Electrosynthetic access to unsymmetrical oxaza[8]helicenes with high chiral stability and strong circularly polarized luminescence (CPL)
- Tin Zar Aye,
- Rubal Sharma,
- Muthu Karuppasamy,
- Daiya Suzuki,
- Haruka Nakajima,
- Yoshitane Imai,
- Mitsuhiro Arisawa,
- Mohamed S. H. Salem and
- Shinobu Takizawa
Beilstein J. Org. Chem. 2026, 22, 372–382, doi:10.3762/bjoc.22.25
Graphical Abstract
Scheme 1: Recent examples of hetero[8]helicenes: (A) symmetric hetero[8]helicenes; (B) unsymmetrical hetero[8...
Scheme 2: Short-step synthesis of unsymmetrical oxaza[8]helicenes 5.
Figure 1: A plausible reaction mechanism: cyclic voltammetry (CV) analyses of hydroxycarbazole derivative 3 a...
Figure 2: Aromaticity of oxaza[8]helicenes: (A) NICS(0)zz and NICS(1)zz values of 5a and 5b calculated at MN1...
Figure 3: (P/M) Enantiomerization process of 5a (A), 5b (B), 6a (C), and 6b (D); relative Gibbs free energies...
Figure 4: Photophysical characters of oxaza[n]helicenes: (A) and (B) UV–vis absorption and PL spectra; (C) Fr...
Figure 5: Chiroptical properties of oxaza[n]helicenes: (A) CD spectra measured in chloroform (1 × 10−5 M); CP...
Non-central chirality in organic chemistry
- Ken Tanaka and
- Naohiko Yoshikai
Beilstein J. Org. Chem. 2026, 22, 370–371, doi:10.3762/bjoc.22.24
Recent advances in the cleavage of non-activated amides
- Eun-Sol Choi and
- Hyo-Jun Lee
Beilstein J. Org. Chem. 2026, 22, 352–369, doi:10.3762/bjoc.22.23
Graphical Abstract
Scheme 1: a) Resonance structure of amide. b) Concept of twisted amides. c) Transition-metal-catalyzed activa...
Scheme 2: Esterification of amides catalyzed by CeO2.
Scheme 3: Hydrolysis of amides catalyzed by Nb2O5.
Scheme 4: Manganese-catalyzed esterification of tertiary amides.
Scheme 5: Tungsten-catalyzed transamidation of hindered tertiary amides.
Scheme 6: Palladium-catalyzed transamidation of amides.
Scheme 7: Synthesis of benzyl esters via electrophilic activation of amides using DPT-BM.
Scheme 8: Esterification of amides promoted by SO2F2.
Scheme 9: α-Fluorinative cleavage of pyrrolidine-based tertiary amides via double electrophilic activation wi...
Scheme 10: Esterification of primary amides using TCCA via the generation of RCONCl2.
Scheme 11: Esterification of amides via electrophilic activation with Me2SO4.
Scheme 12: HBF4-mediated esterification of amides.
Scheme 13: Synthesis of 2,2,2-trifluoroethyl esters via electrophilic esterification of amide promoted by 67.
Scheme 14: Electrochemical activation of C–N bonds for esterification.
Scheme 15: Catalyst- and reagent-free transamidation of amide using aniline hydrochloride salt.
Scheme 16: CO2-catalyzed transamidation of amides.
Scheme 17: Transamidation of formamides using cyclic dihydrogen tetrametaphosphate.
Scheme 18: BF3·OEt2-mediated transamidation of primary amides.
Scheme 19: Acyl iodide intermediate 121 generation from amides for the transamidation using HOTf and KI.
Scheme 20: Esterification of N,N-dimethyl amides via electrophilic generation of acyl iodide intermediates.
Scheme 21: Transamidation of DMAc promoted by KOt-Bu.
Scheme 22: a) LiHMDS-mediated transamidation of tertiary amides. b) Computed reactivities of selected amides. ...
Scheme 23: Zn-catalyzed chemoselective cleavage of amides directed by tert-butyl nicotinate.
Scheme 24: Chemoselective cleavage of N-PMB anilide for transamidation via acyl fluoride 194 generation. a) Cu...
