synthesis and catalytic functionalization of biologically active indoles

1 Palladium-catalyzed Coupling Reactions of Indoles 56
the coupling product 182 after 5 h heating in a yield of 40%, while on leaving the
reaction overnight the yield was increased to 63%.
Pd(OAc) 2 (3 mol%)
Br
BINAP (4 mol%)
HN
H2N Cs2CO3 (1.4 equiv)
CO2Et CO2Et S
N toluene, 100 °C, 21 h
S
H
181 175 182 (63%)
Scheme 46. Palladium-catalyzed amination of ethyl-3-bromo-benzo[b]thiophene-2-carboxylate with
5-aminoindole.
In attendance of 3 mol% Pd(OAc)2 as palladium source, 4 mol% BINAP and 1.4
equiv Cs2CO3 as base in toluene at 100 °C resulted the diarylamine
benzo[b]thiophene 182 in good yield. Benzo[b]thiophenes are important
heterocycles, either in biologically active molecules or as luminescent components
used in organic materials. [129]
Pujol and co-workers were also interested in obtaining new compounds with
biological activity. Therefore they required an easy source of N-aryl derivatives to
serve as precursors. Aryl bromides were coupled with N-compounds to give the
corresponding arylamines in the presence of palladium catalyst, suitable ligand,
and weak base. [130] They prepared arylamines from interesting substrates by using
Pd[P(o-tolyl)3]2Cl2 (0.12 mol%) as catalyst, BINAP (0.0075 mol%) or PPh3 as
chelating ligands, and Cs2CO3 as base (1 mmol) without solvent or a few drops of
toluene when the starting material was a solid compound. Table 9 shows the
coupled products from the synthesis of indoles with different substrates. When 5bromoindole
(Table 9, entries 6-9) was treated with 3-fluoroaniline, the arylation
took place exclusively at the 1-position over the N-atom.
The corresponding N-arylindole was obtained as a single isomeric product at a
temperature near 150 °C (Table 9, entries 7 and 8). and the expected 5-(3fluorophenylamimo)indole
was not detected under these conditions.
NH