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

• 77% yield. The cinnamamide-derived sulfenamide, bearing a C–C double bond, also reacted smoothly under the oxidative conditions without noticeable side reactions, delivering the product 3i’ in 75% yield. Furthermore, carbamate-type sulfenamides were well tolerated under the standard conditions

• enrichment of one enantiomer in the product mixture. To further probe this possibility, the two diastereomers of 5 were carefully separated and individually subjected to Grignard substitution. Reactions of the isolated diastereomers with MeMgI and PhMgBr afforded 6a-1 and 6b-1 with 92% ee and 93% ee

• . Yields are of isolated products. Substrate scope of sulfenamides derived from various amides. Reaction conditions: sulfenamide 1 (0.15 mmol), NBS (1.2 equiv), NaHCO3 (1.5 equiv), MeOH (1.5 mL), room temperature, 30 min. Yields are of isolated products. Substrate scope of reactions between sulfenamides 1a

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

• been used in the synthesis of numerous pharmaceuticals and natural products [7]. The application of asymmetric synthesis enables access to enantiomerically pure targets. Earlier, metal catalysis was used for Mannich reactions [8][9], but in recent years, methods of asymmetric organocatalysis have been

• widely used to achieve these valuable compounds [10][11][12]. Enamine activation was one of the first organocatalytic methods applied in Mannich reactions [13][14]. Concurrently, hydrogen-bond catalysis has emerged as a significant strategy for promoting asymmetric Mannich reactions [15][16]. This has

• efficient in Mannich reactions, as demonstrated by our studies [18] and those of others [19][20][21]. Halogen bonding has also been introduced to further broaden the field of noncovalent interactions. Despite the limited number of asymmetric transformations driven solely by halogen-bond activation [22

Symmetrical D–π–A–π–D indanone dyes: a new design for nonlinear optics and cyanide detection

• Ergin Keleş,
• Alberto Barsella,
• Nurgül Seferoğlu,
• Zeynel Seferoğlu and
• Burcu Aydıner

Beilstein J. Org. Chem. 2026, 22, 131–142, doi:10.3762/bjoc.22.6

• ). The vinyl bridges were added to the design, which have the potential to open nucleophilic addition reactions (Michael type) due to their electron deficiencies, in addition to acting as π-bridges for the D–A conjugation. Furthermore, a symmetric design with increased π-conjugation was planned to shift

Highly electrophilic, gem- and spiro-activated trichloromethylnitrocyclopropanes: synthesis and structure

• Ilia A. Pilipenko,
• Mikhail V. Grigoriev,
• Olga Yu. Ozerova,
• Igor A. Litvinov,
• Darya V. Spiridonova,
• Aleksander V. Vasilyev and
• Sergey V. Makarenko

Beilstein J. Org. Chem. 2026, 22, 123–130, doi:10.3762/bjoc.22.5

• nitro group upon breaking the C–C bond [16][17]. Substituted nitrocyclopropanes in reactions with various nucleophiles form linear precursors for the synthesis of γ-substituted α-aminobutyric acids [18][19], cyclic nitropyrrolines [20] and isoxazoline N-oxides [18]. The nitrocyclopropane fragment is a

• by several approaches: forming of the CF3-group in a nitrocyclopropane (reaction of 2-nitrocyclopropanecarboxylic acid with sulfur tetrafluoride [31][32]), cyclopropane formation from a nitroethene substrate and a CF3-containing reagent (Corey–Chaykovsky reaction [33]), as well as reactions involving

• Michael-initiated ring closure (MIRC) reaction of gem-halonitroalkenes and CH-acids [37][38]. Thus, 2-nitrocyclopropanecarboxylates were obtained based on the tandem reactions of cyclic CH-acids with alkyl 3-bromo-3-nitroacrylates [39]. Despite the structural proximity and high activity of 1-bromo-1-nitro

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

• strategies. The integration of photochemistry [13] and electrochemistry [14] into total synthesis has further extended the realm. Synthesis of complex natural product structures can promote the discovery of new reactions and the generation of new strategies [15]. However, despite careful design, the primary

• ][19][20]. In recent years, promoted by the rapid development of asymmetric catalysis, a wealth of reactions applicable to aromatic systems – including substitution reactions, transition-metal-coupling reactions, and even dearomatization [21][22][23] – have been reported, further extending their

• in the presence of metal catalysts including Pd or Ir and different ligands. In 2021 and 2022, Wang and co-workers reported two impressive hydroboration–hydrogenation reactions catalyzed by FLP (triarylphenylborane) that reduced pyridine compounds 11 or 15 to dihydropyridine compounds 12 or chiral

