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

• lactams in high yields and excellent enantioselectivities (2a, 2b, and 2d). It was observed that the steric environment affected both reactivity and enantioselectivity (2c). Six-membered lactams featuring propargylic (2e) and alkenyl (2f) motifs were also obtained with excellent regioselectivity and

• -triazole analogues 6. Both dioxazolones 4 and N-iminoquinolinium ylides 5 demonstrated excellent tolerance in this transformation. Notably, electron-rich dioxazolones exhibited slightly higher reactivity. The proposed catalytic cycle for the copper-catalyzed synthesis of 1,2,4-triazole derivatives is

• dioxazolone bearing a phenyl group showed no reactivity toward benzoyl amidine under the optimized reaction conditions. Instead, the authors employed a less bulky copper iodide catalyst in the absence of phosphine, successfully affording aryloyl amidine 10f. Furthermore, the electron-rich ethynylanisole

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

• electron transfer to the metal catalyst without the need for chemical redox agents, thus providing milder and more sustainable reaction conditions (Figure 2) [32]. Electrochemical reactions can be performed at low potentials, thereby suppressing side reactions, and chemoselectivity and reactivity can be

• achieved by precisely controlling the potential. Additionally, the merging of electrochemistry and transition-metal catalysis offers advantages in controlling substrate activation, intermediate reactivity, and bond formation, as well as facilitating asymmetric transformations. As a result, electrochemical

Nickel-catalyzed cross-coupling of 2-fluorobenzofurans with arylboronic acids via aromatic C–F bond activation

• Takeshi Fujita,
• Haruna Yabuki,
• Ryutaro Morioka,
• Kohei Fuchibe and
• Junji Ichikawa

Beilstein J. Org. Chem. 2025, 21, 146–154, doi:10.3762/bjoc.21.8

• distinct aryl groups onto a benzofuran ring through orthogonal coupling reactions, exploiting the reactivity difference between C–F and C–Br bonds (Scheme 4). Using a palladium catalyst, 5-bromo-2-fluorobenzofuran (1e) was coupled with [4-(trifluoromethyl)phenyl]boronic acid (2g). In this reaction, only

Cu(OTf)₂-catalyzed multicomponent reactions

• Sara Colombo,
• Camilla Loro,
• Egle M. Beccalli,
• Gianluigi Broggini and
• Marta Papis

Beilstein J. Org. Chem. 2025, 21, 122–145, doi:10.3762/bjoc.21.7

• behavior or reactivity properties. The ambiguity related to the role of Cu(OTf)2 is particularly relevant for cycloaddition reactions, where it is even more difficult to justify the activation of the copper species as a Lewis acid or metal catalyst [12][13][14]. The reaction mechanism involved can be ionic

Recent advances in organocatalytic atroposelective reactions

• Henrich Szabados and
• Radovan Šebesta

Beilstein J. Org. Chem. 2025, 21, 55–121, doi:10.3762/bjoc.21.6

• %. An extensive study on the reactivity of o-naphthoquinones 117 and 122 with 2-naphthylamines, 2-naphthols (118, 120), and indoles 123 was done in 2019 (Scheme 37) [65]. Four organocatalysts ((S)-C23, C31, C32, (R)-C23) proved the most efficient, and stereoinformation was effectively transferred in all

• indole nitrogen in control experiments led to halted reactivity or loss of enantiocontrol. These results suggest the importance of hydrogen bonding between the NH group and the organocatalyst. Bisindoles 142 reacted with ninhydrin-derived 3-indoylmethanol 143 in the presence of the CPA (S)-C22 to afford

• just one nitrogen resulted in retarded or halted reactivity. The combination of 2-naphthols 151 and alkynylhydroxyisoindolinones 152 in the presence of two chiral Brønsted acids C35 and C36 provided axially chiral isoindolinones 153 (Scheme 45) [73]. The optimized reaction conditions led to the handful

Synthesis of acenaphthylene-fused heteroarenes and polyoxygenated benzo[j]fluoranthenes via a Pd-catalyzed Suzuki–Miyaura/C–H arylation cascade

• Merve Yence,
• Dilgam Ahmadli,
• Damla Surmeli,
• Umut Mert Karacaoğlu,
• Sujit Pal and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2024, 20, 3290–3298, doi:10.3762/bjoc.20.273

• ). Finally, due to our interest in the structural features and chemistry of 1,8-dihydroxynaphthalene (1,8-DHN) [48][49], we were curious to check the reactivity of the previously unknown boronic ester 17d, which was prepared in one step from thiophene-3-ylboronic acid (17a) and 1,8-DHN [50]. Note that

