Chemistry Reference
In-Depth Information
Palucki et al. at Merck & Co., Inc. investigated the allylic alkylation, especially the
formation of the chiral catalyst from Mo(CO)
6
in detail [213]. The complete catalyst
formation is necessary to avoid unselective background reactions by Mo(CO)
6
. While
the activation needed 4 h at 90°C if the reaction was carried out in toluene, the same
result was obtained in THF after 2-3 h at 65°C, although the allylation reaction gave
slightly better results in toluene (97% ee, 95% vs). Comparison studies carried out with
Mo(CO)
6
, (EtCN)
3
Mo(CO)
3
, and (C
7
H
8
)Mo(CO)
3
indicate that the same active chiral
catalyst is formed, as all these precatalysts give comparable results.
Nearly at the same time, Hallberg, Moberg, and others reported asymmetric allylation
with Mo(CO)
6
using microwave heating [214]. In the “standard reaction” using cinnamyl
methyl carbonate as substrate and ligand
L43a
, the reaction was complete after 4 min at
165°C (Table 8B.31, entry 1). The yield and the regioselectivity were somewhat lower
if the reaction was run in an oil bath at the same temperature for the same time (entry
2). They showed that this protocol is also suitable for solid-phase allylic alkylations. The
optimized conditions were also used to investigate the effect of substituents with differ-
ent electronic and steric properties (
L44
) on the outcome of the reaction (Table 8B.31)
[215] . The infl uence of 4-substituents (R
1
) on the enantioselectivity was marginal (96-
99% ee), but the regioselectivity varied signifi cantly (entries 3-6). Interestingly, substitu-
TABLE 8B.31. Allylic Alkylations Under Microwave Irradiation
MeO
2
C
CO
2
Me
+
NaCH(CO
2
Me)
2
CO
2
Me
Ph
Ph
OCO
2
Me
Mo(CO)
6
(4 mol %),
L*
Ph
CO
2
Me
b
l
R
1
=OMe,R
2
=H
R
1
=Cl,R
2
=H
R
1
=NC
4
H
8,
R
2
=H
R
1
=NO
2
,R
2
=H
R
1
=H,R
2
=Me
R
1
=H,R
2
=OMe
L44
a
b
c
d
e
f
RR
O
O
NH
HN
R
1
N
N
R
1
R
2
R
2
Ligand
b
Entry
T ( ° C)
t (min)
Yield (%)
b
:
l
ee (%)
1
L43a
165
4
86
19:1
98 (
S
)
2
L43a
165
a
5
59
11:1
98 (
S
)
3
L44a
165
4
88
41:1
99 (
S
)
4
L44b
165
6
89
74:1
96 (
S
)
5
L44c
170
12
91
88:1
96 (
S
)
6
L44d
150
15
37
16:1
97 (
S
)
7
L44e
165
5
30
13:1
79 (
S
)
8
L44f
160
6
0
0
0
9
L43b
160
25
95
99:1
97 (
S
)
a
Conventional heating.
b
Ligands
L43a - f
are listed in (Figure 8B.22).
