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

• -mediated N–O bond cleavage afforded carbamate 90. The carbamate was converted to a carbonyl group via Boc deprotection with TFA, oxidation of the resulting amine to the oxime with Na2WO4 and H2O2, and subsequent reduction with TiCl3·HCl to give 91. The LaCl3·2LiCl-mediated methyl addition to the carbonyl

Rapid access to the core of malayamycin A by intramolecular dipolar cycloaddition

• Yilin Liu,
• Yuchen Yang,
• Chen Yang,
• Sha-Hua Huang,
• Jian Jin and
• Ran Hong

Beilstein J. Org. Chem. 2025, 21, 2542–2547, doi:10.3762/bjoc.21.196

• cleavage of the N–O bond, oxidation and Baeyer–Villiger oxidation. The starting functional groups (including alkyne and nitrone) for the proposed oxazoline were established in literature precedents [29][30][31]. Moreover, the readily available intermediate 8 [32] bearing three defined stereogenic centers

• ]-ring necessitates tedious optimization to properly install three continuous tertiary centers (C2, C3, and C4). To circumvent the influence of the electron-withdrawing group on the nitrogen atom, we anticipated that cleaving the N–O bond prior to breaking the C2–C2’ bond would be feasible. However

• , several conditions to cleave the N–O bond in 11 or 12 had not yielded any successful outcome. Therefore, we turned to adjust the synthetic sequence to switch the oxidation states at C2 and C3 (Scheme 4). It should be noted that compound 16 [38] was obtained as a stereoisomeric mixture of olefin, resulting

An Fe(II)-catalyzed synthesis of spiro[indoline-3,2'-pyrrolidine] derivatives

• Elizaveta V. Gradova,
• Nikita A. Ozhegov,
• Roman O. Shcherbakov,
• Alexander G. Tkachenko,
• Larisa Y. Nesterova,
• Elena Y. Mendogralo and
• Maxim G. Uchuskin

Beilstein J. Org. Chem. 2025, 21, 2383–2388, doi:10.3762/bjoc.21.183

• pathway (Scheme 4). Initial Fe(II)-mediated reductive cleavage of the N–O bond in the ketoxime acetate generates an iminyl radical. This is followed by a 5-exo-trig cyclization to form a carbon-centered radical. Final single-electron oxidation by Fe(III) delivers the desired spirocyclic product. All

• . For instance, an intramolecular SN2-type cyclization of β-3-indolyl ketone oximes using MsCl and Et₃N affords spiro[indoline-3,2'-pyrrolidines] (Scheme 1, path f) [13]. A subsequent Cu-catalyzed spirocyclization of β-3-indolyl ketone oxime acetates was developed. This process involves homolytic N–O

• bond cleavage to generate an N-imidoyl radical intermediate that undergoes intramolecular cyclization to yield the spirocyclic product (Scheme 1, path g) [14]. Notably, iron is known to exhibit similar behavior in single-electron transfer (SET) processes [15][16][17]. In fact, we previously

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

• nucleophilic cyclization to give D. The fracture of the N–O bond in D yielded E. Elimination of selenium cation A from E and the following cyclization afforded 38a. This transformation, combining selenium catalysis and organic electrosynthesis, proceeded smoothly at rt without external oxidants and metal

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

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

• (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

• a central role in this photocatalytic system. This strategy demonstrated good chemical selectivity for the functionalization of pyridine and alkanes, resulting in 55% to 86% yields of products 38, 39, 40, and 41, respectively. Amidyl radical from N–O bond cleavage In 2022, Alexanian’s group

• demonstrated the homolytic cleavage of the N–O bond using N-(tert-butyl)-O-(1-phenylvinyl)-phenylhydroxyamide as a HAT reagent [78][79]. This compound was capable of initiating the formation of amidyl radicals through visible light activation. Although their controlled experiments showed that this method was

Dioxazolones as electrophilic amide sources in copper-catalyzed and -mediated transformations

• Seungmin Lee,
• Minsuk Kim,
• Hyewon Han and
• Jongwoo Son

Beilstein J. Org. Chem. 2025, 21, 200–216, doi:10.3762/bjoc.21.12

• depicted in Figure 2. The reaction is initiated by formation of the five-membered copper-containing intermediate INT-5 through coordination of Cu(OAc)2 with the N-iminoquinolinium ylide species 5. This process is followed by decarboxylative N–O bond insertion into 4, yielding the N-acyl copper(III

• ) chloride reacts with boronic acids, forming the copper aryl complex INT-16, which then undergoes decarboxylative N–O bond insertion to generate the copper nitrenoid intermediate INT-17. Thereafter, nitrene insertion into the copper–carbon bond occurs, forming a new C(sp2)–N bond (INT-18). Finally, the

• and silane, undergoes the enantio-determining hydrocupration of the vinylarene, affording INT-25 [25]. Next, oxidative insertion of INT-25 into the N–O bond of the dioxazolone, forms INT-26, followed by decarboxylative reductive elimination to generate INT-27. Further incorporation of silane delivers

