An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

Marcus Baumann and
Ian R. Baxendale

Review
Published 30 Oct 2013

696 Accesses

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Album
1. Graphical Abstract
2. Scheme 1: Scaled industrial processes for the synthesis of simple pyridines.
  
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3. Scheme 2: Synthesis of nicotinic acid from 2-methyl-5-ethylpyridine (1.11).
  
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4. Scheme 3: Synthesis of 3-picoline and nicotinic acid.
  
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5. Scheme 4: Synthesis of 3-picoline from 2-methylglutarodinitrile 1.19.
  
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6. Scheme 5: Picoline-based synthesis of clarinex (no yields reported).
  
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7. Scheme 6: Mode of action of proton-pump inhibitors and structures of the API’s.
  
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8. Scheme 7: Hantzsch-like route towards the pyridine rings in common proton pump inhibitors.
  
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9. Figure 1: Structures of rosiglitazone (1.40) and pioglitazone (1.41).
  
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10. Scheme 8: Synthesis of rosiglitazone.
  
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11. Scheme 9: Syntheses of 2-pyridones.
  
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12. Scheme 10: Synthesis and mechanism of 2-pyrone from malic acid.
  
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13. Scheme 11: Polymer-assisted synthesis of rosiglitazone.
  
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14. Scheme 12: Synthesis of pioglitazone.
  
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15. Scheme 13: Meerwein arylation reaction towards pioglitazone.
  
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16. Scheme 14: Route towards pioglitazone utilising tyrosine.
  
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17. Scheme 15: Route towards pioglitazone via Darzens ester formation.
  
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18. Scheme 16: Syntheses of the thiazolidinedione moiety.
  
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19. Scheme 17: Synthesis of etoricoxib utilising Negishi and Stille cross-coupling reactions.
  
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20. Scheme 18: Synthesis of etoricoxib via vinamidinium condensation.
  
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21. Figure 2: Structures of nalidixic acid, levofloxacin and moxifloxacin.
  
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22. Scheme 19: Synthesis of moxifloxacin.
  
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23. Scheme 20: Synthesis of (S,S)-2,8-diazabicyclo[4.3.0]nonane 1.105.
  
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24. Scheme 21: Synthesis of levofloxacin.
  
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25. Scheme 22: Alternative approach to the levofloxacin core 1.125.
  
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26. Figure 3: Structures of nifedipine, amlodipine and clevidipine.
  
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27. Scheme 23: Mg₃N₂-mediated synthesis of nifedipine.
  
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28. Scheme 24: Synthesis of rac-amlodipine as besylate salt.
  
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29. Scheme 25: Aza Diels–Alder approach towards amlodipine.
  
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30. Scheme 26: Routes towards clevidipine.
  
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31. Figure 4: Examples of piperidine containing drugs.
  
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32. Figure 5: Discovery of tiagabine based on early leads.
  
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33. Scheme 27: Synthetic sequences to tiagabine.
  
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34. Figure 6: Structures of solifenacin (2.57) and muscarine (2.58).
  
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35. Scheme 28: Enantioselective synthesis of solifenacin.
  
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36. Figure 7: Structures of DPP-4 inhibitors of the gliptin-type.
  
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37. Scheme 29: Formation of inactive diketopiperazines from cis-rotameric precursors.
  
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38. Figure 8: Co-crystal structure of carmegliptin bound in the human DPP-4 active site (PDB 3kwf).
  
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39. Scheme 30: Improved route to carmegliptin.
  
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40. Figure 9: Structures of lamivudine and zidovudine.
  
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41. Scheme 31: Typical routes accessing uracil, thymine and cytosine.
  
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42. Scheme 32: Coupling between pyrimidones and riboses via the Vorbrüggen nucleosidation.
  
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43. Scheme 33: Synthesis of lamivudine.
  
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44. Scheme 34: Synthesis of raltegravir.
  
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45. Scheme 35: Mechanistic studies on the formation of 3.22.
  
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46. Figure 10: Structures of selected pyrimidine containing drugs.
  
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47. Scheme 36: General preparation of pyrimidines and dihydropyrimidones.
  
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48. Scheme 37: Synthesis of imatinib.
  
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49. Scheme 38: Flow synthesis of imatinib.
  
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50. Scheme 39: Syntheses of erlotinib.
  
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51. Scheme 40: Synthesis of erlotinib proceeding via Dimroth rearrangement.
  
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52. Scheme 41: Synthesis of lapatinib.
  
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53. Scheme 42: Synthesis of rosuvastatin.
  
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54. Scheme 43: Alternative preparation of the key aldehyde towards rosuvastatin.
  
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55. Figure 11: Structure comparison between nicotinic acetylcholine receptor agonists.
  
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56. Scheme 44: Syntheses of varenicline and its key building block 4.5.
  
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57. Scheme 45: Synthetic access to eszopiclone and brimonidine via quinoxaline intermediates.
  
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58. Figure 12: Bortezomib bound in an active site of the yeast 20S proteasome ([114], pdb 2F16).
  
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59. Scheme 46: Asymmetric synthesis of bortezomib.
  
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60. Figure 13: Structures of some prominent piperazine containing drugs.
  
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61. Figure 14: Structural comparison between the core of aplaviroc (4.35) and a type-1 β-turn (4.36).
  
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62. Scheme 47: Examplary synthesis of an aplaviroc analogue via the Ugi-MCR.
  
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63. Scheme 48: Syntheses of azelastine (5.1).
  
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64. Figure 15: Structures of captopril, enalapril and cilazapril.
  
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65. Scheme 49: Synthesis of cilazapril.
  
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66. Figure 16: Structures of lamotrigine, ceftriaxone and azapropazone.
  
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67. Scheme 50: Synthesis of lamotrigine.
  
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68. Scheme 51: Alternative synthesis of lamotrigine (no yields reported).
  
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69. Figure 17: Structural comparison between imiquimod and the related adenosine nucleoside.
  
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70. Scheme 52: Conventional synthesis of imiquimod (no yields reported).
  
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71. Scheme 53: Synthesis of imiquimod.
  
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72. Scheme 54: Synthesis of imiquimod via tetrazole formation (not all yields reported).
  
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73. Figure 18: Structures of various anti HIV-medications.
  
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74. Scheme 55: Synthesis of abacavir.
  
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75. Figure 19: Structures of diazepam compared to modern replacements.
  
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76. Scheme 56: Synthesis of ocinaplon.
  
