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Search for "sulfonamide" in Full Text gives 136 result(s) in Beilstein Journal of Organic Chemistry.
Synthesis of heterocycles based on azomethine ylides from α-amino acids (or amines) and carbonyl compounds
- Ekaterina V. Berezhnaya,
- Alexander I. Ponyaev,
- Vitali M. Boitsov and
- Alexander V. Stepakov
Beilstein J. Org. Chem. 2026, 22, 705–741, doi:10.3762/bjoc.22.55
- cycloaddition occurs. In 2014, an article [96] was published that examined the enantioselective 1,3-dipolar cycloaddition of cyclohexenone 143 to azomethine ylides obtained in situ from isatins 140 and aminomalonic diesters 141, catalyzed by readily available proline sulfonamide L22 (Scheme 47). Spirooxindoles
Graphical Abstract
Scheme 1: Strategies for the preparation of pyrrolidine derivatives by (3 + 2) cycloaddition of azomethine yl...
Scheme 2: (3 + 2) Cycloaddition of iminoesters to dimethylmaleate.
Scheme 3: Cycloaddition of 1 with various dipolarophiles catalyzed by Ag(I)-L1.
Scheme 4: Cycloaddition of 1 with tert-butyl acrylate catalyzed by Ag(I)-L2.
Scheme 5: Cycloaddition of 1 with dimethyl maleate catalyzed by Cu(I)-L3.
Scheme 6: Cycloaddition of 1 with alkenes catalyzed by Zn(II)-t-Bu-BOX (L4).
Scheme 7: (3 + 2) Cycloaddition of iminoesters to acrylates.
Scheme 8: Catalytic double (3 + 2) cycloaddition to form pyrrolizidine derivatives.
Scheme 9: (3 + 2) Cycloaddition of iminoethers to vinyl phenyl sulfone.
Scheme 10: Regiodivergent and enantioselective synthesis of pyrrolidines 16 and 17.
Scheme 11: Substrate-controlled regioreversible "normal" and "incomplete" 1,3-dipolar cycloaddition.
Scheme 12: Enantioselective synthesis of exo-/endo-pyrrolidines.
Scheme 13: (3 + 2) Cycloaddition of iminoethers 21 to dipolarophiles 22–24.
Scheme 14: Synthesis of bicyclic pyrrolidines 29 from cyclopentene-1,3-diones.
Scheme 15: (3 + 2) Cycloaddition of aldimine esters and allyl alcohols using copper-ruthenium catalysis.
Scheme 16: Synthesis of 3,3-difluoro- and 3,3,4-trifluoropyrrolidine derivatives.
Scheme 17: Use of iminoesters from natural compounds and pharmaceuticals for reactions with 1,1-difluoro- and ...
Scheme 18: Reaction of iminoesters with 1,3-enynes.
Scheme 19: Synthesis of pyrrolidines from iminoesters and vinyl(hetero)arenes.
Scheme 20: Synthesis of exo-pyrrolidines 42 and 43.
Scheme 21: Enantioselective synthesis of heteroarylpyrrolidines 45 and 46.
Scheme 22: Catalytic reaction of (3 + 2) cycloaddition of imines 12 to benzofulvenes 47.
Scheme 23: Fullerene as a dipolarophile in (3 + 2) cycloaddition reactions.
Scheme 24: Asymmetric synthesis of optically active tetrasubstituted pyrrolidines 54.
Scheme 25: (3 + 2) Cycloaddition reaction of imines 55 and α,β-unsaturated aldehydes.
Scheme 26: Probable mechanism of enantioselective (3 + 2) cycloaddition of azomethine ylides to α,β-unsaturate...
Scheme 27: Cycloaddition between iminoesters 12 and sulfinylimines 58.
Scheme 28: (3 + 2) Cycloaddition between triarylideneacetylacetone and azomethine ylides in the presence of ti...
Scheme 29: Stereoselective synthesis of decahydropyrrolo[2,1,5-cd]indolizine 66.
Scheme 30: Synthesis of policyclic derivatives 71 and 72.
Scheme 31: Catalytic аsymmetric (3 + 2) сycloaddition of 2-pyridylimines with N-methylmaleimide.
Scheme 32: Catalytic аsymmetric (3 + 2) сycloaddition of 2-pyridylimines 1 with other dipolarophiles.
Scheme 33: Enantioselective (3 + 2) cycloaddition of silylimine with various dipolarophiles.
Scheme 34: Proposed mechanism of formation of pyrrolidines 78.
Scheme 35: Synthesis of polyheterocyclic pyrrolidines 82–91.
Scheme 36: Synthesis of spirocyclic (95) and fused (96) pyrrolidines.
Scheme 37: (3 + 2) Cycloaddition involving aromatic aldehydes 97, N-propargylmaleimide (98) and α-amino acids ...
Scheme 38: Synthesis of pyrrolizidines 106 and by-product 107.
Scheme 39: Iridium-catalyzed three-component cascade (3 + 2) cycloaddition.
Scheme 40: Intramolecular (3 + 2) cycloaddition of N-alkenylpyrrole-2-carbaldehyde 110 and α-amino acids.
Scheme 41: Three-component (3 + 2) cycloaddition involving fullerene.
Scheme 42: Four-component stereoselective one-pot synthesis of spiro-cycloadducts 119–122.
Scheme 43: Reactions of azomethine ylide 123 with cyclopropenes.
Scheme 44: Three-component reactions involving ninhydrin, cyclopropenes and acyclic α-amino acids.
Scheme 45: Reaction of cyclopropenes 138 with the N-protonated form of Ruhemann purple 137.
Scheme 46: Enantioselective (3 + 2) cycloaddition of azomethine ylides generated in situ from isatins and amin...
Scheme 47: (3 + 2) Cycloaddition of cyclohexenone 143, isatins 140 and aminomalonic diesters 141, catalyzed by...
Scheme 48: Enantioselective (3 + 2) cycloaddition of azomethine ylides generated in situ from isatins and amin...
Scheme 49: Enantioselective (3 + 2) cycloaddition of azomethine ylides generated in situ from isatins and benz...
Scheme 50: (3 + 2) Cycloaddition involving isatins, azetidine-2-carboxylic acid, maleimides or itaconimides.
Scheme 51: (3 + 2) Cycloaddition involving isatins, amino acids and tetraethylvinylidenebis(phosphonate).
Scheme 52: Synthesis of spirooxindoles 156 from triarylideneacetylacetones 155.
Scheme 53: Synthesis of spirooxindole derivatives 157–160.
Scheme 54: Synthesis of hybrid spiro-heterocycles 164–166.
Scheme 55: Formation of azomethine ylide from isatin and sarcosine.
Scheme 56: (3 + 2) Cycloaddition involving isatins, amino acids and trans-3-benzoylacrylic acid.
Scheme 57: Regioselective synthesis of spirooxindoles 170.
Scheme 58: Synthesis of hybrid spiro-heterocycles 86.
Scheme 59: (3 + 2) Cycloaddition involving acenaphthenequinones, amino acids and cyclopropenes.
Scheme 60: Synthesis of hybrid glyco-3-nitrochromane cycloadducts 179.
Scheme 61: Synthesis of spiro[indenoquinoxaline-(thia)pyrrolizidines] 90a.
Scheme 62: Three-component reactions of cyclopropenes, 11H-indeno[1,2-b]quinoxalin-11-onesand α-amino acids, s...
Scheme 63: Synthesis of hybrid glyco-3-nitrochromane cycloadducts 92.
Scheme 64: (3 + 2) Cycloaddition of 11H-benzo[4,5]imidazo[1,2-a]indol-11-one (189) with cyclopropenes and male...
Scheme 65: Diastereoselective synthesis of spiro derivatives of barbituric acid from alloxan 193, α-amino acid...
Scheme 66: Probable mechanism of formation of azomethine ylide from alloxan and ʟ-proline.
Scheme 67: Three-component reactions involving tryptanthrin 196, α-amino acids and cyclopropenes.
Regioselective approach to 5-arylsulfonylisoxazoles and their antimicrobial activity
- Artem S. Sazonov,
- Dmitry A. Vasilenko,
- Denis V. Porfiriev,
- Yuri K. Grishin,
- Rimma A. Gazzaeva,
- Alisa P. Chernyshova,
- Maxim A. Kryakvin,
- Anna A. Baranova,
- Vera A. Alferova and
- Elena B. Averina
Beilstein J. Org. Chem. 2026, 22, 592–602, doi:10.3762/bjoc.22.45
- pyridine ring and carboxyl group [6][7][8][9]. On the other hand, the sulfonamide and sulfone groups are commonly found in the design of potential therapeutics with various types of biological activities, such as antimicrobial, antitubercular, antileishmanial, antiviral, anticancer, antidiabetic, anti
Graphical Abstract
Figure 1: Examples of sulfonylisoxazoles with biological activities.
Scheme 1: Reactions for preparing 5-sulfonylisoxazoles.
Scheme 2: Scope of 5-nitroisoxazoles 1a–g in the reaction with thiophenols.
Scheme 3: Scope of 5-thioisoxazoles 2a-p in the reaction with mCPBA.
