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

• , particularly the synergistic combination of N-heterocyclic carbenes (NHCs) with organic photocatalysts, has opened new avenues in molecular construction, particularly for the novel, practical preparation of carbonyl group-containing compounds [13][14][15][16]. These ubiquitous ketone, ester, and amide

• presence of NHC (10 mol %) and 4CzIPN (2 mol %) and Na2HPO4 in DMSO at rt for 10–24 h. The key to success lies in the photocatalytic dual system, which combines two organocatalysts (NHC/4CzIPN) and visible light irradiation to permit a novel umpolung single-electron reduction of respective imino ester 2

• 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

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

• , which was subsequently subjected to a one-pot desilylation to afford 24. Reduction of both the ester and ketone functionalities in 24, followed by selective protection of the primary alcohol and re-oxidation of the secondary alcohol to ketone, furnished compound 25 in three steps. The ketone in 25 was

• NaOH facilitated a retro-Claisen reaction, yielding the intermediate 106, which subsequently underwent an intramolecular aldol reaction to form the five-membered ring. The resulting carboxylic acid was then esterified with TMSCHN2 to furnish ester 107, which possesses the characteristic tricyclo

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

• activities and serves as a potent modulator of intracellular calcium release channels. In contrast to ryanodol (4), compound 1 possesses a pyrrole-2-carboxylate ester moiety at the C3 position. This ester group can be cleaved via hydrolysis to yield 4. However, the reverse transformation – the synthesis of

• reported the first total synthesis of ryanodine from ryanodol [47] (Scheme 5). Their strategy utilized a novel boronate protecting group to mask the four syn-oriented hydroxy groups. A critical step was the in-situ generation of the pyrrole-2-carboxylate unit from a glycine ester and 1,3-bis(dimethylamino

• effectively resolved a major obstacle in the synthesis of ryanodine (1) and established a versatile approach for introducing diverse C3 ester substituents for future SAR studies [49]. The synthesis commenced from advanced intermediate 71 (from their prior work). Sequential SeO2-mediated oxidation, triflation

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

• File 1). The generated ester 10 was then converted into the corresponding acyl chloride by saponification and subsequent reaction with pivaloyl chloride. The resulting acyl chloride was then trapped by (S)-4-phenyl-2-oxazolidinone (11) to produce the desired α,β-unsaturated amide 7. Next, 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

• % of the final desired monomer 8 was also isolated in the coupling step, presumably due to hydrolysis of the allyl ester in the iron reduction step. The remaining allyl ester 7 was deallylated via Pd(PPh3)4 to afford the monomer 8 in 51% yield. Db2 Synthesis Db2 was prepared through a convergent

• perform equally well using conventional heating methods. Aniline 10 and carboxylic acid 13 were combined under standard (HBTU) amide coupling conditions to afford benzyl ester 14 in 52% yield. Compound 14 was subsequently debenzylated via hydrogenolysis to afford the target Db2 monomer 15 in 77% yield

• -nitroaniline into benzyl acrylate to afford compound 17 in 57% yield (Scheme 3). Aniline 17 then was subjected to a three-step Boc protection, nitro reduction, and coupling with isoorotic acid derivative 6 that afforded 18 in 39% yield over 3 steps. The benzyl ester was then cleaved under hydrogenolysis

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

• the nucleophilic substitution of the nitro group in 2-nitrobenzonitriles using Na2S in a DMF/water medium, followed by alkylation of the resulting 2-cyanophenylthiolates and subsequent cyclization [31]. However, in our case, the reaction of ester 1 with Na2S in either acetone or a DMF/water mixture

• to be an unsuitable route for nucleophilic substitution of its nitro group. Next, we explored an alternative route using potassium thioacetate (KSAc) as a softer nucleophile. Unexpectedly, the reaction of ester 1 with KSAc in acetone gave a mixture of products other than the desired 3-AcS-substituted

• , necessitates consideration of a reaction mechanism beyond straightforward nucleophilic substitution of the nitro group in ester 1. Although the initial reaction probably involves a nucleophilic attack by the S-nucleophile on the activated thiophene ring, resulting in displacement of the nitro group, the

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

• pentacyclic structure, 2,11-dioxo-A-norolean-12,18(19)-dien-30-oic acid 39, from pharmaceutical 18,19-dehydroglycyrrhetic acid (18,19-dehydro-GLA) 33. Compound 33 was converted to its methyl ester 34 and oxidized by pyridinium dichromate (PDC) in CH2Cl2 to 3-oxo-18,19-dehydro-GLA 35 with a 75% yield. α

• -Ethylformylation of compound 35 and subsequent oxidation of ketoenol 36 with 30% aqueous H2O2 in the presence of a 28% MeONa/MeOH solution resulted in the formation of a diacid, which was then converted into dimethyl ester 37 with a yield of 55%. Refluxing ester 37 with an excess of t-BuOK in benzene gave acid 39

