1 - Science of Synthesis: Knowledge Updates 2010/2 [Seite 1]
1.1 - Title page [Seite 5]
1.2 - Imprint [Seite 7]
1.3 - Preface [Seite 8]
1.4 - Abstracts [Seite 10]
1.5 - Overview [Seite 12]
1.6 - Table of Contents [Seite 14]
1.7 - Volume 10: Fused Five-Membered Hetarenes with One Heteroatom [Seite 24]
1.7.1 - 10.13 Product Class 13: Indole and Its Derivatives [Seite 24]
1.7.1.1 - 10.13.1 Product Subclass 1: Indoles [Seite 24]
1.7.1.1.1 - 10.13.1.1 Synthesis by Ring-Closure Reactions [Seite 29]
1.7.1.1.1.1 - 10.13.1.1.1 By Annulation to an Arene [Seite 29]
1.7.1.1.1.1.1 - 10.13.1.1.1.1 By Formation of Two N--C Bonds and One C--C Bond [Seite 29]
1.7.1.1.1.1.1.1 - 10.13.1.1.1.1.1 With Formation of 1--2, 1--7a, and 3--3a Bonds [Seite 29]
1.7.1.1.1.1.1.1.1 - 10.13.1.1.1.1.1.1 Method 1: From 1,2-Dihaloarenes [Seite 29]
1.7.1.1.1.1.2 - 10.13.1.1.1.2 By Formation of Two N--C Bonds [Seite 30]
1.7.1.1.1.1.2.1 - 10.13.1.1.1.2.1 With Formation of 1--2 and 1--7a Bonds [Seite 30]
1.7.1.1.1.1.2.1.1 - 10.13.1.1.1.2.1.1 Method 1: From 2-(2-Haloalkenyl)haloarenes [Seite 30]
1.7.1.1.1.1.2.1.2 - 10.13.1.1.1.2.1.2 Method 2: From 2-(2-Haloaryl)oxiranes [Seite 32]
1.7.1.1.1.1.2.1.3 - 10.13.1.1.1.2.1.3 Method 3: From (2-Haloaryl)alkynes [Seite 33]
1.7.1.1.1.1.3 - 10.13.1.1.1.3 By Formation of One N--C and One C--C Bond [Seite 35]
1.7.1.1.1.1.3.1 - 10.13.1.1.1.3.1 With Formation of 1--2 and 3--3a Bonds [Seite 35]
1.7.1.1.1.1.3.1.1 - 10.13.1.1.1.3.1.1 Method 1: From Arylhydrazones [Seite 35]
1.7.1.1.1.1.3.1.1.1 - 10.13.1.1.1.3.1.1.1 Variation 1: From 4-Chlorobutanal and Arylhydrazines [Seite 52]
1.7.1.1.1.1.3.1.1.2 - 10.13.1.1.1.3.1.1.2 Variation 2: From ß-Oxo Esters and Arenediazonium Ions [Seite 53]
1.7.1.1.1.1.3.1.1.3 - 10.13.1.1.1.3.1.1.3 Variation 3: From Nb-Aryl Benzophenone Hydrazones and Ketones [Seite 58]
1.7.1.1.1.1.3.1.1.4 - 10.13.1.1.1.3.1.1.4 Variation 4: From Alkynes and Arylhydrazines [Seite 60]
1.7.1.1.1.1.3.1.1.5 - 10.13.1.1.1.3.1.1.5 Variation 5: From Alkenes via Hydroformylation [Seite 62]
1.7.1.1.1.1.3.1.2 - 10.13.1.1.1.3.1.2 Method 2: From O-Alkenyl N-Arylhydroxylamines [Seite 64]
1.7.1.1.1.1.3.1.3 - 10.13.1.1.1.3.1.3 Method 3: From ortho-Substituted Nitroarenes [Seite 69]
1.7.1.1.1.1.3.1.4 - 10.13.1.1.1.3.1.4 Method 4: From Arylamines and Alkylsulfanylmethyl Ketones [Seite 72]
1.7.1.1.1.1.3.1.5 - 10.13.1.1.1.3.1.5 Method 5: From Arylamines and Ketones [Seite 74]
1.7.1.1.1.1.3.1.6 - 10.13.1.1.1.3.1.6 Method 6: From o-Haloarylamines and Ketones or Aldehydes [Seite 74]
1.7.1.1.1.1.3.1.7 - 10.13.1.1.1.3.1.7 Method 7: From Arylamines and 1,2-Diols [Seite 77]
1.7.1.1.1.1.3.1.8 - 10.13.1.1.1.3.1.8 Method 8: From Arylamines and a-Halo Ketones [Seite 78]
1.7.1.1.1.1.3.1.9 - 10.13.1.1.1.3.1.9 Method 9: From o-Haloarylamines and Alkynes [Seite 79]
1.7.1.1.1.1.3.1.9.1 - 10.13.1.1.1.3.1.9.1 Variation 1: Larock Synthesis [Seite 79]
1.7.1.1.1.1.3.1.9.2 - 10.13.1.1.1.3.1.9.2 Variation 2: With Concomitant Introduction of a 3-Substituent [Seite 86]
1.7.1.1.1.1.3.1.9.3 - 10.13.1.1.1.3.1.9.3 Variation 3: Using a Copper Catalyst [Seite 87]
1.7.1.1.1.1.3.1.9.4 - 10.13.1.1.1.3.1.9.4 Variation 4: Using Hydroamination [Seite 88]
1.7.1.1.1.1.3.1.9.5 - 10.13.1.1.1.3.1.9.5 Variation 5: Using Allenes [Seite 89]
1.7.1.1.1.1.3.1.10 - 10.13.1.1.1.3.1.10 Method 10: From N-Acyl-o-bromoarylamines and a-Halo Ketones [Seite 90]
1.7.1.1.1.1.3.1.11 - 10.13.1.1.1.3.1.11 Method 11: From ortho-Thallated N-Acylarylamines and 3-Chloroprop-1-ene [Seite 91]
1.7.1.1.1.1.3.1.12 - 10.13.1.1.1.3.1.12 Method 12: From N-Alkyl-N-arylhydroxylamines and Alkynes Carrying Electron-Withdrawing Groups [Seite 92]
1.7.1.1.1.1.3.1.13 - 10.13.1.1.1.3.1.13 Method 13: From N-Sulfinylarylamines and Grignard Reagents [Seite 93]
1.7.1.1.1.1.3.1.14 - 10.13.1.1.1.3.1.14 Method 14: From N-Arylarenesulfonamides and Phenyl(propynyl)iodonium Trifluoromethanesulfonate [Seite 93]
1.7.1.1.1.1.3.1.15 - 10.13.1.1.1.3.1.15 Method 15: From Nitroarenes [Seite 94]
1.7.1.1.1.1.3.1.16 - 10.13.1.1.1.3.1.16 Method 16: From N-Propargylanilines [Seite 94]
1.7.1.1.1.1.3.1.17 - 10.13.1.1.1.3.1.17 Method 17: From o-Bromoiodoarenes [Seite 95]
1.7.1.1.1.1.3.1.18 - 10.13.1.1.1.3.1.18 Method 18: From Anilines and Alkynes [Seite 95]
1.7.1.1.1.1.3.1.19 - 10.13.1.1.1.3.1.19 Method 19: From Aniline and Epoxides [Seite 96]
1.7.1.1.1.1.3.2 - 10.13.1.1.1.3.2 With Formation of 1--2 and 2--3 Bonds [Seite 96]
