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

1140 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

Full Text

The synthesis of active pharmaceutical ingredients (APIs) using continuous flow chemistry

Marcus Baumann and
Ian R. Baxendale

Review
Published 17 Jul 2015

643 Accesses

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Album
1. Graphical Abstract
2. Figure 1: Pharmaceutical structures targeted in early flow syntheses.
  
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3. Scheme 1: Flow synthesis of 6-hydroxybuspirone (9). Inserted photograph reprinted with permission from [45]. Copy...
  
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4. Figure 2: Configuration of a baffled reactor tube (left) and its schematic working principle (right).
  
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5. Scheme 2: McQuade’s flow synthesis of ibuprofen (16).
  
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6. Scheme 3: Jamison’s flow synthesis of ibuprofen sodium salt (17).
  
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7. Scheme 4: Flow synthesis of imatinib (23).
  
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8. Scheme 5: Flow synthesis of the potent 5HT1B antagonist 28.
  
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9. Scheme 6: Flow synthesis of a selective δ-opioid receptor agonist 33.
  
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10. Scheme 7: Flow synthesis of a casein kinase I inhibitor library (38).
  
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11. Scheme 8: Flow synthesis of fluoxetine (46).
  
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12. Scheme 9: Flow synthesis of artemisinin (55).
  
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13. Scheme 10: Telescoped flow synthesis of artemisinin (55) and derivatives (62–64).
  
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14. Scheme 11: Flow approach towards AZD6906 (65).
  
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15. Scheme 12: Pilot scale flow synthesis of key intermediate 73.
  
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16. Scheme 13: Semi-flow synthesis of vildagliptine (77).
  
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17. Scheme 14: Pilot scale asymmetric flow hydrogenation towards 83. Inserted photograph reprinted with permission...
  
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18. Figure 3: Schematic representation of the ‘tube-in-tube’ reactor.
  
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19. Scheme 15: Flow synthesis of fanetizole (87) via tube-in-tube system.
  
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20. Scheme 16: Flow synthesis of diphenhydramine^.HCl (92).
  
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21. Scheme 17: Flow synthesis of rufinamide (95).
  
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22. Scheme 18: Large scale flow synthesis of rufinamide precursor 102.
  
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23. Scheme 19: First stage in the flow synthesis of meclinertant (103).
  
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24. Scheme 20: Completion of the flow synthesis of meclinertant (103).
  
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25. Scheme 21: Flow synthesis of olanzapine (121) utilising inductive heating techniques.
  
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26. Scheme 22: Flow synthesis of amitriptyline·HCl (127).
  
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27. Scheme 23: Flow synthesis of E/Z-tamoxifen (132) using peristaltic pumping modules.
  
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28. Figure 4: Container sized portable mini factory (photograph credit: INVITE GmbH, Leverkusen Germany).
  
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29. Scheme 24: Flow synthesis of imidazo[1,2-a]pyridines 136 linked to frontal affinity chromatography (FAC).
  
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30. Figure 5: Structures of zolpidem (142) and alpidem (143).
  
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31. Scheme 25: Synthesis and screening loops in the discovery of new Abl kinase inhibitors.
  
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32. Figure 6: Schotten–Baumann approach towards LY573636^.Na (147).
  
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33. Scheme 26: Pilot scale flow synthesis of LY2886721 (146).
  
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34. Scheme 27: Continuous flow manufacture of alikiren hemifumarate 152.
  
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Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

Full Text

An overview of the key routes to the best selling 5-membered ring heterocyclic pharmaceuticals

Marcus Baumann,
Ian R. Baxendale,
Steven V. Ley and
Nikzad Nikbin

Review
Published 18 Apr 2011

570 Accesses

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Album
1. Graphical Abstract
2. Figure 1: Structures of atorvastatin and other commercial statins.
  
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3. Figure 2: Structure of compactin.
  
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4. Scheme 1: Synthesis of pentasubstituted pyrroles.
  
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5. Scheme 2: [3 + 2] Cycloaddition to prepare 5-isopropylpyrroles.
  
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6. Scheme 3: Regiospecific [3 + 2] cycloaddition to prepare the pyrrole scaffold.
  
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7. Scheme 4: Formation of the pyrrole core of atorvastatin via [3 + 2] cycloaddition.
  
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8. Scheme 5: Formation of pyrrole 33 via the Paal–Knorr reaction.
  
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9. Scheme 6: Convergent synthesis towards atorvastatin.
  
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10. Figure 3: Binding pocket of sunitinib in the TRK KIT.
  
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11. Scheme 7: Synthesis of sunitinib.
  
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12. Scheme 8: Alternative synthesis of sunitinib.
  
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13. Scheme 9: Key steps in the syntheses of sumatriptan and zolmitriptan.
  
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14. Scheme 10: Introduction of the N,N-dimethylaminoethyl side chain.
  
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15. Scheme 11: Japp–Klingemann reaction in the synthesis of sumatriptan.
  
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16. Scheme 12: Synthesis of the intermediate sulfonyl chlorides 62 and 63.
  
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17. Scheme 13: Alternative introduction of the sulfonamide.
  
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18. Scheme 14: Negishi-type coupling to benzylic sulfonamides.
  
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19. Scheme 15: Heck reaction used to introduce the sulfonamide side chain of naratriptan.
  
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20. Scheme 16: Synthesis of the oxazolinone appendage of zolmitriptan.
  
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21. Scheme 17: Grandberg indole synthesis used in the preparation of rizatriptan.
  
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22. Scheme 18: Improved synthesis of rizatriptan.
  
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23. Scheme 19: Larock-type synthesis of rizatriptan.
  
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24. Scheme 20: Synthesis of eletriptan.
  
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25. Scheme 21: Heck coupling for the indole system in eletriptan.
  
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26. Scheme 22: Attempted Fischer indole synthesis of elatriptan.
  
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27. Scheme 23: Successful Fischer indole synthesis for eletriptan.
  
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28. Scheme 24: Mechanistic rationale for the Bischler–Möhlau reaction.
  
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29. Scheme 25: Bischler-type indole synthesis used in the fluvastatin sodium synthesis.
  
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30. Scheme 26: Palladium-mediated synthesis of ondansetron.
  
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31. Scheme 27: Fischer indole synthesis of ondansetron.
  