• %, Table 2, entry 4). Afterwards, we sought to examine the reactivity of six-membered aromatic nitrogen heterocycles. The reactions of (2-methoxypyridin-3-yl)boronic acid with the dihalonaphthalenes 12 and 14 afforded substituted azafluoranthenes 15f and 15g in 90 and 51% yields, respectively (Table 2

Reactivity of hypervalent iodine(III) reagents bearing a benzylamine with sulfenate salts

• Beatriz Dedeiras,
• Catarina S. Caldeira,
• José C. Cunha,
• Clara S. B. Gomes and
• M. Manuel B. Marques

Beilstein J. Org. Chem. 2024, 20, 3281–3289, doi:10.3762/bjoc.20.272

• Beatriz Dedeiras Catarina S. Caldeira Jose C. Cunha Clara S. B. Gomes M. Manuel B. Marques LAQV-REQUIMTE, Department of Chemistry, NOVA School of Science and Technology, NOVA FCT , 2829-516 Caparica, Portugal 10.3762/bjoc.20.272 Abstract The reactivity of our recently disclosed hypervalent iodine

• reagents (HIRs) bearing a benzylamine with in situ-generated sulfenate salts was investigated. Under the studied conditions sulfonamides have been obtained in up to 52% yield. This reaction has been extended to a variety of HIRs and sulfenate salts to explore the different reactivity of these new reagents

• reactivity, yielding numerous derivatives with wide applications [2][3][4][6][7][8]. Their enhanced stability, compared to other HIRs, is due to: (i) the molecular geometry, which allows better overlap between the non-bonding electrons of the central iodine atom and the π-orbitals of the aromatic ring [2][9

Giese-type alkylation of dehydroalanine derivatives via silane-mediated alkyl bromide activation

• Perry van der Heide,
• Michele Retini,
• Fabiola Fanini,
• Giovanni Piersanti,
• Francesco Secci,
• Daniele Mazzarella,
• Timothy Noël and
• Alberto Luridiana

Beilstein J. Org. Chem. 2024, 20, 3274–3280, doi:10.3762/bjoc.20.271

• approaches have also gained widespread attention for their unique advantages in these transformations [4]. Radical chemistry often exhibits complementary reactivity to two-electron pathways and can be performed with high selectivity, atom economy, and functional group tolerance [5]. A well-known radical

Intramolecular C–H arylation of pyridine derivatives with a palladium catalyst for the synthesis of multiply fused heteroaromatic compounds

• Yuki Nakanishi,
• Shoichi Sugita,
• Kentaro Okano and
• Atsunori Mori

Beilstein J. Org. Chem. 2024, 20, 3256–3262, doi:10.3762/bjoc.20.269

• with the case of 1a. The reactivity toward the palladium-catalyzed cyclization was thus shown as 3 ≈ 1a >> 1b > 1c. The related trend was also observed in the reaction of phenanthroline monoamide 5a and diamide 5b. The reaction of 5a afforded the cyclized product in 51% yield, which contrasted with our

• previous result for the cyclization of 5b to afford the doubly cyclized product 6b (reported yield: 85% [23]), suggesting that the superior reactivity was found for bifunctional bisamides compared to monoamides. It was also found that the reaction also is applicable to a carbocyclic amide derivative. When

Non-covalent organocatalyzed enantioselective cyclization reactions of α,β-unsaturated imines

• Sergio Torres-Oya and
• Mercedes Zurro

Beilstein J. Org. Chem. 2024, 20, 3221–3255, doi:10.3762/bjoc.20.268

• leading to the synthesis of spirooxindole derivatives 6 bearing a thiourea moiety in high yields (91–97%), and with good to excellent diastereoselectivities (10:1–20:1 dr) and enantioselectivities (61–96%) (Scheme 2). Furthermore, the authors also investigated the reactivity of ketimines and dienimines

• straightforward methodology which enables the synthesis of structurally distinct N-heterocycles, which are difficult to access by other methodologies. Although in recent years a number of studies have been reported, further novel transformations are likely to be reported in the future. Reactivity of α,β

Germanyl triazoles as a platform for CuAAC diversification and chemoselective orthogonal cross-coupling

• John M. Halford-McGuff,
• Thomas M. Richardson,
• Aidan P. McKay,
• Frederik Peschke,
• Glenn A. Burley and
• Allan J. B. Watson

