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Search for "ring opening" in Full Text gives 554 result(s) in Beilstein Journal of Organic Chemistry. Showing first 200.
Photoswitches beyond azobenzene: a beginner’s guide
- Michela Marcon,
- Christoph Haag and
- Burkhard König
Beilstein J. Org. Chem. 2025, 21, 1808–1853, doi:10.3762/bjoc.21.143
- to a low activation energy barrier for the ground-state ring-opening [127]. Heterocycles with lower aromatic stabilisation energies are less susceptible to thermal ring-opening (Figure 21). The substituent nature of the aromatic groups was also demonstrated to influence the thermal stability
Graphical Abstract
Figure 1: Energy diagram of a two-state photoswitch. Figure 1 was redrawn from [2].
Figure 2: Example of the absorption spectra of the isomers of a photoswitch with most efficient irradiation w...
Scheme 1: Photoswitch classes described in this review.
Figure 3: Azoheteroarenes.
Scheme 2: E–Z Isomerisation (top) and mechanisms of thermal Z–E isomerisation (bottom).
Scheme 3: Rotation mechanism favoured by the electron displacement in push–pull systems. Selected examples of...
Figure 4: A) T-shaped and twisted Z-isomers determine the thermal stability and the Z–E-PSS (selected example...
Figure 5: Effect of di-ortho-substitution on thermal half-life and PSS.
Figure 6: Selected thermal lifetimes of azoindoles in different solvents and concentrations. aConcentration o...
Figure 7: Aryliminopyrazoles: N-pyrazoles (top) and N-phenyl (bottom).
Scheme 4: Synthesis of symmetrical heteroarenes through oxidation (A), reduction (B), and the Bayer–Mills rea...
Scheme 5: Synthesis of diazonium salt (A); different strategies of azo-coupling: with a nucleophilic ring (B)...
Scheme 6: Synthesis of arylazothiazoles 25 (A) and heteroaryltriazoles 28 (B).
Scheme 7: Synthesis of heteroarylimines 31a,b [36-38].
Figure 8: Push–pull non-ionic azo dye developed by Velasco and co-workers [45].
Scheme 8: Azopyridine reported by Herges and co-workers [46].
Scheme 9: Photoinduced phase transitioning azobispyrazoles [47].
Figure 9: Diazocines.
Scheme 10: Isomers, conformers and enantiomers of diazocine.
Scheme 11: Partial overlap of the ππ* band with electron-donating substituents and effect on the PSS. Scheme 11 was ada...
Figure 10: Main properties of diazocines with different bridges. aMeasured in n-hexane [56]. bMeasured in THF. cMe...
Scheme 12: Synthesis of symmetric diazocines.
Scheme 13: Synthesis of asymmetric diazocines.
Scheme 14: Synthesis of O- and S-heterodiazocines.
Scheme 15: Synthesis of N-heterodiazocines.
Scheme 16: Puromycin diazocine photoswitch [60].
Figure 11: Indigoids.
Figure 12: The main representatives of the indigoid photoswitch class.
Scheme 17: Deactivation process that prevents Z-isomerisation of indigo.
Figure 13: Stable Z-indigo derivative synthesised by Wyman and Zenhäusern [67].
Figure 14: Selected examples of indigos with aliphatic and aromatic substituents [68]. Dashed box: proposed π–π in...
Scheme 18: Resonance structures of indigo and thioindigo involving the phenyl ring.
Scheme 19: Possible deactivation mechanism for 4,4'-dihydroxythioindigo [76].
Scheme 20: Effect of different heteroaryl rings on the stability and the photophysical properties of hemiindig...
Figure 15: Thermal half-lives of red-shifted hemithioindigos in toluene [79]. aMeasured in toluene-d8.
Scheme 21: Structures of pyrrole [81] and imidazole hemithioindigo [64].
Figure 16: Examples of fully substituted double bond hemithioindigo (left), oxidised hemithioindigos (centre),...
Scheme 22: Structure of iminothioindoxyl 72 (top) and acylated phenyliminoindolinone photoswitch 73 (bottom). ...
Scheme 23: (top) Transition states of iminothioindoxyl 72. The planar transition state is associated with a lo...
Scheme 24: Baeyer–Drewsen synthesis of indigo (top) and N-functionalisation strategies (bottom).
Scheme 25: Synthesis of hemiindigo.
Scheme 26: Synthesis of hemithioindigo and iminothioindoxyl.
Scheme 27: Synthesis of double-bond-substituted hemithioindigos.
Scheme 28: Synthesis of phenyliminoindolinone.
Scheme 29: Hemithioindigo molecular motor [85].
Figure 17: Arylhydrazones.
Scheme 30: Switching of arylhydrazones. Note: The definitions of stator and rotor are arbitrary.
Scheme 31: Photo- and acidochromism of pyridine-based phenylhydrazones.
Scheme 32: A) E–Z thermal inversion of a thermally stable push–pull hydrazone [109]. B) Rotation mechanism favoured...
Scheme 33: Effect of planarisation on the half-life.
Scheme 34: The longest thermally stable hydrazone switches reported so far (left). Modulation of thermal half-...
Figure 18: Dependency of t1/2 on concentration and hypothesised aggregation-induced isomerisation.
Figure 19: Structure–property relationship of acylhydrazones.
Scheme 35: Synthesis of arylhydrazones.
Scheme 36: Synthesis of acylhydrazones.
Scheme 37: Photoswitchable fluorophore by Aprahamian et al. [115].
Scheme 38: The four-state photoswitch synthesised by the Cigáň group [116].
Figure 20: Diarylethenes.
Scheme 39: Isomerisation and oxidation pathway of E-stilbene to phenanthrene.
Scheme 40: Strategies adapted to avoid E–Z isomerisation and oxidation.
Scheme 41: Molecular orbitals and mechanism of electrocyclisation for a 6π system.
Figure 21: Aromatic stabilisation energy correlated with the thermal stability of the diarylethenes [127,129].
Figure 22: Half-lives of diarylethenes with increasing electron-withdrawing groups [128,129].
Scheme 42: Photochemical degradation pathway promoted by electron-donating groups [130].
Figure 23: The diarylethenes studied by Hanazawa et al. [134]. Increased rigidity leads to bathochromic shift.
Scheme 43: The dithienylethene synthesised by Nakatani's group [135].
Scheme 44: Synthesis of perfluoroalkylated diarylethenes.
Scheme 45: Synthesis of 139 and 142 via McMurry coupling.
Scheme 46: Synthesis of symmetrical derivatives 145 via Suzuki–Miyaura coupling.
Scheme 47: Synthesis of acyclic 148, malonic anhydride 149, and maleimide derivatives 154.
Figure 24: Gramicidin S (top left) and two of the modified diarylethene derivatives: first generation (bottom ...
Scheme 48: Pyridoxal 5'-phosphate and its reaction with an amino acid (top). The analogous dithienylethene der...
Figure 25: Fulgides.
Scheme 49: The three isomers of fulgides.
Scheme 50: Thermal and photochemical side products of unsubstituted fulgide [150].
Figure 26: Maximum absorption λc of the closed isomer compared with the nature of the aromatic ring and the su...
Scheme 51: Possible rearrangement of the excited state of 5-dimethylaminoindolylfulgide [153].
Figure 27: Quantum yields of ring closure (ΦE→C) and E–Z isomerisation (ΦE→Z) correlated with the increasing s...
Scheme 52: Active (Eα) and inactive (Eβ) conformers (left) and the bicyclic sterically blocked fulgide 169 (ri...
Scheme 53: Quantum yield of ring-opening (ΦC→E) and E–Z isomerisation (ΦE→Z) for different substitution patter...
Scheme 54: Stobbe condensation pathway for the synthesis of fulgides 179, fulgimides 181 and fulgenates 178.
Scheme 55: Alternative synthesis of fulgides through Pd-catalysed carbonylation.
Scheme 56: Optimised synthesis of fulgimides [166].
Scheme 57: Photoswitchable FRET with a fulgimide photoswitch [167].
Scheme 58: Three-state fulgimide strategy by Slanina's group.
Figure 28: Spiropyrans.
Scheme 59: Photochemical (left) and thermal (right) ring-opening mechanisms for an exemplary spiropyran with a...
Figure 29: Eight possible isomers of the open merocyanine according to the E/Z configurations of the bonds hig...
Scheme 60: pH-Controlled photoisomerisation between the closed spiropyran 191-SP and the open E-merocyanine 19...
Scheme 61: Behaviour of spiropyran in water buffer according to Andréasson and co-workers [180]. 192-SP in an aqueo...
Scheme 62: (left box) Proposed mechanism of basic hydrolysis of MC [184]. (right box) Introduction of electron-dona...
Scheme 63: Photochemical interconversion of naphthopyran 194 (top) and spirooxazine 195 (bottom) photoswitches...
Scheme 64: Synthesis of spiropyrans and spirooxazines 198 and the dicondensation by-product 199.
Scheme 65: Alternative synthesis of spiropyrans and spirooxazines with indolenylium salt 200.
Scheme 66: Synthesis of 4’-substituted spiropyrans 203 by condensation of an acylated methylene indoline 201 w...
Scheme 67: Synthesis of spironaphthopyrans 210 by acid-catalysed condensation of naphthols and diarylpropargyl...
Scheme 68: Photoswitchable surface wettability [194].
Figure 30: Some guiding principles for the choice of the most suitable photoswitch. Note that this guide is ve...
