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

• intermediate 5 will be converted into the final target after installation of the urea and uracil motifs. Accordingly, a nitrone-based latent functionality approach [28] would be tunable from fully substituted tetrahydrofuran-derived nitrone 7. The cis-1,2-hydroxy amine could be derived from oxazoline 6 through

• 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

• smoothly to deliver the aldehyde which was immediately subjected to the condensation reaction with benzylhydroxylamine. The corresponding nitrone 10 then underwent an intramolecular cycloaddition. Adduct 11 was isolated as the major product in 42% yield for 2 steps. Comprehensive NMR analysis revealed the

The high potential of methyl laurate as a recyclable competitor to conventional toxic solvents in [3 + 2] cycloaddition reactions

• Ayhan Yıldırım and
• Mustafa Göker

Beilstein J. Org. Chem. 2025, 21, 2389–2415, doi:10.3762/bjoc.21.184

• -based nitrone with some maleimides via a mechanochemical route in a solvent-free medium [67][68]. The development of environmentally friendly green methodologies for the preparation of heterocyclic compounds via such cycloaddition reactions is a significant and ongoing research area that should not be

• potential hazard associated with their utilization as a solvent in the aforementioned reactions. For the solute component C,N-diphenylnitrone, the dispersion, polarity, and hydrogen bonding values for nitrone were determined as δD = 16.6, δP = 7.6 and δH = 8.7. Figure 8b clearly shows the position of the

• experiment was conducted in which a series of organic solvents and water were subjected to solubility tests. For the purposes of this experiment, approximately 15 mg of nitrone was mixed with 1 mL of solvent in a 10 mL test tube at room temperature (22 °C). As demonstrated in Figure 8c, the solvents under

C2 to C6 biobased carbonyl platforms for fine chemistry

• Jingjing Jiang,
• Muhammad Noman Haider Tariq,
• Florence Popowycz,
• Yanlong Gu and
• Yves Queneau

Beilstein J. Org. Chem. 2025, 21, 2103–2172, doi:10.3762/bjoc.21.165

Preparation of spirocyclic oxindoles by cyclisation of an oxime to a nitrone and dipolar cycloaddition

• Beth L. Ritchie,
• Alexandra Longcake and
• Iain Coldham

Beilstein J. Org. Chem. 2025, 21, 1890–1896, doi:10.3762/bjoc.21.146

• an important class of compounds with significant biological activities. Spirocyclic derivatives are present in a variety of natural products. We describe here the formation of spirooxindoles using an intermolecular nitrone cycloaddition reaction. The nitrone dipole was prepared in situ by cyclisation

• -containing compounds makes use of intramolecular 1,3-dipolar cycloaddition reactions [15], including examples with nitrone ylides [16][17][18][19][20][21][22]. Our research group has exploited this approach for the synthesis of alkaloids such as myrioxazine A and aspidospermidine [23][24]. With a nitrone 1,3

• possibility to access the core of this ring system with the nitrone intermediate shown in Scheme 1A. As a model study, we describe here efforts towards an intermolecular variant with the oxindole shown in Scheme 1B; in this case a leaving group X will be displaced by the oxime to give an intermediate nitrone

Exploring the role of halogen bonding in iodonium ylides: insights into unexpected reactivity and reaction control

• Carlee A. Montgomery and
• Graham K. Murphy

Beilstein J. Org. Chem. 2023, 19, 1171–1190, doi:10.3762/bjoc.19.86

• ]. The authors discounted a free carbene-based C–H insertion because conducting the reaction in the presence of the radical trap phenyl N-tert-butyl nitrone (PBN) and the radical scavenger TEMPO resulted in decreased yields and isolation of their iodonium ylide adducts. Additional kinetic isotope effect

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

• first prepared synthetically before its isolation from natural crude material, employing a stereoselective addition of an aryl Grignard reagent to a five-membered chiral cyclic nitrone derived from ᴅ-arabinose [2]. Its analytical data were consistent with those for the later isolated natural product