Beilstein J. Org. Chem. 2024, 20, 3198–3204, doi:10.3762/bjoc.20.265

• ]. As such, the reaction has been used extensively throughout drug discovery [20][21], chemical biology [22][23], and materials science [24][25][26][27]. Orthogonal alkyne reactivity can also be observed under certain systems [28][29][30]. The reaction typically uses a Cu(II) pre-catalyst, which is

• reactivity compared to other alkynes, which typically require much shorter reaction times. Extending the reaction time provided a higher conversion to the product 14. Yields were observed to be greater for aryl azides (e.g., 4 vs 6). Heterocycles such as pyridine (1), pyrimidine (10), phenothiazine (11), and

Direct trifluoroethylation of carbonyl sulfoxonium ylides using hypervalent iodine compounds

• Radell Echemendía,
• Carlee A. Montgomery,
• Fabio Cuzzucoli,
• Antonio C. B. Burtoloso and
• Graham K. Murphy

Beilstein J. Org. Chem. 2024, 20, 3182–3190, doi:10.3762/bjoc.20.263

• versatile intermediates in organic synthesis due to their unique reactivity and ability to participate in a wide range of chemical transformations. In this scenario, sulfoxonium ylides are excellent substrates for bifunctionalization reactions, due to the ambiphilic character in their ylidic carbon [16

• fluoroalkyliodonium salts as sources of electrophilic trifluoroethyl synthon. Given the non-nucleophilic nature of the iodoarene byproduct, this protocol should not suffer from further reactivity that decomposes the ylide. We describe here the coupling of α-carbonyl sulfoxonium ylides with polyfluoroalkyl(aryl

• discovered by Umemoto has proven an effective electrophilic trifluoroethyl transfer reagent [34][35], and to further explore the potential of fluoroalkyliodonium salts we evaluated the reactivity of such compounds in the context of sulfoxonium ylide derivatization. As depicted in Table 1, we began our

Controlled oligomerization of [1.1.1]propellane through radical polarity matching: selective synthesis of SF₅- and CF₃SF₄-containing [2]staffanes

• Jón Atiba Buldt,
• Wang-Yeuk Kong,
• Yannick Kraemer,
• Masiel M. Belsuzarri,
• Ansh Hiten Patel,
• James C. Fettinger,
• Dean J. Tantillo and
• Cody Ross Pitts

Beilstein J. Org. Chem. 2024, 20, 3134–3143, doi:10.3762/bjoc.20.259

• point of comparison, we examined the reactivity of 1 with CF3SF4Cl. This reagent is known to behave comparably to SF5Cl in radical chain reactions [17][59][60][61] and can also be prepared conveniently in house [62]. In an analogous equivalents screen, we found that the 5:3 product ratio shifts from 7.7

• dramatic change in bicyclopentyl radical philicity would arise after incorporation of the second BCP unit. In addition to charge models, we evaluated global reactivity indices (ω: electrophilicity index [70] and N: nucleophilicity index [71]) within the conceptual density functional theory (CDFT) framework

• relative to CF3SF4Cl on selectivity.a Key indices computed to compare reactivity. Partial charges (q) and condensed Fukui functions are evaluated at the reacting carbon or chlorine atom and are in units of elementary charge (e).a Supporting Information Supporting Information File 15: Experimental

Hypervalent iodine-mediated intramolecular alkene halocyclisation

• Charu Bansal,
• Oliver Ruggles,
• Albert C. Rowett and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 3113–3133, doi:10.3762/bjoc.20.258

• structures. HVI reagents are characterized by their diverse reactivity as oxidants and electrophilic reagents. In addition, they are inexpensive, non-toxic and considered to be environmentally friendly. An important application of HVI reagents is the synthesis of halogenated cyclic compounds, in particular

Advances in the use of metal-free tetrapyrrolic macrocycles as catalysts

• Mandeep K. Chahal

Beilstein J. Org. Chem. 2024, 20, 3085–3112, doi:10.3762/bjoc.20.257

• affect the optical and electronic properties, as well as the reactivity of porphyrins, mainly introducing non-planarity with easier access to the inner pyrrolic –NHs and –N-lone pairs. Additionally, these alterations potentially increase Lewis basicity that further improves interactions with substrates

Synthesis of the 1,5-disubstituted tetrazole-methanesulfonylindole hybrid system via high-order multicomponent reaction