Catalytic asymmetric reactions of isocyanides for constructing non-central chirality
- Jia-Yu Liao
Beilstein J. Org. Chem. 2025, 21, 1648–1660, doi:10.3762/bjoc.21.129
- lactones with carbon nucleophiles. The success lies in the tandem enantioselective ring-opening of lactones with α-acidic isocyanides, followed by a rapid cyclization driven by aromatization, overcoming the long-standing stereochemical leakage problem caused by the undesired lactol formation [45
- ]. Encouraged by the above results, we turned our attention to biaryl lactams [49]. However, in this case, the inherent resonance stability of the amide bond makes the ring-opening process rather challenging. To solve this problem, we envisioned that a cooperative catalytic system merging silver catalysis and
Graphical Abstract
Figure 1: a) Common types of chirality. b) Representative functional molecules bearing non-central chirality.
Scheme 1: Construction of planar chirality.
Scheme 2: Construction of axial chirality.
Scheme 3: Construction of inherent chirality.
Scheme 4: Construction of helical chirality.
Scheme 5: CPA-catalyzed enantioselective Groebke–Blackburn–Bienaymé reaction.
Scheme 6: Construction of axially chiral 3-arylpyrroles via de novo pyrrole formation.
Scheme 7: Synthesis of atropoisomeric 3-arylpyrroles via central-to-axial chirality transfer.
Scheme 8: Dynamic kinetic resolution of bridged biaryls with α-acidic isocyanides.
Scheme 9: Desymmetrization of prochiral compounds with α-acidic isocyanides.
3-Aryl-2H-azirines as annulation reagents in the Ni(II)-catalyzed synthesis of 1H-benzo[4,5]thieno[3,2-b]pyrroles
- Julia I. Pavlenko,
- Pavel A. Sakharov,
- Anastasiya V. Agafonova,
- Derenik A. Isadzhanyan,
- Alexander F. Khlebnikov and
- Mikhail S. Novikov
Beilstein J. Org. Chem. 2025, 21, 1595–1602, doi:10.3762/bjoc.21.123
- method for the synthesis of 3-arylbenzo[4,5]thieno[3,2-b]pyrroles has been developed via pyrrole ring annulation to the aromatic benzo[b]thiophene system, using 3-arylazirines as a N‒C=C synthon. The reaction is catalyzed by Ni(hfacac)2 and proceeds through the azirine ring opening across the N=C3 bond
- to the azirine C=N bond, followed by cyclization and the aziridine ring opening into the [3 + 2] cycloaddition product 5 (Scheme 3). It is noteworthy that the annulation proceeds via the azirine N‒C3 bond cleavage. Elimination of the methoxycarbonyl group most likely occurs under the action of
- proceeds through azirine ring opening across the N–C3 bond. Azirines with both electron-donating and electron-withdrawing C3-aryl substituents tolerate the reaction conditions, and give the annulation products in high yields. The synthesized 3-aryl-1H-benzo[4,5]thieno[3,2-b]pyrroles can be effectively
Graphical Abstract
Scheme 1: Synthesis of fused pyrroles and azoles by [3 + 2] annulation reactions of azirines.
Scheme 2: Synthesis of benzo[4,5]thieno[3,2-b]pyrroles 3.
Scheme 3: Plausible mechanism for the formation of compounds 3.
Scheme 4: Post-modifications of 1H-benzo[4,5]thieno[3,2-b]pyrrole (3b).
Scheme 5: Synthesis of pyrrolo[3,2-b]indole 10.
Scheme 6: IPrCuCl-catalyzed reactions of indoles 9b,c with azirine 2a.
Scheme 7: Ni(II)- and Cu(I)-catalyzed reactions of indole 15 with azirine 2a.
General method for the synthesis of enaminones via photocatalysis
- Paula Pérez-Ramos,
- Raquel G. Soengas and
- Humberto Rodríguez-Solla
Beilstein J. Org. Chem. 2025, 21, 1535–1543, doi:10.3762/bjoc.21.116
- function (Scheme 4B). Furthermore, when the reaction of chromone 10 was carried out under standard conditions, the starting material was recovered unaltered, evidencing that the photocatalyzed dehalogenation step is crucial to enable the ring opening (Scheme 4C). In order to determine the role of Ni(II) in
Graphical Abstract
Figure 1: Examples of compounds with medicinal effects containing an enaminone structural moiety.
Scheme 1: Synthesis of enaminones.
Scheme 2: Substrate scope.
Scheme 3: Scale-up synthesis of enaminone 9a.
Scheme 4: Mechanistic studies.
Scheme 5: Proposed mechanism.
Ambident reactivity of enolizable 5-mercapto-1H-tetrazoles in trapping reactions with in situ-generated thiocarbonyl S-methanides derived from sterically crowded cycloaliphatic thioketones
- Grzegorz Mlostoń,
- Małgorzata Celeda,
- Marcin Palusiak,
- Heinz Heimgartner,
- Marta Denel-Bobrowska and
- Agnieszka B. Olejniczak
Beilstein J. Org. Chem. 2025, 21, 1508–1519, doi:10.3762/bjoc.21.113
- heterocycles like saccharin and phthalimide, reacted with 1a and 1b yielding the corresponding N–H insertion products [13][14] (Scheme 1, lower part). In a recent publication, ring opening reactions of so-called D–A cyclopropanes (dimethyl 2-arylcyclopropane-1,1-dicarboxylates 3), initiated by a nucleophilic
Graphical Abstract
Scheme 1: Typical [3 + 2] cycloaddition (above) and trapping (below) reactions of thiocarbonyl S-methanides 1a...
Scheme 2: Ambident reactivity of 5-mercapto-1H-tetrazoles 4 towards dimethyl 2-arylcyclopropane dicarboxylate...
Scheme 3: Regioselectivity of [3 + 2] cycloadditions of diazomethane with adamantanethione (7a) [22,24,25], and sterica...
Scheme 4: The in situ generation of sterically crowded thiocarbonyl S-methanides 1c,d (via a 1,3-dipolar cycl...
Scheme 5: Reactions of the in situ-generated thiocarbonyl S-methanides 1 (from 1,3,4-thiadiazolines 2) with e...
Figure 1: (a) Molecular structure of the N-insertion product (thioaminal) 9i. Atoms are represented by therma...
Scheme 6: Stepwise mechanism of the competitive N- and S-insertion reactions between the in situ-generated th...
Scheme 7: Mechanism of the isomerization of initially formed thioaminals 9 to dithioacetals 10.
Microwave-enhanced additive-free C–H amination of benzoxazoles catalysed by supported copper
- Andrei Paraschiv,
- Valentina Maruzzo,
- Filippo Pettazzi,
- Stefano Magliocco,
- Paolo Inaudi,
- Daria Brambilla,
- Gloria Berlier,
- Giancarlo Cravotto and
- Katia Martina
Beilstein J. Org. Chem. 2025, 21, 1462–1476, doi:10.3762/bjoc.21.108
- determine the percentage composition of starting material and products 2a, 2a-o and 2a-o-hydrol. The reaction was perfectly reproducible and no other derivatives were observed. As shown in Figure 1b, when the reaction was conducted without a catalyst, only ring opening was observed, accounting for 47%. By
Graphical Abstract
Scheme 1: Representative synthetic routes for the C–H amination of benzoxazole using supported copper catalys...
Figure 1: Reaction of benzimidazole with piperidine. a) Reaction scheme including intermaidates and b) conver...
Figure 2: Reaction rate comparison between conventional (oil bath) and MW heating. Reaction conditions: benzo...
Scheme 2: Graphical representation of Si-MonoAm-Cu(I) and Si-DiAm-Cu(I) preparation.
Figure 3: TGA profiles of SIPERNAT silica and Si-MonoAm and Si-DiAm.
Scheme 3: Scope of the MW-promoted C2-amination of benzoxazole catalysed by Si-MonoAm-Cu(I). Reaction conditi...
Scheme 4: C2-Amination of substituted benzoxazoles. Reaction conditions: benzoxazole (1.0 mmol), piperidine (...
Figure 4: Hot filtration test for the Si-MonoAm-Cu(I)-catalysed C2-amination of benzoxazole with piperidine i...
Figure 5: FTIR spectra of samples on the left 3800–2400 cm−1 wavenumber on the right 1750–1350 cm−1 wavenumbe...
Figure 6: Si-MonoAm-Cu(I) catalyst reuse.
Figure 7: FESEM images of sample a) Si-MonoAm-Cu(I) 5 wt % and c) Si-MonoAm-Cu(I) 5 wt % used.
Figure 8: EDS maps of a) Si-MonoAm-Cu(I) and b) Si-MonoAm-Cu(I) used.
Advances in nitrogen-containing helicenes: synthesis, chiroptical properties, and optoelectronic applications
- Meng Qiu,
- Jing Du,
- Nai-Te Yao,
- Xin-Yue Wang and
- Han-Yuan Gong
Beilstein J. Org. Chem. 2025, 21, 1422–1453, doi:10.3762/bjoc.21.106
- thia-bridged triarylamine[4]helicene-functionalized polynorbornenes 63a–c via ring-opening metathesis polymerization (ROMP), introducing helicene chirality into polymer backbones with tunable electrochromic behavior [78]. These polymers exhibit reversible pH-responsive color changes. For instance, 63a
Oxetanes: formation, reactivity and total syntheses of natural products
- Peter Gabko,
- Martin Kalník and
- Maroš Bella
Beilstein J. Org. Chem. 2025, 21, 1324–1373, doi:10.3762/bjoc.21.101
- of ring-opening and ring-expansion reactions, and finally total syntheses of selected oxetane-containing natural products. The literature review primarily covers reports made after the year 2015, but a few older contributions that were considered relevant are also discussed. Keywords: medicinal
- -, particularly 2-methylideneoxetanes have become valuable intermediates in oxetane chemistry as they readily undergo a variety of chemical transformations, including ring-opening reactions with nucleophiles, epoxidations, cyclopropanations and [3 + 2] cycloadditions with nitrile oxides [51][52]. In addition
- traced back to 3-oxetanone. In 2018, Bull and co-workers disclosed the first lithium-catalysed thiol alkylation using electron-rich 3-aryloxetan-3-ols 142 (Scheme 35) [84]. This protocol is completely chemoselective as no ring-opening was observed and the resulting oxetane sulphides 143 were obtained in
Graphical Abstract
Figure 1: Bond lengths and bond angles in oxetane at 140 K [2].
