synthesis and catalytic functionalization of biologically active indoles

1 Palladium-catalyzed Coupling Reactions of Indoles 50
1.5 Buchwald-Hartwig Amination
Functionalized aromatic and heteroaromatic amines are important building blocks
for the synthesis of pharmaceuticals. In many areas in organic synthesis
arylamines play an important role. They are not only parts in natural compounds
but also in conductive polymers and photographic materials. [122] So it is not very
amazing that an easy synthetic access becomes very interesting for the chemical
industry. The classical exposure to these compounds is carried out by nitration-
/reduction sequences or by reductive amination of aniline derivatives. These
methods requires often many synthetic steps and expensive reagents. Additionally
the scope for a range of functional moieties is limited because of the reaction
conditions. Buchwald and Hartwig developed an effective synthesis for arylamines.
Aryl halides and -triflates were coupled with amines in the presence of a palladium
catalyst. The palladium-catalyzed Buchwald-Hartwig amination has matured from
a synthetic laboratory procedure to a technique that is widely used in natural
synthesis as well as in other fields of academic interests. Furthermore due to the
versatility and reliability of this reaction, researchers in industrial environments
have included this methodology in their toolbox as a standard procedure for the
synthesis of amine derivatives. The process is in many points similar to palladiumcatalyzed
Suzuki-, Heck-, or Stille reaction. The crucial influence for the reaction
success is dependent on the catalytically active Pd(0) binding ligand. Extensive
synthesis of new amino-substituted indoles is restrained due to the lack of a
general regioselective method for introduction of amino-groups into this
heterocycle. In recent years palladium-catalyzed arylation of amines was
successfully used for building new C-N bonds. Nevertheless, this reaction still
remains rare in the series of indoles and its derivatives. In all conscience there are
only three publication until 2002 containing palladium-catalyzed amination of
indoles. [123]
Hooper et al. reported about palladium-catalyzed intermolecular amination of 2-
and 3-bromoindoles in 2003. [124] They studied the activity of palladium catalysts for
the amination of five-membered heterocyclic halides and determined the factors
that control the scope of this reaction. Table 8 represents the amination reaction of