Of the myriad of heterocycles known to man, the indole ring stands foremost for its remarkably versatile chemistry, its enormous range of biological activities, and its ubiquity in the terrestrial and marine environments.
The indole ring continues to be discovered in natural products and to be employed in man-made pharmaceuticals and other materials. Given the enormous resurgence in indole ring synthesis over the past decade — highlighted by the power of transition metal catalysis — this authoritative guide addresses the need for a comprehensive presentation of the myriad of methods for constructing the indole ring, from the ancient to the modern, and from the obscure to the well-known.
Following presentation of the classic indole ring syntheses and many newer methods, coverage continues with indole ring syntheses via pyrroles, indolines, oxindoles, isatins, radical and photochemical reactions, aryne cycloadditions. This extensive volume concludes with the modern transition metal–catalyzed indole ring syntheses that utilize copper, palladium, rhodium, gold, ruthenium, platinum, and other metals to fashion the indole ring
Indole Ring Synthesis is a comprehensive, authoritative and up-to-date guide to the synthesis of this important heterocycle for organic chemists, pharmaceutical researchers and those interested in the chemistry of natural products.
Table of Contents:
1 Introduction 1
1.1 Preview 1
1.2 Indole‐Containing Natural Products 1
1.3 Biological Activity of Indoles 4
1.4 Indole‐Containing Pharmaceuticals 15
1.5 Indole‐Containing Materials 21
1.6 Indole‐Containing Ligands 28
1.7 Reviews of Indole‐Ring Synthesis 32
1.7.1 General Reviews on Indole Ring Synthesis 32
1.7.2 Specialized Reviews 32
1.7.3 Name Reactions 33
1.7.4 Miscellaneous Reviews 33
1.7.5 Synthesis of Carbazoles, Carbolines, and Indolocarbazoles 34
1.7.6 Reviews of Indole Analogues 34
References 34
PART I Sigmatropic Rearrangements 39
2 Fischer Indole Synthesis 41
2.1 Preview 41
2.2 Methods 41
2.2.1 Traditional Methods 41
2.2.2 Metal‐Catalyzed Methods 44
2.2.3 Solid‐Phase Fischer Indolization Method 56
2.2.4 Other General Methods 57
2.2.5 Hydrazones 63
2.2.6 Other Variations of Fischer Indole Synthesis 66
2.3 Applications of Fischer Indolizations 68
2.3.1 Drug Targets 68
2.3.2 Natural Products 82
2.3.3 Materials 97
2.3.4 General 98
References 108
3 Gassman Indole Synthesis 116
4 Bartoli Indole Synthesis 121
5 Thyagarajan Indole Synthesis 131
6 Julia Indole Synthesis 137
7 Miscellaneous Sigmatropic Rearrangements 139
PART II Nucleophilic Cyclization 145
8 Madelung Indole Synthesis 147
9 Wittig–Madelung Indole Synthesis 156
10 Jones–Schmid Indole Synthesis 165
11 Couture Indole Synthesis 174
12 Wender Indole Synthesis 176
13 Smith Indole Synthesis 181
14 Kihara Indole Synthesis 186
15 Nenitzescu 5‐Hydroxyindole Synthesis 188
16 Engler‐Kita Indole Synthesis 206
17 Bailey–Liebeskind–O’Shea Indoline–Indole Synthesis 213
18 Wright Indoline Synthesis 219
19 Saegusa Indole Synthesis 221
20 Ichikawa Indole Synthesis 228
21 Miscellaneous Nucleophilic Cyclizations that Form the Indole Ring 230
22 Sugasawa Indole Synthesis 244
PART III Electrophilic Cyclization 247
23 Bischler Indole Synthesis 249
24 The Nordlander Indole Synthesis 260
25 Nitrene Cyclization 264
26 Cadogan–Sundberg Indole Synthesis 266
