Synthesis of heterocycles based on azomethine ylides from α-amino acids (or amines) and carbonyl compounds
- Ekaterina V. Berezhnaya,
- Alexander I. Ponyaev,
- Vitali M. Boitsov and
- Alexander V. Stepakov
Beilstein J. Org. Chem. 2026, 22, 705–741, doi:10.3762/bjoc.22.55
Graphical Abstract
Scheme 1: Strategies for the preparation of pyrrolidine derivatives by (3 + 2) cycloaddition of azomethine yl...
Scheme 2: (3 + 2) Cycloaddition of iminoesters to dimethylmaleate.
Scheme 3: Cycloaddition of 1 with various dipolarophiles catalyzed by Ag(I)-L1.
Scheme 4: Cycloaddition of 1 with tert-butyl acrylate catalyzed by Ag(I)-L2.
Scheme 5: Cycloaddition of 1 with dimethyl maleate catalyzed by Cu(I)-L3.
Scheme 6: Cycloaddition of 1 with alkenes catalyzed by Zn(II)-t-Bu-BOX (L4).
Scheme 7: (3 + 2) Cycloaddition of iminoesters to acrylates.
Scheme 8: Catalytic double (3 + 2) cycloaddition to form pyrrolizidine derivatives.
Scheme 9: (3 + 2) Cycloaddition of iminoethers to vinyl phenyl sulfone.
Scheme 10: Regiodivergent and enantioselective synthesis of pyrrolidines 16 and 17.
Scheme 11: Substrate-controlled regioreversible "normal" and "incomplete" 1,3-dipolar cycloaddition.
Scheme 12: Enantioselective synthesis of exo-/endo-pyrrolidines.
Scheme 13: (3 + 2) Cycloaddition of iminoethers 21 to dipolarophiles 22–24.
Scheme 14: Synthesis of bicyclic pyrrolidines 29 from cyclopentene-1,3-diones.
Scheme 15: (3 + 2) Cycloaddition of aldimine esters and allyl alcohols using copper-ruthenium catalysis.
Scheme 16: Synthesis of 3,3-difluoro- and 3,3,4-trifluoropyrrolidine derivatives.
Scheme 17: Use of iminoesters from natural compounds and pharmaceuticals for reactions with 1,1-difluoro- and ...
Scheme 18: Reaction of iminoesters with 1,3-enynes.
Scheme 19: Synthesis of pyrrolidines from iminoesters and vinyl(hetero)arenes.
Scheme 20: Synthesis of exo-pyrrolidines 42 and 43.
Scheme 21: Enantioselective synthesis of heteroarylpyrrolidines 45 and 46.
Scheme 22: Catalytic reaction of (3 + 2) cycloaddition of imines 12 to benzofulvenes 47.
Scheme 23: Fullerene as a dipolarophile in (3 + 2) cycloaddition reactions.
Scheme 24: Asymmetric synthesis of optically active tetrasubstituted pyrrolidines 54.
Scheme 25: (3 + 2) Cycloaddition reaction of imines 55 and α,β-unsaturated aldehydes.
Scheme 26: Probable mechanism of enantioselective (3 + 2) cycloaddition of azomethine ylides to α,β-unsaturate...
Scheme 27: Cycloaddition between iminoesters 12 and sulfinylimines 58.
Scheme 28: (3 + 2) Cycloaddition between triarylideneacetylacetone and azomethine ylides in the presence of ti...
Scheme 29: Stereoselective synthesis of decahydropyrrolo[2,1,5-cd]indolizine 66.
Scheme 30: Synthesis of policyclic derivatives 71 and 72.
Scheme 31: Catalytic аsymmetric (3 + 2) сycloaddition of 2-pyridylimines with N-methylmaleimide.
Scheme 32: Catalytic аsymmetric (3 + 2) сycloaddition of 2-pyridylimines 1 with other dipolarophiles.
Scheme 33: Enantioselective (3 + 2) cycloaddition of silylimine with various dipolarophiles.
Scheme 34: Proposed mechanism of formation of pyrrolidines 78.
Scheme 35: Synthesis of polyheterocyclic pyrrolidines 82–91.
Scheme 36: Synthesis of spirocyclic (95) and fused (96) pyrrolidines.
Scheme 37: (3 + 2) Cycloaddition involving aromatic aldehydes 97, N-propargylmaleimide (98) and α-amino acids ...
Scheme 38: Synthesis of pyrrolizidines 106 and by-product 107.
Scheme 39: Iridium-catalyzed three-component cascade (3 + 2) cycloaddition.
Scheme 40: Intramolecular (3 + 2) cycloaddition of N-alkenylpyrrole-2-carbaldehyde 110 and α-amino acids.
