synthesis and catalytic functionalization of biologically active indoles

1 Palladium-catalyzed Coupling Reactions of Indoles 10
A wide-ranging study for Suzuki reaction of nitrogen-containing cross-coupling
partners has been performed by Fu and co-workers. [31] The authors reported on a
new catalyst system that achieved Suzuki-Miyaura cross-couplings of an array of
nitrogen-containing boronic acids and aryl halides. The presence of amino groups
and nitrogen heterocycles, which are pervasive in medicinal chemistry, led often to
lower reactivity in coupling reactions. For that reason the development of a general
method for substrates including nitrogen heterocycles [32] continues to be an
important issue. Table 2 shows the general method with one single procedure for
all indole examples. In all cases under an argon atmosphere the heteroarylboronic
acid, Pd2(dba)3 and PCy3 were added to a Schlenk flask and dissolved in dioxane.
Finally the (hetero)aryl halide and aqueous K3PO4 were added. After 18 h at 100
°C the coupling products were isolated in good yields. Thereby the indole was
always posed as the boronic acid and led to interesting new indole structures,
even with unprotected nitrogen. [33] This seems to be an efficient method and was
used with inactivated aryl chlorides as well.
Table 2. Suzuki-Miyaura cross-couplings of heteroarylboronic acids with inactivated aryl halides.
Ar
X
Ar = aryl, heteroaryl
heteroaryl B(OH) 2
Pd 2(dba) 3 (1mol%)
PCy 3 (2.4 mol%)
K 3PO 4(1.7 equiv)
dioxane/H 2O
100 °C
heteroaryl Ar
Entry Heteroaryl boronic acid Ar-X Yield [%] [a]
1
2
3
4
(HO) 2B
(HO) 2B
N
H
N
H
B(OH) 2
N
Ts
N
Boc
B(OH) 2
[a] Isolated yield. [b] Boc-protecting group was removed during the Suzuki reaction.
Cl
Cl
Cl
Br
N
N
78
85
89
30 [b]