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32. Scheme 28: Optimised Pictet–Spengler reaction towards tadalafil.
  
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33. Figure 4: Structures of carvedilol 136 and propranolol 137.
  
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34. Scheme 29: Synthesis of the carbazole core of carvedilol.
  
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35. Scheme 30: Alternative syntheses of 4-hydroxy-9H-carbazole.
  
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36. Scheme 31: Convergent synthesis of etodolac.
  
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37. Scheme 32: Alternative synthesis of etodolac.
  
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38. Figure 5: Structures of imidazole-containing drugs.
  
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39. Scheme 33: Synthesis of functionalised imidazoles towards losartan.
  
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40. Scheme 34: Direct synthesis of the chlorinated imidazole in losartan.
  
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41. Scheme 35: Synthesis of trisubstituted imidazoles.
  
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42. Scheme 36: Preparation of the imidazole ring in olmesartan.
  
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43. Scheme 37: Synthesis of ondansetron.
  
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44. Scheme 38: Alternative route to ondansetron and its analogues.
  
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45. Scheme 39: Proton pump inhibitors and synthesis of esomeprazole.
  
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46. Scheme 40: Synthesis of benzimidazole core pantoprazole.
  
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47. Figure 6: Structure of rabeprazole 194.
  
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48. Scheme 41: Synthesis of candesartan.
  
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49. Scheme 42: Alternative access to the candesartan key intermediate 216.
  
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50. Scheme 43: .Medicinal chemistry route to telmisartan.
  
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51. Scheme 44: Improved synthesis of telmisartan.
  
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52. Scheme 45: Synthesis of zolpidem.
  
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53. Scheme 46: Copper-catalysed 3-component coupling towards zolpidem.
  
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54. Figure 7: Structure of celecoxib.
  
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55. Scheme 47: Preparation of celecoxib.
  
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56. Scheme 48: Alternative synthesis of celecoxib.
  
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57. Scheme 49: Regioselective access to celecoxib.
  
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58. Scheme 50: Synthesis of pazopanib.
  
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59. Scheme 51: Syntheses of anastrozole, rizatriptan and letrozole.
  
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60. Scheme 52: Regioselective synthesis of anastrozole.
  
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61. Scheme 53: Triazine-mediated triazole formation towards anastrozole.
  
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62. Scheme 54: Alternative routes to 1,2,4-triazoles.
  
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63. Scheme 55: Initial synthetic route to sitagliptin.
  
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64. Figure 8: Binding of sitagliptin within DPP-IV.
  
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65. Scheme 56: The process route to sitagliptin key intermediate 280.
  
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66. Scheme 57: Synthesis of maraviroc.
  
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67. Scheme 58: Synthesis of alprazolam.
  
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68. Scheme 59: The use of N-nitrosoamidine derivatives in the preparation of fused benzodiazepines.
  
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69. Figure 9: Structures of itraconazole, ravuconazole and voriconazole.
  
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70. Scheme 60: Synthesis of itraconazole.
  
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71. Scheme 61: Synthesis of rufinamide.
  
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72. Scheme 62: Representative tetrazole formation in valsartan.
  
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73. Figure 10: Structure of tetrazole containing olmesartan, candesartan and irbesartan.
  
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74. Scheme 63: Early stage introduction of the tetrazole in losartan.
  
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75. Scheme 64: Synthesis of cilostazol.
  
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76. Figure 11: Structure of cefdinir.
  
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77. Scheme 65: Semi-synthesis of cefdinir.
  
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78. Scheme 66: Thiazole syntheses towards ritonavir.
  
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79. Scheme 67: Synthesis towards pramipexole.
  
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80. Scheme 68: Alternative route to pramipexole.
  
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81. Scheme 69: Synthesis of famotidine.
  
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82. Scheme 70: Efficient synthesis of the hyperuricemic febuxostat.
  
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83. Scheme 71: Synthesis of ziprasidone.
  
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84. Figure 12: Structure of mometasone.
  
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85. Scheme 72: Industrial access to 2-furoic acid present in mometasone.
  
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86. Scheme 73: Synthesis of ranitidine from furfuryl alcohol.
  
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87. Scheme 74: Synthesis of nitrofurantoin.
  
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88. Scheme 75: Synthesis of benzofuran.
  
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89. Scheme 76: Synthesis of amiodarone.
  
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90. Scheme 77: Synthesis of raloxifene.
  
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91. Scheme 78: Alternative access to the benzo[b]thiophene core of raloxifene.
  
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92. Scheme 79: Gewald reaction in the synthesis of olanzapine.
  
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93. Scheme 80: Alternative synthesis of olanzapine.
  
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94. Figure 13: Access to simple thiophene-containing drugs.
  
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95. Scheme 81: Synthesis of clopidogrel.
  
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96. Scheme 82: Pictet–Spengler reaction in the preparation of tetrahydrothieno[3,2-c]pyridine (422).
  
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97. Scheme 83: Alternative synthesis of key intermediate 422.
  
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98. Figure 14: Co-crystal structures of timolol (left) and carazolol (right) in the β-adrenergic receptor.
  
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99. Scheme 84: Synthesis of timolol.
  
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100. Scheme 85: Synthesis of tizanidine 440.
  
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101. Scheme 86: Synthesis of leflunomide.
  
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102. Scheme 87: Synthesis of sulfamethoxazole.
  
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103. Scheme 88: Synthesis of risperidone.
  
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104. Figure 15: Relative abundance of selected transformations.
  
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105. Figure 16: The abundance of heterocycles within top 200 drugs (5-membered rings).
  
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Beilstein J. Org. Chem. 2011, 7, 442–495, doi:10.3762/bjoc.7.57

Full Text

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

Gagandeep Kour Reen,
Ashok Kumar and
Pratibha Sharma

Review
Published 19 Jul 2019

449 Accesses

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Album
1. Graphical Abstract
2. Figure 1: Various drugs having IP nucleus.
  
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3. Figure 2: Participation percentage of various TMs for the syntheses of IPs.
  
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4. Scheme 1: CuI–NaHSO₄·SiO₂-catalyzed synthesis of imidazo[1,2-a]pyridines.
  
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5. Scheme 2: Experimental examination of reaction conditions.
  
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6. Scheme 3: One-pot tandem reaction for the synthesis of 2-haloimidazopyridines.
  
