A Route to Carbasugar Analogues - Jonathan Clayden - The ...

1.2 – Electrophilic dearomatisation
the γ-carboxylic acid; stereospecifically forming diastereomeric tetrahydroindenes 12a
and 12b.
H
H
i) Li, NH 3 , THF
MeO
CO 2 H
H
CO 2 H
ii) MeI
MeO
Me
H
CO2 H CO 2 H
12a 51%
H
i) Li, NH 3 , THF
H
MeO
CO 2 H
H
CO 2 H
ii) MeI
MeO
Me
CO2 H
12b
H
CO 2 H
46%
Scheme 1.5 – facial selectivity in gibberellin synthesis 10
1.2.2.a Asymmetric Birch reductions
The development of stereocontrol in the Birch reduction by use of chiral auxiliary was
pioneered by Schultz and co-workers, and was reviewed in 1999. 9 Schultz used a
chiral amide to activate the aromatic ring to reduction, and the resulting enolates (14)
trapped by a facially selective electrophilic quench (Scheme 1.6).
13
O
N
OMe
OMe
Na/K, NH 3 ,
t-BuOH
THF, −78 °C
N
O
O M
14
OMe
−78 °C
MeI
i) rt
ii) −78 °C
MeI
O
Me
O
Me
N
N
OMe
OMe
OMe
85%
15 dr 260:1
product of chelate
OMe
80%
dr 99:1
16
product in absence of chelate
11
Scheme 1.6 – use of a chiral auxiliary in the Birch reduction
When used in conjunction with an ortho-methoxy group (13), the proline-derived
amide is found to offer excellent diastereomeric excesses. At low temperature,
chelation by metal ions or ammonia allows the trapping enolate 14 giving diene 15.
However, raising the temperature to 25 °C is afforded the diastereomer 16 in good
18