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

• % overall yields. A relevant consideration in Holmes’s synthesis is: the nitrone is the same common intermediate as Gössinger’s [25], which is cyclized to form the tricyclic adducts. While the Gössinger route started from the cyclic 1-hydroxypiperidine, Holmes performed in situ cyclization to prepare the

• nitrone. Murahashi synthesis – 2000 Starting from secondary amines, Murahashi et al. developed a method for preparing homochiral β-sulfinyl nitrones [41]. Accordingly, (+)-euphococcinine (2) was prepared through allylation followed by the 1,3-dipolar cycloaddition of β-sulfinyl nitrone 20 derived from

• provide β-sulfinyl hydroxylamine 19 in a diastereoisomeric ratio of 67:33 in 52% yield. Oxidation of 19 to nitrone 20 occurred chemoselectivelly through treatment with a solution of hydrogen peroxide in 3 mol % of 5-ethyluminiflavin perchlorate (FIEt+.ClO4) as a catalyst in 55% yield. The reaction of β

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

• fluorinated piperidines based on an accidentally discovered annelation reaction proceeding under reductive conditions. Results and Discussion Nitrone 1a was selected as a model substrate and it was combined with commercially available dibromide 2a under blue light irradiation in the presence of an iridium

• iodine by treatment with zinc, followed by the reaction with iodine monochloride. The iodide 2b reacted quite rapidly with the nitrone but the expected fluoroalkylation product was not observed. Instead, the tetrafluorinated piperidine 3a was obtained in a moderate yield (Table 1, entry 2). Apparently

Recent developments in enantioselective photocatalysis

• Callum Prentice,
• James Morrisson,
• Andrew D. Smith and
• Eli Zysman-Colman

Beilstein J. Org. Chem. 2020, 16, 2363–2441, doi:10.3762/bjoc.16.197

• •−, which adds to the nitrone via a proposed 6-membered transition state to afford radical cation 286•+. Subsequent hydrogen atom abstraction from TEEDA•+ generates complex 286−. Protonation and displacement by other substrate molecules releases the desired 1,2-amino alcohol products 287 in excellent yields

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

• rule, a C–O bond is formed in intermolecular reactions, intramolecular cyclization generally occurs with the formation of a five-membered cycle of isoxazoline (C–O bond formation) or nitrone (C–N bond formation). Application of the oxime radicals in organic synthesis: intermolecular reactions Selective

• with the formation of alkyl radical 94. The latter attacked the nitrone moiety to form the bicyclic nitroxyl radical 95. When oxime 96 was oxidized with lead(IV) acetate, products 98 and 99 were observed. This result can be explained by the intramolecular attack of iminoxyl radical 97 on the phenyl π

• -unsaturated aliphatic and aryl oximes with TEMPO yielded cyclic nitrones (products 145a–j). The majority of the synthesized cyclic nitrones were disubstituted in α-position to the C=NO group (145a–f,h–j), the unsubstituted nitrone 145g was synthesized in the lowest yield. In the case of 145j–145j’ the

Synthesis of 1-azaspiro[4.4]nonan-1-oxyls via intramolecular 1,3-dipolar cycloaddition

• Yulia V. Khoroshunova,
• Denis A. Morozov,
• Andrey I. Taratayko,
• Polina D. Gladkikh,
• Yuri I. Glazachev and
• Igor A. Kirilyuk

Beilstein J. Org. Chem. 2019, 15, 2036–2042, doi:10.3762/bjoc.15.200

• synthesis of new pyrrolidine nitroxides from 5,5-dialkyl-1-pyrroline N-oxides via the introduction of a pent-4-enyl group to the nitrone carbon followed by an intramolecular 1,3-dipolar cycloaddition reaction and isoxazolidine ring opening. The kinetics of reduction of the new nitroxides with ascorbate were

• -enylmagnesium bromide to the corresponding nitrone, oxidation to alkenylnitrone, intramolecular 1,3-dipolar cycloaddition, and isoxazolidine ring opening. Nitroxide 1 showed both an unexpectedly low reduction rate [6] and long relaxation times t1 and tm at room temperature [4]. Unexpectedly high resistance of

