Chemistry Reference
In-Depth Information
laboratory in routes towards the tricyclic sesquiterpenes,
-cedrene and 2-epi-
-cedren-3-
one.
6, 34g,42
In relation to how these Lewis base additives operate to enhance the efficiency of PK
reactions, it had been assumed that such species accelerate the decarbonylative-Lewis base
ligand exchange process and, in turn, promote the loss of a further CO ligand to provide a
vacant coordination site for olefin complexation. Despite these assumptions, a more recent
theoretical study by Milet and Gimbert has provided quite a different scenario, and leading
to the proposal that the Lewis base promoters achieve their PK annulation enhancing effects
by making the olefin insertion step of the reaction pathway an irreversible process.
44
1.5 Catalytic Pauson-Khand Protocols
Moving the cobalt-based PK reaction into the catalytic domain would allow this already
widely utilised transformation to assume magnified importance not only within industrial
settings but within the synthetic community as a whole. In this regard, attempts were made
to employ sub-stoichiometric quantities of octacarbonyldicobalt in some of the earliest
studies on the PK annulation process,
2a,21
with efficient cyclisations only being achieved
at relatively high catalyst loadings and when the most reactive strained alkenes were used.
In 1990 an appreciably more productive catalytic system was divulged by Rautenstrauch
and co-workers.
45
Despite the employment of only 0.22 mol% catalyst leading to a high
turnover number of 220 for Co
2
(CO)
8
, the reaction conditions for this PK annulation
between 1-heptyne and ethylene required partial pressures at room temperature of 100 bar
CO and 40 bar C
2
H
4
, and heating to 150
◦
C (to deliver a total pressure of 310-360 bar)
over 16 h reaction time, leading to a 49% yield of the desired cyclopentenone product.
From this stage and over recent years a number of significantly more effective Co-catalysed
processes have been formulated by a number of research groups.
5j
Since the protocols
using cobalt-based catalysts will be discussed in more detail elsewhere (Chapter 3), only a
selection of methods will be discussed here to provided a flavour of the advances made to
date.
In 1994 Jeong and co-workers divulged the first practically efficient catalytic PK sys-
tem.
46
As illustrated in Scheme 1.22, with the key introduction of a phosphite ligand, low
levels of Co
2
(CO)
8
could be employed combined with relatively modest CO pressures.
Despite the obvious successes of this approach, this method appeared to be limited to
intermolecular examples, coupled with a requirement for 120
◦
C reaction temperatures.
Following on from this, Krafft has also formulated a series of equally effective catalytic
Co
2
(CO)
8
-based protocols (at lower temperatures and CO pressures) with cyclohexylamine
as the reaction additive.
47
EtO
2
C
EtO
2
C
Co
2
(CO)
8
(3 mol%), P(OPh)
3
(10 mol%)
CO (3 atm), DME, 120 °C, 24 h
O
EtO
2
CCO
2
Et
82%
Scheme 1.22
