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

Synthesis and biological activity of methylated derivatives of the Pseudomonas metabolites HHQ, HQNO and PQS

• Sven Thierbach,
• Max Wienhold,
• Susanne Fetzner and
• Ulrich Hennecke

Beilstein J. Org. Chem. 2019, 15, 187–193, doi:10.3762/bjoc.15.18

• methylated HHQ derivatives. The N–O bond appeared to be unstable under these alkylation conditions. Therefore, the synthesis of the 4-methoxy derivative was carried out starting from OMe-HHQ (3). Upon treatment of 3 with mCPBA the compound was cleanly oxidized to 4OMe-HQNO (7, Scheme 2). Purification by

• and the HQNO derivative 6 elicited PQS and HQNO production by P. aeruginosa PAO1, suggesting quorum sensing activity. However, the significant activity of the HQNO derivative 6 is unexpected, as HQNO is not a signal. We assume that the weak N–O bond is cleaved under the assay conditions and HHQ is

Transition metal-free oxidative and deoxygenative C–H/C–Li cross-couplings of 2H-imidazole 1-oxides with carboranyl lithium as an efficient synthetic approach to azaheterocyclic carboranes

• Lidia A. Smyshliaeva,
• Mikhail V. Varaksin,
• Pavel A. Slepukhin,
• Oleg N. Chupakhin and
• Valery N. Charushin

Beilstein J. Org. Chem. 2018, 14, 2618–2626, doi:10.3762/bjoc.14.240

• and 5a–d, respectively. In accordance with the current SNH concept, the first step of both protocols, SNH(AE) and SNH(AO), involves a reversible formation of unstable anionic σH-adducts 3(a–d)-OLi as a result of nucleophilic attack of carboranyllithium 2 at the CH=N+–O− bond of 2H-imidazole 1-oxides

Cationic cobalt-catalyzed [1,3]-rearrangement of N-alkoxycarbonyloxyanilines

• Itaru Nakamura,
• Mao Owada,
• Takeru Jo and
• Masahiro Terada

Beilstein J. Org. Chem. 2018, 14, 1972–1979, doi:10.3762/bjoc.14.172

• catalyst; concerted reaction; N–O bond; rearrangement; Introduction The 2-aminophenol moiety is ubiquitously found as a core structure of biologically active compounds, such as tigecycline [1], iguratimod [2], and phosalone (Scheme 1) [3]. The scaffolds have also been frequently utilized as synthetic

• driven by cleavage of the N–O bond is an ideal approach to selectively synthesize O-protected 2-aminophenols 2 while maintaining the oxidation state during the transformation (Scheme 2a) [4][5][6][7][8][9][10][11]. However, there is a significant drawback, these [3,3]-rearrangements of carboxylic acyloxy

• -catalysed cascade reaction involving rearrangement via N–O bond cleavage [14]. While divalent copper acetate and copper chloride did not show any catalytic activities (Table 1, entries 1 and 2), more Lewis acidic copper complexes, such as [Cu(MeCN)4](PF6)2 and [Cu(OTf)]2·toluene, afforded the corresponding

Acid-catalyzed ring-opening reactions of a cyclopropanated 3-aza-2-oxabicyclo[2.2.1]hept-5-ene with alcohols

• Katrina Tait,
• Alysia Horvath,
• Nicolas Blanchard and
• William Tam

Beilstein J. Org. Chem. 2017, 13, 2888–2894, doi:10.3762/bjoc.13.281

• represent the first examples of ring-openings of cyclopropanated 3-aza-2-oxabicyclo[2.2.1]alkenes that lead to the cleavage of the C–O bond instead of the N–O bond. Different acid catalysts were tested and it was found that pyridinium toluenesulfonate in methanol gave the best yields in the ring-opening

• reactivity of the cyclopropanated derivative (Scheme 4) and in both studies, cleavage of the N–O bond (b) was observed. While the Buono group demonstrated the reductive N–O bond cleavage to produce compound 25 as proof-of-principle [16], the Miller group reported the use of the cyclopropanated compound for

• -oxabicyclo[2.2.1]alkenes reductively cleave the N–O bond (a) (Scheme 4), therefore, no examples cleaving the C–O bond have been reported in the literature. In this paper, we aim to explore the use of an acid catalyst with an alcohol nucleophile on the ring-opening of cyclopropanated 3-aza-2-oxabicyclic

