Chemistry Reference
In-Depth Information
were probed with dibenzyl malonate as pronucleophile, which gave products with mod-
erate enantiomeric excess (
81% ee). However, for the reaction shown in Scheme 8B.13,
two ligands out of a set of 14 induced 99% ee. The synthetic scheme had been earlier
devised by Mori et al. [50], who used
BINAPO
as ligand, which induced 40% ee (66%
yield) in the alkylation step.
<
8B.2.2.1.2. Alkylations of Allylic
gem
- Dicarboxylates
The allylic alkylation at a geminal
dicarboxylate
A2
(Fig. 8B.2) is synthetically equivalent to an asymmetric addition to an
aldehyde, that is, an aldol reaction. It is important to note that regioselectivity of the
allylic substitution follows the general rule that a terminal O-substituent at the allylic
moiety favors proximal addition of a nucleophile. Apparently, reactions of substrates of
type
A2
have so far only been studied by the Trost group. Most of the results obtained
with C-nucleophiles as well as excellent procedures for the synthesis of the allylic sub-
strates have been documented by Trost and Lee in two full papers [51,52]. Mechanistic
rationalization has also been presented, using the general model described above.
Typical results are described in Scheme 8B.14 and Table 8B.2. As in the case of
substitutions at substrates of type
A1
, the ligand
DPPBA - 1
proved particularly well
suited, especially concerning enantioselectivity. Regioselectivities of the reactions of the
diacetates, obtained from corresponding enones, with dimethyl malonates were a func-
tion of the size of the group R
1
. They were perfect with R
1
=Ph or CH2OSi
t
- BuPh2.
However, with small groups, erosion down to 2.3:1 was found. The scope and the limita-
tions of this process were evaluated with a wide range of C- and heteronucleophiles.
R
2
MeO
2
C
CO
2
Me
OAc
OAc
NaCR
2
(CO
2
Me)
2
R
2
R
1
R
1
R
1
OAc
OAc
[Pd(
-C
3
H
5
)Cl]
2
(1-2.5 mol %),
(
R
,
R
)-
DPPBA-1
(3-7.5 mol %),
THF, 0°C or rt
π
MeO
2
C
CO
2
Me
A
B
Scheme 8B.14.
Pd-catalyzed asymmetric allylic alkylations of geminal diacetates.
TABLE 8B.2. Asymmetric Allylic Alkylations of Geminal Diacetates according to Scheme 8B.14
R
1
R
2
A
/
B
ee (%)
a
Yield (%)
Reference
CH
2
OSi
t
- BuPh
2
CH
3
100:0
93
87
52
CH
2
OSi
t
- BuPh
2
OCH
2
OCH
3
100:0
93
79
52
CH
2
OSi
t
- BuPh
2
NHCO
2
CH
2
CCl
3
100:0
89
92
52
Ph
CH
3
100:0
>
95
92
51
Ph
Bn
100:0
75
51
>
95
H
CH
3
5.5:1
13
81
b
5 1
CH
3
C H
3
11:1
92
86
b
,
c
5 1
CH
3
Bn
2.3:1
90
67
b
,
c
5 1
73
b
,
c
n
- C
3
H
7
CH
3
12:1
93
5 1
a
ee value of
A
.
b
Combined yield of
A
and
B
.
c
(
S
,
S
) -
DPPBA - 1
was used; ee value for
ent
-
A
.