Synthesis of tricyclic fused pyrrolidine nitroxides from 2-alkynylpyrrolidine-1-oxyls
- Mark M. Gulman,
- Yuliya F. Polienko,
- Sofia Yu. Trakhininа,
- Yuri V. Gatilov,
- Tatyana V. Rybalova,
- Sergey A. Dobrynin and
- Igor A. Kirilyuk
Beilstein J. Org. Chem. 2026, 22, 344–351, doi:10.3762/bjoc.22.22
Graphical Abstract
Scheme 1: Synthesis of nitroxides 2a–f.
Figure 1: X-ray structure of nitroxide 2d.
Scheme 2: Synthesis of mesyl 3a–f and triazole 4a–f derivatives.
Figure 2: X-ray structures of nitroxides 4a–c.
Scheme 3: Synthesis of alkynones 6a,b.
Scheme 4: Synthesis of vinyl ether 8.
Figure 3: X-ray structures of nitroxides 8 and 9a.
Scheme 5: Synthesis of pyrazole derivatives 9a–c.
Figure 4: Spin–spin coupling constants for reduced nitroxides 9a–c.
Ring contraction and ring expansion reactions in terpenoid biosynthesis and their application to total synthesis
- Nicolas Kratena,
- Nicolas Heinzig and
- Peter Gärtner
Beilstein J. Org. Chem. 2026, 22, 289–343, doi:10.3762/bjoc.22.21
Graphical Abstract
Scheme 1: Mechanistic overview of enzymes involved in ring-size-altering reactions: A: Difference in ionisati...
Scheme 2: A: Ring contraction through involvement of carbocationic intermediates in thujane monoterpene biosy...
Scheme 3: Examples of concerted ring expansions of carbocation intermediates in PxaTPS8-catalysed cyclisation...
Scheme 4: Sequential ring expansions during astellifadiene (17) synthesis reported by Abe and co-workers.
Scheme 5: Cyclobutane ring expansion and sequential ring contractions catalysed by the synthase AITS in the b...
Scheme 6: Ring expansion and transannular ring contraction of a cyclopentane to cyclobutane in the biosynthes...
Scheme 7: Computationally elucidated concerted cyclisations/alkyl/hydride shifts during the biosynthesis of t...
Scheme 8: Cyclisation events and 6→5-ring contraction during the construction of epi-isozizaene (26) catalyse...
Scheme 9: Transannular cyclisations and 4→5-membered ring expansion through dyotropic 1,2-rearrangement of al...
Scheme 10: Ring expansion in presilphiperfolan-8b-ol (31) biosynthesis and ring contraction of the presilphipe...
Scheme 11: Ring contraction via transannular cyclopropanation and opening of cyclopropane in the biosynthesis ...
Scheme 12: The crucial CYP450-catalysed oxidative rearrangement defining the skeleton in gibberellin biosynthe...
Scheme 13: CYP450-mediated oxidation of cyclopentane methylene expanding the 8-membered ring in the biosynthes...
Scheme 14: CYP450-mediated oxidation of an exocyclic methyl group to effect transannular cyclisation across th...
Scheme 15: Non-enzymatic transannular aldol reaction enables the formation of the 5/13/3-tricyclic ring system...
Scheme 16: A: Oxidative ring expansion of a cyclopentane by incorporation of a methyl group in the biosynthesi...
Scheme 17: Rearrangement and ring expansion in the construction of the complex bridged carbon framework of and...
Scheme 18: Ketoglutarate-mediated oxidations of preaustinoid A1 (53) en route to complex meroterpenoids, B-rin...
Scheme 19: Proposed putative biosynthetic formation of the tigliane skeleton from an E,E,Z-triene.
Scheme 20: Photocatalytic tandem ring expansion/contraction of santonin to give photosantonin products and gua...
Scheme 21: A: Proposed biosynthesis of stelleroid B (66) from stelleranoid I (65) by ketol rearrangement; B: o...
Scheme 22: Singular examples of A,B-ring contractions and expansions in the biosynthesis of sesquiterpenoids e...
Scheme 23: A: plausible proposed biosynthetic pathway for the tigliane/ingenane skeletal rearrangement and 1,2...
Scheme 24: A: Multiple ring-size alterations during xenovulene A (90) biosynthesis; B: Ring contraction and re...
