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

1253 Accesses

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

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

628 Accesses

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

Beilstein J. Org. Chem. 2015, 11, 1194–1219, doi:10.3762/bjoc.11.134

Full Text

Nanoreactors for green catalysis

M. Teresa De Martino,
Loai K. E. A. Abdelmohsen,
Floris P. J. T. Rutjes and
Jan C. M. van Hest

Review
Published 29 Mar 2018

573 Accesses

PDF
Album
1. Graphical Abstract
2. Figure 1: Assembly of catalyst-functionalized amphiphilic block copolymers into polymer micelles and vesicles...
  
  Jump to Figure 1
3. Scheme 1: C–N bond formation under micellar catalyst conditions, no organic solvent involved. Adapted from re...
  
  Jump to Scheme 1
4. Scheme 2: Suzuki−Miyaura couplings with, or without, ppm Pd. Conditions: ArI 0.5 mmol 3a, Ar’B(OH)₂ (0.75–1.0...
  
  Jump to Scheme 2
5. Figure 2: PQS (4a), PQS attached proline catalyst 4b. Adapted from reference [26]. Copyright 2012 American Chemic...
  
  Jump to Figure 2
6. Figure 3: 3a) Schematic representation of a Pickering emulsion with the enzyme in the water phase (i), or wit...
  
  Jump to Figure 3
7. Scheme 3: Cascade reaction with GOx and Myo. Adapted from reference [82].
  
  Jump to Scheme 3
8. Figure 4: Cross-linked polymersomes with Cu(OTf)₂ catalyst. Reprinted with permission from [15].
  
  Jump to Figure 4
9. Figure 5: Schematic representation of enzymatic polymerization in polymersomes. (A) CALB in the aqueous compa...
  
  Jump to Figure 5
10. Figure 6: Representation of DSN-G₀. Reprinted with permission from [100].
  
  Jump to Figure 6
11. Figure 7: The multivalent esterase dendrimer 5 catalyzes the hydrolysis of 8-acyloxypyrene 1,3,6-trisulfonate...
  
  Jump to Figure 7
12. Figure 8: Conversion of 4-NP in five successive cycles of reduction, catalyzed by Au@citrate, Au@PEG and Au@P...
  
  Jump to Figure 8

Beilstein J. Org. Chem. 2018, 14, 716–733, doi:10.3762/bjoc.14.61

Full Text

Recent advances in synthetic approaches for medicinal chemistry of C-nucleosides

Kartik Temburnikar and
Katherine L. Seley-Radtke

Review
Published 05 Apr 2018

562 Accesses

PDF
Album
1. Graphical Abstract
2. Figure 1: Structural components of nucleic acids. Shown is the monomeric building block of nucleic acids. Cha...
  
  Jump to Figure 1
3. Figure 2: Formation of oxocarbenium ion during glycosidic bond cleavage in nucleosides [31]. The extent of leavin...
  
  Jump to Figure 2
4. Figure 3: Structural modifications to nucleobase-sugar connectivity. The O–C–N bond between nucleobase and su...
  
  Jump to Figure 3
5. Figure 4: Examples of natural and synthetic C-nucleosides. Pseudouridine and formcycin are among several natu...
  
  Jump to Figure 4
6. Figure 5: Synthetic approaches to C-nucleosides. A. Two common strategies for C-nucleoside synthesis involve ...
  
  Jump to Figure 5
7. Figure 6: Steroselective C-nucleoside synthesis using D-ribonolactone. A. Nucleophilic substitution of D-ribo...
  
  Jump to Figure 6
8. Figure 7: Synthesis of C1'-substituted 4-aza-7,9-dideazaadenine C-nucleosides [63-65,69,70]. A. Reaction of D-ribonolacton...
  
  Jump to Figure 7
9. Figure 8: Pyrrolo- and imidazo[2,1-f][1,2,4]triazine C-nucleosides. A series of sugar- and nucleobase-substit...
  
  Jump to Figure 8
10. Figure 9: Synthesis of 1',2'-cyclopentyl C-nucleoside [73]. Functional groups at C1' and C2' were installed and e...
  
  Jump to Figure 9
11. Figure 10: Anti-influenza C-nucleosides mimicking favipiravir riboside [74]. A. Structure of favipiravir and its r...
  
  Jump to Figure 10
12. Figure 11: Alternative method for synthesis of 2'-substituted C-nucleosides [75]. A. Synthesis of C2'-substituted ...
  