Scheme 4: Oxidation of 5-thioisoxazoles into 5-sulfinylisoxazoles.
Figure 2: The samples of isoxazole derivatives trigger SOS response in E. coli reporter strains. A) Agar plat...
Figure 3: Inhibition of Klenow fragment of E. coli DNA polymerase I. A) The principal scheme of the Klenow fr...
Figure 4: Inhibition of E. coli DNA gyrase and Topo IV cleavage activity. A) The principal scheme of E. coli ...
Figure 5: Inhibition of E. coli DNA Topo I cleavage activity. A) The principal scheme of E. coli DNA Topo I c...
Figure 6: Inhibition of E. coli DNA gyrase supercoiling activity. A) The principal scheme of E. coli DNA gyra...
Figure 7: Inhibition of E. coli DNA Topo IV decatenation activity. A) The principal scheme of of E. coli DNA ...
Arene activation via π-bond localization: concepts and opportunities
- Paul Meiners,
- Julian J. Melder and
- Tobias Morack
Beilstein J. Org. Chem. 2026, 22, 257–273, doi:10.3762/bjoc.22.19
- cyclohexene derivatives beyond sulfone and sulfonamide motifs. By combining ester enolate and amine addition sequences, this methodology was subsequently extended to the synthesis of architecturally complex polyheterocyclic frameworks (Scheme 3B) [62]. Such scaffolds are scarcely represented in contemporary
Graphical Abstract
Figure 1: Aromatic molecules as the foundation of modern molecular chemistry.
Figure 2: Arenes as springboards to three-dimensional chemical space and strategies toward arene activation v...
Figure 3: Structure and synthetic utilization of strained arenes; NICS: nucleus independent chemical shifts [26-28].
Figure 4: Bonding and reactivity of η2-coordinated aromatic systems [44,46].
Figure 5: Illustrative selection of η2-coordinating dearomatization agents; MeIm: N-methylimidazole, NHE: nor...
Figure 6: Preparation, lability and most stable linkage isomers of pentaammineosmium(II) complexes.
Scheme 1: Heteroatom-directed reactions of η2-arene complexes [45,50].
Figure 7: Latent functionality through transient metal binding.
Figure 8: Selective hydrogenation of η2-coordinated benzene to cyclohexene under ambient conditions [53,54].
Scheme 2: Synthesis and utilization of enantioenrichted Mo(η2-arene) complexes in enantioselective synthesis [55]....
Scheme 3: Synthesis of trisubstituted cyclohexenes from phenyl sulfones enabled by tungsten-mediated dearomat...
Scheme 4: Diels–Alder reactions of η2-arene complexes with alkenes and alkynes; NMM: N-methylmaleimide [64,65].
Scheme 5: Binding characteristics and pioneering examples of isolable η3-benzyl complexes.
Figure 9: Divergent functionalization of benzyl electrophiles leveraging η3-benzyl complexes toward benzylic ...
Scheme 6: p-Selective allylation of benzyl chlorides with allylstannanes and subsequent synthetic expansion o...
Figure 10: Strategies for para- and ortho-selective arene functionalization/dearomatization via η3-benzyl comp...
Scheme 7: Substrate-dependent ortho- and para-selective dearomatization of naphthyl chlorides and leveraging ...
Figure 11: η4-Arene coordination as an underexplored but promising pathway for arene activation [96,98-100].
Configuration–packing synergy enabling integrated crystalline-state RTP and amorphous-state TADF
- Ruiyan Wang and
- Yunan Wu
Beilstein J. Org. Chem. 2026, 22, 224–236, doi:10.3762/bjoc.22.16
- of both intra- and intermolecular non-radiative decay pathways [20][21][22]. Several strategies have been developed to enhance RTP in organic materials, such as incorporating functional groups with n→π* characteristics, such as carbonyl [23], sulfone [24], or sulfonamide groups [25], constructing
Graphical Abstract
Figure 1: a) Single-crystal structure of 1, b) HOMO distribution calculated on the crystallographic geometry,...
Figure 2: Photophysical properties of 1 in solvents of varying polarity: a) UV–vis absorption spectra and b) ...
Figure 3: Fluorescence and phosphorescence spectra of 1 in THF (excitation wavelength: 365 nm).
Figure 4: a) Steady-state and delayed emission spectra of 1, b) room-temperature emission lifetimes monitored...
Figure 5: a) Phosphorescence spectra of 1 in the powder state at room temperature and at 77 K, and in dilute ...
Figure 6: a) The bimolecular packing arrangement in the crystal of 1 and intersystem crossing pathways of 1 i...
Figure 7: Photoluminescence lifetime of vacuum-deposited 1 films at different temperatures (excitation wavele...
Figure 8: a) TG curve of 1 and b) DSC curve of 1.
Figure 9: a) Electroluminescence spectrum of the device with 1 as the emissive layer, b) relationship between...
Scheme 1: Synthetic pathway to 1 via imide formation and Suzuki–Miyaura cross-coupling.
Recent advancements in the synthesis of Veratrum alkaloids
- Morwenna Mögel,
- David Berger and
- Philipp Heretsch
Beilstein J. Org. Chem. 2025, 21, 2657–2693, doi:10.3762/bjoc.21.206
- gave the protected sulfonamide 30. For the isomerization of the exo-double bond, an Alder-ene reaction with N-sulfinylbenzenesulfonamide and subsequent desulfurization was the way of choice. Finally, both remaining protecting groups were removed to furnish cyclopamine (6). In total, 6 was prepared in
Graphical Abstract
Scheme 1: Representatives of steroid alkaloid classes. Marked in blue is the steroidal cholestane framework, ...
Scheme 2: Subclasses of Veratrum alkaloids: jervanine, veratramine and cevanine-type [8].
Scheme 3: Flow chart presentation of the synthesis of (−)-englerin A developed by the Christmann group [10].
Scheme 4: Structures and year of synthesis of the three types of Veratrum alkaloids reported in the literatur...
Scheme 5: Key step in the synthesis of cyclopamine (6) by the Giannis group [21].
Scheme 6: Overview of the semisynthesis of cyclopamine (6) reported by the Giannis group in 2009 [21].
Scheme 7: Key steps in the synthesis of cyclopamine (6) by the Baran group [23].
Scheme 8: Overview of the total synthesis of cyclopamine (6) by the Baran group in 2023 [23].
Scheme 9: Key steps in the synthesis of cyclopamine (6) by the Zhu/Gao group [25].
Scheme 10: Overview of the total synthesis of cyclopamine (6) by the group of Zhao/Gao in 2023 [25].
Scheme 11: Key steps in the synthesis of cyclopamine (6) by the Liu/Qin group [26].
Scheme 12: Overview of the semisynthesis of cyclopamine (6) by the Liu/Qin group in 2024 [26].
Scheme 13: Key steps in the synthesis of jervine (12) by the Masamune group [14].
Scheme 14: Overview of the total synthesis of jervine (12) by the Masamune group in 1968 [14].
Scheme 15: Color-coded schemes of the presented cyclopamine (6) syntheses by Giannis, Baran, Zhu/Gao, and Liu/...
Scheme 16: Key steps in the total synthesis of veratramine (13) by the Johnson group [15].
Scheme 17: Overview of the total synthesis of veratramine (13) by the Johnson group in 1967 [15].
Scheme 18: Key steps in the synthesis of veratramine (13) by the Zhu/Gao group [25].
Scheme 19: Shortened overview of the total synthesis of veratramine (13) by the Zhu/Gao group in 2023 [25].
Scheme 20: Key steps in the synthesis of veratramine by the Liu/Qin group [26].
Scheme 21: Overview of the semisynthesis of veratramine (13) by the Liu/Qin group in 2024 [26].
Scheme 22: Key steps in the synthesis of veratramine (13) by the Trauner group [27].
Scheme 23: Overview of the total synthesis of veratramine (13) by the Trauner group in 2025 [27].
Scheme 24: Key steps in the synthesis of verarine (14) by the Kutney group [16-19].
Scheme 25: Overview of the total synthesis of verarine (14) by the Kutney group reported 1962–1968 [16-19].
Scheme 26: Color-coded schemes of the presented veratramine-type alkaloid synthesis of Zhu/Gao, Liu/Qin and Tr...
Scheme 27: Structures of veracevine (86), veratridine (87), and cevadine (88).
Scheme 28: Key step in the semisynthesis of verticine (15) by the Kutney group (1977) [20,46].
Scheme 29: Overview of the semisynthesis of verticine (15) by the Kutney group (1977) [20,46].
Scheme 30: Key step of the total synthesis of (±)-4-methylenegermine (17) by the Stork group (2017) [22].
Scheme 31: Overview of the total synthesis of (±)-4-methylenegermine (17) by the Stork group (2017) [22].
Scheme 32: Key step of the total synthesis of heilonine (16) by Cassaidy and Rawal (2021) [24].
Scheme 33: Overview of the total synthesis of heilonine (16) by Cassaidy and Rawal (2021) [24]. FGI: functional gr...
Scheme 34: Key steps of the synthesis of heilonine (16) by Dai and co-workers (2024) [28].