1.7.1.1.1.1.3.2.1 - 10.13.1.1.1.3.2.1 Method 1: From o-Alkylarylamines [Seite 96]
1.7.1.1.1.1.3.2.2 - 10.13.1.1.1.3.2.2 Method 2: From o-Acylarylamines [Seite 101]
1.7.1.1.1.1.3.2.3 - 10.13.1.1.1.3.2.3 Method 3: From 1-(o-Aminoaryl)alkenes [Seite 103]
1.7.1.1.1.1.3.2.4 - 10.13.1.1.1.3.2.4 Method 4: From o-(Benzoylamino)aryl Nitriles [Seite 104]
1.7.1.1.1.1.3.3 - 10.13.1.1.1.3.3 With Formation of 1--7a and 3--3a Bonds [Seite 104]
1.7.1.1.1.1.3.3.1 - 10.13.1.1.1.3.3.1 Method 1: From Benzo-1,4-quinones and Enamines [Seite 104]
1.7.1.1.1.1.3.4 - 10.13.1.1.1.3.4 With Formation of 1--7a and 1--2 Bonds [Seite 108]
1.7.1.1.1.1.3.4.1 - 10.13.1.1.1.3.4.1 Method 1: From 1-(m-Hydroxyaryl)alkenes [Seite 108]
1.7.1.1.1.1.3.5 - 10.13.1.1.1.3.5 With Formation of 1--7a and 2--3 Bonds [Seite 108]
1.7.1.1.1.1.3.5.1 - 10.13.1.1.1.3.5.1 Method 1: From o-Bromoaryl Ketones or Aldehydes [Seite 108]
1.7.1.1.1.1.4 - 10.13.1.1.1.4 By Formation of One N--C Bond [Seite 109]
1.7.1.1.1.1.4.1 - 10.13.1.1.1.4.1 With Formation of the 1--2 Bond [Seite 109]
1.7.1.1.1.1.4.1.1 - 10.13.1.1.1.4.1.1 Method 1: From a-(o-Aminoaryl) Ketones, 2-(o-Aminoaryl)aldehydes, or Synthons Thereof [Seite 109]
1.7.1.1.1.1.4.1.1.1 - 10.13.1.1.1.4.1.1.1 Variation 1: From (o-Aminoaryl)pyruvates [3-(o-Aminoaryl)-2-oxopropanoates] [Seite 110]
1.7.1.1.1.1.4.1.1.2 - 10.13.1.1.1.4.1.1.2 Variation 2: From a-(o-Aminoaryl) Ketones [Seite 112]
1.7.1.1.1.1.4.1.1.3 - 10.13.1.1.1.4.1.1.3 Variation 3: From 2-(o-Aminoaryl)acetaldehydes [Seite 123]
1.7.1.1.1.1.4.1.1.4 - 10.13.1.1.1.4.1.1.4 Variation 4: From 2-(o-Aminoaryl)acetaldehyde Acetals or Hemiacetals [Seite 125]
1.7.1.1.1.1.4.1.1.5 - 10.13.1.1.1.4.1.1.5 Variation 5: From 2-(o-Amidoaryl)enol Ethers and 2-(o-Nitroaryl)enol Ethers [Seite 129]
1.7.1.1.1.1.4.1.1.6 - 10.13.1.1.1.4.1.1.6 Variation 6: From 2-(o-Nitroaryl)enamines [Seite 131]
1.7.1.1.1.1.4.1.1.7 - 10.13.1.1.1.4.1.1.7 Variation 7: From 1-Nitro-2-(o-nitroaryl)ethenes [Seite 137]
1.7.1.1.1.1.4.1.2 - 10.13.1.1.1.4.1.2 Method 2: From o-Alkynylarylamines [Seite 139]
1.7.1.1.1.1.4.1.2.1 - 10.13.1.1.1.4.1.2.1 Variation 1: Closure Using a Base [Seite 139]
1.7.1.1.1.1.4.1.2.2 - 10.13.1.1.1.4.1.2.2 Variation 2: Closure in Water Alone [Seite 144]
1.7.1.1.1.1.4.1.2.3 - 10.13.1.1.1.4.1.2.3 Variation 3: Closure Using an Acid, Lewis Acid, or Metal Cation [Seite 144]
1.7.1.1.1.1.4.1.2.4 - 10.13.1.1.1.4.1.2.4 Variation 4: Closure Using Palladium Catalysis [Seite 147]
1.7.1.1.1.1.4.1.2.5 - 10.13.1.1.1.4.1.2.5 Variation 5: Closure with Concomitant Introduction of a 3-Substituent [Seite 149]
1.7.1.1.1.1.4.1.2.6 - 10.13.1.1.1.4.1.2.6 Variation 6: Closure with Concomitant Introduction of a 2-Substituent [Seite 155]
1.7.1.1.1.1.4.1.2.7 - 10.13.1.1.1.4.1.2.7 Variation 7: Closure with Concomitant Introduction of a 1-Substituent [Seite 156]
1.7.1.1.1.1.4.1.3 - 10.13.1.1.1.4.1.3 Method 3: From o-Alkenylnitroarenes and o-Alkenylaryl Azides [Seite 157]
1.7.1.1.1.1.4.1.4 - 10.13.1.1.1.4.1.4 Method 4: From o-Alkenylarylamines and N-Acyl Derivatives Thereof [Seite 163]
1.7.1.1.1.1.4.1.5 - 10.13.1.1.1.4.1.5 Method 5: From o-Acetamidoaryl Alkynyl Carbinols [Seite 166]
1.7.1.1.1.1.4.1.6 - 10.13.1.1.1.4.1.6 Method 6: From (o-Nitroaryl)acetonitriles [Seite 167]
1.7.1.1.1.1.4.1.7 - 10.13.1.1.1.4.1.7 Method 7: From 1-(2-Aminoaryl)alk-2-yn-1-ols [Seite 168]
1.7.1.1.1.1.4.1.8 - 10.13.1.1.1.4.1.8 Method 8: From o-Acyl-N-tosylanilines [Seite 168]
1.7.1.1.1.1.4.1.9 - 10.13.1.1.1.2.1.9 Method 9: From o-Aminoaryl Allenes [Seite 168]
1.7.1.1.1.1.4.1.10 - 10.13.1.1.1.4.1.10 Method 10: From (o-Aminoaryl)methyl Sulfones [Seite 169]
1.7.1.1.1.1.4.1.11 - 10.13.1.1.1.4.1.11 Method 11: From Anilines and Pyrrolidin-3-one [Seite 169]
1.7.1.1.1.1.4.1.12 - 10.13.1.1.1.4.1.12 Method 12: From o-(Chloroacetyl)arylamines [Seite 170]
1.7.1.1.1.1.4.2 - 10.13.1.1.1.4.2 With Formation of the 1--7a Bond [Seite 171]
1.7.1.1.1.1.4.2.1 - 10.13.1.1.1.4.2.1 Method 1: From 2-Arylalkenyl Azides [Seite 171]
1.7.1.1.1.1.4.2.2 - 10.13.1.1.1.4.2.2 Method 2: From 2-(o-Haloaryl)-2-hydroxyethanamines [Seite 173]
1.7.1.1.1.1.4.2.3 - 10.13.1.1.1.4.2.3 Method 3: From 1-(m-Hydroxyaryl)alkan-2-amines [Seite 174]
1.7.1.1.1.1.4.2.4 - 10.13.1.1.1.4.2.4 Method 4: From 2-(2-Chlorophenyl)ethanal N,N-Dimethylhydrazones [Seite 176]
1.7.1.1.1.1.4.2.5 - 10.13.1.1.1.4.2.5 Method 5: From 2-Aryl-1-nitroethenes [Seite 177]