Figure 2: Analogy of 3-substituted oxetanes to carbonyl and gem-dimethyl groups [12].
Figure 3: Use of oxetanes in drug design – selected examples.
Figure 4: Examples of oxetane-containing natural products.
Scheme 1: Synthetic strategies towards construction of the oxetane ring.
Scheme 2: Overview of intramolecular Williamson etherification and competing Grob fragmentation.
Scheme 3: Synthesis of spiro-oxetanes via 1,4-C–H insertion and Williamson etherification.
Scheme 4: Use of phenyl vinyl selenone in the synthesis of spirooxindole oxetanes.
Scheme 5: Synthesis of bicyclic 3,5-anhydrofuranoses via double epoxide opening/etherification.
Scheme 6: Preparation of spirooxetanes by cycloisomerisation via MHAT/RPC.
Scheme 7: Oxetane synthesis via alcohol C–H functionalisation.
Scheme 8: Access to oxetanes 38 from α-acetyloxy iodides.
Scheme 9: The kilogram-scale synthesis of oxetane intermediate 41.
Scheme 10: Overview of the intramolecular opening of 3-membered rings.
Scheme 11: Synthesis of 4,7-dioxatricyclo[3.2.1.03,6]octane skeletons.
Scheme 12: Silicon-directed electrophilic cyclisation of homoallylic alcohols.
Scheme 13: Hydrosilylation–iodocyclisation of homopropargylic alcohols.
Scheme 14: Cu-catalysed intramolecular O-vinylation of γ-bromohomoallylic alcohols.
Scheme 15: Cu-catalysed intramolecular cross-coupling of hydroxyvinylstannanes.
Scheme 16: Isomerisation of oxiranyl ethers containing weakly carbanion-stabilising groups.
Scheme 17: Cyclisation of diethyl haloalkoxymalonates.
Scheme 18: Synthesis of oxetanes through a 1,5-HAT/radical recombination sequence.
Scheme 19: General approach to oxetanes via [2 + 2] cycloadditions.
Scheme 20: Synthesis of tricyclic 4:4:4 oxetanes through a photochemical triple cascade reaction.
Scheme 21: Iridium-catalysed Paternò–Büchi reaction between α-ketoesters and simple alkenes.
Scheme 22: Three-step synthesis of spirocyclic oxetanes 83 via Paternò–Büchi reaction, nucleophilic ring openi...
Scheme 23: Enantioselective Paternò–Büchi reaction catalysed by a chiral iridium photocatalyst.
Scheme 24: Synthesis of polysubstituted oxetanes 92 via Cu(II)-mediated formal [2 + 2] cycloadditions.
Scheme 25: Synthesis of alkylideneoxetanes via NHC- and DBU-mediated formal [2 + 2] cycloadditions.
Scheme 26: Use of sulphur-stabilised carbanions in ring expansions.
Scheme 27: Synthesis of α,α-difluoro(arylthio)methyl oxetanes.
Scheme 28: Ring expansion in an industrial synthesis of PF-06878031.
Scheme 29: Ring contraction of triflated 2-hydroxy-γ-lactones.
Scheme 30: Ring contraction in an industrial synthesis of PF-06878031.
Scheme 31: Photochemical ring contraction of 2,5-dihydrofurans by aryldiazoacetic acid esters.
Scheme 32: Synthesis of 3-oxetanones via O-H insertion of carbenes.
Scheme 33: Synthesis of phosphonate oxetanones via gold-mediated alkyne oxidation/O–H insertion.
Scheme 34: Syntheses and common derivatisations of 3-oxetanone.
Scheme 35: SN1 substitution of 3-aryloxetan-3-ols by thiols and alcohols.
Scheme 36: Fe–Ni dual-catalytic olefin hydroarylation towards 3-alkyl-3-(hetero)aryloxetanes.
Scheme 37: Synthesis of 3-aryloxetan-3-carboxylic acids.
Scheme 38: Decarboxylative alkylation of 3-aryloxetan-3-carboxylic acids.
Scheme 39: Synthesis of 3-amino-3-aryloxetanes via photoredox/nickel cross-coupling catalysis.
Scheme 40: Intermolecular cross-selective [2 + 2] photocycloaddition towards spirooxetanes.
Scheme 41: Synthesis of 3-aryl-3-aminooxetanes via defluorosulphonylative coupling.
Scheme 42: Two-step synthesis of amide bioisosteres via benzotriazolyl Mannich adducts 170.
Scheme 43: Functionalisation of oxetanyl trichloroacetimidates 172.
Scheme 44: Synthesis of oxetane-amino esters 176.
Scheme 45: Tandem Friedel–Crafts alkylation/intramolecular ring opening of 3-aryloxetan-3-ols.
Scheme 46: Synthesis of polysubstituted furans and pyrroles.
Scheme 47: Synthesis of oxazolines and bisoxazolines.
Scheme 48: Tandem, one-pot syntheses of various polycyclic heterocycles.
Scheme 49: Synthesis of 1,2-dihydroquinolines via skeletal reorganisation of oxetanes.
Scheme 50: Synthesis of benzoindolines and 2,3-dihydrobenzofurans and their derivatisations.
Scheme 51: Synthesis of polysubstituted 1,4-dioxanes.
Scheme 52: Preparation of various lactones via ring opening of oxetane-carboxylic acids 219.
Scheme 53: Tsuji-Trost allylation/ring opening of 3-aminooxetanes.
Scheme 54: Arylative skeletal rearrangement of 3-vinyloxetan-3-ols to 2,5-dihydrofurans.
Scheme 55: Reductive opening of oxetanes using catalytic Mg–H species.
Scheme 56: Opening of oxetanes by silyl ketene acetals.
Scheme 57: Rhodium-catalysed hydroacylation of oxetanes.
Scheme 58: Generation of radicals from oxetanes mediated by a vitamin B12-derived cobalt catalyst.
Scheme 59: Reductive opening of oxetanes by B–Si frustrated Lewis pairs.
Scheme 60: Zirconocene-mediated reductive opening of oxetanes.
Scheme 61: Enantioselective syntheses of small and medium-size rings using chiral phosphoric acids.
Scheme 62: Asymmetric synthesis of 2,3-dihydrobenzo[b]oxepines catalysed by a chiral scandium complex.
Scheme 63: Enantioselective synthesis of 1,3-bromohydrins under a chiral squaramide catalysis.
Scheme 64: Enantioselective opening of 2-aryl-2-ethynyloxetanes by anilines.
Scheme 65: Ru-catalysed insertion of diazocarbonyls into oxetanes.
Scheme 66: Ring expansion of oxetanes by stabilised carbenes generated under blue light irradiation.
Scheme 67: Expansion of oxetanes via nickel-catalysed insertion of alkynyltrifluoroborates.
Scheme 68: Nickel-catalysed expansion of oxetanes into ε-caprolactones.
Scheme 69: Expansion of oxetanes via cobalt-catalysed carbonyl insertion.
Scheme 70: Gold-catalysed intramolecular 1,1-carboalkoxylation of oxetane-ynamides.
Scheme 71: Expansion of oxetanes by stabilised sulphoxonium ylides.
Scheme 72: Cu-catalysed ring expansion of 2-vinyloxetanes by diazoesters.
Scheme 73: Total synthesis of (+)-oxetin.
Scheme 74: Total synthesis of racemic oxetanocin A.
Scheme 75: Total synthesis of (−)-merrilactone A.
Scheme 76: Total synthesis of (+)-dictyoxetane.
Scheme 77: Total synthesis of ent-dichrocephone B.
Scheme 78: Total synthesis of (−)-mitrephorone A.
Scheme 79: Total synthesis of (−)-taxol.
Recent advances in oxidative radical difunctionalization of N-arylacrylamides enabled by carbon radical reagents
- Jiangfei Chen,
- Yi-Lin Qu,
- Ming Yuan,
- Xiang-Mei Wu,
- Heng-Pei Jiang,
- Ying Fu and
- Shengrong Guo
Beilstein J. Org. Chem. 2025, 21, 1207–1271, doi:10.3762/bjoc.21.98
Graphical Abstract
Scheme 1: DTBP-mediated oxidative alkylarylation of activated alkenes.
Scheme 2: Iron-catalyzed oxidative 1,2-alkylarylation.
Scheme 3: Possible mechanism for the iron-catalyzed oxidative 1,2-alkylation of activated alkenes.
Scheme 4: A metal-free strategy for synthesizing 3,3-disubstituted oxindoles.
Scheme 5: Iminoxyl radical-promoted cascade oxyalkylation/alkylarylation of alkenes.
Scheme 6: Proposed mechanism for the iminoxyl radical-promoted cascade oxyalkylation/alkylarylation of alkene...
Scheme 7: Bicyclization of 1,n-enynes with alkyl nitriles.
Scheme 8: Possible reaction mechanism for the bicyclization of 1,n-enynes with alkyl nitriles.
Scheme 9: Radical cyclization of N-arylacrylamides with isocyanides.
Scheme 10: Plausible mechanism for the radical cyclization of N-arylacrylamides with isocyanides.
