Synthetic approach to borrelidin fragments: focus on key intermediates

• Yudhi Dwi Kurniawan,
• Zetryana Puteri Tachrim,
• Teni Ernawati,
• Faris Hermawan,
• Ima Nurasiyah and
• Muhammad Alfin Sulmantara

Beilstein J. Org. Chem. 2025, 21, 1135–1160, doi:10.3762/bjoc.21.91

• the correct stereochemistry of the newly formed three stereocenters. Additionally, replacing cesium carbonate with triethylamine proved crucial for achieving efficient asymmetric hydrogenation in this case. Subsequently, the carboxylic acid group of 57 was reduced with LiAlH4 in THF to produce primary

• %), followed by protection of the secondary alcohol as TBDMS ether 81 (98%). The primary alcohol was then liberated using ammonium fluoride in hot methanol (60 °C). Oxidation of this alcohol to a carboxylic acid was achieved using TEMPO and (diacetoxyiodo)benzene (BAIB), completing the synthesis of the target

• treatment with Ph3P/I2/imidazole reagents and reacted with lithiated pseudoephedrine propionamide. The resulting product 144 was obtained in 88% yield. Basic hydrolysis of this compound successfully removed the chiral auxiliary, yielding acid 145 in 91% yield. Sequential reduction of this carboxylic acid

A versatile route towards 6-arylpipecolic acids

• Erich Gebel,
• Cornelia Göcke,
• Carolin Gruner and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 1104–1115, doi:10.3762/bjoc.21.88

• acid (7-ACA) from cephalosporin C by cephalosporin C acylase [37], was used as a chiral starting material. After esterification of both carboxylic acid functions followed by cyclization to the lactam [38][39], the six-membered ring structure was established as (R)-methyl 6-oxopipecolate (7) with a high

Recent advances in synthetic approaches for bioactive cinnamic acid derivatives

• Betty A. Kustiana,
• Galuh Widiyarti and
• Teni Ernawati

Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85

• and co-workers (2021) utilized oxime chloride and cinnamic acid to synthesize O-acylhydroxamate 68 in good yield (Scheme 23A) [57]. In the presence of a base, oxime chloride was converted to electrophilic nitrile oxide 69 and reacted with carboxylic acid to form the cyclic intermediate 70. On the

On the photoluminescence in triarylmethyl-centered mono-, di-, and multiradicals

• Daniel Straub,
• Markus Gross,
• Mona E. Arnold,
• Julia Zolg and
• Alexander J. C. Kuehne

Beilstein J. Org. Chem. 2025, 21, 964–998, doi:10.3762/bjoc.21.80

Silver(I) triflate-catalyzed post-Ugi synthesis of pyrazolodiazepines

• Muhammad Hasan,
• Anatoly A. Peshkov,
• Syed Anis Ali Shah,
• Andrey Belyaev,
• Chang-Keun Lim,
• Shunyi Wang and
• Vsevolod A. Peshkov

Beilstein J. Org. Chem. 2025, 21, 915–925, doi:10.3762/bjoc.21.74

• [20][21][22][23]. For example, the Ugi four-component reaction (U4CR), involving a carbonyl compound, a primary amine, a carboxylic acid, and an isocyanide, provides a straightforward method for constructing dipeptide-like adducts [24][25][26][27]. These adducts can subsequently be rigidified into

• carboxylic acid component 3 and additional keto-carbonyl group in aryl glyoxal 1. This approach was further advanced by Ding's group to produce a broader range of benzodiazepines with diverse substitution patterns by shuffling the necessary functional groups within the Ugi reaction components [34][35][36

Cu–Bpin-mediated dimerization of 4,4-dichloro-2-butenoic acid derivatives enables the synthesis of densely functionalized cyclopropanes

• Patricia Gómez-Roibás,
• Andrea Chaves-Pouso and
• Martín Fañanás-Mastral

Beilstein J. Org. Chem. 2025, 21, 877–883, doi:10.3762/bjoc.21.71

• functionalized cyclopropane scaffolds depending on the nature of the carboxylic acid derivative. Chemodivergent reactivity observed in copper-catalyzed borylative couplings of allylic gem-dichlorides. Cu-Bpin-mediated dimerization of 4,4-dichoro-2-butenoic acid derivatives. Control experiments. Proposed

Synthesis and photoinduced switching properties of C₇-heteroatom containing push–pull norbornadiene derivatives

