Organic Letters
Letter
formation requires that aryl iodide can compete with di-t-
butyldiaziridinone (1) for the oxidative addition by Pd0
catalyst to start the envisioned reaction sequence as described
in Scheme 2. Herein, we report our preliminary studies on this
subject.
2-Iodostyrene 9a was used as the substrate for our initial
studies. To our delight, indole 14a was isolated in 55% yield
when 9a was treated with 5 mol % Pd(PPh3)4, di-t-
butyldiaziridinone (1) (1.5 equiv), and Cs2CO3 (2.0 equiv)
in PhCH3 at 100 °C for 48 h (Table 1, entry 1). Studies
investigated for the reaction (Table 1, entries 14−27). The
product yield varied with the ligand used. Good yields were
obtained with some of the ligands. For example, indole 14a
was isolated in 83% yield with dppf [1,1′-bis-
(diphenylphosphino)ferrocene] (Table 1, entry 27). Overall,
Pd(PPh3)4 was found to be the choice of the catalyst.
To gain some insights about the reaction mechanism,
deuterium-labeling experiments with 9a′ and 9a″ were
prepared and examined for the reaction process (Scheme 3).
Scheme 3. Deuterium-Labeling Experiments
a
Table 1. Studies on Reaction Conditions
b
yield
entry
catalyst
ligand
additive
solvent
PhMe
PhMe
PhMe
mesitylene
1,4-dioxane
DCE
(%)
1
2
3
4
5
6
7
8
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(PPh3)4
Pd(dba)2
Pd(OAc)2
PdCl2
Pd(NO3)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
Pd(TFA)2
55
61
91
83
73
39
34
31
58
66
62
30
80
44
67
78
48
26
51
5
PivOK
PivOH
PivOH
PivOH
PivOH
PivOH
PivOH
PivOH
PivOH
PivOH
PivOH
PivOH
PivOH
PivOH
PivOH
PivOH
PivOH
PivOH
PivOH
PivOH
PivOH
PivOH
PivOH
PivOH
PivOH
PivOH
Subjecting 9a′ to the reaction conditions gave 14a′ in 52%
yield with 97% D at the 2-position of the indole. With 9a″ as
the substrate, indole 14a″ was obtained in 63% yield with 93%
D at the methyl group. These results suggest that the reaction
selectively proceeded through the oxidative addition of the Pd
to aryl iodide and subsequent vinyl C−H activation (Scheme
2, path b).
MeCN
DMF
9
PPh3
PPh3
PPh3
PPh3
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
PhMe
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
PPh3
The efficient formation of indole 14a from 9a prompted us
to further explore the reaction substrate scope. As shown in
Table 2, the bisamination process can be extended to various
2-iodostyrenes (Table 2, entries 1−17). For disubstituted
terminal olefins, indoles 14a−14d were obtained in 61−90%
yields with Me, Et, Bu, and Ph substituents on the olefins
(Table 2, entries 1−4). Various substituents on the phenyl
groups, including Me, F, Cl, CF3, can be tolerated, giving the
corresponding substituted indoles (14e−14j) in 60−80%
yields. When a substituent such as an Me group was
introduced to the o-position of iodide, a low yield (25%)
was obtained for the indole product, possibly due to the steric
congestion (Table 2, entry 11). The reaction process can also
apply to trisubstituted olefins. Both an electron-donating group
like OMe and electron-withdrawing groups like CO2Et and
CN were compatible with the reaction, giving the correspond-
ing 2,3-disubstituted indoles (14l−14n) in 76−96% yields
(Table 2, entries 12−14). Cyclic olefin 9o was also effective for
the reaction, giving six-membered ring-fused indole 14o in
90% yield (Table 2, entry 15). Under the reaction conditions,
carbazole 14p was obtained with 90% yield when the olefin
was replaced with a phenyl group (Table 2, entry 16).8a
Thiophene fused indole 14q was obtained in 58% yield from 3-
(2-iodophenyl)thiophene 9q (Table 2, entry 17). However, no
reaction was observed when the thiophene was replaced with a
furan group.
P(o-tolyl)3
P(p-tolyl)3
P(p-MeOPh)3
P(p-FPh)3
P(p-ClPh)3
P(p-CF3Ph)3
P(2-furyl)3
CyPPh2
Cy2PPh
Cy3P
65
75
79
45
41
56
83
dppe
dppp
dppb
dppf
a
All reactions were performed with substrate 9a (0.30 mmol), di-t-
butyldiaziridinone 1 (0.45 mmol), Pd (0.015 mmol; Pd/P = 1/4),
additive (0.015 mmol), Cs2CO3 (0.60 mmol), and solvent (0.30 mL)
b
under Ar at 100 °C for 48 h unless otherwise noted. Isolated yield.
showed that the reaction outcome could be further influenced
by additives (Table 1, entries 2 and 3). The reaction yield was
dramatically increased to 91% with the addition of 5 mol %
PivOH (Table 1, entry 3). The PivO− is likely bound to the Pd
and facilitates the deprotonation of the C−H activation step.12
Among the solvents examined (Table 1, entries 3−8), PhCH3
gave the best result (Table 1, entry 3). The reaction process
was further investigated with different Pd catalysts and ligands.
Among Pd catalysts studied (Table 1, entries 9−13),
Pd(TFA)2 (TFA = trifluoroacetic acid) was found to be the
most effective with PPh3 as ligand (Table 1, entry 13). With
Pd(TFA)2 as the catalyst, various ligands were subsequently
The reaction can also be performed on a relatively large
scale. For example, 1.61 g of indole 14a was obtained in 86%
yield (Scheme 4). As illustrated in the case of 14a, the t-butyl
group can be removed with CF3SO3H/cyclohexane, giving
deprotected indole in 70% yield (Scheme 5).
3647
Org. Lett. 2021, 23, 3646−3651