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Search for "organic synthesis" in Full Text gives 769 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.
Synthesis of disulfides and 3-sulfenylchromones from sodium sulfinates catalyzed by TBAI
- Zhenlei Zhang,
- Ying Wang,
- Xingxing Pan,
- Manqi Zhang,
- Wei Zhao,
- Meng Li and
- Hao Zhang
Beilstein J. Org. Chem. 2025, 21, 253–261, doi:10.3762/bjoc.21.17
- groups in organic synthesis [1][2][3][4]. In chemistry and biology, disulfide bonds play crucial roles in protein folding and stabilization [5][6][7][8] and in the rubber industry, they are used to link different polymer chains [9][10]. The disulfide bond backbone is commonly used as a linker for
- antibody–drug coupling (ADCs), in which the active drug released in the target cell by selectively breaking the disulfide bond [11]. Given the wide applicability of disulfides, the development of efficient, green, mild, and cost-effective methods for the organic synthesis of disulfides is of significant
- sulfinate (Scheme 1) [29][30][31][32]. Among the available alternatives, sodium sulfinate is particularly interesting because it is more stable and easier to transport, and it is widely used in organic synthesis [33][34][35][36][37]. When using sodium sulfite as the starting material for the construction of
Graphical Abstract
Scheme 1: Different strategies for the synthesis of disulfides and 3-sulfenylchromones.
Scheme 2: Substrate scope for the synthesis of disulfides. Reaction conditions: 1 (1 mmol), TBAI (0.2 mmol), H...
Scheme 3: Substrate scope for the synthesis of 3-sulfenylchromones. Reaction conditions: 1 (1 mmol), 3 (0.5 m...
Scheme 4: Gram-scale synthesis of 2a and 4a and one-pot synthesis of 4a.
Scheme 5: Control experiments.
Scheme 6: Plausible reaction mechanism.
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
- increasing interest as affordable, versatile, and sustainable catalytic systems. These catalysts are extensively employed in organic synthesis owing to their cost-effectiveness, reduced toxicity, and natural abundance [20][21][22][23][24][25][26][27][28]. The use of copper salts has enabled a variety of
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 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
- –heteroatom (C–X, where X = N, O, or halogens) bonds in organic synthesis. Copper was one of the first transition metals employed in cross-coupling to form C–C and C–X bonds [1][2]. In 1901, Ullmann reported the first cross-coupling reaction for the formation of biaryl compounds in the presence of
- ’ and Fu’s asymmetric C–N bond cross-coupling reactions by merging photoredox catalysis with copper catalysis [29][30]. Building on the success of photoredox catalysis, electrochemistry has emerged as a complementary and attractive strategy for promoting sustainability of organic synthesis. By offering
- catalysis to organic synthesis, focusing on recent developments in Cu-catalyzed electrochemical reaction categorized into four types: 1) C–H functionalization, 2) olefin addition, 3) decarboxylative functionalization, and 4) coupling reactions (Figure 3). This review aims to provide insight into the
Graphical Abstract
Figure 1: General mechanisms of traditional and radical-mediated cross-coupling reactions.
Figure 2: Types of electrocatalysis (using anodic oxidation).
Figure 3: Recent developments and features of electrochemical copper catalysis.
Figure 4: Scheme and proposed mechanism for Cu-catalyzed alkynylation and annulation of benzamide.
Figure 5: Scheme and proposed mechanism for Cu-catalyzed asymmetric C–H alkynylation.
Figure 6: Scheme for Cu/TEMPO-catalyzed C–H alkenylation of THIQs.
Figure 7: Scheme and proposed mechanism for Cu-catalyzed electrophotochemical enantioselective cyanation of b...
Figure 8: Scheme and proposed mechanism for Cu-catalyzed electrophotochemical asymmetric heteroarylcyanation ...
Figure 9: Scheme and proposed mechanism for Cu-catalyzed enantioselective regiodivergent cross-dehydrogenativ...
Figure 10: Scheme and proposed mechanism for Cu/Ni-catalyzed stereodivergent homocoupling of benzoxazolyl acet...
Figure 11: Scheme and proposed mechanism for Cu-catalyzed electrochemical amination.
Figure 12: Scheme and proposed mechanism for Cu-catalyzed electrochemical azidation of N-arylenamines and annu...
Figure 13: Scheme and proposed mechanism for Cu-catalyzed electrochemical halogenation.
Figure 14: Scheme and proposed mechanism for Cu-catalyzed asymmetric cyanophosphinoylation of vinylarenes.
Figure 15: Scheme and proposed mechanism for Cu/Co dual-catalyzed asymmetric hydrocyanation of alkenes.
Figure 16: Scheme and proposed mechanism for Cu-catalyzed electrochemical diazidation of olefins.
Figure 17: Scheme and proposed mechanism for Cu-catalyzed electrochemical azidocyanation of alkenes.
Figure 18: Scheme and proposed mechanism for Cu-catalyzed electrophotochemical asymmetric decarboxylative cyan...
Figure 19: Scheme and proposed mechanism for electrocatalytic Chan–Lam coupling.
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
- ; heteropolycycles; multicomponent reactions; one-pot reaction; Introduction Copper has gained a relevant role in organic synthesis as an alternative to precious metals due to its low toxicity, ease of handling, high catalytic activity, and cost-effectiveness [1][2]. In recent years, Cu(OTf)2 has significantly
- known processes, a particular Mannich-type reaction was realized in water in the presence of a dendritic 2,2’-bipyridine ligand 2 and Cu(OTf)2 (Scheme 2) [16]. The hydrophobic ligand surrounding the metal revealed to be essential for the organic synthesis in water, thus increasing the reaction yields
Graphical Abstract
Figure 1: Plausible general catalytic activation for ionic or radical mechanisms.
Scheme 1: Synthesis of α-aminonitriles 1.
Scheme 2: Synthesis of β-amino ketone or β-amino ester derivatives 3.
Scheme 3: Synthesis of 1-(α-aminoalkyl)-2-naphthol derivatives 4.
Scheme 4: Synthesis of thioaminals 5.
Scheme 5: Synthesis of aryl- or amine-containing alkanes 6 and 7.
Scheme 6: Synthesis of 1-aryl-2-sulfonamidopropanes 8.
Scheme 7: Synthesis of α-substituted propargylamines 10.
Scheme 8: Synthesis of N-propargylcarbamates 11.
Scheme 9: Synthesis of (E)-vinyl sulfones 12.