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

• Hiroshige Ogawa Hugh Nakamura The Hong Kong University of Science and Technology (HKUST), Clear Water Bay, New Territories, Hong Kong SAR, China 10.3762/bjoc.22.3 Abstract Radical reactions, which have been reported in large numbers in recent years, have exerted major influence across fields

• and discovery of two-electron ionic transformations dominated the early stages. Over time, pericyclic reactions exemplified by the Woodward–Hoffmann rules and one-electron radical processes became prominent research topics. Today, many of these classical transformations have been further refined to

• afford reactions that are cheaper, safer, and less toxic. In this context, we focus on mild radical reactions mediated by zirconium (Zr), which has recently attracted attention because of its low toxicity and ease of handling. We discuss the utility of Zr in such radical processes and consider prospects

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

• reactions mainly involve the initial electrophilic attack onto the α-position relative to the hydrogen atom. The selectivity is either due to the high stability of the α-nucleophilic conformer or due to the promotion by the adjacent ester group. Cascade reactions upon the target connection, if installed

• , include the formation of norcaradienes, dihydroindazoles, a tetracyclodecene and a hydrazonocycloheptatriene derivative. Keywords: azo shift; cascade reactions; cycloheptatriene; relief of antiaromaticity; umpolung; Introduction Reactivity umpolung [1] is a synthetic concept in organic chemistry that

• contraposes the expected and the unexpected in terms of polarity in either reactions or synthetic strategies (Figure 1). Most effective reactions within this concept involve the in situ generation of a species exhibiting reversed polarity and the original group is reestablished at later reaction stages [2

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

• previous reviews that have addressed this class of compounds in part or within broader contexts. Figure 3 offers a structured overview of prior reviews to facilitate orientation within the existing literature. The earliest comprehensive account is found in Jacobs’ 1949 Organic Reactions chapter, “The

• group in the α-position (e.g., aldehyde, ketone, sulfone, nitro) is beyond the scope of this review. In 2011, Guinchard and Roulland reviewed Pd-catalyzed cross-couplings of 1,1-dichloroalkenes and boron-chlorination reactions in the context of natural product synthesis (Figure 3C) [33]. Takai’s

• contribution to the field, particularly via chromium-mediated olefinations, is covered in a Comprehensive Organic Synthesis chapter (Figure 3D) [34][35]. Carbochlorination and carbonylchlorination reactions were reviewed by Petrone, Ye, and Lautens in their Chemical Reviews article on transition-metal

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

• nucleophilicity of the intermediate lithium alkoxides and to the softer nucleophilic character at C vs O for lithium dienolates. While the dianion strategy was able to convert maltol (2) to ethylmaltol (1) in yields of up to 57%, the reactions suffered from an unsatisfactory purity profile. First, interconversion

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

• approaches focus mainly on intramolecular radical cyclizations [42][54][55][56][57][58][59][60][61][62][63], while intermolecular [1][64][65][66][67][68] N–N coupling remains a poorly studied area. In addition to the preparation of azo compounds [69][70], intermolecular N–N coupling reactions are of

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

• prenylindoles (Figure 1, approach B) which would rely on a Negishi cross-coupling reaction [37][38] using Jackson’s iodozinc N-Boc-ʟ-serine methyl ester [39] and 3-iodoallyl- or 3-iodoprenylindoles (Figure 3). Related Negishi cross-coupling reactions have been reported for bromoindoles [40] and 3-iodo-N-Boc-7

• reactions was attributed in part to the nature of the organozinc reagent 29. In contrast, a similar coupling using the organozinc reagent prepared from iodo N-Boc-ᴅ-alanyl methyl ester (S)-35 with 4-allylindole under the same conditions afforded a significantly improved yield of 65%. Steric bulk due to the

• Negishi cross-coupling reactions took place in excellent yield with the iodozinc N-Boc reagent 35, in contrast to the organozinc reagent derived from iodo N-Fmoc-ᴅ-alanyl anthranilamide methyl ester 29. Conclusion In summary, we have accomplished the total synthesis of asperdinones 1–4 and terezine D (6

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

• -trifluoroacetoacetate and methyl ketones enables the synthesis to be carried out for octahydropyrido[1,2-a]pyrimidin-6-ones and hexahydrooxazolo[3,2-a]pyridin-5-ones, the preferential formation of which depends on the substituent in the methyl ketone component. Dual acid–base catalysis of the reactions with alkyl

• to be obtained in one stage using commercially available reagents [1][2][3]. Their ambident properties make 3-oxo esters convenient reagents for the use in multicomponent syntheses, with the Hantzsch [4][5] and Biginelli [6][7][8] reactions being the best known. In the transformations, 3-oxo esters

