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 corresponding free acids or sodium salts [15][46][47][48]. According to Figure 3, each diaryl phosphate was isolated with a yield of approximately 60%, except for some derivatives. It was presumed that 2-hydroxy-m-xylol (1c) having methyl groups at the ortho-positions, led to a diminished yield of

Screwing the helical chirality through terminal peri-functionalization

• Devesh Chandra,
• Sachin and
• Upendra Sharma

Beilstein J. Org. Chem. 2026, 22, 205–212, doi:10.3762/bjoc.22.14

• , biosensors and other forms of the materials sciences continuing its relevance to cutting edge research [1][2]. However, precise control and manipulation of helical chirality in synthetic systems remain technically challenging. This complexity may have led to underestimation of its potential, as research

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

• led to the intermediate A. Elimination of ethyl/methyl acetate from intermediate A afforded anion B. The latter reacted in ethanolic solution with molecular oxygen [52] with the formation of peroxide anion C. The protonation of anion C with proton sources (residual water or/and solvent or 3a can serve

A new synthesis of Tyrian purple (6,6’-dibromoindigo) and its corresponding sulfonate salts

• Holly Helmers,
• Mark Horton,
• Julie Concepcion,
• Jeffrey Bjorklund and
• Nicholas C. Boaz

Beilstein J. Org. Chem. 2026, 22, 167–174, doi:10.3762/bjoc.22.10

• reaction step of this strategy was done with commercially available 3. As shown in Scheme 4A, reaction of 3 with N-bromosuccinimide (NBS) and azobisisobutyronitrile (AIBN) in acetonitrile, as previously described, led to benzylic bromination, but in inconsistent yields [20][21]. Use of 1,3-dibromo-5,5

• -dimethylhydantoin (DBDMH) as an alternative bromine source led to more consistent yields (57%) of the desired benzyl bromide (Scheme 4B). Systematic variation of the stoichiometric amount of DBDMH indicated that the yield of 4-bromo-2-nitrobenzylbromide (6) was optimized using 0.6 equiv or 1.2 equiv of available

Circumventing Mukaiyama oxidation: selective S–O bond formation via sulfenamide–alcohol coupling

• Guoling Huang,
• Huarui Zhu,
• Shuting Zhou,
• Wanlin Zheng,
• Fangpeng Liang,
• Zhibo Zhao,
• Yifei Chen and
• Xunbo Lu

Beilstein J. Org. Chem. 2026, 22, 158–166, doi:10.3762/bjoc.22.9

• , we selected the reaction between model sulfenamide 1a and methanol (2a) as the benchmark system (Table 1). Initial attempts in the absence of base led to only trace product formation (Table 1, entry 1), highlighting the essential role of a base in facilitating the transformation. Among several bases

• , decreasing the loading of NaHCO3 to 1.2 equiv resulted in a noticeably lower yield of 3a (83%, Table 1, entry 8), underscoring the importance of using a sufficient amount of base. We next examined the effect of different oxidants. While NBS was optimal, yielding 3a in 99%, the use of NCS or TCCA led to

• employed in an attempt to access the bis-substituted product. However, these more forcing conditions led to complex mixtures and only modest isolated yield of the monosubstituted product. In contrast, when the equivalents of the alcohol, NBS, and NaHCO3 were reduced (conditions e), the reaction proceeded

Asymmetric Mannich reaction of aromatic imines with malonates in the presence of multifunctional catalysts

• Kadri Kriis,
• Harry Martõnov,
• Annette Miller,
• Mia Peterson,
• Ivar Järving and
• Tõnis Kanger

Beilstein J. Org. Chem. 2026, 22, 151–157, doi:10.3762/bjoc.22.8

• led to the use of multifunctional catalysts of “homocooperativity,” where multiple units of the same catalyst perform different but complementary roles [17]. These catalysts employing noncovalent interactions via hydrogen bonds and also possess Lewis basic and π–π-interaction sites have been highly

• (Table 2, entry 2). Substituting a sterically demanding iodine atom in the phenyl ring with the methyl group (catalyst K-Me) increased the stereoselectivity (Table 2, entry 3, 56% ee). However, the N-methylated catalyst led to a diminished reaction rate and exhibited complete loss of selectivity