Scheme 35: Overview of the total synthesis of heilonine (16) by Dai and co-workers (2024) [28].
Scheme 36: Key steps of the total synthesis of zygadenine (18) reported by Luo and co-workers [29].
Scheme 37: Overview of the total synthesis of zygadenine (18) by Luo and co-workers (2023) [29].
Scheme 38: Key step of the divergent total syntheses of highly oxidized cevanine-type alkaloids by Luo and co-...
Scheme 39: Divergent syntheses of highly oxidized cevanine-type alkaloids by Luo and co-workers (2024) [30].
Scheme 40: Color-coded overview of the presented cevanine-type alkaloid syntheses [10,20,22,24,28-30,46]. LLS: longest linear sequen...
Synthesis of new tetra- and pentacyclic, methylenedioxy- and ethylenedioxy-substituted derivatives of the dibenzo[c,f][1,2]thiazepine ring system
- Gábor Berecz,
- András Dancsó,
- Mária Tóthné Lauritz,
- Loránd Kiss,
- Gyula Simig and
- Balázs Volk
Beilstein J. Org. Chem. 2025, 21, 2645–2656, doi:10.3762/bjoc.21.205
- ethylenedioxy moiety attached to positions 7 and 8 of the dibenzo[c,f][1,2]thiazepine (2) core (instead of positions 8 and 9) has also been carried out in the traditional way (Scheme 7). Sulfonamide 39, obtained in the reaction of sulfonyl chloride 9 with 2,3-dihydro-1,4-benzodioxin-5-amine was transformed via
Graphical Abstract
Figure 1: Reported ring systems incorporating the dibenzo[c,f][1,2]thiazepine (1) skeleton.
Figure 2: Drugs exhibiting a 1,3-benzodioxole or 1,4-benzodioxane structural unit marketed or in development.
Scheme 1: Synthesis of tetracyclic key intermediates 6 and 7. Conditions: i) 1,3-benzodioxol-5-amine (n = 1)/...
Scheme 2: Synthesis of tetracyclic compounds 20 and 21. Conditions: i) NaBH4, DMF, EtOH, rt, 4.5 h/23 h, 95%/...
Figure 3: X-ray structures of compounds 20e and 21g.
Scheme 3: Synthesis of tianeptine analogues 20b and 21b. Conditions: 20b: NaOH, EtOH/H2O, rt, 25 h, 80%; 21b:...
Scheme 4: Synthesis of tetracyclic ethers 23 and thioether 24. Conditions: i) ROH, MeCN, rt, 2–3 h, 38–84%; i...
Figure 4: X-ray structure of compound 23a.
Scheme 5: Synthesis of pentacyclic compounds 25–27. Conditions: i) Py·HCl, 180 °C, 27 h, 51%; ii) Br(CH2)2Br,...
Figure 5: X-ray structures of compounds 25, 26, and 27.
Scheme 6: Synthesis of tetracyclic compounds 38. Conditions: i) NaBH4, DMF/EtOH, rt, 3 h, 89%; ii) SOCl2, DCM...
Scheme 7: Synthesis of tetracyclic compounds 45 and 46. Conditions: i) 2,3-dihydro-1,4-benzodioxin-5-amine, P...
Scheme 8: Synthesis of tetracyclic compounds 54. Conditions: i) methyl anthranilate, pyridine, 0–5 °C, 4 h, r...
Thiadiazino-indole, thiadiazino-carbazole and benzothiadiazino-carbazole dioxides: synthesis, physicochemical and early ADME characterization of representatives of new tri-, tetra- and pentacyclic ring systems and their intermediates
- Gyöngyvér Pusztai,
- László Poszávácz,
- Anna Vincze,
- András Marton,
- Ahmed Qasim Abdulhussein,
- Judit Halász,
- András Dancsó,
- Gyula Simig,
- György Tibor Balogh and
- Balázs Volk
Beilstein J. Org. Chem. 2025, 21, 2220–2233, doi:10.3762/bjoc.21.169
- case of 7c and 7h, a substantial amount of (Z)-isomer was also obtained. In view of the expected similar electronic effect of the sulfonamide and the nitro functional groups on the Fischer indole cyclization, first we applied those reaction conditions for the 7a → 3a transformation (Scheme 1) which
Graphical Abstract
Figure 1: Phthalazinones 1, benzothiadiazine dioxides 2, and thiadiazinoindole dioxides 3.
Scheme 1: Synthesis of tri- and tetracyclic thiadiazinoindole dioxides 3.
Figure 2: 1H NMR and selective 1D NOESY (with the excitation of NH) spectra of (E)-7h.
Figure 3: 1H NMR and selective 1D NOESY (with the excitation of NH) spectra of (Z)-7h.
Scheme 2: Synthesis of pentacyclic compounds 10.
Figure 4: X-ray structures of compounds 3d (A), 7d (B), (Z)-7h (C), and (E)-9a (D).
Figure 5: The capacity factor (logk) vs calculated partition coefficients (clogP) by ACD Labs/Percepta [36]); the...
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
- used as an inhibitor of cyclin dependent kinase (CDK8) [31]. Sulfonamide-N-benzoxaborole analog GSK8175 is an inhibitor against hepatitis C virus (HCV) [20] (Figure 1). The construction of five-membered rings obtained growing attention [32][33][34][35][36][37][38], and alkynes [39][40][41][42][43][44
Graphical Abstract
Figure 1: Natural products and functional molecules possessing five-membered rings.
Scheme 1: Electrochemical intramolecular coupling of ureas to form indoles.
Scheme 2: Electrochemical dehydrogenative annulation of alkynes with anilines.
Scheme 3: Electrochemical annulations of o-arylalkynylanilines.
Scheme 4: Electrochemical cyclization of 2-ethynylanilines.
Scheme 5: Electrochemical selenocyclization of diselenides and 2-ethynylanilines.
Scheme 6: Electrochemical cascade approach towards 3-selenylindoles.
Scheme 7: Electrochemical C–H indolization.
Scheme 8: Electrochemical annulation of benzamides and terminal alkynes.
Scheme 9: Electrochemical synthesis of isoindolinone by 5-exo-dig aza-cyclization.
Scheme 10: Electrochemical reductive cascade annulation of o-alkynylbenzamide.
Scheme 11: Electrochemical intramolecular 1,2-amino oxygenation of alkyne.
Scheme 12: Electrochemical multicomponent reaction of nitrile, (thio)xanthene, terminal alkyne and water.
Scheme 13: Electrochemical aminotrifluoromethylation/cyclization of alkynes.
Scheme 14: Electrochemical cyclization of o-nitrophenylacetylene.
Scheme 15: Electrochemical annulation of alkynyl enaminones.
Scheme 16: Electrochemical annulation of alkyne and enamide.
Scheme 17: Electrochemical tandem Michael addition/azidation/cyclization.
Scheme 18: Electrochemical [3 + 2] cyclization of heteroarylamines.
Scheme 19: Electrochemical CuAAC to access 1,2,3-triazole.
Aryl iodane-induced cascade arylation–1,2-silyl shift–heterocyclization of propargylsilanes under copper catalysis
- Rasma Kroņkalne,
- Rūdolfs Beļaunieks,
- Armands Sebris,
- Anatoly Mishnev and
- Māris Turks
Beilstein J. Org. Chem. 2025, 21, 1984–1994, doi:10.3762/bjoc.21.154
- optimization see Supporting Information File 1. Next, we switched to internal N-nucleophiles. N-Nosylated starting material 7f under standard arylation conditions gave the 2-(1-(tert-butyldimethylsilyl)vinyl)-1-((4-nitrophenyl)sulfonyl)pyrrolidine (14) with a 56% yield. Most likely in this case sulfonamide N–H
Graphical Abstract
Scheme 1: Alkyne arylation with diaryl-λ3-iodanes in the context of 1,2-silyl shift and potential cyclization....
Scheme 2: Competing mechanistic pathways for diene 10 and indene 11 formation.
Scheme 3: Reaction scope for the synthesis of arylated tetrahydrofurans 8. Conditions: All reactions were per...
Scheme 4: Synthesis of lactone and pyrrolidine derivatives. Conditions: ac7e = 0.1 mmol/mL. bReaction conditi...
Scheme 5: Proposed arylation–heterocyclization mechanism for internal nucleophile-containing silanes 7.
Scheme 6: Arylation of C5-chain containing acylamides 16a–c. aThe reaction was performed under modified condi...
Enantioselective desymmetrization strategy of prochiral 1,3-diols in natural product synthesis
- Lihua Wei,
- Rui Yang,
- Zhifeng Shi and
- Zhiqiang Ma
Beilstein J. Org. Chem. 2025, 21, 1932–1963, doi:10.3762/bjoc.21.151
- , including (−)-ψ-akuammigine (Scheme 33) [81]. The synthesis commenced with dibenzoate 274, which underwent a Pd-catalyzed Trost desymmetrization using sulfonamide 275 and ligand 276. Deprotection of the resulting adduct furnished alcohol 277, which was subsequently converted to silyl enol ether 278 in two
Graphical Abstract
Scheme 1: General mechanism of a lipase-catalyzed esterification.