• with a yield of 53% yield. The excess of base (t-BuOK) caused simultaneous decarboxylation and hydrolysis of ester 37, forming the new nortriterpenoid 39 with a pentacyclic ring A (Scheme 7). In the work of Rath et al. [32], a similar method was proposed for the interconversion of cycles in the

The high potential of methyl laurate as a recyclable competitor to conventional toxic solvents in [3 + 2] cycloaddition reactions

• Ayhan Yıldırım and
• Mustafa Göker

Beilstein J. Org. Chem. 2025, 21, 2389–2415, doi:10.3762/bjoc.21.184

• characteristics, arising from the ester group and the non-polar hydrocarbon chain, respectively. The nitrone contains a polar functional group (N–O) and two aromatic rings, which serve to generate both polar and dispersion forces. Consequently, these findings indicate that fatty acid methyl esters may possess

Synthetic study toward vibralactone

• Liang Shi,
• Jiayi Song,
• Yiqing Li,
• Jia-Chen Li,
• Shuqi Li,
• Li Ren,
• Zhi-Yun Liu and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2025, 21, 2376–2382, doi:10.3762/bjoc.21.182

• , although the corresponding enone product was not isolated. Facing a dead-end, the synthetic route to precursor 14 needed to be revised. From 15, after sodium methoxide-mediated ring opening of lactone, the Fráter–Seebach alkylation [39][40][41] was applied to afford β-hydroxy ester 18. At this stage, the

• the β-lactone was converted into the linear methyl ester 19 to decrease the potential steric hinderance associated with the fused bicyclic skeleton, substrates containing a free hydroxy group or the corresponding TES ether still failed to close the cyclopentene ring. In this scenario, it was necessary

Rotaxanes with integrated photoswitches: design principles, functional behavior, and emerging applications

• Jullyane Emi Matsushima,
• Khushbu,
• Zuliah Abdulsalam,
• Udyogi Navodya Kulathilaka Conthagamage and
• Víctor García-López

Beilstein J. Org. Chem. 2025, 21, 2345–2366, doi:10.3762/bjoc.21.179

• macrocycle occurs along a thread containing fumaramide and succinic amide ester units as recognition sites, with highly fluorescent perylene bisimide and pyrene serving as stoppers [67]. The macrocycle features two pyridine units that, upon protonation, effectively quench the fluorescence of both

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

• lycodine 34 underwent Ir-catalyzed C3–H borylation mainly guided by steric factors to provide boronic ester 35 in 75% yield. With the boronic ester handle at the C3 position, the subsequent Suzuki–Miyaura cross coupling between 35 and 33 occurred smoothly to deliver pseudo-dimer 36, which upon acidic

• used in the Sarpong synthesis was again utilized here to introduce a boronic ester at the C3 position, which was further converted to 3-bromopyridine 55 with CuBr2. With both 54 and 55, Tsukano and co-workers employed a remarkable pyridine N-oxide directed C–H arylation method developed by Fagnou et al

• skeleton and the newly developed C–H borylation to install a boronic ester handle at the desired position for a Suzuki–Miyaura cross coupling to build the C2–C3’ linkage which was hidden in bis(trimethylsilyl)butadiyne (20) of the Siegel synthesis. Both the groups of Tsukano and Dai utilized a pyridine N

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

• by the Yang group [22]. Installation of the hydroxymethyl group in 4 was achieved through sequential formylation and reduction. Compound 4 then underwent a one-pot, substrate-controlled diastereoselective Johnson−Claisen rearrangement/acetylation to install ester 5. Treating 5 with m-CPBA (meta

• . This transformation proceeded via sequential regio- and stereoselective Norrish−Yang annulation, followed by intramolecular lactonization mediated by 12a. Notably, when the ethyl ester in 12 was replaced with a methyl group to form 14 with R = Et (Scheme 3), photoreaction of 14 led to 15 in 95% yield

• drives this migration, due to the highly sterically congested environment – exacerbated by the 1,3-strain between the methyl groups at C10 and C14. The observed 1,2-methyl migration also underscores the critical role of the preinstalled ester group in 12: it suppresses potential methyl migration

Halogenated butyrolactones from the biomass-derived synthon levoglucosenone

• Johannes Puschnig,
• Martyn Jevric and
• Ben W. Greatrex

Beilstein J. Org. Chem. 2025, 21, 2297–2301, doi:10.3762/bjoc.21.175

• the intermediate formate ester. Fluorination of enamine 9a with Selectfluor (SF) resulted only in hydrolysis with conditions adapted from Peng and Shreeves work [28]; and likewise, the base-promoted (KOt-Bu, LHMDS) fluorination of ketone 6 with Selectfluor was unsuccessful. However, when ketone 6 was