Scheme 11: Electrochemical dehydrogenative cyclization of 1,3-dicarbonyl compounds.
Scheme 12: Plausible mechanism for the dehydrogenative cyclization of 1,3-dicarbonyl compounds.
Scheme 13: Photocatalyzed cyclization of N-arylacrylamide and N,N-dimethylaniline.
Scheme 14: Proposed mechanism for the photocatalyzed cyclization of N-arylacrylamides and N,N-dimethylanilines....
Scheme 15: Electrochemical monofluoroalkylation cyclization of N-arylacrylamides with dimethyl 2-fluoromalonat...
Scheme 16: Proposed mechanism for the electrochemical radical cyclization of N-arylacrylamides with dimethyl 2...
Scheme 17: Photoelectrocatalytic carbocyclization of unactivated alkenes using simple malonates.
Scheme 18: Plausible mechanism for the photoelectrocatalytic carbocyclization of unactivated alkenes with simp...
Scheme 19: Bromide-catalyzed electrochemical trifluoromethylation/cyclization of N-arylacrylamides.
Scheme 20: Proposed mechanism for the electrochemical trifluoromethylation/cyclization of N-arylacrylamides.
Scheme 21: Visible light-mediated trifluoromethylarylation of N-arylacrylamides.
Scheme 22: Plausible reaction mechanism for the visible light-mediated trifluoromethylarylation of N-arylacryl...
Scheme 23: Electrochemical difluoroethylation cyclization of N-arylacrylamides with sodium difluoroethylsulfin...
Scheme 24: Electrochemical difluoroethylation cyclization of N-methyacryloyl-N-alkylbenzamides with sodium dif...
Scheme 25: Photoredox-catalyzed radical aryldifluoromethylation of N-arylacrylamides with S-(difluoromethyl)su...
Scheme 26: Proposed mechanism for the photoredox-catalyzed radical aryldifluoromethylation of N-arylacrylamide...
Scheme 27: Visible-light-induced domino difluoroalkylation/cyclization of N-cyanamide alkenes.
Scheme 28: Proposed mechanism of photoredox-catalyzed radical domino difluoroalkylation/cyclization of N-cyana...
Scheme 29: Palladium-catalyzed oxidative difunctionalization of alkenes.
Scheme 30: Two possible mechanisms of palladium-catalyzed oxidative difunctionalization.
Scheme 31: Silver-catalyzed oxidative 1,2-alkyletherification of unactivated alkenes with α-bromoalkylcarbonyl...
Scheme 32: Photochemical radical cascade cyclization of dienes.
Scheme 33: Proposed mechanism for the photochemical radical cascade 6-endo cyclization of dienes with α-carbon...
Scheme 34: Photocatalyzed radical coupling/cyclization of N-arylacrylamides and.
Scheme 35: Photocatalyzed radical-type couplings/cyclization of N-arylacrylamides with sulfoxonium ylides.
Scheme 36: Possible mechanism of visible-light-induced radical-type couplings/cyclization of N-arylacrylamides...
Scheme 37: Visible-light-promoted difluoroalkylated oxindoles systhesis via EDA complexes.
Scheme 38: Possible mechanism for the visible-light-promoted radical cyclization of N-arylacrylamides with bro...
Scheme 39: A dicumyl peroxide-initiated radical cascade reaction of N-arylacrylamide with DCM.
Scheme 40: Possible mechanism of radical cyclization of N-arylacrylamides with DCM.
Scheme 41: An AIBN-mediated radical cascade reaction of N-arylacrylamides with perfluoroalkyl iodides.
Scheme 42: Possible mechanism for the reaction with perfluoroalkyl iodides.
Scheme 43: Photoinduced palladium-catalyzed radical annulation of N-arylacrylamides with alkyl halides.
Scheme 44: Radical alkylation/cyclization of N-Alkyl-N-methacryloylbenzamides with alkyl halides.
Scheme 45: Possible mechanism for the alkylation/cyclization with unactivated alkyl chlorides.
Scheme 46: Visible-light-driven palladium-catalyzed radical cascade cyclization of N-arylacrylamides with unac...
Scheme 47: NHC-catalyzed radical cascade cyclization of N-arylacrylamides with alkyl bromides.
Scheme 48: Possible mechanism of NHC-catalyzed radical cascade cyclization.
Scheme 49: Electrochemically mediated radical cyclization reaction of N-arylacrylamides with freon-type methan...
Scheme 50: Proposed mechanistic pathway of electrochemically induced radical cyclization reaction.
Scheme 51: Redox-neutral photoinduced radical cascade cylization of N-arylacrylamides with unactivated alkyl c...
Scheme 52: Proposed mechanistic hypothesis of redox-neutral radical cascade cyclization.
Scheme 53: Thiol-mediated photochemical radical cascade cylization of N-arylacrylamides with aryl halides.
Scheme 54: Proposed possible mechanism of thiol-mediated photochemical radical cascade cyclization.
Scheme 55: Visible-light-induced radical cascade bromocyclization of N-arylacrylamides with NBS.
Scheme 56: Possible mechanism of visible-light-induced radical cascade cyclization.
Scheme 57: Decarboxylation/radical C–H functionalization by visible-light photoredox catalysis.
Scheme 58: Plausible mechanism of visible-light photoredox-catalyzed radical cascade cyclization.
Scheme 59: Visible-light-promoted tandem radical cyclization of N-arylacrylamides with N-(acyloxy)phthalimides....
Scheme 60: Plausible mechanism for the tandem radical cyclization reaction.
Scheme 61: Visible-light-induced aerobic radical cascade alkylation/cyclization of N-arylacrylamides with alde...
Scheme 62: Plausible mechanism for the aerobic radical alkylarylation of electron-deficient amides.
Scheme 63: Oxidative decarbonylative [3 + 2]/[5 + 2] annulation of N-arylacrylamide with vinyl acids.
Scheme 64: Plausible mechanism for the decarboxylative (3 + 2)/(5 + 2) annulation between N-arylacrylamides an...
Scheme 65: Rhenium-catalyzed alkylarylation of alkenes with PhI(O2CR)2.
Scheme 66: Plausible mechanism for the rhenium-catalyzed decarboxylative annulation of N-arylacrylamides with ...
Scheme 67: Visible-light-induced one-pot tandem reaction of N-arylacrylamides.
Scheme 68: Plausible mechanism for the visible-light-initiated tandem synthesis of difluoromethylated oxindole...
Scheme 69: Copper-catalyzed redox-neutral cyanoalkylarylation of activated alkenes with cyclobutanone oxime es...
Scheme 70: Plausible mechanism for the copper-catalyzed cyanoalkylarylation of activated alkenes.
Scheme 71: Photoinduced alkyl/aryl radical cascade for the synthesis of quaternary CF3-attached oxindoles.
Scheme 72: Plausible photoinduced electron-transfer (PET) mechanism.
Scheme 73: Photoinduced cerium-mediated decarboxylative alkylation cascade cyclization.
Scheme 74: Plausible reaction mechanism for the decarboxylative radical-cascade alkylation/cyclization.
Scheme 75: Metal-free oxidative tandem coupling of activated alkenes.
Scheme 76: Control experiments and possible mechanism for 1,2-carbonylarylation of alkenes with carbonyl C(sp2...
Scheme 77: Silver-catalyzed acyl-arylation of activated alkenes with α-oxocarboxylic acids.
Scheme 78: Proposed mechanism for the decarboxylative acylarylation of acrylamides.
Scheme 79: Visible-light-mediated tandem acylarylation of olefines with carboxylic acids.
Scheme 80: Proposed mechanism for the radical cascade cyclization with acyl radical via visible-light photored...
Scheme 81: Erythrosine B-catalyzed visible-light photoredox arylation-cyclization of N-arylacrylamides with ar...
Scheme 82: Electrochemical cobalt-catalyzed radical cyclization of N-arylacrylamides with arylhydrazines or po...
Scheme 83: Proposed mechanism of radical cascade cyclization via electrochemical cobalt catalysis.
Scheme 84: Copper-catalyzed oxidative tandem carbamoylation/cyclization of N-arylacrylamides with hydrazinecar...
Scheme 85: Proposed reaction mechanism for the radical cascade cyclization by copper catalysis.
Scheme 86: Visible-light-driven radical cascade cyclization reaction of N-arylacrylamides with α-keto acids.
Scheme 87: Proposed mechanism of visible-light-driven cascade cyclization reaction.
Scheme 88: Peroxide-induced radical carbonylation of N-(2-methylallyl)benzamides with methyl formate.
Scheme 89: Proposed cyclization mechanism of peroxide-induced radical carbonylation with N-(2-methylallyl)benz...
Scheme 90: Persulfate promoted carbamoylation of N-arylacrylamides and N-arylcinnamamides.
Scheme 91: Proposed mechanism for the persulfate promoted radical cascade cyclization reaction of N-arylacryla...
Scheme 92: Photocatalyzed carboacylation with N-arylpropiolamides/N-alkyl acrylamides.
Scheme 93: Plausible mechanism for the photoinduced carboacylation of N-arylpropiolamides/N-alkyl acrylamides.
Scheme 94: Electrochemical Fe-catalyzed radical cyclization with N-arylacrylamides.
Scheme 95: Plausible mechanism for the electrochemical Fe-catalysed radical cyclization of N-phenylacrylamide.
Scheme 96: Substrate scope of the selective functionalization of various α-ketoalkylsilyl peroxides with metha...
Scheme 97: Proposed reaction mechanism for the Fe-catalyzed reaction of alkylsilyl peroxides with methacrylami...
