and similar compounds

• Lidia Zaharieva,
• Vera Deneva,
• Fadhil S. Kamounah,
• Nikolay Vassilev,
• Ivan Angelov,
• Michael Pittelkow and
• Liudmil Antonov

Beilstein J. Org. Chem. 2025, 21, 1404–1421, doi:10.3762/bjoc.21.105

• ). Simulated absorption spectra of the tautomers of 1 in toluene. The spectra in acetonitrile are shown in Figure S1 in Supporting Information File 1. Normalized absorption spectra of 1. Absorption spectra of 1 in acetonitrile with stepwise addition of water. VT 1H NMR spectra of compound 1 in acetonitrile-d3

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

• substrate scope revealed that the reaction stereoselectivity is highly dependent on the structure of the ketoester component and tends to be unpredictable. 1.3.2 Formal cycloadditions: These stepwise processes typically take place between an enolate or enol ether and a carbonyl under Lewis acid or base

Recent advances in amidyl radical-mediated photocatalytic direct intermolecular hydrogen atom transfer

• Hao-Sen Wang,
• Lin Li,
• Xin Chen,
• Jian-Li Wu,
• Kai Sun,
• Xiao-Lan Chen,
• Ling-Bo Qu and
• Bing Yu

Beilstein J. Org. Chem. 2025, 21, 1306–1323, doi:10.3762/bjoc.21.100

• the photocatalyst [Ir(dF(CF3)ppy)2(4,4'-d(CF3)bpy)]PF6 in combination with a base (NBu4OP(O)(OBu)2) (Scheme 1) [59]. The generation of amidyl radical 5 involved a stepwise PCET process catalyzed by the combined effect, in the presence of photocatalyst and the base. Subsequently, amidyl radical 5

• these bonds through high selectivity, efficiency, and a stepwise approach. In the presence of amidyl radicals, hydrogen atoms are directly abstracted from C–H, Si–H, Ge–H, and B–H bonds, leading to the formation of corresponding radicals. We summarize and emphasize notable pioneering experiments in this

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

• synthetic strategy was used by Jiang and co-workers for the synthesis of very stable non-alternant nanographene with a triplet ground state [41]. Zhang and co-workers reported the synthesis of diazulenorubicene 29, a non-benzenoid isomer of peri-tetracene (Scheme 5) [42]. The stepwise oxidation of compound

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

Beyond symmetric self-assembly and effective molarity: unlocking functional enzyme mimics with robust organic cages

• Keith G. Andrews

Beilstein J. Org. Chem. 2025, 21, 421–443, doi:10.3762/bjoc.21.30

• ][344][345], which show early promise for low-symmetry cavities with catalytic potential [42][43][44][340]. Notably, Otte has used semi-stepwise self-assembly via imine formation/reduction to access a robust organic cage with reduced-symmetry and internal functionality able to chelate a copper(I) ion

• purification possibilities available for robust organic cages mean access to structural families via stepwise synthesis or statistical methods followed by separation is facile, as demonstrated by Otte [42][43][44] and ourselves [41]. The lack of internal functionality in cavities doesn’t just reduce the

The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

• in attaining the required stereospecific glycosylation outputs. Apart from the widely convenient stepwise synthesis, recently one-pot glycosylations have also made an important mark which minimise the tedious purification of the intermediate molecules in each step [53][54][55][56][57][58]. In the

Oxidation of [3]naphthylenes to cations and dications converts local paratropicity into global diatropicity

• Abel Cárdenas,
• Zexin Jin,
• Yong Ni,
• Jishan Wu,
• Yan Xia,
• Francisco Javier Ramírez and
• Juan Casado

Beilstein J. Org. Chem. 2025, 21, 277–285, doi:10.3762/bjoc.21.20

• theoretical Raman band at 1730 cm−1. FT-Raman spectra in CH2Cl2 (approx. 10−2 to 10−3 M) of: top) 1 (black), 1•+ (blue), and 12+ (red). Bottom) 2 (black), 2•+ (blue), and 22+ (red). Oxidations are carried out by stepwise addition of NOBF4 in CH2Cl2. Force constants for the CC stretching vibrational

Facile one-pot reduction of β-nitrostyrenes to phenethylamines using sodium borohydride and copper(II) chloride

• Laura D’Andrea and
• Simon Jademyr

Beilstein J. Org. Chem. 2025, 21, 39–46, doi:10.3762/bjoc.21.4

• reduction can be accomplished via catalytic hydrogenation, involving stepwise reactions and workup, use of additional reagents, and reaction time between 3 and 24 hours [11][12]. Most commonly, metal hydrides are employed, typically lithium aluminum hydride [13][14][15][16][17][18], requiring an inert

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• azadiene in a stepwise mechanism: firstly, the vinylogous Michael addition of the dienolate to the double bond of the α,β-unsaturated N-sulfonylimine occurs in a stereoselective fashion. Subsequently, cyclization due to an intramolecular aza-Michael reaction and protonation leads to the enantioenriched

• alcohol E isomer and it coordinated to the squaramide in an effective orientation, a stepwise mechanism is taking place. Firstly, the dienolate adds to the azadiene which is followed by cyclization with formation of the C–N bond. Finally, protonation leads to the formation of the desired derivative. The

• excellent enantioselectivities (70–95% ee) when using chiral phosphoric acid XIV (Scheme 16). Mechanistic studies were performed to unveil whether a concerted or stepwise mechanism is taking place, such as trying to trap a possible iminium ion intermediate. The outcome of those experiments pointed towards a