Chemistry Reference
In-Depth Information
6.1
Introduction
In the Pauson-Khand reaction (PKR), one or two new chiral sp
3
carbons (originating from
the alkene component) arise at the newly formed cyclopentenone core. Soon after the first
PK adducts were fully characterized by Pauson and co-workers in 1973 (Scheme 6.1),
1
research and development on stereoselective versions of the reaction began. The bulk
of this work has comprised diastereoselective reactions, including syntheses based on
chiral auxiliaries (covered in the previous chapter), and stereospecific syntheses, which
require optical resolution or asymmetric transformations prior to the cyclization. Despite the
numerous examples of the latter type in the literature (chiefly, as intramolecular reactions),
they will not be discussed here.
2
O
CO OC
CO
CO
OC
R
1
= R
2
= H
R
1
= Me, R
2
= H
R
1
= Ph, R
2
= H
R
1
= R
2
= Ph
R
1
= R
2
= Et
Co
OC
Co
CO
2
(CO)
8
R
1
R
1
R
2
R
1
R
2
R
2
Scheme 6.1
The first-ever reported carbonylative cycloadditions (Pauson
et al.
).
In this chapter we aim to cover those transformations in which prochiral or racemic
substrates are transformed into homochiral (or enantioenriched) products through cobalt-
promoted PK reactions. In the absence of covalently attached chiral auxiliaries, this chem-
istry obviously requires a chiral promoter or ligand. Research on dicobalt clusters with
chiral ligands dates back to 1988, with the pioneering work of Brunner.
3
Since then,
numerous related strategies have been devised that deliver high levels of asymmetric in-
duction. However, it is fair to say that the rapid progression of asymmetric catalysis has
left the PKR behind. Synthetically useful induction levels are only attained in a few in-
tramolecular cyclizations of enynes. Nevertheless, the current state-of-the-art in ligand
design for asymmetric PKRs holds promise that these limitations will be overcome in the
near future.
6.2 Mechanistic Considerations. Topology of Alkyne-Dicobalt Clusters
Based on the general mechanism initially proposed byMagnus
4
and subsequently confirmed
by molecular orbital calculations,
5
we can outline the different pathways in the reaction of
a terminal alkyne with norbornadiene to give each enantiomer (Scheme 6.2). As observed,
the dicobalt scaffold in the complex
I
clamps the alkyne substrate by orthogonally fixing it
to the Co-Co axis, thereby giving it less conformational freedom than that of monometallic
alkyne complexes. The presence of two cobalt centers raises the degrees of freedom in
the system, since the alkene can substitute carbon monoxide at either center, leading to
the intermediates
IIA
and
IIB
. The stereochemistry of the newly formed chiral centers is
determined during the next step, in which the olefin is inserted into the less substituted
Co-C bond. Depending on the orientation of the norbornadiene,
IIA
and
IIB
can each