Scheme 25: Proposed biosyntheses of the complex, polycyclic terpenoid illisimonin A (97) and the bridged antro...
Scheme 26: Proposed biogenetic origin for the meroterpenoid liphagal (104) via epoxide-mediated ring expansion....
Scheme 27: Proposed biogenetic origin for the ring-contracted members of the taiwaniaquinol family.
Scheme 28: A: Schenck ene/Hock/Aldol cascade effecting B-ring contraction in atheronal B (113); B: Selective C...
Scheme 29: A: D-ring expansion of buxenone (118) via cyclopropanation towards buxaustroine A (119); B: Propose...
Scheme 30: Biosynthetic origin of alstoscholarinoids A (124) and B (125) via cascade oxidative rearrangement c...
Scheme 31: Biogenetic origin of the hedgehog signalling inhibitor cyclopamine (129) by tandem ring contraction...
Scheme 32: Proposed biogenetic origin of the B-ring contracted spirocyclic triterpenoid spirochensilide A (131...
Scheme 33: A: Proposed B-ring contraction during the biosynthesis of holophyllane A (133); B: B-ring contracti...
Scheme 34: Radical and ionic/polar mechanisms for the C-ring-contracted triterpenoids phomopsterone B (139) an...
Scheme 35: A: Plausible mechanism for the formation of schiglautone A (144) from anwuweizic acid (145); B: Pro...
Scheme 36: Reported biosynthetic proposal for the formation of B-ring expanded triterpenoids rhodoterpenoids A...
Scheme 37: A: Final reaction step in the synthesis of euphorikanin A (154), benzilic acid-type ring contractio...
Scheme 38: Tricyclic ring expansion in the Gui synthesis of gibbosterol A (158) and sarocladione (160) via Ru-...
Scheme 39: A: A-ring expansion during the Gui synthesis of rubriflordilactone B (161); B: Mechanism for the bi...
Scheme 40: Photosantonin rearrangement effects A/B ring contraction/expansion in Li’s synthesis of the complex...
Scheme 41: Tandem A/B ring expansion/contraction of an ergosterol derivative via pinacol rearrangement in the ...
Scheme 42: Synthetic studies towards cyclocitrinol (179) by A) the semisynthetic approach by Gui et al. using ...
Scheme 43: A: Bioinspired synthesis of spirochensilide A (131) by the Heretsch group via selective 8,9-epoxida...
Scheme 44: Baran’s synthesis of cortistatin A (191), expanding the B-ring through a cyclopropane fragmentation....
Scheme 45: Ding’s total synthesis of retigeranic acid (198) showcasing sequential 6→5 ring contractions.
Scheme 46: A: Oxa-di-π-methane (ODPM) rearrangement of a bicyclic ketone en route to silphiperfolenone (203); ...
Scheme 47: Biomimetic synthesis of liphagal (104) from sclareolide (221) by George and co-workers.
Scheme 48: Wu’s bioinspired synthesis of cucurbalsaminones B (224) and C (225) by photocatalytic oxa-di-π-meth...
Scheme 49: Baran’s total synthesis of maoecrystal V (230) featuring a pinacol rearrangement for ring expansion...
Scheme 50: A: Ketol rearrangement leading to ring contraction in the total synthesis of preaustinoid B; B: Ben...
Scheme 51: A: Scheidt’s synthesis of isovelleral (251) by pinacol rearrangement triggered by Mitsunobu conditi...
Scheme 52: Biomimetic transformations of simplified test substrates related to Euphorbia diterpenoids.
Scheme 53: A: First generation synthesis of taiwaniaquinones by benzilic acid-type rearrangement of the B-ring...
Scheme 54: A: Norrish type 1 radical recombination leading to ring contraction en route to cuparenone (272): 1...
Scheme 55: Ring contraction of a bridged D-ring system in the total synthesis of andrastatin D (280), terrenoi...
Scheme 56: Biomimetic synthesis of hyperjapone A (284) and hyperjaponol C (285) by George et al.
Scheme 57: Heretsch’ synthesis of dankastarones A (288) and B (289), swinhoeisterol A (290), and periconiaston...