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

• diazoester 24 to furnish a Co(III)-bonded α-ester radical (α-Co(III)-ester radical) with extrusion of nitrogen was proposed by the authors. Further steps include (a) 5-exo cyclization by α-Co(III)-ester radical and (b) homolytic substitution at the carbon atom by 3-exo-tet-cyclization to generate bicyclic

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

• ] intermediate 62 (Scheme 14, path a). When a less nucleophilic indole was used as the nucleophile, a Wagner–Meerwein rearrangement occurred, leading to the formation of a pyrido[4,3-b]indole product 63. When Hantzsch ester (HEH) was used as the nucleophile, the imine intermediate 62 was reduced to product 64

• Wagner–Meerwein rearrangement from the six-membered spirocyclic intermediate 88. The addition of Hantzsch ester or indole as the nucleophile effectively trapped the imine intermediate 88, preventing Wagner–Meerwein rearrangement and yielding spirocyclic indole framework 90 (Scheme 19, path a). When PPh3

• intermediate 167. Subsequent treatment with triethylamine/pinacol induced ring closure, affording the phenanthreno[1,3-b]cyclobutane borate ester 168. In contrast, when the temperature was elevated to 60 °C, the reaction underwent a BCl3-driven skeletal rearrangement involving methyl migration and alkyne

Research towards selective inhibition of the CLK3 kinase

• Vinay Kumar Singh,
• Frédéric Justaud,
• Dabbugoddu Brahmaiah,
• Nangunoori Sampath Kumar,
• Blandine Baratte,
• Thomas Robert,
• Stéphane Bach,
• Chada Raji Reddy,
• Nicolas Levoin and
• René L. Grée

Beilstein J. Org. Chem. 2025, 21, 2250–2259, doi:10.3762/bjoc.21.172

• series of molecules: the ones without chlorine in meta position on this group (series a) and the others which kept this chlorine, like in DB18 (series b). These syntheses are reported in Scheme 2. A Suzuki-type Pd-catalyzed coupling of 7a with 4-(methoxycarbonyl)phenylboronic acid dimethyl ester (8) gave

• reagent the 3-(methoxycarbonyl)phenylboronic acid ester 11. All derivatives have spectral and analytical data in agreement with the proposed structures (see experimental section and Supporting Information File 1). Kinase inhibition studies Our molecules have been submitted first to a primary screening

• also evidenced by the better affinity for DYRK1A of the acidic molecules as compared to their ester analogues. Therefore, this new interaction could explain the higher affinity of VS-77 toward Hs_DYRK1A, as compared to DB-18. Conclusion In the present work, we disclosed a new strategy to improve 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

• the stereochemical assignment of (+)-capsulactone (1). Keywords: chemical degradation; chiral LC–MS analysis; methyl 3-hydroxy-2-methylbutanoate; 3-methylpent-4-en-2-ol moiety; p-nitrobenzoyl ester; Introduction Configurational elucidation of natural products is essential for progress in diverse

• derivatization. Several derivatization methods using chiral anisotropic reagents, including α-methoxy-α-trifluoromethylphenylacetic acid (MTPA), phenylglycine methyl ester (PGME), and Marfey’s reagents, are widely used [8][9][10], although their applicability is restricted by the presence of specific functional

• investigated. First, alcohol 3 was converted to (R)-MTPA ester 4 (Scheme 1B). Despite numerous attempts to optimize the chromatographic conditions, the resulting diastereomers could not be separated (Figure S1, Supporting Information File 1). Next, p-bromobenzoyl ester 5 was synthesized (Scheme 1B). Although

Pd-catalyzed dehydrogenative arylation of arylhydrazines to access non-symmetric azobenzenes, including tetra-ortho derivatives

• Loris Geminiani,
• Kathrin Junge,
• Matthias Beller and
• Jean-François Soulé

Beilstein J. Org. Chem. 2025, 21, 2234–2242, doi:10.3762/bjoc.21.170

• azobenzenes were obtained in purified yields between 70 and 85%. Various functional groups at the ortho- or para-position were well tolerated in this reaction, including electron-withdrawing groups such as trifluoromethoxy (3c, 69%), nitrile (3e, 81%), methyl ester (3h, 74%), N,N-dimethylamide (3i, 73%) and

A m-quaterphenyl probe for absolute configurational assignments of primary and secondary amines

• Yuka Takeuchi,
• Mutsumi Kobayashi,
• Yuuka Gotoh,
• Mari Ikeda,
• Yoichi Habata,
• Tomohiko Shirai and
• Shunsuke Kuwahara

Beilstein J. Org. Chem. 2025, 21, 2211–2219, doi:10.3762/bjoc.21.168

• Cotton effects compared with (S)-2a. We consider that the hydroxymethyl group is sterically more hindered than the planar phenyl groups in the conjugates. This tendency is the same as that of the previously reported 1–(S)-2-phenylethylamine conjugates [41]. The CD spectra of 1-ʟ-amino acid ester

