Chemistry Reference
In-Depth Information
Following on from the establishment of ferrocene preparation and reactivity, throughout
the 1950s, 1960s, and 1970s Pauson became an internationally-leading contributor
to preparative organometallic chemistry and the discovery of the “Khand Reaction”
further enhanced his impact on the world stage, which continued well beyond his formal
retirement. As for Dr Khand, despite returning to secondary school and college teaching
employment from 1971, on an entirely voluntary basis he would appear in the Pauson
laboratory most evenings, as well as at weekends and during school holidays, and
throughout these periods established much of the original scope of this cycloaddition
reaction. Based on this level of drive and dedication, perhaps one can see some of the
reasons behind Peter Pauson's desire to have the reaction named as he did. Sadly, at the
age of 44, Ihsan Khand passed away in January 1980.
1.2 The Intermolecular Pauson-Khand Reaction
The intermolecular Pauson-Khand (P-K) process has an appreciably wide tolerance in rela-
tion to substrate structure and functionality. In relation to the alkyne component, acetylene
and terminal alkynes operate most effectively, whilst internal alkynes tend to deliver gener-
ally lower yields.
5c
With regards to the alkene partner, strained cyclic species tend to give
good yields of cyclopentenone products, whereas increasing the sterics around the olefin
reduces annulation effectiveness. In relation to these points relating to alkene reactivity, it
is noteworthy that ethylene has been shown to be an effective and widely used PK cycli-
sation component, although elevated temperatures (80-160
◦
C) and pressures of ethylene
(50-120 atm) were traditionally required.
7
Associated with the alkene strain considerations,
a theoretical study by Milet, Gimbert, and co-workers has rationalised that the reactivity of
the alkene component within P-K reactions is correlated to the back-donation of electrons
from the metal centre to the
∗
orbital (LUMO) of the olefin.
8
Furthermore, these authors
have noted that a relationship exists between the C
C C bond angle and the energy of
the LUMO: the smaller the angle, the lower the LUMO energy. This is in direct accord
with the reactivity pattern previously displayed across an olefin series: norbornene (107
◦
)
=
cyclohexene (128
◦
).
2, 9
One distinct limitation in relation to alkene applicability relates to olefins with conjugated
electron-withdrawing units, which react to deliver conjugated dienes, where the new C-C
bond has formed between the two most accessible carbon atoms of both the alkyne and
alkene components. In relation to this, styrene substrates display intermediate behaviour.
In the example shown in Scheme 1.3, following reflux in toluene, the phenylacetylene
complex
1
couples with styrene
2
to give the conjugated diene
3
as the predominant
product (39%), along with the cyclopentenone
4
in a more moderate 12% yield.
9
This
outcome is in contrast with the more recent developments from Wender and co-workers,
cyclopentene (112
◦
)
O
Tol., 110 °C
6 h
Ph
Ph
Ph
+
+
Ph
H
Co
2
(CO)
6
Ph
Ph
39%
12%
1
2
3
4
Scheme 1.3
