Chemistry Reference
In-Depth Information
this problem is a one-pot combination of conjugate addition and Peterson olefination, de-
vised by P. Evans.
47
In this approach, the intermediate enolate (formed by treatment of
the adduct with organocuprate reagents) is trapped with an aldehyde, thereby facilitating
access to cross-conjugated enones.
O
O
H
1) R-M
r-D-A
2) TBAF
O
H
O
H
R
R
TMS
O
O
H
H
1) R-M
r-D-A
3 iii
2) R'CHO
R'
R'
H
R
R
Scheme 6.28
Formation of homochiral substituted cyclopentenones through a sequence
comprising conjugate addition, Peterson olefination and retro-Diels-Alder reaction. The PK
cycloadduct
3i
can be regarded as a chiral cyclopentadienone synthon.
Natural products containing a five-membered carbon ring are ubiquitous. These include
prostaglandins and phytoprostanes, which constitute an important family of biologically
active compounds. Some of these contain a cyclopentenone ring substituting two side
chains at positions 4 and 5. Evans, in collaboration with the Riera and Verdaguer group
envisioned that the conjugate addition/Peterson olefination methodology would be ideal
for preparing unsaturated prostaglandins and phytoprostanes. They exploited this method
to synthesize two of these compounds, the dehydrophytoprostanes dPPJ
1
-I and dPPJ
1
-II, in
enantiomerically pure form from the PK cycloadduct
(
)-3i
.
48
As shown in Scheme 6.29,
treatment of the starting material with lithium diethyl cuprate, followed by addition of the
+
O
1)
Et
2
CuLi
O
H
H
Et
2
O/pentane
COOMe
TMS
7
2)
O
H
COOMe
H
H
7
(+)-
3i
(99% ee)
47
46
O
COOMe
MeAlCl
2
/maleic anhydride
DCM, microwave
(16
S
,9E,11E)-dPPJ
1
-I methyl ester
99% ee
Scheme 6.29
Synthesis of dPPJ
1
-I methyl ester from enantiopure (
+
)-
3i
.