Design and synthesis of an axially chiral platinum(II) complex and its CPL properties in PMMA matrix

• Daiki Tauchi,
• Sota Ogura,
• Misa Sakura,
• Kazunori Tsubaki and
• Masashi Hasegawa

Beilstein J. Org. Chem. 2026, 22, 143–150, doi:10.3762/bjoc.22.7

• of 300 nm. Fluorescence lifetimes were measured for solutions and powder samples with a HORIBA DeltaFlex spectrometer with a 370 nm LED light source for excitation. For the lifetime measurements of solution, a conventional 1 cm quartz cell was used. Optical rotation values were measured with a JASCO

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

• , including hydroxylation of aryl halide, partial lactam reduction with cyanide trapping, and oxidation of the phenol, enabled the total synthesis of jorunnamycin A in 15 steps. The acetylation of the hydroxy group in jorunnamycin A followed by cyano hydrolysis led to the total synthesis of another natural

• functional group manipulations, including a pivotal intramolecular SN2 cyclization, ultimately completing the total synthesis of (−)-senepodine F. Notably, this work also led to the structural revision of the originally assigned natural product, as reported in earlier isolation studies. Hydrogenation

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

• regioselectivity. In a related study, Ota and Yamaguchi et al. reported the regioselective ring-opening of oxetanes using zirconocene catalysis (Scheme 6) [21]. Treatment of oxetane 27 with zirconocene in the presence of an Ir-photoredox catalyst led to ring opening via the less substituted radical intermediate

• . Heating these precursors under flash vacuum pyrolysis conditions at 230 °C led to the removal of the Boc group and intramolecular dehydration–condensation, thereby constructing the diketopiperazine core and enabling the total syntheses of ditryptophenaline (70), dibrevianamide F (71), and tetratryptomycin

Reactivity umpolung of the cycloheptatriene core in hexa(methoxycarbonyl)cycloheptatriene

• Dmitry N. Platonov,
• Alexander Yu. Belyy,
• Rinat F. Salikov,
• Kirill S. Erokhin and
• Yury V. Tomilov

Beilstein J. Org. Chem. 2026, 22, 64–70, doi:10.3762/bjoc.22.2

• dynamic equilibrium or total rearrangement of 5 into 6 upon formation. Thus, halogenation of hexa(methoxycarbonyl)cycloheptatrienyl anion 2 formed from 3 led to different outcomes with chlorine, bromine and iodine (Scheme 1). Chlorination gave exclusively i-substituted symmetric cycloheptatriene 4a in an

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

• to alkenyl chlorides with phosphorous pentachloride (PCl5): Friedel first reported the reaction of PCl5 with acetophenone (1) in 1868 (Scheme 1A) [45]. Treatment of the resulting intermediate 2 – then presumed to be a gem-dichloride – with aqueous KOH led to the formation of phenylacetylene (3). In

• , aligned with the axis of the vacant orbital. In the case depicted in Scheme 40B, the face syn to the hydrogen is significantly more accessible than the face syn to the bulky tert-butyl group, accounting for the high E-selectivity observed. In contrast, alkyl groups with reduced steric demand led to

• of the reaction in which TiCl4 was employed in place of BCl3 (Scheme 43) [147]. Interestingly, this modification led to an improved E/Z ratio compared to the values reported by Melloni (compare selectivity for compound 219 in Scheme 38 and Scheme 41). The enhanced selectivity is likely attributable

One-pot synthesis of ethylmaltol from maltol

• Immanuel Plangger,
• Marcel Jenny,
• Gregor Plangger and
• Thomas Magauer

Beilstein J. Org. Chem. 2025, 21, 2755–2760, doi:10.3762/bjoc.21.212

• between dianionic species led to the formation of, in part, inseparable overalkylation products. Second, excess of base was required for complete conversion of maltol (2), which in turn promoted further overalkylation. These challenges, combined with the need for sub-zero temperatures, prompted us to

• to ethylmaltol (1) combined with the rather harsh deprotection conditions, led us to investigate other masking groups. Next, we turned towards silyl protecting groups as they offered (a) facile tuning of stability and (b) the opportunity for acid-mediated deprotection during aqueous work-up

