Chemistry Reference
In-Depth Information
OH
slow linear
hydroformylation
O
HO
HO
CHO
4.182
4.183
4.170
± L
L
L
CHO
CHO
fast directed
hydroformylation
±
L
O
O
HO
4.171
4.173
4.174
Scheme 4.66
Me
OH
OH
1. Rh(acac)(CO)
2
,
TsOH, CO, H
2
2. NaClO
2
N
CO
2
H
O
i
-Pr
P
Ph
Ph
Ph
4.184
4.185
4.186
Me
N
via
O
Ph
P
Ph
4.187
Scheme 4.67
Me
O
O
O
O
N
Rh(acac)(CO)
2
,
Ts O H , C O , H
2
F
3
C
S
F
3
C
S
O
i
-Pr
H
H
P
CHO
Ph
CF
3
CF
3
4.188
4.189
4.190
Scheme 4.68
4.4.2 Asymmetric Hydroformylation
Branched hydroformylation introduces a new stereogenic centre and, therefore, there is the opportunity to
control the new centre by the use of chiral ligands. An early application of this concept is in an industrial
synthesis of the anti-inflammatory drug, naproxen
4.193
from the corresponding styrene (Scheme 4.69).
70
The ligand for the hydroformylation reaction, chiraphite
4.194
, consisted of two bulky phosphates linked by
a chiral tether. Many other chiral ligands have been developed.
71
A problem with generating aldehydes with
an
-chiral centre is their facile racemization via their enol or enolate form. One solution to this problem is
to protect the product as its acetal
4.195
in situ
(Scheme 4.70).
72
