Recent advances in the electrochemical synthesis of organophosphorus compounds

• Babak Kaboudin,
• Milad Behroozi,
• Sepideh Sadighi and
• Fatemeh Asgharzadeh

Beilstein J. Org. Chem. 2025, 21, 770–797, doi:10.3762/bjoc.21.61

• -yield products were obtained when two methyl groups were positioned at the para or meta positions. The evaluation of the synthetic potential of the C−P bond formation revealed that the cleavage of the C−H bond in thiophene likely does not participate in the rate-determining step. Based on the

Synthesis of HBC fluorophores with an electrophilic handle for covalent attachment to Pepper RNA

• Raphael Bereiter and
• Ronald Micura

Beilstein J. Org. Chem. 2025, 21, 727–735, doi:10.3762/bjoc.21.56

• provide fluorophore 19. Subsequent palladium-catalyzed cross-coupling with tributyl(vinyl)tin resulted in the installation of the vinyl group (compound 20). Finally, cleavage of the silyl ether gave the free alcohol 21, which was converted into the corresponding mesyloxypropyl HBC ligand 22. The

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

• in three steps (62% overall yield) from commercially available diethyl acetamidomalonate by an alkylation/hydrolysis/Boc-cleavage sequence (Scheme 1). The development of decarboxylative amidation commenced by examining the published conditions for anodic decarboxylation/etherification [4

• 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

Total synthesis of (±)-simonsol C using dearomatization as key reaction under acidic conditions

• Xiao-Yang Bi,
• Xiao-Shuai Yang,
• Shan-Shan Chen,
• Jia-Jun Sui,
• Zhao-Nan Cai,
• Yong-Ming Chuan and
• Hong-Bo Qin

Beilstein J. Org. Chem. 2025, 21, 601–606, doi:10.3762/bjoc.21.47

• 14 was performed next and the desired iodide was isolated and, to our delight, the cleavage of the MOM group occurred concomitantly, affording compound 15 in 75% yield. This reaction is likely triggered by the in situ-generated acid. As in our previously reported synthesis, a Zn/AcOH reductive

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

• " of the methyl sulfur group in intermediate 22 for the cleavage of the C–S bond. In the end, the C–C bond is formed between intermediate 23 and the enol form from the methyl ketone 18. Sodium carbonate is added to prevent too much acidification of the reaction medium and to deprotonate the NH that

• (75 °C) are needed. The selectivity of the reaction shown in Scheme 27 could be explained according to the proposed mechanism (Scheme 28a). The first step is the generation of the trialkyl(chloromethyl)ammonium chloride species 36 from the amine compound and CH2Cl2. Then, 36 decomposes by a cleavage

• product 35b was obtained, confirming that the dihaloalkane compound is the source of the methylene unit (Scheme 28c). Depending on the stability of the leaving carbocation, the selectivity of the R–N cleavage follows the decreasing order for the R groups: H, t-Bu, allyl, benzyl > methyl > primary

Cryptophycin unit B analogues

• Thomas Schachtsiek,
• Jona Voss,
• Maren Hamsen,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2025, 21, 526–532, doi:10.3762/bjoc.21.40

• macrolactamisation [21]. The syntheses of required unit A [28], C [29][30], and D [31] building blocks were accomplished as described previously. tert-Butyl-protected leucic acid 14 and Fmoc-β-aminopivalic acid (15) were connected by Steglich esterification (Scheme 2) and after cleavage of the tert-butyl ester group

• obtained through Grubbs metathesis and subsequent acetonide cleavage in a superior yield of 76%. The finalising steps to obtain epoxides 26 and 2 (Scheme 3) were a diol–epoxide transformation [11][19][32], including firstly the formation of a cyclic orthoester, secondly the formation of a bromohydrin

• formate, and thirdly ring closure to obtain the epoxides 26 and 2 in 89% and 14% yield over three steps each, respectively. While the synthesis of tertiary amine 2 was finished, final Alloc cleavage from 26 under Tsuji–Trost-like conditions [19] provided secondary amine 1 in 74% yield. The cytotoxicity of

Identification and removal of a cryptic impurity in pomalidomide-PEG based PROTAC