1.7.1.1.1.1.4.2.6 - 10.13.1.1.1.4.2.6 Method 6: From (2-Arylvinyl)amines [Seite 177]
1.7.1.1.1.1.5 - 10.13.1.1.1.5 By Formation of One C--C Bond [Seite 178]
1.7.1.1.1.1.5.1 - 10.13.1.1.1.5.1 With Formation of the 2--3 Bond [Seite 178]
1.7.1.1.1.1.5.1.1 - 10.13.1.1.1.5.1.1 Method 1: From N-(o-Methylaryl)amides [Seite 178]
1.7.1.1.1.1.5.1.1.1 - 10.13.1.1.1.5.1.1.1 Variation 1: From N-[o-(Acylmethyl)-, N-[o-(Cyanomethyl)-, N-[o-(Alkoxycarbonylmethyl)-, or N-[o-(Phenylsulfonylmethyl)aryl]amides [Seite 181]
1.7.1.1.1.1.5.1.1.2 - 10.13.1.1.1.5.1.1.2 Variation 2: From [(o-Acylaminoaryl)methyl]phosphonium Salts [Seite 182]
1.7.1.1.1.1.5.1.1.3 - 10.13.1.1.1.5.1.1.3 Variation 3: From [(o-Acylaminoaryl)methyl]silanes [Seite 185]
1.7.1.1.1.1.5.1.2 - 10.13.1.1.1.5.1.2 Method 2: From o-Acylarylamines [Seite 186]
1.7.1.1.1.1.5.1.3 - 10.13.1.1.1.5.1.3 Method 3: From o-Alkylaryl Isocyanides and o-Alkenyl Isocyanides [Seite 188]
1.7.1.1.1.1.5.1.4 - 10.13.1.1.1.5.1.4 Method 4: From o-Alkenylaryl Isocyanides [Seite 192]
1.7.1.1.1.1.5.1.5 - 10.13.1.1.1.5.1.5 Method 5: From N-(o-Acylaryl)amides [Seite 195]
1.7.1.1.1.1.5.1.6 - 10.13.1.1.1.5.1.6 Method 6: From o-Aminobenzonitriles [Seite 198]
1.7.1.1.1.1.5.1.7 - 10.13.1.1.1.5.1.7 Method 7: From N-(o-Alkylaryl)imidates and -imines [Seite 199]
1.7.1.1.1.1.5.1.8 - 10.13.1.1.1.5.1.8 Method 8: From Anilides and Thioanilides via Radical Processes [Seite 204]
1.7.1.1.1.1.5.1.9 - 10.13.1.1.1.5.1.9 Method 9: From o-Alkenylaniline Enol Phosphates [Seite 204]
1.7.1.1.1.1.5.2 - 10.13.1.1.1.5.2 With Formation of the 3--3a Bond [Seite 205]
1.7.1.1.1.1.5.2.1 - 10.13.1.1.1.5.2.1 Method 1: From 2-(Arylamino)aldehydes, a-(Arylamino) Ketones, or Synthons Thereof [Seite 205]
1.7.1.1.1.1.5.2.2 - 10.13.1.1.1.5.2.2 Method 2: From 3-Arylamino-1-(trialkylsilyl)prop-1-ynes [Seite 208]
1.7.1.1.1.1.5.2.3 - 10.13.1.1.1.5.2.3 Method 3: From (o-Haloarylamino)alkenes [Seite 209]
1.7.1.1.1.1.5.2.4 - 10.13.1.1.1.5.2.4 Method 4: From Arylaminoalkenes [Seite 212]
1.7.1.1.1.1.5.2.5 - 10.13.1.1.1.5.2.5 Method 5: From N-(o-Haloaryl)prop-2-ynylamines [Seite 213]
1.7.1.1.1.1.5.2.6 - 10.13.1.1.1.5.2.6 Method 6: From N-(o-Haloaryl)allylamines [Seite 213]
1.7.1.1.1.1.5.2.7 - 10.13.1.1.1.5.2.7 Method 7: From N-(m-Haloaryl)imines [Seite 215]
1.7.1.1.1.1.5.2.8 - 10.13.1.1.1.5.2.8 Method 8: From 1-Aryl-1,2,3-triazoles [Seite 216]
1.7.1.1.1.1.5.2.9 - 10.13.1.1.1.5.2.9 Method 9: From N-Arylethanolamines [Seite 216]
1.7.1.1.1.1.5.2.10 - 10.13.1.1.1.5.2.10 Method 10: From N-Aryl-2-chloroprop-2-enylamines [Seite 218]
1.7.1.1.1.1.5.2.11 - 10.13.1.1.1.5.2.11 Method 11: From N-(2-Aminoaryl)-2-bromo-N-mesylallylamines [Seite 218]
1.7.1.1.1.1.5.2.12 - 10.13.1.1.1.5.2.12 Method 12: From N-Alkynyl-N-tosyl-2-iodoarylamines [Seite 219]
1.7.1.1.1.1.5.2.13 - 10.13.1.1.1.5.2.13 Method 13: From N-Tosyl(2-iodoaryl)aminoallenes [Seite 219]
1.7.1.1.1.2 - 10.13.1.1.2 By Annulation to a Pyrrole [Seite 220]
1.7.1.1.1.2.1 - 10.13.1.1.2.1 By Formation of Three C--C Bonds [Seite 220]
1.7.1.1.1.2.1.1 - 10.13.1.1.2.1.1 With Formation of 3a--4, 4--5, and 6--7 Bonds [Seite 220]
1.7.1.1.1.2.1.1.1 - 10.13.1.1.2.1.1.1 Method 1: From Pyrrole Chromium Carbene Complexes [Seite 220]
1.7.1.1.1.2.2 - 10.13.1.1.2.2 By Formation of Two C--C Bonds [Seite 221]
1.7.1.1.1.2.2.1 - 10.13.1.1.2.2.1 With Formation of 3a--4 and 5--6 Bonds [Seite 222]
1.7.1.1.1.2.2.1.1 - 10.13.1.1.2.2.1.1 Method 1: From 2-Alkenylpyrroles [Seite 222]
1.7.1.1.1.2.2.2 - 10.13.1.1.2.2.2 With Formation of 5--6 and 7--7a Bonds [Seite 223]
1.7.1.1.1.2.2.2.1 - 10.13.1.1.2.2.2.1 Method 1: From 3-Alkenylpyrroles [Seite 223]
1.7.1.1.1.2.2.3 - 10.13.1.1.2.2.3 With Formation of 3a--4 and 7--7a Bonds [Seite 225]
1.7.1.1.1.2.2.3.1 - 10.13.1.1.2.2.3.1 Method 1: From Pyrroles and 1,4-Diones [Seite 225]
1.7.1.1.1.2.2.4 - 10.13.1.1.2.2.4 With Formation of 3a--4 and 4--5 Bonds [Seite 225]
1.7.1.1.1.2.2.4.1 - 10.13.1.1.2.2.4.1 Method 1: From 2-(3-Acyloxyprop-1-enyl)pyrroles and Carbon Monoxide [Seite 225]
1.7.1.1.1.2.3 - 10.13.1.1.2.3 By Formation of One C--C Bond [Seite 226]
1.7.1.1.1.2.3.1 - 10.13.1.1.2.3.1 With Formation of the 3a--4 Bond [Seite 226]
1.7.1.1.1.2.3.1.1 - 10.13.1.1.2.3.1.1 Method 1: From Pyrroles with a C4-Chain at C2 [Seite 226]
1.7.1.1.1.2.3.2 - 10.13.1.1.2.3.2 With Formation of the 7--7a Bond [Seite 230]