Scheme 98: EDA-complex mediated C(sp2)–C(sp3) cross-coupling of TTs and N-methyl-N-phenylmethacrylamides.
Scheme 99: Proposed mechanism for the synthesis of oxindoles via EDA complex.
A multicomponent reaction-initiated synthesis of imidazopyridine-fused isoquinolinones
- Ashutosh Nath,
- John Mark Awad and
- Wei Zhang
Beilstein J. Org. Chem. 2025, 21, 1161–1169, doi:10.3762/bjoc.21.92
- , indicating a smooth transition from the transition state to the product. The final dehydrative ring-opening gives products by decreasing the energy to 0.978 kJ/mol. Computational analysis indicates that the IMDA step has a high energy barrier which needs a catalyst, while the dehydrative re-aromatization
- were heated at 180 °C for 4 h (Scheme 3). The reaction mixtures were checked by LC–MS to follow the formation of DA adducts 7 and the ring opening products 8 (Figure S1, Supporting Information File 1). After 4 h, the reaction mixtures were worked up and the crude products were purified by flash
Graphical Abstract
Figure 1: Bioactive compounds bearing imidazopyridine (red) and isoquinolinone-kind (blue) rings.
Scheme 1: GBB-initiated synthesis of imidazopyridine-fused isoquinolinones.
Scheme 2: GBB reaction and N-acylation for the preparation of imidazo[1,2-a]pyridines 6.
Scheme 3: Substrate scope for IMDA and dehydrative aromatization in making 8. Reaction conditions: 6 and AlCl3...
Figure 2: Transition state analysis of IMDA reactions for 6a, 6j, 6h and 6r.
Figure 3: Relative energy diagram for the synthesis of 8a from 6a.
Scheme 4: Using thiophene-2-carbaldehyde for the synthesis of 8t.
Scheme 5: Proposed mechanisms for IMDA reaction and dehydration re-aromatization.
Salen–scandium(III) complex-catalyzed asymmetric (3 + 2) annulation of aziridines and aldehydes
- Linqiang Wang and
- Jiaxi Xu
Beilstein J. Org. Chem. 2025, 21, 1087–1094, doi:10.3762/bjoc.21.86
- carboxylate groups followed by a ring opening of the aziridine ring, forming azomethine ylide intermediates A. The intermediates A further undergo a [2 + 3] annulation (or cycloaddition) with aldehydes 2 through endo transition state TS to generate intermediates B, which release products 3 with regeneration
Graphical Abstract
Figure 1: Oxazolidine-containing bioactive compounds.
Scheme 1: Asymmetric catalytic synthetic methods of oxazolidine derivatives.
Scheme 2: Scope of aziridines and aldehydes.
Scheme 3: Proposed reaction mechanism.
Scheme 4: Gram-scale synthesis.
Recent advances in synthetic approaches for bioactive cinnamic acid derivatives
- Betty A. Kustiana,
- Galuh Widiyarti and
- Teni Ernawati
Beilstein J. Org. Chem. 2025, 21, 1031–1086, doi:10.3762/bjoc.21.85
- relatively new prima donna of functional groups explored in drug design, were smoothly prepared. 2.4 Miscellaneous reactions Cyclopropenone, the smallest Hückel aromatic system, has been subjected to the ring opening reactions, driven by the release of ring strain. Numerous transformations of cyclopropenone
- bond of cyclopropenone to give a cyclic intermediate 316 (Scheme 74A) [125]. On the other hand, Wu and co-workers (2022) developed a Pd-catalyzed selective ring-opening of cyclopropenones and vinyl epoxide 318 to give the corresponding esters 319–321 in good yields via a π–allyl palladium intermediate
- 323 (Scheme 74B) [126]. In addition, Sun and co-workers (2020) utilized diphenylcyclopropenone (309) and nitrones to access the corresponding imides 324–327 via a Ag-mediated β-carbon elimination promoted ring-opening reaction involving species 328 and 329 (Scheme 75A) [127]. The method could be
Graphical Abstract
Figure 1: Biologically active cinnamic acid derivatives.
Scheme 1: General synthetic strategies for cinnamic acid derivatizations.
Scheme 2: Cinnamic acid coupling via isobutyl anhydride formation.
Scheme 3: Amidation reaction via O/N-pivaloyl activation.
Scheme 4: Cinnamic acid amidation using TCCA/PPh3 reagent.
Scheme 5: Cinnamic acid amidation using triazine-based reagents.
Scheme 6: Cinnamic acid amidation using continuous flow mechanochemistry.
Scheme 7: Cinnamic acid amidation using COMU as coupling reagent.
Scheme 8: Cinnamic acid amidation using allenone coupling reagent.
Scheme 9: Cinnamic acid amidation using 4-acetamidophenyl triflimide as reagent.
Scheme 10: Cinnamic acid amidation using methyltrimethoxysilane (MTM).
Scheme 11: Cinnamic acid amidation utilizing amine–borane reagent.
Scheme 12: Cinnamic acid amidation using TCCA/PPh3 reagent.
Scheme 13: Cinnamic acid amidation using PPh3/I2 reagent.
Scheme 14: Cinnamic acid amidation using PCl3 reagent.
Scheme 15: Cinnamic acid amidation utilizing pentafluoropyridine (PFP) as reagent.
Scheme 16: Cinnamic acid amidation using hypervalent iodine(III).
Scheme 17: Mechanochemical amidation using 1,1,2,2-tetrafluoroethyl-N,N-dimethylamine (TFEDMA) reagent.
Scheme 18: Methyl ester preparation using tris(2,4,6-trimethoxyphenyl)phosphine (TMPP).
Scheme 19: N-Trifluoromethyl amide preparation using isothiocyanate and AgF.
Scheme 20: POCl3-mediated amide coupling of carboxylic acid and DMF.
Scheme 21: O-Alkylation of cinnamic acid using alkylating agents.
Scheme 22: Glycoside preparation via Mitsunobu reaction.
Scheme 23: O/N-Acylation via rearrangement reactions.
Scheme 24: Amidation reactions using sulfur-based alkylating agents.
Scheme 25: Amidation reaction catalyzed by Pd0 via C–N cleavage.
Scheme 26: Amidation reaction catalyzed by CuCl/PPh3.
Scheme 27: Cu(II) triflate-catalyzed N-difluoroethylimide synthesis.
Scheme 28: Cu/Selectfluor-catalyzed transamidation reaction.
Scheme 29: CuO–CaCO3-catalyzed amidation reaction.
Scheme 30: Ni-catalyzed reductive amidation.
Scheme 31: Lewis acidic transition-metal-catalyzed O/N-acylations.
Scheme 32: Visible-light-promoted amidation of cinnamic acid.
Scheme 33: Sunlight/LED-promoted amidation of cinnamic acid.
Scheme 34: Organophotocatalyst-promoted N–O cleavage of Weinreb amides to synthesize primary amides.
Scheme 35: Cinnamamide synthesis through [Ir] photocatalyst-promoted C–N-bond cleavage of tertiary amines.
Scheme 36: Blue LED-promoted FeCl3-catalyzed reductive transamidation.
Scheme 37: FPyr/TCT-catalyzed amidation of cinnamic acid derivative 121.
Scheme 38: Cs2CO3/DMAP-mediated esterification.
Scheme 39: HBTM organocatalyzed atroposelective N-acylation.
Scheme 40: BH3-catalyzed N-acylation reactions.
Scheme 41: Borane-catalyzed N-acylation reactions.
Scheme 42: Catalytic N-acylation reactions via H/F bonding activation.
Scheme 43: Brønsted base-catalyzed synthesis of cinnamic acid esters.
Scheme 44: DABCO/Fe3O4-catalyzed N-methyl amidation of cinnamic acid 122.
Scheme 45: Catalytic oxidation reactions of acylating agents.
Scheme 46: Preparation of cinnamamide-substituted benzocyclooctene using I(I)/I(III) catalysis.
Scheme 47: Pd-colloids-catalyzed oxidative esterification of cinnamyl alcohol.
Scheme 48: Graphene-supported Pd/Au alloy-catalyzed oxidative esterification via hemiacetal intermediate.
Scheme 49: Au-supported on A) carbon nanotubes (CNT) and B) on porous boron nitride (pBN) as catalyst for the ...
Scheme 50: Cr-based catalyzed oxidative esterification of cinnamyl alcohols with H2O2 as the oxidant.
Scheme 51: Co-based catalysts used for oxidative esterification of cinnamyl alcohol.
Scheme 52: Iron (A) and copper (B)-catalyzed oxidative esterification of cinnamaldehyde.
Scheme 53: NiHPMA-catalyzed oxidative esterification of cinnamaldehyde.
Scheme 54: Synthesis of cinammic acid esters through NHC-catalyzed oxidative esterification via intermolecular...
Scheme 55: Redox-active NHC-catalyzed esterification via intramolecular oxidation.
Scheme 56: Electrochemical conversion of cinnamaldehyde to methyl cinnamate.
Scheme 57: Bu4NI/TBHP-catalyzed synthesis of bisamides from cinnamalaldehyde N-tosylhydrazone.
Scheme 58: Zn/NC-950-catalyzed oxidative esterification of ketone 182.
Scheme 59: Ru-catalyzed oxidative carboxylation of terminal alkenes.
Scheme 60: Direct carboxylation of alkenes using CO2.
Scheme 61: Carboxylation of alkenylboronic acid/ester.
Scheme 62: Carboxylation of gem-difluoroalkenes with CO2.
Scheme 63: Photoredox-catalyzed carboxylation of difluoroalkenes.
Scheme 64: Ru-catalyzed carboxylation of alkenyl halide.
Scheme 65: Carboxylation of alkenyl halides under flow conditions.