Scheme 2: Shishido’s synthesis of (−)-xanthorrhizol (4) and (+)-heliannuol D (8).
Scheme 3: Shishido’s synthesis of a) (−)-heliannuol A (15) and b) heliannuol G (20) and heliannuol H (21).
Scheme 4: Deska’s synthesis of hyperione A (30) and ent-hyperione B (31).
Scheme 5: Huang’s synthesis of (+)-brazilin (37).
Scheme 6: Shishido’s synthesis of (−)-heliannuol D (42) and (+)-heliannuol A (43).
Scheme 7: Chênevert’s synthesis of (S)-α-tocotrienol (49).
Scheme 8: Kita’s synthesis of monoester 53.
Scheme 9: Kita’s synthesis of fredericamycin A (60).
Scheme 10: Takabe’s synthesis of (E)-3,7-dimethyl-2-octene-1,8-diol (64).
Scheme 11: Takabe’s synthesis of (18S)-variabilin (70).
Scheme 12: Kawasaki’s synthesis of (S)-Rosaphen (74) and (R)-Rosaphen (75).
Scheme 13: Tokuyama’s synthesis of a) (−)-petrosin (84) and b) (+)-petrosin (86).
Scheme 14: Fukuyama’s synthesis of leustroducsin B (96).
Scheme 15: Nanda’s synthesis of a) fragment 100, b) fragment 106 and c) (−)-rasfonin (109).
Scheme 16: Davies’ synthesis of (+)-pilocarpine (115) and (+)-isopilocarpine (116).
Scheme 17: Ōmura’s synthesis of salinosporamide A (125).
Scheme 18: Kang’s synthesis of ʟ-cladinose (124) and its derivative.
Scheme 19: Kang’s preparation of fragment 139.
Scheme 20: Kang’s synthesis of azithromycin (149).
Scheme 21: Kang’s synthesis of (−)-dysiherbaine (156).
Scheme 22: Kang’s synthesis of (−)-kaitocephalin (166).
Scheme 23: Kang’s synthesis of laidlomycin (180).
Scheme 24: Snyder’s synthesis of arboridinine (190).
Scheme 25: Ma’s synthesis of (+)-alstrostine G (203).
Scheme 26: Trost’s synthesis of (−)-18-epi-peloruside A (215).
Scheme 27: Lindel’s synthesis of (–)-dihydroraputindole (223).
Scheme 28: Iwata’s synthesis of a) (−)-talaromycin B (232) and b) (+)-talaromycin A (235).
Scheme 29: Cook’s synthesis of a) (−)-vincamajinine (240) and b) (−)-11-methoxy-17-epivincamajine (245).
Scheme 30: Cook’s synthesis of (+)-dehydrovoachalotine (249) and voachalotine (250).
Scheme 31: Cook’s synthesis of a) (−)-12-methoxy-Nb-methylvoachalotine (257) and b) (+)-polyneuridine, macusin...
Scheme 32: Trauner’s synthesis of stephadiamine (273).
Scheme 33: Garg’s synthesis of (–)-ψ-akuammigine (285).
Scheme 34: Ding’s synthesis of (+)-18-benzoyldavisinol (293) and (+)-davisinol (294).
Rhodium-catalysed connective synthesis of diverse reactive probes bearing S(VI) electrophilic warheads
- Scott Rice,
- Julian Chesti,
- William R. T. Mosedale,
- Megan H. Wright,
- Stephen P. Marsden,
- Terry K. Smith and
- Adam Nelson
Beilstein J. Org. Chem. 2025, 21, 1924–1931, doi:10.3762/bjoc.21.150
- reaction modes of dirhodium carbenoids that were possible [14]. Overall, products were formed via O–H insertion into an alcohol (to give 14 products) or phenol (→ 2-4 and 3-4a); N–H insertion into an indole (→ 1-3a, 1-15b, 2-3a, 2-15b and 4-3), sulfonamide (→ 2-6), aminopyrimidine (→ 2-13 and 4-13) or
Graphical Abstract
Figure 1: Envisaged connective synthesis of reactive probes 3 bearing S(VI) electrophilic warheads (WH). Dive...
Scheme 1: Synthesis of α-diazoamide substrates D1–5 of general structure 2 bearing S(VI) electrophiles. Panel...
Figure 2: Structures and reactions of co-substrates. Panel A: structures of the 16 selected co-substrates C1–...
Figure 3: Structures and structure elucidation of intermolecular reaction products. The relevant reactivity m...
Synthesis of chiral cyclohexane-linked bisimidazolines
- Changmeng Xi,
- Qingshan Sun and
- Jiaxi Xu
Beilstein J. Org. Chem. 2025, 21, 1786–1790, doi:10.3762/bjoc.21.140
- nucleophilically attacks the phosphonium in A to generate intermediate B by loss of triphenylphosphine oxide and triflic acid. The nucleophilic sulfonamide in B intramolecularily attacks the generated imine moiety in B to form intermediate C, in which triflic acid may protonate the imine moiety in B to assist the
Graphical Abstract
Figure 1: Bisoxazoline and bisimidazoline ligands.
Scheme 1: Synthesis of chiral cyclohexane-linked bisimidazoline ligands.
Scheme 2: Attempted synthesis of chiral cyclohexane-linked bisimidazoline 5h.
Scheme 3: Proposed reaction mechanism.
Unique halogen–π association detected in single crystals of C–N atropisomeric N-(2-halophenyl)quinolin-2-one derivatives and the thione analogue
- Mai Uchibori,
- Nanami Murate,
- Kanako Shima,
- Tatsunori Sakagami,
- Ko Kanehisa,
- Gary James Richards,
- Akiko Hori and
- Osamu Kitagawa
Beilstein J. Org. Chem. 2025, 21, 1748–1756, doi:10.3762/bjoc.21.138
- diverse C–N atropisomeric compounds possessing carboxamide, imide, lactam, sulfonamide, indole, pyrrole, imidazole, carbazole and amine skeletons have been reported by many groups [1][2][3][4][5][6][7][8][9]. C–N atropisomers are attractive compounds from the viewpoint of not only synthetic organic
Graphical Abstract
Figure 1: Various C–N atropisomeric compounds and their intermolecular interactions in single crystals.
Scheme 1: Synthesis of N-(2-halophenyl)quinolin-2-ones 1a,b and quinoline-2-thione 2a.
Figure 2: Intramolecular associations detected in crystals of rac-1a and rac-1b.
Figure 3: Intramolecular association detected in the crystals of (P)-1a and (P)-1b.
Figure 4: Angles (θ, α) and distances (d) in racemate rac-1a,b and (P)-1a,b.
Figure 5: Crystal structure of racemic quinoline-2-thione rac-2a.
Reactions of acryl thioamides with iminoiodinanes as a one-step synthesis of N-sulfonyl-2,3-dihydro-1,2-thiazoles
- Vladimir G. Ilkin,
- Pavel S. Silaichev,
- Valeriy O. Filimonov,
- Tetyana V. Beryozkina,
- Margarita D. Likhacheva,
- Pavel A. Slepukhin,
- Wim Dehaen and
- Vasiliy A. Bakulev
Beilstein J. Org. Chem. 2025, 21, 1397–1403, doi:10.3762/bjoc.21.104
- -thiazole 3 was isolated. Method B. The corresponding aryl sulfonamide (1.2 equiv), PhI(OAc)2 (1.5 equiv) and DCM (0.5 mL) was added to an oven-dried standard microwave vial with a volume of 10 mL. The resulting suspension was stirred for 10 min in an ice bath, then thioamide 1 (1.0 equiv) dissolved in DCM
- 3. Conditions: aMethod A: thioamide 1 (1.0 equiv), PhINMs or PhINTs (2a, 1.5–2.0 equiv), 0→24 °C, 6‒60 min. bMethod B: thioamide 1 (1 equiv), aryl sulfonamide (1.2 equiv), PhI(OAc)2 (1.5 equiv), 0→24 °C, 10–30 min. Optimization of the reaction of thioamide 1a with iodonium salts [I]. Supporting
Graphical Abstract
Figure 1: Representatives of biologically active 1,2-thiazoles.
Scheme 1: Synthesis of 2,5-dihydro-1,2-thiazoles.
Scheme 2: Synthesis of 2,3-dihydro-N-sulfonyl-1,2-thiazoles 3. Conditions: aMethod A: thioamide 1 (1.0 equiv)...
Figure 2: Compound 3aa in thermal ellipsoids 50% probability.
Origami with small molecules: exploiting the C–F bond as a conformational tool
- Patrick Ryan,
- Ramsha Iftikhar and
- Luke Hunter
Beilstein J. Org. Chem. 2025, 21, 680–716, doi:10.3762/bjoc.21.54
Graphical Abstract
Figure 1: Fundamental characteristics of the C–F bond.
Figure 2: Incorporation of fluorine at the end of an alkyl chain.
Figure 3: Incorporation of fluorine into the middle of a linear alkyl chain.
Figure 4: Incorporation of fluorine across much, or all, of a linear alkyl chain.
Figure 5: Incorporation of fluorine into cycloalkanes.
