Photoswitches beyond azobenzene: a beginner’s guide

• Michela Marcon,
• Christoph Haag and
• Burkhard König

Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143

Fe-catalyzed efficient synthesis of 2,4- and 4-substituted quinolines via C(sp²)–C(sp²) bond scission of styrenes

• Prafull A. Jagtap,
• Manish M. Petkar,
• Vaishnavi R. Sawant and
• Bhalchandra M. Bhanage

Beilstein J. Org. Chem. 2025, 21, 1799–1807, doi:10.3762/bjoc.21.142

• -disubstituted and 4-substituted quinoline molecules. The developed strategy involves an earth-abundant Fe-catalyzed C(sp2)–C(sp2) bond cleavage of styrene, followed by the hydroamination of the cleaved synthons with arylamines and subsequent C–H annulation to yield two valuable quinoline derivatives. Key

• promising industrial relevance. Oxidative cleavage of alkenes to yield carbonyl compounds is one of the key transformations in synthetic organic chemistry [41][42]. Over the past two decades, this field has witnessed significant advancements, primarily through the use of organic oxidants and transition

• -metal catalysts. One of the key transformations in organic synthesis is the selective oxidative cleavage of alkenes to yield ketones or aldehydes [43][44][45][46][47]. Traditionally, such transformations have been achieved using various oxidizing agents, transition-metal-based systems, organo- and

Preparation of a furfural-derived enantioenriched vinyloxazoline building block and exploring its reactivity

• Madara Darzina,
• Anna Lielpetere and
• Aigars Jirgensons

Beilstein J. Org. Chem. 2025, 21, 1737–1741, doi:10.3762/bjoc.21.136

• methoxymethyl group cleavage, O-to-N rearrangement, and isomerization of the double bond. An oxazoline ring formation in the resulting unsaturated amides provided the corresponding enantioenriched vinyloxazoline. The reactivity of the electron-deficient double bond in the vinyloxazoline was explored in several

• . Cleavage of the N-Alloc group leading to a mixture of isomers cis-S-5 and trans-S-5. Cleavage of the N-Alloc group with PdCl2(S-BINAP) leading to trans-S-5 and trans-R-5. Cyclization of amides trans-S-5 and trans-R-5 to oxazolines S-6 and R-6. aza-Diels–Alder reaction of vinyloxazoline S-6 with TsNCO. The

3-Aryl-2H-azirines as annulation reagents in the Ni(II)-catalyzed synthesis of 1H-benzo[4,5]thieno[3,2-b]pyrroles

• Julia I. Pavlenko,
• Pavel A. Sakharov,
• Anastasiya V. Agafonova,
• Derenik A. Isadzhanyan,
• Alexander F. Khlebnikov and
• Mikhail S. Novikov

Beilstein J. Org. Chem. 2025, 21, 1595–1602, doi:10.3762/bjoc.21.123

• to the azirine C=N bond, followed by cyclization and the aziridine ring opening into the [3 + 2] cycloaddition product 5 (Scheme 3). It is noteworthy that the annulation proceeds via the azirine N‒C3 bond cleavage. Elimination of the methoxycarbonyl group most likely occurs under the action of

• the NHC-complex, IPrCuCl, the formation of cycloadduct 11 was detected, which was isolated in 10% yield (Scheme 6). The formation of this compound implies the cleavage of the azirine N−C2 bond, indicating that the IPrCuCl-catalyzed reaction proceeds by a different mechanism, likely involving the

Wittig reaction of cyclobisbiphenylenecarbonyl

• Taito Moribe,
• Junichiro Hirano,
• Hideaki Takano,
• Hiroshi Shinokubo and
• Norihito Fukui

Beilstein J. Org. Chem. 2025, 21, 1454–1461, doi:10.3762/bjoc.21.107

• dibenzo[g,p]chrysene (DBC, 2) via oxidative inner-bond cleavage (Figure 1) [16][17]. CBBC 1 was first synthesized by Suszko and Schillak in 1934 using sodium dichromate as an oxidant [16]. Recently, our group developed a scalable, catalytic, and enantioselective protocol to furnish CBBC 1 [17]. Several

Oxetanes: formation, reactivity and total syntheses of natural products

• Peter Gabko,
• Martin Kalník and
• Maroš Bella

Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101

• from simple cyclopentenones 71 and symmetric alkenes 72 (Scheme 20) [60]. Although the reaction is rather low-yielding (mostly below 30%), it tends to give high diastereoselectivities. The mechanism is believed to proceed through the following steps: [2 + 2] photocycloaddition, Norrish-type I cleavage