Scheme 66: Cinnamic acid ester syntheses through carboxylation of alkenyl sulfides/sulfones.
Scheme 67: Cinnamic acid derivatives synthesis through a Ag-catalyzed decarboxylative cross-coupling proceedin...
Scheme 68: Pd-catalyzed alkyne hydrocarbonylation.
Scheme 69: Fe-catalyzed alkyne hydrocarbonylation.
Scheme 70: Alkyne hydrocarboxylation using CO2.
Scheme 71: Alkyne hydrocarboxylation using HCO2H as CO surrogate.
Scheme 72: Co/AlMe3-catalyzed alkyne hydrocarboxylation using DMF.
Scheme 73: Au-catalyzed oxidation of Au–allenylidenes.
Scheme 74: Pd-catalyzed C–C-bond activation of cyclopropenones to synthesize unsaturated esters and amides.
Scheme 75: Ag-catalyzed C–C-bond activation of diphenylcyclopropenone.
Scheme 76: Cu-catalyzed C–C bond activation of diphenylcyclopropenone.
Scheme 77: PPh3-catalyzed C–C-bond activation of diphenylcyclopropenone.
Scheme 78: Catalyst-free C–C-bond activation of diphenylcyclopropenone.
Scheme 79: Cu-catalyzed dioxolane cleavage.
Scheme 80: Multicomponent coupling reactions.
Scheme 81: Pd-catalyzed partial hydrogenation of electrophilic alkynes.
Scheme 82: Nickel and cobalt as earth-abundant transition metals used as catalysts for the partial hydrogenati...
Scheme 83: Metal-free-catalyzed partial hydrogenation of conjugated alkynes.
Scheme 84: Horner–Wadsworth–Emmons reaction between triethyl 2-fluoro-2-phosphonoacetate and aldehydes with ei...
Scheme 85: Preparation of E/Z-cinnamates using thiouronium ylides.
Scheme 86: Transition-metal-catalyzed ylide reactions.
Scheme 87: Redox-driven ylide reactions.
Scheme 88: Noble transition-metal-catalyzed olefination via carbenoid species.
Scheme 89: TrBF4-catalyzed olefination via carbene species.
Scheme 90: Grubbs catalyst (cat 7)/photocatalyst-mediated metathesis reactions.
Scheme 91: Elemental I2-catalyzed carbonyl-olefin metathesis.
Scheme 92: Cu-photocatalyzed E-to-Z isomerization of cinnamic acid derivatives.
Scheme 93: Ni-catalyzed E-to-Z isomerization.
Scheme 94: Dehydration of β-hydroxy esters via an E1cB mechanism to access (E)-cinnamic acid esters.
Scheme 95: Domino ring-opening reaction induced by a base.
Scheme 96: Dehydroamination of α-aminoester derivatives.
Scheme 97: Accessing methyl cinnamate (44) via metal-free deamination or decarboxylation.
Scheme 98: The core–shell magnetic nanosupport-catalyzed condensation reaction.
Scheme 99: Accessing cinnamic acid derivatives from acetic acid esters/amides through α-olefination.
Scheme 100: Accessing cinnamic acid derivatives via acceptorless α,β-dehydrogenation.
Scheme 101: Cu-catalyzed formal [3 + 2] cycloaddition.
Scheme 102: Pd-catalyzed C–C bond formation via 1,4-Pd-shift.
Scheme 103: NHC-catalyzed Rauhut–Currier reactions.
Scheme 104: Heck-type reaction for Cα arylation.
Scheme 105: Cu-catalyzed trifluoromethylation of cinnamamide.
Scheme 106: Ru-catalyzed alkenylation of arenes using directing groups.
Scheme 107: Earth-abundant transition-metal-catalyzed hydroarylation of α,β-alkynyl ester 374.
Scheme 108: Precious transition-metal-catalyzed β-arylation of cinnamic acid amide/ester.
Scheme 109: Pd-catalyzed β-amination of cinnamamide.
Scheme 110: S8-mediated β-amination of methyl cinnamate (44).
Scheme 111: Pd-catalyzed cross-coupling reaction of alkynyl esters with phenylsilanes.
Scheme 112: Pd-catalyzed β-cyanation of alkynyl amide/ester.
Scheme 113: Au-catalyzed β-amination of alkynyl ester 374.
Scheme 114: Metal-free-catalyzed Cβ-functionalizations of alkynyl esters.
Scheme 115: Heck-type reactions.
Scheme 116: Mizoroki–Heck coupling reactions using unconventional functionalized arenes.
Scheme 117: Functional group-directed Mizoroki–Heck coupling reactions.
Scheme 118: Pd nanoparticles-catalyzed Mizoroki–Heck coupling reactions.
Scheme 119: Catellani-type reactions to access methyl cinnamate with multifunctionalized arene.
Scheme 120: Multicomponent coupling reactions.
Scheme 121: Single atom Pt-catalyzed Heck coupling reaction.
Scheme 122: Earth-abundant transition metal-catalyzed Heck coupling reactions.
Scheme 123: Polymer-coated earth-abundant transition metals-catalyzed Heck coupling reactions.
Scheme 124: Earth-abundant transition-metal-based nanoparticles as catalysts for Heck coupling reactions.
Scheme 125: CN- and Si-based directing groups to access o-selective cinnamic acid derivatives.
Scheme 126: Amide-based directing group to access o-selective cinnamic acid derivatives.
Scheme 127: Carbonyl-based directing group to access o-selective cinnamic acid derivatives.
Scheme 128: Stereoselective preparation of atropisomers via o-selective C(sp2)–H functionalization.
Scheme 129: meta-Selective C(sp2)–H functionalization using directing group-tethered arenes.
Scheme 130: para-Selective C(sp2)–H functionalization using directing group-tethered arenes.
Scheme 131: Non-directed C(sp2)–H functionalization via electrooxidative Fujiwara–Moritani reaction.
Scheme 132: Interconversion of functional groups attached to cinnamic acid.
Scheme 133: meta-Selective C(sp2)–H functionalization of cinnamate ester.
Scheme 134: C(sp2)–F arylation using Grignard reagents.
Scheme 135: Truce–Smiles rearrangement of N-aryl metacrylamides.
Scheme 136: Phosphine-catalyzed cyclization of γ-vinyl allenoate with enamino esters.
Harnessing tethered nitreniums for diastereoselective amino-sulfonoxylation of alkenes
- Shyam Sathyamoorthi,
- Appasaheb K. Nirpal,
- Dnyaneshwar A. Gorve and
- Steven P. Kelley
Beilstein J. Org. Chem. 2025, 21, 947–954, doi:10.3762/bjoc.21.78
- regioselective, diastereoselective, and metal-free protocol for alkene amino-hydroxylation, which compared favorably to prior art in this area [25][26][27][28][29][30][31][32]. Naturally, we wondered if other O-nucleophiles were competent in the ring-opening of the aziridinium intermediate. Indeed, almost all
Graphical Abstract
Scheme 1: Existing reports of intramolecular alkene functionalization reactions with nitreniums have focused ...
Figure 1: Poor performers.
Scheme 2: Putative reaction mechanism.
Scheme 3: (A) Scale-up and (B) applications.
Recent advances in controllable/divergent synthesis
- Jilei Cao,
- Leiyang Bai and
- Xuefeng Jiang
Beilstein J. Org. Chem. 2025, 21, 890–914, doi:10.3762/bjoc.21.73
- ) and (3 + 2) cyclization strategies. Two distinct pathways were established: (1) The titanium-catalyzed ring opening of bicyclobutane (BCB) 32 generates a γ-carbonyl radical intermediate Int-42, which undergoes trapping by vinylazide 33. Subsequent dinitrogen extrusion produces an iminyl radical
Graphical Abstract
Scheme 1: Ligand-controlled regiodivergent C1 insertion into arynes [19].
Scheme 2: Ligand effect in homogenous gold catalysis enabling regiodivergent π-bond-activated cyclization [20].
Scheme 3: Ligand-controlled palladium(II)-catalyzed regiodivergent carbonylation of alkynes [21].
Scheme 4: Catalyst-controlled annulations of strained cyclic allenes with π-allyl palladium complexes and pro...
Scheme 5: Ring expansion of benzosilacyclobutenes with alkynes [23].
Scheme 6: Photoinduced regiodivergent and enantioselective cross-coupling [24].
Scheme 7: Catalyst-controlled regiodivergent and enantioselective formal hydroamination of N,N-disubstituted ...
Scheme 8: Catalyst-tuned regio- and enantioselective C(sp3)–C(sp3) coupling [31].
Scheme 9: Catalyst-controlled annulations of bicyclo[1.1.0]butanes with vinyl azides [32].
Scheme 10: Solvent-driven reversible macrocycle-to-macrocycle interconversion [39].
Scheme 11: Unexpected solvent-dependent reactivity of cyclic diazo imides and mechanism [40].
Scheme 12: Palladium-catalyzed annulation of prochiral N-arylphosphonamides with aromatic iodides [41].
Scheme 13: Time-dependent enantiodivergent synthesis [42].
Scheme 14: Time-controlled palladium-catalyzed divergent synthesis of silacycles via C–H activation [43].
Scheme 15: Proposed mechanism for the time-controlled palladium-catalyzed divergent synthesis of silacycles [43].
Scheme 16: Metal-free temperature-controlled regiodivergent borylative cyclizations of enynes [45].
Scheme 17: Nickel-catalyzed switchable site-selective alkene hydroalkylation by temperature regulation [46].
Scheme 18: Copper-catalyzed decarboxylative amination/hydroamination sequence [48].
