Chemistry Reference
In-Depth Information
positions of the biphenyl moiety has a benefi cial effect of enantioselectivity. Therefore,
ligand
64b
provided excellent regio- (up to 96%) and enantioselectivities (up to 80%),
while ligand
64a
provided much lower enantioselecitivy (5% ee) [35].
10.2.6. Rhodium - Catalyzed Asymmetric Hydroformylation of Heterocyclic Olefi ns
Although aldehydes obtained through the hydroformylation of heterocyclic olefi ns are
interesting building blocks for organic synthesis, few studies have been reported on this
subject. For these substrates, regioselectivity is of special interest because it is different
from that of the corresponding acyclic ones. For example, in the hydroformylation of
2,5 - dihydrofurane, the expected product is tetrahydrofuran - 3 - carbaldehyde
A
(Scheme
10.6 ). However, considerable amounts of 2,3 - dihydrofuran and tetrahydrofuran - 2 - carb-
aldehyde
B
were present due to an isomerization process. This isomerization takes place
simultaneously with the hydroformylation reaction. When the 2,5-dihydrofuran reacts
with the rhodium hydride complex, the 3-alkyl intermediate is formed. This can evolve
to the 2,3-dihydrofuran 3 via β-hydride elimination reaction. This new substrate can
similarly evolve to produce the 2- and 3-alkyl intermediates. Although the formation of
the 3-alkyl intermediate is thermodynamically favored, the acylation occurs faster in the
2-alkyl intermediate. Regioselectivity is therefore dominated by the rate of formation
of the acyl complex [36b,c].
O
O
O
O
H[Rh]
CO
[Rh]
CHO
[Rh]
H
A
3-alkyl
O
O
O
O
[Rh]
CHO
H[Rh]
CO
[Rh]
H
B
2-alkyl
Scheme 10.6.
The modifi cation of the phosphorus ligand and the conditions of the reaction make
it possible to control the regioselectivity and prepare the 2- or 3-substituted aldehyde as
the major product [36c]. As far as we know, only two reports have been published on
the asymmetric hydroformylation of heterocyclic olefi ns using phosphine - phosphite [37]
and diphosphite [38] ligands.
The phosphine - phosphite
R
,
S
- BINAPHOS ligand
33
(Fig. 10.5) was fi rst used in the
Rh-catalyzed asymmetric hydroformylation of hereocyclic olefi ns such as 2,5-dihydrofu-
ran, 3 - pyrroline derivatives, and 4,7 - dihydro - 1,3 - dioxepin derivatives (Table 10.2 ). It
provided the optically active aldehydes as single products with enantioselectivities
between 64-97% ee. In the hydroformylation of 2,5-dihydrofuran, the Rh-
33
system
gave up to 64%, with total regioselectivity in tetrahydrofuran-3-carbaldehyde
A
.
Interestingly, the hydroformylation of 2,3-dihydrofuran led to a mixture of
A
and
B
(50/50) with an ee of 38% in
A
. The confi guration of aldehyde
A
obtained from the