Scheme 10: Synthesis of o-halo-substituted aryl chalcogenides 13.
Scheme 11: Synthesis of α-aminophosphonates 14.
Scheme 12: Synthesis of unsaturated furanones and pyranones 15–17.
Scheme 13: Synthesis of substituted dihydropyrimidines 18.
Scheme 14: Regioselective synthesis of 1,4-dihydropyridines 20.
Scheme 15: Synthesis of tetrahydropyridines 21.
Scheme 16: Synthesis of furoquinoxalines 22.
Scheme 17: Synthesis of 2,4-substituted quinolines 23.
Scheme 18: Synthesis of cyclic ether-fused tetrahydroquinolines 24.
Scheme 19: Practical route for 1,2-dihydroisoquinolines 25.
Scheme 20: Synthesis of 2,3-dihydroquinazolin-4(1H)-one derivatives 26.
Scheme 21: Synthesis of polysubstituted pyrroles 27.
Scheme 22: Enantioselective synthesis of polysubstituted pyrrolidines 30 directed by the copper complex 29.
Scheme 23: Synthesis of 4,5-dihydropyrazoles 31.
Scheme 24: Synthesis of 2 arylisoindolinones 32.
Scheme 25: Synthesis of imidazo[1,2-a]pyridines 33.
Scheme 26: Synthesis of isoxazole-linked imidazo[1,2-a]azines 35.
Scheme 27: Synthesis of 2,3-dihydro-1,2,4-triazoles 36.
Scheme 28: Synthesis of naphthopyrans 37.
Scheme 29: Synthesis of benzo[g]chromene derivatives 38.
Scheme 30: Synthesis of naphthalene annulated 2-aminothiazoles 39, piperazinyl-thiazoloquinolines 40 and thiaz...
Scheme 31: Synthesis of furo[3,4-b]pyrazolo[4,3-f]quinolinones 42.
Scheme 32: Synthesis of spiroindoline-3,4’-pyrano[3,2-b]pyran-4-ones 43.
Scheme 33: Synthesis of N-(α-alkoxy)alkyl-1,2,3-triazoles 44.
Scheme 34: Synthesis of 4-(α-tetrasubstituted)alkyl-1,2,3-triazoles 45.
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
- ; Introduction Stereoselective catalytic formation of chiral compounds is one of the critical tasks of modern organic synthesis [1]. The catalytic formation of compounds with a center of chirality has been the focus of countless works and can now be considered a matured area. On the other hand, the generation of
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.
Emerging trends in the optimization of organic synthesis through high-throughput tools and machine learning
- Pablo Quijano Velasco,
- Kedar Hippalgaonkar and
- Balamurugan Ramalingam
Beilstein J. Org. Chem. 2025, 21, 10–38, doi:10.3762/bjoc.21.3
- reactors; data processing; high-throughput experimentation; machine learning; reaction optimization; Introduction Organic synthesis plays a crucial role in drug discovery, polymer synthesis, materials science, agrochemicals, and specialty chemicals. Their synthesis and process optimization require
- . In addition to organic synthesis, the slug flow methodology has found application in polymer synthesis. A flow platform capable of polymerizing 397 unique copolymer compositions was developed by Reis et al. [51] using a droplet flow reactor. The methodology and high-fidelity data enabled them to
- Bédard et al. [62] to mitigate some of the challenges in traditional organic synthesis by the integration of hardware, software, and analytics. Comprising an array of modular components, including units for heating, cooling, LED light exposure, and packed bed reactors, it provides a flexible platform for
Graphical Abstract
Figure 1: A high-level representation of the workflow and framework used for the optimization of organic reac...
Figure 2: (a) Photograph showing a Chemspeed HTE platform using 96-well reaction blocks. (b) Mobile robot equ...
Figure 3: (a) Description of a slug flow platform developed using segments of gas as separation medium for hi...
Figure 4: Schematic representation (a) and photograph (b) of the flow parallel synthesizer intelligently desi...
Figure 5: (a) Schematic representation of an ASFR for obtaining an optimal solution with minimal human interv...
Figure 6: (a) A modular flow platform developed for a wider variety of chemical syntheses. (b) Various catego...
Figure 7: Implementation of four complementary PATs into the optimization process of a three-step synthesis.
Figure 8: Overlay of several Raman spectra of a single condition featuring the styrene vinyl region (a) and t...
Figure 9: (a) Schematic description of the process of chemical reaction optimization through ML methods. (b) ...
Figure 10: (a) Comparison between a standard GP (single-task) and a multitask GP. Training an auxiliary task u...
Figure 11: Comparison of the reaction yield between optimizations campaign where the catalyst ligand selection...
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
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...
Ceratinadin G, a new psammaplysin derivative possessing a cyano group from a sponge of the genus Pseudoceratina
- Shin-ichiro Kurimoto,
- Kouta Inoue,
- Taito Ohno and
- Takaaki Kubota
Beilstein J. Org. Chem. 2024, 20, 3215–3220, doi:10.3762/bjoc.20.267
- , the first asymmetric total synthesis of psammaplysin A was accomplished by Smith and Morrow, and the absolute configuration of compound 1 was also confirmed through organic synthesis [7]. In our ongoing research focused on uncovering new bioactive secondary metabolites from Okinawan marine sponges, we
Graphical Abstract
Figure 1: Structures of ceratinadin G (1) and psammaplysin F (2).
Figure 2: Selected 2D NMR correlations for ceratinadin G (1).
Figure 3: ECD spectra of ceratinadin G (1) and psammaplysin F (2) in MeOH.
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
Graphical Abstract
Figure 1: Representative examples of fluorine containing, biologically active compounds.
Scheme 1: Strategies for the synthesis of α-alkyl sulfoxonium ylides.
Scheme 2: Exploring substrate scope in the direct α-fluoroalkylation of sulfoxonium ylides.
Scheme 3: Synthetic applications of fluoroalkylated sulfoxonium ylides.
Figure 2: Possible mechanisms for the reaction of 1a and 2a leading to 3a (via B), proceeding via either halo...
Figure 3: Electrostatic potential of 2a’ from 0.075 e to 0.21 e, showing two sigma holes of potentials 0.20 a...
Figure 4: The optimized reaction coordinate diagrams for the halogen bond-mediated mechanism (path 1, left) a...