• Cesia M. Aguilar-Morales,
• América A. Frías-López,
• Nadia V. Emilio-Velázquez,
• Alejandro Islas-Jácome,
• Angelica Judith Granados-López,
• Jorge Gustavo Araujo-Huitrado,
• Yamilé López-Hernández,
• Hiram Hernández-López,
• Luis Chacón-García,
• Jesús Adrián López and
• Carlos J. Cortés-García

Beilstein J. Org. Chem. 2024, 20, 3077–3084, doi:10.3762/bjoc.20.256

• studies, we employed benzaldehyde derivatives with various stereoelectronic decoration, excluding aliphatic ones due to their decreased reactivity resulting in failures to proceed [24][25][26][27]. Commercially available isocyanides utilized were cyclohexyl and tert-butyl isocyanide. Notably, an isolation

Enantioselective regiospecific addition of propargyltrichlorosilane to aldehydes catalyzed by biisoquinoline N,N’-dioxide

• Noble Brako,
• Sreerag Moorkkannur Narayanan,
• Amber Burns,
• Layla Auter,
• Valentino Cesiliano,
• Rajeev Prabhakar and
• Norito Takenaka

Beilstein J. Org. Chem. 2024, 20, 3069–3076, doi:10.3762/bjoc.20.255

• systematic catalyst structure–reactivity and selectivity relationship study. The observed catalyst structure–enantioselectivity relationship of the present allenylation reaction was found exactly opposite to that of the analogous allylation reaction. The method provided eleven α-allenic alcohols in 22–99

• ][15][16][17][18][19], the separation of which is by no means trivial [20] (Scheme 1). Nonetheless, substituents at the carbon atom indicated by γ (R2) of these reagents have been shown to bias the metallotropic rearrangement and/or the kinetic reactivity of the competing regioisomeric intermediates

• stable allenyltrichlorosilane that affords undesired homopropargylic alcohols [35][36] (Scheme 2b). Furthermore, Iseki [35] and Nakajima [36] evaluated only one chiral catalyst in their independent studies (i.e., no catalyst structure–reactivity and selectivity relationship study). In this context, we

Chemical structure metagenomics of microbial natural products: surveying nonribosomal peptides and beyond

• Thomas Ma and
• John Chu

Beilstein J. Org. Chem. 2024, 20, 3050–3060, doi:10.3762/bjoc.20.253

• structure of a molecule defines its properties and reactivity, and therefore dictates how it interacts with other molecules. Microorganisms need to communicate with each other and the environment, secreting signals of friendship, disdain, and many other sentiments in between. Natural products are the

Advances in radical peroxidation with hydroperoxides

• Oleg V. Bityukov,
• Pavel Yu. Serdyuchenko,
• Andrey S. Kirillov,
• Gennady I. Nikishin,
• Vera A. Vil’ and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2024, 20, 2959–3006, doi:10.3762/bjoc.20.249

• , either by themselves or with the aid of metal complex catalysis, and to provide an insight into the reactivity of these species. The present work is divided into sections, according to the type of the substrate: C(sp3)–H substrates; aromatic systems; compounds with unsaturated C–C or C–Het bonds. The

• involving radical intermediates from hydroperoxides under redox conditions (Scheme 3). The reactivity of O-centered radicals is less predictable and more diverse depending on radical structure and substrate pattern than the chemistry of C-centered radicals [29][30]. Generally, peroxy radicals have a

gem-Difluorovinyl and trifluorovinyl Michael acceptors in the synthesis of α,β-unsaturated fluorinated and nonfluorinated amides

• Monika Bilska-Markowska,
• Marcin Kaźmierczak,
• Wojciech Jankowski and
• Marcin Hoffmann

Beilstein J. Org. Chem. 2024, 20, 2946–2953, doi:10.3762/bjoc.20.247

• Poznań, Poland 10.3762/bjoc.20.247 Abstract The incorporation of fluorine atoms within the structure of organic compounds is known to exert a significant impact on their electronic properties, thereby modulating their reactivity in diverse chemical transformations. In the context of our investigation

• characteristic (Table 1, entry 7). A slightly higher reactivity was achieved when the BF3·(OEt2) was used instead of TiCl4 (Table 1, entry 8) [28]. The reactions were monitored by 19F NMR of the crude mixtures. The full conversion was reached by applying exclusively n-BuLi, but the formed product was not the