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

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

Multicomponent syntheses of pyrazoles via (3 + 2)-cyclocondensation and (3 + 2)-cycloaddition key steps

• Ignaz Betcke,
• Alissa C. Götzinger,
• Maryna M. Kornet and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2024, 20, 2024–2077, doi:10.3762/bjoc.20.178

Generation of alkyl and acyl radicals by visible-light photoredox catalysis: direct activation of C–O bonds in organic transformations

• Mithu Roy,
• Bitan Sardar,
• Itu Mallick and
• Dipankar Srimani

Beilstein J. Org. Chem. 2024, 20, 1348–1375, doi:10.3762/bjoc.20.119

• homolytic N–O bond breaking that yields phthalimide and an alkoxyl radical. This alkoxyl radical can easily extract hydrogen or undergo β-fragmentation. When P(OMe)3 is present, the alkoxyl radical combines with it to generate a phosphoranyl radical. This radical easily undergoes β-scission, resulting in

Synthesis of 1,2,3-triazoles containing an allomaltol moiety from substituted pyrano[2,3-d]isoxazolones via base-promoted Boulton–Katritzky rearrangement

• Constantine V. Milyutin,
• Andrey N. Komogortsev and
• Boris V. Lichitsky

Beilstein J. Org. Chem. 2024, 20, 1334–1340, doi:10.3762/bjoc.20.117

• a valuable recyclization of various systems containing an N–O bond in the ring. This approach is a powerful synthetic tool allowing to obtain diverse types of nitrogen-containing five-membered heterocycles [1][2]. Among the wide variety of recyclizations of this class the processes with

Mechanisms for radical reactions initiating from N-hydroxyphthalimide esters

• Carlos R. Azpilcueta-Nicolas and
• Jean-Philip Lumb

Beilstein J. Org. Chem. 2024, 20, 346–378, doi:10.3762/bjoc.20.35

• photochemical instability, as evidenced by their low N–O bond dissociation energy (BDE ≈ 42 kcal/mol) [28], the reliance on toxic tin hydrides as reductants and the undesired radical recombination with reactive 2-pyridylthiyl radicals that leads to (alkylthio)pyridine byproducts [26]. More recently, N

• transfer complexes with a donor species 6 or via LUMO lowering activation with Brønsted and Lewis acids 7 (Scheme 2B), collectively offering a number of variables to influence their reactivity. Upon reduction, RAEs give rise to a radical anion 8 with a weakened N–O bond (BDE < 70 kcal/mol) [33]. While

• (PC•–) (Scheme 4A). This strong reducing agent mediates the one-electron reduction of the NHPI ester 10, forming radical anion intermediate 11. Fragmentation of 11 via N–O bond homolysis and decarboxylation forms the key tertiary radical 12 with concomitant formation of phthalimidyl anion (–Nphth) and

Recent advancements in iodide/phosphine-mediated photoredox radical reactions

• Tinglan Liu,
• Yu Zhou,
• Junhong Tang and
• Chengming Wang

Beilstein J. Org. Chem. 2023, 19, 1785–1803, doi:10.3762/bjoc.19.131

• -dihydronaphthalenes 47 with yields of up to 92%, as depicted in Scheme 21 [38]. The key aspect of the approach involved the simultaneous cleavage of dual C–C bonds and a single N–O bond, which was facilitated by the utilization of LiI/PPh3 as the photoredox system. Amination Anilines play important roles in both

One-pot nucleophilic substitution–double click reactions of biazides leading to functionalized bis(1,2,3-triazole) derivatives

• Hans-Ulrich Reissig and
• Fei Yu

Beilstein J. Org. Chem. 2023, 19, 1399–1407, doi:10.3762/bjoc.19.101

• on carbon and provided the expected (propyloxy)methyl-substituted aminopyran 22 in 81% yield (Scheme 7, reaction 1). The reductive removal of the N-benzyl group and the cleavage of the N–O bond occurred apparently without problems. With the second model compound, 1,2,3-triazole 23, which is almost

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

Synthesis of aliphatic nitriles from cyclobutanone oxime mediated by sulfuryl fluoride (SO₂F₂)

• Xian-Lin Chen and
• Hua-Li Qin

Beilstein J. Org. Chem. 2023, 19, 901–908, doi:10.3762/bjoc.19.68

• works, we contemplated that the N–O bond of cyclobutanone oxime derivatives could be activated by SO2F2 in situ to enable cleavage of the C–C bond, which could achieve this transformation without going through inefficient pre-introduction of electrophores. Herein, we describe how this concept has been

Transition-metal-catalyzed domino reactions of strained bicyclic alkenes

• Austin Pounder,
• Eric Neufeld,
• Peter Myler and
• William Tam

Beilstein J. Org. Chem. 2023, 19, 487–540, doi:10.3762/bjoc.19.38

• forms 164. Next, cleavage of the N–O bond followed by an oxidative addition of the Rh(III) to the N–O bond forms intermediate 165 which can finally undergo reductive elimination giving the final product 160a. In 2013, Li reported the domino coupling reaction of 2-phenylpyridines 165 with oxa- and

