Transition Metal-Catalysed, Direct and Site-Selective N1-, C2-or C3-Arylation of the Indole Nucleus: 20 Years of Improvements

The direct and site-selective transition metal-catalysed N1-, C2- or C3-arylations of indoles have been the subject of almost continuous improvements since their discovery in early 1980s. This research area is mainly motivated by the biological relevance of this class of compounds in order to propose catalytic alternative syntheses to the well known methodologies involving the formation of the indole ring like the Fischer, Larock, Cacchi, Lautens etc. reactions. Since the late 1990s it has experienced new impulses related to the intensive development of catalytic C-H activation. Today, through the intensive studies of Buchwald and Hartwig, the N1-arylation of indoles has reached sufficient maturity for both academic and industrial applications. On the other hand, the selective C2- or C3-arylation of indoles, initiated by Ohta in the middle 1980s, has become a hot research area these last years following the reports of Sames. Surprisingly, only few reports concern the use of heterogeneous catalysts; however, the application of these emerging methodologies seems to be related to the discovery of industrially attractive systems.