• halogens, nitriles, alkenes and heteroaryls. On the other hand, this methodology suffers from relatively low diastereoselectivity as the dr lies between 1:1 and 2:1. DFT calculations suggested the reaction proceeds through nitrogen elimination, oxonium ylide 119 formation, homolytic cleavage and radical

• 2020, Bull et al. published a short synthesis of 3-aryloxetan-3-carboxylic acids 152 employing a Friedel–Crafts alkylation (which builds on their previous alkylation of phenols [87]) and a selective furan oxidative cleavage (Scheme 37) [88]. The oxidation protocol uses a catalytic amount of a high

Recent advances in amidyl radical-mediated photocatalytic direct intermolecular hydrogen atom transfer

• Hao-Sen Wang,
• Lin Li,
• Xin Chen,
• Jian-Li Wu,
• Kai Sun,
• Xiao-Lan Chen,
• Ling-Bo Qu and
• Bing Yu

Beilstein J. Org. Chem. 2025, 21, 1306–1323, doi:10.3762/bjoc.21.100

• amidyl radicals from HRP: (a) direct single-electron oxidation of amide HRP in the presence of photocatalyst and a base via a proton-coupled electron transfer (PCET) process by the cleavage of the N–H bond; (b) single-electron reduction of HRP catalyzed by photocatalyst via a single-electron transfer

• (SET) process by the cleavage of the N–O bond; (c) direct homolytic cleavage of weak N–S or N–X bonds in HRP initiated in the presence of visible light; (d) the intersystem crossing (ISC) of S1 to T1 state directly from the amide anion. This review is organized by bond cleavage type, offering a deep

• with a systematic understanding and strategic toolkit, thereby propelling the development of direct functionalization of C–H, B–H, Si–H, and Ge–H techniques in modern organic synthesis. Most of the photocatalysts used in this review are listed in Figure 3. Review Amidyl radical from N–H bond cleavage N

Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents

• Jiangfei Chen,
• Yi-Lin Qu,
• Ming Yuan,
• Xiang-Mei Wu,
• Heng-Pei Jiang,
• Ying Fu and
• Shengrong Guo

Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98

• -methylpiperidine, proved compatible with the reaction conditions, yielding the corresponding 3-(2-oxoethyl)indolin-2-ones 5a–g in 40–78% yields. Following a detailed investigation, a plausible mechanism was proposed, as illustrated in Scheme 3. Initially, TBHP undergoes cleavage by Fe2+ to generate a tert-butoxy

• demonstrated that both primary and secondary alcohols were compatible substrates (7a, 7f). The proposed reaction mechanism involves oxidative radical cyclization. Initially, TBHP undergoes homolytic cleavage to generate a tert-butoxy radical, which then forms an α-hydroxy carbon radical. This radical

• -substituents induced steric hindrance effects that led to lower yields. To gain further insight into the mechanism, several control experiments were performed. The results indicated that an iminoxyl radical is generated as the initiator of the reaction (Scheme 6). Initially, TBHP undergoes homolytic cleavage

A multicomponent reaction-initiated synthesis of imidazopyridine-fused isoquinolinones

• Ashutosh Nath,
• John Mark Awad and
• Wei Zhang

Beilstein J. Org. Chem. 2025, 21, 1161–1169, doi:10.3762/bjoc.21.92

• reaction followed by the cleavage of the alkyl group to give intermediate II as a free amine. Annulation of II with CDI gave product B which is an HIV reverse transcriptase inhibitor (Scheme 1B) [17]. We have reported a three-component [3 + 2] cycloaddition followed by IMDA reaction for making heterocyclic

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

• , reductive cleavage of the chiral auxiliary using a combination of LDA and BH3·NH3 provided the target molecule 82 in a 76% yield. The authors emphasized that the Theodorakis’ C3–C11 fragment 82 of borrelidin was synthesized via a concise 8-step route, achieving a 36% overall yield from the chiral pool

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

• cinnamic acid. For example, Chen and co-workers (2020) reported the Pd-catalyzed N-acylation of cinnamic acids using tertiary amines to generate the corresponding amides 83 and 84 in good yields via C–N cleavage (Scheme 25) [61]. The active Pd0 species was inserted into the carboxylate group to afford the