• Bingnan Wang,
• Yong Lu and
• Chuo Chen

Beilstein J. Org. Chem. 2025, 21, 407–411, doi:10.3762/bjoc.21.28

• instability, where the cleavage of the phthalimide and glutarimide rings comprises the major metabolic pathways [9][10]. Computational analysis confirms that C1, C3, C2’, and C4’ are the most electrophilic sites of thalidomide (Figure 4). As expected, introducing a fluorine atom to C4 activates it toward SNAr

The effect of neighbouring group participation and possible long range remote group participation in O-glycosylation

• Rituparna Das and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2025, 21, 369–406, doi:10.3762/bjoc.21.27

• as the participating group facilitating the formation of a 1,2-trans glycoside (Scheme 2). In general, the cleavage of the activated anomeric leaving group of the glycosyl donor 9 leads to the formation of an electron-deficient oxocarbenium ion 10. The participating vicinal acyl group interacts with

• first introduced the 2,2-dimethylpentenoate protecting group 32 (Figure 1) similar to the pivalate group which showed versatility in its cleavage principle [101]. Hydroboration oxidation of the olefinic bond helped in the removal of the protecting group. On the other hand, dihydroxylation with osmium

• tetroxide and 4-methylmorpholine N-oxide also successfully cleaved the ester reductively by relay-type cleavage. Thus, the tertiary ester could be removed either oxidatively or reductively depending on the sensitivity and requirement of the molecule developed. Similarly, Trost and Hembre devised the 4-(tert

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

• reactions, particularly in controlling the high reactivity and selectivity of radical intermediates [13][14]. Early studies on copper-mediated radical reactions, such as Julia’s work on radical cyclization reaction [15], along with advancements in dimerization [16][17], oxidative cleavage [18][19], and

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• the final step of the reaction, ring opening by the C–C bond cleavage yields the desired product 203. The first phosphoric acid C39-catalyzed asymmetric cycloaddition–elimination cascade reaction of 2-naphthol or phenol enamide derivatives 204 with azonaphthalenes 205 was done by Xu et al. in 2021

• cyclization takes place, subsequent β-H elimination, and C–N-bond cleavage lead to the axially chiral indolylaniline 212. Heterobiaryl aldehydes 217a–o and aminobenzamides 218a–g reacted in the presence of CPA C50 leading to axially chiral products 219 (Scheme 64) [94]. Investigating various combinations of

Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning

• Pablo Quijano Velasco,
• Kedar Hippalgaonkar and
• Balamurugan Ramalingam

Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3

• photocatalytic reactions for water molecule cleavage to produce hydrogen. The mobile robot (Figure 2b) acted as a substitute of a human experimenter by executing tasks and linking eight separate experimental stations, including solid and liquid dispensing, sonication, several characterization equipments, and

Synthesis of acenaphthylene-fused heteroarenes and polyoxygenated benzo[j]fluoranthenes via a Pd-catalyzed Suzuki–Miyaura/C–H arylation cascade

• Merve Yence,
• Dilgam Ahmadli,
• Damla Surmeli,
• Umut Mert Karacaoğlu,
• Sujit Pal and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2024, 20, 3290–3298, doi:10.3762/bjoc.20.273

• -based natural product, which was discovered to induce topoisomerase I-mediated DNA cleavage [16][17]. For the construction of the fluoranthene skeleton, a broad range of synthetic strategies including C–H arylation [18][19][20][21][22], Diels–Alder [7][8][23][24][25] and [2 + 2 + 2] cycloadditions [26

Reactivity of hypervalent iodine(III) reagents bearing a benzylamine with sulfenate salts

• Beatriz Dedeiras,
• Catarina S. Caldeira,
• José C. Cunha,
• Clara S. B. Gomes and
• M. Manuel B. Marques

Beilstein J. Org. Chem. 2024, 20, 3281–3289, doi:10.3762/bjoc.20.272

• reactions could undergo disproportionation, a radical process resulting in the homolytic cleavage of the S–O bond [35]. The formation of disulfide 7 isolated in the experiments can be explained by combining two radical sulfur species. Furthermore, the oxygen species generated in this radical reaction may

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

• complex, which facilitates the cleavage of the N–O bond and subsequent 1,3-cyclization, ultimately leading to the formation of 2H-azirine. Therefore, the isomerization of isoxazole 1j was carried out at a higher temperature, 82 °C, but after hydrolysis of the reaction mixture, instead of the expected