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

• alternative approach to C-7 functionalization of Nα-Boc-tryptophan methyl ester, we chose a CH activation protocol [33]. Treatment of N1-Piv-Nα-Boc-tryptophan methyl ester (10) with but-3-en-2-one (MVK) in the presence of [RhCp*Cl2]2 catalyst according to Ma et al. [34] led to the 7-(3-keto-1-butyl)-alkylated

• product 11 in 37% yield (Scheme 2). Despite the modest yield, product 11 was transformed to the corresponding tertiary alcohol 12. Removal of the N-Piv group and dehydration with the Burgess reagent [35] led to an inseparable mixture of olefins slightly in favor of the exo-olefin isomer. Dehydration in

• the presence of the N-pivaloyl group led to the same mixture of isomers. Numerous conditions to change the ratio were not successful [36] (Supporting Information File 1, Table S1). In view of the above mentioned issues, we considered chemically more challenging protocols starting with allyl- or

Competitive cyclization of ethyl trifluoroacetoacetate and methyl ketones with 1,3-diamino-2-propanol into hydrogenated oxazolo- and pyrimido-condensed pyridones

• Svetlana O. Kushch,
• Marina V. Goryaeva,
• Yanina V. Burgart,
• Marina A. Ezhikova,
• Mikhail I. Kodess,
• Pavel A. Slepukhin,
• Alexandrina S. Volobueva,
• Vladimir V. Zarubaev and
• Victor I. Saloutin

Beilstein J. Org. Chem. 2025, 21, 2716–2729, doi:10.3762/bjoc.21.209

• composition of the products, increasing the content of the trans,cis-form 4atc to 20%. The use of 1,4-dioxane with acetic acid catalysis at different molar ratios (Table 1, entries 7, 8) led to the formation of a large fraction of unidentified by-products (42–61%), whereas the base catalysis with

• without catalysis or using triethylamine–acetic acid as a bifunctional catalyst (Scheme 2). The reactions with alkyl methyl ketones 2b,c in 1,4-dioxane without catalysis led to the formation of a mixture of octahydropyrido[1,2-a]pyrimidinones 4b,c and hexahydrooxazolo[3,2-a]pyridones 5b,c, but with a

• octahydropyrido[1,2-a]pyrimidinones 4bcс (δF 80.00 ppm) and 4btс (δF 79.50 ppm) were obtained in a mixture at a ratio of 4:1 (Scheme 2). The transformations with 2-hexanone (2c) led to the formation of two diastereomers of 4cct (δF 80.09 ppm) and 4ccc (δF 80.00 ppm), two diastereomers of 5ctc (δF 79.65 ppm) and

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

• hydrothiocyanation of ynones using KSCN in AcOH at 70 °C. They also demonstrated that the adducts of ynones are readily cyclized in situ via a second thiocyanation to form thiazine-2-thiones at a slightly higher temperature and for a longer time. Meanwhile the reaction with ynamides led to decyanative amido

• ). A TFA-mediated cascade cyclization of 2-propynolphenols using KSCN as the thiocyanation source led to the efficient formation of various 4-thiocyanated 2H-chromenes has been developed [23]. 1,3-Oxathiolan-2-ones were obtained by treating 4-hydroxy-2-alkynonitriles with the KSCN/KHSO4 system [24]. In

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

• alkylation was diasteroselective. In the next steps, addition of isopropenyllithium to the lactone moiety led to a hemiketal, which was then opened and a protecting group on the hydroxy group was installed, furnishing fragment 42. Key convergent coupling of this total synthesis was performed by lithium

• was performed by attachment of an alkyl chain, which was later cyclized to the desired piperidine ring (Scheme 16). 25 steps were needed for the construction of the ABCD-ring system in 62 (Scheme 17). Attachment of amine 66, F-ring closure, a reduction and protecting group manipulations led to

• cevanine-type alkaloids derived from the core alkamine veracevine (86) (see Scheme 27) [45]. Extracts containing Veratrum alkaloids have been explored as potential treatments for hypertension. However, their narrow therapeutic window led to their replacement by other medications [43]. Verticine The first

Thiazolidinones: novel insights from microwave synthesis, computational studies, and potentially bioactive hybrids

• Luan A. Martinho,
• Victor H. J. G. Praciano,
• Guilherme D. R. Matos,
• Claudia C. Gatto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2025, 21, 2618–2636, doi:10.3762/bjoc.21.203