Figure 6: Conformational effects of introducing fluorine into an ether (geminal to oxygen).
Figure 7: Conformational effects of introducing fluorine into an ether (vicinal to oxygen).
Figure 8: Effects of introducing fluorine into alcohols (and their derivatives).
Figure 9: Controlling the ring pucker of sugars through fluorination.
Figure 10: Controlling bond rotations outside the sugar ring through fluorination.
Figure 11: Effects of incorporating fluorine into amines.
Figure 12: Effects of incorporating fluorine into amine derivatives, such as amides and sulfonamides.
Figure 13: Effects of incorporating fluorine into organocatalysts.
Figure 14: Effects of incorporating fluorine into carbonyl compounds, focusing on the “carbon side.”
Figure 15: Fluoroproline-containing peptides and proteins.
Figure 16: Further examples of fluorinated linear peptides (besides fluoroprolines). For clarity, sidechains a...
Figure 17: Fluorinated cyclic peptides.
Figure 18: Fluorine-derived conformational control in sulfur-containing compounds.
Entry to 2-aminoprolines via electrochemical decarboxylative amidation of N‑acetylamino malonic acid monoesters
- Olesja Koleda,
- Janis Sadauskis,
- Darja Antonenko,
- Edvards Janis Treijs,
- Raivis Davis Steberis and
- Edgars Suna
Beilstein J. Org. Chem. 2025, 21, 630–638, doi:10.3762/bjoc.21.50
- tethered nitrogen nucleophiles such as sulfonamides, carbamates, and benzamide. The decarboxylative cyclization of a stereogenic center-containing sulfonamide proceeds with excellent diastereoselectivity (97:3 dr). The N-protected 2-aminoproline derivatives can be incorporated into dipeptides by an ester
Graphical Abstract
Figure 1: Selected examples of α,α-disubstituted cyclic amino acids in drug design.
Figure 2: Electrochemical decarboxylative amination reactions.
Scheme 1: Preparation of malonic acid monoester 9a.
Figure 3: A) Cyclic voltammograms of 6a and 9a at 3 mM and 6 mM concentration, respectively, in 5:1 MeCN/H2O ...
Scheme 2: Electrolysis of acid 9d in deuterated solvents.
Figure 4: Plausible mechanism for formation of pyrrolidine 6a and hemiaminal 10a.
Scheme 3: Scope of the decarboxylative amidation. aStainless-steel cathode; bgraphite cathode; cyield determi...
Scheme 4: Synthetic modifications of 2-aminoproline derivatives 6.
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
- were tolerated, while a dioxazolone containing bromobenzene displayed lower reactivity (26c). The enamide 26d, derived from lobatamide, was successfully produced without altering the stereochemistry of the oxime ether. Terminal alkynes with linear alkyl group, protected alcohol, and sulfonamide
Graphical Abstract
Scheme 1: Formation of isocyanates and amidated arenes from dioxazolones.
Scheme 2: Copper-catalyzed synthesis of δ-lactams via open-shell copper nitrenoid transfer. aCuBr (10 mol %) ...
Figure 1: Proposed reaction pathway for the copper-catalyzed synthesis of δ-lactams from dioxazolones.
Scheme 3: Copper(II)-catalyzed synthesis of 1,2,4-triazole derivatives.
Figure 2: Proposed reaction mechanism for the copper-catalyzed synthesis of 1,2,4-triazole analogues from dio...
Scheme 4: Copper(I)-catalyzed synthesis of N-acyl amidines from dioxazolones, acetylenes, and amines. aPerfor...
Figure 3: Proposed reaction mechanism for the copper(I)-catalyzed synthesis of N-acyl amidines.
Scheme 5: Preparation of N-arylamides from dioxazolones and boronic acids using a copper salt.
Figure 4: Proposed reaction pathway for the copper-mediated synthesis of N-arylamides from dioxazolones.
Scheme 6: Copper-catalyzed preparation of N-acyl iminophosphoranes from dioxazolones.
Figure 5: Proposed reaction pathway for the copper-catalyzed synthesis of N-acyl iminophosphoranes from dioxa...
Scheme 7: Copper-catalyzed synthesis of N-acyl sulfenamides. a1.0 equiv of 18 and 2.0 equiv of 19 were used. b...
Figure 6: Proposed reaction mechanism for the copper-catalyzed S-amidation of thiols.
Scheme 8: Copper-catalyzed asymmetric hydroamidation of vinylarenes. a4 mol % + 2 mol % catalyst was used. b4...
Figure 7: Proposed reaction mechanism for the copper-catalyzed hydroamidation of vinylarenes.
Scheme 9: Copper-catalyzed anti-Markovnikov hydroamidation of alkynes.
Figure 8: Proposed reaction mechanism for the copper-catalyzed amidation of alkynes.
Scheme 10: Copper-catalyzed preparation of primary amides through N–O bond reduction using reducing agent.
Figure 9: Proposed catalytic cycle for the copper-catalyzed reduction of dioxazolones.
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
- either debenzylated and subsequently transformed into a thiourea organocatalyst or turned into an axially chiral sulfonamide. In 2022, Yang et al. presented their (3 + 2) formal cycloaddition of alkynylindoles 184 with azonaphthalenes 185 catalyzed by the SPINOL-based CPA C26 (Scheme 54) [82]. The
Graphical Abstract
Scheme 1: Formation of axially chiral styrenes 3 via iminium activation.
Scheme 2: Synthesis of axially chiral 2-arylquinolines 6.
Scheme 3: Atroposelective intramolecular (4 + 2) annulation leading to aryl-substituted indolines.
Scheme 4: Atroposelective formation of biaryl via twofold aldol condensation.
Scheme 5: Strategy towards diastereodivergent formation of axially chiral oligonaphthylenes.
Scheme 6: Atroposelective formation of chiral biaryls based on a Michael/Henry domino reaction.
Scheme 7: Organocatalytic Michael/aldol cascade followed by oxidative aromatization.
Scheme 8: Atroposelective formation of C(sp2)–C(sp3) axially chiral compounds.
Scheme 9: NHC-catalyzed synthesis of axially chiral styrenes 26.
Scheme 10: NHC-catalyzed synthesis of biaxial chiral pyranones.
Scheme 11: Formation of bridged biaryls with eight-membered lactones.
Scheme 12: The NHC-catalyzed (3 + 2) annulation of urazoles 37 and ynals 36.
Scheme 13: NHC-catalyzed synthesis of axially chiral 4‑aryl α‑carbolines 41.
Scheme 14: NHC-catalyzed construction of N–N-axially chiral pyrroles and indoles.
Scheme 15: NHC-catalyzed oxidative Michael–aldol cascade.
Scheme 16: NHC-catalyzed (4 + 2) annulation for the synthesis of benzothiophene-fused biaryls.
Scheme 17: NHC-catalyzed desymmetrization of N-aryl maleimides.
Scheme 18: NHC-catalyzed deracemization of biaryl hydroxy aldehydes 55a–k into axially chiral benzonitriles 56a...
Scheme 19: NHC-catalyzed desymmetrization of 2-aryloxyisophthalaldehydes.
Scheme 20: NHC-catalyzed DKR of 2-arylbenzaldehydes 62.
Scheme 21: Atroposelective biaryl amination.
Scheme 22: CPA-catalyzed atroposelective amination of 2-anilinonaphthalenes.
Scheme 23: Atroposelective DKR of naphthylindoles.
Scheme 24: CPA-catalyzed kinetic resolution of binaphthylamines.
Scheme 25: Atroposelective amination of aromatic amines with diazodicarboxylates.
Scheme 26: Atroposelective Friedländer heteroannulation.
Scheme 27: CPA-catalyzed formation of axially chiral 4-arylquinolines.
Scheme 28: CPA-catalyzed Friedländer reaction of arylketones with cyclohexanones.
Scheme 29: CPA-catalyzed atroposelective Povarov reaction.
Scheme 30: Atroposelective CPA-catalyzed Povarov reaction.
Scheme 31: Paal–Knorr formation of axially chiral N-pyrrolylindoles and N-pyrrolylpyrroles.
Scheme 32: Atroposelective Paal–Knorr reaction leading to N-pyrrolylpyrroles.
Scheme 33: Atroposelective Pictet–Spengler reaction of N-arylindoles with aldehydes.
Scheme 34: Atroposelective Pictet–Spengler reaction leading to tetrahydroisoquinolin-8-ylanilines.
Scheme 35: Atroposelective formation of arylindoles.
Scheme 36: CPA-catalyzed arylation of naphthoquinones with indolizines.
Scheme 37: Atroposelective reaction of o-naphthoquinones.
Scheme 38: CPA-catalyzed formation of axially chiral arylquinones.
Scheme 39: CPA-catalyzed axially chiral N-arylquinones.
Scheme 40: Atroposelective additions of bisindoles to isatin-based 3-indolylmethanols.
Scheme 41: CPA-catalyzed synthesis of axially chiral arylindolylindolinones.
Scheme 42: CPA-catalyzed reaction between bisindoles and ninhydrin-derived 3-indoylmethanols.