Structure and thermal stability of phosphorus-iodonium ylids

• Andrew Greener,
• Stephen P. Argent,
• Coby J. Clarke and
• Miriam L. O’Duill

Beilstein J. Org. Chem. 2024, 20, 2931–2939, doi:10.3762/bjoc.20.245

• synthetic organic chemistry, becoming indispensable tools in total synthesis, late-stage functionalisation and radiolabelling [1][2][3][4][5][6][7][8][9]. Due to their great mechanistic flexibility, including reactivity as oxidants, electrophiles, radical precursors and transmetalating agents, they often

• vital to gain a fundamental understanding of the structural factors affecting their stability and reactivity. Previous reports have suggested a link between structural factors and thermal stability of hypervalent iodine compounds [10][11][12][13][14][15][16]. Iodine(III) compounds are generally trigonal

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

• arylation; rearrangement reaction; Introduction The chemistry of hypervalent iodine compounds is well-established and they are prevalent as oxidants and electrophilic reagents in organic conversions [1][2][3]. They have gained significant attention due to their high reactivity and ability to carry out

• ]. They offer several advantages over traditional reagents, including low toxicity, high reactivity, and excellent selectivity [43] under simple reaction conditions. The distinctive reactivity of DIAS enables the smooth arylation of various carbon and heteroatom nucleophiles under gentle conditions, with

• (Scheme 17) suggests that the reaction initiates with an SNAr at the ortho-carbon, forming a Meisenheimer complex I and a novel iodine(III) intermediate II. This type of reactivity is unprecedented, as past reactions between nucleophiles and diaryliodonium salts usually lead to a reduction of iodine(III

Synthesis of pyrrole-fused dibenzoxazepine/dibenzothiazepine/triazolobenzodiazepine derivatives via isocyanide-based multicomponent reactions

• Marzieh Norouzi,
• Mohammad Taghi Nazeri,
• Ahmad Shaabani and
• Behrouz Notash

Beilstein J. Org. Chem. 2024, 20, 2870–2882, doi:10.3762/bjoc.20.241

• for this reaction. By replacing cyclohexyl isocyanide with tert-butyl- and isopropyl isocyanide, the corresponding products were obtained with similar yields. To investigate the reactivity of other cyclic imines in this protocol, we performed the reaction of triazolobenzodiazepine with gem-diactivated

Multicomponent synthesis of α-branched amines using organozinc reagents generated from alkyl bromides

• Baptiste Leroux,
• Alexis Beaufils,
• Federico Banchini,
• Olivier Jackowski,
• Alejandro Perez-Luna,
• Fabrice Chemla,
• Marc Presset and
• Erwan Le Gall

Beilstein J. Org. Chem. 2024, 20, 2834–2839, doi:10.3762/bjoc.20.239

• amines. Interestingly, whereas previously reported work describing the preparation and reaction of organozinc iodides in acetonitrile showed higher reactivity of secondary organozinc reagents over primary ones, reactions in THF in the presence of LiCl led to opposite results, with higher reactivity of

• organometallic Mannich couplings involving nonstabilized organometallics are uncommon and mostly limited to dialkylzinc reagents, likely due to their commercial availability, their significant reactivity, and their functional-group tolerance [7][8][9][10]. However, the molecular diversity accessible with these

• alkyl iodides [24]. It was indeed noticed that the reactivity of primary iodides in the multicomponent carbonyl alkylative amination (CAA) reaction was quite sluggish compared to the secondary counterparts. In addition, primary alkyl bromides were found to be almost inactive in the process. Therefore

C–C Coupling in sterically demanding porphyrin environments

• Liam Cribbin,
• Brendan Twamley,
• Nicolae Buga,
• John E. O’ Brien,
• Raphael Bühler,
• Roland A. Fischer and
• Mathias O. Senge

Beilstein J. Org. Chem. 2024, 20, 2784–2798, doi:10.3762/bjoc.20.234

• porphyrins [34] and tetrabromoanthracenyl porphyrins [35]. In general, the halogen atom needed for the Suzuki coupling reaction resides on the porphyrin; however, Suzuki–Miyaura reactivity has also been shown to be reversed whereby the synthesis of borolanylporphyrins leads to a different approach to

• reactivity [36]. Borolanylporphyrins can be synthesized by Miyaura-borylation of the halogenated porphyrin [24][37]. There are also reported instances of borolanylporphyrins being synthesized under condensation conditions [36][38]. Despite the many synthetic advancements for the decoration of porphyrins

• the starting material porphyrin 13 being left unreacted. On switching the substrate from boronic acid to the boronic acid ester and opting for the weaker base Cs2CO3 instead of K3PO4, a significant difference in reactivity was observed with a 72% yield accomplished in the synthesis of porphyrin 29