• was carried out in the presence of 2,2,6,6-tetramethylpiperidine-1-oxyl. It should be noted that heating of alkenyl nitrones 7a and 7b gives the corresponding cycloadducts with yields close to quantitative, whereas for nitrone 7c, the complete conversion could not be achieved either at 145 °C or at a

Synthesis and selected transformations of 2-unsubstituted 1-(adamantyloxy)imidazole 3-oxides: straightforward access to non-symmetric 1,3-dialkoxyimidazolium salts

• Grzegorz Mlostoń,
• Małgorzata Celeda,
• Katarzyna Urbaniak,
• Marcin Jasiński,
• Vladyslav Bakhonsky,
• Peter R. Schreiner and
• Heinz Heimgartner

Beilstein J. Org. Chem. 2019, 15, 497–505, doi:10.3762/bjoc.15.43

• interest as so-called ‘nitrone like’ reagents for the synthesis of more complex, imidazole containing systems (Scheme 1) [6]. These imidazole N-oxides are easily accessible via heterocyclization reactions comprising condensation of α-hydroxyiminoketones 2 with formaldimines 3. The latter are known to exist

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

• diastereoselectivities of 1,3-dipolar cycloadditions which allow to control stereochemistries at C3 and C5 [79][80]. To illustrate this concept the E/Z mixture of nitrone 70 was reacted with acrylamide 71 prepared from (2S)-bornane-10,2-sultam to afford mainly (20:1) the isoxazolidine (3S,5S)-72 easily separable from

Oxidative cycloaddition of hydroxamic acids with dienes or guaiacols mediated by iodine(III) reagents

• Hisato Shimizu,
• Akira Yoshimura,
• Keiichi Noguchi,
• Victor N. Nemykin,
• Viktor V. Zhdankin and
• Akio Saito

Beilstein J. Org. Chem. 2018, 14, 531–536, doi:10.3762/bjoc.14.39

• adducts 3aa in 96 and 90% yields, respectively (Table 1, entries 10 and 11), BTI showed better results (Table 1, entries 8 and 9). On the other hand, the use of IBA-OTf, which was effective in the oxidative cycloaddition reaction of oximes [20][21], gave nitrone-trifluoromethanesulfonic acid (TfOH

• test this hypothesis, the oxazine 3aa was treated with TfOH in DCM at 40 °C for 18 h and afforded 4 quantitatively. Furthermore, the TfOH-mediated formation of nitrone from such HDA adducts has been reported [23]. It should be mentioned that the structures of 3aa and 4 were determined by single crystal

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• afforded azafulvene derivatives 91 (Scheme 34) [82]. Remarkably, the formation of five-membered cyclic nitrone through N-attack of the oxime on the cyano group is more preferable over the six-membered N–O heterocycle. C-Nucleophiles possessing leaving groups have been also used in the construction of N–O

Synthesis of spiro[isoindole-1,5’-isoxazolidin]-3(2H)-ones as potential inhibitors of the MDM2-p53 interaction

• Salvatore V. Giofrè,
• Santa Cirmi,
• Raffaella Mancuso,
• Francesco Nicolò,
• Giuseppe Lanza,
• Laura Legnani,
• Agata Campisi,
• Maria A. Chiacchio,
• Michele Navarra,
• Bartolo Gabriele and
• Roberto Romeo

Beilstein J. Org. Chem. 2016, 12, 2793–2807, doi:10.3762/bjoc.12.278

• -ethynylbenzamides 1. The latter are easily accessible through ethynylation of N-substituted 2-iodobenzamides, with secondary amines (Scheme 1). Compounds 2a–e, as E/Z mixtures, have been reacted with nitrone 4. Different experimental conditions have been exploited: by reacting the nitrone and dipolarophile in

• toluene solution under reflux, the formation of products was not observed, even after extension of the reaction time to 72 h. Under these conditions the process led only to decomposition of the nitrone with the recovery of unaltered isoindolinone. The best results have been obtained by performing the 1,3