Scheme 43: Atroposelective reaction of bisindoles and isatin-derived imines.
Scheme 44: CPA-catalyzed formation of axially chiral bisindoles.
Scheme 45: Atroposelective reaction of 2-naphthols with alkynylhydroxyisoindolinones.
Scheme 46: CPA-catalyzed reaction of indolylnaphthols with propargylic alcohols.
Scheme 47: Atroposelective formation of indolylpyrroloindoles.
Scheme 48: Atroposelective reaction of indolylnaphthalenes with alkynylnaphthols.
Scheme 49: CPA-catalyzed addition of naphthols to alkynyl-2-naphthols and 2-naphthylamines.
Scheme 50: CPA-catalyzed formation of axially chiral aryl-alkene-indoles.
Scheme 51: CPA-catalyzed formation of axially chiral styrenes.
Scheme 52: Atroposelective formation of alkenylindoles.
Scheme 53: Atroposelective formation of axially chiral arylquinolines.
Scheme 54: Atroposelective (3 + 2) cycloaddition of alkynylindoles with azonaphthalenes.
Scheme 55: CPA-catalyzed formation of axially chiral 3-(1H-benzo[d]imidazol-2-yl)quinolines.
Scheme 56: Atroposelective cyclization of 3-(arylethynyl)-1H-indoles.
Scheme 57: Atroposelective three-component heteroannulation.
Scheme 58: CPA-catalyzed formation of arylbenzimidazols.
Scheme 59: CPA-catalyzed reaction of N-naphthylglycine esters with nitrosobenzenes.
Scheme 60: CPA-catalyzed formation of axially chiral N-arylbenzimidazoles.
Scheme 61: CPA-catalyzed formation of axially chiral arylbenzoindoles.
Scheme 62: CPA-catalyzed formation of pyrrolylnaphthalenes.
Scheme 63: CPA-catalyzed addition of naphthols and indoles to nitronaphthalenes.
Scheme 64: Atroposelective reaction of heterobiaryl aldehydes and aminobenzamides.
Scheme 65: Atroposelective cyclization forming N-arylquinolones.
Scheme 66: Atroposelective formation of 9H-carbazol-9-ylnaphthalenes and 1H-indol-1-ylnaphthalene.
Scheme 67: CPA-catalyzed formation of pyrazolylnaphthalenes.
Scheme 68: Atroposelective addition of diazodicarboxamides to azaborinephenols.
Scheme 69: Catalytic formation of axially chiral arylpyrroles.
Scheme 70: Atroposelective coupling of 1-azonaphthalenes with 2-naphthols.
Scheme 71: CPA-catalyzed formation of axially chiral oxindole-based styrenes.
Scheme 72: Atroposelective electrophilic bromination of aminonaphthoquinones.
Scheme 73: Atroposelective bromination of dienes.
Scheme 74: CPA-catalyzed formation of axially chiral 5-arylpyrimidines.
Scheme 75: Atroposelective hydrolysis of biaryloxazepines.
Scheme 76: Atroposelective opening of dinaphthosiloles.
Scheme 77: Atroposelective reduction of naphthylenals.
Scheme 78: Atroposelective allylic substitution with 2-naphthols.
Scheme 79: Atroposelective allylic alkylation with phosphinamides.
Scheme 80: Atroposelective allylic substitution with aminopyrroles.
Scheme 81: Atroposelective allylic substitution with aromatic sulfinamides.
Scheme 82: Atroposelective sulfonylation of naphthylynones.
Scheme 83: Squaramide-catalyzed reaction of alkynyl-2-naphthols with 5H-oxazolones.
Scheme 84: Formation of axially chiral styrenes via sulfonylative opening of cyclopropanols.
Scheme 85: Atroposelective organo-photocatalyzed sulfonylation of alkynyl-2-naphthols.
Scheme 86: Thiourea-catalyzed atroposelective cyclization of alkynylnaphthols.
Scheme 87: Squaramide-catalyzed formation of axially chiral naphthylisothiazoles.
Scheme 88: Atroposelective iodo-cyclization catalyzed by squaramide C69.
Scheme 89: Squaramide-catalyzed formation of axially chiral oligoarenes.
Scheme 90: Atroposelective ring-opening of cyclic N-sulfonylamides.
Scheme 91: Thiourea-catalyzed kinetic resolution of naphthylpyrroles.
Scheme 92: Atroposelective ring-opening of arylindole lactams.
Scheme 93: Atroposelective reaction of 1-naphthyl-2-tetralones and diarylphosphine oxides.
Scheme 94: Atroposelective reaction of iminoquinones with indoles.
Scheme 95: Kinetic resolution of binaphthylalcohols.
Scheme 96: DKR of hydroxynaphthylamides.
Scheme 97: Atroposelective N-alkylation with phase-transfer catalyst C75.
Scheme 98: Atroposelective allylic substitution via kinetic resolution of biarylsulfonamides.
Scheme 99: Atroposelective bromo-functionalization of alkynylarenes.
Scheme 100: Sulfenylation-induced atroposelective cyclization.
Scheme 101: Atroposelective O-sulfonylation of isochromenone-indoles.
Scheme 102: NHC-catalyzed atroposelective N-acylation of anilines.
Scheme 103: Peptide-catalyzed atroposelective ring-opening of lactones.
Scheme 104: Peptide-catalyzed coupling of 2-naphthols with quinones.
Scheme 105: Atroposelective nucleophilic aromatic substitution of fluoroarenes.
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
- . A plausible mechanism is proposed, suggesting a possible radical pathway. Keywords: electrophilic amination; hypervalent iodine reagents; sulfinamide; sulfonamide; Introduction Iodine(III) compounds, known as λ3-iodanes, have been extensively applied in organic synthesis. Although initially used
- reactivity with in situ-generated sulfenate anions, from β-sulfinyl esters, to achieve S–N bond formation. The importance of establishing this S–N bond results from the widespread presence of sulfonyl-containing bioactive compounds, such as the sulfonamide group which can be found in many pharmaceuticals
- , commonly referred to as sulfa drugs. These include top seller drugs, e.g., antimicrobials, anti-inflammatories, antihypertensives, and antitumor agents [24][25][26]. Particularly, the sulfonamide motif can act as a bioisostere of carboxylic acids, establishing a set of hydrogen bonds similar to those
Graphical Abstract
Figure 1: Examples of cyclic HIRs with a nitrogen-based group transfer [4,10,13-20].
Scheme 1: Electrophilic α‑amination of indanone-based β-ketoesters [4].
Scheme 2: Scope of the different (benzylamino)benziodoxolones (BBXs) 2 with ORTEP-3 diagram of compound 2d, u...
Scheme 3: Scope of the different β-sulfinyl esters 4 [32,33]. Isolated yields. rt – room temperature.
Scheme 4: Scope of the primary amine electrophilic reaction of sulfenate salts. Reaction conditions: 4 (2 equ...
Scheme 5: Electrophilic amination reaction in the presence of TEMPO. Reaction conditions: 4a (2 equiv), NaH (...
Scheme 6: Mechanism proposed for sulfonamide 5, β-sulfinyl ester 4, disulfide 7, and sulfide 3 formations. Th...
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
- cyclic derivatives. Conjugated imines are usually synthesized from the corresponding carbonyl precursors by reaction with a sulfonamide in the presence of Lewis acids and a dehydrating agent such as molecular sieves [3]. Also, recently a palladium-catalyzed dehydrogenation of aliphatic imines was
Graphical Abstract
Figure 1: Reactivity of α,β-unsaturated imines and variety of structures.
Figure 2: The hetero-Diels–Alder and inverse electron demand hetero-Diels–Alder reactions.
Figure 3: Different strategies to promote the activation of dienes and dienophiles in IEDADA reactions.
Figure 4: Examples of non-covalent interactions in organocatalysis.
Scheme 1: Enantioselective bifunctional thiourea-catalyzed inverse electron demand Diels–Alder reaction of N-...
Scheme 2: Cinchona-derived thiourea-catalyzed stereoselective (3 + 2) reaction of α,β-unsaturated imines and ...
Scheme 3: Cinchona-derived thiourea-catalyzed stereoselective (3 + 2)/(4 + 2) cascade reaction of α,β-unsatur...
Scheme 4: Enantioselective bifunctional squaramide-catalyzed formal [4 + 2] cycloaddition of malononitrile wi...
Scheme 5: Bifunctional squaramide-catalyzed IEDADA reaction of saccharin-derived 1-azadienes and azlactones.
Scheme 6: Chiral guanidine-catalyzed enantioselective (4+1) cyclization of benzofuran-derived azadienes with ...
Scheme 7: Bifunctional squaramide-catalyzed [4 + 2] cyclization of benzofuran-derived azadienes and azlactone...
Scheme 8: Chiral bifunctional squaramide-catalyzed domino Mannich/formal [4 + 2] cyclization of 2-benzothiazo...
Scheme 9: Chiral bifunctional thiourea-catalyzed formal IEDADA reaction of β,γ-unsaturated ketones and benzof...
Scheme 10: Dihydroquinine-derived squaramide-catalyzed (3 + 2) cycloaddition reaction of isocyanoacetates and ...
