Chemistry Reference
In-Depth Information
In a very detailed study Diéguez and Claver systematically varied the configura-
tions of endocyclic furanose position 3 and exocyclic pyranose position 5, thus
creating three new ligand scaffolds that are diastereomers of successful ligand
12c
[8]. Scheme 9.3 summarizes the synthesis of all four diastereomeric ligand scaf-
folds with d-
gluco,
l-
ido
, d-
allo,
and l-
talo
configuration (
12c-15c
). For this route,
d-glucose was first transformed into its 1:2,5:6-diiisopropylidene derivative
20
as
a key intermediate. This was subsequently elaborated into d-
gluco
configured
precursor
21
and d-
allo
configured precursor
26
by known methods [9]. The
gluco
configured diol
23
and the
allo
configured diol
28
were obtained in three straight-
forward steps from precursors
21
and
26,
respectively. The synthesis of l-
ido
diol
25b
from d-
gluco
precursor
21
and l-
talo
diol
30
from d-
allo
compound
26
involved
four steps, consisting of inversion of the stereocenter at C5 via an
S
N
2 reaction.
All four diols where then transformed into the corresponding diphosphite ligands
by treatment with chlorophosphites
24a
and
24b,
yielding a total of eight ligands
(
12b,c-15b,c
).
Hydroformylation experiments with ligands
13-15
(Figure 9.2) confirmed the
previous finding that biphenyl substitution with
tert
-butyl groups in the
ortho
posi-
tion and methoxy groups in the
para
position improved stereoselectivity. Further-
more, it was again observed that the configuration of the carbohydrate scaffold has
a substantial influence on the stereoselectivity, and this time strong matched/
mismatched effects could be observed for the respective configurations of the
stereocenters at positions 3 and 5. The absolute configuration of the product was
predominantly determined by the configuration of the endocyclic stereocenter at
position 3. For d-
gluco
-configured ligand
12c
and l-
talo
-configured ligand
15c
the
configuration of the exocyclic stereocenter at position 5 enhanced the enantiose-
lectivity and, therefore, can be regarded as matched to the one at position 3. Both
ligands gave the hydroformylation products of styrene as well as two styrene
derivatives in high conversion and ee and, importantly, in opposite absolute con-
figuration. Thus these ligands, which are both accessible from d-glucose, act as
an efficient pair of
pseudo
-enantiomers. In contrast, the use of d-
allo
ligand
14c
and l-
ido
ligand
13c
resulted in a severe drop of stereoselectivity. Therefore, these
ligands can be viewed as a mismatched combination of the stereocenters at posi-
tions 3 and 5.
Diéguez [10] explored structural changes around the phosphorus donors and
incorporated both enantiomers of axially chiral BINOL into the phosphinite
residues of selected ligands
.
As the results obtained with the diastereomeric
xylo
-configured ligands
4eR
ax
and
4eS
ax
clearly demonstrated, the sense of asym-
metric induction was governed by the configuration of the respective binaphthyl
residue, which completely overrode the influence of the carbohydrate configura-
tion (Figure 9.2). The same phenomenon was observed for
gluco
- and
allo
-config-
ured ligands
12eR
ax
,S
ax
and
14eR
ax
,S
ax
with axially chiral residues. The ee remained
in all cases well below the high levels obtained with
gluco
- and
talo
-ligands
12c
and
15c.
Ligand
12d,
with an achiral biphenyl unit containing two
o
-TMS groups, was
also inferior to the ligands
12c
and
15c.
A more recent study by Claver and
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