1.7.1.1.1.2.3.2.1 - 10.13.1.1.2.3.2.1 Method 1: From Pyrroles with a C4-Chain at C3 [Seite 230]
1.7.1.1.1.2.3.3 - 10.13.1.1.2.3.3 With Formation of the 5--6 Bond [Seite 234]
1.7.1.1.1.2.3.3.1 - 10.13.1.1.2.3.3.1 Method 1: From 2-Acyl-3-(2-haloaryl)pyrroles [Seite 234]
1.7.1.1.1.2.3.3.2 - 10.13.1.1.2.3.3.2 Method 2: From 2-Alk-1-enyl-1-methyl-4-nitro-3-styrylpyrroles or 2-Alk-1-enyl-3-allenylpyrroles [Seite 235]
1.7.1.1.2 - 10.13.1.2 Synthesis by Ring Transformation [Seite 236]
1.7.1.1.2.1 - 10.13.1.2.1 Method 1: From Other Heterocyclic Systems [Seite 236]
1.7.1.1.3 - 10.13.1.3 Aromatization [Seite 239]
1.7.1.1.3.1 - 10.13.1.3.1 Method 1: Dehydrogenation of 2,3-Dihydro-1H-indoles [Seite 239]
1.7.1.1.3.2 - 10.13.1.3.2 Method 2: Dehydrogenation of Benzene Ring Reduced Indoles [Seite 244]
1.7.1.1.3.3 - 10.13.1.3.3 Method 3: Reduction and Other Transformations of 1H-Indole-2,3-diones (Isatins), 1,2-Dihydro-3H-indol-3-ones (Indoxyls), 1H-Indol-1-ols, and 1,3-Dihydro-2H-indol-2-ones (Oxindoles) [Seite 244]
1.7.1.1.4 - 10.13.1.4 Synthesis by Substitution [Seite 245]
1.7.1.1.4.1 - 10.13.1.4.1 Substitution of N-Hydrogen [Seite 245]
1.7.1.1.4.1.1 - 10.13.1.4.1.1 Method 1: Giving N-Halogen Indoles [Seite 246]
1.7.1.1.4.1.2 - 10.13.1.4.1.2 Method 2: Giving N-Nitrogen Indoles [Seite 246]
1.7.1.1.4.1.3 - 10.13.1.4.1.3 Method 3: Giving N-Phosphorus Indoles [Seite 246]
1.7.1.1.4.1.4 - 10.13.1.4.1.4 Method 4: Giving N-Silicon Indoles [Seite 246]
1.7.1.1.4.1.5 - 10.13.1.4.1.5 Method 5: Giving N-Carbon Indoles [Seite 246]
1.7.1.1.4.1.6 - 10.13.1.4.1.6 Method 6: Giving N-Metal Indoles [Seite 254]
1.7.1.1.4.2 - 10.13.1.4.2 Substitution of C-Hydrogen [Seite 255]
1.7.1.1.4.2.1 - 10.13.1.4.2.1 Electrophilic Substitution [Seite 255]
1.7.1.1.4.2.1.1 - 10.13.1.4.2.1.1 On the Five-Membered Ring [Seite 255]
1.7.1.1.4.2.1.1.1 - 10.13.1.4.2.1.1.1 Method 1: Giving C-Deuterium/Tritium Indoles [Seite 255]
1.7.1.1.4.2.1.1.2 - 10.13.1.4.2.1.1.2 Method 2: Giving C-Halogen Indoles [Seite 256]
1.7.1.1.4.2.1.1.3 - 10.13.1.4.2.1.1.3 Method 3: Giving C-Sulfur Indoles [Seite 259]
1.7.1.1.4.2.1.1.4 - 10.13.1.4.2.1.1.4 Method 4: Giving C-Nitrogen Indoles [Seite 263]
1.7.1.1.4.2.1.1.5 - 10.13.1.4.2.1.1.5 Method 5: Giving C-Carbon Indoles [Seite 266]
1.7.1.1.4.2.1.1.5.1 - 10.13.1.4.2.1.1.5.1 Variation 1: Introduction of Carboxy and Cyano Groups [Seite 266]
1.7.1.1.4.2.1.1.5.2 - 10.13.1.4.2.1.1.5.2 Variation 2: Introduction of Acyl Groups [Seite 267]
1.7.1.1.4.2.1.1.5.3 - 10.13.1.4.2.1.1.5.3 Variation 3: Introduction of Hydroxyalkyl and Related Groups [Seite 274]
1.7.1.1.4.2.1.1.5.4 - 10.13.1.4.2.1.1.5.4 Variation 4: Introduction of Aminoalkyl Groups [Seite 281]
1.7.1.1.4.2.1.1.5.5 - 10.13.1.4.2.1.1.5.5 Variation 5: Introduction of Sulfanylalkyl Groups [Seite 292]
1.7.1.1.4.2.1.1.5.6 - 10.13.1.4.2.1.1.5.6 Variation 6: Introduction of Alkyl Groups [Seite 293]
1.7.1.1.4.2.1.1.6 - 10.13.1.4.2.1.1.6 Method 6: Giving C-Silicon Indoles [Seite 315]
1.7.1.1.4.2.1.1.7 - 10.13.1.4.2.1.1.7 Method 7: Giving C-Mercury Indoles [Seite 315]
1.7.1.1.4.2.1.1.8 - 10.13.1.4.2.1.1.8 Method 8: Giving C-Thallium Indoles [Seite 315]
1.7.1.1.4.2.1.1.9 - 10.13.1.4.2.1.1.9 Method 9: Giving C-Palladium Indoles [Seite 315]
1.7.1.1.4.2.1.2 - 10.13.1.4.2.1.2 On the Benzene Ring [Seite 316]
1.7.1.1.4.2.1.2.1 - 10.13.1.4.2.1.2.1 Method 1: Substitution of Indoles [Seite 316]
1.7.1.1.4.2.1.2.2 - 10.13.1.4.2.1.2.2 Method 2: Substitution of 2,3-Dihydro-1H-indoles (Indolines) [Seite 321]
1.7.1.1.4.2.2 - 10.13.1.4.2.2 Nucleophilic Substitution [Seite 326]
1.7.1.1.4.2.2.1 - 10.13.1.4.2.2.1 Method 1: Giving C-Oxygen Indoles [Seite 326]
1.7.1.1.4.2.2.2 - 10.13.1.4.2.2.2 Method 2: Giving C-Nitrogen Indoles [Seite 329]
1.7.1.1.4.2.2.3 - 10.13.1.4.2.2.3 Method 3: Giving C-Carbon Indoles [Seite 329]
1.7.1.1.4.2.3 - 10.13.1.4.2.3 Radical and Carbene Substitution [Seite 333]
1.7.1.1.4.2.3.1 - 10.13.1.4.2.3.1 Method 1: Giving C-Carbon Indoles [Seite 333]
1.7.1.1.4.2.3.2 - 10.13.1.4.2.3.2 Method 2: Giving C-Heteroatom Indoles [Seite 337]
1.7.1.1.4.2.4 - 10.13.1.4.2.4 Transition-Metal-Catalyzed Substitution [Seite 338]
1.7.1.1.4.2.4.1 - 10.13.1.4.2.4.1 Method 1: Giving C-Carbon Indoles [Seite 338]
1.7.1.1.4.2.4.1.1 - 10.13.1.4.2.4.1.1 Variation 1: Giving 3-Substituted Indoles [Seite 338]
1.7.1.1.4.2.4.1.2 - 10.13.1.4.2.4.1.2 Variation 2: Giving 2-Substituted Indoles [Seite 342]
