Chemistry Reference
In-Depth Information
TFA, 65-70 °C, 3 h
26%
+
N
N
N
S
S
1
29
30
Scheme 14 Arylation of thiophene by reaction with an aryltriazene [
57
]
Ar
1
N
2
BF
4,
KOAc (2 equiv),
5 mol% 18-crown-6, 90 min
Ar
1
38-62%
S
S
1
31
Scheme 15 Gomberg-Bachmann coupling of diazonium salts [
61
]
Table 9 Gomberg-
Bachmann coupling of
diazonium salts [
61
]
Ar
1
Conditions
Yield (%)
Ref.
4-ClC
6
H
4
KOAc, 18-crown-6
62
[
62
,
63
]
4-ClC
6
H
4
KOAc
33
[
64
]
4-BrC
6
H
4
KOAc, 18-crown-6
56
[
63
]
4-BrC
6
H
4
KOAc
20
[
58
]
4-O
2
NC
6
H
4
KOAc, 18-crown-6
38
[
62
]
4-O
2
NC
6
H
4
KOAc
23
[
58
]
Direct Arylation of Thiophenes Without a Palladium Catalyst
The synthesis of arylated thiophenes without the requirement for a palladium
catalyst is possible using aryltriazenes (Scheme
14
)[
57
] or aromatic diazonium
salts (Gomberg-Bachmann reaction) [
58
]. The usually low to moderate yields of this
type of arylation can be improved by adding phase-transfer catalysts to the reaction
medium [
59
-
61
]. Phase-transfer agents like crown ethers or quaternary salts
enhance the reactivity of the Gomberg-Bachmann reaction (Scheme
15
, Table
9
)
[
62
]. Hypervalent iodines, such as phenyliodine(III) bis(trifluoroacetate) (PIFA),
can also be utilized to promote the metal-free cross-coupling between thiophenes
and nucleophilic alkylbenzenes [
65
]. The cross-coupling proceeds via a thiophene
cation radical, which is generated by hypervalent iodine-induced SET oxidation.
One-Pot C-H Borylation/Suzuki-Miyaura Cross-Coupling
An alternative method for the direct arylation of thiophenes via C-H bond
functionalization is a one-pot C-H borylation/Suzuki-Miyaura reaction sequence
(Scheme
16
)[
66
]. The first step is the generation of the organoboron intermediates
33 and 36 from the thiophenes 32 and 35 by means of an iridium catalyst. The
second step, the Suzuki-Miyaura cross-coupling, can be accomplished subse-
quently by adding an aryl bromide to the solution of crude boronate esters without
the necessity to remove the spent iridium catalyst beforehand.