Scheme 11: Enantioselective squaramide-catalyzed asymmetric IEDADA reaction of benzofuran-derived azadienes an...
Scheme 12: Scale up and derivatizations of benzofuran-fused 2-piperidinol derivatives.
Scheme 13: Dihydroquinine-derived squaramide-catalyzed Mannich-type reaction of isocyanoacetates with N-(2-ben...
Figure 5: Structure of a cinchona alkaloid and (DHQD)2PHAL.
Scheme 14: Enantioselective modified cinchona alkaloid-catalyzed [4 + 2] annulation of γ-butenolides and sacch...
Scheme 15: Chiral tertiary amine-catalyzed [2 + 4] annulation of cyclic 1-azadiene with γ-nitro ketones.
Scheme 16: Inverse electron demand aza-Diels–Alder reaction (IEDADA) of 1-azadienes with enecarbamates catalyz...
Scheme 17: Phosphoric acid-catalyzed enantioselective [4 + 2] cycloaddition of benzothiazolimines and enecarba...
Scheme 18: Phosphoric acid-catalyzed enantioselective inverse electron demand aza-Diels–Alder reaction of in s...
Scheme 19: Proposed reaction mechanism for the phosphoric acid-catalyzed enantioselective inverse electron dem...
Scheme 20: Enantioselective dearomatization of indoles by a (3 + 2) cyclization with azoalkenes catalyzed by a...
Scheme 21: Synthetic applicability of the pyrroloindoline derivatives.
Scheme 22: Chiral phosphoric acid-catalyzed (2 + 3) dearomative cycloaddition of 3-alkyl-2-vinylindoles with a...
Scheme 23: Chiral phosphoric acid-catalyzed asymmetric [4 + 2] cycloaddition of aurone-derived 1-azadienes and...
Scheme 24: Phosphoric acid-catalyzed enantioselective formal [4 + 2] cycloaddition of dienecarbamates and 2-be...
Scheme 25: Chiral phosphoric acid-catalyzed asymmetric inverse electron demand aza-Diels–Alder reaction of 1,3...
Scheme 26: Chiral phosphoric acid-catalyzed asymmetric Attanasi reaction between 1,3-dicarbonyl compounds and ...
Scheme 27: Synthetic applicability of the NPNOL derivatives.
Scheme 28: Chiral phosphoric acid-catalyzed asymmetric intermolecular formal (3 + 2) cycloaddition of azoalken...
Scheme 29: Enantioselective [4 + 2] cyclization of α,β-unsaturated imines and azlactones.
Scheme 30: Catalytic cycle for the chiral phosphoric acid-catalyzed enantioselective [4 + 2] cyclization of α,...
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
- , an intramolecular cyclization takes place, facilitated by CuI. This step involves a 5-endo-dig cyclization, where the negatively nitrogen atom of the sulfonamide 25 attacks intramolecularly to yield the intermediate 26. The final product is formed when iodide is regenerated as CuI, allowing it to re
- -enter into the catalytic cycle. On the other hand, the sulfonyl group in its sulfonamide form is typically associated with antibacterial activity. However, it has been little studied the sulfonyl group regarding biological activity when attached to the indole nitrogen. Although scarce, some recent
Graphical Abstract
Scheme 1: Synthetic approaches to obtain the 1,5-disubstituted tetrazole-indole system and our synthetic appr...
Scheme 2: High-order multicomponent reaction for the synthesis of 1,5-disubstituted tetrazol-methanesulfonyli...
Scheme 3: Plausible reaction mechanism for the synthesis of target molecules 18a–n.
Figure 1: Differential effect of the 1,5-disubstituted tetrazole-indole hybrid compounds 18a–j on proliferati...
A review of recent advances in electrochemical and photoelectrochemical late-stage functionalization classified by anodic oxidation, cathodic reduction, and paired electrolysis
- Nian Li,
- Ruzal Sitdikov,
- Ajit Prabhakar Kale,
- Joost Steverlynck,
- Bo Li and
- Magnus Rueping
Beilstein J. Org. Chem. 2024, 20, 2500–2566, doi:10.3762/bjoc.20.214
- cation is formed by oxidation of the substrate at the anode. This radical cation is subsequently deprotonated to produce an allyl radical. The allyl radical is further oxidized to form the allyl cation, which is then attacked by the nucleophilic sulfonamide, leading to the formation of the desired C–N
- protocol for the installation of sulfonamide groups using commercially available SO2 and amines (Scheme 12) [20]. This method is highly appealing for industrial applications and LSF. The proposed mechanism begins with the anodic oxidation of the arene substrate. The resulting radical cation intermediate is
- then attacked by the nucleophilic amidosulfinate, which also functions as an electrolyte. The amidosulfinate is generated through the formation of a Lewis acid–base adduct. A subsequent oxidation step, accompanied by deprotonation, yields the sulfonamide product. SO2 captures the excess electrons via
Graphical Abstract
Figure 1: Classification of LSF reactions in this review.
Scheme 1: C(sp2)–H trifluoromethylation of heteroarenes.
Scheme 2: C(sp2)–H and C(sp3)–H alkylation of complex molecules.
Scheme 3: Electrochemical oxidation-induced intermolecular aromatic C–H sulfonamidation.
Scheme 4: Bioconjugation of tyrosine with (a) phenothiazine and (b) urazole derivatives.
Scheme 5: Electrochemical iodoamination of indoles using unactivated amines.
Scheme 6: Allylic C(sp3)–H aminations with sulfonamides.
Scheme 7: Electrochemical benzylic oxidation of C–H bonds.
Scheme 8: Site-selective electrooxidation of methylarenes to aromatic acetals.
Scheme 9: Electrochemical activation of C–H by electron-deficient W2C nanocrystals.
Scheme 10: α-Acyloxy sulfide preparation via C–H/OH cross-dehydrogenative coupling.
Scheme 11: Aromatic C–H-bond thiolation.
Scheme 12: C(sp2)–H functionalization for the installation of sulfonamide groups.
Scheme 13: Preparation of (hetero)aryl chlorides and vinyl chloride with 1,2-dichloroethane. aCu(OAc)2 (0.05 e...
Scheme 14: Electrochemical dual-oxidation enables access to α-chlorosulfoxides.
Scheme 15: Regio- and chemoselective formyloxylation–bromination/chlorination/trifluoromethylation of alkenes.
Scheme 16: Aziridine formation by coupling amines and alkenes.
Scheme 17: Formation of iminosulfide ethers via difunctionalization of an isocyanide.
Scheme 18: Synthesis of 1,3-difunctionalized molecules via C–C-bond cleavage of arylcyclopropane.
Scheme 19: Electrooxidative amino- and oxyselenation of alkenes. VBImBr = 1-butyl-3-vinylimidazolium bromide.
Scheme 20: Electrooxidative dehydrogenative [4 + 2] annulation of indole derivatives.
Scheme 21: Electrochemical cyclization combined with alkoxylation of triticonazole.
Scheme 22: Electrochemically tuned oxidative [4 + 2] annulation of olefins with hydroxamic acids.
Scheme 23: Electrosynthesis of indole derivatives via cyclization of 2-ethynylanilines.
Scheme 24: Allylic C–H oxidation of mono-, di-, and sesquiterpenes.
Scheme 25: Oxidation of unactivated C–H bonds.
Scheme 26: Fluorination of C(sp3)–H bonds. rAP = rapid alternating polarity.
Scheme 27: C(sp3)–H α-cyanation of secondary piperidines.
Scheme 28: Selective electrochemical hydrolysis of hydrosilanes to silanols.
Scheme 29: Organocatalytic electrochemical amination of benzylic C–H bonds.
Scheme 30: Iodide ion-initiated anodic oxidation reactions.
Scheme 31: Mn(III/IV) electro-catalyzed C(sp3)–H azidation.
Scheme 32: Tailored cobalt–salen complexes enable electrocatalytic intramolecular allylic C–H functionalizatio...
Scheme 33: Cobalt–salen complexes-induced electrochemical (cyclo)additions.
Scheme 34: Electrochemical 1,2-diarylation of alkenes enabled by direct dual C–H functionalization of electron...
Scheme 35: Cobalt-electrocatalyzed atroposelective C–H annulation.
Scheme 36: Nickel-electrocatalyzed C(sp2)–H alkoxylation with secondary alcohols.
Scheme 37: Nickel-catalyzed electrochemical enantioselective amination.
Scheme 38: Ruthenium-electrocatalyzed C(sp2)–H mono- and diacetoxylation.
Scheme 39: Rhodium(III)-catalyzed aryl-C–H phosphorylation enabled by anodic oxidation-induced reductive elimi...
Scheme 40: Asymmetric Lewis-acid catalysis for the synthesis of non-racemic 1,4-dicarbonyl compounds.
Scheme 41: Electrochemical enantioselective C(sp3)–H alkenylation.
Scheme 42: Palladium-catalyzed electrochemical dehydrogenative cross-coupling.
Scheme 43: Ir-electrocatalyzed vinylic C(sp2)–H activation for the annulation between acrylic acids and alkyne...
