Chemistry Reference
In-Depth Information
O
Boc
2
O,
DMAP,
CH
3
CN
O
O
OH
O
t
-Boc
I
2
, CH
3
CN
- 20 °C
I
Ph
Ph
Ph
8.330
8.331
8.332
TBSO
1. MeOH, K
2
CO
3
2. TBSCl, imid.
TBSO
OH
MgBr
CuBr
O
Ph
Ph
8
.
8
3
O
OH
SO
3
H
MeOH
Ph
TBSO
OH
O
O
Grubbs II
Ph
Ph
Ph
O
Ph
8
3
8
3
Scheme 8.93
Cross-metathesis was employed to couple the two sides of the molecule in a synthesis of nupharamine
8.340
(Scheme 8.94).
107
Reduction of the alkene
8.339
and removal of the two protecting groups enabled
stereoselective reductive amination to give the alkaloid
8.340
.
All three of the alkenes in the C1-C14 fragment
8.347
of amphidinolide were installed by a combination
of asymmetric allylation and cross-metathesis (Scheme 8.95).
108
Cross-metathesis of the homoallylic alcohol
8.341
with acrolein gave the aldehyde
8.342
that was subjected to asymmetric allylation with the Duthaler
titanium reagent
8.343
. The resulting alcohol was acetylated because it was found that acetylation deactivates
the nearest double bond to cross-metathesis, thereby promoting selectivity for the next cross-metathesis, also
using acrolein, at the terminal alkene
8.344
. Another asymmetric allylation-acetylation-cross-metathesis
sequence, this time with ethyl acrylate, gave the desired natural product fragment
8.347
.
Ethenolysis, the cross-metathesis with ethene, while an important process for bulk chemicals, is only
occasionally used in organic synthesis. It was used in a synthesis of tuberostemonine
8.351
to convert an
allyl group to an ethyl group (Scheme 8.96).
109
The allyl group was introduced by Keck allylation of selenide
8.348
. The alkene was then isomerized to the internal isomer
8.350
using a catalyst derived from the Grubbs
II metathesis catalyst (see Section 8.3.10), then subjected to cross-metathesis to excise the unwanted carbon
atom, followed by alkene hydrogenation to give the natural product
8.351
.
O
O
HG II
+
O
NH
t
-Boc
NH
t
-Boc
O
OH
OH
8.337
8
.
3
3
8
8
.
3
3
1. H
2
, Pd/C
2. CF
3
CO
2
H
3. NaBH
4
H
H
H
OH
O
8.340
Scheme 8.94