• Daniel Krappmann and
• Andreas Hirsch

Beilstein J. Org. Chem. 2025, 21, 807–816, doi:10.3762/bjoc.21.64

• , various light-, heat-, and acid-induced rearrangements have been reported [35], complicating the distinct structural determination of these compounds. In comparison to published NMR and UV–vis data, formation of neither known species can be assumed with certainty. Last, through addition of mono-carboxylic

• acid-CoII-porphyrin (POR, see Supporting Information File 1), which was already available within our group [4], regeneration of the parent N-NBD1 was unsuccessful (Supporting Information File 1). Consequently, the presence of N-QC1 can be excluded, and the spectroscopic data likely corresponds to an

Entry to 2-aminoprolines via electrochemical decarboxylative amidation of N‑acetylamino malonic acid monoesters

• Olesja Koleda,
• Janis Sadauskis,
• Darja Antonenko,
• Edvards Janis Treijs,
• Raivis Davis Steberis and
• Edgars Suna

Beilstein J. Org. Chem. 2025, 21, 630–638, doi:10.3762/bjoc.21.50

• initial deprotonation of carboxylic acid 9a by cathodically generated hydroxide is followed by anodic oxidation/decarboxylation of the formed carboxylate 9a-I to generate stabilized cation 9a-II. The latter undergoes intramolecular cyclization with the tethered N-nucleophile into cyclic aminal 6a. In a

• 13a,d,e in 71–83% yield (Scheme 4). Carboxylic acid 13a could be reacted with glycine benzyl ester in the presence of HATU and Et3N to form dipeptide 16 (66%). In contrast, N-unprotected 2-aminoprolines are unstable and could not be isolated. Thus, the cleavage of the N-Cbz protecting group in 6b

• ester moiety with LiBH4. In the meantime, the hydrogenolysis of the benzyl ester in dipeptide 16 proceeded smoothly and afforded carboxylic acid 17 in 81% yield (Scheme 4) [16]. Conclusion In summary, the developed electrochemical decarboxylative amidation of readily accessible malonic acid monoesters

Formaldehyde surrogates in multicomponent reactions

• Cecilia I. Attorresi,
• Javier A. Ramírez and
• Bernhard Westermann

Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45

• catalyst. Another recent example for the use of DMSO as C1 synthon was reported by Bhattacharjee et al. They used DMSO in a 3CR to install a methylene unit between an indazole 24 and a carboxylic acid 25 (Scheme 18) [52]. Under radical conditions using K2S2O8, they obtained a series of carboxylic acid

• ). The alkyne reacts with the in situ-generated carbanion through a 5-endo-dig-cycloisomerization process to yield a nitrogen-containing five-membered heterocycle (Scheme 44). Examples in which the propargyl group is incorporated into the amine [106] or the carboxylic acid components [107] are known

Synthesis of N-acetyl diazocine derivatives via cross-coupling reaction

• Thomas Brandt,
• Pascal Lentes,
• Jeremy Rudtke,
• Michael Hösgen,
• Christian Näther and
• Rainer Herges

Beilstein J. Org. Chem. 2025, 21, 490–499, doi:10.3762/bjoc.21.36

• . Non- or less polar aromatic substituents were not characterized in detail since their solubility in pure water is decreased by the additional phenyl substituent. The pH values were chosen to make sure that the amine 21 is completely protonated and the carboxylic acid 13 is completely deprotonated. UV

• pH values. The half-lives of the metastable E isomers are significantly longer in water than in less polar solvents like acetonitrile. For carboxylic acid-substituted 13, the Z→E conversion upon irradiation with 405 nm drops from 77% to 53% upon changing the solvent from acetonitrile to water (pH 7.4

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

• there to be wide-ranging potential across low-symmetry cavity research [205][208][309][366][370][371][372][373][374] if new and more explicit emergent geometric rules can be codified and exploited [39]. We were also able to statistically access a cage with a single internal carboxylic acid group and

• positions of the two active carboxylic acid groups in cages such as 1, there are several levels of tuning possible in terms of the rigidity. Hexapyridine cage 2 is calculated (and observed) to exist exclusively (>99.9%) in the C13 conformer (Figure 8B and Figure 9A) [41]. Since the amide groups rarely