  Jump to Figure 11
13. Figure 12: Synthesis of carbocyclic C-nucleosides using cyclopentanone [53]. A. Nucleophlic substitution on cyclop...
  
  Jump to Figure 12
14. Figure 13: Synthesis of carbocyclic C-nucleosides via Suzuki coupling [53]. A. Synthesis of OTf-cyclopentene that ...
  
  Jump to Figure 13

Beilstein J. Org. Chem. 2018, 14, 772–785, doi:10.3762/bjoc.14.65

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

523 Accesses

PDF
Album
1. Graphical Abstract
2. Scheme 1: AlCl₃-mediated reaction between amyl chloride and benzene as developed by Friedel and Crafts.
  
  Jump to Scheme 1
3. Figure 1: Most often used metal salts for catalytic FC alkylations and hydroarylations of arenes.
  
  Jump to Figure 1
4. Figure 2: 1,1-diarylalkanes with biological activity.
  
  Jump to Figure 2
5. Scheme 2: Alkylating reagents and side products produced.
  
  Jump to Scheme 2
6. Scheme 3: Initially reported TeCl₄-mediated FC alkylation of 1-penylethanol with toluene.
  
  Jump to Scheme 3
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.
  
  Jump to Scheme 8
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.
  
  Jump to Scheme 20
24. Scheme 21: (A) Ti(IV)-mediated rearrangement of an N-benzylated aniline to the corresponding ortho-alkylated a...
  
  Jump to Scheme 21
25. Scheme 22: Dibenzylation of aniline gives potentially useful amine-based ligands in a one-step procedure.
  
  Jump to Scheme 22
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.
  
  Jump to Scheme 26
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.
  
  Jump to Scheme 31
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...
  
  Jump to Scheme 34
38. Scheme 35: Diruthenium-catalyzed formation of chromenes and 1H-naphtho[2,1-b]pyrans.
  
  Jump to Scheme 35
39. Scheme 36: Rhenium(V)-catalyzed FC propargylations as a first step in the total synthesis of podophyllotoxin, ...
  
  Jump to Scheme 36
40. Scheme 37: Scandium-catalyzed arylation of 3-sulfanyl- and 3-selanylpropargyl alcohols.
  
  Jump to Scheme 37
41. Scheme 38: Synthesis of 1,3-diarylpropynes via direct coupling of propargyl trichloracetimidates and arenes.
  
  Jump to Scheme 38
42. Scheme 39: Diastereoselective substitutions of benzyl alcohols.
  
  Jump to Scheme 39
43. Scheme 40: (A) First diastereoselective FC alkylations developed by Bach et al. (B) anti-Selective FC alkylati...
  
  Jump to Scheme 40
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.
  
  Jump to Scheme 43
47. Scheme 44: Nucelophilic substitution of enantioenriched ferrocenyl alcohols.
  
  Jump to Scheme 44
48. Scheme 45: First catalytic enantioselective propargylation of arenes.
  
  Jump to Scheme 45

Beilstein J. Org. Chem. 2010, 6, No. 6, doi:10.3762/bjoc.6.6

Full Text

Volatiles from the xylarialean fungus Hypoxylon invadens

Jeroen S. Dickschat,
Tao Wang and
Marc Stadler

Full Research Paper
Published 29 Mar 2018

517 Accesses

PDF
Album
1. Graphical Abstract
2. Figure 1: Structures of the widespread fungal volatiles oct-1-en-3-ol (1) and 6-pentyl-2H-pyran-2-one (2), th...
  
  Jump to Figure 1
3. Figure 2: Total-ion chromatogram of the bouquet from Hypoxylon invadens MUCL 54175 obtained by the CLSA heads...
  
  Jump to Figure 2
4. Figure 3: Identified volatile organic compounds from Hypoxylon invadens MUCL 54175.
  
  Jump to Figure 3
5. Figure 4: Mass spectra of volatiles from Hypoxylon invadens MUCL 54175. Mass spectra of A) 2,5-dimethylphenol...
  
  Jump to Figure 4
6. Scheme 1: Proposed common biosynthetic pathway to volatile aromatic compounds from Hypoxylon invadens.
  
  Jump to Scheme 1
7. Scheme 2: Synthesis of 5-hydroxy-2-methyl-4H-chromen-4-one (19).
  
