Chemistry Reference
In-Depth Information
arising from the intramolecular PKR of the minor (
Z
)isomerof
27
were detected, in
accordance with the low PK reactivity exhibited by the
cis
-alkoxyenynes
14b
.
28
The abso-
lute configuration of the major isomer of
28
was secured by X-ray diffraction analysis, and
was fully coincident to that predicted by the working model depicted in Scheme 5.24 above.
The final steps of the synthesis consisted in the conjugate addition of a
p
-tolyl group to
28
,
Raney-nickel-promoted transformation of the five-membered ring in
29
into a
vic
-dimethyl
moiety, reductive removal (with 95% recovery) of the auxiliary alcohol, introduction of a
double bond in
30
via selenium chemistry, and a methyl conjugate addition to the enone
31
.
7-Alkoxy-4-oxy-6-hepten-1-ynes arising from the camphor-derived alcohols
4a
and
4b
undergo cobalt-promoted bicyclization with moderate yields and with good diastereos-
electivity (up to 9:1 dr).
18
The asymmetric synthesis of bicyclo[4.3.0]nonan-8-ones by
intramolecular PKR was achieved starting from 1-alkoxy-1-octen-7-ynes derived from
trans
-2-phenylcyclohexanol (Scheme 5.28).
28, 31
Ph
O
H
O
Ph
Co
2
(CO)
8
O
Isooctane, rt, 1.5 h;
reflux, 1.5 h
R
R
(Major isomer)
33a
(R = H): 45%,10:1 dr
33b
(R=Me): 65%, > 11:1 dr
32a
(R = H)
32b
(R = Me)
Scheme 5.28
The resulting diastereomers were easily separable by column chromatography, allowing
the preparation of enantiopure bicyclononanones. Thus (Scheme 5.29), the major isomer
of
33b
was submitted to Birch reduction and to samarium diiodide reductive cleavage to
afford the ketone
34
(along with a 98% recovery of the chiral auxiliary). The absolute
configuration of
34
, established by circular dichroism, confirmed that the stereochemical
outcome of the bicyclization could be correctly predicted by the now familiar mechanistic
working model of Scheme 5.24.
31
Ph
Ph
O
O
H
H
H
Li, liq NH
3
S
mI
2,
THF-Me
OH
O
O
O
60%
95%
H
H
34
Me
Me
Me
33a
Scheme 5.29