Multicomponent reactions driving the discovery and optimization of agents targeting central nervous system pathologies
- Lucía Campos-Prieto,
- Aitor García-Rey,
- Eddy Sotelo and
- Ana Mallo-Abreu
Beilstein J. Org. Chem. 2024, 20, 3151–3173, doi:10.3762/bjoc.20.261
- organic synthesis, particularly through MCRs, have streamlined the synthesis of benzodiazepines, making it more efficient and environmentally friendly [55]. For example, olanzapine as a benzodiazepine-based clinical drug was appropriately and concisely synthesized via MCR [56][57]. Over the last twenty
Graphical Abstract
Figure 1: Classical MCRs.
Figure 2: Different scaffolds that can be formed with the Ugi adduct.
Scheme 1: Oxoindole-β-lactam core produced in a U4C-3CR.
Figure 3: Most active oxoindole-β-lactam compounds developed by Brãndao et al. [33].
Scheme 2: Ugi-azide synthesis of benzofuran, pyrazole and tetrazole hybrids.
Figure 4: The most promising hybrids synthesized via the Ugi-azide multicomponent reaction reported by Kushwa...
Scheme 3: Four-component Ugi reaction for the synthesis of novel antioxidant compounds.
Figure 5: Most potent antioxidant compounds obtained through the Ugi four-component reaction developed by Pac...
Scheme 4: Four-component Ugi reaction to synthesize β-amiloyd aggregation inhibitors.
Figure 6: The most potential β-amiloyd aggregation inhibitors generated by Galante et al. [37].
Scheme 5: Four-component Ugi reaction to obtain FATH hybrids and the best candidate synthesized.
Scheme 6: Four-component Ugi reaction for the synthesis of FATMH hybrids and the best candidate synthesized.
Scheme 7: Petasis multicomponent reaction to produce pyrazine-based MTDLs.
Figure 7: Best pyrazine-based MTDLs synthesized by Madhav et al. [40].
Scheme 8: Synthesis of BCPOs employing a Knoevenagel-based multicomponent reaction and the best candidate syn...
Scheme 9: Hantzsch multicomponent reaction for the synthesis of DHPs as novel MTDLs.
Figure 8: Most active 1,4-dihydropyridines developed by Malek et al. [43].
Scheme 10: Chromone–donepezil hybrid MTDLs obtained via the Passerini reaction.
Figure 9: Best CDH-based MTDLs as AChE inhibitors synthesized by Malek et al. [46].
Scheme 11: Replacement of the nitrogen in lactams 11 with an oxygen in 12 to influence hydrogen-bond donating ...
Scheme 12: MCR 3 + 2 reaction to develop spirooxindole, spiroacenaphthylene, and bisbenzo[b]pyran compounds.
Figure 10: SIRT2 activity of best derivatives obtained by Hasaninejad et al. [49].
Scheme 13: Synthesis of ML192 analogs using the Gewald multicomponent reaction and the best candidate synthesi...
Scheme 14: Development of 1,5-benzodiazepines via Ugi/deprotection/cyclization (UDC) approach by Xu et al. [59].
Scheme 15: Synthesis of polysubstituted 1,4-benzodiazepin-3-ones using UDC strategy.
Scheme 16: Synthetic procedure to obtain 3-carboxamide-1,4-benzodiazepin-5-ones employing Ugi–reduction–cycliz...
Scheme 17: Ugi cross-coupling (U-4CRs) to synthesize triazolobenzodiazepines.
Scheme 18: Azido-Ugi four component reaction cyclization to obtain imidazotetrazolodiazepinones.
Scheme 19: Synthesis of oxazolo- and thiazolo[1,4]benzodiazepine-2,5-diones via Ugi/deprotection/cyclization a...
Scheme 20: General synthesis of 2,3-dichlorophenylpiperazine-derived compounds by the Ugi reaction and Ugi/dep...
Figure 11: Best DRD2 compounds synthesized using a multicomponent strategy.
Scheme 21: Bucherer–Bergs multicomponent reaction to obtain a key intermediate in the synthesis of pomaglumeta...
Scheme 22: Ugi reaction to synthesize racetam derivatives and example of two racetams synthesized by Cioc et a...
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
- , including ligand coupling, oxidative addition, intermolecular nucleophilic attack, 1,2-aryl migration, reductive elimination, and intramolecular nucleophilic attack. This approach offers a rapid and effective way to produce 5-fluoro-2-aryloxazoline compounds, which are valuable building blocks in organic
- synthesis. Carbon nucleophiles In addition to intramolecular aminofluorination and oxyfluorination, Szabó and co-workers reported alkene carbofluorination in 2015 (Scheme 22) [31]. Using 1-fluoro-3,3-dimethylbenziodoxole (12) and [Cu(MeCN)4]BF4 as a catalyst to activate it, the authors reported the
Graphical Abstract
Figure 1: Example bioactive compounds containing cyclic scaffolds potentially accessible by HVI chemistry.
Figure 2: A general mechanism for HVI-mediated endo- or exo-halocyclisation.
Scheme 1: Metal-free synthesis of β-fluorinated piperidines 6. Ts = tosyl.
Scheme 2: Intramolecular aminofluorination of unactivated alkenes with a palladium catalyst.
Scheme 3: Aminofluorination of alkenes in the synthesis of enantiomerically pure β-fluorinated piperidines. P...
Scheme 4: Synthesis of β-fluorinated piperidines.
Scheme 5: Intramolecular fluoroaminations of unsaturated amines published by Li.
Scheme 6: Intramolecular aminofluorination of unsaturated amines using 1-fluoro-3,3-dimethylbenziodoxole (12)...
Scheme 7: 3-fluoropyrrolidine synthesis. aDiastereomeric ratio (cis/trans) determined by 19F NMR analysis.
Scheme 8: Kitamura’s synthesis of 3-fluoropyrrolidines. Values in parentheses represent the cis:trans ratio.
Scheme 9: Jacobsen’s enantio- and diastereoselective protocol for the synthesis of syn-β-fluoroaziridines 15.
Scheme 10: Different HVI reagents lead to different diastereoselectivity in aminofluorination competing with c...
Scheme 11: Fluorocyclisation of unsaturated alcohols and carboxylic acids to make tetrahydrofurans, fluorometh...
Scheme 12: Oxyfluorination of unsaturated alcohols.
Scheme 13: Synthesis and mechanism of fluoro-benzoxazepines.
Scheme 14: Intramolecular fluorocyclisation of unsaturated carboxylic acids. Yield of isolated product within ...
Scheme 15: Synthesis of fluorinated tetrahydrofurans and butyrolactone.