• conjugates (S)-2d,e exhibited positive first and negative second Cotton effects indicating that the two long axes in the methoxybiphenyl chromophores constitute a P twist. The methyl ester group is estimated to be sterically more hindered than the planar ester carbonyl group in (S)-2d,e. The CD spectra of

• the methylene protons. In contrast, in the M conformer, the medium-sized methyl group (denoted as M) is located near the seven-membered ring, reducing the steric repulsion involving the hydroxymethyl group with the methylene protons. Moreover, considering that the phenyl ring and the ester carbonyl

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

•  2). Functional groups including ester, azido, and alkynyl present in the starting materials are responsible for the post-Ugi transformations. Results and Discussion We first attempted the Ugi–azide 4-CR at a 0.2 mmol scale with equal molar amounts of 2-azidobenzaldehyde (1a), propargylamine (2a

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

• in 66%–87% yields. Boc-amino ester (2e), dipeptide (2f), apivalate ester (2g) and ethinyl estradiol (2h) skeletons were also tolerated well. According to the previous works [163] and the experimental results, the authors proposed a plausible mechanism. Firstly, the anodic oxidation of [Cp2Fe

• involved at the ethyne moiety like substituted phenyl (30b–e), benzodioxole (30f), naphthyl (30g), thienyl (30h), pyridinyl (30i), furyl (30j), benzofuranyl (30k), alkyl (30l, 30m), cycloalkyl (30n–p) and trimethylsilyl (30r). This reaction was also compatible with benzyl ester (30s), propynyl ester (30t

• rt for 9 h. The reaction was compatible with numerous amines such as substituted benzylamines 46b–d, 1-(2-naphthyl)methanamine 46e, 3,4-methylenedioxybenzylamine 46f, furfurylamine 46g and 2-thiophenemethylamine 46h. Alkynes with ester and trifluoromethyl groups worked well under this 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

• level of oxygen content in biomass, small molecules arising from biomass often possess a carbonyl group. This is why biobased platform molecules possessing a carbonyl group, either under the form of an aldehyde, a ketone, an acid or an ester, play a dominant role in biobased chemistry. This review aims

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

• modification of the terminal double bond afforded ketoaldehyde 31. The 2-bromoallylation [15] of 31 with boronic ester 32 stereoselectively constructed the C3–OH group to give homoallylic alcohol 33. Next, a successive manipulation by removal of TBS group, CSA-catalyzed ketalization, and DMP oxidation of the

• hydroxyketone 86 in 60% yield with 92% ee and 8.4:1 dr. A secondary hydroxy-directed Grignard reagent addition of 86 followed by selective protection, generated alcohol ester 87. After one recrystallization, the ee value of 87 could be increased to 99%. Subsequently, TMSOTf-promoted transacetalation and in situ

• ,8R,11R based on the X-ray single-crystal analysis of its corresponding p-bromobenzoic ester (not shown). Total synthesis of (−)-conidiogenones B–F and (−)-12β-hydroxyconidiogenone C Conidiogenones are unique diterpenoids which possess a highly congested 6/5/5/5-fused framework with four all-carbon

Further elaboration of the stereodivergent approach to chaetominine-type alkaloids: synthesis of the reported structures of aspera chaetominines A and B and revised structure of aspera chaetominine B

• Jin-Fang Lü,
• Jiang-Feng Wu,
• Jian-Liang Ye and
• Pei-Qiang Huang

Beilstein J. Org. Chem. 2025, 21, 2072–2081, doi:10.3762/bjoc.21.162

• ], we re-synthesized tripepetide derivative 25 from ᴅ-tryptophan (ᴅ-Trp) and ʟ-isoleucine (ʟ-Ile) methyl ester hydrochloride salt (24) in three steps (Scheme 4). Treating 25 with DMDO followed by work-up with a saturated aqueous solution of Na2SO3 at 30 °C provided the proposed structure of aspera

Discovery of cytotoxic indolo[1,2-c]quinazoline derivatives through scaffold-based design

• Daniil V. Khabarov,
• Valeria A. Litvinova,
• Lyubov G. Dezhenkova,
• Dmitry N. Kaluzhny,
• Alexander S. Tikhomirov and
• Andrey E. Shchekotikhin

Beilstein J. Org. Chem. 2025, 21, 2062–2071, doi:10.3762/bjoc.21.161

• interest, compound 2 applied as a useful substrate for a Baeyer–Villiger oxidation mediated by oxone, which selectively converted the aldehyde to the formate ester, yielding 6-oxo-5,6-dihydroindolo[1,2-c]quinazolin-12-yl formate (4). Subsequent hydrolysis of 4 furnished indolo[1,2-c]quinazoline-6,12-dione