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77. Scheme 57: Access to zaleplon and indiplon.
  
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78. Scheme 58: Different routes towards the required N-methylpyrazole 6.65 of sildenafil.
  
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79. Scheme 59: Polymer-supported reagents in the synthesis of key aminopyrazole 6.72.
  
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80. Scheme 60: Early synthetic route to sildenafil.
  
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81. Scheme 61: Convergent preparations of sildenafil.
  
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82. Figure 20: Comparison of the structures of sildenafil, tadalafil and vardenafil.
  
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83. Scheme 62: Short route to imidazotriazinones.
  
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84. Scheme 63: Alternative route towards vardenafils core imidazotriazinone (6.95).
  
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85. Scheme 64: Bayer’s approach to the vardenafil core.
  
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86. Scheme 65: Large scale synthesis of vardenafil.
  
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87. Scheme 66: Mode of action of temozolomide (6.105) as methylating agent.
  
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88. Scheme 67: Different routes to temozolomide.
  
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89. Scheme 68: Safer route towards temozolomide.
  
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90. Figure 21: Some unreported heterocyclic scaffolds in top market drugs.
  
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Beilstein J. Org. Chem. 2013, 9, 2265–2319, doi:10.3762/bjoc.9.265

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Breaking paracyclophane: the unexpected formation of non-symmetric disubstituted nitro[2.2]metaparacyclophanes

Suraj Patel,
Tyson N. Dais,
Paul G. Plieger and
Gareth J. Rowlands

Full Research Paper
Published 29 Jun 2021

553 Accesses

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Album
1. Graphical Abstract
2. Figure 1: The common [2.2]cyclophanes.
  
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3. Scheme 1: Nitration of [2.2]paracyclophane (1) and the synthesis of 4-hydroxy-5-nitro[2.2]metaparacyclophane (...
  
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4. Figure 2: Crystal structure of 5. Ellipsoids are drawn at a 50% probability level [63-66].
  
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5. Figure 3: Crystal structure of 6. Ellipsoids are drawn at a 50% probability level [63].
  
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6. Scheme 2: Possible mechanism for the formation of [2.2]metaparacyclophane 5 and cyclohexadienone cyclophane 6...
  
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7. Scheme 3: Conjugate addition of methanol and subsequent elimination.
  
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8. Figure 4: Crystal structure of 14. Ellipsoids are drawn at a 50% probability level [63].
  
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9. Figure 5: Crystal structure of 15. Ellipsoids are drawn at a 50% probability level [63].
  
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10. Figure 6: Possible origin of stereoselectivity.
  
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Beilstein J. Org. Chem. 2021, 17, 1518–1526, doi:10.3762/bjoc.17.109

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A straightforward conversion of 1,4-quinones into polycyclic pyrazoles via [3 + 2]-cycloaddition with fluorinated nitrile imines

Greta Utecht-Jarzyńska,
Karolina Nagła,
Grzegorz Mlostoń,
Heinz Heimgartner,
Marcin Palusiak and
Marcin Jasiński

Full Research Paper
Published 28 Jun 2021

498 Accesses

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Album
1. Graphical Abstract
2. Figure 1: Structures of exemplary benzo- and heteroaromatic fused 1,4-quinone drugs and natural products.
  
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3. Scheme 1: First [3 + 2]-cycloaddition of 1,4-naphthoquinone (1a) with intermediate nitrile imine 2, generated...
  
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4. Scheme 2: Selected applications of trifluoroacetonitrile imines 7 in the synthesis of S-containing 5- and 6-m...
  
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5. Scheme 3: Synthesis of [3 + 2]-cycloadducts 9a–l derived from CF₃-substituted nitrile imines 7a–h and 1,4-qui...
  
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6. Figure 2: X-ray structure of 3-trifluoromethylpyrazole derivative 9d. The labeling scheme of the asymmetric u...
  
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7. Scheme 4: Thermal elimination of MeOH from the initial [3 + 2]-cycloadduct of 1d and nitrile imine 7d generat...
  
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8. Scheme 5: Formation of the thermally stable, initially formed [3 + 2]-cycloadduct 10c obtained from 1e and ni...
  
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9. Figure 3: Electronic absorption spectra for selected a) naphthoquinone-derived (9c, 9d, 9g) and b) anthraquin...
  
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Beilstein J. Org. Chem. 2021, 17, 1509–1517, doi:10.3762/bjoc.17.108

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Copper-mediated oxidative C−H/N−H activations with alkynes by removable hydrazides

Feng Xiong,
Bo Li,
Chenrui Yang,
Liang Zou,
Wenbo Ma,
Linghui Gu,
Ruhuai Mei and
Lutz Ackermann

Full Research Paper
Published 08 Jul 2021

461 Accesses

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Album
1. Graphical Abstract
2. Figure 1: Assembly of 3-methyleneisoindolin-1-one via 3d transition metal-mediated/catalyzed oxidative C−H/N−...
  
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3. Scheme 1: Copper-mediated oxidative C−H/N−H functionalization of hydrazides 1 with ethynylbenzene (2a).
  
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4. Scheme 2: Copper-mediated oxidative C−H/N−H functionalization of 1 with alkynes 2.
  
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5. Scheme 3: Decaboxylative C−H/N−H activation and cleavage of the directing group.
  
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6. Scheme 4: Summary of key mechanistic findings.
  
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7. Scheme 5: Proposed reaction pathway.
  
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Beilstein J. Org. Chem. 2021, 17, 1591–1599, doi:10.3762/bjoc.17.113

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Recent advances in the application of isoindigo derivatives in materials chemistry

Andrei V. Bogdanov and
Vladimir F. Mironov

Review
Published 06 Jul 2021

459 Accesses

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Album
1. Graphical Abstract
2. Scheme 1: Representatives of isomeric bisoxindoles.
  
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3. Scheme 2: Isoindigo-based OSCs with the best efficiency.
  
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4. Scheme 3: Monoisoindigos with preferred 6,6'-substitution.
  
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5. Scheme 4: Possibility of aromatic–quinoid structural transition.
  
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6. Scheme 5: Isoindigo structures with incorporated acceptor nitrogen heterocycles.
  
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7. Scheme 6: Monoisoindigos bearing pyrenyl substituents.
  
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8. Scheme 7: p-Alkoxyphenylene-embedded thienylisoindigo with different acceptor anchor units.
  
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9. Scheme 8: Nonfullerene OSC based on perylene diimide-derived isoindigo.
  