Scheme 16: Synthesis of fluorinated oxazolines 32. aReaction time increased to 40 hours. Yields refer to isola...
Scheme 17: Electrochemical synthesis of fluorinated oxazolines.
Scheme 18: Electrochemical synthesis of chromanes.
Scheme 19: Synthesis of fluorinated oxazepanes.
Scheme 20: Enantioselective oxy-fluorination with a chiral aryliodide catayst.
Scheme 21: Catalytic synthesis of 5‑fluoro-2-aryloxazolines using BF3·Et2O as a source of fluoride and an acti...
Scheme 22: Intramolecular carbofluorination of alkenes.
Scheme 23: Intramolecular chlorocyclisation of unsaturated amines.
Scheme 24: Synthesis of chlorinated cyclic guanidines 44.
Scheme 25: Synthesis of chlorinated pyrido[2,3-b]indoles 46.
Scheme 26: Chlorolactonization and chloroetherification reactions.
Scheme 27: Proposed mechanism for the synthesis of chloromethyl oxazolines 49.
Scheme 28: Oxychlorination to form oxazine and oxazoline heterocycles promoted by BCl3.
Scheme 29: Aminobromocyclisation of homoallylic sulfonamides 53. The cis:trans ratios based on the 1H NMR of t...
Scheme 30: Synthesis of cyclic imines 45.
Scheme 31: Synthesis of brominated pyrrolo[2,3-b]indoles 59.
Scheme 32: Bromoamidation of alkenes.
Scheme 33: Synthesis of brominated cyclic guanidines 61 and 61’.
Scheme 34: Intramolecular bromocyclisation of N-oxyureas.
Scheme 35: The formation of 3-bromoindoles.
Scheme 36: Bromolactonisation of unsaturated acids 68.
Scheme 37: Synthesis of 5-bromomethyl-2-oxazolines.
Scheme 38: Synthesis of brominated chiral morpholines.
Scheme 39: Bromoenolcyclisation of unsaturated dicarbonyl groups.
Scheme 40: Brominated oxazines and oxazolines with BBr3.
Scheme 41: Synthesis of 5-bromomethtyl-2-phenylthiazoline.
Scheme 42: Intramolecular iodoamination of unsaturated amines.
Scheme 43: Formation of 3-iodoindoles.
Scheme 44: Iodoetherification of 2,2-diphenyl-4-penten-1-carboxylic acid (47’) and 2,2-diphenyl-4-penten-1-ol (...
Scheme 45: Synthesis of 5-iodomethyl-2-oxazolines.
Scheme 46: Synthesis of chiral iodinated morpholines. aFrom the ʟ-form of the amino acid starting material. Th...
Scheme 47: Iodoenolcyclisation of unsaturated dicarbonyl compounds 74.
Scheme 48: Synthesis of 5-iodomethtyl-2-phenylthiazoline (87).
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
- macrocycles as photocatalysts in organic synthesis, involving both single electron transfer (SET) and energy transfer (ET) mechanistic approaches [84]. This review does not only focus on the metal-free porphyrin macrocycles, but it also covers the area of different porphyrinoid systems, such as heteroatom
Graphical Abstract
Figure 1: Chemical structures of the main tetrapyrrolic macrocycles studied in this review for their role as ...
Figure 2: Calix[4]pyrroles 3 and 4 and an their acyclic analogue 5 used for the transformation of Danishefsky...
Figure 3: Calixpyrrole-based organocatalysts 11 and 12 for the diastereoselective addition reaction of TMSOF ...
Figure 4: (a) Chemical structures of macrocyclic organocatalysts used for the synthesis of cyclic carbonates ...
Figure 5: Cuprous chloride-catalyzed aziridination of styrene (22) by chloramine-T (23) providing 1-tosyl-2-p...
Figure 6: Chemical structures of the various porphyrin macrocycles (18, 25–41) screened as potential catalyst...
Figure 7: Organocatalytic activity of distorted porphyrins explored by Senge and co-workers. Planar macrocycl...
Figure 8: Chemical structures of H2EtxTPP (x = 0, 2, 4, 6, 8) compounds with incrementally increasing nonplan...
Figure 9: Chemical structures of OxP macrocycles tested as potential organocatalysts for the conjugate additi...
Figure 10: a) Fundamental structure of the J-aggregates of diprotonated TPPS3 53 and b) its use as a catalyst ...
Figure 11: Chemical structures of amphiphilic porphyrin macrocycles used as pH-switchable catalysts based on i...
Figure 12: a) Chemical structures of porphyrin macrocycles for the cycloaddition of CO2 to N-alkyl/arylaziridi...
Figure 13: Electron and energy-transfer processes typical for excited porphyrin molecules (Por = porphyrin mac...
Figure 14: Proposed mechanism for the light-induced α-alkylation of aldehydes with EDA in the presence of H2TP...
Figure 15: a) Chemical structures of porphyrins screened as photoredox catalysts, b) model reaction of furan (...
Figure 16: Porphyrin macrocycles H2TPP (18) and PPIX 78 as photoreductants for the red light-induced C–H aryla...
Figure 17: Porphyrin macrocycles H2TPP (18) and PPIX 78 as photoredox catalyst for (a) α-alkylation of an alde...
Figure 18: Corrole macrocycles 98–100 as photoredox catalysts for C–H arylation and borylation reactions. Adap...
Figure 19: Proposed catalytic cycle of electrocatalytic generation of H2 evolution using tetrapyrrolic macrocy...
Figure 20: a) Chemical structures of tetrapyrrolic macrocycles 109, 73, and 110 used for oxygen reductions in ...
Figure 21: a) Absorption spectra (left) of the air-saturated DCE solutions containing: 5 × 10−5 M H2TPP (black...
Figure 22: Chemical structures of N,N’-dimethylated saddle-distorted porphyrin isomers, syn-Me2P 111 and anti-...
Figure 23: Reaction mechanisms for the two-electron reduction of O2 by a) syn-Me2Iph 113 and b) anti-Me2Iph 114...
Figure 24: O2/H2O2 interconversion using methylated saddle-distorted porphyrin and isophlorin (reduced porphyr...
Figure 25: Chemical structures of distorted dodecaphenylporphyrin macrocycle 117 and its diprotonated form 118...