• failed, leading to the degradation of the nitrone and the isolation of the unaltered dipolarophile, so clearly indicating that the steric factors play a crucial role in the cycloaddition process (see computational data). Theoretical calculations The obtained results and stereochemical outcome of the 1,3

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• process involves the 1,3-dipolar cycloaddition of alkynes 182 with in situ generated nitrone 185 to afford isoxazolines 186 which rapidly rearrange to aziridinylphosphonates 183. An efficient method for the synthesis of 1,2,3-triazoles is the copper(I)-catalyzed Husigen cycloaddition of azides with

Copper-mediated synthesis of N-alkenyl-α,β-unsaturated nitrones and their conversion to tri- and tetrasubstituted pyridines

• Dimitra Kontokosta,
• Daniel S. Mueller,
• Dong-Liang Mo,
• Wiktoria H. Pace,
• Rachel A. Simpson and
• Laura L. Anderson

Beilstein J. Org. Chem. 2015, 11, 2097–2104, doi:10.3762/bjoc.11.226

• . Keywords: Chan–Lam; copper; nitrone; oxygen transfer; pyridine; Introduction While most applications of the Chan–Lam reaction are focused on the synthesis of aryl ethers and aryl amines, our group has been interested in the use of the Chan–Lam reaction for the synthesis of O-alkenyl oximes and

• using reaction conditions that we had previously identified as optimal for analogous N-alkenylnitrone syntheses from fluorenone oxime [7]. Nitrone 8aa was successfully isolated in 40% yield using 2 equiv of Cu(OAc)2 and the reaction conditions indicated in Table 1, entry 1. Only the E-nitrone isomer was

• , the scope of the nitrone synthesis was explored by varying the oxime and alkenylboronic acid reagents. As shown in Table 2, chalcone oximes with both electron-rich and electron-poor aryl substituents, as well as heteroaryl substituents, were tolerated for the transformation with electron-donating

Novel stereocontrolled syntheses of tashiromine and epitashiromine

• Loránd Kiss,
• Enikő Forró and
• Ferenc Fülöp

Beilstein J. Org. Chem. 2015, 11, 596–603, doi:10.3762/bjoc.11.66

• intramolecular cyclization of a chiral alkenylated pyrrolidinone, followed by hydroxylation [32], or by the intramolecular ring closure of chiral pyrrolidine diesters followed by ester and oxo group reduction [33], while the syntheses of (+)-epitashiromine starts from a chiral morpholine derivative, with nitrone

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

• . Unnatural divalent rigid p-terphenyl-linked C-aryl glycosides with 2.0 nm dimension are available using Suzuki cross-couplings. The key compound, a p-bromophenyl-substituted 1,2-oxazine, was prepared by a stereoselective [3 + 3]-cyclization of a D-isoascorbic acid-derived (Z)-nitrone and lithiated TMSE

• ]-cyclization of D-isoascorbic acid-derived (Z)-nitrone 6 and lithiated TMSE-allene 5. Results and Discussion For our synthesis of new divalent carbohydrate mimetics we required 1,2-oxazine derivatives derived from (Z)-nitrone 6 and lithiated alkoxyallenes. The 4-bromophenyl group should allow transition metal

• -promoted coupling reactions to a variety of new compounds. For this purpose the D-erythrose-configured ester 7, easily available from D-isoascorbic acid [28], was converted into nitrone 6 in a three step procedure (Scheme 2). Its reduction with lithium aluminum hydride was performed under standard

N-Alkylated dinitrones from isosorbide as cross-linkers for unsaturated bio-based polyesters

• Oliver Goerz and
• Helmut Ritter

Beilstein J. Org. Chem. 2014, 10, 902–909, doi:10.3762/bjoc.10.88

• -configuration of 3a/b is evident from the signal at 7.90 ppm. With the formation of the nitrone with an E-configuration the proton of the nitron group is exposed to a strong deshielding effect of the N-oxide group, which causes a movement of the signal to higher ppm values [11]. The appearance of the Z-isomer

