Base-promoted deacylation of 2-acetyl-2,5-dihydrothiophenes and their oxygen-mediated hydroxylation

• Vladimir G. Ilkin,
• Margarita Likhacheva,
• Igor V. Trushkov,
• Tetyana V. Beryozkina,
• Vera S. Berseneva,
• Vladimir T. Abaev,
• Wim Dehaen and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2026, 22, 192–204, doi:10.3762/bjoc.22.13

• oxidation of ketones includes C‒C-bond cleavage, and carboxylic acids are predominantly formed. This can be achieved by the treatment of acyclic ketones with hypohalites [13], in the nitroarene-catalyzed oxidation with oxygen under basic conditions [14] or by the use of hypervalent iodine compounds (Scheme

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

• was introduced via Fe-mediated HAT and sulfone cleavage. This 10-step asymmetric synthesis demonstrates that, in the case of indole monoterpene alkaloids, the rational application of aromatic ring hydrogenation can markedly reduce step count and enhance overall efficiency. Total synthesis of matrine

Advances in Zr-mediated radical transformations and applications to total synthesis

• Hiroshige Ogawa and
• Hugh Nakamura

Beilstein J. Org. Chem. 2026, 22, 71–87, doi:10.3762/bjoc.22.3

• molecules such as allose (23i) and cholesterol (23k), delivering the desired alcohols in good yields with excellent regioselectivity. The proposed mechanism is shown in Scheme 5C. Homolytic cleavage of the C–O bond in the epoxide generates a strong Zr–O bond, while the resulting alkyl radical abstracts a

• range of α-fluorocarbonyl substrates and olefins (Scheme 9B). In 2025, Ota and Yamaguchi et al. reported a zirconocene-mediated selective cleavage of C–O bonds (Scheme 10A) [35]. The authors had previously demonstrated regioselective ring-opening reactions of epoxides and oxetanes by exploiting the

• strong affinity of zirconium for oxygen atoms [4][21]. Building on this concept, they envisioned that a similar reaction system could be applied to the homolytic cleavage of C–O bonds in alcohols and ethers. When benzyl alcohol and ether derivatives 49 were treated with zirconocene in the presence of a

Sustainable electrochemical synthesis of aliphatic nitro-NNO-azoxy compounds employing ammonium dinitramide and their in vitro evaluation as potential nitric oxide donors and fungicides

• Alexander S. Budnikov,
• Nikita E. Leonov,
• Michael S. Klenov,
• Andrey A. Kulikov,
• Igor B. Krylov,
• Timofey A. Kudryashev,
• Aleksandr M. Churakov,
• Alexander O. Terent’ev and
• Vladimir A. Tartakovsky

Beilstein J. Org. Chem. 2025, 21, 2739–2754, doi:10.3762/bjoc.21.211

• 68% yield without cleavage of the acetonide protecting group. Note that compound 2f is not accessible using the known approach (see Scheme 1a), because the dioxane ring is opened during the nitration step. Surprisingly, nitro-NNO-azoxylation products 2g and 2h were obtained from methyl and ethyl 2

• further demonstrated by performing the model reaction on a 6 mmol scale of 1f (Scheme 3, reaction 1). The corresponding product 2f was obtained without any erosion of the yield (1.02 g, 4.08 mmol, 68%). The acidic cleavage of the acetonide group in 2f with AcCl in MeOH afforded diol 3f in a 94% yield

Total synthesis of asperdinones B, C, D, E and terezine D

• Ravi Devarajappa and
• Stephen Hanessian

Beilstein J. Org. Chem. 2025, 21, 2730–2738, doi:10.3762/bjoc.21.210

• (6) and ent-asperdinone E, now using an N-Boc protecting group (Scheme 8). Treatment of 3-iodoindole 39 with the iodozinc reagent prepared from N-Boc-ʟ-alanine methyl ester ((R)-35) under Negishi coupling conditions afforded 40 in excellent yield. Cleavage of the N-Boc group and amide formation with

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

• ][18][19]. The earlier publications provide an access to the ABCD-skeleton with a C-nor-D-homo motif through a diol cleavage (Malaprade reaction) and intramolecular aldol reaction to furnish the five-membered C-ring. The F-ring is later attached, first as a pyridine, which then gets hydrogenated to a