  Jump to Scheme 2

Beilstein J. Org. Chem. 2018, 14, 734–746, doi:10.3762/bjoc.14.62

Full Text

Biocatalytic synthesis of the Green Note trans-2-hexenal in a continuous-flow microreactor

Morten M. C. H. van Schie,
Tiago Pedroso de Almeida,
Gabriele Laudadio,
Florian Tieves,
Elena Fernández-Fueyo,
Timothy Noël,
Isabel W. C. E. Arends and
Frank Hollmann

Letter
Published 26 Mar 2018

493 Accesses

PDF
Album
1. Graphical Abstract
2. Scheme 1: Enzymatic reaction schemes for the selective oxidation of trans-hex-2-enol. A: Alcohol dehydrogenas...
  
  Jump to Scheme 1
3. Figure 1: Michaelis–Menten kinetics of the PeAAOx-catalysed oxidation of trans-hex-2-enol. Conditions: 50 mM ...
  
  Jump to Figure 1
4. Figure 2: The influence of the residence time on the conversion of trans-hex-2-enol (red squares) to trans-2-...
  
  Jump to Figure 2
5. Figure 3: Increasing the PeAAOx turnover numbers (TN) by increasing the residence time. Conditions: 6 mL flow...
  
  Jump to Figure 3
Supp. Info

Beilstein J. Org. Chem. 2018, 14, 697–703, doi:10.3762/bjoc.14.58

Full Text

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

434 Accesses

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

Beilstein J. Org. Chem. 2013, 9, 1977–2001, doi:10.3762/bjoc.9.234

Full Text

Photo, thermal and chemical degradation of riboflavin

Muhammad Ali Sheraz,
Sadia Hafeez Kazi,
Sofia Ahmed,
Zubair Anwar and
Iqbal Ahmad

Review
Published 26 Aug 2014

354 Accesses

PDF
Album
1. Graphical Abstract
2. Figure 1: Structures of RF and its photoproducts.
  
  Jump to Figure 1
3. Figure 2: A general scheme for the photodegradation of RF in aqueous solution.
  
  Jump to Figure 2
4. Figure 3: log k–pH profiles for the photolysis of RF in aqueous solution using UV light (∆) and visible light...
  
  Jump to Figure 3
5. Figure 4: log k–pH profiles for the photolysis of FMF (10⁻⁴ M) in alkaline solution under aerobic (○) and ana...
  
  Jump to Figure 4
6. Figure 5: k'–pH profiles for the photolysis of FMF (10⁻⁴ M) in acidic solution under aerobic (○) and anaerobi...
  
  Jump to Figure 5
7. Figure 6: Plots of k` versus pH for phosphate (▲) and sulfate (●) anion-catalyzed photodegradation of RF (5 ×...
  
  Jump to Figure 6
8. Figure 7: log k_obs–pH profiles for the photolysis of RF (5 × 10⁻⁵ M) in 0.1–0.5 M borate buffer. Experimental...
  
  Jump to Figure 7
9. Figure 8: log k_obs–pH profiles for the photolysis of RF (5 × 10⁻⁵ M) in 0.2–1.0 M citrate buffer. Experimenta...
  
  Jump to Figure 8
10. Figure 9: k'–pH profile for the photolysis of RF (5 × 10⁻⁵ M) in the presence of CF (0.5–2.5 × 10⁻⁴ M). Exper...
  
  Jump to Figure 9

Beilstein J. Org. Chem. 2014, 10, 1999–2012, doi:10.3762/bjoc.10.208

Full Text

Cobalt-catalyzed directed C–H alkenylation of pivalophenone N–H imine with alkenyl phosphates

Wengang Xu and
Naohiko Yoshikai

Full Research Paper
Published 28 Mar 2018

348 Accesses

PDF
Album
1. Graphical Abstract
2. Scheme 1: Cobalt–NHC-catalyzed C–H alkenylation reactions with alkenyl electrophiles.
  
  Jump to Scheme 1
3. Scheme 2: Reaction of substituted pivalophenone N–H imines with 2a. ^aThe major regioisomer is shown (rr = reg...
  
  Jump to Scheme 2
4. Scheme 3: Reaction of 1a with various alkenyl phosphates. ^aA mixture of E- and Z-alkenyl phosphate (ca. 1:1) ...
  
  Jump to Scheme 3
5. Scheme 4: The cyclization of o-alkenylpivalophenone N–H imine.
  
  Jump to Scheme 4
6. Scheme 5: Proposed catalytic cycle (R = t-BuCH₂, R' = P(O)(OEt)₂).
  
  Jump to Scheme 5
Supp. Info

Beilstein J. Org. Chem. 2018, 14, 709–715, doi:10.3762/bjoc.14.60

Full Text

Keep Informed