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7. Scheme 4: Mechanistic scheme for the synthesis of 2-haloimidazopyridine.
  
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8. Scheme 5: Copper-MOF-catalyzed three-component reaction (3-CR) for imidazo[1,2-a]pyridines.
  
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9. Scheme 6: Mechanism for copper-MOF-driven synthesis.
  
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10. Scheme 7: Heterogeneous synthesis via titania-supported CuCl₂.
  
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11. Scheme 8: Mechanism involving oxidative C–H functionalization.
  
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12. Scheme 9: Heterogeneous synthesis of IPs.
  
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13. Scheme 10: One-pot regiospecific synthesis of imidazo[1,2-a]pyridines.
  
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14. Scheme 11: Vinyl azide as an unprecedented substrate for imidazo[1,2-a]pyridines.
  
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15. Scheme 12: Radical pathway.
  
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16. Scheme 13: Cu(I)-catalyzed transannulation approach for imidazo[1,5-a]pyridines.
  
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17. Scheme 14: Plausible radical pathway for the synthesis of imidazo[1,5-a]pyridines.
  
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18. Scheme 15: A solvent-free domino reaction for imidazo[1,2-a]pyridines.
  
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19. Scheme 16: Cu-NPs-mediated synthesis of imidazo[1,2-a]pyridines.
  
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20. Scheme 17: CuI-catalyzed synthesis of isoxazolylimidazo[1,2-a]pyridines.
  
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21. Scheme 18: Functionalization of 4-bromo derivative via Sonogashira coupling reaction.
  
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22. Scheme 19: A plausible reaction pathway.
  
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23. Scheme 20: Cu(I)-catalyzed intramolecular oxidative C–H amidation reaction.
  
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24. Scheme 21: One-pot synthetic reaction for imidazo[1,2-a]pyridine.
  
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25. Scheme 22: Plausible reaction mechanism.
  
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26. Scheme 23: Cu(OAc)₂-promoted synthesis of imidazo[1,2-a]pyridines.
  
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27. Scheme 24: Mechanism for aminomethylation/cycloisomerization of propiolates with imines.
  
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28. Scheme 25: Three-component synthesis of imidazo[1,2-a]pyridines.
  
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29. Figure 3: Scope of pyridin-2(1H)-ones and acetophenones.
  
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30. Scheme 26: CuO NPS-promoted A³ coupling reaction.
  
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31. Scheme 27: Cu(II)-catalyzed C–N bond formation reaction.
  
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32. Scheme 28: Mechanism involving Chan–Lam/Ullmann coupling.
  
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33. Scheme 29: Synthesis of formyl-substituted imidazo[1,2-a]pyridines.
  
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34. Scheme 30: A tandem sp³ C–H amination reaction.
  
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35. Scheme 31: Probable mechanistic approach.
  
  Jump to Scheme 31
36. Scheme 32: Dual catalytic system for imidazo[1,2-a]pyridines.
  
  Jump to Scheme 32
37. Scheme 33: Tentative mechanism.
  
  Jump to Scheme 33
38. Scheme 34: CuO/CuAl₂O₄/ᴅ-glucose-promoted 3-CCR.
  
  Jump to Scheme 34
39. Scheme 35: A tandem CuO_x/OMS-2-based synthetic strategy.
  
  Jump to Scheme 35
40. Figure 4: Biomimetic catalytic oxidation in the presence of electron-transfer mediators (ETMs).
  
  Jump to Figure 4
41. Scheme 36: Control experiment.
  
  Jump to Scheme 36
42. Scheme 37: Copper-catalyzed C(sp³)–H aminatin reaction.
  
  Jump to Scheme 37
43. Scheme 38: Reaction of secondary amines.
  
  Jump to Scheme 38
44. Scheme 39: Probable mechanistic pathway.
  
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45. Scheme 40: Coupling reaction of α-azidoketones.
  
  Jump to Scheme 40
46. Scheme 41: Probable pathway.
  
  Jump to Scheme 41
47. Scheme 42: Probable mechanism with free energy calculations.
  
  Jump to Scheme 42
48. Scheme 43: MCR for cyanated IP synthesis.
  
  Jump to Scheme 43
49. Scheme 44: Substrate scope for the reaction.
  
  Jump to Scheme 44
50. Scheme 45: Reaction mechanism.
  
  Jump to Scheme 45
51. Scheme 46: Probable mechanistic pathway for Cu/ZnAl₂O₄-catalyzed reaction.
  
  Jump to Scheme 46
52. Scheme 47: Copper-catalyzed double oxidative C–H amination reaction.
  
  Jump to Scheme 47
53. Scheme 48: Application towards different coupling reactions.
  
  Jump to Scheme 48
54. Scheme 49: Reaction mechanism.
  
  Jump to Scheme 49
55. Scheme 50: Condensation–cyclization approach for the synthesis of 1,3-diarylated imidazo[1,5-a]pyridines.
  
  Jump to Scheme 50
56. Scheme 51: Optimized reaction conditions.
  
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57. Scheme 52: One-pot 2-CR.
  
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58. Scheme 53: One-pot 3-CR without the isolation of chalcone.
  
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59. Scheme 54: Copper–Pybox-catalyzed cyclization reaction.
  
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60. Scheme 55: Mechanistic pathway catalyzed by Cu–Pybox complex.
  
  Jump to Scheme 55
61. Scheme 56: Cu(II)-promoted C(sp³)-H amination reaction.
  
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62. Scheme 57: Wider substrate applicability for the reaction.
  
  Jump to Scheme 57
63. Scheme 58: Plausible reaction mechanism.
  
  Jump to Scheme 58
64. Scheme 59: CuI assisted C–N cross-coupling reaction.
  
  Jump to Scheme 59
65. Scheme 60: Probable reaction mechanism involving sp³ C–H amination.
  
  Jump to Scheme 60
66. Scheme 61: One-pot MCR-catalyzed by CoFe₂O₄/CNT-Cu.
  
  Jump to Scheme 61
67. Scheme 62: Mechanistic pathway.
  
  Jump to Scheme 62
68. Scheme 63: Synthetic scheme for 3-nitroimidazo[1,2-a]pyridines.
  
  Jump to Scheme 63
69. Scheme 64: Plausible mechanism for CuBr-catalyzed reaction.
  