Scheme 58: A: Zhang’s ring contraction during the synthesis of stemar-13-ene (295) by pinacol rearrangement; B...
Scheme 59: Trauner’s biomimetic synthesis of preuisolactone A (307) featuring a ring contraction via benzilic ...
Scheme 60: Bioinspired approaches for ring contraction/expansion reactions in the synthesis of alstoscholarino...
Scheme 61: A: Sarpong and Li, Wang and co-workers’ ring expansion of cephanolide A (313) to reach harringtonol...
Spirobarbiturates with a pyrrolizidine moiety: synthesis, structure and biological evaluation
- Arthur A. Puzyrkov,
- Andrew S. Drachuk,
- Ekaterina A. Popova,
- Alexander V. Stepakov and
- Vitali M. Boitsov
Beilstein J. Org. Chem. 2026, 22, 274–288, doi:10.3762/bjoc.22.20
Graphical Abstract
Scheme 1: Biologically active compounds with a spirobarbiturate moiety in their structure [7-12].
Scheme 2: Biologically active alkaloids with a pyrrolizidine moiety.
Scheme 3: Previous studies on the three-component synthesis of spirobarbiturates.
Scheme 4: Synthesis of racemic spirobarbiturates 4a–p via one-pot three-component reaction of alloxan (1), ʟ-...
Scheme 5: A plausible mechanism of spirobarbiturate formation from alloxan (1), ʟ-proline (2), and N-substitu...
Figure 1: Schematic structures of endo- and exo-adducts of spirobarbiturates 4.
Figure 2: X-ray crystal structures of compounds 4b (CCDC 2391172, left) and 4c (CCDC 2391171, right).
Figure 3: Unit cell packing of products 4b (left) and 4c (right).
Figure 4: HS mapped with dnorm for compounds 4b (left) and 4c (right).
Figure 5: A segment of the crystal structure of compound 4b with the HS (dnorm), showing intermolecular conta...
Figure 6: A segment of the crystal structure of compound 4c with the HS (dnorm), showing intermolecular conta...
Figure 7: Microscopic images of treated cells and state of the actin cytoskeleton of Sk-mel-2 cells after cul...
Figure 8: Docked view of compounds 4f, 4g, 4i, 4k, and 4l with the target protein (PDB ID: 8DNH).
Arene activation via π-bond localization: concepts and opportunities
- Paul Meiners,
- Julian J. Melder and
- Tobias Morack
Beilstein J. Org. Chem. 2026, 22, 257–273, doi:10.3762/bjoc.22.19
Graphical Abstract
Figure 1: Aromatic molecules as the foundation of modern molecular chemistry.
Figure 2: Arenes as springboards to three-dimensional chemical space and strategies toward arene activation v...
Figure 3: Structure and synthetic utilization of strained arenes; NICS: nucleus independent chemical shifts [26-28].
Figure 4: Bonding and reactivity of η2-coordinated aromatic systems [44,46].
Figure 5: Illustrative selection of η2-coordinating dearomatization agents; MeIm: N-methylimidazole, NHE: nor...
Figure 6: Preparation, lability and most stable linkage isomers of pentaammineosmium(II) complexes.
Scheme 1: Heteroatom-directed reactions of η2-arene complexes [45,50].
Figure 7: Latent functionality through transient metal binding.
Figure 8: Selective hydrogenation of η2-coordinated benzene to cyclohexene under ambient conditions [53,54].
Scheme 2: Synthesis and utilization of enantioenrichted Mo(η2-arene) complexes in enantioselective synthesis [55]....
Scheme 3: Synthesis of trisubstituted cyclohexenes from phenyl sulfones enabled by tungsten-mediated dearomat...
Scheme 4: Diels–Alder reactions of η2-arene complexes with alkenes and alkynes; NMM: N-methylmaleimide [64,65].
Scheme 5: Binding characteristics and pioneering examples of isolable η3-benzyl complexes.
Figure 9: Divergent functionalization of benzyl electrophiles leveraging η3-benzyl complexes toward benzylic ...
Scheme 6: p-Selective allylation of benzyl chlorides with allylstannanes and subsequent synthetic expansion o...
Figure 10: Strategies for para- and ortho-selective arene functionalization/dearomatization via η3-benzyl comp...
