Chemistry Reference
In-Depth Information
MeO
MeO
MeO
MeO
Rh(acac)(CO)
2
,
BIPHEPHOS
4.130
,
CO, H
2
, H
+
HO
-H
2
O
N
N
O
O
4.153
4.152
MeO
MeO
MeO
MeO
LiAlH
4
, Et
3
NHCl
N
N
O
4
5
4
1
5
Scheme 4.57
H
H
2
, Pd(OH)
2
N
Rh(acac)(CO)
2
,
BIPHEPHOS
4.130
,
CO, H
2
, H
+
4.158
CHO
N
3
N
3
N
N
Me
4.156
4.157
1. CF
3
CO
2
H
2. HCHO, HCO
2
H
N
4.159
Scheme 4.58
The hemi-aminal or enamide intermediates can also be used for C-C bond formation, via iminium ion
intermediates, as in a short synthesis of crispine
4.155
(Scheme 4.57).
60
Hydroformylation can be highly tolerant of functional groups. An azide, normally highly reactive towards
transition metals, can survive. This property has been exploited in a synthesis of the pyridine alkaloids anaba-
sine
4.158
and nicotine
4.159
from the same hydroformylation reaction (Scheme 4.58).
61
Another approach
to both of these alkaloids can be found in Chapter 8, Schemes 8.76 and 8.77. Double hydroformylation of the
azido diene
4.160
gave the bis-aldehyde
4.161
(Scheme 4.59). Tandem azide reduction and double reductive
amination then gave the indolizidine alkaloid, lupinine
4.162
.
62
4.4.1 Directed Hydroformylation
The typical regioselectivity of hydroformylation can be perturbed if the substrate contains a good ligand for
rhodium. If the substrate is an aliphatic alkene, the ligand can then direct rhodium to the internal position.
Nitrogen derivatives are often capable of doing this: hydroformylation of 4-pentenamide
4.163
yielded
dihydropyridone
4.164
due to coordination of the carbonyl oxygen to rhodium (Scheme 4.60),
63
while an
amine derivative
4.166
underwent a tandem hydroformylation-condensation-hydrogenation sequence to give
a piperidine
4.169
(Scheme 4.61).
64