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
- Andrew Greener Stephen P. Argent Coby J. Clarke Miriam L. O'Duill School of Chemistry, University of Nottingham, University Park, Nottingham NG7 2RD, UK 10.3762/bjoc.20.245 Abstract Hypervalent iodine(III) reagents have become indispensable tools in organic synthesis, but gaps remain in the
- the rational design and synthesis of novel, unstabilised hypervalent iodine(III) compounds and expand the application of these powerful reagents in organic synthesis. Results and Discussion Structural data Twelve phosphorus-iodonium ylids were synthesised (Figure 2). X-ray diffraction data (XRD) of
- will stimulate the design and synthesis of new hypervalent iodine compounds, expanding the functionalisation reactions currently available through these useful reagents in organic synthesis. Structure and stability of hypervalent iodine compounds. Phosphorus-iodonium ylids investigated in this study
Graphical Abstract
Figure 1: Structure and stability of hypervalent iodine compounds.
Figure 2: Phosphorus-iodonium ylids investigated in this study: Yields (for synthetic procedures, see Supporting Information File 1), stru...
Figure 3: (a) Selected TGA thermograms of phosphorus-iodonium ylids at 10 °C min−1 in N2 (full dataset in Supporting Information File 1). ...
Figure 4: (a) Proposed decomposition mechanism based on ex situ analysis (1H, 31P NMR, ESI-MS) following abor...
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
- or without the use of transition metals [44]. Thus, they address both the financial and environmental challenges associated with organic synthesis by acting as environmentally benign substitutes for costly organometallic catalysts and heavy-metal-based oxidants. Diaryl iodide salts consist of two
Graphical Abstract
Figure 1: Various structures of iodonium salts.
Scheme 1: Αrylation of α-fluoroacetoacetamides 5 to α-aryl-α-fluoroacetoacetamides 7 and α-fluoroacetamides 8...
Scheme 2: Proposed mechanism for the arylation of α-fluoroacetoacetamides 5 to α-aryl-α-fluoroacetoacetamides ...
Scheme 3: α-Arylation of α-nitro- and α-cyano derivatives of α-fluoroacetamides 9 employing unsymmetrical DAI...
Scheme 4: Synthesis of α,α-difluoroketones 13 by reacting α,α-difluoro-β-keto acid esters 11 with aryl(TMP)io...
Scheme 5: Coupling reaction of arynes generated by iodonium salts 6 and arynophiles 14 for the synthesis of t...
Scheme 6: Metal-free arylation of quinoxalines 17 and quinoxalinones 19 with DAISs 16.
Scheme 7: Transition-metal-free, C–C cross-coupling of 2-naphthols 21 to 1-arylnapthalen-2-ols 22 employing d...
Scheme 8: Arylation of vinyl pinacol boronates 23 to trans-arylvinylboronates 24 in presence of hypervalent i...
Scheme 9: Light-induced selective arylation at C2 of quinoline N-oxides 25 and pyridine N-oxides 28 in the pr...
Scheme 10: Plaussible mechanism for the light-induced selective arylation of N-heterobiaryls.
Scheme 11: Photoinduced arylation of heterocycles 31 with the help of diaryliodonium salts 16 activated throug...
Scheme 12: Arylation of MBH acetates 33 with DIPEA and DAIRs 16.
Scheme 13: Aryl sulfonylation of MBH acetates 33 with DABSO and diphenyliodonium triflates 16.
Scheme 14: Synthesis of oxindoles 37 from N-arylacrylamides 36 and diaryliodonium salts 26.
Scheme 15: Mechanically induced N-arylation of amines 38 using diaryliodonium salts 16.
Scheme 16: o-Fluorinated diaryliodonium salts 40-mediated diarylation of amines 38.
Scheme 17: Proposed mechanism for the diarylation of amines 38 using o-fluorinated diaryliodonium salts 40.
Scheme 18: Ring-opening difunctionalization of aliphatic cyclic amines 41.
Scheme 19: N-Arylation of amino acid esters 44 using hypervalent iodonium salts 45.
Scheme 20: Regioselective N-arylation of triazole derivatives 47 by hypervalent iodonium salts 48.
Scheme 21: Regioselective N-arylation of tetrazole derivatives 50 by hypervalent iodonium salt 51.
Scheme 22: Selective arylation at nitrogen and oxygen of pyridin-2-ones 53 by iodonium salts 16 depending on t...
Scheme 23: N-Arylation using oxygen-bridged acyclic diaryliodonium salt 56.
Scheme 24: The successive C(sp2)–C(sp2)/O–C(sp2) bond formation of naphthols 58.
Scheme 25: Synthesis of diarylethers 62 via in situ generation of hypervalent iodine salts.
Scheme 26: O-Arylated galactosides 64 by reacting protected galactosides 63 with hypervalent iodine salts 16 i...
Scheme 27: Esterification of naproxen methyl ester 65 via formation and reaction of naproxen-containing diaryl...
Scheme 28: Etherification and esterification products 72 through gemfibrozil methyl ester-derived diaryliodoni...
Scheme 29: Synthesis of iodine containing meta-substituted biaryl ethers 74 by reacting phenols 61 and cyclic ...
Scheme 30: Plausible mechanism for the synthesis of meta-functionalized biaryl ethers 74.
Scheme 31: Intramolecular aryl migration of trifluoromethane sulfonate-substituted diaryliodonium salts 75.
Scheme 32: Synthesis of diaryl ethers 80 via site-selective aryl migration.
Scheme 33: Synthesis of O-arylated N-alkoxybenzamides 83 using aryl(trimethoxyphenyl)iodonium salts 82.
Scheme 34: Synthesis of aryl sulfides 85 from thiols 84 using diaryliodonium salts 16 in basic conditions.
Scheme 35: Base-promoted synthesis of diarylsulfoxides 87 via arylation of general sulfinates 86.
Scheme 36: Plausible mechanism for the arylation of sulfinates 86 via sulfenates A to give diaryl sulfoxides 87...
Scheme 37: S-Arylation reactions of aryl or heterocyclic thiols 88.
Scheme 38: Site-selective S-arylation reactions of cysteine thiol groups in 91 and 94 in the presence of diary...
Scheme 39: The selective S-arylation of sulfenamides 97 using diphenyliodonium salts 98.
Scheme 40: Plausible mechanism for the synthesis of sulfilimines 99.
Scheme 41: Synthesis of S-arylxanthates 102 by reacting DAIS 101 with potassium alkyl xanthates 100.
Figure 2: Structured of the 8-membered and 4-membered heterotetramer I and II.
Scheme 42: S-Arylation by diaryliodonium cations 103 using KSCN (104) as a sulfur source.
