Chemistry Reference
In-Depth Information
Stereochemically pure adduct
ent
-
47
(obtained in a 58% yield from the intermolecu-
lar PKR between norbornadiene and the dicobalt hexacarbonyl complex of (1
S
,2
R
)-(2-
phenylcyclohexyloxy)ethyne)
35
was converted into the tricyclic ketone
58
byatwo-step
sequence involving cuprate addition and samarium-mediated reductive cleavage (52% over-
all yield). It is worth noting that the same compound was obtained in 92% ee and in 47%
overall yield from adduct
ent
-
55
. The Lewis-acid mediated retro Diels-Alder reaction read-
ily furnished the cyclopentenone
59
, which under lithium perchlorate catalysis experienced
the stereoselective Michael addition of a ketene acetal to yield on acidic workup the known
(
+
)-brefeldin A precursor
60
.
5.3.2 Chiral Acetylene Thioethers
The first studies on the use of chiral acetylene thioethers in the intermolecular PKR, reported
by Pericas, Riera, and co-workers in 1997,
23
showed that the applicability of these com-
pounds was rather limited. Interestingly enough, however, cycloaddition with relatively
unreactive olefins such as cyclopentene took place with promising diastereoselectivities
(Scheme 5.43). The reaction of this acetylene thioether with norbornadiene in the same
reaction conditions took place with a good yield (85%), but with very poor diastereoselec-
tivities (1.7:1 dr). The diastereomers were not easily separable by column chromatography,
and no efforts were made to ascertain the stereochemical sense of induction of the process.
Me
Me
Me
Me
S
*
Co
2
(CO)
8
;
H
O
S
Me
O
Me
Me
Me
*
Cyclopentene,
6 equiv NMO,
CH
2
Cl
2
, -20
°
C,
48 h
O
Me
Me
Me
Me
48%, 4.6:1 dr
Scheme 5.43
Somewhat better diastereoselectivities (but much lower yields) were achieved through
chiral acetylene dithioethers (Scheme 5.44).
45
Me
Me
Me
Me
O
Me
Me
Co
2
(CO)
8
;
S
O
*RS
O
S
Norbornadiene,
6 equiv NMO,
CH
2
Cl
2
, 0 °C,
15 h
Me
Me
Me
*RS
Me
Me
Me
25%, 6:1 dr
Scheme 5.44