• starting substrates in multicomponent syntheses [17][18][19]; at the same time, they often show extraordinary reactivity. For example, the introduction of polyfluoroalkyl-3-oxo esters into the aforementioned Hantzsch and Biginelli reactions leads to the hydrated heterocycles, which can provide insight into

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

• rearrangement is one of the important reactions induced by HTIB. Similar to other hypervalent iodine(III) compounds, HTIB is known to have higher electrophilicity towards olefinic bonds. HTIB dissociates, adds onto the olefinic bond and subsequently acts as a good leaving group resulting in generation of a

• )3/CH3OH, PhI(OCOCH3)2/CH3OH and PhI(OH)OTs/CH3OH in polar nucleophilic solvents [24][25][26][27][28]. A number of experimental and computational studies have explored the reaction pathway for these oxidative rearrangement reactions under metal-free conditions with the use of hypervalent iodine(III

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

• The hydrofunctionalization of alkynes is one of the most effective and convenient ways of synthesizing polysubstituted alkenes [1][2][3][4][5]. Such reactions can also afford more complex products, provided that the vinyl intermediates formed during the reaction undergo further transformations [6][7

• ][8]. However, this is mainly possible in the case of functionalized alkynes, where these intramolecular reactions usually involve other functional groups that are contained in the same intermediate. Among the numerous hydrofunctionalization reactions, hydrothiocyanation has attracted much attention

• , thioethers, disulfides, phosphonothioates, and trifluoromethyl sulfides. Additionally, due to the presence of two electrophilic sites (the sulfur atom and the carbon of the nitrile function), thiocyanates can readily undergo domino-type intramolecular cyclization reactions to form heterocycles. So, if a

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

• of green for strategic connections, yellow for neutral, e.g., functional group interconversion and isomerization, orange for non-strategic reactions, and red for protecting group (PG) manipulations (Scheme 3). Protecting group manipulations refer to any protection or deprotection of a functional

• transformation carried out in one flask terminated by a purification [11]. Nevertheless, to point out reaction telescoping (i.e., performing several reactions in one flask by sequentially adding reagents, including solvent-swaps) we opted for a visual representation indicated by black frames around the boxes

• , color-coding each transformation in this one-pot procedure. Cascade reactions, as well as reactions, where a single set of reaction conditions and reagents transform two or more groups simultaneously (e.g., global deprotections) and reactions, that occur upon work-up, are still regarded as one step and

Synthesis of new tetra- and pentacyclic, methylenedioxy- and ethylenedioxy-substituted derivatives of the dibenzo[c,f][1,2]thiazepine ring system

• Gábor Berecz,
• András Dancsó,
• Mária Tóthné Lauritz,
• Loránd Kiss,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2025, 21, 2645–2656, doi:10.3762/bjoc.21.205

• substitution reactions of benzo-1,3-dioxoles and benzo-1,4-dioxanes [20]. Reduction of ketones 6 and 7 with NaBH4 gave alcohols 16 and 17, which were chlorinated with SOCl2 to result in compounds 18 and 19. Treatment of the latter with the appropriate amines gave amino derivatives 20a, 20c–e, and 21a, 21c–p

• numbers: CCDC 2470493 (20e), CCDC 2470491 (21g), CCDC 2470492 (23a), CCDC 2470490 (25), CCDC 2470489 (26), CCDC 2472402 (27). All reagents were purchased from commercial sources and were used without further purification. Reactions were followed by analytical thin-layer chromatography on silica gel 60

• . Acknowledgements The authors are grateful to Mrs. Erika Koren-Ausländer for technical assistance in the synthetic reactions, to Mrs. Mónika Mezővári for LC-MS and HRMS TOF EI, and to Mr. Péter Kővágó for IR and NMR measurements. Funding This work was prepared in the framework of 2020-1.1.2-PIACI-KFI-2020-00039

Chemoenzymatic synthesis of the cardenolide rhodexin A and its aglycone sarmentogenin

• Fuzhen Song,
• Mengmeng Zheng,
• Dongkai Wang,
• Xudong Qu and
• Qianghui Zhou

Beilstein J. Org. Chem. 2025, 21, 2637–2644, doi:10.3762/bjoc.21.204

• reactive C17 side chain including an α-hydroxycarbonyl group, a set of side reactions (e.g., reduction of the C20 carbonyl, hydrogenation of Δ4 and Δ14 double bonds, etc.) occurred under the Mukaiyama hydration conditions [30][31]. Therefore, it was necessary to alter the side chain before installing the