1,4-Dithianes: attractive C2-building blocks for the synthesis of complex molecular architectures

• Bram Ryckaert,
• Ellen Demeyere,
• Frederick Degroote,
• Hilde Janssens and
• Johan M. Winne

Beilstein J. Org. Chem. 2023, 19, 115–132, doi:10.3762/bjoc.19.12

• reactions, as pseudo-heteroarylzinc reagents. Another example developed by Knochel uses the zincated 1,4-dithiin 22 as a nucleophile to add across the N–O bond in anthranil [44], which spontaneously cyclizes to a heterocycle-fused quinoline via a Friedel–Crafts-type pathway onto the released aldehyde moiety

Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• –elimination pathway (SNHAE), where deoxygenation of imidazole 1-oxide resulted in the formation of perfluoroarylated 2H-imidazoles; and (B) addition–oxidation pathway (SNHAO), where without affecting the N–O bond of imidazole 1-oxides, perfluoroarylated 2H-imidazole 1-oxides were obtained as final products

Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition

• Anaïs Rousseau,
• Guillaume Vincent and
• Cyrille Kouklovsky

Beilstein J. Org. Chem. 2022, 18, 1385–1395, doi:10.3762/bjoc.18.143

• –O bond from an 1,2-oxazine, itself obtained by a nitroso Diels–Alder reaction from a chiral nitroso derivative and a functionalized diene (Figure 3). The nitroso Diels–Alder cycloaddition reaction has been well studied and has been used as a powerful tool for synthesis [19][20][21][22]. We have

• both fragments for the synthesis of an advanced intermediate. The synthetic strategy for the synthesis of the central fragment takes advantage of the proximity between the terminal amino function and the hydroxy function at C9. It was anticipated that both functions could arise from the cleavage of a N

Direct C–H amination reactions of arenes with N-hydroxyphthalimides catalyzed by cuprous bromide

• Dongming Zhang,
• Bin Lv,
• Pan Gao,
• Xiaodong Jia and
• Yu Yuan

Beilstein J. Org. Chem. 2022, 18, 647–652, doi:10.3762/bjoc.18.65

• -electron transfer (SET) between CuBr and intermediate 5 forms intermediate 6, which initiates the N–O bond homolytic cleavage resulting in forming an N-centred phthalimidyl radical 7 (PhthN•) and anion 8. Meanwhile, Cu(I) is oxidized to Cu(II) in this step. Next, radical 7 attacks the benzene via radical

Organocatalytic asymmetric nitroso aldol reaction of α-substituted malonamates

• Ekta Gupta,
• Narendra Kumar Vaishanv,
• Sandeep Kumar,
• Raja Krishnan Purshottam,
• Ruchir Kant and
• Kishor Mohanan

Beilstein J. Org. Chem. 2022, 18, 217–224, doi:10.3762/bjoc.18.25

• encountered in organic synthesis as precursors for the synthesis of nitrogen and oxygen-containing molecules [1][2][3][4][5]. The high reactivity caused by the polarization of the N–O bond enables the nitrosoarenes to undergo a wide range of transformations in a chemo- and regioselective manner [6][7][8]. The

• ). Disappointingly, the reactions carried out by varying the α-substitution did not afford the desired product. In order to demonstrate the synthetic utility of the oxyaminated compounds, the reductive cleavage of the N–O bond was attempted under Zn/AcOH conditions. Pleasingly, the reaction afforded the aniline

Iron-catalyzed domino coupling reactions of π-systems

• Austin Pounder and
• William Tam

Beilstein J. Org. Chem. 2021, 17, 2848–2893, doi:10.3762/bjoc.17.196

• to the breadth of reactions viable from iminyl radicals, generating through the homolytic cleavage of the N–O bond, a number of Fe-catalyzed domino reactions have been investigated. In 2018, Okamoto and Ohe reported an iminoarylation of γ,δ-unsaturated oxime esters 165 with arenes 166 (Scheme 35

Highly stereocontrolled total synthesis of racemic codonopsinol B through isoxazolidine-4,5-diol vinylation

• Lukáš Ďurina,
• Anna Ďurinová,
• František Trejtnar,
• Ľuboš Janotka,
• Lucia Messingerová,
• Jana Doháňošová,
• Ján Moncol and
• Róbert Fischer

Beilstein J. Org. Chem. 2021, 17, 2781–2786, doi:10.3762/bjoc.17.188

• the expected high syn diol diastereoselectivity (Scheme 1). The obtained anti,syn-(hydroxyamino)alkenol 4 will be then subjected to reductive cleavage of the N–O bond. Next, a key intermediate epoxide 5 with the desired syn (threo) configuration between the hydroxy group and the epoxide oxygen could