Scheme 43: S-Arylation of phosphorothioate diesters 107 through the utilization of diaryliodonium salts 108.
Scheme 44: Transfer of the aryl group from the hypervalent iodonium salt 108 to phosphorothioate diester 107.
Scheme 45: Synthesis of diarylselenides 118 via diarylation of selenocyanate 115.
Scheme 46: Light-promoted arylation of tertiary phosphines 119 to quaternary phosphonium salts 121 using diary...
Scheme 47: Arylation of aminophosphorus substrate 122 to synthesize phosphine oxides 123 using aryl(mesityl)io...
Scheme 48: Reaction of diphenyliodonium triflate (16) with DMSO (124) via thia-Sommelet–Hauser rearrangement.
Scheme 49: Synthesis of biaryl compounds 132 by reacting diaryliodonium salts 131 with arylhydroxylamines 130 ...
Scheme 50: Synthesis of substituted indazoles 134 and 135 from N-hydroxyindazoles 133.
C–H Trifluoromethylthiolation of aldehyde hydrazones
- Victor Levet,
- Balu Ramesh,
- Congyang Wang and
- Tatiana Besset
Beilstein J. Org. Chem. 2024, 20, 2883–2890, doi:10.3762/bjoc.20.242
- using the synthetic potential of hydrazones in organic synthesis. Experimental General procedure for the preparation of trifluoromethylthiolated products 2–6: An oven-dried 10 mL reaction tube equipped with a stirring bar was charged with the hydrazone derivative (0.3 mmol, 1.0 equiv) and CH3CN (0.7 mL
Graphical Abstract
Scheme 1: State of the art and this work.
Scheme 2: Reaction conditions: hydrazone (0.3 mmol, 1.0 equiv), NBS (0.33 mmol, 1.1 equiv), in CH3CN (0.4 M),...
Scheme 3: Scope of the reaction. Reaction conditions: 1 (0.3 mmol, 1.0 equiv), NBS (0.33 mmol, 1.1 equiv) in ...
Scheme 4: Mechanistic investigations and post-functionalization reactions. a19F NMR yields using α,α,α-triflu...
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
- primary organozinc reagents. Keywords: alkyl bromides; branched amines; Mannich reaction; multicomponent reaction; zinc; Introduction The multicomponent Mannich reaction is one of the most powerful tools available in organic synthesis for the straightforward generation of α-branched amines [1][2][3
Graphical Abstract
Scheme 1: Scope of organozinc reagents. Yield was determined by titration with I2. Reaction conditions: Zn du...
Scheme 2: Scope of the reaction. Yield of isolated product is given.
Mechanochemical difluoromethylations of ketones
- Jinbo Ke,
- Pit van Bonn and
- Carsten Bolm
Beilstein J. Org. Chem. 2024, 20, 2799–2805, doi:10.3762/bjoc.20.235
- ; mechanochemistry; Introduction In recent years, mechanochemical organic synthesis has been advanced significantly, prompting organic chemists to reconsider the necessity of solvents in their reactions [1][2][3][4][5][6][7][8][9][10][11]. Eliminating hazardous solvents substantially reduces the ecological
Graphical Abstract
Scheme 1: Overview over difluoromethyl enol ether syntheses from acyclic and cyclic 1,3-diones (A), acyclic k...
Scheme 2: Attempted difluoromethylation of 1a in solution. The reactions were performed on a 0.2 mmol scale. ...
Scheme 3: Scope of ketones. The yields were determined by 1H NMR spectroscopy using 1,2-dichloroethane as the...
Scheme 4: Proposed mechanism (A) and mechanistic investigations (B and C). The yields were determined by 1H N...
Copper-catalyzed yne-allylic substitutions: concept and recent developments
- Shuang Yang and
- Xinqiang Fang
Beilstein J. Org. Chem. 2024, 20, 2739–2775, doi:10.3762/bjoc.20.232
- transformed into a series of useful molecules, enabling them an important backbone in organic synthesis. Lin et al. [66] used sodium sulfinates as the nucleophiles to realize the asymmetric sulfonylation of yne-allylic esters. The reaction can be carried out under mild conditions with good to excellent regio
Graphical Abstract
Scheme 1: Copper-catalyzed allylic and yne-allylic substitution.
Scheme 2: Challenges in achieving highly selective yne-allylic substitution.
Scheme 3: Yne-allylic substitutions using indoles and pyroles.
Scheme 4: Yne-allylic substitutions using amines.
Scheme 5: Yne-allylic substitution using 1,3-dicarbonyls.
Scheme 6: Postulated mechanism via copper acetylide-bonded allylic cation.
Scheme 7: Amine-participated asymmetric yne-allylic substitution.
Scheme 8: Asymmetric decarboxylative yne-allylic substitution.
Scheme 9: Asymmetric yne-allylic alkoxylation and alkylation.
Scheme 10: Proposed mechanism for Cu(I) system.
Scheme 11: Asymmetric yne-allylic dialkylamination.
Scheme 12: Proposed mechanism of yne-allylic dialkylamination.
Scheme 13: Asymmetric yne-allylic sulfonylation.
Scheme 14: Proposed mechanism of yne-allylic sulfonylation.
Scheme 15: Aymmetric yne-allylic substitutions using indoles and indolizines.
Scheme 16: Double yne-allylic substitutions using pyrrole.
Scheme 17: Proposed mechanism of yne-allylic substitution using electron-rich arenes.
Scheme 18: Aymmetric yne-allylic monofluoroalkylations.
Scheme 19: Proposed mechanism.
Scheme 20: Aymmetric yne-allylic substitution of yne-allylic esters with anthrones.
Scheme 21: Aymmetric yne-allylic substitution of yne-allylic esters with coumarins.
Scheme 22: Aymmetric yne-allylic substitution of with coumarins by Lin.
Scheme 23: Proposed mechanism.
Scheme 24: Amination by alkynylcopper driven dearomatization and rearomatization.
Scheme 25: Arylation by alkynylcopper driven dearomatization and rearomatization.
Scheme 26: Remote substitution/cyclization/1,5-H shift process.
Scheme 27: Proposed mechanism.
Scheme 28: Arylation or amination by alkynylcopper driven dearomatization and rearomatization.
Scheme 29: Remote nucleophilic substitution of 5-ethynylthiophene esters.
Scheme 30: Proposed mechanism.
Scheme 31: [4 + 1] annulation of yne-allylic esters and cyclic 1,3-dicarbonyls.