  Jump to Scheme 64
70. Scheme 65: Regioselective synthesis of halo-substituted imidazo[1,2-a]pyridines.
  
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71. Scheme 66: Synthesis of 2-phenylimidazo[1,2-a]pyridines.
  
  Jump to Scheme 66
72. Scheme 67: Synthesis of diarylated compounds.
  
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73. Scheme 68: CuBr₂-mediated one-pot two-component oxidative coupling reaction.
  
  Jump to Scheme 68
74. Scheme 69: Decarboxylative cyclization route to synthesize 1,3-diarylimidazo[1,5-a]pyridines.
  
  Jump to Scheme 69
75. Scheme 70: Mechanistic pathway.
  
  Jump to Scheme 70
76. Scheme 71: C–H functionalization reaction of enamines to produce diversified heterocycles.
  
  Jump to Scheme 71
77. Scheme 72: A plausible mechanism.
  
  Jump to Scheme 72
78. Scheme 73: CuI-promoted aerobic oxidative cyclization reaction of ketoxime acetates and pyridines.
  
  Jump to Scheme 73
79. Scheme 74: CuI-catalyzed pathway for the formation of imidazo[1,2-a]pyridine.
  
  Jump to Scheme 74
80. Scheme 75: Mechanistic pathway.
  
  Jump to Scheme 75
81. Scheme 76: Mechanistic rationale for the synthesis of products.
  
  Jump to Scheme 76
82. Scheme 77: Copper-catalyzed synthesis of vinyloxy-IP.
  
  Jump to Scheme 77
83. Scheme 78: Regioselective product formation with propiolates.
  
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84. Scheme 79: Proposed mechanism for vinyloxy-IP formation.
  
  Jump to Scheme 79
85. Scheme 80: Regioselective synthesis of 3-hetero-substituted imidazo[1,2-a]pyridines with different reaction su...
  
  Jump to Scheme 80
86. Scheme 81: Mechanistic pathway.
  
  Jump to Scheme 81
87. Scheme 82: CuI-mediated synthesis of 3-formylimidazo[1,2-a]pyridines.
  
  Jump to Scheme 82
88. Scheme 83: Radical pathway for 3-formylated IP synthesis.
  
  Jump to Scheme 83
89. Scheme 84: Pd-catalyzed urea-cyclization reaction for IPs.
  
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90. Scheme 85: Pd-catalyzed one-pot-tandem amination and intramolecular amidation reaction.
  
  Jump to Scheme 85
91. Figure 5: Scope of aniline nucleophiles.
  
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92. Scheme 86: Pd–Cu-catalyzed Sonogashira coupling reaction.
  
  Jump to Scheme 86
93. Scheme 87: One-pot amide coupling reaction for the synthesis of imidazo[4,5-b]pyridines.
  
  Jump to Scheme 87
94. Scheme 88: Urea cyclization reaction for the synthesis of two series of pyridines.
  
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95. Scheme 89: Amidation reaction for the synthesis of imidazo[4,5-b]pyridines.
  
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96. Figure 6: Amide scope.
  
  Jump to Figure 6
97. Scheme 90: Pd NPs-catalyzed 3-component reaction for the synthesis of 2,3-diarylated IPs.
  
  Jump to Scheme 90
98. Scheme 91: Plausible mechanistic pathway for Pd NPs-catalyzed MCR.
  
  Jump to Scheme 91
99. Scheme 92: Synthesis of chromenoannulated imidazo[1,2-a]pyridines.
  
  Jump to Scheme 92
100. Scheme 93: Mechanism for the synthesis of chromeno-annulated IPs.
  
  Jump to Scheme 93
101. Scheme 94: Zinc oxide NRs-catalyzed synthesis of imidazo[1,2-a]azines/diazines.
  
  Jump to Scheme 94
102. Scheme 95: Zinc oxide-catalyzed isocyanide based GBB reaction.
  
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103. Scheme 96: Reaction pathway for ZnO-catalyzed GBB reaction.
  
  Jump to Scheme 96
104. Scheme 97: Mechanistic pathway.
  
  Jump to Scheme 97
105. Scheme 98: ZnO NRs-catalyzed MCR for the synthesis of imidazo[1,2-a]azines.
  
  Jump to Scheme 98
106. Scheme 99: Ugi type GBB three-component reaction.
  
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107. Scheme 100: Magnetic NPs-catalyzed synthesis of imidazo[1,2-a]pyridines.
  
  Jump to Scheme 100
108. Scheme 101: Regioselective synthesis of 2-alkoxyimidazo[1,2-a]pyridines catalyzed by Fe-SBA-15.
  
  Jump to Scheme 101
109. Scheme 102: Plausible mechanistic pathway for the synthesis of 2-alkoxyimidazopyridine.
  
  Jump to Scheme 102
110. Scheme 103: Iron-catalyzed synthetic approach.
  
  Jump to Scheme 103
111. Scheme 104: Iron-catalyzed aminooxygenation reaction.
  
  Jump to Scheme 104
112. Scheme 105: Mechanistic pathway.
  
  Jump to Scheme 105
113. Scheme 106: Rh(III)-catalyzed double C–H activation of 2-substituted imidazoles and alkynes.
  
  Jump to Scheme 106
114. Scheme 107: Plausible reaction mechanism.
  
  Jump to Scheme 107
115. Scheme 108: Rh(III)-catalyzed non-aromatic C(sp²)–H bond activation–functionalization for the synthesis of imid...
  
  Jump to Scheme 108
116. Scheme 109: Reactivity and selectivity of different substrates.
  
  Jump to Scheme 109
117. Scheme 110: Rh-catalyzed direct C–H alkynylation by Li et al.
  
  Jump to Scheme 110
118. Scheme 111: Suggested radical mechanism.
  
  Jump to Scheme 111
119. Scheme 112: Scandium(III)triflate-catalyzed one-pot reaction and its mechanism for the synthesis of benzimidazo...
  
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120. Scheme 113: RuCl₃-assisted Ugi-type Groebke–Blackburn condensation reaction.
  
  Jump to Scheme 113
121. Scheme 114: C-3 aroylation via Ru-catalyzed two-component reaction.
  
  Jump to Scheme 114
122. Scheme 115: Regioselective synthetic mechanism.
  