Scheme 44: Electrochemical gold-catalyzed C(sp3)–C(sp) coupling of alkynes and arylhydrazines.
Scheme 45: Photoelectrochemical alkylation of C–H heteroarenes using organotrifluoroborates.
Scheme 46: Mn-catalyzed photoelectro C(sp3)–H azidation.
Scheme 47: Photoelectrochemical undirected C–H trifluoromethylations of (Het)arenes.
Scheme 48: Photoelectrochemical dehydrogenative cross-coupling of heteroarenes with aliphatic C–H bonds.
Scheme 49: C–H amination via photoelectrochemical Ritter-type reaction.
Scheme 50: Photoelectrochemical multiple oxygenation of C–H bonds.
Scheme 51: Accelerated C(sp3)–H heteroarylations by the f-EPC system.
Scheme 52: Photoelectrochemical cross-coupling of amines.
Scheme 53: Birch electroreduction of arenes. GSW = galvanized steel wire.
Scheme 54: Electroreductive deuterations.
Scheme 55: Chemoselective electrosynthesis using rapid alternating polarity.
Scheme 56: Electroreductive olefin–ketone coupling.
Scheme 57: Electroreductive approach to radical silylation.
Scheme 58: Electrochemical borylation of alkyl halides. CC = carbon close.
Scheme 59: Radical fluoroalkylation of alkenes.
Scheme 60: Electrochemical defluorinative hydrogenation/carboxylation.
Scheme 61: Electrochemical decarboxylative olefination.
Scheme 62: Electrochemical decarboxylative Nozaki–Hiyama–Kishi coupling.
Scheme 63: Nickel-catalyzed electrochemical reductive relay cross-coupling.
Scheme 64: Electrochemical chemo- and regioselective difunctionalization of 1,3-enynes.
Scheme 65: Electrocatalytic doubly decarboxylative crosscoupling.
Scheme 66: Electrocatalytic decarboxylative crosscoupling with aryl halides.
Scheme 67: Nickel-catalyzed electrochemical reductive coupling of halides.
Scheme 68: Nickel-electrocatalyzed enantioselective carboxylation with CO2.
Scheme 69: Reductive electrophotocatalysis for borylation.
Scheme 70: Electromediated photoredox catalysis for selective C(sp3)–O cleavages of phosphinated alcohols to c...
Scheme 71: Stereoselective electro-2-deoxyglycosylation from glycals. MFE = methyl nonafluorobutyl ether.
Scheme 72: Electrochemical peptide modifications.
Scheme 73: Electrochemical α-deuteration of amides.
Scheme 74: Electrochemical synthesis of gem-diselenides.
Scheme 75: Site-selective electrochemical aromatic C–H amination.
Scheme 76: Electrochemical coupling of heteroarenes with heteroaryl phosphonium salts.
Scheme 77: Redox-neutral strategy for the dehydroxyarylation reaction.
Scheme 78: Nickel-catalyzed electrochemical C(sp3)–C(sp2) cross-coupling of benzyl trifluoroborate and halides....
Scheme 79: Paired electrocatalysis for C(sp3)–C(sp2) coupling.
Scheme 80: Redox-neutral strategy for amination of aryl bromides.
Scheme 81: Redox-neutral cross-coupling of aryl halides with weak N-nucleophiles. aProtocol with (+) RVC | RVC...
Scheme 82: Nickel-catalyzed N-arylation of NH-sulfoximines with aryl halides.
Scheme 83: Esterification of carboxylic acids with aryl halides.
Scheme 84: Electrochemically promoted nickel-catalyzed carbon–sulfur-bond formation. GFE = graphite felt elect...
Scheme 85: Electrochemical deoxygenative thiolation by Ni-catalysis. GFE = graphite felt electrode; NFE = nick...
Scheme 86: Electrochemical coupling of peptides with aryl halides.
Scheme 87: Paired electrolysis for the phosphorylation of aryl halides. GFE = graphite felt electrode, FNE = f...
Scheme 88: Redox-neutral alkoxyhalogenation of alkenes.
Stereoselective mechanochemical synthesis of thiomalonate Michael adducts via iminium catalysis by chiral primary amines
- Michał Błauciak,
- Dominika Andrzejczyk,
- Błażej Dziuk and
- Rafał Kowalczyk
Beilstein J. Org. Chem. 2024, 20, 2313–2322, doi:10.3762/bjoc.20.198
- by extended reaction times, sometimes up to 168 hours. An intriguing example involves the use of a bifunctional primary amine-sulfonamide catalyst, which activates benzylideneacetone towards dibenzyl malonate, with the presence of water accelerating the reaction [25]. An alternative approach, where
Graphical Abstract
Scheme 1: Two examples of base-catalyzed addition of thiomalonates to enones and the scope of the work.
Scheme 2: Tested reactions of cyclohexanone with dibenzyl thiomalonate 1.
Scheme 3: Impact of the bisthiomalonate on the yield and the stereoselectivity of the products.
Scheme 4: Plausible stereochemical model of the addition to cyclohexenone.
Scheme 5: Addition of bisthiomalonates 1–3 to cyclopentenone.
Scheme 6: Acyclic enone in reactions with thiomalonates 1–4.
Scheme 7: Reaction of β-ketothioesters with acceptor E1.
Hydrogen-bond activation enables aziridination of unactivated olefins with simple iminoiodinanes
- Phong Thai,
- Lauv Patel,
- Diyasha Manna and
- David C. Powers
Beilstein J. Org. Chem. 2024, 20, 2305–2312, doi:10.3762/bjoc.20.197
- selected as it underwent efficient aziridination with PhINTs. A family of iminoiodinanes 2 was synthesized from PIDA and the corresponding sulfonamide derivative. Reaction of phenylsulfonamide-derived iminoiodinane with cyclopentene afforded N-phenylsulfonylaziridine 6b in 45% yield, while N-(p
- with the stability of the relevant iminoiodinane reagent, with higher yields attributed to more electron-rich sulfonamide substitution such as 2a. Relatively electron-deficient iminoiodinanes are less efficient but are also more prone to decomposition (see Supporting Information File 1, Figure S2 for
- of the sulfonamide resulted in O–H proton signal of HFIP being at 5.64 ppm with FWHM = 11.3 Hz. Second, to evaluate the impact of HFIP on the redox chemistry of PhINTs, we collected cyclic voltammograms (CVs) of iminoiodinane 2c in MeCN in the presence of varying HFIP increments (Scheme 4b). The CV
Graphical Abstract
Scheme 1: a) Lewis acid activation of hypervalent iodine reagents can enhance the reactivity of these reagent...
Scheme 2: Scope and limitations of HFIP-promoted direct aziridination with iminoiodinane reagents. Conditions...
Scheme 3: Scope of nitrogen group transfer in the aziridination of aliphatic olefins. Conditions using synthe...
Scheme 4: a) The broadening of the hydroxide proton (denoted by asterisk *) of HFIP in the presence of iminoi...
Factors influencing the performance of organocatalysts immobilised on solid supports: A review
- Zsuzsanna Fehér,
- Dóra Richter,
- Gyula Dargó and
- József Kupai
Beilstein J. Org. Chem. 2024, 20, 2129–2142, doi:10.3762/bjoc.20.183
- organocatalyst was demonstrated by List and co-workers, who showcased the robustness of a cinchona alkaloid-based sulfonamide organotextile catalyst 36 (immobilised on nylon 6,6) through hundreds of recycling experiments (Scheme 11) [15]. The organotextile catalyst 36 exhibited a very similar enantioselectivity
- asymmetric Michael addition of pentane-2,4-dione (32) and trans-β-nitrostyrene (11). Alcoholytic desymmetrisation of a cyclic anhydride 34 catalysed by polyamide-supported cinchona sulfonamide 36. Funding This research was funded by the National Research, Development, and Innovation Office (grant number
Graphical Abstract
Scheme 1: Esterification of oleic acid (1) with propylsulfonic acid (Pr-SO3H)-functionalised mesoporous silic...
Scheme 2: Using confinement of organocatalytic units for improving the enantioselectivity of silica-supported...
Scheme 3: Michael addition catalysed by cinchona thiourea immobilised on magnetic nanoparticles (13).
Scheme 4: Michael addition catalysed by cinchona thiourea in the presence of magnetic nanoparticles.
Scheme 5: Benzoin condensation catalysed by N-benzylthiazolium salt attached to mesoporous material.
Scheme 6: Photoinduced RAFT polymerisation of n-butyl acrylate (19) catalysed by silica nanoparticle-supporte...
Scheme 7: Pressure and temperature dependence of the 1,4-addition of propanal to trans-β-nitrostyrene under c...
Scheme 8: α-Amination of ethyl 2-oxocyclopentanecarboxylate catalysed by PS-THU which could be recycled over ...
Scheme 9: Preparation of supported catalysts C29–C31 from cinchona squaramides 29–31 modified with a primary ...
Scheme 10: Application of PGMA-supported organocatalysts C29–C31 in the asymmetric Michael addition of pentane...
Scheme 11: Alcoholytic desymmetrisation of a cyclic anhydride 34 catalysed by polyamide-supported cinchona sul...
