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

Synthesis of phenanthridines via a novel photochemically-mediated cyclization and application to the synthesis of triphaeridine

• Songeziwe Ntsimango,
• Kennedy J. Ngwira,
• Moira L. Bode and
• Charles B. de Koning

Beilstein J. Org. Chem. 2021, 17, 2340–2347, doi:10.3762/bjoc.17.152

• hypothesized that oxime 7 undergoes a homolytic cleavage of the N–O bond giving the iminyl radical 11 [14] followed by an intramolecular cyclization with concomitant expulsion of the ortho-methoxy group, liberating phenanthridine 9. To the best of our knowledge, such a reaction in which the aromatic methoxy

α,γ-Dioxygenated amides via tandem Brook rearrangement/radical oxygenation reactions and their application to syntheses of γ-lactams

• Mikhail K. Klychnikov,
• Radek Pohl,
• Ivana Císařová and
• Ullrich Jahn

Beilstein J. Org. Chem. 2021, 17, 688–704, doi:10.3762/bjoc.17.58

• trans-12b can be also easily deprotected by a rhodium-catalyzed isomerization to the corresponding N-propenyl lactam followed by osmium tetroxide-catalyzed oxidative cleavage, providing lactam trans-17 in 62% yield. Additionally, the diastereomeric mixture of lactam 12o was subjected to oxidative N–O

• bond cleavage by mCPBA furnishing bicyclo[3.3.0]octandiones 18. The isolation of a mixture of four diastereomers as in the starting material indicates that radical coupling by TEMPO proceeds with exclusive diastereoselectivity (vide infra). Discussion The sequence nucleophilic epoxide opening/Brook

Novel library synthesis of 3,4-disubstituted pyridin-2(1H)-ones via cleavage of pyridine-2-oxy-7-azabenzotriazole ethers under ionic hydrogenation conditions at room temperature

• Romain Pierre,
• Anne Brethon,
• Sylvain A. Jacques,
• Aurélie Blond,
• Sandrine Chambon,
• Sandrine Talano,
• Catherine Raffin,
• Branislav Musicki,
• Claire Bouix-Peter,
• Loic Tomas,
• Gilles Ouvry,
• Rémy Morgentin,
• Laurent F. Hennequin and
• Craig S. Harris

Beilstein J. Org. Chem. 2021, 17, 156–165, doi:10.3762/bjoc.17.16

• -azabenzotriazole ring to the 7-azabenzotriazoline ring 18 and cleavage of the N–O bond through delocalization of the lone pair at N-2 to liberate 1 and 1H-[1,2,3]triazolo[4,5-b]pyridine as the byproduct. The second pathway occurs through 4 key steps: a) activation of the pyridine in the acidic media; b) ring

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• to intramolecular dipolar cycloaddition to give racemic adducts (±)-13 and (±)-14, with good yields. The synthesis was complete according to the procedure used by Gössinger [25]. Thus, the reductive cleavage of the N–O bond in the presence of Raney-Ni and hydrogen provided the bicyclic alcohols

• azatricyclo[3.3.1.1]decane (+)-23a in 54% yield. Treatment of (+)-23a with Raney nickel resulted in the cleavage of the sulfinyl group and the N–O bond, providing the bicyclic alcohol 24, which was oxidized with PCC to give (+)-euphococcinine (2). The same protocol was applied to (+)-21b, furnishing the

Synthesis of tetrafluorinated piperidines from nitrones via a visible-light-promoted annelation reaction

• Vyacheslav I. Supranovich,
• Igor A. Dmitriev and
• Alexander D. Dilman

Beilstein J. Org. Chem. 2020, 16, 3104–3108, doi:10.3762/bjoc.16.260

• photocatalyst activated by blue light. The annelation is a result of a radical addition at the nitrone, intramolecular nucleophilic substitution, and reduction of the N–O bond. Keywords: difluoroalkylation; nitrones; organofluorine compounds; photocatalysis; radical addition; Introduction Nitrogen-containing

• , after the fluoroalkylation event, the reduction of the N–O bond had occurred. The corresponding addition of an additional amount of the reductant and performing the reaction in DMF led to product 3a in 84% isolated yield (Table 1, entry 4). Under the optimized conditions, a series of nitrones were

• from nitrones and a fluorinated building block is described. The annelation is based on a sequence of visible-light-promoted redox processes and a substitution reaction, and involves the cleavage of the N–O bond. The construction of tetrafluorinated piperidines from nitrones. The scope of the

Synthesis of new fluorescent molecules having an aggregation-induced emission property derived from 4-fluoroisoxazoles

• Kazuyuki Sato,
• Akira Kawasaki,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2020, 16, 1411–1417, doi:10.3762/bjoc.16.117

• diketone (Scheme 5). As an alternative method to synthesize F-BKIs 9, we turned our attention to the ring-opening reaction of isoxazoles. The reductive cleavage of the N–O bond in isoxazoles can be achieved by transition metals or their complexes to give the corresponding enaminoketones [35][37