  Jump to Scheme 115
123. Scheme 116: La(III)-catalyzed one-pot GBB reaction.
  
  Jump to Scheme 116
124. Scheme 117: Mechanistic approach for the synthesis of imidazo[1,2-a]pyridines.
  
  Jump to Scheme 117
125. Scheme 118: Synthesis of imidazo[1,2-a]pyridine using LaMnO₃ NPs under neat conditions.
  
  Jump to Scheme 118
126. Scheme 119: Mechanistic approach.
  
  Jump to Scheme 119
127. Scheme 120: One-pot 3-CR for regioselective synthesis of 2-alkoxy-3-arylimidazo[1,2-a]pyridines.
  
  Jump to Scheme 120
128. Scheme 121: Formation of two possible products under optimization of the catalysts.
  
  Jump to Scheme 121
129. Scheme 122: Mechanistic strategy for NiFe₂O₄-catalyzed reaction.
  
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130. Scheme 123: Two-component reaction for synthesizing imidazodipyridiniums.
  
  Jump to Scheme 123
131. Scheme 124: Mechanistic scheme for the synthesis of imidazodipyridiniums.
  
  Jump to Scheme 124
132. Scheme 125: CuI-catalyzed arylation of imidazo[1,2-a]pyridines.
  
  Jump to Scheme 125
133. Scheme 126: Mechanism for arylation reaction.
  
  Jump to Scheme 126
134. Scheme 127: Cupric acetate-catalyzed double carbonylation approach.
  
  Jump to Scheme 127
135. Scheme 128: Radical mechanism for double carbonylation of IP.
  
  Jump to Scheme 128
136. Scheme 129: C–S bond formation reaction catalyzed by cupric acetate.
  
  Jump to Scheme 129
137. Scheme 130: Cupric acetate-catalyzed C-3 formylation approach.
  
  Jump to Scheme 130
138. Scheme 131: Control experiments for signifying the role of DMSO and oxygen.
  
  Jump to Scheme 131
139. Scheme 132: Mechanism pathway.
  
  Jump to Scheme 132
140. Scheme 133: Copper bromide-catalyzed CDC reaction.
  
  Jump to Scheme 133
141. Scheme 134: Extension of the substrate scope.
  
  Jump to Scheme 134
142. Scheme 135: Plausible radical pathway.
  
  Jump to Scheme 135
143. Scheme 136: Transannulation reaction for the synthesis of imidazo[1,5-a]pyridines.
  
  Jump to Scheme 136
144. Scheme 137: Plausible reaction pathway for denitrogenative transannulation.
  
  Jump to Scheme 137
145. Scheme 138: Cupric acetate-catalyzed C-3 carbonylation reaction.
  
  Jump to Scheme 138
146. Scheme 139: Plausible mechanism for regioselective C-3 carbonylation.
  
  Jump to Scheme 139
147. Scheme 140: Alkynylation reaction at C-2 of 3H-imidazo[4,5-b]pyridines.
  
  Jump to Scheme 140
148. Scheme 141: Two-way mechanism for C-2 alkynylation of 3H-imidazo[4,5-b]pyridines.
  
  Jump to Scheme 141
149. Scheme 142: Palladium-catalyzed SCCR approach.
  
  Jump to Scheme 142
150. Scheme 143: Palladium-catalyzed Suzuki coupling reaction.
  
  Jump to Scheme 143
151. Scheme 144: Reaction mechanism.
  
  Jump to Scheme 144
152. Scheme 145: A phosphine free palladium-catalyzed synthesis of C-3 arylated imidazopyridines.
  
  Jump to Scheme 145
153. Scheme 146: Palladium-mediated Buchwald–Hartwig cross-coupling reaction.
  
  Jump to Scheme 146
154. Figure 7: Structure of the ligands optimized.
  
  Jump to Figure 7
155. Scheme 147: Palladium acetate-catalyzed direct arylation of imidazo[1,2-a]pyridines.
  
  Jump to Scheme 147
156. Scheme 148: Palladium acetate-catalyzed mechanistic pathway.
  
  Jump to Scheme 148
157. Scheme 149: Palladium acetate-catalyzed regioselective arylation reported by Liu and Zhan.
  
  Jump to Scheme 149
158. Scheme 150: Mechanism for selective C-3 arylation of IP.
  
  Jump to Scheme 150
159. Scheme 151: Pd(II)-catalyzed alkenylation reaction with styrenes.
  
  Jump to Scheme 151
160. Scheme 152: Pd(II)-catalyzed alkenylation reaction with acrylates.
  
  Jump to Scheme 152
161. Scheme 153: A two way mechanism.
  
  Jump to Scheme 153
162. Scheme 154: Double C–H activation reaction catalyzed by Pd(OAc)₂.
  
  Jump to Scheme 154
163. Scheme 155: Probable mechanism.
  
  Jump to Scheme 155
164. Scheme 156: Palladium-catalyzed decarboxylative coupling.
  
  Jump to Scheme 156
165. Scheme 157: Mechanistic cycle for decarboxylative arylation reaction.
  
  Jump to Scheme 157
166. Scheme 158: Ligand-free approach for arylation of imidazo[1,2-a]pyridine-3-carboxylic acids.
  
  Jump to Scheme 158
167. Scheme 159: Mechanism for ligandless arylation reaction.
  
  Jump to Scheme 159
168. Scheme 160: NHC-Pd(II) complex assisted arylation reaction.
  
  Jump to Scheme 160
169. Scheme 161: C-3 arylation of imidazo[1,2-a]pyridines with aryl bromides catalyzed by Pd(OAc)₂.
  
  Jump to Scheme 161
170. Scheme 162: Pd(II)-catalyzed C-3 arylations with aryl tosylates and mesylates.
  
  Jump to Scheme 162
171. Scheme 163: CDC reaction for the synthesis of imidazo[1,2-a]pyridines.
  
  Jump to Scheme 163
172. Scheme 164: Plausible reaction mechanism for Pd(OAc)₂-catalyzed synthesis of imidazo[1,2-a]pyridines.
  
  Jump to Scheme 164
173. Scheme 165: Pd-catalyzed C–H amination reaction.
  
  Jump to Scheme 165
174. Scheme 166: Mechanism for C–H amination reaction.
  