1.7.1.1.4.2.4.2 - 10.13.1.4.2.4.2 Method 2: Giving C-Silicon Indoles [Seite 348]
1.7.1.1.4.2.4.3 - 10.13.1.4.2.4.3 Method 3: Giving C-Boron Indoles [Seite 349]
1.7.1.1.4.2.5 - 10.13.1.4.2.5 Metalation [Seite 350]
1.7.1.1.4.2.5.1 - 10.13.1.4.2.5.1 Method 1: Giving C-Lithium Indoles [Seite 350]
1.7.1.1.4.3 - 10.13.1.4.3 Substitution of N-Metal [Seite 357]
1.7.1.1.4.3.1 - 10.13.1.4.3.1 Giving N-Substituted Products [Seite 357]
1.7.1.1.4.3.1.1 - 10.13.1.4.3.1.1 Method 1: Giving N-Halogen Indoles [Seite 357]
1.7.1.1.4.3.1.2 - 10.13.1.4.3.1.2 Method 2: Giving N-Sulfur Indoles [Seite 358]
1.7.1.1.4.3.1.3 - 10.13.1.4.3.1.3 Method 3: Giving N-Nitrogen Indoles [Seite 359]
1.7.1.1.4.3.1.4 - 10.13.1.4.3.1.4 Method 4: Giving N-Carbon Indoles [Seite 359]
1.7.1.1.4.3.1.4.1 - 10.13.1.4.3.1.4.1 Variation 1: Introduction of Carboxy, Cyano, and Related Groups [Seite 359]
1.7.1.1.4.3.1.4.2 - 10.13.1.4.3.1.4.2 Variation 2: Introduction of Acyl Groups [Seite 360]
1.7.1.1.4.3.1.4.3 - 10.13.1.4.3.1.4.3 Variation 3: Introduction of Alkenyl Groups [Seite 362]
1.7.1.1.4.3.1.4.4 - 10.13.1.4.3.1.4.4 Variation 4: Introduction of Aryl Groups [Seite 362]
1.7.1.1.4.3.1.4.5 - 10.13.1.4.3.1.4.5 Variation 5: Introduction of Alkyl Groups [Seite 363]
1.7.1.1.4.3.1.5 - 10.13.1.4.3.1.5 Method 5: Giving Other N-Metal Indoles [Seite 367]
1.7.1.1.4.3.2 - 10.13.1.4.3.2 Giving C-Substituted Products [Seite 368]
1.7.1.1.4.3.2.1 - 10.13.1.4.3.2.1 Method 1: Giving C-Halogen Indoles [Seite 368]
1.7.1.1.4.3.2.2 - 10.13.1.4.3.2.2 Method 2: Giving C-Sulfur Indoles [Seite 369]
1.7.1.1.4.3.2.3 - 10.13.1.4.3.2.3 Method 3: Giving C-Nitrogen Indoles [Seite 369]
1.7.1.1.4.3.2.4 - 10.13.1.4.3.2.4 Method 4: Giving C-Carbon Indoles [Seite 369]
1.7.1.1.4.4 - 10.13.1.4.4 Substitution of C-Metal [Seite 373]
1.7.1.1.4.4.1 - 10.13.1.4.4.1 Method 1: Giving C-Halogen Indoles [Seite 373]
1.7.1.1.4.4.2 - 10.13.1.4.4.2 Method 2: Giving C-Oxygen Indoles [Seite 374]
1.7.1.1.4.4.3 - 10.13.1.4.4.3 Method 3: Giving C-Sulfur Indoles [Seite 374]
1.7.1.1.4.4.4 - 10.13.1.4.4.4 Method 4: Giving C-Nitrogen Indoles [Seite 375]
1.7.1.1.4.4.5 - 10.13.1.4.4.5 Method 5: Giving C-Phosphorus Indoles [Seite 375]
1.7.1.1.4.4.6 - 10.13.1.4.4.6 Method 6: Giving C-Carbon Indoles [Seite 375]
1.7.1.1.4.4.6.1 - 10.13.1.4.4.6.1 Variation 1: Reactions with Carbon Electrophiles [Seite 375]
1.7.1.1.4.4.6.2 - 10.13.1.4.4.6.2 Variation 2: Via Reactions with Boron Electrophiles [Seite 376]
1.7.1.1.4.4.6.3 - 10.13.1.4.4.6.3 Variation 3: Via Ipso Displacement of Silicon [Seite 377]
1.7.1.1.4.4.6.4 - 10.13.1.4.4.6.4 Variation 4: Via Organopalladium Intermediates Using Metalated Indoles [Seite 378]
1.7.1.1.4.4.6.5 - 10.13.1.4.4.6.5 Variation 5: Via Organopalladium Intermediates Using Indole Halides and Trifluoromethanesulfonates [Seite 389]
1.7.1.1.4.4.6.6 - 10.13.1.4.4.6.6 Variation 6: Synthetic Applications of Hapto Metal Complexes of Indoles [Seite 394]
1.7.1.1.4.4.7 - 10.13.1.4.4.7 Method 7: Giving Other C-Metal Indoles [Seite 396]
1.7.1.1.5 - 10.13.1.5 Synthesis by Substituent Modification [Seite 396]
1.7.1.1.5.1 - 10.13.1.5.1 Modification of N-Carbon Functionalities [Seite 396]
1.7.1.1.5.1.1 - 10.13.1.5.1.1 Method 1: Giving N-Hydrogen Indoles [Seite 396]
1.7.1.1.5.1.2 - 10.13.1.5.1.2 Method 2: Giving N-Carbon Indoles [Seite 397]
1.7.1.1.5.2 - 10.13.1.5.2 Modification of C-Carbon Functionalities [Seite 399]
1.7.1.1.5.2.1 - 10.13.1.5.2.1 Method 1: Giving C-Hydrogen Indoles [Seite 399]
1.7.1.1.5.2.2 - 10.13.1.5.2.2 Method 2: Giving C-Oxygen Indoles [Seite 400]
1.7.1.1.5.2.3 - 10.13.1.5.2.3 Method 3: Giving C-Nitrogen Indoles [Seite 400]
1.7.1.1.5.2.4 - 10.13.1.5.2.4 Method 4: Giving C-Carbon Indoles [Seite 400]
1.7.1.1.5.3 - 10.13.1.5.3 Modification of N-Heteroatom Functionality [Seite 413]
1.7.1.1.5.3.1 - 10.13.1.5.3.1 Method 1: Modification of N-Sulfur Functionality [Seite 413]
1.7.1.1.5.3.2 - 10.13.1.5.3.2 Method 2: Modification of N-Silicon Functionality [Seite 415]
1.7.1.1.5.4 - 10.13.1.5.4 Modification of C-Heteroatom Functionality [Seite 415]
1.7.1.1.5.4.1 - 10.13.1.5.4.1 Method 1: Of C-Halogen Indoles [Seite 415]
1.7.1.1.5.4.2 - 10.13.1.5.4.2 Method 2: Of C-Oxygen Indoles [Seite 416]
1.7.1.1.5.4.3 - 10.13.1.5.4.3 Method 3: Of C-Sulfur Indoles. [Seite 417]
1.7.1.1.5.4.4 - 10.13.1.5.4.4 Method 4: Of C-Nitrogen Indoles [Seite 417]