27 Sundberg Indole Synthesis 278
28 Hemetsberger Indole Synthesis 287
29 Taber Indole Synthesis 296
30 Knochel Indole Synthesis 299
31 Täuber Carbazole Synthesis 301
32 Quéguiner Azacarbazole Synthesis 304
33 Iwao Indole Synthesis 307
34 Hewson Indole Synthesis 309
35 Magnus Indole Synthesis 310
36 Feldman Indole Synthesis 311
37 Butin Indole Synthesis 313
38 Miscellaneous Electrophilic Cyclizations 317
PART IV Reductive Cyclization 323
39 Nenitzescu o,β‐Dinitrostyrene Reductive Cyclization 325
40 Reissert Indole Synthesis 332
41 Leimgruber–Batcho Indole Synthesis 338
42 Pschorr–Hoppe Indole Synthesis 349
43 Mąkosza Indole Synthesis 354
44 Rawal Indole Synthesis 361
45 The Baeyer–Jackson Indole Synthesis and Miscellaneous Reductive Cyclization Indole Syntheses 363
PART V Oxidative Cyclization 381
46 Watanabe Indole Synthesis 383
47 Knölker Carbazole Synthesis 391
48 Miscellaneous Oxidative Cyclizations 396
PART VI Radical Cyclization 403
49 Fukuyama Indole Synthesis 405
50 Other Tin‐Mediated Indole Syntheses 409
51 The Murphy Indole Synthesis 412
52 Miscellaneous Radical‐Promoted Indole Syntheses 414
53 The Graebe–Ullmann Carbazole‐Carboline Synthesis 424
PART VII Cycloaddition and Electrocyclization 435
54 Diels–Alder Cycloaddition 437
55 Plieninger Indole Synthesis 464
56 Photochemical Synthesis of Indoles and Carbazoles 468
57 Dipolar Cycloaddition, Anionic, and Electrocyclization Reactions 483
PART VIII Indoles from Pyrroles 493
58 Electrophilic Cyclization of Pyrrole 495
59 Palladium‐Catalyzed Cyclization of Pyrroles 503
60 Cycloaddition Syntheses from Vinyl Pyrroles 506
61 Electrocyclization of Pyrroles 512
62 Indoles from Pyrrolo‐2,3‐Quinodimethanes 517
63 Indoles via Dehydrogenation of Pyrroles 520
64 Miscellaneous Indole Syntheses from Pyrroles 525
65 Indoles via Arynes 528
PART IX Indoles from Indolines 537
66 Indoline Dehydrogenation 539
67 Indolines to Indoles by Functionalized Elimination 553
68 Indolines from Oxindoles, Isatins, and Indoxyls 558
PART X Metal‐Catalyzed Indole Synthesis 573
69 Copper‐Catalyzed Indole Synthesis 575
70 Palladium‐Catalyzed Indole Ring Synthesis: Hegedus 588
71 Palladium‐Catalyzed Indole Ring Synthesis: Mori–Ban–Heck 592
72 Palladium‐Catalyzed Indole Ring Synthesis: Aryl‐Heck 597
73 Palladium‐Catalyzed Indole Ring Synthesis: Oxidative Cyclization 600
74 Palladium‐Catalyzed Indole Ring Synthesis: Watanabe–Cenini–Söderberg 604
75 Palladium‐Catalyzed Indole Ring Synthesis: Yamanaka–Sakamoto–Sonogashira 607
76 Palladium‐Catalyzed Indole Ring Synthesis: Larock 611
77 Palladium‐Catalyzed Indole Ring Synthesis: Cacchi 615
78 Palladium‐Catalyzed Indole Ring Synthesis: Buchwald–Hartwig 619
79 Palladium‐Catalyzed Indole Ring Synthesis: Miscellaneous 623
80 Rhodium‐Catalyzed Indole Ring Synthesis 632
81 Gold‐Catalyzed Indole Ring Synthesis 640
82 Ruthenium‐Catalyzed Indole Ring Synthesis 645
83 Platinum‐Catalyzed Indole Ring Synthesis 648
84 Silver‐ and Zinc‐Catalyzed Indole Ring Synthesis 651
85 Iron‐, Iridium‐, and Indium‐Catalyzed Indole Ring Syntheses 655
86 Nickel‐, Cobalt‐, and Molybdenum‐Catalyzed Indole Ring Syntheses 660
87 Mercury‐ and Chromium‐Catalyzed Indole Ring Syntheses 663
88 Miscellaneous Metal‐Catalyzed Indole Ring Syntheses 666
PART XI Miscellaneous 669
89 Miscellaneous Indole Ring Syntheses 671
Index 676