  Jump to Scheme 166
175. Scheme 167: One-pot synthesis for 3,6-di- or 2,3,6-tri(hetero)arylimidazo[1,2-a]pyridines.
  
  Jump to Scheme 167
176. Scheme 168: C–H/C–H cross-coupling reaction of IPs and azoles catalyzed by Pd(II).
  
  Jump to Scheme 168
177. Scheme 169: Mechanistic cycle.
  
  Jump to Scheme 169
178. Scheme 170: Rh-catalyzed C–H arylation reaction.
  
  Jump to Scheme 170
179. Scheme 171: Mechanistic pathway for C–H arylation of imidazo[1,2-a]pyridine.
  
  Jump to Scheme 171
180. Scheme 172: Rh(III)-catalyzed double C–H activation of 2-phenylimidazo[1,2-a]pyridines and alkynes.
  
  Jump to Scheme 172
181. Scheme 173: Rh(III)-catalyzed mechanistic pathway.
  
  Jump to Scheme 173
182. Scheme 174: Rh(III)-mediated oxidative coupling reaction.
  
  Jump to Scheme 174
183. Scheme 175: Reactions showing functionalization of the product obtained by the group of Kotla.
  
  Jump to Scheme 175
184. Scheme 176: Mechanism for Rh(III)-catalyzed oxidative coupling reaction.
  
  Jump to Scheme 176
185. Scheme 177: Rh(III)-catalyzed C–H activation reaction.
  
  Jump to Scheme 177
186. Scheme 178: Mechanistic cycle.
  
  Jump to Scheme 178
187. Scheme 179: Annulation reactions of 2-arylimidazo[1,2-a]pyridines and alkynes.
  
  Jump to Scheme 179
188. Scheme 180: Two-way reaction mechanism for annulations reaction.
  
  Jump to Scheme 180
189. Scheme 181: [RuCl₂(p-cymene)]₂-catalyzed C–C bond formation reaction.
  
  Jump to Scheme 181
190. Scheme 182: Reported reaction mechanism.
  
  Jump to Scheme 182
191. Scheme 183: Fe(III) catalyzed C-3 formylation approach.
  
  Jump to Scheme 183
192. Scheme 184: SET mechanism-catalyzed by Fe(III).
  
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193. Scheme 185: Ni(dpp)Cl₂-catalyzed KTC coupling.
  
  Jump to Scheme 185
194. Scheme 186: Pd-catalyzed SM coupling.
  
  Jump to Scheme 186
195. Scheme 187: Vanadium-catalyzed coupling of IP and NMO.
  
  Jump to Scheme 187
196. Scheme 188: Mechanistic cycle.
  
  Jump to Scheme 188
197. Scheme 189: Selective C3/C5–H bond functionalizations by mono and bimetallic systems.
  
  Jump to Scheme 189
198. Scheme 190: rGO-Ni@Pd-catalyzed C–H bond arylation of imidazo[1,2-a]pyridine.
  
  Jump to Scheme 190
199. Scheme 191: Mechanistic pathway for heterogeneously catalyzed arylation reaction.
  
  Jump to Scheme 191
200. Scheme 192: Zinc triflate-catalyzed coupling reaction of substituted propargyl alcohols.
  
  Jump to Scheme 192

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

Full Text

A review of new developments in the Friedel–Crafts alkylation – From green chemistry to asymmetric catalysis

Magnus Rueping and
Boris J. Nachtsheim

Review
Published 20 Jan 2010

428 Accesses

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Album
1. Graphical Abstract
2. Scheme 1: AlCl₃-mediated reaction between amyl chloride and benzene as developed by Friedel and Crafts.
  
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3. Figure 1: Most often used metal salts for catalytic FC alkylations and hydroarylations of arenes.
  
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4. Figure 2: 1,1-diarylalkanes with biological activity.
  
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5. Scheme 2: Alkylating reagents and side products produced.
  
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6. Scheme 3: Initially reported TeCl₄-mediated FC alkylation of 1-penylethanol with toluene.
  
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7. Scheme 4: Sc(OTf)₃-catalyzed FC benzylation of arenes.
  
  Jump to Scheme 4
8. Scheme 5: Reductive FC alkylation of arenes with arenecarbaldehydes.
  
  Jump to Scheme 5
9. Scheme 6: Iron(III)-catalyzed FC benzylation of arenes and heteroarenes.
  
  Jump to Scheme 6
10. Scheme 7: A gold(III)-catalyzed route to beclobrate.
  
  Jump to Scheme 7
11. Scheme 8: Catalytic FC-type alkylations of 1,3-dicarbonyl compounds.
  
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12. Scheme 9: Iron(III)-catalyzed synthesis of phenprocoumon.
  
  Jump to Scheme 9
13. Scheme 10: Bi(OTf)₃-catalyzed FC alkylation of benzyl alcohols developed by Rueping et al.
  
  Jump to Scheme 10
14. Scheme 11: (A) Bi(OTf)₃-catalyzed intramolecular FC alkylation as an efficient route to substituted fulvenes. ...
  
  Jump to Scheme 11
15. Scheme 12: FC-type glycosylation of 1,2-dimethylindole and trimethoxybenzene.
  
  Jump to Scheme 12
16. Scheme 13: FC alkylation with highly reactive ferrocenyl- and benzyl alcohols. The reaction proceeds even with...
  
  Jump to Scheme 13
17. Scheme 14: Reductive FC alkylation of arenes with benzaldehyde and acetophenone catalyzed by the Ir-carbene co...
  
  Jump to Scheme 14
18. Scheme 15: Formal synthesis of 1,1-diarylalkanes from benzyl alcohols and styrenes.
  
  Jump to Scheme 15
19. Scheme 16: (A) Mo-catalyzed hydroarylation of styrenes and cyclohexenes. (B) Hydroalkylation–cyclization casca...
  
  Jump to Scheme 16
20. Scheme 17: Bi(III)-catalyzed hydroarylation of styrenes with arenes and heteroarenes.
  
  Jump to Scheme 17
21. Scheme 18: BiCl₃-catalyzed ene/FC alkylation reaction cascade – A fast access to highly arylated dihydroindene...
  
  Jump to Scheme 18
22. Scheme 19: Au(I)/Ag(I)-catalyzed hydroarylation of indoles with styrenes, aliphatic and cyclic alkenes.
  