1.7.1.1.5.4.5 - 10.13.1.5.4.5 Method 5: Of C-Silicon Indoles [Seite 417]
1.7.1.1.5.5 - 10.13.1.5.5 Rearrangement of N-Substituents [Seite 417]
1.7.1.1.5.5.1 - 10.13.1.5.5.1 Method 1: Giving C-Halogen Indoles [Seite 417]
1.7.1.1.5.5.2 - 10.13.1.5.5.2 Method 2: Giving C-Carbon Indoles [Seite 417]
1.7.1.1.5.6 - 10.13.1.5.6 Rearrangement of C-Substituents [Seite 418]
1.7.1.1.5.6.1 - 10.13.1.5.6.1 Method 1: Giving C-Nitrogen Indoles [Seite 418]
1.7.1.1.5.6.2 - 10.13.1.5.6.2 Method 2: Giving C-Carbon Indoles [Seite 418]
1.7.1.2 - 10.13.2 Product Subclass 2: 1H-Indol-1-ols (1-Hydroxy-1H-indoles) [Seite 419]
1.7.1.2.1 - 10.13.2.1 Synthesis by Ring-Closure Reactions [Seite 422]
1.7.1.2.1.1 - 10.13.2.1.1 By Annulation to an Arene [Seite 422]
1.7.1.2.1.1.1 - 10.13.2.1.1.1 By Formation of One N--C and One C--C Bond [Seite 422]
1.7.1.2.1.1.1.1 - 10.13.2.1.1.1.1 With Formation of 1--2 and 3--3a Bonds [Seite 422]
1.7.1.2.1.1.1.1.1 - 10.13.2.1.1.1.1.1 Method 1: From Nitrosoarenes and Alkynes [Seite 422]
1.7.1.2.1.1.2 - 10.13.2.1.1.2 By Formation of One N--C Bond [Seite 422]
1.7.1.2.1.1.2.1 - 10.13.2.1.1.2.1 With Formation of the 1--2 Bond [Seite 422]
1.7.1.2.1.1.2.1.1 - 10.13.2.1.1.2.1.1 Method 1: From (Arylmethyl)(o-nitroaryl)acetonitriles [Seite 422]
1.7.1.2.1.1.2.1.2 - 10.13.2.1.1.2.1.2 Method 2: From 2-(o-Nitroaryl)enamines [Seite 423]
1.7.1.2.1.1.2.1.3 - 10.13.2.1.1.2.1.3 Method 3: From 2-(o-Nitroaryl)acetic Acids and Esters [Seite 424]
1.7.1.2.1.1.2.1.4 - 10.13.2.1.1.2.1.4 Method 4: From o-Nitrobenzyl Ketones/Aldehydes [Seite 425]
1.7.1.2.1.1.2.1.5 - 10.13.2.1.1.2.1.5 Method 5: From Dimethyl 2-Alkyl-2-(o-nitrophenyl)malonates [Seite 425]
1.7.1.2.1.1.2.1.6 - 10.13.2.1.1.2.1.6 Method 6: From 3-(2-Bromo-6-nitrophenyl)-2-oxobut-3-enoates [Seite 426]
1.7.1.2.1.1.2.2 - 10.13.2.1.1.2.2 With Formation of the 1--7a Bond [Seite 427]
1.7.1.2.1.1.2.2.1 - 10.13.2.1.1.2.2.1 Method 1: From 1-Aryl-2-nitroalkenes [Seite 427]
1.7.1.2.2 - 10.13.2.2 Aromatization [Seite 428]
1.7.1.2.2.1 - 10.13.2.2.1 Method 1: Oxidation of 2,3-Dihydro-1H-indoles (Indolines) [Seite 428]
1.7.1.2.2.2 - 10.13.2.2.2 Method 2: Reduction of 1-Hydroxy-1,3-dihydro-2H-indol-2-ones [Seite 428]
1.7.1.3 - 10.13.3 Product Subclass 3: 1,3-Dihydro-2H-indol-2-ones (1H-Indol-2-ols, 2-Hydroxy-1H-indoles, or Oxindoles) [Seite 429]
1.7.1.3.1 - 10.13.3.1 Synthesis by Ring-Closure Reactions [Seite 433]
1.7.1.3.1.1 - 10.13.3.1.1 By Annulation to an Arene [Seite 433]
1.7.1.3.1.1.1 - 10.13.3.1.1.1 By Formation of One N--C and One C--C Bond [Seite 433]
1.7.1.3.1.1.1.1 - 10.13.3.1.1.1.1 With Formation of 1--2 and 3--3a Bonds [Seite 433]
1.7.1.3.1.1.1.1.1 - 10.13.3.1.1.1.1.1 Method 1: From Arylamines and an a-(Alkylsulfanyl) Ester [Seite 433]
1.7.1.3.1.1.1.1.1.1 - 10.13.3.1.1.1.1.1.1 Variation 1: From Arylamines and (Methylsulfinyl)acetates [Seite 434]
1.7.1.3.1.1.1.1.2 - 10.13.3.1.1.1.1.2 Method 2: From Arylhydrazides [Seite 435]
1.7.1.3.1.1.1.1.3 - 10.13.3.1.1.1.1.3 Method 3: From [(Arylamino)sulfanyl]alkynes [Seite 436]
1.7.1.3.1.1.1.2 - 10.13.3.1.1.1.2 With Formation of 1--2 and 2--3 Bonds [Seite 437]
1.7.1.3.1.1.1.2.1 - 10.13.3.1.1.1.2.1 Method 1: From N-Protected o-Alkylanilines [Seite 437]
1.7.1.3.1.1.1.2.2 - 10.13.3.1.1.1.2.2 Method 2: From o-Alkynylanilines [Seite 438]
1.7.1.3.1.1.2 - 10.13.3.1.1.2 By Formation of One N--C Bond [Seite 438]
1.7.1.3.1.1.2.1 - 10.13.3.1.1.2.1 With Formation of the 1--2 Bond [Seite 438]
1.7.1.3.1.1.2.1.1 - 10.13.3.1.1.2.1.1 Method 1: From (o-Nitroaryl)acetic Acids and Esters [Seite 438]
1.7.1.3.1.1.2.1.2 - 10.13.3.1.1.2.1.2 Method 2: From N,O-Diacylarylhydroxylamines [Seite 439]
1.7.1.3.1.1.2.1.3 - 10.13.3.1.1.2.1.3 Method 3: From Nitroarenes [Seite 440]
1.7.1.3.1.1.2.1.4 - 10.13.3.1.1.2.1.4 Method 4: From (o-Nitroaryl)pyruvates [3-(o-Nitroaryl)-2-oxopropanoates] [Seite 441]
1.7.1.3.1.1.2.1.5 - 10.13.3.1.1.2.1.5 Method 5: From (o-Nitroaryl)acetonitriles [Seite 441]
1.7.1.3.1.1.2.2 - 10.13.3.1.1.2.2 With Formation of the 1--7a Bond [Seite 443]
1.7.1.3.1.1.2.2.1 - 10.13.3.1.1.2.2.1 Method 1: From (o-Haloaryl)acetamides [Seite 443]
1.7.1.3.1.1.2.2.2 - 10.13.3.1.1.2.2.2 Method 2: From N-Methoxyarylacetamides [Seite 443]
1.7.1.3.1.1.3 - 10.13.3.1.1.3 By Formation of One C--C Bond [Seite 444]
1.7.1.3.1.1.3.1 - 10.13.3.1.1.3.1 With Formation of the 3--3a Bond [Seite 444]
1.7.1.3.1.1.3.1.1 - 10.13.3.1.1.3.1.1 Method 1: From N-Arylchloroacetamides and Related Amides [Seite 444]
