Chemistry Reference
In-Depth Information
excess above 34% ee, and 73-81% ee could be obtained with good yields (72-81%) for
79
[124,191] .
Synthetic applications of this chemistry were showcased by Hashimoto and cowork-
ers, who applied the site-controlled
γ
-lactam formation to the syntheses of (
R
) - (
−
) -
baclofen (
56
) [124] , a GABA
B
receptor agonist, and (
R
) - (
) - rolipram (
83
) [193] , a
phosphodiesterase type IV inhibitor (Scheme 4.16), where the C-H insertion was the
key step. In the (
R
) - (
−
)-rolipram synthesis, the desired intermediate
82
was formed in
74% yield and with 88% ee. Rh
2
(
S
- BPTTL)
4
was the optimal catalyst for this reaction
[193]. In the synthesis of (
R
) - (
−
) - baclofen, Rh
2
(
S
- PTTL)
4
was found to be optimal and
gave 83% yield of the desired intermediate
84
in 82% ee [124]. The 1,3-oxazine tethered
compound
85
was used in the key step of a synthesis of trinem
87
(Scheme 4.17 ) [194] .
Exclusive formation of the
−
-lactam was observed in this system. The optimal catalyst
was found to be Rh
2
(
S
- PTA)
4
, which gave the desired intermediate
86
in 71% yield and
with 84% ee [194] .
β
O
2
N
O
HN
O
N
Rh
2
(
S
-BPTTL)
4
CH
2
Cl
2
, 23°C
O
CO
2
Me
O
74% yield
88% ee
O
2
N
OMe
82
83
O
OMe
(
R
)-(-)-rolipram
N
CO
2
Me
N
2
O
2
N
NH
2
R
81
CO
2
H
O
N
Rh
2
(
S
-PTTL)
4
CH
2
Cl
2
, 23°C
CO
2
Me
HCl
83% yield
82% ee
Cl
84
56
(
R
)-(-)-baclofen HCl
Cl
Scheme 4.16.
Synthetic applications of enantioselective
γ
- lactam formation.
O
N
O
Rh
2
(
S
-PTA)
4
O
O
O
N
N
O
Toluene, 0°C
H
H
TBSO
CO
2
Me
Me
H
H
N
2
CO
2
Me
71% yield
84% ee
85
87
86
Scheme 4.17.
β
- Lactam formation of
85
in the synthesis of trinem
87
.
