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O
O
Cu(OAc)
2
.2H
2
O
o-
xylene, 135 °C
4h,N
2
H
H
N
N
N
H
+
O
non-acidic C-H
N
H
O
acidic C-H
Scheme 12.96
Site-selective arylation of benzoic acid derivatives with 1,3-azoles.
O
Q
O
H
N
N
Cu(OAc)
2
-AcOH
N
H
Cu(OAc)
Cu
N
O
O
N
O
Cu(OAc)
2
-Cu(OAc)
O
O
O
H
AcOH
-Cu(OAc)
N
N
N
Cu
N
Cu
N
-AcOH
N
N
N
AcO
O
O
O
Scheme 12.97 Plausible reaction mechanism for the arylation of benzoic acid
derivatives with 1,3-azoles.
A dearomatizing ''oxy-cupration'' aided by the coordination of anilide oxygen
with the highly electrophilic Cu
III
was held responsible for such an unexpected
outcome. Later, the scope of this transformation was significantly expanded as
Weinreb amides and even simple a-aryl ketones were selectively meta-arylated.
168
Surprisingly, these transformations can also be achieved even without Cu
at a slightly elevated temperature. A detailed understanding of the mech-
anism requires further investigation as the role of Cu and the diaryliodine
reagent are not clear at present.
169
Miura and co-workers exploited the inherent C-H acidity of electron-rich
heteroarenes on one side and directing groups on other coupling partners to
devise a C-C coupling through double C-H activation (Scheme 12.96). In an
elegant study with a bidentate directing group, even non-acidic arene C-H
bonds were selectively arylated with synthetically useful yields. This rigid
coordination with the 8-aminoquinoline scaffold broadened the scope with
respect to 1,3-azoles.
170
For instance, previously unreacted thiazole, imida-
zole and oxadiazole derivatives were found to be useful substrates under the
present conditions.
171,172
A preliminary understanding suggested acetate-mediated cupration of
azoles followed by oxidative activation of relatively non-acidic arene C-H
bonds to be the key steps in the desired transformation (Scheme 12.97).
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