synthesis and catalytic functionalization of biologically active indoles

1 Palladium-catalyzed Coupling Reactions of Indoles 54
Scheme 43 imaged on one hand the palladium-catalyzed amination of 2chlorobenzothiazole
167 and indole 1 as the coupling partner (a) and on the other
hand the amination of 5-bromoindole 12 and 6-chloroindole 169 as the halide
component with different amines to the desired coupling products 168 and 170a-d
(b). Bulky electron-rich biaryl ligands F and G were employed for these reactions.
The product 168 from the coupling of 2-chlorobenzothiazole 167, in the presence
of Pd2(dba)3/ligand F (1:4) as catalyst system, tert-BuONa as base in toluene at
100 °C, was isolated in a yield of 73%. Finally, 5-bromoindole 12 and
6-chloroindole 169, possessing a free NH, were viable coupling partners with
anilines and acyclic and cyclic secondary alkylamines. Using the procedure in
Scheme 43 (b) with Pd2(dba)3/ligand F or G as catalyst system and 2.2 equiv
LiHMDS as base in THF at 65 °C for 24 h gave the according products 170a-d in
excellent to good yields, respectively. The more difficult reaction with n-BuNH2
afforded 51% of the desired product 170c. An acceptable yield for the coupling of
6-chloroindole 169 with piperidine to structure 170d was only obtained with ligand
F in a yield of 66%.
Ligand F was also used in the palladium-catalyzed amination of aryl
benzenesulfonates, reported by the same group. [127] The use of
benzenesulfonates typically provided higher yields and shorter reaction times as
tosylates. As can be seen in Scheme 44, the reaction of a benzenesulfonate 171
and an aryl tosylate 172 with indole 1 led to the wanted products 173 and 174 in
excellent yields. In both cases it was necessary to add a catalytic quantity of
phenyl boronic acid to ensure complete conversion of the Pd(II) precatalyst to
Pd(0).
tBu
171
172
OSO 2Ph
OTos
1
N
H
Pd(OAc) 2 (2 mol%)
ligand F (5 mol%)
PhB(OH) 2 (5 mol%)
K 3PO 4
toluene, tBuOH (5:1)
90-110 °C
N
173 (>99%)
174(>99%)
Scheme 44. Palladium-catalyzed amination of aryl benzene-sulfonate and aryl tosylate with indole.
N
tBu