  Jump to Scheme 19
23. Scheme 20: First transition-metal-catalyzed ortho-hydroarylation developed by Beller et al.
  
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24. Scheme 21: (A) Ti(IV)-mediated rearrangement of an N-benzylated aniline to the corresponding ortho-alkylated a...
  
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25. Scheme 22: Dibenzylation of aniline gives potentially useful amine-based ligands in a one-step procedure.
  
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26. Scheme 23: FC-type alkylations with allyl alcohols as alkylating reagents – linear vs. branched product format...
  
  Jump to Scheme 23
27. Scheme 24: (A) First catalytic FC allylation and cinnamylation using allyl alcohols and its derivatives. (B) E...
  
  Jump to Scheme 24
28. Scheme 25: FC allylation/cyclization reaction yielding substituted chromanes.
  
  Jump to Scheme 25
29. Scheme 26: Synthesis of (all-rac)-α-tocopherol utilizing Lewis- and strong Brønsted-acids.
  
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30. Scheme 27: Au(III)-catalyzed cinnamylation of arenes.
  
  Jump to Scheme 27
31. Scheme 28: “Exhaustive” allylation of benzene-1,3,5-triol.
  
  Jump to Scheme 28
32. Scheme 29: Palladium-catalyzed allylation of indole.
  
  Jump to Scheme 29
33. Scheme 30: Pd-catalyzed synthesis of pyrroloindoles from L-tryptophane.
  
  Jump to Scheme 30
34. Scheme 31: Ru(IV)-catalyzed allylation of indole and pyrroles with unique regioselectivity.
  
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35. Scheme 32: Silver(I)-catalyzed intramolecular FC-type allylation of arenes and heteroarenes.
  
  Jump to Scheme 32
36. Scheme 33: FC-type alkylations of arenes using propargyl alcohols.
  
  Jump to Scheme 33
37. Scheme 34: (A) Propargylation of arenes with stoichiometric amounts of the Ru-allenylidene complex 86. (B) Fir...
  
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38. Scheme 35: Diruthenium-catalyzed formation of chromenes and 1H-naphtho[2,1-b]pyrans.
  
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39. Scheme 36: Rhenium(V)-catalyzed FC propargylations as a first step in the total synthesis of podophyllotoxin, ...
  
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40. Scheme 37: Scandium-catalyzed arylation of 3-sulfanyl- and 3-selanylpropargyl alcohols.
  
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41. Scheme 38: Synthesis of 1,3-diarylpropynes via direct coupling of propargyl trichloracetimidates and arenes.
  
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42. Scheme 39: Diastereoselective substitutions of benzyl alcohols.
  
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43. Scheme 40: (A) First diastereoselective FC alkylations developed by Bach et al. (B) anti-Selective FC alkylati...
  
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44. Scheme 41: Diastereoselective AuCl₃-catalyzed FC alkylation.
  
  Jump to Scheme 41
45. Scheme 42: Bi(OTf)₃-catalyzed alkylation of α-chiral benzyl acetates with silyl enol ethers.
  
  Jump to Scheme 42
46. Scheme 43: Bi(OTf)₃-catalyzed diastereoselective substitution of propargyl acetates.
  
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47. Scheme 44: Nucelophilic substitution of enantioenriched ferrocenyl alcohols.
  
  Jump to Scheme 44
48. Scheme 45: First catalytic enantioselective propargylation of arenes.
  
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Beilstein J. Org. Chem. 2010, 6, No. 6, doi:10.3762/bjoc.6.6

Full Text

Functional panchromatic BODIPY dyes with near-infrared absorption: design, synthesis, characterization and use in dye-sensitized solar cells

Quentin Huaulmé,
Cyril Aumaitre,
Outi Vilhelmiina Kontkanen,
David Beljonne,
Alexandra Sutter,
Gilles Ulrich,
Renaud Demadrille and
Nicolas Leclerc

Full Research Paper
Published 24 Jul 2019

389 Accesses

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1. Graphical Abstract
2. Figure 1: Molecular structures of the two target compounds BOD-TTPA-alk and BOD-TTPA, and the chemical struct...
  
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3. Figure 2: a) Geometrical optimization of four representative BODIPY-based materials for DSSCs application. b)...
  
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4. Figure 3: Predicted absorption spectra of the four dyes.
  
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5. Figure 4: Synthetic scheme of the selected materials. a) hydroxylamine hydrochloride, NaHCO₃, DMSO, 60 °C the...
  
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6. Figure 5: a) Absorption spectra of compounds BOD-TTPA-alk and BOD-TTPA (THF, ≈10⁻⁶ M, 25 °C). b) Absorbance s...
  
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7. Figure 6: J(V) curves of the best performing DSSCs devices sensitized with compounds BOD-TTPA-alk (blue trace...
  
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8. Figure 7: Photovoltaic parameters evolution with the increasing concentration of ^tBP in the electrolyte.
  
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Supp. Info

Beilstein J. Org. Chem. 2019, 15, 1758–1768, doi:10.3762/bjoc.15.169

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Nanopatterns of arylene–alkynylene squares on graphite: self-sorting and intercalation

Tristan J. Keller,
Joshua Bahr,
Kristin Gratzfeld,
Nina Schönfelder,
Marcin A. Majewski,
Marcin Stępień,
Sigurd Höger and
Stefan-S. Jester

Full Research Paper
Published 02 Aug 2019

350 Accesses

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1. Graphical Abstract
2. Figure 1: Chemical structures of the molecular squares 1a/b, the kekulene derivative 2, and octulene derivati...
  
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3. Figure 2: (a)–(c) Scanning tunneling microscopy images, (d)–(f) supramolecular models, and (g)–(l) schematic ...
  
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4. Figure 3: (a) Overview scanning tunneling microscopy image of a nanopattern of 1a with intermolecularly inter...
  
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5. Figure 4: (a–c) Scanning tunneling microscopy images of a nanopattern of 1a with intermolecularly intercalate...
  
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Supp. Info

Beilstein J. Org. Chem. 2019, 15, 1848–1855, doi:10.3762/bjoc.15.180

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Computational methods in drug discovery

Sumudu P. Leelananda and
Steffen Lindert

Review
Published 12 Dec 2016

325 Accesses

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1. Graphical Abstract
2. Figure 1: Schematic representation of a computer-aided drug discovery (CADD) pipeline. CADD methods are broad...
  
