Chemistry Reference
In-Depth Information
H
P
P
H
65
Figure 10.16.
TangPhos ligand
65
.
Their hydroformylation is interesting due to the following features: (a) desymme-
trization of the olefi n will generate three chiral carbon centers upon one C- C bond
formation; (b) there are no regioselectivity issues due to the symmetry of such olefi ns,
although high enantio-, endo-, and exoselectivities are important; and (c) functional
groups located opposite to the C=C bond could be versatile, which may lead to inter-
esting building blocks [39]. Despite these, the initial work in this fi eld provided low
selectivities (20-60 % ee) [40]. However, recently, Bunel and coworkers used a com-
binatorial approach (screening 130 chiral phosphine, phosphite, phosphine-phosphite,
and phosphoroamidite ligands) and found that diphospholane ligand TangPhos
65
(Fig. 10.16) showed the highest enantioselectivities. It provided enantioselectivities up
to 93% in the Rh-catalyzed asymmetric hydroformylation of several [2.2.1]-bicyclic
olefi ns [39] .
10.3. ASYMMETRIC ALKOXYCARBONYLATION AND
RELATED REACTIONS
10.3.1 General Aspects
The asymmetric synthesis of carboxylic acids and their related esters is performed from
olefi ns, carbon monoxide, and water or alcohols (represented as R
2
OH in Scheme 10.8)
in the presence of a chiral palladium catalyst. Considering that these chiral carboxylic
acids are usually obtained from the oxidation of chiral aldehydes synthesized by hydro-
formylation of vinylarenes, the asymmetric hydroxy- and alkoxycarbonylation reactions
attract much attention from both academic and industrial research groups [4b,6e,41].
However, less successful work has yet been reported on these reactions than on hydro-
formylation due to the diffi culty of obtaining simultaneously both high regio- and enan-
tioselectivities. The alkoxycarbonylation of vinylarenes is of particular relevance, as the
products (2-arylpropionic acid and derivatives) are precursors for nonsteroidal anti-
infl ammatory drugs, particularly ibuprofen and naproxen [42].
O
R
1
O
[Pd]
R
1
+ CO + R
2
OH
+
R
1
OR
2
*
2
OR
R
2
= H, alkyl
Scheme 10.8.