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

• yields and used directly in the next step without further purification (Scheme 2). In the case of Boc-protected hydrazones, the reaction must be carefully followed and reacted less than 2 hours in order to avoid the cleavage of the Boc group. The hydrazones 3e and 3f substituted by N-Cbz-ʟ-phenylalanine

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

• in Kwon’s review [34]. Cu-catalyzed oxygen atom transfer with TBHP were discussed in the review [35]. The review by Xiao considered visible light-driven C–C bond cleavage enabled with organic peroxides [36]. This comprehensive review summarizes all ever published studies on radical peroxidation with

• ][84][85]. The authors rationalized that RuCl2(PPh3)3 reacts with TBHP to give the (alkylperoxido)ruthenium(II) complex, which subsequently undergoes heterolytic cleavage of the O–O bond to form the (oxido)ruthenium(IV) species. HAT from the phenols by Ru(IV)=O intermediate leads to the phenoxyl

• hydroxyperoxide A (Scheme 38a). The homolytic bond cleavage in B produces the resonance-stabilized ketone radical C and a tert-butoxyl radical D. Radical D abstracts a hydrogen atom from TBHP, forming the tert-butylperoxy radical E. Addition of the ketone radical C to the starting alkene 107 results in the C

Recent advances in transition-metal-free arylation reactions involving hypervalent iodine salts

• Ritu Mamgain,
• Kokila Sakthivel and
• Fateh V. Singh

Beilstein J. Org. Chem. 2024, 20, 2891–2920, doi:10.3762/bjoc.20.243

• group with a less hindered portion is observed. The mechanism revealed the reaction undergoes the homolytic cleavage of the diaryliodonium salt to produce an iodoaryl radical cation, which further reacts with the amine to acquire the corresponding diaryl amines. Moreover, a similar reaction tried with a

• diaryliodonium salts 40 (Scheme 18) [69], which however, does not produce the diarylated compounds. The intramolecular aryl migration from the iodine to the nitrogen leads to a quaternary ammonium ion intermediate A. Consequently, a nucleophilic ring opening of cyclic amine in 42 occurred via cleavage of the

N-Glycosides of indigo, indirubin, and isoindigo: blue, red, and yellow sugars and their cancerostatic activity

• Peter Langer

Beilstein J. Org. Chem. 2024, 20, 2840–2869, doi:10.3762/bjoc.20.240

• -galactose and subsequent perbenzoylation afforded an anomeric mixture (α:β = 87:13) of tribenzoyl-4,6-benzylidene-ᴅ-galactose from which the pure α-anomer 10a was separated (Scheme 6) [20]. Cleavage of the acetal and subsequent regioselective replacement of the hydroxy group OH-6 with an iodide by

• , albeit, in low yield (Scheme 19) [25]. Cleavage of the benzyl groups using boron tribromide afforded β-31a. In contrast to indirubin-N-rhamnoside 17a, its isomer β-31a proved to be rather unstable. This fact was already earlier observed for indigo-N-rhamnoside 5d and again suggests that compounds

• % yield (Scheme 38) [59]. Unfortunately, all attempts to achieve a deprotection failed, due to cleavage of the lactone moiety. Starting with α-configured isatin-N-rhamnoside α-16a, anomerically pure α-64a could be prepared in 43% yield. Likewise, N-rhamnoside β-64b, N-glucoside β-64c, N-mannoside β-64d

Synthesis and antimycotic activity of new derivatives of imidazo[1,2-a]pyrimidines

• Dmitriy Yu. Vandyshev,
• Daria A. Mangusheva,
• Khidmet S. Shikhaliev,
• Kirill A. Scherbakov,
• Oleg N. Burov,
• Alexander D. Zagrebaev,
• Tatiana N. Khmelevskaya,
• Alexey S. Trenin and
• Fedor I. Zubkov

Beilstein J. Org. Chem. 2024, 20, 2806–2817, doi:10.3762/bjoc.20.236

• , the HB-5 proton would undergo additional cleavage at the proton of the adjacent NH group of the pyrimidine ring. Additionally, in the probable structures 10 and 12 the protons HA-5 and HA-6 should have been magnetically equivalent. The same reasoning can be applied to the spectra of 5a−e. The

The scent gland composition of the Mangshan pit viper, Protobothrops mangshanensis