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10. Scheme 9: Isoindigo as an additive in all-polymer OSCs.
  
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11. Scheme 10: Bisisoindigos with different linker structures.
  
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12. Scheme 11: Nonthiophene oligomeric monoisoindigos for OSCs.
  
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13. Scheme 12: The simplest examples of polymers with a monothienylisoindigo monomeric unit.
  
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14. Scheme 13: Monothienylisoindigos bearing π-extended electron-donor backbones.
  
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15. Scheme 14: Role of fluorination and the molecular weight on OSC efficiency on the base of the bithiopheneisoin...
  
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16. Scheme 15: Trithiopheneisoindigo polymers with variation in the substituent structure.
  
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17. Scheme 16: Polymeric thienyl-linked bisisoindigos for OSCs.
  
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18. Scheme 17: Isoindigo bearing the thieno[3,2-b]thiophene structural motif as donor component of OSCs.
  
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19. Scheme 18: Thienylisoindigos with incorporated aromatic unit.
  
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20. Scheme 19: One-component nonfullerene OSCs on the base of isoindigo.
  
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21. Scheme 20: Isoindigo-based nonthiophene aza aromatic polymers as acceptor components of OSCs.
  
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22. Scheme 21: Polymers with isoindigo substituent as side-chain photon trap.
  
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23. Scheme 22: Isoindigo derivatives for OFET technology with the best mobility.
  
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24. Scheme 23: Monoisoindigos as low-molecular-weight semiconductors.
  
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25. Scheme 24: Polymeric bithiopheneisoindigos for OFET creation.
  
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26. Scheme 25: Fluorination as a tool to improve isoindigo-based OFET devices.
  
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27. Scheme 26: Diversely DPP–isoindigo-conjugated polymers for OFETs.
  
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28. Scheme 27: Isoindigoid homopolymers with differing rigidity.
  
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29. Scheme 28: Isoindigo-based materials with extended π-conjugation.
  
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30. Scheme 29: Poly(isoindigothiophene) compounds as sensors for ammonia.
  
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31. Scheme 30: Sensor devices based on poly(isoindigoaryl) compounds.
  
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32. Scheme 31: Isoindigo polymers for miscellaneous applications.
  
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33. Scheme 32: Mono-, rod-like, and polymeric isoindigos as agents for photoacoustic and photothermal cancer thera...
  
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Beilstein J. Org. Chem. 2021, 17, 1533–1564, doi:10.3762/bjoc.17.111

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Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

Thiago S. Silva and
Fernando Coelho

Review
Published 07 Jul 2021

457 Accesses

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Album
1. Graphical Abstract
2. Figure 1: Some examples of natural products and drugs containing quaternary carbon centers.
  
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3. Scheme 1: Simplified mechanism for olefin hydrofunctionalization using an electrophilic transition metal as a...
  
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4. Scheme 2: Selected examples of quaternary carbon centers formed by the intramolecular hydroalkylation of β-di...
  
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5. Scheme 3: Control experiments and the proposed mechanism for the Pd(II)-catalyzed intermolecular hydroalkylat...
  
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6. Scheme 4: Intermolecular olefin hydroalkylation of less reactive ketones under Pd(II) catalysis using HCl as ...
  
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7. Scheme 5: A) Selected examples of Pd(II)-mediated quaternary carbon center synthesis by intermolecular hydroa...
  
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8. Scheme 6: Selected examples of quaternary carbon center synthesis by gold(III) catalysis. This is the first r...
  
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9. Scheme 7: Selected examples of inter- (A) and intramolecular (B) olefin hydroalkylations promoted by a silver...
  
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10. Scheme 8: A) Intermolecular hydroalkylation of N-alkenyl β-ketoamides under Au(I) catalysis in the synthesis ...
  
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11. Scheme 9: Asymmetric pyrrolidine synthesis through intramolecular hydroalkylation of α-substituted N-alkenyl ...
  
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12. Scheme 10: Proposed mechanism for the chiral gold(I) complex promotion of the intermolecular olefin hydroalkyl...
  
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13. Scheme 11: Selected examples of carbon quaternary center synthesis by gold and evidence of catalytic system pa...
  
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14. Scheme 12: Synthesis of a spiro compound via an aza-Michael addition/olefin hydroalkylation cascade promoted b...
  
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15. Scheme 13: A selected example of quaternary carbon center synthesis using an Fe(III) salt as a catalyst for th...
  
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16. Scheme 14: Intermolecular hydroalkylation catalyzed by a cationic iridium complex (Fuji (2019) [47]).
  
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17. Scheme 15: Generic example of an olefin hydrofunctionalization via MHAT (Shenvi (2016) [51]).
  
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18. Scheme 16: The first examples of olefin hydrofunctionalization run under neutral conditions (Mukaiyama (1989) [56]...
  
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19. Scheme 17: A) Aryl olefin dimerization catalyzed by vitamin B₁₂ and triggered by HAT. B) Control experiment to...
  
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20. Scheme 18: Generic example of MHAT diolefin cycloisomerization and possible competitive pathways. Shenvi (2014...
  
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21. Scheme 19: Selected examples of the MHAT-promoted cycloisomerization reaction of unactivated olefins leading t...
  
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22. Scheme 20: Regioselective carbocyclizations promoted by an MHAT process (Norton (2008) [76]).
  
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23. Scheme 21: Selected examples of quaternary carbon centers synthetized via intra- (A) and intermolecular (B) MH...
  
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24. Scheme 22: A) Proposed mechanism for the Fe(III)/PhSiH₃-promoted radical conjugate addition between olefins an...
  
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25. Scheme 23: Examples of cascade reactions triggered by HAT for the construction of trans-decalin backbone uniti...
  
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26. Scheme 24: A) Selected examples of the MHAT-promoted radical conjugate addition between olefins and p-quinone ...
  
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27. Scheme 25: A) MHAT triggered radical conjugate addition/E1cB/lactonization (in some cases) cascade between ole...
  
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28. Scheme 26: A) Spirocyclization promoted by Fe(III) hydroalkylation of unactivated olefins. B) Simplified mecha...
  
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29. Scheme 27: A) Selected examples of the construction of a carbon quaternary center by the MHAT-triggered radica...
  
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30. Scheme 28: Hydromethylation of unactivated olefins under iron-mediated MHAT (Baran (2015) [95]).
  
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31. Scheme 29: The hydroalkylation of unactivated olefins via iron-mediated reductive coupling with hydrazones (Br...
  