Scheme 19: Proposed mechanism of copper-catalyzed decarboxylative amination/hydroamination sequence [48].
Scheme 20: Enantioselective chemodivergent three-component radical tandem reactions [49].
Scheme 21: Substrate-controlled synthesis of indoles and 3H-indoles [52].
Scheme 22: Controlled mono- and double methylene insertions into nitrogen–boron bonds [53].
Scheme 23: Copper-catalyzed substrate-controlled carbonylative synthesis of α-keto amides and amides [54].
Scheme 24: Divergent sulfur(VI) fluoride exchange linkage of sulfonimidoyl fluorides and alkynes [55].
Scheme 25: Modular and divergent syntheses of protoberberine and protonitidine alkaloids [56].
Light-enabled intramolecular [2 + 2] cycloaddition via photoactivation of simple alkenylboronic esters
- Lewis McGhie,
- Hannah M. Kortman,
- Jenna Rumpf,
- Peter H. Seeberger and
- John J. Molloy
Beilstein J. Org. Chem. 2025, 21, 854–863, doi:10.3762/bjoc.21.69
- excitation [66][67], product derivatization was explored (Scheme 2A). While initial efforts for oxidation proved challenging, due to a competing retro-aldol ring-opening reaction, employing a buffered system enabled access to β-alcohol 5. Given the previous power of trifluoroborates in cross-coupling
Graphical Abstract
Figure 1: A) Energy transfer catalysis of alkenes in organic synthesis. B) Energy transfer catalysis of conju...
Figure 2: Probing boron effects on reactivity (A) and confirming the generation of a photostationary state eq...
Figure 3: Probing EnT catalysis enabled [2 + 2] cycloaddition of simple alkenylboronic esters.
Scheme 1: Establishing the substrate scope. Conditions: 3 (1 equiv), xanthone (20 mol %), MeCN (0.03 M), unde...
Scheme 2: A) Product derivatization and B) transition-metal EnT catalysis. Reaction conditions A): 4d (1 equi...
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
- under Pd-catalyzed hydrogenolysis afforded diamino acid ester 14 (75% yield) that was likely formed by ring-opening of the unstable N-unprotected 2-aminoproline followed by the reduction of the open-chain imine tautomer. Likewise, the open-chain amino alcohol 15 was formed also upon the reduction of the
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.
Formaldehyde surrogates in multicomponent reactions
- Cecilia I. Attorresi,
- Javier A. Ramírez and
- Bernhard Westermann
Beilstein J. Org. Chem. 2025, 21, 564–595, doi:10.3762/bjoc.21.45
Graphical Abstract
Scheme 1: Features of the ideal reaction (redrawn from P. A. Wender et al. [1]).
Scheme 2: Some of the most popular MCRs with formaldehyde as the carbonyl component.
Scheme 3: Ugi reaction under a catalyzed electro-oxidation process using TEMPO (2,2,6,6-tetramethyl-1-piperid...
Scheme 4: Examples of different products obtained by MCRs in which DMSO serves as -SCH3 source.
Scheme 5: Mechanism of the decomposition of DMSO under acidic or thermal conditions. a) In situ generation of...
Scheme 6: Povarov multicomponent reaction to quinolines.
Scheme 7: Example of the Povarov reaction with formaldehyde with a julolidine derivative as main product.
Scheme 8: Povarov multicomponent reaction to quinoline derivatives I and II using DMSO as formaldehyde surrog...
Scheme 9: Example of a Povarov three-component reaction with change of catalyst, yielding regioisomer III. In...
Scheme 10: The Povarov three-component reactions carried out under acidic catalysis to afford quinoline regios...
Scheme 11: Different MCR routes involving DMSO to synthesize complex heterocycles such as diarylpyridines and ...
Scheme 12: Pyrazole synthesis by a three-component reaction using DMSO as a source of a C-1 unit.
Scheme 13: Three-component reactions for the synthesis of aliphatic heterocycles 13 and 14 using DMSO as a for...
Scheme 14: Proposed mechanism for the 3CR between homoallylic amines, disulfides, and DMSO.
Scheme 15: Mannich-type reaction using DMSO as formaldehyde surrogate.
Scheme 16: Mechanism for the 3CR-Mannich-type reaction between aryl ketone 18, saccharine (19), and DMSO. The ...
Scheme 17: Mannich-type reaction using DMSO as formaldehyde surrogate and under oxidative activation.
Scheme 18: Three-component reaction between an indazole, a carboxylic acid, and DMSO.
Scheme 19: Amine–aldehyde–alkyne (AAA) coupling reaction and plausible mechanism.
Scheme 20: AHA coupling for the synthesis of propargylamines using dihalomethanes as C1 building blocks.
Scheme 21: AHA coupling using CH2Cl2 as both solvent and methylene source.
Scheme 22: Examples of propargylamines synthesized under catalytic AHA protocols.
Scheme 23: Proposed mechanism for the synthesis of propargylamines using dichloromethane as a C1 source.
Scheme 24: Mechanism proposed for the generation of the aminal intermediate E by Buckley et al. [68].
Scheme 25: Pudovic and Kabachnik–Fields reactions for the synthesis of α-aminophosphonates.
Scheme 26: a) Abramov side reaction that generates α-hydroxy phosphonate as a byproduct during the Kabachnik-F...
Scheme 27: Catalyst-free three component reaction to afford α-amino phosphorus product 35 using 1,1-dihaloalka...
Scheme 28: a) Proposed mechanism for the three-component reaction of dichloromethane, amine and phosphorus com...
Scheme 29: Ugi-ammonia strategy using HMTA as a formaldehyde surrogate.
Scheme 30: Glyoxylate and its derivatives as C1 building blocks.
Scheme 31: The Groebke–Blackburn–Bienaymé multicomponent reaction (GBB) and its mechanism.
Scheme 32: a) Byproducts in the GBB multicomponent reaction (GBB) when formaldehyde is used as the carbonyl co...
Scheme 33: Possible regioisomers in the GBB multicomponent reaction when formaldehyde is used as the carbonyl ...
Scheme 34: The multicomponent GBB reaction yields 2-unsubstituted 3-aminoimidazo heterocycles 42a using MP-gly...
Scheme 35: GBB multicomponent reaction to 2-unsubstituted 3-amino imidazo heterocycles 42a using glyoxylic aci...
Scheme 36: GBB reaction using glyoxylic acid immobilized on silica as formaldehyde surrogate.
Scheme 37: Bioactive products synthesized by the GBB reaction using glyoxylic acid.
Scheme 38: van Leusen three-component reaction to imidazoles.
Scheme 39: Side reaction during the synthesis of imidazoles with formaldehyde as the carbonyl compound.
Scheme 40: Optimization of the van Leusen three component reaction to 1,4-disubstituted imidazoles 43 using gl...
Scheme 41: Application of the Sisko strategy [96] for the synthesis of CB1 receptor antagonist compounds [97].
Scheme 42: Side reaction, when NH4OH is used as amine component.
Scheme 43: Ugi-type adducts with the ester moiety and the acidic CH to be used for post-cyclization sequences.
Scheme 44: Ugi/cycloisomerization process to pyrrolones 51, butenolides 52, and pyrroline 53.
Scheme 45: Radical cyclization reactions from Ugi adducts promoted by TEMPO.
Scheme 46: Hydrolysis and decarboxylation reactions to products with incorporation of a C1 unit of ethyl glyox...
Scheme 47: One-step synthetic route to pyrrolones 60 using phenylglyoxal.
Scheme 48: Ugi-pseudo-Knoevenagel-pseudo-Dieckmann cascade sequence for the synthesis of fused heterocycles.
Scheme 49: Ugi-pseudo-Knoevenagel reaction from ethyl glyoxylate.
Synthesis of the aggregation pheromone of Tribolium castaneum
- Biyu An,
- Xueyang Wang,
- Ao Jiao,
- Qinghua Bian and
- Jiangchun Zhong
Beilstein J. Org. Chem. 2025, 21, 510–514, doi:10.3762/bjoc.21.38
- is a destructive stored product pest. The aggregation pheromone of this pest was prepared via a new and effective strategy. The key steps include the ring-opening reaction of chiral 2-methyloxirane, the stereospecific inversion of chiral secondary tosylate, Li2CuCl4-catalyzed coupling of tosylate
- -amine reduction and tosylation from diethyl (S)-2-(hex-5-en-2-yl)malonate ((S)-6). The stereocenter in geminal ester (S)-6 could be derived from (R)-2-methyloxirane ((R)-2) via a ring-opening reaction and a stereospecific inversion of the chiral secondary tosylate (R)-5. Following the similar procedure
- for (4R,8R)-1, the other constituents of the aggregation pheromone (4R,8S)-1, (4S,8R)-1 and (4S,8S)-1 could be prepared. Based on the retrosynthetic analysis of the aggregation pheromone (4R,8R)-1, our synthesis began with the preparation of chiral tosylate (S)-10 (Scheme 2). The ring-opening reaction
Graphical Abstract
Figure 1: The aggregation pheromone of Tribolium castaneum.
Scheme 1: Retrosynthetic analysis of the aggregation pheromone (4R,8R)-1.
Scheme 2: Synthesis of chiral tosylate (S)-10.
Scheme 3: Synthesis of chiral tosylate (R)-10.
Scheme 4: Synthesis of the aggregation pheromone of Tribolium castaneum.
