N
N
N
Br
Cl
N
NH 2
+
Pd(OAc) 2 (5 mol %)
Johnphos (10 mol %)
N
N
N
Br
H
N
N
75%
NaOt Bu, THF
70 ºC
ð31Þ
Amide and electron-poor aniline nucleophiles have also been employed in
heteroaryl halide amination reactions. For example, an organic synthesis procedure
was recently reported for the synthesis of ethyl 4-[(6-chloropyridin-3-yl)amino]
benzoate via N-arylation of ethyl 4-aminobenzoate with 2-chloro-4-iodopyridine
(Eq. 32) [220]. Beletskaya has illustrated that bromoindole derivatives can be
coupled with amides utilizing either Xantphos or 3,5-(CF 3 ) 2 Xantphos (22) as the
ligand in good yield (Eq. 33) [169].
N
I
Cl
H 2 N
O
OEt
+
Pd(OAc) 2 (2 mol %)
BINAP (2 mol %)
H
N
O
OEt
N
Cl
85%
Cs 2 CO 3 , toluene
110 ºC
ð32Þ
N Me
Me
EtO 2 C
MeO
Br
Me
O
NH 2
+
Pd 2 (dba) 3 (1 mol %)
22 (3 mol %)
N
Me
Me
CO 2 Et
MeO
HN
O
Me
96%
O
PAr 2
PAr 2
Ar = 3,5-(CF 3 ) 2 Ph
22
Cs 2 CO 3 , dioxane
100ºC
ð33Þ
N
Cl
Br
PdCl 2 L (2 mol %)
NH
O
NH
O
NH
NH
1.
2.
1.
2.
N
N
N
O
N
N
N
O
78 %
85 %
L = Fe
PR 2
PR 2
R =
NaOt-Bu, dioxane
100ºC
Scheme 5 Sequential Chemoselective N-Arylation of 6-Bromo-4-Chloroquinoline
Palladium-Catalyzed sp
2 C–N Bond Forming Reactions. . .
19