Chemistry Reference
In-Depth Information
A most useful feature of the intramolecular PKR is its ability to generate, in a single syn-
thetic operation, tricyclic
19
or even tetracyclic
20
frameworks. Camphor-derived alcohol
4b
proved to be a practical chiral auxiliary for the asymmetric synthesis of angular triquinanes
(Scheme 5.16).
21
Me
Me
Me
Me
Me
O
Me
Me
Me
Me
Me
O
O
Co
2
(CO)
8
Me
X
O
O
Isooctane,
80-100 °C, 8-12 h
Me
H
X
(Major diastereomer)
52%, 3.3:1 dr (X = O)
29%, 2.8:1 dr (X = CH
2
)
Scheme 5.16
Although both the yields and diastereoselectivities were only moderate, the two diastere-
omers of the resulting angular triquinane were readily separated by column chromatography.
The absolute configuration of the major diastereomer showed that a mechanistic working
model similar to that depicted in Scheme 5.15 above was also operative in this case.
Other alcohols such as
trans
-2-phenylcyclohexanol or
4a
gave lower diastereoselectivities,
without the added benefit of easy separability of the diastereomeric products.
The synthesis of (
)-15-nor-pentalenene, outlined in Scheme 5.17, constituted the first
application of chiral 1-alkoxyenynes to the enantioselective preparation of natural products
by intramolecular PKR.
22
It is worth noting that the key intramolecular PKR afforded the
stereochemically pure major cycloadduct in 69% after chromatographic purification.
10-Methylthioisoborneol
9a
, that as we shall see later on gives outstanding results in
intermolecular PKRs, was also tested in intramolecular PK cyclizations.
21, 22
As can be
seen in Scheme 5.18, very good diastereoselectivities (up to 12:1 dr) were obtained in
the cyclization of alkoxyenynes derived from
9a
and leading to angular triquinanes, al-
though the fact that the resulting diastereomeric products were not separable by column
chromatography somewhat limited its applicability.
+
5.2.2 Chiral Acetylene Thioethers
The use of thiols as chiral auxiliaries in intramolecular (as well as in intermolecular) PKRs
was briefly examined by Pericas, Riera and co-workers in 1997.
23
Unfortunately only very
low diastereoselectivities could be achieved (Scheme 5.19). As we will see later, somewhat
more promising results were obtained in intermolecular reactions.