Red light excitation: illuminating photocatalysis in a new spectrum

• Lucas Fortier,
• Corentin Lefebvre and
• Norbert Hoffmann

Beilstein J. Org. Chem. 2025, 21, 296–326, doi:10.3762/bjoc.21.22

Recent advances in electrochemical copper catalysis for modern organic synthesis

• Yemin Kim and
• Won Jun Jang

Beilstein J. Org. Chem. 2025, 21, 155–178, doi:10.3762/bjoc.21.9

• (IV) species 113 coordinates with carboxylic acid and undergoes photoinduced ligand-to-metal charge transfer (LMCT) and regeneration of the Ce(III) species to produce a benzylic radical 115. The chiral Cu(II) catalyst 117 reacts with benzylic radical 115 to yield Cu(III) intermediate 118, which then

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

• that, up to 24 hours, this method shows some degree of functional group tolerance, as the amido and carboxylic acid functionalities of benzamide and benzoic acid, were left untouched, and the starting materials were finally fully recovered. 1-Bromo-4-nitrobenzene (8a) and 3-chlorophenol were used to

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

• -workers reported a dihydroquinine-derived squaramide-catalyzed (3 + 2) cycloaddition reaction of isocyanoacetates 26 and saccharin-derived 1-azadienes 14 [32]. In this work, the azadiene works as a C2 synthon, while the isocyanoacetate, bearing a protected carboxylic acid and a carbene-like divalent

Discovery of ianthelliformisamines D–G from the sponge Suberea ianthelliformis and the total synthesis of ianthelliformisamine D

• Sasha Hayes,
• Yaoying Lu,
• Bernd H. A. Rehm and
• Rohan A. Davis

Beilstein J. Org. Chem. 2024, 20, 3205–3214, doi:10.3762/bjoc.20.266

• carbon signal. Although a downfield exchangeable CO2H proton was not observed in the 1H NMR spectrum of 5, a carboxylic acid moiety was assigned based on the 13C NMR shift value (δC 173.6) [17], and analysis of the HRESIMS ion at m/z 477.0022 [M + H]+, which confirmed the molecular formula to be

Synthesis of 2H-azirine-2,2-dicarboxylic acids and their derivatives

• Anastasiya V. Agafonova,
• Mikhail S. Novikov and
• Alexander F. Khlebnikov

Beilstein J. Org. Chem. 2024, 20, 3191–3197, doi:10.3762/bjoc.20.264

• chlorides have been developed. Keywords: azirine-2,2-dicarboxamides; azirine-2,2-dicarboxylic acids; isomerization; isoxazoles; Introduction The isomerization of isoxazoles, containing a heteroatomic substituent at C5, to 2H-azirines is a powerful method for the preparation of 2H-azirine-2-carboxylic acid

• derivatives [1]. In particular, the catalytic isomerization of 5-chloroisoxazoles allows the generation of azirine-2-carbonyl chlorides, which can be easily converted into a variety of azirine-2-carboxylic acid derivatives by reactions with nucleophilic reagents. Using this approach, numerous 2-(1H-pyrazol-1

• -carboxylic acid derivatives are not only valuable synthetic building blocks [3][4][5][6][7][8][9][10][11] but also show useful biological activities [12][13][14][15][16][17][18]. Although many 2,2-bifunctionalized azirines have been synthesized [3][4][5][6][7][8][9][10][11], the synthesis of only one 2H

Synthesis of extended fluorinated tripeptides based on the tetrahydropyridazine scaffold

• Thierry Milcent,
• Pascal Retailleau,
• Benoit Crousse and
• Sandrine Ongeri

Beilstein J. Org. Chem. 2024, 20, 3174–3181, doi:10.3762/bjoc.20.262

• electronic and structural properties of the fluorinated groups (CF3 or CF2H) and the geometric constraints due to its partially unsaturated cycle, which could help in the design of peptidomimetics. To our knowledge, only a few publications report the synthesis of tetrahydropyridazines with a carboxylic acid

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• enough to displace the iodane to form the oxonium species A. When the carboxylic acid is used, the oxygen in the lactone intermediate is less reactive and so substitution of the iodane by fluoride is more favourable and the branched product is formed. In addition to aminofluorination, Szabó also reported

• , iodoetherification of 2,2-diphenyl-4-penten-1-carboxylic acid (47') and 2,2-diphenyl-4-penten-1-ol (47) was reported by Liu and Li in 2014 (Scheme 26) [30]. The authors reported using PhI(OAc)2 and KI in the synthesis of iodonated γ-butyrolactone 83 and iodomethyltetrahydrofuran 82 in excellent yields (Scheme 44

• . Iodoetherification of 2,2-diphenyl-4-penten-1-carboxylic acid (47’) and 2,2-diphenyl-4-penten-1-ol (47). Synthesis of 5-iodomethyl-2-oxazolines. Synthesis of chiral iodinated morpholines. aFrom the ʟ-form of the amino acid starting material. The dr values were determined by 1H NMR given in parentheses