• sequence of redox manipulations and acetylation, olefin 90 was transformed into 3,18-diacetate 92. The degradation of the superfluous side chain was realized by acidic cleavage of the spiroketal moiety, followed by redox manipulations. A seven-step sequence afforded methyl ketone 93 [20]. The F-ring was

• C12,15-glycol 102. The glycol was subjected to periodate cleavage, which was followed by intramolecular aldol reaction to effect contraction of the C-ring. The observed regioselectivity was rationalized by steric influence of the C19-methyl group hindering deprotonation at C11. Thus, desired cyclization

Efficient solid-phase synthesis and structural characterization of segetalins A–H, J and K

• Liangyu Liu,
• Wanqiu Lu,
• Quanping Guo and
• Zhaoqing Xu

Beilstein J. Org. Chem. 2025, 21, 2612–2617, doi:10.3762/bjoc.21.202

• resin as the solid support, enabling mild cleavage of the partially protected linear peptide precursor [21]. Efficient Fmoc deprotection was achieved using a solution of 1% pyridine and 1% 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in N,N-dimethylformamide (DMF) [22]. For the assembly of the linear

• , successful macrocyclization was achieved by employing benzotriazol-1-yloxytripyrrolidinophosphonium hexafluorophosphate (PyBOP) as the coupling reagent in DMF at a concentration of 10−3 M. After cleavage from the resin and global side-chain deprotection, the crude cyclic peptides were purified by preparative

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

• cleavage and the new C–O bond formation process were achieved using NHC (10 mol %), a photocatalyst (2 mol %), and DABCO (1.5 equiv), providing the corresponding aryl salicylates 27 in moderate to good yields. Mechanistic studies support the oxidation of the Breslow intermediate by oxygen in the presence

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

• protected prior to the RCM step. Oxidative cleavage of the cyclopentene followed by Pinnick oxidation of the resulting aldehyde to the carboxylic acid and esterification yielded ketoester 56. Dieckmann condensation of 56, esterification of the resulting enolate with 57, and subsequent one-pot partial

• -mediated N–O bond cleavage afforded carbamate 90. The carbamate was converted to a carbonyl group via Boc deprotection with TFA, oxidation of the resulting amine to the oxime with Na2WO4 and H2O2, and subsequent reduction with TiCl3·HCl to give 91. The LaCl3·2LiCl-mediated methyl addition to the carbonyl

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

• pericyclic reactions [31][32][33][34][35][36][37][38][39][40][41][42][43][44], to control the formation of the crucial C5 chiral center precisely. Subsequent oxidative cleavage of the carbon–carbon double bond introduced in the Diels–Alder reaction, followed by an intramolecular aldol reaction, efficiently

• natural product. Similarly, starting from 57, installation of an allyl group at C2, followed by oxidative cleavage, reduction, and deprotection, provided cinncassiol B (7). Subjecting this compound to an acid-promoted fragmentation reaction then completed the total synthesis of cinncassiol A (9

• route commenced from (−)-pulegone. After introducing oxidation states at C6 and C10 and installing an alkynyl group at C11, oxidative cleavage of a double bond yielded the key propargylic alcohol intermediate 66. This compound underwent a 1,2-addition with alkynyl Grignard reagent 67, and the resulting

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

• is secured from the commercial source. Results and Discussion Based on the known protocol [33], diacetone-ᴅ-allofuranose 8 was first introduced with a propargyl group (Scheme 2A). Upon treatment of AcOH to afford diol 9, oxidative cleavage with Shing’s protocol (NaIO4 on silica gel) [34] proceeded

• 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

Isoorotamide-based peptide nucleic acid nucleobases with extended linkers aimed at distal base recognition of adenosine in double helical RNA

• Grant D. Walby,
• Brandon R. Tessier,
• Tristan L. Mabee,
• Jennah M. Hoke,
• Hallie M. Bleam,
• Angelina Giglio-Tos,
• Emily E. Harding,
• Vladislavs Baskevics,
• Martins Katkevics,
• Eriks Rozners and
• James A. MacKay