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3. Figure 2: FDA approved drugs Saquinavir and Amprenavir for the treatment of HIV infections. (a) The structure...
  
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4. Figure 3: (a) The crystal structure showing the binding of Dorzolamide (orange) to carbonic anhydrase II (pur...
  
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5. Figure 4: The best ligand binding site identified by SiteHound in HIV-1 protease. The ligand binding pocket i...
  
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6. Figure 5: Binding mode prediction. The known inhibitor Dorzolamide is docked into Carbonic anhydrase II cryst...
  
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7. Figure 6: The molecular structure of Raltegravir. Raltegravir is an FDA approved drug used in the treatment o...
  
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8. Figure 7: An example alchemical thermodynamic cycle for a protein–ligand binding free energy calculation. The...
  
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9. Figure 8: Schematic diagram showing the steps involved in QSAR. Known drug molecule activity and descriptor d...
  
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10. Figure 9: A few drugs discovered with the help of ligand-based drug discovery tools. (a) Zolmitriptan: used a...
  
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Beilstein J. Org. Chem. 2016, 12, 2694–2718, doi:10.3762/bjoc.12.267

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Metal-free mechanochemical oxidations in Ertalyte^® jars

Andrea Porcheddu,
Francesco Delogu,
Lidia De Luca,
Claudia Fattuoni and
Evelina Colacino

Full Research Paper
Published 25 Jul 2019

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1. Graphical Abstract
2. Scheme 1: Oxidation of 3-pheny-1-propanol (1a) with N-chlorosuccinimide (NCS) in the presence of (2,2,6,6-tet...
  
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3. Scheme 2: Hypothesized pathways for the TEMPO-assisted oxidation of alcohols in a) basic or b) acidic reactio...
  
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4. Scheme 3: TEMPO-assisted oxidation of 3-pheny-1-propanol (1a) under mechanical activation conditions. ^aPercen...
  
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5. Scheme 4: Scope of primary alcohol oxidation under mechanical activation conditions. ^aAll yields refer to iso...
  
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6. Scheme 5: Proposed mechanism for the oxidation of benzylic alcohols 6a and 7a under mechanochemical condition...
  
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7. Scheme 6: Scope of secondary alcohols in the oxidation under mechanical activation conditions. ^aAll yields re...
  
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8. Scheme 7: Possible mechanism for the TEMPO-mediated oxidation of primary and secondary alcohols by using NaOC...
  
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Beilstein J. Org. Chem. 2019, 15, 1786–1794, doi:10.3762/bjoc.15.172

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The chemistry of amine radical cations produced by visible light photoredox catalysis

Jie Hu,
Jiang Wang,
Theresa H. Nguyen and
Nan Zheng

Review
Published 01 Oct 2013

305 Accesses

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Album
1. Graphical Abstract
2. Scheme 1: Amine radical cations’ mode of reactivity.
  
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3. Scheme 2: Reductive quenching of photoexcited Ru complexes by Et₃N.
  
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4. Scheme 3: Photoredox aza-Henry reaction.
  
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5. Scheme 4: Formation of iminium ions using BrCCl₃ as stoichiometric oxidant.
  
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6. Scheme 5: Oxidative functionalization of N-aryltetrahydroisoquinolines using Eosin Y.
  
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7. Scheme 6: Synthetic and mechanistic studies of Eosin Y-catalyzed aza-Henry reaction.
  
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8. Scheme 7: Oxidative functionalization of N-aryltetrahydroisoquinolines using RB and GO.
  
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9. Scheme 8: Merging Ru-based photoredox catalysis and Lewis base catalysis for the Mannich reaction.
  
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10. Scheme 9: Merging Au-based photoredox catalysis and Lewis base catalysis for the Mannich reaction.
  
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11. Scheme 10: Merging Ru-based photoredox catalysis and Cu-catalyzed alkynylation reaction.
  
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12. Scheme 11: Merging Ru-based photoredox catalysis and NHC catalysis.
  
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13. Scheme 12: 1,3-Dipolar cycloaddition of photogenically formed azomethine ylides.
  
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14. Scheme 13: Plausible mechanism for photoredox 1,3-dipolar cycloaddition.
  
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15. Scheme 14: Photoredox-catalyzed cascade reaction for the synthesis of fused isoxazolidines.
  
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16. Scheme 15: Plausible mechanism for the photoredox-catalyzed cascade reaction.
  
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17. Scheme 16: Photoredox-catalyzed α-arylation of glycine derivatives.
  
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18. Scheme 17: Photoredox-catalyzed α-arylation of amides.
  
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19. Scheme 18: Intramolecular interception of iminium ions by sulfonamides.
  
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20. Scheme 19: Intramolecular interception of iminium ions by alcohols and sulfonamides.
  
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21. Scheme 20: Intermolecular interception of iminium ions by phosphites.
  
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22. Scheme 21: Photoredox-catalyzed oxidative phosphonylation by Eosin Y.
  
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23. Scheme 22: Conjugated addition of α-amino radicals to Michael acceptors.
  
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24. Scheme 23: Conjugated addition of α-amino radicals to Michael acceptors assisted by a Brønsted acid.
  
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25. Scheme 24: Conjugated addition of α-amino radicals derived from anilines to Michael acceptors.
  
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26. Scheme 25: Oxygen switch between two pathways involving α-amino radicals.
  
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27. Scheme 26: Interception of α-amino radicals by azodicarboxylates.
  
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28. Scheme 27: α-Arylation of amines.
  
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29. Scheme 28: Plausible mechanism for α-arylation of amines.
  
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30. Scheme 29: Photoinduced C–C bond cleavage of tertiary amines.
  
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31. Scheme 30: Photoredox cleavage of C–C bonds of 1,2-diamines.
  
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32. Scheme 31: Proposed mechanism photoredox cleavage of C–C bonds.
  
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33. Scheme 32: Intermolecular [3 + 2] annulation of cyclopropylamines with olefins.
  
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34. Scheme 33: Proposed mechanism for intermolecular [3 + 2] annulation.
  
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35. Scheme 34: Photoinduced clevage of N–N bonds of aromatic hydrazines and hydrazides.
  
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Beilstein J. Org. Chem. 2013, 9, 1977–2001, doi:10.3762/bjoc.9.234

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