Cyclodextrin-based rotaxanes for polymer materials: challenge on simultaneous realization of inexpensive production and defined structures

• Yosuke Akae

Beilstein J. Org. Chem. 2024, 20, 3026–3049, doi:10.3762/bjoc.20.252

• , such as carboxylic acid or sulfonic acid groups must be integrated into the system, thus limiting the flexibility of the molecular design of rotaxane. Even after appropriately integrating these hydrophilic groups into the molecular design, the yield of the rotaxanation step is likely to be as low as 10

• , most of their rotaxane structures required a complicated multistep synthesis as well as the introduction of polar substituents, such as carboxylic acid or sulfonic acid groups, to generate a water-soluble system, and these prevent the direct application of those frameworks to polymer systems. As the

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• -AcrClO4 as the photocatalyst has been disclosed (Scheme 24) [67]. According to the authors, the irradiation of the photocatalyst (Acr+-Mes) A with a blue LED leads to the excited state (Acr·-Mes·+) B. The aliphatic carboxylic acid 66 is converted by deprotonation to the corresponding carboxylate, which is

• to generate the iodoperoxidate intermediate C. Finally, nucleophilic addition of anion of carboxylic acid to intermediate C generates the desired product 216. Based on the iodination/peroxidation strategy the approach to α-hydroxy-β-peroxyethylarenes 219 and α-alkoxy-β-peroxyethylarenes 218 from

Synthesis of fluorinated acid-functionalized, electron-rich nickel porphyrins

• Mike Brockmann,
• Jonas Lobbel,
• Lara Unterriker and
• Rainer Herges

Beilstein J. Org. Chem. 2024, 20, 2954–2958, doi:10.3762/bjoc.20.248

• Mike Brockmann Jonas Lobbel Lara Unterriker Rainer Herges Otto Diels-Institute of Organic Chemistry, Christian-Albrechts-Universität zu Kiel, Otto-Hahn-Platz 4, 24118 Kiel, Germany 10.3762/bjoc.20.248 Abstract In this study, novel fluorinated carboxylic acid esters of the generic structure TfO

Synthesis of tricarbonylated propargylamine and conversion to 2,5-disubstituted oxazole-4-carboxylates

• Kento Iwai,
• Akari Hikasa,
• Kotaro Yoshioka,
• Shinki Tani,
• Kazuto Umezu and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2024, 20, 2827–2833, doi:10.3762/bjoc.20.238

• acid amides and acetylides, respectively. When adduct 4 was treated with a base or ammonium acetate, ring closure proceeded to form a five-membered ring, accompanied by the elimination of the ethoxycarbonyl group. 2,5-Disubstituted oxazole-4-carboxylic acid derivatives are frequently found in

A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis

• Nian Li,
• Ruzal Sitdikov,
• Ajit Prabhakar Kale,
• Joost Steverlynck,
• Bo Li and
• Magnus Rueping

Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214

• constant voltage (CV) conditions and light irradiation under a nitrogen atmosphere. This method demonstrates broad compatibility with various functional groups and complex substrates, including alcohol, carboxylic acid, esters, alkyl chloride, and tosylate groups. Notably, the LSF of compounds such as

HFIP as a versatile solvent in resorcin[n]arene synthesis

• Hormoz Khosravi,
• Valeria Stevens and
• Raúl Hernández Sánchez

Beilstein J. Org. Chem. 2024, 20, 2469–2475, doi:10.3762/bjoc.20.211

• described in the introduction (Scheme 1a and b) [56][58][59][63][66][80][84][85][86][87][88]. Furthermore, we successfully synthesized carboxylic acid-containing resorcin[4]arenes 1o–s employing HFIP under an optimized reaction time of 48 hours. Compounds 1o–s are reported here for the first time. Their

• , chlorinated species 1h and 1i, and carboxylic acid-containing 1s, developed high quality crystals from standing solutions in dimethyl sulfoxide for 1h and 1i, and methanol for 1s. Their molecular crystal structures were determined and are shown in Figure 1b displaying the classic cone conformation for both

• translated to the formation of other macrocycles as long as they share a similar reaction mechanism. (a) Control experiment testing deiodination of 2-iodoresorcinol. (b) Molecular crystal structure of chlorinated resorcin[4]arenes 1h and 1i, and carboxylic acid-containing 1s at 100 K. Thermal ellipsoids are