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32. Scheme 30: Selected examples of the Co(II)-catalyzed bicyclization of dialkenylarenes through the olefin hydro...
  
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33. Scheme 31: Proposed mechanism for the bicyclization of dialkenylarenes triggered by a MHAT process (Vanderwal ...
  
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34. Scheme 32: Enantioconvergent cross-coupling between olefins and tertiary halides (Fu (2018) [108]).
  
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35. Scheme 33: Proposed mechanism for the Ni-catalyzed cross-coupling reaction between olefins and tertiary halide...
  
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36. Scheme 34: Proposed catalytic cycles for a MHAT/Ni cross-coupling reaction between olefins and halides (Shenvi...
  
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37. Scheme 35: Selected examples of the hydroalkylation of olefins by a dual catalytic Mn/Ni system (Shenvi (2019) ...
  
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38. Scheme 36: A) Selected examples of quaternary carbon center synthesis by reductive atom transfer; TBC: 4-tert-...
  
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39. Scheme 37: A) Selected examples of quaternary carbon centers synthetized by radical addition to unactivated ol...
  
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40. Scheme 38: A) Selected examples of organophotocatalysis-mediated radical polyene cyclization via a PET process...
  
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41. Scheme 39: A) Sc(OTf)₃-mediated carbocyclization approach for the synthesis of vicinal quaternary carbon cente...
  
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42. Scheme 40: Scope of the Lewis acid-catalyzed methallylation of electron-rich styrenes. Method A: B(C₆F₅)₃ (5.0...
  
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43. Scheme 41: The proposed mechanism for styrene methallylation (Oestreich (2019) [123]).
  
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Beilstein J. Org. Chem. 2021, 17, 1565–1590, doi:10.3762/bjoc.17.112

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A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

Guido Gambacorta,
James S. Sharley and
Ian R. Baxendale

Review
Published 18 May 2021

439 Accesses

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Album
1. Graphical Abstract
2. Figure 1: Representative shares of the global F&F market (2018) segmented on their applications [1].
  
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3. Figure 2: General structure of an international fragrance company [2].
  
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4. Figure 3: The Michael Edwards fragrance wheel.
  
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5. Figure 4: Examples of oriental (1–3), woody (4–7), fresh (8–10), and floral (11 and 12) notes.
  
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6. Figure 5: A basic depiction of batch vs flow.
  
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7. Scheme 1: Examples of reactions for which flow processing outperforms batch.
  
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8. Scheme 2: Some industrially important aldol-based transformations.
  
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9. Scheme 3: Biphasic continuous aldol reactions of acetone and various aldehydes.
  
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10. Scheme 4: Aldol synthesis of 43 in flow using LiHMDS as the base.
  
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11. Scheme 5: A semi-continuous synthesis of doravirine (49) involving a key aldol reaction.
  
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12. Scheme 6: Enantioselective aldol reaction using 5-(pyrrolidin-2-yl)tetrazole (51) as catalyst in a microreact...
  
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13. Scheme 7: Gröger's example of asymmetric aldol reaction in aqueous media.
  
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14. Figure 6: Immobilised reagent column reactor types.
  
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15. Scheme 8: Photoinduced thiol–ene coupling preparation of silica-supported 5-(pyrrolidin-2-yl)tetrazole 63 and...
  
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16. Scheme 9: Continuous-flow approach for enantioselective aldol reactions using the supported catalyst 67.
  
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17. Scheme 10: Ötvös’ employment of a solid-supported peptide aldol catalyst in flow.
  
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18. Scheme 11: The use of proline tetrazole packed in a column for aldol reaction between cyclohexanone (65) and 2...
  
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19. Scheme 12: Schematic diagram of an aminosilane-grafted Si-Zr-Ti/PAI-HF reactor for continuous-flow aldol and n...
  
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20. Scheme 13: Continuous-flow condensation for the synthesis of the intermediate 76 to nabumetone (77) and Microi...
  
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21. Scheme 14: Synthesis of ψ-Ionone (80) in continuous-flow via aldol condensation between citral (79) and aceton...
  
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22. Scheme 15: Synthesis of β-methyl-ionones (83) from citral (79) in flow. The steps are separately described, an...
  
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23. Scheme 16: Continuous-flow synthesis of 85 from 84 described by Gavriilidis et al.
  
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24. Scheme 17: Continuous-flow scCO2 apparatus for the synthesis of 2-methylpentanal (87) and the self-condensed u...
  
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25. Scheme 18: Chen’s two-step flow synthesis of coumarin (90).
  
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26. Scheme 19: Pechmann condensation for the synthesis of 7-hydroxyxcoumarin (93) in flow. The setup extended to c...
  
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27. Scheme 20: Synthesis of the dihydrojasmonate 35 exploiting nitro derivative proposed by Ballini et al.
  
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28. Scheme 21: Silica-supported amines as heterogeneous catalyst for nitroaldol condensation in flow.
  
  Jump to Scheme 21
29. Scheme 22: Flow apparatus for the nitroaldol condensation of p-hydroxybenzaldehyde (102) to nitrostyrene 103 a...
  
  Jump to Scheme 22
30. Scheme 23: Nitroaldol reaction of 64 to 105 employing a quaternary ammonium functionalised PANF.
  
  Jump to Scheme 23
31. Scheme 24: Enantioselective nitroaldol condensation for the synthesis of 108 under flow conditions.
  
  Jump to Scheme 24
32. Scheme 25: Enatioselective synthesis of 1,2-aminoalcohol 110 via a copper-catalysed nitroaldol condensation.
  
  Jump to Scheme 25
33. Scheme 26: Examples of Knoevenagel condensations applied for fragrance components.
  
  Jump to Scheme 26
34. Scheme 27: Flow apparatus for Knoevenagel condensation described in 1989 by Venturello et al.
  
  Jump to Scheme 27
35. Scheme 28: Knoevenagel reaction using a coated multichannel membrane microreactor.
  
  Jump to Scheme 28
36. Scheme 29: Continuous-flow apparatus for Knoevenagel condensation employing sugar cane bagasse as support deve...
  
  Jump to Scheme 29
37. Scheme 30: Knoevenagel reaction for the synthesis of 131–135 in flow using an amine-functionalised silica gel. ...
  
  Jump to Scheme 30
38. Scheme 31: Continuous-flow synthesis of compound 137, a key intermediate for the synthesis of pregabalin (138)...
  