Beilstein J. Org. Chem. 2025, 21, 2513–2523, doi:10.3762/bjoc.21.193

• conditions to afford carboxylic acid 19 in 65% yield, followed by coupling with the PNA benzyl backbone 12 [38] to provide ester 20 in 54% yield. The final Db3 monomer 21 was obtained in 90% yield through benzyl cleavage using the standard hydrogenolysis conditions, similar to previous monomers. PNA

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

• ]. In route IV, cleavage of the ethyl xanthate group in the starting substrate by NaOMe generates a thiolate intermediate, which undergoes S-alkylation and subsequent NaOMe-promoted cyclization to afford the 3-hydroxy-TT [28]. In our recent works, it was presented an effective strategy for synthesizing

• reaction conditions to release thiolate species capable of reacting separately with ester 1 to form compound 2. Disulfide 3 was found to be an accessible and stable precursor of dimethyl 3-mercaptothiophene-2,5-dicarboxylate, a molecule that is suitable for S-alkylation. In this regard, reductive cleavage

• cleavage of the S–S bond and the subsequent S-alkylation reaction were successful. To suppress the side reaction and improve reduction efficiency, we next employed DMF as a polar aprotic solvent. In Table 2, entry 4, reduction of disulfide 3 in DMF at 75 °C with NaBH4 was complete within 15 min. The excess

Palladium-catalyzed regioselective C1-selective nitration of carbazoles

• Vikash Kumar,
• Jyothis Dharaniyedath,
• Aiswarya T P,
• Sk Ariyan,
• Chitrothu Venkatesh and
• Parthasarathy Gandeepan

Beilstein J. Org. Chem. 2025, 21, 2479–2488, doi:10.3762/bjoc.21.190

• after 2 hours, indicating that C–H bond cleavage is kinetically relevant and likely involved in the rate-determining step (Scheme 5b). To gain additional mechanistic insight, we synthesized palladacycle intermediate 6 following the reported procedure [58]. Then, the reaction was carried out using

• ][78][79][80], a plausible catalytic cycle is proposed (Figure 2). The catalytic cycle commences with the formation of active palladium(II) species 7 in the presence of AgNO3. Coordination of the pyridyl group of 1a to Pd(NO₃)₂ is followed by irreversible C–H bond cleavage via cyclopalladation to form

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

• photoredox catalysis) processes [8][9][10]. Cyclobutenone (A) is a versatile C4 synthon [11] – its [2 + 2] photocyclization yields B, featuring a strained bicyclo[2.2.0]hexane unit [12], which can fragment to form C (Figure 1a) [13][14]. However, competitive C1–C4 bond cleavage under irradiation or heating

• current interest in the synthesis of complex natural products via photochemical reactions, we decided to achieve such an unusual bond cleavage (Figure 1a, path A) of cyclobutenone by generating a radical cation species via a PET reaction. The synthetic plan is shown in Figure 1c and includes a PET

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

• contraction of six-membered cycles in the synthesis of functionalized cyclopentane/enones, which are biologically active compounds. The main synthetic methods of ring contraction (ozonolysis–aldol condensation, ozonolysis–Dieckmann reaction, Baeyer–Villiger cleavage–Dieckmann reaction) and rearrangements

• cyclohexane/ene ring contraction. The structure of the review includes examples of simple transformations (ozonolysis–aldol condensation, ozonolysis–Dieckmann reaction, and Baeyer–Villiger cleavage–Dieckmann reaction) and rearrangements (photochemical, benzil, semi-pinacol, Wolff, Meinwald, Wagner–Meerwein

• and Favorskii reaction), using oxidants based on thallium and iodine, with a focus on recent works published in the period from 2014 to 2024. Review 1 Recyclization A common method for converting cyclohexene 1 into cyclopentene 2 is the ozonolytic cleavage of the double bond followed by intramolecular

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

• bond cleavage to generate an N-imidoyl radical intermediate that undergoes intramolecular cyclization to yield the spirocyclic product (Scheme 1, path g) [14]. Notably, iron is known to exhibit similar behavior in single-electron transfer (SET) processes [15][16][17]. In fact, we previously

• pathway (Scheme 4). Initial Fe(II)-mediated reductive cleavage of the N–O bond in the ketoxime acetate generates an iminyl radical. This is followed by a 5-exo-trig cyclization to form a carbon-centered radical. Final single-electron oxidation by Fe(III) delivers the desired spirocyclic product. All