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

• chosen as model substrates, and various parameters were systematically screened under microwave heating. Microwave-assisted reactions usually improve selectivities and yields, while significantly reduce reaction times. This approach has consistently yielded positive results in our research group (Table 1

• ) [63]. Glacial acetic acid (AcOH) was initially selected as a hydrophilic (polar) protic solvent due to its high dipole moment, which makes it ideal for microwave reactions, as well as its ability to facilitate simple work-up procedures by simple addition of water [64]. Using sodium acetate (NaOAc) as

• disubstitution processes involving sulfur-to-nitrogen displacement, likely promoted by the nucleophilic character of the amine. These limitations are likely due to the reaction conditions employed, including the high temperature and acidic environment, which may favor side reactions over the desired

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

• against Gram-positive bacteria), will be conducted in our laboratory. Cyclization reactions to segetalins A–H, J and K. The CD spectra of segetalins A–H, J and K. Preparation of segetalins A–H, J and K. Preparation of linear peptides for segetalins A–H, J and K. Supporting Information Supporting

Silica gel with covalently attached bambusuril macrocycle for dicyanoaurate sorption from water

• Michaela Šusterová and
• Vladimír Šindelář

Beilstein J. Org. Chem. 2025, 21, 2604–2611, doi:10.3762/bjoc.21.201

• functionalized, for instance by carboxylic moieties [13], making them available for further reactions with different substrates. We have recently presented a material (SG-BnBU) based on silica gel containing dodecabenzylbambus[6]uril (BnBU) non-covalently bound on its surface [14]. We showed that this material

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

• asymmetric reactions and are functional transformations in synthetic organic chemistry. Especially, 1,2,3-triazole-based NHCs are generally more reactive and stronger σ-donors than imidazole or thiazole analogues. Triazolium NHC enhances their ability to stabilize reactive radical intermediates or acyl anion

• equivalents, which is crucial in dual or triple catalytic cycles. The electron-rich carbene center facilitates faster SET processes in photocatalytic reactions. Triazolium-based NHCs exhibit higher oxidative and photochemical stability, making them well-suited for visible-light-driven catalytic

• ], Enders [21], Rafinski [22], Scheidt [23], Connon [24], Chi [25], Milo [26][27], Gravel [28][29] and others [30]. These NHC-catalyzed developments have drastically improved the achievable diastereo- and enantioselectivity, including common named reactions such as benzoin reactions, Stetter reactions

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

• deprotection and oxidation of the secondary alcohol, yielded the cyclization precursor 35. A B(C6F5)3-catalyzed tandem Nazarov/ene cyclization of 35 provided the key spirocyclic intermediate 37. The tertiary alcohol was protected in situ with TESOTf to suppress retro-aldol side reactions. Notably, prior TES

• – particularly the critical reactions responsible for skeletal diversity – Yang and co-workers first introduced a comprehensive and detailed biosynthetic pathway for Illicium sesquiterpenes, with the route to illisimonin A depicted in Scheme 5. The transformations from farnesyl diphosphate to the allo-cedryl

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

• diterpenoids; synthetic strategy; total synthesis; Introduction Organic synthesis, as a cornerstone of chemical research, is dedicated to constructing complex natural products or target molecules from simple and readily available starting materials via a series of precise and efficient chemical reactions

• 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

• the correct relative configuration undergoes hydrolysis of its spirocyclic lactone moiety under basic conditions to yield 13, establishing the critical C5 chiral center. Under acidic conditions, intermediate 13 undergoes ketal deprotection followed by successive intramolecular aldol reactions

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

• synthesis of both enantiomers of aglacins A (1), B (2), and E (4) by asymmetric photoenolization/Diels–Alder reactions as the key steps for the construction of the C7–C8 and C7′–C8′ bonds [8]. During the past decade, we had developed nickel-catalyzed or -promoted reductive coupling/cyclization reactions for

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

• tandem approach preparing 7–12 ranged from 43–85%, which were similar to running the deprotection and cycloaddition reactions sequentially. Pd-catalyzed annulation using a modification of previously reported reaction conditions [46] under microwave irradiation instead of thermal heating converted 1,5

• -diaryl-1,2,3-triazoles 7–12 into target pentacyclic aromatic heterocycles 13–18. Yields of annulation reactions for naphthalene-containing analog 13 (90%) was appreciably higher than for quinoline and isoquinoline derivatives 14–18 (31–72%). Due to triazole subunit connectivity to the napththalene

• thermal heating conditions [46] was successful for preparing these compounds. Yields of annulation reactions for the naphthalene-containing analog 31 (65%) was once again appreciably higher than that of the quinoline and isoquinoline derivatives 32–36 (31–51%), but there appeared to be no significant