Scheme 41: Three-component (3 + 2) cycloaddition involving fullerene.
Scheme 42: Four-component stereoselective one-pot synthesis of spiro-cycloadducts 119–122.
Scheme 43: Reactions of azomethine ylide 123 with cyclopropenes.
Scheme 44: Three-component reactions involving ninhydrin, cyclopropenes and acyclic α-amino acids.
Scheme 45: Reaction of cyclopropenes 138 with the N-protonated form of Ruhemann purple 137.
Scheme 46: Enantioselective (3 + 2) cycloaddition of azomethine ylides generated in situ from isatins and amin...
Scheme 47: (3 + 2) Cycloaddition of cyclohexenone 143, isatins 140 and aminomalonic diesters 141, catalyzed by...
Scheme 48: Enantioselective (3 + 2) cycloaddition of azomethine ylides generated in situ from isatins and amin...
Scheme 49: Enantioselective (3 + 2) cycloaddition of azomethine ylides generated in situ from isatins and benz...
Scheme 50: (3 + 2) Cycloaddition involving isatins, azetidine-2-carboxylic acid, maleimides or itaconimides.
Scheme 51: (3 + 2) Cycloaddition involving isatins, amino acids and tetraethylvinylidenebis(phosphonate).
Scheme 52: Synthesis of spirooxindoles 156 from triarylideneacetylacetones 155.
Scheme 53: Synthesis of spirooxindole derivatives 157–160.
Scheme 54: Synthesis of hybrid spiro-heterocycles 164–166.
Scheme 55: Formation of azomethine ylide from isatin and sarcosine.
Scheme 56: (3 + 2) Cycloaddition involving isatins, amino acids and trans-3-benzoylacrylic acid.
Scheme 57: Regioselective synthesis of spirooxindoles 170.
Scheme 58: Synthesis of hybrid spiro-heterocycles 86.
Scheme 59: (3 + 2) Cycloaddition involving acenaphthenequinones, amino acids and cyclopropenes.
Scheme 60: Synthesis of hybrid glyco-3-nitrochromane cycloadducts 179.
Scheme 61: Synthesis of spiro[indenoquinoxaline-(thia)pyrrolizidines] 90a.
Scheme 62: Three-component reactions of cyclopropenes, 11H-indeno[1,2-b]quinoxalin-11-onesand α-amino acids, s...
Scheme 63: Synthesis of hybrid glyco-3-nitrochromane cycloadducts 92.
Scheme 64: (3 + 2) Cycloaddition of 11H-benzo[4,5]imidazo[1,2-a]indol-11-one (189) with cyclopropenes and male...
Scheme 65: Diastereoselective synthesis of spiro derivatives of barbituric acid from alloxan 193, α-amino acid...
Scheme 66: Probable mechanism of formation of azomethine ylide from alloxan and ʟ-proline.
Scheme 67: Three-component reactions involving tryptanthrin 196, α-amino acids and cyclopropenes.
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).
Synthesis of bis-spirocyclic derivatives of 3-azabicyclo[3.1.0]hexane via cyclopropene cycloadditions to the stable azomethine ylide derived from Ruhemann's purple
- Alexander S. Filatov,
- Olesya V. Khoroshilova,
- Anna G. Larina,
- Vitali M. Boitsov and
- Alexander V. Stepakov
Beilstein J. Org. Chem. 2022, 18, 769–780, doi:10.3762/bjoc.18.77
Graphical Abstract
Scheme 1: Early studies concerning cyclopropene cycloadditions to azomethine ylides and cycloaddition reactio...
Scheme 2: The pilot experiment aimed at studying the cycloaddition reaction between the protonated form of Ru...
Scheme 3: Synthesis of meso-3'-azadispiro[indene-2,2'-bicyclo[3.1.0]hexane-4',2''-indene] derivatives 3b–g vi...
Figure 1: ORTEP representation of the molecular structure of 3e.
Scheme 4: The reaction of protonated Ruhemann's purple (1) with 3-methyl-3-phenylcyclopropene (2j).
Scheme 5: Attempts to carry out the cycloaddition reactions between 3,3-disubstituted cyclopropenes 2k,l and ...
Scheme 6: The reactions of protonated Ruhemann's purple (1) with unstable cyclopropenes 2m–p.
Scheme 7: The acid–base reaction of Ruhemann's purple with hydrochloric acid and relative Gibbs free energy c...
Scheme 8: Plausible mechanism of the 1,3-DC reaction of protonated Ruhemann's purple (1) with 3-methyl-3-phen...
Scheme 9: Plausible mechanism of the 1,3-DC reaction of protonated Ruhemann's purple (1) with 1-chloro-2-phen...
