Chemistry Reference
In-Depth Information
Br
Br
(Ph
3
P)
2
PdCl
2
,
CuI, Et
2
NH
1. PBr
3
2.
o
-iodophenol, K
2
CO
3
OH
OH
I
5.158
5.159
(HO)
2
B
NO
2
Br
Br
O
O
5.161
I
Pd(OAc)
2
, Na
2
CO
3
5
1
6
5
.
2
PdL
n
I
Br
O
5.163
X = NO
2
couplin
g
1. Pt/C/S, H
2
2. HCl
5.164
X = NH
3
Cl
X
Scheme 5.45
A tandem alkene insertion-Suzuki coupling was used to synthesize an intermediate
5.164
for a hormone
receptor modulator on a 302 g scale (Scheme 5.45).
44
The starting material
5.160
was prepared by a selective
Sonogashira coupling, followed by installation of an iodoaryl moiety. The tandem alkene insertion-Suzuki
coupling also proceeded selectively: oxidative addition at the iodide site, followed by alkyne insertion and
coupling with the boronic acid
5.161
gave the tandem product
5.163
via the
1
-intermediate
5.162
After the
coupling, the nitro group could be chemoselectively reduced using hydrogenation over a sulfided platinum
on carbon catalyst.
A Heck-type ring closure, using formate as the reducing agent was used to form a five-membered ring and
a stereodefined
exo
-cyclic alkene in a synthesis of streptazolin
5.166
(Scheme 5.46).
45
Another synthesis of
this natural product may be found in Scheme 11.87. The mechanism of reduction by formate is shown in
Scheme 5.50.
Careful design of the substrate allows multiple bond formation in a single reaction. In the multiply
unsaturated iodide
5.167
, after oxidative addition, two alkyne insertions occur, followed by an alkene insertion
(Scheme 5.47).
46
This insertion generates a neopentyl complex, which undergoes a second alkene insertion.
The sequence is terminated by an eventual
-hydride elimination giving the steroid-like
5.168
.
Br
1. Pd(OAc)
2
, Ph
3
P,
NaOCHO
2. TBAF
OH
N
N
OTBS
H
H
O
O
O
O
5.165
5.166
Scheme 5.46
