Chemistry Reference
In-Depth Information
PdL
n
X
PdL
n
X
exo
endo
PdL
n
X
5.101
5
.
1
5
1
0
3
Scheme 5.31
1. Pd(OAc)
2
, P(
o
-tol)
3
, Et
3
N
2. Pd(OAc)
2
, P(
o
-tol)
3
,
CO
2
H
F
F
Br
H
H
Br
5.104
5.105
CO
2
H
Scheme 5.32
TfO
OTBS
OTBS
(Ph
3
P)
4
Pd,
K
2
CO
3
O
O
O
H
H
O
OBn
OBn
OO
O
5.106
5.107
O
Scheme 5.33
An intramolecular Heck reaction was employed in a synthesis of morphine
5.113
(Scheme 5.34).
32
An
azadecalin
5.108
was treated with a palladium catalyst to generate a fourth ring
5.109
by formation of
a quaternary centre through a Heck reaction in the
exo
-mode. After debenzylation under Lewis-acidic
conditions, epoxidation of the alkene
5.109
and
in situ
ring opening established the final ring. Oxidation
of the alcohol
5.111
and a one-pot removal of the nitrogen-protecting group and reductive amination gave
dihydrocodeinone
5.112
, which could be converted to morphine
5.113
through a known sequence.
33
5.1.9 The Asymmetric Heck Reaction
Although the Heck reaction mainly involves the formation of bonds between sp
2
-hybridized carbon atoms,
there are asymmetric versions.
34
One approach is to capture the chirality of the insertion intermediate by
ensuring the
-hydride elimination either occurs away from the site of the original alkene (Scheme 5.35), or is
pre-empted by a different step such as another insertion in a tandem process. Another approach is to provide
a symmetrical substrate with two enantiotopic alkenes (Scheme 5.36), an approach also used in metathesis
chemistry (Section 8.3.6). In all of these reactions, the source of chirality is from the employment of chiral
ligands for the palladium catalyst, often chelating bisphosphines.
The asymmetric Heck reaction is often carried out in the presence of silver salts, implying the formation of
a cationic palladium intermediate (Section 5.1.3); triflate substrates would be expected to also proceed in this
way. There are also examples of Heck reactions carried out without silver, implying that a neutral palladium
