Chemistry Reference
In-Depth Information
Br
O
O
1. LDA,
2. repeat
Grubbs I
8.220
8.221
Br
O
1.
Zn, )))
2. PCC
1. Li, NH
3
(l)
2.
Br
O
8.222
8.223
Grubbs I
O
O
8.224
8.225
Scheme 8.62
to the required bicyclic structure
8.243
by a transannular reaction. To achieve the transannular reaction, the
protecting-group regime was modified, presumably to provide greater flexibility for the later steps. The alkene
formed by RCM was epoxidized. Hydrolysis of the carbamate then resulted in transannular ring opening of
the epoxide by the released amine
8.242
. Finally, debenzylation gave the natural product
8.244
.
Much larger rings can be constructed using RCM. Perhaps the first example of the use of ring-closing
metathesis in natural product synthesis is in Martin's synthesis of manzamine
8.249
, with two challenging
O
O
OH
O
O
CHO
+
n
-Bu
2
BOTf, Et
3
N
N
N
O
O
8.226
8.227
8.228
Bn
Bn
OH
1. MeONHMe.HCl, Me
3
Al
2. TBSOTf, 2,6-lutidine
3.
TBSO
O
1. Grubbs II
2. Red-Al
®
MgCl
TBSO
8.229
8.230
MeO OMe
1.
H
NMe
2
O
O
2. I
2
3.
n
-Bu
3
SnH
O
O
HO
TBSO
H
8.232
8.231
Scheme 8.63
