Chemistry Reference
In-Depth Information
O
(Ph
3
P)
2
PdCl
2
,
CuI, Et
3
N
O
+
Ph
Ph
Cl
Ph
Ph
2.399
2.400
Scheme 2.124
O
dppfPdCl
2
,
CuI, P(2-Fu)
3
O
+
Ph
SEt
Ph
MeO
2.401
MeO
2.402
Scheme 2.125
OEt
OEt
2.404
OEt
(Ph
3
P)
2
PdCl
2
,
CuI, Et
3
N
Me
OEt
2.405
Me
I
2.403
OEt
Me
CO
2
Et
1.
OEt
OEt
2.406
2.407
(Ph
3
P)
2
PdCl
2
, CuI, Et
3
N
2. H
3
O
+
Scheme 2.126
The Sonogashira reaction can also be used to prepare diynes from terminal alkynes and haloalkynes. This
coupling is, however, a known reaction, the Cadiot-Chodkiewitz reaction, using only copper(I). The reaction
may proceed better under Sonogashira conditions in some cases.
146
Acid chlorides couple with alkynes under
Sonogashira conditions to give alkynyl ketones
2.400
(Scheme 2.124).
147
This is most efficient with aryl or
-unsaturated acid chlorides. Acid chlorides of simple aliphatic acids will tend to decompose via ketenes
under Sonogashira conditions. Thioesters, on the other hand, show no such tendency. A wide range may
be coupled with alkynes using palladium catalysis (Scheme 2.125).
148
In contrast to the usual Sonogashira
procedure, an excess of the copper(I) salt is required, probably because it becomes bound to the thiol released.
Certain alkynes may not be suitable for the Sonogashira reaction. The highly sensitive ethoxyacetylene
often fails, and use of its tin or zinc derivatives may be better.
149
Alkynes conjugated to electron-withdrawing
groups are frequently not effective partners, and a protected form may be required (Scheme 2.126), or the
corresponding Negishi or Stille reactions may have to be used.
150
Thus, propiolaldehyde is better replaced
by its acetal
2.404
, and propiolate esters are better replaced by the
ortho
-ester
2.406
.
A common by-product in the Sonogashira reaction is the homo-coupled diyne (Scheme 2.127). This is
usually due to the presence of O
2
. This is a long-known copper-catalysed reaction called Glaser coupling,
which is a form of homo-coupling (Section 2.10).
151
,
Palladium may also catalyse this reaction.
