Chemistry Reference
In-Depth Information
52
(3 equiv),
NMP, 23 °C, 48 h
I
CO
2
Cu
S
S
S
S
77%
51
53
52
Scheme 23 Synthesis of 2,2
0
-bithiophene by Ullmann-like reductive coupling [
120
]
1. BuLi, C uI
2. R
1
I
R
1
S
S
1
54
Scheme 24 Coupling of thiophenes via 2-thienylcopper [
121
]
Table 13 Coupling of
thiophenes via
2-thienylcopper [
121
]
R
1
Yield (%)
Ph
41
4-Tol
36
2,6-(MeO)
2
C
6
H
3
28
2-thienyl
2
indicating the significance of the base for a successful Suzuki-Miyaura reaction.
The addition of a second aryl halide in combination with potassium phosphate to
the reaction pot leads to a subsequent Suzuki-Miyaura cross-coupling reaction.
2.2.2 Substitution Reactions Involving Organocopper Derivatives
The synthesis of symmetrical bithienyls is possible via the Ullmann reaction [
116
-
119
]. Here, halogenated thiophenes are coupled with one another at elevated tem-
peratures via copper catalysis forming the corresponding biaryls in low to moderate
yields. 2,2
0
-Bithiophene 53 can as well be generated at room temperature through an
Ullmann-like reductive coupling of 2-iodothiophene 51, which is promoted by
copper(I) thiophene-2-carboxylate 52 (Scheme
23
)[
120
]. The high reaction temper-
atures required for an Ullmann reaction are achieved using high boiling solvents such
as nitrobenzene, quinoline, or
N
,
N
-dimethylformamide; however, the use of the last
increases the chance of a dehalogenation side reaction (ArX
ArH) [
117
]. In order
to avoid the replacement of halogen by hydrogen, the synthesis of bithienyls via
copper intermediates is a more convenient method [
121
-
128
]. For instance, the
synthesis of 2-arylthiophenes 54 is possible via the initial preparation of
2-thienylcopper by the reaction between 2-thienyllithium and copper(I) salts
(Scheme
24
, Table
13
)[
121
]. 2-Thienylcopper subsequently reacts with various
iodoarenes giving rise to the corresponding products 54 in moderate yields.
The utilization of organocuprates is another useful method for the formation of
carbon-carbon bonds. Typical organocuprate-assisted reactions are conjugate
!