  Jump to Scheme 31
39. Scheme 32: Continuous solvent-free apparatus applied for the synthesis of compounds 140–143 using a TSE. Throu...
  
  Jump to Scheme 32
40. Scheme 33: Lewis et al. developed a spinning disc reactor for Darzens condensation of 144 and a ketone to furn...
  
  Jump to Scheme 33
41. Scheme 34: Some key industrial applications of conjugate additions in the F&F industry.
  
  Jump to Scheme 34
42. Scheme 35: Continuous-flow synthesis of 4-(2-hydroxyethyl)thiomorpholine 1,1-dioxide (156) via double conjugat...
  
  Jump to Scheme 35
43. Scheme 36: Continuous-flow system for Michael addition using CsF on alumina as the catalyst.
  
  Jump to Scheme 36
44. Scheme 37: Calcium chloride-catalysed asymmetric Michael addition using an immobilised chiral ligand.
  
  Jump to Scheme 37
45. Scheme 38: Continuous multistep synthesis for the preparation of (R)-rolipram (173). Si-NH₂: primary amine-fun...
  
  Jump to Scheme 38
46. Scheme 39: Continuous-flow Michael addition using ion exchange resin Amberlyst^® A26.
  
  Jump to Scheme 39
47. Scheme 40: Preparation of the heterogeneous catalyst 181 developed by Paixão et al. exploiting Ugi multicompon...
  
  Jump to Scheme 40
48. Scheme 41: Continuous-flow system developed by the Paixão’s group for the preparation of Michael asymmetric ad...
  
  Jump to Scheme 41
49. Scheme 42: Continuous-flow synthesis of nitroaldols catalysed by supported catalyst 184 developed by Wennemers...
  
  Jump to Scheme 42
50. Scheme 43: Heterogenous polystyrene-supported catalysts developed by Pericàs and co-workers.
  
  Jump to Scheme 43
51. Scheme 44: PANF-supported pyrrolidine catalyst for the conjugate addition of cyclohexanone (65) and trans-β-ni...
  
  Jump to Scheme 44
52. Scheme 45: Synthesis of (−)-paroxetine precursor 195 developed by Ötvös, Pericàs, and Kappe.
  
  Jump to Scheme 45
53. Scheme 46: Continuous-flow approach for the 5-step synthesis of (−)-oseltamivir (201) as devised by Hayashi an...
  
  Jump to Scheme 46
54. Scheme 47: Continuous-flow enzyme-catalysed Michael addition.
  
  Jump to Scheme 47
55. Scheme 48: Continuous-flow copper-catalysed 1,4 conjugate addition of Grignard reagents to enones. Reprinted w...
  
  Jump to Scheme 48
56. Scheme 49: A collection of commonly encountered hydrogenation reactions.
  
  Jump to Scheme 49
57. Figure 7: The ThalesNano H-Cube^® continuous-flow hydrogenator.
  
  Jump to Figure 7
58. Scheme 50: Chemoselective reduction of an α,β-unsaturated ketone using the H-Cube^® reactor.
  
  Jump to Scheme 50
59. Scheme 51: Incorporation of Lindlar’s catalyst into the H-Cube^® reactor for the reduction of an alkyne.
  
  Jump to Scheme 51
60. Scheme 52: Continuous-flow semi-hydrogenation of alkyne 208 to 209 using SACs with H-Cube^® system.
  
  Jump to Scheme 52
61. Figure 8: The standard setups for tube-in-tube gas–liquid reactor units.
  
  Jump to Figure 8
62. Scheme 53: Homogeneous hydrogenation of olefins using a tube-in-tube reactor setup.
  
  Jump to Scheme 53
63. Scheme 54: Recyclable heterogeneous flow hydrogenation system.
  
  Jump to Scheme 54
64. Scheme 55: Leadbeater’s reverse tube-in-tube hydrogenation system for olefin reductions.
  
  Jump to Scheme 55
65. Scheme 56: a) Hydrogenation using a Pd-immobilised microchannel reactor (MCR) and b) a representation of the i...
  
  Jump to Scheme 56
66. Scheme 57: Hydrogenation of alkyne 238 exploiting segmented flow in a Pd-immobilised capillary reactor.
  
  Jump to Scheme 57
67. Scheme 58: Continuous hydrogenation system for the preparation of cyrene (241) from (−)-levoglucosenone (240).
  
  Jump to Scheme 58
68. Scheme 59: Continuous hydrogenation system based on CSMs developed by Hornung et al.
  
  Jump to Scheme 59
69. Scheme 60: Chemoselective reduction of carbonyls (ketones over aldehydes) in flow.
  
  Jump to Scheme 60
70. Scheme 61: Continuous system for the semi-hydrogenation of 256 and 258, developed by Galarneau et al.
  
  Jump to Scheme 61
71. Scheme 62: Continuous synthesis of biodiesel fuel 261 from lignin-derived furfural acetone (260).
  
  Jump to Scheme 62
72. Scheme 63: Continuous synthesis of γ-valerolacetone (263) via CTH developed by Pineda et al.
  
  Jump to Scheme 63
73. Scheme 64: Continuous hydrogenation of lignin-derived biomass (products 265, 266, and 267) using a sustainable...
  
  Jump to Scheme 64
74. Scheme 65: Ru/C or Rh/C-catalysed hydrogenation of arene in flow as developed by Sajiki et al.
  
  Jump to Scheme 65
75. Scheme 66: Polysilane-immobilized Rh–Pt-catalysed hydrogenation of arenes in flow by Kobayashi et al.
  
  Jump to Scheme 66
76. Scheme 67: High-pressure in-line mixing of H₂ for the asymmetric reduction of 278 at pilot scale with a 73 L p...
  
  Jump to Scheme 67
77. Figure 9: Picture of the PFR employed at Eli Lilly & Co. for the continuous hydrogenation of 278 [287]. Reprinted ...
  
  Jump to Figure 9
78. Scheme 68: Continuous-flow asymmetric hydrogenation using Oppolzer's sultam 280 as chiral auxiliary.
  
  Jump to Scheme 68
79. Scheme 69: Some examples of industrially important oxidation reactions in the F&F industry. CFL: compact fluor...
  
  Jump to Scheme 69
80. Scheme 70: Gold-catalysed heterogeneous oxidation of alcohols in flow.
  
  Jump to Scheme 70
81. Scheme 71: Uozumi’s ARP-Pt flow oxidation protocol.
  