1.7.1.3.1.1.3.1.2 - 10.13.3.1.1.3.1.2 Method 2: From 2-(Alkoxycarbonyl)- or 2-Acyl-N-aryl-2-diazoacetamides [Seite 447]
1.7.1.3.1.1.3.1.3 - 10.13.3.1.1.3.1.3 Method 3: From N-Aryltrichloroacetamides [Seite 448]
1.7.1.3.1.1.3.1.4 - 10.13.3.1.1.3.1.4 Method 4: From N-(o-Haloaryl)alkanamides [Seite 449]
1.7.1.3.1.1.3.1.5 - 10.13.3.1.1.3.1.5 Method 5: From a,ß-Unsaturated N-(o-Haloaryl)alkanamides [Seite 449]
1.7.1.3.1.1.3.1.6 - 10.13.3.1.1.3.1.6 Method 6: 1,3-Dihydro-2H-indol-2-ones via Copper(II)-Mediated C--H, Aryl--H Coupling [Seite 451]
1.7.1.3.2 - 10.13.3.2 Synthesis by Substituent Modification [Seite 452]
1.7.1.3.2.1 - 10.13.3.2.1 Method 1: Oxidation of Indoles [Seite 452]
1.7.1.3.2.2 - 10.13.3.2.2 Method 2: Reduction of 1H-Indole-2,3-diones (Isatins) [Seite 455]
1.7.1.3.2.3 - 10.13.3.2.3 Method 3: Reaction of 1H-Indole-2,3-diones (Isatins) with 4-Hydroxyproline [Seite 456]
1.7.1.3.2.4 - 10.13.3.2.4 Method 4: Nucleophilic Displacements of Halogen/Alkoxy Groups from 3-Halo- or 3-Alkoxy-1,3-dihydro-2H-indol-2-ones [Seite 456]
1.7.1.3.2.5 - 10.13.3.2.5 Method 5: Cyclization of 2-Chloro-3-(2-aminoethyl)indoles (2-Chlorotryptamines) [Seite 457]
1.7.1.3.2.6 - 10.13.3.2.6 Method 6: From Methyl 1H-Indole-3-carboxylate by Chlorination Then Reaction with an Allylic Alcohol [Seite 458]
1.7.1.4 - 10.13.4 Product Subclass 4: 1,2-Dihydro-3H-indol-3-ones (1H-Indol-3-ols, 3-Hydroxy-1H-indoles, or Indoxyls) [Seite 459]
1.7.1.4.1 - 10.13.4.1 Synthesis by Ring-Closure Reactions [Seite 460]
1.7.1.4.1.1 - 10.13.4.1.1 By Annulation to an Arene [Seite 460]
1.7.1.4.1.1.1 - 10.13.4.1.1.1 By Formation of One N--C and One C--C Bond [Seite 460]
1.7.1.4.1.1.1.1 - 10.13.4.1.1.1.1 With Formation of 1--2 and 3--3a Bonds [Seite 460]
1.7.1.4.1.1.1.1.1 - 10.13.4.1.1.1.1.1 Method 1: From Arylamines and Glyoxal Derivatives [Seite 460]
1.7.1.4.1.1.1.1.2 - 10.13.4.1.1.1.1.2 Method 2: From Arylamines, Aldehydes/Ketones, and Isocyanides [Seite 460]
1.7.1.4.1.1.2 - 10.13.4.1.1.2 By Formation of One N--C Bond [Seite 462]
1.7.1.4.1.1.2.1 - 10.13.4.1.1.2.1 With Formation of the 1--2 Bond [Seite 462]
1.7.1.4.1.1.2.1.1 - 10.13.4.1.1.2.1.1 Method 1: From 1-(o-Aminoaryl)allyl Silyl Ethers [Seite 462]
1.7.1.4.1.1.2.1.2 - 10.13.4.1.1.2.1.2 Method 2: From o-Aminoaryl Halomethyl Ketones [Seite 462]
1.7.1.4.1.1.3 - 10.13.4.1.1.3 By Formation of One C--C Bond [Seite 463]
1.7.1.4.1.1.3.1 - 10.13.4.1.1.3.1 With Formation of the 2--3 Bond [Seite 463]
1.7.1.4.1.1.3.1.1 - 10.13.4.1.1.3.1.1 Method 1: From [(o-Carboxyaryl)amino]acetic Acids and {[o-(Alkoxycarbonyl)aryl]amino}acetic Acid Esters [Seite 463]
1.7.1.4.1.1.3.2 - 10.13.4.1.1.3.2 With Formation of the 3--3a Bond [Seite 465]
1.7.1.4.1.1.3.2.1 - 10.13.4.1.1.3.2.1 Method 1: From N-Arylglycines [Seite 465]
1.7.1.4.2 - 10.13.4.2 Synthesis by Substituent Modification [Seite 465]
1.7.1.4.2.1 - 10.13.4.2.1 Method 1: Oxidation of Indoles [Seite 465]
1.7.1.5 - 10.13.5 Product Subclass 5: 1H-Indole-2,3-diones (Isatins) [Seite 469]
1.7.1.5.1 - 10.13.5.1 Synthesis by Ring-Closure Reactions [Seite 469]
1.7.1.5.1.1 - 10.13.5.1.1 By Annulation to an Arene [Seite 469]
1.7.1.5.1.1.1 - 10.13.5.1.1.1 By Formation of One N--C and One C--C Bond [Seite 469]
1.7.1.5.1.1.1.1 - 10.13.5.1.1.1.1 With Formation of the 1--2 Bond and the 3--3a Bond [Seite 469]
1.7.1.5.1.1.1.1.1 - 10.13.5.1.1.1.1.1 Method 1: From Anilines and Chloral [Seite 469]
1.8 - Author Index [Seite 510]
1.9 - Abbreviations [Seite 544]
1.10 - List of All Volumes [Seite 550]
10.13 Product Class 13: Indole and Its Derivatives
J. A. Joule
10.13.1 Product Subclass 1: Indoles
The word indole is derived from the word India: indigo (3), the blue dye, was first exported from India to Europe in the 16th century. Indoles are generally crystalline colorless solids, the simpler ones having characteristic odors: pure 1H-indole itself has a jasmine-like odor while that of 3-methyl-1H-indole (skatole) is notorious for its fecal character. The electron-rich character of indoles brings a tendency to light-catalyzed autoxidation; indoles should be stored away from oxygen and light. Simple indoles are also sensitive to strong acids, a point that must be taken into account in designing synthetic manipulations. Electron-withdrawing substituents have a stabilizing effect on each of these sensitivities.
