Chemistry Reference
In-Depth Information
R
2 mol% [Cp*RhCl
2
]
2
,
Cu(OAc)
2
X
2
O (2 equiv),
DMF, 140 °C, 6-8 h
R
1
= Ph 63% (70% GC)
R
1
=CO
2
Bu
+
R
1
CO
2
H
S
S
13
84%
11
12
Scheme 7 Coupling of thiophene-2-carboxylic acid derivatives with alkenes [
32
]
0.2 mol% [Pd
2
(dba)
3
],
Cs
2
CO
3
(1 equiv), PivOH (2 equiv),
Ag
2
O (1.5 equiv), NEt
3
(0.5 equiv),
DME, 90 °C, 4-10 h
R
2
+
R
1
H
R
1
S
53-81%
S
R
2
14
15
16
Scheme 8 Oxidative coupling of thiophenes with terminal alkynes [
33
]
palladium(II) acetate in the presence of silver acetate and pyridine (Scheme
6
,
Table
2
)[
29
].
Alternatively, 3-vinylthiophenes 13 can be prepared through regioselective
oxidative coupling of thiophene-2-carboxylic acid derivatives 11 with different
alkenes 12 in the presence of a rhodium catalyst ([Cp*RhCl
2
]
2
) and copper
(II) acetate monohydrate as oxidant (Scheme
7
)[
32
]. Thereby, the carboxylic
group facilitates
ortho
-olefination and is subsequently removed by decarboxylation
in a one-pot sequence. Additionally, benzo[
b
]thiophenes can equally be coupled
effectively with butyl acrylate giving rise to the vinylated product in a yield of 70%.
The most common method for the introduction of alkyne groups is the catalytic
Sonogashira cross-coupling reaction. However, the direct alkynylation of thio-
phenes represents a suitable alternative, not least due to its step, and atom economy.
The palladium-catalyzed oxidative cross-coupling between differently functionali-
zed thiophenes 14 and a variety of terminal alkynes 15 proceeds efficiently with
extremely low catalyst loadings of 0.2 mol% (Scheme
8
, Table
3
)[
33
]. Notably, the
reaction is compatible with thiophenes bearing various substituents such as ketone,
aldehyde, ester, alkenyl, or halide. Of particular note is the iodo group, which is
actually extremely reactive towards Sonogashira coupling reactions. Additionally,
the utilization of terminal aryl alkynes with either electron-withdrawing or
electron-donating groups also furnishes the corresponding products 16 in good
yields.
2.1.5
Introduction of Aryl Groups
Transition Metal-Catalyzed Direct Arylation of Thiophenes with Aryl
Halides
The most convenient method for the preparation of arylated thiophenes is palladium-
catalyzed direct arylation [
34
-
36
]. This methodology is an atom-economical