  Jump to Scheme 71
82. Scheme 72: High-throughput screening of aldehyde oxidation in flow using an in-line GC.
  
  Jump to Scheme 72
83. Scheme 73: Permanganate-mediated Nef oxidation of nitroalkanes in flow with the use of in-line sonication to p...
  
  Jump to Scheme 73
84. Scheme 74: Continuous-flow aerobic anti-Markovnikov Wacker oxidation.
  
  Jump to Scheme 74
85. Scheme 75: Continuous-flow oxidation of 2-benzylpyridine (312) using air as the oxidant.
  
  Jump to Scheme 75
86. Scheme 76: Continuous-flow photo-oxygenation of monoterpenes.
  
  Jump to Scheme 76
87. Scheme 77: A tubular reactor design for flow photo-oxygenation.
  
  Jump to Scheme 77
88. Scheme 78: Glucose oxidase (GOx)-mediated continuous oxidation of glucose using compressed air and the FFMR re...
  
  Jump to Scheme 78
89. Scheme 79: Schematic continuous-flow sodium hypochlorite/TEMPO oxidation of alcohols.
  
  Jump to Scheme 79
90. Scheme 80: Oxidation using immobilised TEMPO (344) was developed by McQuade et al.
  
  Jump to Scheme 80
91. Scheme 81: General protocol for the bleach/catalytic TBAB oxidation of aldehydes and alcohols.
  
  Jump to Scheme 81
92. Scheme 82: Continuous-flow PTC-assisted oxidation using hydrogen peroxide. The process was easily scaled up by...
  
  Jump to Scheme 82
93. Scheme 83: Continuous-flow epoxidation of cyclohexene (348) and in situ preparation of m-CPBA.
  
  Jump to Scheme 83
94. Scheme 84: Continuous-flow epoxidation using DMDO as oxidant.
  
  Jump to Scheme 84
95. Scheme 85: Mukayama aerobic epoxidation optimised in flow mode by the Favre-Réguillon group.
  
  Jump to Scheme 85
96. Scheme 86: Continuous-flow asymmetric epoxidation of derivatives of 359 exploiting a biomimetic iron catalyst.
  
  Jump to Scheme 86
97. Scheme 87: Continuous-flow enzymatic epoxidation of alkenes developed by Watts et al.
  
  Jump to Scheme 87
98. Scheme 88: Engineered multichannel microreactor for continuous-flow ozonolysis of 366.
  
  Jump to Scheme 88
99. Scheme 89: Continuous-flow synthesis of the vitamin D precursor 368 using multichannel microreactors. MFC: mas...
  
  Jump to Scheme 89
100. Scheme 90: Continuous ozonolysis setup used by Kappe et al. for the synthesis of various substrates employing ...
  
  Jump to Scheme 90
101. Scheme 91: Continuous-flow apparatus for ozonolysis as developed by Ley et al.
  
  Jump to Scheme 91
102. Scheme 92: Continuous-flow ozonolysis for synthesis of vanillin (2) using a film-shear flow reactor.
  
  Jump to Scheme 92
103. Scheme 93: Examples of preparative methods for ajoene (386) and allicin (388).
  
  Jump to Scheme 93
104. Scheme 94: Continuous-flow oxidation of thioanisole (389) using styrene-based polymer-supported peroxytungstat...
  
  Jump to Scheme 94
105. Scheme 95: Continuous oxidation of thiosulfinates using Oxone^®-packed reactor.
  
  Jump to Scheme 95
106. Scheme 96: Continuous-flow electrochemical oxidation of thioethers.
  
  Jump to Scheme 96
107. Scheme 97: Continuous-flow oxidation of 400 to cinnamophenone (235).
  
  Jump to Scheme 97
108. Scheme 98: Continuous-flow synthesis of dehydrated material 401 via oxidation of methyl dihydrojasmonate (33).
  
  Jump to Scheme 98
109. Scheme 99: Some industrially important transformations involving Grignard reagents.
  
  Jump to Scheme 99
110. Scheme 100: Grachev et al. apparatus for continuous preparation of Grignard reagents.
  
  Jump to Scheme 100
111. Scheme 101: Example of fluidized Mg bed reactor with NMR spectrometer as on-line monitoring system.
  
  Jump to Scheme 101
112. Scheme 102: Continuous-flow synthesis of Grignard reagents and subsequent quenching reaction.
  
  Jump to Scheme 102
113. Figure 10: Membrane-based, liquid–liquid separator with integrated pressure control [52]. Adapted with permission ...
  
  Jump to Figure 10
114. Scheme 103: Continuous-flow synthesis of 458, an intermediate to fluconazole (459).
  
  Jump to Scheme 103
115. Scheme 104: Continuous-flow synthesis of ketones starting from benzoyl chlorides.
  
  Jump to Scheme 104
116. Scheme 105: A Grignard alkylation combining CSTR and PFR technologies with in-line infrared reaction monitoring....
  
  Jump to Scheme 105
117. Scheme 106: Continuous-flow preparation of 469 from Grignard addition of methylmagnesium bromide.
  
  Jump to Scheme 106
118. Scheme 107: Continuous-flow synthesis of Grignard reagents 471.
  
  Jump to Scheme 107
119. Scheme 108: Preparation of the Grignard reagent 471 using CSTR and the continuous process for synthesis of the ...
  
  Jump to Scheme 108
120. Scheme 109: Continuous process for carboxylation of Grignard reagents in flow using tube-in-tube technology.
  
  Jump to Scheme 109
121. Scheme 110: Continuous synthesis of propargylic alcohols via ethynyl-Grignard reagent.
  
  Jump to Scheme 110
122. Scheme 111: Silica-supported catalysed enantioselective arylation of aldehydes using Grignard reagents in flow ...
  
  Jump to Scheme 111
123. Scheme 112: Acid-catalysed rearrangement of citral and dehydrolinalool derivatives.
  
  Jump to Scheme 112
124. Scheme 113: Continuous stilbene isomerisation with continuous recycling of photoredox catalyst.
  
  Jump to Scheme 113
125. Scheme 114: Continuous-flow synthesis of compound 494 as developed by Ley et al.
  
  Jump to Scheme 114
126. Scheme 115: Selected industrial applications of DA reaction.
  
  Jump to Scheme 115
127. Scheme 116: Multistep flow synthesis of the spirocyclic structure 505 via employing DA cycloaddition.
  
  Jump to Scheme 116
128. Scheme 117: Continuous-flow DA reaction developed in a plater flow reactor for the preparation of the adduct 508...
  