Synthesis of new enantiopure poly(hydroxy)aminooxepanes as building blocks for multivalent carbohydrate mimetics

• Léa Bouché,
• Maja Kandziora and
• Hans-Ulrich Reissig

Beilstein J. Org. Chem. 2014, 10, 213–223, doi:10.3762/bjoc.10.17

• )-nitrones 3, 6 and 8 were synthesized essentially following known pathways [35] (Scheme 2 and Scheme 3). The new D-erythrose-derived nitrone 3 containing a p-bromophenyl moiety in the dioxolane ring was obtained in a straightforward manner (Scheme 2). Commercially available D-isoascorbic acid (1) was

• ]. Protection with a TBS-group proceeded quantitatively to gain 2 in very good overall efficacy. Final transformation into the desired nitrone 3 was achieved in 83% yield (over two steps) by reduction of the ester using DIBAL-H at low temperature, followed by condensation with N-benzylhydroxylamine according to

• a Dondoni protocol [29]. This route allows the synthesis of enantiopure nitrone 3 in multi-gram scale. The enantiopure (Z)-configured nitrones 6, 8 and 3 were treated with in situ lithiated TMSE-allene at −78 °C furnishing the expected 1,2-oxazines syn-7 [37], syn-9 and syn-10 in high yields and

Gold(I)-catalyzed enantioselective cycloaddition reactions

• Fernando López and
• José L. Mascareñas

Beilstein J. Org. Chem. 2013, 9, 2250–2264, doi:10.3762/bjoc.9.264

• the species that participates in the cycloaddition to the nitrone, probably in a concerted pathway, and thus providing the corresponding products with high levels of stereoselectivity [82][83]. Previously, in 2009, J. Zhang had reported a gold(I)-catalyzed 1,3-dipolar [3 + 3] cycloaddition between 2

• . This key intermediate is then trapped by the nitrone to afford XIV, which eventually evolves to the product by an intramolecular cyclization (Scheme 17). Finally, the same group recently reported a related reaction of 1-(1-alkynyl)cyclopropyl ketones such as 28, by means of a gold(I)-catalyzed

• asymmetric [4 + 3] cycloaddition. In this article, the authors demonstrated that a chiral gold catalyst generated from MeO-DTBM-Biphep was able to promote the [4 + 3] cycloaddition between ketone 28 and the nitrone 29, to afford the corresponding 5,7-fused bicyclic furo[3,4-d][1,2]oxazepine 30 in good yield

The chemistry of amine radical cations produced by visible light photoredox catalysis

• Jie Hu,
• Jiang Wang,
• Theresa H. Nguyen and
• Nan Zheng

Beilstein J. Org. Chem. 2013, 9, 1977–2001, doi:10.3762/bjoc.9.234

• oxidized to nitrone 64. Finally, an intramolecular 1,3-dipolar cycloaddition of 64 furnishes isoxazolidine 55. Tetrahydroisoquinolines are arguably the most exploited amines in visible light photoredox catalysis. However, efforts towards expanding the scope of amines have been recently reported. Li [82

Gold-catalyzed cyclization of allenyl acetal derivatives

• Dhananjayan Vasu,
• Samir Kundlik Pawar and
• Rai-Shung Liu

Beilstein J. Org. Chem. 2013, 9, 1751–1756, doi:10.3762/bjoc.9.202

• ]. We postulate that compounds 2 arise from the attack of 1,3-diones at initially generated allyl cation intermediates I. In the case of electrophilic nitrones, allyl cations I release a proton to form reactive 1-methoxyfulvenes II to achieve a [3 + 2]-nitrone cycloaddition. The versatility of cationic

• alternative route involving the protonation of the fulvene intermediate D because this route would water as a proton source. The formation of the fulvene intermediate D from allyl cation B is assisted by a weak base like nitrone [18]. We envisage that a 1,2-hydrogen shift for the allyl cation B fails to