Scheme 32: Asymmetric [4 + 1] annulation of yne-allylic esters.
Scheme 33: Proposed mechanism.
Scheme 34: Asymmetric [3 + 2] annulation of yne-allylic esters.
Scheme 35: Postulated annulation step.
Scheme 36: [4 + 1] Annulations of vinyl ethynylethylene carbonates and 1,3-dicarbonyls.
Scheme 37: Proposed mechanism.
Scheme 38: Formal [4 + 1] annulations with amines.
Scheme 39: Formal [4 + 2] annulations with hydrazines.
Scheme 40: Proposed mechanism.
Scheme 41: Dearomative annulation of 1-naphthols and yne-allylic esters.
Scheme 42: Dearomative annulation of phenols or 2-naphthols and yne-allylic esters.
Scheme 43: Postulated annulation mechanism.
Scheme 44: Dearomative annulation of phenols or 2-naphthols.
Scheme 45: Dearomative annulation of indoles.
Scheme 46: Postulated annulation step.
Scheme 47: Asymmetric [4 + 1] cyclization of yne-allylic esters with pyrazolones.
Scheme 48: Proposed mechanism.
Scheme 49: Construction of C–C axially chiral arylpyrroles.
Scheme 50: Construction of C–N axially chiral arylpyrroles.
Scheme 51: Construction of chiral arylpyrroles with 1,2-di-axial chirality.
Scheme 52: Proposed mechanism.
Scheme 53: CO2 shuttling in yne-allylic substitution.
Scheme 54: CO2 fixing in yne-allylic substitution.
Scheme 55: Proposed mechanism.
5th International Symposium on Synthesis and Catalysis (ISySyCat2023)
- Anthony J. Burke and
- Elisabete P. Carreiro
Beilstein J. Org. Chem. 2024, 20, 2704–2707, doi:10.3762/bjoc.20.227
- Coimbra, 3004-535 Coimbra, Portugal LAQV-REQUIMTE, Institute for Research and Advanced Training (IIFA), University of Évora, Rua Romão Ramalho, 59, 7000-671 Évora, Portugal 10.3762/bjoc.20.227 Organic synthesis and catalysis are two of the main stalwarts of the chemical sciences, and they have undergone
- extraordinary advances over the past 150 years. They are a crucial tool for the development of new molecules across a wide range of fields, including drug discovery, energy, materials science, and many more. The ability to design and create novel compounds through organic synthesis, aided by catalysis, is
- intramolecular aminocarbonylation using Mo(CO)6. Both catalytic approaches successfully produced the desired DBDAPs. As previously mentioned, organic synthesis is a crucial tool for preparing complex molecules of high value to industry. Frackenpohl et al. [13] designed and synthesized a new library of 2,3
Base-promoted cascade recyclization of allomaltol derivatives containing an amide fragment into substituted 3-(1-hydroxyethylidene)tetronic acids
- Andrey N. Komogortsev,
- Constantine V. Milyutin and
- Boris V. Lichitsky
Beilstein J. Org. Chem. 2024, 20, 2585–2591, doi:10.3762/bjoc.20.217
- -hydroxypyran-4-ones these products are widely used in organic synthesis [17][18][19][20][21][22][23]. Among the diverse chemical transformations of allomaltol derivatives the recyclizations of the pyranone ring are of great interest. As a rule, such reactions are realized under action of nitrogen-containing
Graphical Abstract
Scheme 1: Synthesis of tetronic acid derivatives.
Scheme 2: Synthesis of amide derivatives 3.
Scheme 3: Synthesis of target tetronic acids 4a. aReaction conditions: 3a (1 mmol), CDI (0.49 g, 3 mmol), DBU...
Figure 1: The X-ray crystal structure of compound 4a (CCDC 2352876).
Scheme 4: Proposed reaction mechanism for the formation of products 4.
Scheme 5: Synthesis of derivatization products 7 and 9.
Figure 2: The X-ray crystal structure of compound 7 (CCDC 2352878).
Transition-metal-free synthesis of arylboronates via thermal generation of aryl radicals from triarylbismuthines in air
- Yuki Yamamoto,
- Yuki Konakazawa,
- Kohsuke Fujiwara and
- Akiya Ogawa
Beilstein J. Org. Chem. 2024, 20, 2577–2584, doi:10.3762/bjoc.20.216
- are one of the fundamental aryl compounds in organic synthesis, especially in cross-coupling reactions [1][2][3][4][5][6][7][8][9], and their applications are widespread, including dye synthesis, pharmaceutical and agrochemical synthesis, and industrial manufacturing [10][11]. In recent years, a
- diborons can capture the in situ-generated carbon-centered radicals [28][29][30][31][32][33][34][35][36]. Among the aryl sources in organic synthesis, triarylbismuthines are shelf-stable and easy-to-handle reagents with appropriate reactivities in transition-metal-catalyzed reactions and radical reactions
Graphical Abstract
Scheme 1: (a) Conventional methods for the generation of Ar• from Ar3Bi, (b) our previous studies, and (c) th...
Scheme 2: Scope for transition-metal-free synthesis of arylboronates 3 using triaylbismuthines 1 and diboron 2...
Scheme 3: Control experiment of the metal-free borylation under an argon atmosphere.
Figure 1: Comparison of the crude mixture of the reactions under (a) argon atmosphere or (b) open-air.
Scheme 4: Radical-trapping experiments using TEMPO as a radical scavenger.
Scheme 5: A proposed reaction pathway for the synthesis of arylboronates.
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
- the active Ru(II) species, completing the catalytic cycle (Scheme 38). This approach underlines the potential of ruthenium catalysis in achieving site-selective functionalization of complex molecules, thereby expanding the toolkit available for organic synthesis and drug development. 1.3.5 Rh-assisted
- applications of electrochemical methods in organic synthesis. In this context the Meggers group developed an asymmetric Rh catalyst-promoted alkylation [56]. The Rh complex was used as a chiral catalyst and Cp2Fe as an anodic oxidation catalyst to achieve the enantioselective C(sp3)–H alkenylation of 2
- arenes via palladium-catalyzed electrooxidation, further showcasing the versatility and potential of this approach in organic synthesis (Scheme 42b) [58]. These methodologies underline the expanding role of palladium catalysis in electrochemical transformations, offering robust strategies for the
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.