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

• TMSN3 recently developed by Xu and co-workers [34]. Mukaiyama conjugate addition between 60 and 61 promoted by Tf2NH followed by a one-pot enol ether hydrolysis gave 62 as a mixture of inconsequential stereoisomers. Subsequent oxidative cleavage of the terminal olefin of 62 using ozonolysis followed by

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

• Norrish–Yang cyclization, followed by a strain-release Pd-catalyzed C–C cleavage/cross-coupling protocol [9][11]; the strategy was subsequently applied to the total synthesis of lycoplatyrine A (89) in 2021 [38]. Isolated by Low’s group [39], lycoplatyrine A (89) belongs to the lycodine-type Lycopodium

• to construct a β-lactam, an α-metallated piperidine equivalent, overcoming poor yields and stereoselectivity in traditional methods. Its palladium-catalyzed cross-coupling with 2-bromolycodine via β-lactam C–C cleavage enabled stereoretentive coupling, efficiently synthesizing lycoplatyrine A and its

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

• has been largely supplanted by greener methods employing less-toxic reagents. Using alternative methods, radicals can be generated by hydrogen atom transfer (HAT), resulting in the homolytic cleavage of a carbon–hydrogen bond. Other approaches for radical generation in modern radical transformations

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

• cleavage to form the boronated phenanthrene framework 170. It is worth mentioning that a unique skeleton rearrangement, supported by DFT calculations, was proposed in this work, which was unprecedented in BiCl3-promoted cyclization. Conclusion This comprehensive review has systematically delineated the

A chiral LC–MS strategy for stereochemical assignment of natural products sharing a 3-methylpent-4-en-2-ol moiety in their terminal structures

• Rei Suo,
• Raku Irie,
• Hinako Nakayama,
• Yuta Ishimaru,
• Yuya Akama,
• Masato Oikawa and
• Shiro Itoi

Beilstein J. Org. Chem. 2025, 21, 2243–2249, doi:10.3762/bjoc.21.171

• Discussion Our degradation strategy of natural products bearing an MPO moiety includes (1) acylation of hydroxy group, (2) oxidative cleavage of olefin to generate 3-acyloxy-2-methylbutanoic acid, and (3) its methyl esterification (Scheme 1A). We initially investigated derivatization strategies to enable LC

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

• occurred to give a radical cation PhSeSePh•+ at the anode. The subsequent cleavage of Se–Se bond formed a radical PhSe• and a cation PhSe+. Further additional oxidation of PhSe• yielded another PhSe+, which worked as the major reactive species and quickly added to C≡C in 13a to form intermediate A. Finally

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

• hydrogenation to produce furfuryl alcohol. This latter is a versatile intermediate for the production of resins, coatings, polymers and used as a solvent. It can also be converted into other chemicals through oxidative cleavage, over-reduction and etherification (Scheme 49) [177]. Zhang et al. reported the use

• of the system in favor of meta isomer. Acidic cleavage followed by reductive amination afforded m-xylylenediamine (Scheme 54). Tetrahydrofuran-derived amines were prepared from furfural via a one-pot two-step reaction. The condensation of furfural with ketones over Amberlyst-26 as catalyst produced

The application of desymmetric enantioselective reduction of cyclic 1,3-dicarbonyl compounds in the total synthesis of terpenoid and alkaloid natural products

• Dong-Xing Tan and
• Fu-She Han

Beilstein J. Org. Chem. 2025, 21, 2085–2102, doi:10.3762/bjoc.21.164

• group [35][36][37]. This catalytic system efficiently overcame the challenge and furnished the coupling product 46 in high yield. Oxidative cleavage of the double bond in 46 followed by Mg(II)-mediated chelation-controlled Friedel–Crafts cyclization delivered secondary alcohol 47, which was elaborated

• intramolecular Diels–Alder reaction generated tricyclo[3.2.1.02,7]-octene 113. A two-step transformation including HAT hydrogenation and acetal C–H oxidation with RuCl3/NaIO4, 113 was converted into ketoester 114. The TFA-mediated C13–C15 bond cleavage of 114 proceed smoothly to give ring-opening products, which