Chemistry Reference
In-Depth Information
I
Pd(OAc)
2
,
i
-Pr
2
NEt
BnNEt
3
+
Cl
-
+
MeO
OMe
O
NHCO
2
Et
5.90
5.91
OMe
CO
2
Me
O
CF
3
CO
2
H
OMe
N
NHCO
2
Et
CO
2
Et
5
2
5
9
Scheme 5.28
PhI, Et
3
N,
Pd(OAc)
2
, CH
3
CN
Ph
O
OH
5.94
5.95
tautomerism
insertion
β
-hydride
elimination
PdL
n
I
Ph
OH
Ph
OH
5
9
5
.
7
Scheme 5.29
O
Pd(OAc)
2
,
P(
o
-tol)
3
,
n
-Bu
3
N
Br
OH
OH
+
OH
N
N
5.98
5
.
9
9
5
0
0
Scheme 5.30
This chemistry was employed on a 200 g scale to prepare a functionalized pyridyl ketone
5.100
,
an intermediate in a drug candidate synthesis (Scheme 5.30).
28
The choice of base proved to be the key
to minimizing formation of the regular Heck product.
5.1.8 The Intramolecular Heck Reaction
The intramolecular Heck reaction is a powerful method for ring formation.
29
Depending on the substrate
structure, the question of
exo
-or
endo
-ring formation may need to be addressed (Scheme 5.31). In principle,
intramolecular alkene insertion can yield either the
exo
-product
5.101
or the
endo
-product
5.103
. Generally,
the
exo
-product
5.101
is obtained.
Two Heck reactions, the first intramolecular in an
exo
- sense, the second intermolecular, were used to
prepare an intermediate
5.105
for a prostaglandin receptor antagonist on a 2.17 kg scale (Scheme 5.32).
30
An intramolecular Heck reaction of a vinyl triflate
5.106
with an
exo
-ring closure was employed to form an
eight-membered ring in a synthesis of taxol (Scheme 5.33).
31