Scheme 7: Substrate-dependent ortho- and para-selective dearomatization of naphthyl chlorides and leveraging ...
Figure 11: η4-Arene coordination as an underexplored but promising pathway for arene activation [96,98-100].
A mild and atom-efficient four-component cascade strategy for the construction of biologically relevant 4-hydroxyquinolin-2(1H)-one derivatives
- Dmitrii A. Grishin,
- Kseniia I. Sharkovskaia,
- Ilya G. Kolmakov,
- Daria A. Ipatova,
- Rostislav A. Petrov,
- Nikolai D. Dagaev,
- Dmitry A. Skvortsov,
- Maria G. Khrenova,
- Valeriy V. Andreychev,
- Sergei A. Evteev,
- Yan A. Ivanenkov,
- Roman L. Antipin,
- Olga А. Dontsova and
- Elena K. Beloglazkina
Beilstein J. Org. Chem. 2026, 22, 244–256, doi:10.3762/bjoc.22.18
Graphical Abstract
Figure 1: Examples of biologically active quinolin-2(1H)-ones.
Figure 2: Structures obtained via rational design aimed at enhancing antibacterial activity.
Scheme 1: Previously reported and newly developed 3-(4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl)-3-arylpropanoi...
Scheme 2: Retrosynthetic analysis: two alternative approaches to target compounds.
Scheme 3: Two-stage synthesis A) and one-stage one-pot synthesis B) of 6-halogen-4-hydroxyquinoline-2(1H)-one...
Scheme 4: Previous synthetic attempts toward the target chemotype using various approaches.
Scheme 5: Four-component synthesis of 3-(6-halo-4-hydroxy-2-oxo-1,2-dihydroquinolin-3-yl)-3-(3,4-dimethoxyphe...
Scheme 6: The proposed mechanism of the four-component reaction.
Scheme 7: Synthesis of isopropyl (12a–c) and cyclohexyl (13а–с) esters of 3-(4-hydroxy-2-oxo-1,2-dihydroquino...
Figure 3: In vitro antibacterial activity studies. А) In vitro antibacterial activity using the E. coli ΔtolC...
Conformational analysis of difluoromethylornithine: factors influencing its gas-phase and bioactive conformations
- Matheus P. Freitas
Beilstein J. Org. Chem. 2026, 22, 237–243, doi:10.3762/bjoc.22.17
Graphical Abstract
Figure 1: Structure of racemic difluoromethylornithine (DFMO) and conformers I–III of the (S)-enantiomer ((S)...
Figure 2: Representative conformations of (S)-DFMO with their relative electronic energies (in kcal mol−1), s...
Figure 3: (S)-DFMO bound within the active site of human arginase I obtained from the Protein Data Bank (3GN0...
Figure 4: Lowest-energy type-I, type-II, and type-III conformers of the zwitterionic form of (S)-DFMO. Color ...
Configuration–packing synergy enabling integrated crystalline-state RTP and amorphous-state TADF
- Ruiyan Wang and
- Yunan Wu
Beilstein J. Org. Chem. 2026, 22, 224–236, doi:10.3762/bjoc.22.16
Graphical Abstract
Figure 1: a) Single-crystal structure of 1, b) HOMO distribution calculated on the crystallographic geometry,...
Figure 2: Photophysical properties of 1 in solvents of varying polarity: a) UV–vis absorption spectra and b) ...
Figure 3: Fluorescence and phosphorescence spectra of 1 in THF (excitation wavelength: 365 nm).
Figure 4: a) Steady-state and delayed emission spectra of 1, b) room-temperature emission lifetimes monitored...
Figure 5: a) Phosphorescence spectra of 1 in the powder state at room temperature and at 77 K, and in dilute ...
Figure 6: a) The bimolecular packing arrangement in the crystal of 1 and intersystem crossing pathways of 1 i...
Figure 7: Photoluminescence lifetime of vacuum-deposited 1 films at different temperatures (excitation wavele...
Figure 8: a) TG curve of 1 and b) DSC curve of 1.
Figure 9: a) Electroluminescence spectrum of the device with 1 as the emissive layer, b) relationship between...
Scheme 1: Synthetic pathway to 1 via imide formation and Suzuki–Miyaura cross-coupling.
