Chemistry Reference
In-Depth Information
disclose several approaches to a chiral version of the Pauson-Khand reaction using chiral
substrates.
4.2
Intramolecular Diastereoselective Pauson-Khand Reaction
The earliest example of diastereoselective PKR based on chiral pool methodology was
published by Magnus
et al.
They described an elegant, enantiospecific synthesis of a 6a-
carbocycline analogue,
4
, based on stereospecific dicobaltoctacarbonyl-mediated cycliza-
tion of acetonide
2
(Scheme 4.1), which is produced in a few steps from D-ribonolactone
1
.
1
Soon after, the same group published a study on the stereospecific synthesis of cytotoxic
sesquiterpene (
/-)-quadrone based on the same concept, that is, a dicobaltoctacarbonyl-
mediated enyne cyclization reaction.
2
+
H
SiMe
3
O
HO
2
C
HO
Me
3
Si
O
O
H
(i) Co
2
(CO)
8
(ii)
H
HO
H
H
H
Δ
H
OH
R
O
O
H
H
OH
OH
OH
1
2
3
4
Scheme 4.1
Synthesis of 6a-carbocycline analog
4
based on the stereospecific dicobaltoc-
tacarbonyl mediated cyclization.
Subsequently, Mulzer
et al.
independently investigated dicobaltoctacarbonyl-mediated
cyclization of acyclic enynes
6a-d
, which are readily accessible from (
R
)- and (
S
)-2,3-
O
-isopropylidene-glyceraldehyde,
5
.
3
As an example, the treatment of enyne
6b
with
Co
2
(CO)
8
at room temperature followed by thermal decomposition afforded the enan-
tiomerically pure, bicyclic compound
7
in good yield (43%). In contrast, derivatives
6c
and
6d
gave mixtures of diastereoisomers
8
and
9
in 3:1 and 1:1 ratios, respectively, via the
same reaction (Scheme 4.2). The stereoselectivity of the cyclization of
6b
-
6d
is dictated
by the requirement that C-1/C-6 and C-2/C-5 are sufficiently close to allow formation
of the cyclopentenone ring. This is best fulfilled by a roughly parallel alignment of the
olefin and cobalt-complexed alkyne moieties. Based on the stereochemical outcomes of
two possible reactive geometries, that is,
10
and
11
(Scheme 4.3), which leads to the for-
mation of
7
and its C-5 epimer, respectively, transition state
10
is highly favored. This is
probably due to the anti-periplanar arrangement of R
2
with respect to the newly created
C-C bond. For the cyclization of
6c
and
6d
, the same effect dominates; however, the
preference for a geometry like
10
is not as high due to the smaller size of R
2
(OBz). More-
over, it is evident that OR
1
has a stereoregulating influence similar in magnitude to that of
R
2
and directs cyclization to preferentially place OR
1
on the convex face of the bicyclic
system.