• -workers (2022) functionalized Weinreb amides through organophotocatalytic N–O cleavage via 114 and 115 to give the corresponding primary amides 111–113 in good yields (Scheme 34) [27]. Xie and co-workers (2022) synthesized cinnamamide 83 mediated by [Ir(dF(CF3)ppy)2(dtbbpy)]PF6 (PC-1) as photocatalyst

• proceeding via C–N-bond cleavage of the oxidized tertiary amine 116 (Scheme 35) [70]. Cinnamic acid (7) was activated by forming the acyl radical 118 after −OPyf group cleavage from 117. Recently, Li and co-workers (2024) studied visible-light-mediated FeCl3-catalyzed reductive transamidation of nitro

Biobased carbon dots as photoreductants – an investigation by using triarylsulfonium salts

• Valentina Benazzi,
• Arianna Bini,
• Ilaria Bertuol,
• Mariangela Novello,
• Federica Baldi,
• Matteo Hoch,
• Alvise Perosa and
• Stefano Protti

Beilstein J. Org. Chem. 2025, 21, 1024–1030, doi:10.3762/bjoc.21.84

• from direct photoreactivity [24][25], sulfonium salts can be easily reduced under photoredox-catalyzed conditions [20][21][22], and the resulting radical undergoes homolytic cleavage of one of the C–S bonds, releasing an aryl radical Ar• and a diaryl sulfide Ar2S. Subsequently, triarylsulfonium ions

Studies on the syntheses of β-carboline alkaloids brevicarine and brevicolline

• Benedek Batizi,
• Patrik Pollák,
• András Dancsó,
• Péter Keglevich,
• Gyula Simig,
• Balázs Volk and
• Mátyás Milen

Beilstein J. Org. Chem. 2025, 21, 955–963, doi:10.3762/bjoc.21.79

• , versatile key triflate intermediate 3, which allowed the introduction of substituents attached by a C–C bond to position 4 of the β-carboline scaffold by cross-coupling reactions. Sonogashira reaction of compound 3 with N-(3-butynyl)phthalimide (4) led to coupled compound 5. Cleavage of the phthalimide

A convergent synthetic approach to the tetracyclic core framework of khayanolide-type limonoids

• Zhiyang Zhang,
• Jialei Hu,
• Hanfeng Ding,
• Li Zhang and
• Peirong Rao

Beilstein J. Org. Chem. 2025, 21, 926–934, doi:10.3762/bjoc.21.75

• oxidative cleavage [47] was applied to deliver aldehyde 29. Finally, a one-pot acetalization and desilylation effectively afforded the acetal alcohol, which was then oxidized with the aid of TPAP, furnishing acetal aldehyde 14 in 67% yield over two steps. With the two fragments 13 and 14 in hand, the next

Recent advances in controllable/divergent synthesis

• Jilei Cao,
• Leiyang Bai and
• Xuefeng Jiang

Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73

• intermediates Int-53 or Int-53'. Reductive elimination of Int-53 or Int-53' regenerates Pd(0) and produces intermediate 55. With the assistance of the base K2CO3, the ten-membered silacycle 55 undergoes rapid ring contraction via cleavage of two Si–O bonds and formation of one Si–O bond, leading to 56 and Int

• -55. Concurrently, Int-55 dimerizes to form 54, which is further transformed into cyclosiloxanes under K2CO3 and DMA conditions. Intermediate 56 undergoes additional ring contraction through cleavage of Si–O/Si–C bonds and formation of a Si–C bond, yielding 57 and Int-56, with Int-56 polymerizing to

• generate cyclosiloxanes. An alternative pathway involving cleavage of another Si–O bond during the conversion from 55 to 56 and subsequently to 57 cannot be excluded. Temperature control Temperature, as a readily adjustable physical parameter in organic synthesis, offers a simple and versatile approach to

Dicarboxylate recognition based on ultracycle hosts through cooperative hydrogen bonding and anion–π interactions

• Wen-Hui Mi,
• Teng-Yu Huang,
• Xu-Dong Wang,
• Yu-Fei Ao,
• Qi-Qiang Wang and
• De-Xian Wang

Beilstein J. Org. Chem. 2025, 21, 884–889, doi:10.3762/bjoc.21.72

• reorganization likely involves the cleavage and re-formation of the dynamic Ctriazine–OAr bonds, and the presence of an excess of base could facilitate the formation of the thermodynamic-favored reorganized products [29][31]. The benzyl groups were subsequently removed under Pd/C and H2 conditions to afford the

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