• in the aggregated state and exhibited a redshift in the emission intensity. We also achieved the first synthesis of α-fluorinated boron ketoiminates (F-BKIs) by the reductive cleavage of the N–O bond in 4-fluorinated isoxazoles and demonstrated that F-BKIs exhibited AIE property similarly to their

Synthesis of 3-substituted isoxazolidin-4-ols using hydroboration–oxidation reactions of 4,5-unsubstituted 2,3-dihydroisoxazoles

• Lívia Dikošová,
• Júlia Laceková,
• Ondrej Záborský and
• Róbert Fischer

Beilstein J. Org. Chem. 2020, 16, 1313–1319, doi:10.3762/bjoc.16.112

• 8b resulted only in a reductive cleavage of the N–O bond. A successful debenzylation was achieved in a two-step procedure using 2,2,2-trichloroethyl chloroformate (TrocCl). However, the protection of the hydroxy group was required first (for the reaction of 8b with benzoyl chloride, see Supporting

• identified as a readily oxidizable polar component by permanganate detection even at room temperature. The prior attempts to cleave the Troc group by zinc dust in acetic acid [42] failed due to the reduction of the N–O bond. Conclusion In summary, we have developed a new synthetic approach towards 3

Oxime radicals: generation, properties and application in organic synthesis

• Igor B. Krylov,
• Stanislav A. Paveliev,
• Alexander S. Budnikov and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2020, 16, 1234–1276, doi:10.3762/bjoc.16.107

• C=N–O angle and a shortened N–O bond compared to the corresponding oximes (Figure 3) [44][52][70]. One of the important quantitative values that determine the reactivity of O radicals is the O–H bond dissociation enthalpy (BDE) in the parent OH compound (Figure 4). This value affects both the ease

Recent advances in Cu-catalyzed C(sp³)–Si and C(sp³)–B bond formation

• Balaram S. Takale,
• Ruchita R. Thakore,
• Elham Etemadi-Davan and
• Bruce H. Lipshutz

Beilstein J. Org. Chem. 2020, 16, 691–737, doi:10.3762/bjoc.16.67

• bond formation Organoboron compounds are widely used in C–C and C–X (X = N, O) bond constructions. Straightforward methods for their synthesis involve the copper-catalyzed addition of organoboron compounds to alkynes, alkenes, and unsaturated carbonyl compounds, as well as the nucleophilic borylation

p-Pyridinyl oxime carbamates: synthesis, DNA binding, DNA photocleaving activity and theoretical photodegradation studies

• Panagiotis S. Gritzapis,
• Panayiotis C. Varras,
• Nikolaos-Panagiotis Andreou,
• Katerina R. Katsani,
• Konstantinos Dafnopoulos,
• George Psomas,
• Zisis V. Peitsinis,
• Alexandros E. Koumbis and
• Konstantina C. Fylaktakidou

Beilstein J. Org. Chem. 2020, 16, 337–350, doi:10.3762/bjoc.16.33

• , Figure 1) are also recognized as DNA “photocleavage” agents owing their action to the homolysis of their vulnerable N–O bond, at 312 nm [9][39][40][41][42][43] or 365 nm [44][45] yielding photogenerated carbonyloxyl radicals (CRs), which are able to cause oxidative DNA damage. We have recently reported

• radicals are also produced from 2-(1-naphthylmethyl)imidazoline [35], whereas acylaminyl radicals [R(COR)N∙] are formed from the photocleavage of the N–O bond of N,O-diacyl-N-phenylhydroxylamines, along with a carbonyloxyl radical [38]. The photochemistry of O-carbamoyl oximes (or oxime carbamates) is well

• aspects of compounds 11 and 12 The ground state structures (S0) for both molecules 12 and 11 in their Z-conformations are similar (Figure S-8.1A and B, Supporting Information File 1) with the length of the N–O bond varying between r(N–O) = 1.423 (12) and 1.425 Å (11). (Table S-8.1, Supporting Information

Application of chiral 2-isoxazoline for the synthesis of syn-1,3-diol analogs

• Juanjuan Feng,
• Tianyu Li,
• Jiaxin Zhang and
• Peng Jiao

Beilstein J. Org. Chem. 2019, 15, 1840–1847, doi:10.3762/bjoc.15.179

• boronic acid had been widely utilized to disconnect the N–O bond as well as to hydrolyze the resulting imine into a ketone [52]. We applied this method to deprotect the isoxazoline 3. However, the desired β-hydroxy ketone was never obtained. In one instance, the methyl ketone from a retro-aldol reaction

Synthesis of nonracemic hydroxyglutamic acids

• Dorota G. Piotrowska,
• Iwona E. Głowacka,
• Andrzej E. Wróblewski and
• Liwia Lubowiecka

Beilstein J. Org. Chem. 2019, 15, 236–255, doi:10.3762/bjoc.15.22

• with 69 and (2S,4S)-3 [78]. Two other stereoisomers were synthesized in a similar way from (R)-67. By a nitrone–acrylate cycloaddition The isoxazolidine ring can be considered as another cyclic precursor to 4-hydroxyglutamic acids due to the easy cleavage of the N–O bond and high trans