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• to a wide range of alkenes featuring various functional groups. Further reduction of the N–O bond by Mo(CO)6 gave the corresponding alcohols. A protocol free of peroxide initiator was developed by Yang, Vicic and co-workers using a manganese salt and O2 from air [35]. Styrene derivatives were

Iodination of carbohydrate-derived 1,2-oxazines to enantiopure 5-iodo-3,6-dihydro-2H-1,2-oxazines and subsequent palladium-catalyzed cross-coupling reactions

• Michal Medvecký,
• Igor Linder,
• Luise Schefzig,
• Hans-Ulrich Reissig and
• Reinhold Zimmer

Beilstein J. Org. Chem. 2016, 12, 2898–2905, doi:10.3762/bjoc.12.289

• -oxazines that after cleavage of the N–O bond provide the corresponding amino alcohols. In the second reaction step, the hydrogen attacks the C=C bond mainly from the less hindered side (here trans to the fairly bulky 3-dioxolanyl group) leading to the preferred configuration of anti-30a as depicted in

Synthesis of 2,1-benzisoxazole-3(1H)-ones by base-mediated photochemical N–O bond-forming cyclization of 2-azidobenzoic acids

• Daria Yu. Dzhons and
• Andrei V. Budruev

Beilstein J. Org. Chem. 2016, 12, 874–881, doi:10.3762/bjoc.12.86

• an intermediate singlet nitrene. Possibly, similar to the benzofuroxan and 3-amino-6-nitro-2,1-benzisoxazole formation, the carboxylate group of A (Lewis base) donates an electron lone pair to the electron-deficient singlet nitrene fragment of A (Lewis acid) with formation of the N–O bond in 2

Copper-catalyzed aminooxygenation of styrenes with N-fluorobenzenesulfonimide and N-hydroxyphthalimide derivatives

• Yan Li,
• Xue Zhou,
• Guangfan Zheng and
• Qian Zhang

Beilstein J. Org. Chem. 2015, 11, 2721–2726, doi:10.3762/bjoc.11.293

• investigate the synthetic value of our new aminooxygenation method. Then, the selective reduction of 3g was conducted (Scheme 3). The cleavage of the N–O bond in 3g readily occurred with Mo(CO)6/Et3N at 80 °C to give alcohol 4 [36] in 67% yield. Treatment of 3g with NH2NH2·H2O under mild conditions (25 °C) in

Photoinduced 1,2,3,4-tetrahydropyridine ring conversions

• Baiba Turovska,
• Henning Lund,
• Viesturs Lūsis,
• Anna Lielpētere,
• Edvards Liepiņš,
• Sergejs Beljakovs,
• Inguna Goba and
• Jānis Stradiņš

Beilstein J. Org. Chem. 2015, 11, 2166–2170, doi:10.3762/bjoc.11.234

• oxidizing capacity of the hydroperoxide when its concentration is less or comparable with the tetrahydropyridine leading to another versatile intermediate in organic synthesis – oxaziridine – as the inherent strain of the ring and the relatively weak N–O bond makes it unusually reactive. Electrochemical

Copper-catalyzed aerobic radical C–C bond cleavage of N–H ketimines

• Ya Lin Tnay,
• Gim Yean Ang and
• Shunsuke Chiba

Beilstein J. Org. Chem. 2015, 11, 1933–1943, doi:10.3762/bjoc.11.209

• –O bond with radical initiators [7][8][9][10][11][12][13][14][15] (Scheme 1a) or using thermal [16][17][18][19][20] or photoreaction conditions [21][22][23][24][25][26][27] (Scheme 1b). An alternative route to iminyl radicals is the single-electron reduction of oxime derivatives mediated by the

• the synthesis of azaheterocycles through an intramolecular N–C bond formation with the unsaturated systems [1][2][3][4][5][6]. As precursors of iminyl radicals, readily available oximes and their derivatives have commonly been utilized. The generation of iminyl radicals involves the homolysis of the N

Development of variously functionalized nitrile oxides

• Haruyasu Asahara,
• Keita Arikiyo and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2015, 11, 1241–1245, doi:10.3762/bjoc.11.138

• single experimental step [1][2]. In addition, cycloadducts serve as precursors of polyfunctionalized compounds by ring opening reaction followed by N–O bond fission [2][3]. Hence, functionalized nitrile oxides are clearly useful for the preparation of more complex systems. However, because the precursors

Diastereoselective and enantioselective conjugate addition reactions utilizing α,β-unsaturated amides and lactams