• an excellent yield of 96% over different equimolar quantities (Table 1, entries 13–18). Interestingly, the yield was essentially quantitative for a lower catalyst loading of just 10 mol % in a reaction time of 30 minutes (Table 1, entry 18). Attempts to shorten the reaction time led to a slight

• , protonation of these compounds resulted in a lowering of the HOMO energy level, leading to an increase in the HOMO–LUMO gap and, consequently, greater molecular stability. In contrast, deprotonation led to an increase in the LUMO energy level, with little influence on the HOMO energy. Notably, the neutral

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

• (Scheme 1). Building upon previous work [17][18][19], we focused on optimizing key parameters: resin selection, Fmoc deprotection conditions, coupling reagents for linear assembly, and crucially, the cyclization step. Cost-effectiveness and commercial availability led us to select 2-chlorotrityl chloride

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

• higher oxidation potential (E1/2 = +1.52 V). This reaction was examined using different solvents, and it was found that toluene and 1,4-dioxane gave low yields (4–5% yield). Under blue LED irradiation, Ir-based PC is photoexcited, and its excited state is reductively quenched by the electron-rich arene

• 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

• was described. Aromatic C(sp2)–H bond acylation was achieved by dual catalysis through cooperative NHC and organophotoredox-catalyzed C–C cross-coupling of a benzo-fused aryl radical cation C with stable ketyl radical B as the key step. LED irradiation of photocatalyst leads to photoexcited PC*, which

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

• and the installation of the C1 methyl group, then afforded compound 96. However, subjecting 96 to the singlet oxygen cycloaddition again led to rearrangement, producing diketones 98 and 99. The solution was found by employing a nitroso-Diels–Alder reaction with dienophile 87, which provided a stable

• [5.2.1.01,5]decane core of illisimonin A. Conclusion Over the past seventy years, ongoing chemical investigations of the Illicium species have led to the discovery of a great number of Illicium sesquiterpenes. The sterically congested and highly oxygenated skeleton of allo-cedrane-type, anislactone-type, and

• . Its tricyclo[5.2.1.01,5]decane core, which contains a strained trans-pentalene subunit, presents new synthetic challenges. A breakthrough in the total synthesis of illisimonin A was achieved by Rychnovsky and co-workers through a rearrangement strategy that also led to the correction of its absolute

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

• research on Ryania diterpenoid natural products Ryania diterpenoids have garnered sustained interest in the synthetic chemistry community due to their complex, unique molecular structures and potential biological activities. This has motivated extensive research that has led to notable advances. This

Ni-promoted reductive cyclization cascade enables a total synthesis of (+)-aglacin B

• Si-Chen Yao,
• Jing-Si Cao,
• Jian Xiao,
• Ya-Wen Wang and
• Yu Peng

Beilstein J. Org. Chem. 2025, 21, 2548–2552, doi:10.3762/bjoc.21.197

• Abstract The total synthesis of bioactive (+)-aglacin B was achieved. The key steps include an asymmetric conjugate addition reaction induced by a chiral auxiliary and a nickel-promoted reductive tandem cyclization of the elaborated β-bromo acetal, which led to the efficient construction of the

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

• biological agents has led to a rapid emergence of resistance, which in turn diminishes the national-wide and even global-wide food security. Moreover, toxins produced by fungi in diseased crops have serious impacts on animal and human health [2]. There remains high demand to develop new antifungal compounds

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

• shape differences by allowing such subunits to rotate out of coplanarity due to steric strain, diminishing conjugation between subunits. Formation of pentacyclic ring systems via annulation led to several expected spectroscopic signatures indicating the formation of an expanded aromatic π-system. 1H NMR

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

• strong binding so long as the nucleobase lacked significant hydrophobicity [36]. This led to the hypothesis that quite possibly the third hydrogen-bond to the U base may not have been as important as originally believed. Given this result, we set out to design new nucleobases that reach across the entire

• corresponding aniline with iron metal. Notably, the use of HCl as a proton source in the reduction led to significant removal of the Boc group necessitating the use of ammonium chloride as the proton source. The crude aniline was coupled to N-methylisoorotic acid 6 [37] to afford 7 in 50% yield. Surprisingly 10