  Jump to Scheme 117
129. Scheme 118: Continuous-flow DA reaction using a silica-supported imidazolidinone organocatalyst.
  
  Jump to Scheme 118
130. Scheme 119: Batch vs flow for the DA reaction of (cyclohexa-1,5-dien-1-yloxy)trimethylsilane (513) with acrylon...
  
  Jump to Scheme 119
131. Scheme 120: Continuous-flow DA reaction between 510 and 515 using a shell-core droplet system.
  
  Jump to Scheme 120
132. Scheme 121: Continuous-flow synthesis of bicyclic systems from benzyne precursors.
  
  Jump to Scheme 121
133. Scheme 122: Continuous-flow synthesis of bicyclic scaffolds 527 and 528 for further development of potential ph...
  
  Jump to Scheme 122
134. Scheme 123: Continuous-flow inverse-electron hetero-DA reaction to pyridine derivatives such as 531.
  
  Jump to Scheme 123
135. Scheme 124: Comparison between batch and flow for the synthesis of pyrimidinones 532–536 via retro-DA reaction ...
  
  Jump to Scheme 124
136. Scheme 125: Continuous-flow coupled with ultrasonic system for preparation of ʟ-ascorbic acid derivatives 539 d...
  
  Jump to Scheme 125
137. Scheme 126: Two-step continuous-flow synthesis of triazole 543.
  
  Jump to Scheme 126
138. Scheme 127: Continuous-flow preparation of triazoles via CuAAC employing 546-based heterogeneous catalyst.
  
  Jump to Scheme 127
139. Scheme 128: Continuous-flow synthesis of compounds 558 through A3-coupling and 560 via AgAAC both employing the...
  
  Jump to Scheme 128
140. Scheme 129: Continuous-flow photoinduced [2 + 2] cycloaddition for the preparation of bicyclic derivatives of 5...
  
  Jump to Scheme 129
141. Scheme 130: Continuous-flow [2 + 2] and [5 + 2] cycloaddition on large scale employing a flow reactor developed...
  
  Jump to Scheme 130
142. Scheme 131: Continuous-flow preparation of the tricyclic structures 573 and 574 starting from pyrrole 570 via [...
  
  Jump to Scheme 131
143. Scheme 132: Continuous-flow [2 + 2] photocyclization of cinnamates.
  
  Jump to Scheme 132
144. Scheme 133: Continuous-flow preparation of cyclobutane 580 on a 5-plates photoreactor.
  
  Jump to Scheme 133
145. Scheme 134: Continuous-flow [2 + 2] photocycloaddition under white LED lamp using heterogeneous PCN as photocat...
  
  Jump to Scheme 134
146. Figure 11: Picture of the parallel tube flow reactor (PTFR) "The Firefly" developed by Booker-Milburn et al. a...
  
  Jump to Figure 11
147. Scheme 135: Continuous-flow acid-catalysed [2 + 2] cycloaddition between silyl enol ethers and acrylic esters.
  
  Jump to Scheme 135
148. Scheme 136: Continuous synthesis of lactam 602 using glass column reactors.
  
  Jump to Scheme 136
149. Scheme 137: In situ generation of ketenes for the Staudinger lactam synthesis developed by Ley and Hafner.
  
  Jump to Scheme 137
150. Scheme 138: Application of [2 + 2 + 2] cycloadditions in flow employed by Ley et al.
  
  Jump to Scheme 138
151. Scheme 139: Examples of FC reactions applied in F&F industry.
  
  Jump to Scheme 139
152. Scheme 140: Continuous-flow synthesis of ibuprofen developed by McQuade et al.
  
  Jump to Scheme 140
153. Scheme 141: The FC acylation step of Jamison’s three-step ibuprofen synthesis.
  
  Jump to Scheme 141
154. Scheme 142: Synthesis of naphthalene derivative 629 via FC acylation in microreactors.
  
  Jump to Scheme 142
155. Scheme 143: Flow system for rapid screening of catalysts and reaction conditions developed by Weber et al.
  
  Jump to Scheme 143
156. Scheme 144: Continuous-flow system developed by Buorne, Muller et al. for DSD optimisation of the FC acylation ...
  
  Jump to Scheme 144
157. Scheme 145: Continuous-flow FC acylation of alkynes to yield β-chlorovinyl ketones such as 638.
  
  Jump to Scheme 145
158. Scheme 146: Continuous-flow synthesis of tonalide (619) developed by Wang et al.
  
  Jump to Scheme 146
159. Scheme 147: Continuous-flow preparation of acylated arene such as 290 employing Zr⁴⁺-β-zeolite developed by Kob...
  
  Jump to Scheme 147
160. Scheme 148: Flow system applied on an Aza-FC reaction catalysed by the thiourea catalyst 648.
  
  Jump to Scheme 148
161. Scheme 149: Continuous hydroformylation in scCO₂.
  
  Jump to Scheme 149
162. Scheme 150: Two-step flow synthesis of aldehyde 655 through a sequential Heck reaction and subsequent hydroform...
  
  Jump to Scheme 150
163. Scheme 151: Single-droplet (above) and continuous (below) flow reactors developed by Abolhasani et al. for the ...
  
  Jump to Scheme 151
164. Scheme 152: Continuous hydroformylation of 1-dodecene (655) using a PFR-CSTR system developed by Sundmacher et ...
  
  Jump to Scheme 152
165. Scheme 153: Continuous-flow synthesis of the aldehyde 660 developed by Eli Lilly & Co. [32]. Adapted with permissio...
  
  Jump to Scheme 153
166. Scheme 154: Continuous asymmetric hydroformylation employing heterogenous catalst supported on carbon-based sup...
  
  Jump to Scheme 154
167. Scheme 155: Examples of acetylation in F&F industry: synthesis of bornyl (S,R,S-664) and isobornyl (S,S,S-664) ...
  
  Jump to Scheme 155
168. Scheme 156: Continuous-flow preparation of bornyl acetate (S,R,S-664) employing the oscillating flow reactor.
  
  Jump to Scheme 156
169. Scheme 157: Continuous-flow synthesis of geranyl acetate (666) from acetylation of geraniol (343) developed by ...
  
  Jump to Scheme 157
170. Scheme 158: 12-Ttungstosilicic acid-supported silica monolith-catalysed acetylation in flow.
  
  Jump to Scheme 158
171. Scheme 159: Continuous-flow preparation of cyclopentenone 676.
  