• Katherine M. Byrd

Beilstein J. Org. Chem. 2015, 11, 530–562, doi:10.3762/bjoc.11.60

Enantioselective synthesis of polyhydroxyindolizidinone and quinolizidinone derivatives from a common precursor

• Nemai Saha and
• Shital K. Chattopadhyay

Beilstein J. Org. Chem. 2014, 10, 3104–3110, doi:10.3762/bjoc.10.327

• prepared from amide bond formation between the amine IV and acrylic acid (for IIIa) or butenoic acid (for IIIb). The remaining hydroxy group at C-4 could possibly be generated by a reductive cleavage of the N–O bond in 6. Thus, treatment of compound 6 with Zn/AcOH proceeded well to give the all-cis

Come-back of phenanthridine and phenanthridinium derivatives in the 21st century

• Lidija-Marija Tumir,
• Marijana Radić Stojković and
• Ivo Piantanida

Beilstein J. Org. Chem. 2014, 10, 2930–2954, doi:10.3762/bjoc.10.312

• rather expensive; therefore efforts were made to replace them with cheaper analogues. One successful approach included iron(III) acetylacetonate in acetic acid as catalytic agent (Scheme 16) [37], whereby O-acetyl oximes obtained from 2′-arylacetophenones underwent N–O bond cleavage and intramolecular N

N–O Cleavage reactions of heterobicycloalkene-fused 2-isoxazolines

• Jaipal R. Nagireddy,
• Geoffrey K. Tranmer,
• Emily Carlson and
• William Tam

Beilstein J. Org. Chem. 2014, 10, 2200–2205, doi:10.3762/bjoc.10.227

• isoxazoline-cleavage methodology to the preparation of biologically active natural products, including novel antibacterial, antifungal and anticancer treatments [8][9][10][11]. Some common methods of reductive N–O bond cleavage in isoxazolines include hydrogenolysis using Raney nickel, reduction by LiAlH4

• we were able to prepare in a highly regio- and stereoselective manner [21]. Selective cleavage of the N–O bond or simultaneous cleavage of both N–O and bridge C–C bonds of these isoxazolines could provide novel routes to the aforementioned functionalities attached to heterobicyclic ring systems such

• mediation. These results are summarized in Table 2. Compared to the parent compound 10a which gave an appreciable 93% yield of the corresponding β-hydroxyketone (Table 2, entry 1), replacement of two of the arene hydrogens for bromine atoms in 10b resulted in a lower tendency toward N–O bond cleavage (Table

Isoxazolium N-ylides and 1-oxa-5-azahexa-1,3,5-trienes on the way from isoxazoles to 2H-1,3-oxazines

• Alexander F. Khlebnikov,
• Mikhail S. Novikov,
• Yelizaveta G. Gorbunova,
• Ekaterina E. Galenko,
• Kirill I. Mikhailov,
• Viktoriia V. Pakalnis and
• Margarita S. Avdontceva

Beilstein J. Org. Chem. 2014, 10, 1896–1905, doi:10.3762/bjoc.10.197

• very low activation barriers (0.2–1.5 kcal/mol) to give (3Z)-1-oxa-5-azahexa-1,3,5-trienes. This is expected, because the oxazole N–O bond is very weak and the reaction is pseudopericyclic [21][22]. The calculated low thermodynamic and kinetic stabilities of the isoxazolium ylides (Figure 1) give only

Synthesis of rigid p-terphenyl-linked carbohydrate mimetics

• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 1749–1758, doi:10.3762/bjoc.10.182

• -couplings to form biphenyl aminopyran or p-terphenyl-linked dimers. Hydrogenolysis afforded new unnatural aminosugar mimetics. Zinc in the presence of acid or samarium diiodide were examined for the N–O bond cleavage in order to obtain the rigid p-terphenyl-linked C-glycosyl dimers. Keywords: carbohydrate

• simple monocyclic carbohydrate mimetics. To prepare phenyl-substituted aminopyrans the N–O bond of bicyclic compounds 15a and 15b was cleaved by hydrogenolysis. These reactions are challenging because the resulting aminopyrans are apparently poisoning the catalyst and hence large amounts of palladium on

• debromination. The debenzylation and the N–O bond cleavage occur as next steps. Under these improved conditions the isomeric bicyclic 1,2-oxazine 15b was converted into aminopyran 17b in a good yield of 77%. The formed aminopyrans 17a and 17b can be regarded as amino C-glycosides. Compound 17a is related to