Visible-light-mediated flow protocol for Achmatowicz rearrangement
- Joachyutharayalu Oja,
- Sanjeev Kumar and
- Srihari Pabbaraja
Beilstein J. Org. Chem. 2024, 20, 2493–2499, doi:10.3762/bjoc.20.213
- Joachyutharayalu Oja Sanjeev Kumar Srihari Pabbaraja Department of Organic Synthesis & Process Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad-500007, India Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India 10.3762/bjoc.20.213 Abstract The batch
Graphical Abstract
Scheme 1: Strategies for Achmatowicz rearrangement.
Figure 1: Scope of the integrated continuous photo-flow (visible light)-induced Achmatowicz rearrangement rea...
Figure 2: Proposed mechanism for the photochemically induced Achmatowicz rearrangement.
Asymmetric organocatalytic synthesis of chiral homoallylic amines
- Nikolay S. Kondratyev and
- Andrei V. Malkov
Beilstein J. Org. Chem. 2024, 20, 2349–2377, doi:10.3762/bjoc.20.201
- process and the rich toolkit of advanced organic synthesis [5]. Homoallylic amines occupy a significant niche in alkaloid synthesis as they frequently appear as key intermediates in syntheses of the various nitrogen-containing natural products [6][7][8][9][10][11][12][13][14]. Additionally, they can be
Graphical Abstract
Scheme 1: The position of homoallylic amines in the landscape of alkaloid and nitrogen compounds syntheses.
Scheme 2: 3,3’-Diaryl-BINOL-catalysed asymmetric organocatalytic allylation of acylimines [24].
Scheme 3: Aminophenol-catalysed reaction between N-phosphinoylimines and pinacol allylboronic ester. Imine sc...
Scheme 4: Asymmetric geranylation and prenylation of indoles catalysed by (R)- or (S)-3,3’-dibromo-BINOL [25]. aA...
Scheme 5: (R)-3,3’-Di(3,5-di(trifluoromethyl)phenyl-BINOL-catalysed asymmetric geranylation and prenylation o...
Scheme 6: Microwave-induced one-pot asymmetric allylation of in situ-formed arylimines, catalysed by (R)-3,3’...
Scheme 7: Microwave-induced one-pot asymmetric allylation of in situ-formed arylimines, catalysed by (R)-3,3’...
Scheme 8: Kinetic resolution of chiral secondary allylboronates [15,30].
Scheme 9: (E)-Stereospecific asymmetric α-trifluoromethylallylation of cyclic imines and hydrazones [31].
Scheme 10: Hosomi–Sakurai-type allylation of in situ-formed N-Fmoc aldimines [32].
Figure 1: Two different pathways for the Hosomi–Sakurai reaction of allyltrimethylsilane with N-Fmoc aldimine...
Scheme 11: Chiral squaramide-catalysed hydrogen bond-assisted chloride abstraction–allylation of N-carbamoyl α...
Figure 2: The pyrrolidine unit gem-methyl group conformational control in the squaramide-based catalyst [34].
Figure 3: The energetic difference between the transition states of the two proposed modes of the reaction (SN...
Scheme 12: One-pot preparation procedure for oxazaborolidinium ion (COBI) 63 [37].
Scheme 13: Chiral oxazaborolidinium ion (COBI)-catalysed allylation of N-(2-hydroxy)phenylimines with allyltri...
Scheme 14: The two-step N-(2-hydroxy)phenyl group deprotection procedure [37].
Scheme 15: Low-temperature (−40 °C) NMR experiments evidencing the reversible formation of the active COBI–imi...
Figure 4: Two computed reaction pathways for the COBI-catalysed Strecker reaction (TS1 identical to allylatio...
Scheme 16: Highly chemoselective and stereospecific synthesis of γ- and γ,δ-substituted homoallylic amines by ...
Scheme 17: Catalytic cycle for the three-component allylation with HBD/πAr–Ar catalyst [39].
Scheme 18: Reactivity of model electrophiles [39].
Scheme 19: HBD/πAr–Ar catalyst rational design and optimisation [39].
Scheme 20: Scope of the three-component HBD/πAr–Ar-catalysed reaction [39].
Scheme 21: Limitations of the HBD/πAr–Ar-catalysed reaction [39].
Scheme 22: Asymmetric chloride-directed dearomative allylation of in situ-generated N-acylquinolinium ions, ca...
Scheme 23: Chiral phosphoric acid-catalysed aza-Cope rearrangement of in situ-formed N-α,α’-diphenyl-(α’’-ally...
Scheme 24: Tandem (R)-VANOL-triborate-catalysed asymmetric aza-Cope rearrangement of in situ-formed aldimines ...
Scheme 25: (S)-TRIP-catalysed enantioconvergent aza-Cope rearrangement of β-formyl amides, substrate scope [43]. a...
Scheme 26: (S)-TRIP-catalysed enantioconvergent aza-Cope rearrangement of β-formyl amides 16–19, amide and all...
Scheme 27: Synthetic applications of homoallylic N-benzophenone imine products 131 [43].
Scheme 28: Chiral organocatalysed addition of 2,2,2-trifluoroethyl ketimines to isatin-derived Morita–Baylis–H...
Scheme 29: Chiral chinchona-derived amine-catalysed reaction between isatin-based Morita–Baylis–Hilman carbona...
Scheme 30: (R)-VAPOL-catalysed hydrogen atom transfer deracemisation [45].
Scheme 31: Chiral PA-catalysed [1,3]-rearrangement of ene-aldimines [46].
gem-Difluorination of carbon–carbon triple bonds using Brønsted acid/Bu4NBF4 or electrogenerated acid
- Mizuki Yamaguchi,
- Hiroki Shimao,
- Kengo Hamasaki,
- Keiji Nishiwaki,
- Shigenori Kashimura and
- Kouichi Matsumoto
Beilstein J. Org. Chem. 2024, 20, 2261–2269, doi:10.3762/bjoc.20.194
- solution of Bu4NBF4/CH2Cl2 containing substrates might also promote the same reactions (Figure 1, reaction 6, electrochemical method). Currently, electrochemistry can be regarded as a promising technique in organic synthesis, because heavy-metal reagents can be avoided for the oxidation or reduction of
Graphical Abstract
Figure 1: gem-Difluorination of carbon–carbon triple bonds. Selected examples from (1) to (5), and this work ...
Scheme 1: gem-Difluorination promoted by electrogenerated acids (method B).
Scheme 2: Generation and accumulation of EGA followed by the reaction with 1a for 2a.
Scheme 3: Plausible reaction mechanism.
