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N
P(
t
Bu)
2
N
Ph
Ph
R
2
N
N
L2
R
1
X
Ph
R
3
X
R
1
R
2
Step A2.
Step A1.
Method A
H
NaO
t
Bu (1.4 equiv.)
KO
t
Bu (3 equiv.)
R
1
R
2
[Pd(cinnamyl)Cl]
2
(2-4 mol%)
L2
(4-8 mol%)
1,4-dioxane or toluene
110 °C
15 unique examples
54-85 % total
over both steps
N
NH
3
(3 equiv)
R
3
NaO
t
Bu (1.4 equiv.)
KO
t
Bu (1.4 equiv.)
Method B
NH
2
Step B1.
Step B2.
R
3
X
R
2
R
3
R
1
X
Selected product structures (isolated yields over both steps):
N
S
S
N
N
N
N
R
R
Method A (R = H)
(1. X = Br,
2. X = Cl, 82 %)
Method B (R = Me)
(1. X = Cl,
2. X = Br, 83 %)
Method A
(1. X = Cl,
2. X = Cl, 88 %)
Method B
(1. X = Cl,
2. X = Br, 83 %)
Method B
(1. X = Cl,
2. X = Br, 69 %)
Figure 5.4
Scope of the [Pd(cinnamyl)Cl]
2
/BippyPhos (L2)-catalyzed synthesis of
substituted indoles and related heterocyclic derivatives involving select-
ive ammonia monoarylation.
monoarylation of ammonia (Figure 5.4). Two complementary routes for ac-
cessing N-arylated indoles from ammonia in this manner were successfully
established: (a) monoarylation of ammonia with a 2-halo(hetero)aryl-
acetylene in the presence of excess base to form an NH-indole that was
subsequently cross-coupled with an aryl halide to form the corresponding
N-arylated indole (Method A, Figure 5.4); and (b) monoarylation of ammonia
with an aryl halide to form an aniline that in turn was cross-coupled with a
2-halo(hetero)arylacetylene in the presence of excess base to form the cor-
responding substituted N-arylated indole (Method B, Figure 5.4). Collect-
ively, the application of these selective ammonia monoarylation protocols
using the [Pd(cinnamyl)Cl]
2
/L2 catalyst system provided access to a diversity
of functionalized N-arylated indoles and related heterocyclic compounds
in synthetically useful isolated yields [15 unique (hetero)indoles prepared;
54-85% total over both steps]. Moreover, although not exhaustively dem-
onstrated, control experiments indicated that these one-pot indole syntheses
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