NH 2
Br
H
N
O
+
Pd 2 (dba) 3 (1 mol %)
RuPhos (8 mol %)
N
N
86%
PCy 2
Oi-Pr
i-PrO
RuPhos
K 3 PO 4, t-BuOH
110 ºC
ð52Þ
Cl
MeO
NH 2
Br
OMe
+
Pd(OAc) 2 (4 mol %)
P(t-Bu) 3 (5 mol %)
N
H
MeO
OMe
Clausine P
80%
NaOt-Bu, dioxane
µW, 160 ºC
ð53Þ
Several strategies have been developed for the synthesis nitrogen heterocycles from
aryl bromides bearing pendant carbonyl functionality. For example, microwavepromoted acylation of primary amines or anilines followed by intramolecular
N-arylation of the resulting amides was employed for the construction of oxindoles
(Eq. 54) [292]. Intermolecular amidation of 2
0 -bromoacetophenone derivatives
followed by base mediated intramolecular condensation has been used to generate
4-quinolones (Eq. 55) [293]. The preparation of 2-quinolones has been achieved via a
cascade intermolecular Heck arylation/intramolecular N-arylation sequence between
o-bromocinnamide and aryl iodides [294]. The synthesis of quinazolinediones via
a tandem acylation/Pd-catalyzed N-arylation reaction between o-halobenzoates and
monoalkylureas has also been described [295]. An interesting cascade reaction involving Pd-catalyzed C–C and C–N bond formation effects the conversion of
2-bromobenzamide derivatives (2 equiv) to phenanthridones (Eq. 56) [296].
OH
O
Br
NH 2
F 3 C
CF 3
+
1. µW, 300 W, 150 ºC, 30 min
N
O
F 3 C
CF 3
72%
2. Pd(OAc) 2 (3 mol %)
X-Phos (6 mol %)
Cs 2 CO 3 toluene 100 ºC
ð54Þ
O
Br
O
O
H 2 N
+
1. Pd 2 (dba) 3 (1 mol %)
Xantphos (2.5 mol %)
Cs 2 CO 3 dioxane 100 ºC
N
H
O
O
94%
2. NaOtBu 100 ºC
ð55Þ
Br
O
N
H
Bn
Me
Pd(OAc) 2 (6 mol %)
29 (5 mol %)
Cs 2 CO 3 , dioxane
100 °C
67%
OMe
Ph 2 P
29
N
O
Bn
Me
Me
ð56Þ
Our group has developed cascade Pd-catalyzed N-arylation/alkene carboamination
reactions of 2-allylanilines that afford indoline products [297, 298]. For example,
treatment of 2-allylaniline with 4-bromobiphenyl in the presence of NaOtBu and a
26
G.S. Lemen and J.P. Wolfe
Br
H
N
O
+
Pd 2 (dba) 3 (1 mol %)
RuPhos (8 mol %)
N
N
86%
PCy 2
Oi-Pr
i-PrO
RuPhos
K 3 PO 4, t-BuOH
110 ºC
ð52Þ
Cl
MeO
NH 2
Br
OMe
+
Pd(OAc) 2 (4 mol %)
P(t-Bu) 3 (5 mol %)
N
H
MeO
OMe
Clausine P
80%
NaOt-Bu, dioxane
µW, 160 ºC
ð53Þ
Several strategies have been developed for the synthesis nitrogen heterocycles from
aryl bromides bearing pendant carbonyl functionality. For example, microwavepromoted acylation of primary amines or anilines followed by intramolecular
N-arylation of the resulting amides was employed for the construction of oxindoles
(Eq. 54) [292]. Intermolecular amidation of 2
0 -bromoacetophenone derivatives
followed by base mediated intramolecular condensation has been used to generate
4-quinolones (Eq. 55) [293]. The preparation of 2-quinolones has been achieved via a
cascade intermolecular Heck arylation/intramolecular N-arylation sequence between
o-bromocinnamide and aryl iodides [294]. The synthesis of quinazolinediones via
a tandem acylation/Pd-catalyzed N-arylation reaction between o-halobenzoates and
monoalkylureas has also been described [295]. An interesting cascade reaction involving Pd-catalyzed C–C and C–N bond formation effects the conversion of
2-bromobenzamide derivatives (2 equiv) to phenanthridones (Eq. 56) [296].
OH
O
Br
NH 2
F 3 C
CF 3
+
1. µW, 300 W, 150 ºC, 30 min
N
O
F 3 C
CF 3
72%
2. Pd(OAc) 2 (3 mol %)
X-Phos (6 mol %)
Cs 2 CO 3 toluene 100 ºC
ð54Þ
O
Br
O
O
H 2 N
+
1. Pd 2 (dba) 3 (1 mol %)
Xantphos (2.5 mol %)
Cs 2 CO 3 dioxane 100 ºC
N
H
O
O
94%
2. NaOtBu 100 ºC
ð55Þ
Br
O
N
H
Bn
Me
Pd(OAc) 2 (6 mol %)
29 (5 mol %)
Cs 2 CO 3 , dioxane
100 °C
67%
OMe
Ph 2 P
29
N
O
Bn
Me
Me
ð56Þ
Our group has developed cascade Pd-catalyzed N-arylation/alkene carboamination
reactions of 2-allylanilines that afford indoline products [297, 298]. For example,
treatment of 2-allylaniline with 4-bromobiphenyl in the presence of NaOtBu and a
26
G.S. Lemen and J.P. Wolfe