Chemistry Reference
In-Depth Information
intramolecular PK strategy allowed the same research group to deliver an elegant approach
to the cytotoxic sesquiterpene, quadrone, as well as the related biologically-active natural
product, terrecyclic acid.
21
Following on from these seminal examples produced during the early- to mid-1980s,
the intramolecular version of the PK annulation has continued to expand in terms of
substrate scope and reaction selectivity, as well as general utility and effectiveness. In
particular, this growth in PK potential has been driven by a range of emerging procedures
and techniques, which have appreciably enhanced the overall efficiency of the cyclisation
method, and which will be discussed through the following sections of this introductory
chapter.
1.4 Enhancing the Pauson-Khand Annulation by Reaction Promotion
Traditionally, and as detailed in many of the examples cited to this stage, PK reactions
were performed at elevated temperatures (and pressures) in aromatic or hydrocarbon
solvents.
2, 3, 5a-d
Moreover, isolation and purification of the cyclopentenone products in
the face of a plethora of organometallic by-products often presented further practical
difficulties. Additionally and at least as importantly, the PK cyclisation product yields
were more usually low to moderate. Accordingly, from the mid-1980s considerable ef-
forts were applied to the enhancement of PK techniques by a number of researchers
worldwide.
1.4.1 Dry State Adsorption
In 1985-86, Smit and co-workers reported on an appreciable practical advance in PK
methodology.
22
By adsorbing the complexed alkyne onto a support such as silica or alu-
mina and by gently heating in the dry state, reaction times were markedly reduced and
yields dramatically enhanced. To illustrate this, an example that compares a more tradi-
tional thermal process with the dry state adsorption technique is shown in Scheme 1.12.
These authors proposed that the donor sites on the solid surface were acting to enhance
decarbonylative ligand exchange. Additionally, the adsorption of the substrate onto the
(silica) support may well also act to limit conformational movement of the substrate, akin
to the Restricted Rotamer Effect, and promote cyclisation. Through the remainder of the
1980s, Smit, Caple, and co-workers, as well as others, went on expanding the range of
substrates utilised in both intra-
19b,23
and intermolecular
24
processes with this dry state
method.
Co
2
(CO)
6
O
O
O
Conditions
Thermal: isooctane, CO, 60 °C, 24 h: 29%
19a
Dry State Adsorption: SiO
2
, O
2
, 45 °C, 30 min: 75%
22
Scheme 1.12
