Chemistry Reference
In-Depth Information
Tab l e 5 . 4
Me
Me
Me
O
Me
Me
Me
O
S
H
S
Co
2
(CO)
8,
CH
2
Cl
2,
rt;
X
O
X
MeCN, reflux, 15 min
H
36a
-
d
35a
-
d
Enyne
X
Yield (%)
Dr
Product
35a
CH
2
36a
50
> 44:1
35b
CMe
2
36b
65
> 44:1
35c
C(CO
2
Et)
2
36c
60
> 44:1
N(CO
2
t
Bu)
35d
36d
60
> 44:1
5.2.5 Alkenyl Sulfoxides
The use of sulfoxides as chiral controllers in intramolecular PKRs was developed by Adrio
and Carretero in 1999.
32
After testing several sulfinyl groups, these authors found that the in-
tramolecular PKR of (
S
)-
trans
-
tert
-butylsulfinyl-1,6-enynes
35a
-
d
took place with accept-
able yields (50-65%) and with excellent diastereoselectivities (
44:1 dr), when the inter-
mediate dicobalt hexacarbonyl complexes were heated in acetonitrile (Table 5.4). It is worth
noting that only terminal acetylenes could be used in the reaction, and that a single example
of the cyclization of a
tert
-butylsulfinyl-1,7-enyne took place with practically total diastere-
oselectivity towards the expected bicyclononenone but with a much reduced yield (30%).
32
Subsequently, the authors found that the cyclization transcurred without racemization at
the sulfur atom, and that the thermal PKRs of the dicobalt hexacarbonyl complexes of the
tert
-butylsulfoxides
cis
-
35a
and
cis
-
35c
gave the same bicyclooctenones
36a
(41% yield)
and
36c
(56% yield) obtained from the diastereomeric enynes
trans
-
35a
and
trans
-
35c
.
This is particularly gratifying from a practical point of view, since the sulfinylenynes
35
are
initially obtained as
trans/cis
mixtures in a Wadsworth-Emmons olefination step and this
means that these mixtures can be directly used for the PK bicyclization (Scheme 5.30). Most
probably, the bicyclooctenone
37a
, initially formed from the
cis
-enyne
35a
, isomerizes in
the reaction medium towards the thermodynamically more stable enone
36a
, that places
the bulky
tert
-butylsulfinyl substituent in the
exo
face.
The stereochemical outcome of the reaction can be accounted for in the following way
(Scheme 5.31): Both computational studies and experimental evidence has established
that in
trans
,
-unsaturated sulfoxides the most stable conformation has a dihedral an-
C-S-O of
ca
.0
◦
. Thus, complexation by cobalt takes place exclusively in the
gle C
=
