Chemistry Reference
In-Depth Information
R
R
R
Δ
R
O
R'
Co(CO)
3
(OC)
3
Co
R'
R'
R'
7
.
7
.
8
Scheme 7.9
7.3 The Pauson-Khand Reaction
The alkyne complexes undergo a remarkable cyclization reaction on heating with an alkene and carbon
monoxide. This is the Pauson-Khand reaction,
14,15
which is a formal cycloaddition of a complexed alkyne
7.2
, an alkene and a molecule of carbon monoxide to give a cyclopentenone
7.38
(Schemes 7.9 and 7.10).
The mechanismproceeds via initial CO dissociation fromone of the 18 electron cobalt atoms of the complex
7.2
(Scheme 7.11). This opens up a coordination site for an alkene molecule. The coordinated alkene then
inserts into one of the C-Co bonds, starting to open up the tetrahedron. CO insertion into the newly formed
C-Co bond is followed by reductive elimination. This generates a cyclopentenone, still coordinated to cobalt.
Under the reaction conditions, decomplexation occurs to give the product
7.38
.
For unsymmetrical reactions, modest regioselectivity is observed, with the larger alkyne substituent
(Scheme 7.10) and the larger alkene substituent (Scheme 7.12) ending up
- to the carbonyl group. The
reaction is more efficient, and issues of regioselectivity are solved, when the reaction is carried out in an
intramolecular fashion (Scheme 7.13). A chiral centre in the tether may also control the stereoselectivity
of the reaction.
16
Allenes can also provide the alkene component (Scheme 7.14); which of the two alkene
moieties of the allene participates depends upon the precise structure.
17,18
In many cases, yields have been modest. Various “tricks” have been introduced to boost yields. The
Pauson-Khand reaction can be promoted by a wide range of additives, including amine oxides,
19
phosphine
oxides,
20
sulfoxides,
21
amines
22
and sulfides.
23
Water can have an effect.
24
Special reaction conditions,
including ultrasonication,
25
ultraviolet irradiation
26
and “dry-state absorption” on silica gel,
27
have been
employed.
A problem is that the Pauson-Khand reaction uses two equivalents of cobalt. More efficient versions,
many of them catalytic,
28
using other metals have been developed. These include carbonyl complexes of
titanium,
29
molybdenum,
30
tungsten (Scheme 7.15),
31
rhodium
32
and ruthenium (Scheme 7.16).
33
Rhodium,
iridium
34,35
and iron (Scheme 7.17)
36
have also been used with two alkynes to give cyclopentadienones, often
as complexes
7.59
. A version of the Pauson-Khand reaction employing a nickel catalyst and an isonitrile in
place of CO has been developed.
37
The product is an imine, which can be hydrolysed to a cyclopentenone.
A rhodium-catalysed Pauson-Khand reaction of an allenic alkyne
7.60
was employed to form the cy-
clopentenone ring of Achalensolide
7.65
, a guaianolide natural product (Scheme 7.18).
38
The butenolide ring
was then constructed by free radical chemistry.
Me
Me
+
+
Co(CO)
3
Co(CO)
2
(OC)
3
Co
O
7.39
7.40
Scheme 7.10