  Jump to Scheme 159
172. Scheme 160: Two-stage synthesis of coumarin (90) via acetylation of salicylaldehyde (88).
  
  Jump to Scheme 160
173. Scheme 161: Intensification process for acetylation of 5-methoxytryptamine (677) to melatonin (678) developed b...
  
  Jump to Scheme 161
174. Scheme 162: Examples of macrocyclic musky odorants both natural (679–681) and synthetic (682 and 683).
  
  Jump to Scheme 162
175. Scheme 163: Flow setup combined with microwave for the synthesis of macrocycle 686 via RCM.
  
  Jump to Scheme 163
176. Scheme 164: Continuous synthesis of 2,5-dihydro-1H-pyrroles via ring-closing metathesis.
  
  Jump to Scheme 164
177. Scheme 165: Continuous-flow metathesis of 485 developed by Leadbeater et al.
  
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178. Figure 12: Comparison between RCM performed using different routes for the preparation of 696. On the left the...
  
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179. Scheme 166: Continuous-flow RCM of 697 employed the solid-supported catalyst 698 developed by Grela, Kirschning...
  
  Jump to Scheme 166
180. Scheme 167: Continuous-flow RORCM of cyclooctene employing the silica-absorbed catalyst 700.
  
  Jump to Scheme 167
181. Scheme 168: Continuous-flow self-metathesis of methyl oleate (703) employing SILP catalyst 704.
  
  Jump to Scheme 168
182. Scheme 169: Flow apparatus for the RCM of 697 using a nanofiltration membrane for the recovery and reuse of the...
  
  Jump to Scheme 169
183. Scheme 170: Comparison of loadings between RCMs performed with different routes for the synthesis of 709.
  
  Jump to Scheme 170

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

Full Text

Substituted nitrogen-bridged diazocines

Pascal Lentes,
Jeremy Rudtke,
Thomas Griebenow and
Rainer Herges

Full Research Paper
Published 25 Jun 2021

433 Accesses

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1. Graphical Abstract
2. Figure 1: Bridged diazocines synthesized and investigated in this work.
  
  Jump to Figure 1
3. Scheme 1: Synthesis of 3-bromo- and 3-iodo-acetylated CH₂NR diazocines 10 (R = Ac) and formylated diazocines ...
  
  Jump to Scheme 1
4. Figure 2: UV–vis spectra of 3-bromo and 3-iodo, and unsubstituted CH₂NAc-bridged (10a–c) and CH₂NCHO-bridged (...
  
  Jump to Figure 2
5. Figure 3: UV–vis spectra of 3-bromo-NAc-diazocine 10a and N-formyl-diazocine 11c in water. Spectra of Z-isome...
  
  Jump to Figure 3
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Beilstein J. Org. Chem. 2021, 17, 1503–1508, doi:10.3762/bjoc.17.107

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Free-radical cyclization approach to polyheterocycles containing pyrrole and pyridine rings

Ivan P. Mosiagin,
Olesya A. Tomashenko,
Dar’ya V. Spiridonova,
Mikhail S. Novikov,
Sergey P. Tunik and
Alexander F. Khlebnikov

Full Research Paper
Published 23 Jun 2021

418 Accesses

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1. Graphical Abstract
2. Scheme 1: Retrosynthetic analysis of heterocycles A and B.
  
  Jump to Scheme 1
3. Figure 1: Molecular structure of compound 3a, displacement parameters are drawn at 50%.
  
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4. Scheme 2: Free-radical cyclization of N-protected and N-unprotected pyrroles 1a and 2.
  
  Jump to Scheme 2
5. Scheme 3: Synthesis of 2H-pyrido[2,1-a]pyrrolo[3,4-c]isoquinolin-4-ium bromide 8.
  
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6. Scheme 4: Free-radical cyclization of dihalogeno-substituted salts 9 and 12.
  
  Jump to Scheme 4
7. Figure 2: Molecular structure of compound 13, displacement parameters are drawn at 50% probability level.
  
  Jump to Figure 2
8. Scheme 5: N-alkylation of the base 6a.
  
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9. Figure 3: Molecular structure of compound 17a, displacement parameters are drawn at 50% probability level.
  
  Jump to Figure 3
10. Scheme 6: Isomerization of compounds 17a and 18a.
  
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11. Scheme 7: N-Alkylation of compounds 18a and 19.
  
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Beilstein J. Org. Chem. 2021, 17, 1490–1498, doi:10.3762/bjoc.17.105

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Synthesis of spiro[dihydropyridine-oxindoles] via three-component reaction of arylamine, isatin and cyclopentane-1,3-dione

Yan Sun,
Jing Sun and
Chao-Guo Yan

Full Research Paper
Published 03 Jan 2013

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1. Graphical Abstract
2. Scheme 1: The four-component reactions containing dimedone (a) and cyclopentane-1,3-dione (b).
  
  Jump to Scheme 1
3. Figure 1: Molecular structure of spiro[dihydropyridine-oxindole] 1b.
  
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4. Figure 2: The two kinds of spiro compounds from reactions of isatins with arylamines and cyclic 1,3-diketones....
  
  Jump to Figure 2
5. Figure 3: Molecular structure of spiro[dihydropyridine-oxindole] 2f.
  
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6. Scheme 2: Condensation reactions of isatins with cyclopentane-1,3-dione.
  
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7. Figure 4: Molecular structure of compound 3d.
  
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8. Scheme 3: Proposed reaction mechanism for the three-component reaction.
  
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Beilstein J. Org. Chem. 2013, 9, 8–14, doi:10.3762/bjoc.9.2

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An overview of the synthetic routes to the best selling drugs containing 6-membered heterocycles

Breaking paracyclophane: the unexpected formation of non-symmetric disubstituted nitro[2.2]metaparacyclophanes

A straightforward conversion of 1,4-quinones into polycyclic pyrazoles via [3 + 2]-cycloaddition with fluorinated nitrile imines

Copper-mediated oxidative C−H/N−H activations with alkynes by removable hydrazides

Recent advances in the application of isoindigo derivatives in materials chemistry

Methodologies for the synthesis of quaternary carbon centers via hydroalkylation of unactivated olefins: twenty years of advances

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

Substituted nitrogen-bridged diazocines

Free-radical cyclization approach to polyheterocycles containing pyrrole and pyridine rings

Synthesis of spiro[dihydropyridine-oxindoles] via three-component reaction of arylamine, isatin and cyclopentane-1,3-dione

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