• Jonas Holste,
• Paul Weldon,
• Donald Boyer and
• Stefan Schulz

Beilstein J. Org. Chem. 2024, 20, 2644–2654, doi:10.3762/bjoc.20.222

• derivatives with a C-5 double bond are a base peak at m/z 113 and two characteristic ions, m/z 153 resulting from formal cleavage of the double bond, and m/z 180, resulting from allylic cleavage of the C-7–C-8 bond (Supporting Information File 1, Figure S5) [23][24]. A similar pattern can be seen in the

• the first methyl group was at C-4, due to a missing peak at m/z 178 in the corresponding ion series (Supporting Information File 1, Figure S6). The next visible ion in this series, m/z 232 results from cleavage adjacent to the double bond, and the ion m/z 246 results from allylic cleavage. The 40 Da

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

• functionalization method where primary, secondary, and tertiary alkyl radicals can be readily generated through the sequential anodic oxidative fragmentation of alkyl carbazates, enabling the functionalization of N-heteroarenes [7]. This transformation is particularly valuable as the cleavage of the C–O bond to

• oxidized to a carbocation, which is subsequently attacked by the alkoxide to furnish the final product (Scheme 17). The Lei group also demonstrated C–F-bond formations, particularly developing an electrochemical method for the cleavage of C–C bonds and the 1,3-difunctionalization of arylcyclopropanes [26

Hypervalent iodine-mediated cyclization of bishomoallylamides to prolinols

• Smaher E. Butt,
• Konrad Kepski,
• Jean-Marc Sotiropoulos and
• Wesley J. Moran

Beilstein J. Org. Chem. 2024, 20, 2455–2460, doi:10.3762/bjoc.20.209

• ]. Iodoethane was also shown to be an effective reagent furnishing the product in up to 56% upon heating to 40 °C (Table 1, entries 11 and 12). It was envisaged that oxidation of iodoethane led to formation of oxidized forms of iodide by C–I-bond cleavage, therefore tetrabutylammonium iodide was utilized to see

Synthesis and conformational analysis of pyran inter-halide analogues of ᴅ-talose

• Olivier Lessard,
• Mathilde Grosset-Magagne,
• Paul A. Johnson and
• Denis Giguère

Beilstein J. Org. Chem. 2024, 20, 2442–2454, doi:10.3762/bjoc.20.208

• , therefore we were compelled to proceed directly to the next step. Cleavage of the 1,6-anhydro bridges was achieved under acetolysis conditions providing halogenated talopyranoses 12–15 in good yield over 3 steps as α anomers. Luckily, inter-halides 13–15 were crystalline, allowing the absolute configuration

Efficient one-step synthesis of diarylacetic acids by electrochemical direct carboxylation of diarylmethanol compounds in DMSO

• Hisanori Senboku and
• Mizuki Hayama

Beilstein J. Org. Chem. 2024, 20, 2392–2400, doi:10.3762/bjoc.20.203

• Pt cathode and a Mg anode in the presence of carbon dioxide induced reductive C(sp3)−O bond cleavage at the benzylic position in diarylmethanol compounds and subsequent fixation of carbon dioxide to produce diarylacetic acids in good yield. This protocol provides a novel and simple approach to

• diarylacetic acids from diarylmethanol species and carbon dioxide without transformation of the hydroxy group into appropriate leaving groups, such as halides and esters including carbonates. Keywords: C(sp3)–O bond cleavage; diarylacetic acid; diarylmethanol; electrochemical reduction; fixation of carbon

• dioxide; Introduction Electrochemical reduction of benzyl alcohol derivatives can induce reductive cleavage of a C(sp3)–O bond [1] at the benzylic position to generate the corresponding benzylic anion species. This protocol has been frequently applied to electrochemical carboxylation [2][3][4][5][6][7][8

Asymmetric organocatalytic synthesis of chiral homoallylic amines

• Nikolay S. Kondratyev and
• Andrei V. Malkov

Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201

• cleavage of the methoxyphenyl group in aqueous methanol using excess of ceric ammonium nitrate (CAN) as a soft oxidant (Scheme 14). The sequence afforded the target (S)-homoallylic amine 69 in 64% overall yield with a complete retention of chirality. To gain a mechanistic insight into the formation of the