1H-Indole (1) is the only tautomer detectable under normal circumstances; 3H-indole (2, indolenine in older literature) can be generated, but tautomerizes rapidly to 1H-indole at temperatures above –50°C (▶ Scheme 1).[1]
▶ Scheme 1 The Tautomeric Structures of Indole
The indole system occurs in the essential amino acid tryptophan (4; ▶ Scheme 2), and thence in proteins and in thousands of indole and 2,3-dihydro-1H-indole (trivially known as indoline) containing natural products[2] biosynthetically derived therefrom, e.g. the alkaloids reserpine (tranquilizer) and vincristine (cancer chemotherapeutic), in the neurotransmitter substance serotonin (5-hydroxytryptamine), in the plant growth-regulating hormone 1H-indole-3-acetic acid, in lysergic acid diethylamide (LSD), and in several significant modern synthetic drugs, such as indomethacin, ondansetron, pindolol, alosetron, ropinirole, tadalafil, and sumatriptan. As a consequence, the rich chemistry of indoles has been extensively studied, many routes for the ring synthesis of indoles have been developed and some frequently exemplified, as have substitutions and other manipulations of preformed indoles.
Functional group transformations of both ring and side-chain substituents (▶ Section 10.13.1.5) generally proceed normally, with emphasis given at appropriate points in this section to situations where this is not the case; reference should be made to other volumes in this series for particular functional group chemistry; however, many of these transformations are of great importance in the synthesis of indole-containing compounds and consequently are either exemplified in this section and/or reference is made to typical examples. Perhaps most significant to modern indole transformations are: (1) the use of organometallic, particularly organolithium, derivatives as nucleophiles; and (2) cross coupling processes, most often using palladium(0) as catalyst, with halogen, tin, zinc, mercury, thallium, boron, and trifluoromethanesulfonate derivatives of indoles. Enormous use has been made of cross-coupling processes involving both indole halides and trifluoromethanesulfonates and indole boronates and stannanes. There are examples of boronic acids or boronates at all of the carbon positions of the indole ring and there are examples of stannanes at all of the carbon positions of the indole ring (see ▶ Sections 10.13.1.4.2.4.3 and 10.13.1.4.4.6.4).
Several excellent general and specific reviews of indole chemistry are available.[3–6] Reviews on the synthesis of 3-substituted indoles via reactive alkylidene-3H-indole intermediates;[7] the control of enantio- and regioselectivity in asymmetric Friedel–Crafts alkylations;[8] the asymmetric Pictet–Spengler[9] and Bartoli[10] reactions; cross-coupling reactions;[11] the synthesis of indoles from indol-2-ylacyl radicals;[12] the catalytic synthesis of indoles from alkynes,[13] by rhodium[14] or palladium-catalyzed reactions[15–17] or other transition metal reagents;[18] the alkylation of indoles;[19,20] the synthesis of indoles via isocyanides;[21] the solid-phase synthesis of indoles;[22] halogen-,[23] sulfur-,[24] oxygen-containing indoles;[25] the nucleophilic substitution of indoles;[26,27] on methods and applications of indole ring synthesis;[28] and on indoles in general[29,30] are also available.
▶ Scheme 2 The Structures of Indigo, Tryptophan, and Tryptamine
1H-Indole is an electron-rich 10 π-electron aromatic system and as such undergoes electrophilic substitution reactions rapidly in the heterocyclic ring; a protodetritiation study showed the indole 3-position to be 5.5 × 1013 more reactive to electrophilic attack than a benzene position.[31] There is a strong preference for electrophilic attack at C3 (the β-position) though substitution at C2 (the α-position) of 3-substituted indoles 5 also takes place readily (▶ Scheme 3). In at least some instances, the observed α-substituted product 8 arises via initial β-attack producing a 3,3-disubstituted 3H-indolium intermediate 6 and then 1,2-rearrangement of 6 to 7,[32] though direct α-attack (to give 7) has also been demonstrated.[33,34]
▶ Scheme 3 Alternative Mechanisms for Electrophilic 2-Substitution of 3-Substituted Indoles[32–34]
In an elegant experiment (▶ Scheme 4) the intervention of a 3,3-disubstituted 3H-indolium intermediate in an indole overall α-substitution was shown by cyclization of the methanesulfonate of optically active 9 to give an optically inactive product 11, via the achiral, spirocyclic intermediate 10 arising from initial attack at the β-position.[35]
▶ Scheme 4 Demonstration of α-Electrophilic Substitution via Initial Attack at C3[35]
Indoles are weak bases[36,37] with pKa values of about –3, protonation taking place at C3[38,39] to generate 3H-indolium cations (indoleninium ions) 12 (▶ Scheme 5). It is the formation of such species and their further oligomerization and polymerization which is responsible for the acid sensitivity of indoles.[40]
▶ Scheme 5 Protonation of Indoles at C3 (the β-Position)[38,39]
Electrophilic substitution in the benzene ring only occurs in special cases, e.g. where the medium is strongly acidic and attack occurs on a pyrrole-ring-protonated species. Addition of a proton (at C3) then a nucleophile (at C2) can generate 2,3-dihydro-1H-indoles, arylamines in reactivity terms, which can undergo electrophilic substitution in the benzene ring, subsequent reversal of the earlier addition leading overall to benzene-ring-substituted indoles. Selective reduction of the pyrrole ring (best with triethylsilane in trifluoroacetic acid[41]) to produce 2,3-dihydro-1H-indoles (or the use of 2,3-dihydro-1H-indoles from other sources) then benzene ring substitution of these arylamines, and finally dehydrogenation of the five-membered ring, which is easy, can give the same result. However, most benzene-ring-substituted indoles are constructed by ring synthesis, and/or by functional group transpositions.
Indoles with an N-hydrogen have pKa values around 16 (in water)[37] or 21 (in DMSO)[42]for the loss of this proton; the acidity is increased by electron-withdrawing groups, in particular when located at C3.[43,44] Thus, N-deprotonation of indoles is readily achieved using strong bases. The resulting indolyl anions 13, which are ambident (▶ Scheme 6), react with electrophiles to give N-substituted products 14 or 3-substituted products 16 via 15, or mixtures of these depending on the counterion, the reactivity of the electrophile, and the solvent.[45–47] Reaction at nitrogen is favored by polar solvents and by more ionic metal—nitrogen bond character, sodium or potassium counterions; the use especially of zinc and magnesium intermediates can result in a greater proportion of C3 substitution. More reactive alkylating agents favor 3-alkylation.
▶ Scheme 6 Ambident Nature of Indolyl Anions[46–48]
Deprotonation of N-substituted indoles 17 with a strong base, such as butyllithium or lithium diisopropylamide, takes place...
