Chemistry Reference
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YH
via
X
CuI (5 mol%), K
3
PO
4
THF, 80
°
C, 6 h
X
R
X
R
R
X
Y
X
Y
7.32
7.33
7.34
[Cu]
Y = O, S
X = Cl, Br
Selected examples:
MeO
2
C
Br
Br
Br
Br
Br
Y
O
O
O
MeO
Y = O, 93%
= S, 84%
89%
93%
96%
O
2
N
O
Br
Br
Br
Cl
O
S
O
S
S
52%
88%
74%
62%
Scheme 7.14
Scope of Cu-catalyzed intramolecular C-O and C-S coupling of gem-
dihaloolefins.
NH
2
CuI (5 mol%), K
3
PO
4
(2 equiv)
Br
Br
THF
H
Br
(a) at 80
C, no reaction
(b) at 130
°
C, decomposition
°
7.27
7.29
Pd
2
(dba)
3
(2.5 mol%), P
t
Bu
3
.
HBF
4
(10 mol%)
K
3
PO
4
(3 equiv)
PhMe, 100
°
C, 16 h
64%
Scheme 7.15 Modified conditions for Pd-catalyzed synthesis of 2-bromoindole.
substitution with an electrophilic halogen source or selective-lithiation fol-
lowed by electrophilic trapping), which often suffer from poor regio-
selectivity and/or functional group tolerance.
When the optimized Ullmann-type conditions were applied to the aniline
7.27, the corresponding 2-halogenated indole 7.29 could not be obtained
(Scheme 7.15).
84
Taking inspiration from the work of Hartwig and co-
workers on the reductive elimination of aryl halides from Pd(II) (see Sections
7.4.2 and 7.4.3), upon switching to a Pd catalyst in combination with P
t
Bu
3
as ligand, the desired 2-bromoindole was obtained. This preliminary result
suggested that the steric bulk of the phosphine ligand employed may play a
significant role in preventing catalyst inhibition.
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