Streamlined modular synthesis of saframycin substructure via copper-catalyzed three-component assembly and gold-promoted 6-endo cyclization
- Asahi Kanno,
- Ryo Tanifuji,
- Satoshi Yoshida,
- Sota Sato,
- Saori Maki-Yonekura,
- Kiyofumi Takaba,
- Jungmin Kang,
- Kensuke Tono,
- Koji Yonekura and
- Hiroki Oguri
Beilstein J. Org. Chem. 2025, 21, 226–233, doi:10.3762/bjoc.21.14
- degassed solvent and light-shielding flask, the oxidative conversion of 12 to the imidate 18 proceeded smoothly. Notably, the transient intermediate 18, exhibiting a sky-blue fluorescence, further underwent a ring opening to afford the tetracyclic 14 with the simultaneous regeneration of both a nitrile and
- a fluorescent intermediate 18, and subsequent ring opening allowed a streamlined one-pot access to the substructure of THIQ alkaloids 14 in a good yield of 60% from 11. The structure of the resulting 14 was elucidated through comprehensive two-dimensional NMR spectroscopy, complemented by NOE
- followed by cascade oxidative conversion and ring opening giving rise to the skeleton 14. Streamlined synthesis of the substructure 14 for saframycins 1 within just four steps in overall 29% yield. This concise modular synthetic process involves copper(I)-catalyzed three-component coupling, sequential
Graphical Abstract
Figure 1: Representative bis-tetrahydroisoquinoline (THIQ) alkaloids and their analogues. Oxygen atoms on bot...
Scheme 1: Strategies for the construction of the pentacyclic core scaffold of saframycin A (1). (a) Biosynthe...
Scheme 2: Streamlined synthesis of the substructure 14 for saframycins 1 within just four steps in overall 29...
Figure 2: UV–vis absorption (gray solid line), the emission spectrum (blue solid line), and the corresponding...
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
- the final step of the reaction, ring opening by the C–C bond cleavage yields the desired product 203. The first phosphoric acid C39-catalyzed asymmetric cycloaddition–elimination cascade reaction of 2-naphthol or phenol enamide derivatives 204 with azonaphthalenes 205 was done by Xu et al. in 2021
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.
Hot shape transformation: the role of PSar dehydration in stomatocyte morphogenesis
- Remi Peters,
- Levy A. Charleston,
- Karinan van Eck,
- Teun van Berlo and
- Daniela A. Wilson
Beilstein J. Org. Chem. 2025, 21, 47–54, doi:10.3762/bjoc.21.5
- ring-opening polymerization of N-carboxyanhydrides (NCAs), following a protocol adapted from Tian et al. [28]. High-purity monomers were obtained using this method, ensuring the subsequentially polymer synthesis proceeded with minimal impurities. Sequential polymerization commenced with poly(benzyl
- the vesicles at higher temperatures. d–f) Vesicles after shape transformation: illustrated at 60 °C, 70 °C, and 80 °C, respectively. i) Synthesis of benzyl glutamate NCA using phosgene and propylene oxide as a scavenger. ii) Ring-opening polymerization of BnGluNCA using benzylamine as initiator. iii
- ) Synthesis of sarcosine NCA starting from Boc-protected sarcosine using phosgene and propylene oxide as a scavenger. iv) Ring-opening polymerization of Sar NCA using the benzyl glutamate homopolymer as macro initiator. Supporting Information Supporting Information File 70: Experimental part and additional
Graphical Abstract
Scheme 1: i) Synthesis of benzyl glutamate NCA using phosgene and propylene oxide as a scavenger. ii) Ring-op...
Figure 1: i) The PBLG-PSar block copolymers are dissolved in DMF and then assembled though the solvent-exchan...
Figure 2: Progression of shape transformation of PSar-PBLG vesicles at 70 °C (scalebar 0.5 µm). a) Initial (0...
Figure 3: The temperature-dependent behavior of vesicles and shape Transformation: a) Thermograph of PBLG-PSa...
Germanyl triazoles as a platform for CuAAC diversification and chemoselective orthogonal cross-coupling
- John M. Halford-McGuff,
- Thomas M. Richardson,
- Aidan P. McKay,
- Frederik Peschke,
- Glenn A. Burley and
- Allan J. B. Watson
Beilstein J. Org. Chem. 2024, 20, 3198–3204, doi:10.3762/bjoc.20.265
- chromene (12) were tolerated. Benzylic azides were accommodated including those bearing nitro (2), iodo (3), and boronic ester groups (5, 21). Strained rings were effective including cubane (18) and bicyclopentane (20). While 18 and 20 were isolated in lower yield, no evidence of ring opening was observed
Graphical Abstract
Scheme 1: The CuAAC reaction and installation of functional groups for product diversification.
Scheme 2: Scope of germanyl acetylene CuAAC. Alkyne (1.0 equiv), azide (1.1 equiv), CuSO4·5H2O (5.0 mol %), N...
Scheme 3: (a) Application of Ge-alkyne CuAAC to functional molecules. (b) Functionalisation of germylated tri...
Synthesis of 2H-azirine-2,2-dicarboxylic acids and their derivatives
- Anastasiya V. Agafonova,
- Mikhail S. Novikov and
- Alexander F. Khlebnikov
Beilstein J. Org. Chem. 2024, 20, 3191–3197, doi:10.3762/bjoc.20.264
- azirine dicarboxylic acid 6j, oxazole-4-carboxylic acid 9 was isolated. Apparently, azirine 2j underwent ring opening at higher temperature to nitrile ylide 7, which after cyclization and hydrolysis gave acid 9 (Scheme 3) (cf., e.g. [23]). Next, given that the preparation of 2H-azirine-2-carboxamides from
Graphical Abstract
Scheme 1: Approaches to 2H-azirine-2,2-dicarboxylic acid derivatives.
Scheme 2: Synthesis of 2H-azirine-2,2-dicarboxylic acids 6.
Scheme 3: Transformations of 3-(tert-butyl)-5-chloroisoxazole-4-carbonyl chloride (1j).
Scheme 4: Synthesis of amides 10. aFiltration through celite after reaction with amine (without aqueous worku...
Scheme 5: Synthesis of esters 11.
Scheme 6: Synthesis of dicarbonyl azide 12.
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
- , with TBAI as a co-catalyst, up to 74% yields (Table 1). The inactivity of porphyrin 18 was attributed to the inaccessibility of the inner core imine due to its planar structure. The mechanism of the epoxide ring-opening reaction was elucidated by DFT calculations, which suggested that the macrocycle
- state stabilizes the anionic species generated during the reaction pathway and facilitates a backside attack of I− on the epoxide thus resulting in the initial ring opening (Figure 4b). Apart from acting as an organocatalyst, calix[4]pyrrole 11 has been used for the promotion of cuprous chloride
- (Table 5). DFT calculations predicted that the catalytically active species is the adduct of porphyrin and TBACl (18-I), which forms an activated complex (18-II) with the substrate followed by a ring-opening nucleophilic attack of Cl−. The electron-rich nitrogen atom in 18-III further activates
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...
Cyclodextrin-based rotaxanes for polymer materials: challenge on simultaneous realization of inexpensive production and defined structures
- Yosuke Akae
Beilstein J. Org. Chem. 2024, 20, 3026–3049, doi:10.3762/bjoc.20.252
- , [3]rotaxane diol 10 was used as the initiator of the controlled ring-opening polymerization (ROP) of ε-caprolactone in the presence of a diphenyl phosphate catalyst to introduce the polyester main chain into the rotaxane framework; the successive end-capping reactions yielded macromolecular [3
Graphical Abstract
Figure 1: Overview of the CD-based rotaxane as a polymer material covered in this review.
Figure 2: CD structure.
Figure 3: Typical pathway for synthesizing CD-based rotaxanes.
Scheme 1: (A) Synthesis of α-CD-based [2]rotaxane via a metal–ligand complex. (B) Chemical structures of meth...
Scheme 2: Synthesis of α-CD-based polyrotaxane.
Scheme 3: Facile [3]rotaxane synthesis by the urea end-capping method.
Figure 4: (A) Single-crystal structure of α-CD-based [3]rotaxane 3 and PMα-CD-based [3]rotaxane 4. (B) Schema...
Figure 5: Structural control of CD-based [2]rotaxane via (A) light irradiation and (B) light irradiation and ...
Figure 6: Relationship among the plus–minus signs of ICD, the position of the guest molecule, and the axis of...
Figure 7: Structural control of CD-based rotaxane via (A) redox reaction and (B) in a solvent.
Scheme 4: (A) Synthesis of pseudopolyrotaxane bearing an ABA triblock copolymer as an axle. (B) Two synthetic...
Scheme 5: Slippage of size-complementary rotaxanes.
Figure 8: (A) Reversible formation of the CD-based [2]rotaxane. (B) Deslipping reaction of the CD-based size-...
Figure 9: (A) Chemical structures of [3]rotaxanes 2 and 3. (B) Schematic of the deslipping reaction of [3]rot...
Figure 10: (A) Modification of the axle ends of [3]rotaxane by (1) bromination and (2) the Suzuki coupling rea...
Figure 11: (A) ICD spectra of [3]rotaxanes bearing acylated (top) and conventional (bottom) CDs. (B) Schematic...
Figure 12: Synthesis of macromolecular[3]rotaxane via a size-complementary protocol.
Figure 13: Conjugated polymer insulated by (A) β-CD. (B) Triphenylamine-substituted β-CD.
Figure 14: Synthesis of the VSC and successive rotaxane-crosslinked polymer (RCP) preparation.
Figure 15: (A) Chemical structure of the [3]rotaxane crosslinker (RC). (B) Schematic of the synthesis and de-c...
Figure 16: (A) Random vinylation of the CD-based [3]rotaxane; (B) Schematic of the reaction between α-CD and m...
Figure 17: (A) Aggregation of CD-based [3]rotaxane. (B) Schematic of the plausible mechanism of the aggregatio...
