Chemistry Reference
In-Depth Information
OMe
O
3
/O
2
MeOH;
CO
2
Me
CO
2
Me
NaBH
4
O
O
OMe
O
N
MeO
N
MeO
N
thiourea
AcOH
O
MeO
OH
OH
441
(unstable)
442
(81%)
440
O
OMe
Ph
O
O
CO
2
Me
OH
OMe
OMe
O
N
OH
OBn
N
MeO
O
N
MeO
OMe
N
O
OH
OH
O
443
(82%)
444
(81%)
445
(56%)
446
(84%)
CO
2
Me
CO
2
Me
CO
2
Me
OAc
S
O
O
O
O
N
N
MeO
N
MeO
N
MeO
OAc
MeO
S
N
CO
2
Et
OH
447
(88%)
448
(47%)
449
(75%)
450
(27%)
SCHEME 10.71.
Employing this dienone cleavage strategy in concert with diastereoselective
nitrenium ion cyclization, Wardrop and Burge have completed the asymmetric
synthesis of (
),
170
a neuroexcitotoxic amino acid isolated from
the marine sponge
Dysidea herbacea
(Scheme 10.72).
171
In the key transformation,
PIFA-mediated azaspirocyclization of
O-
methyl hydroxamate
)-dysibetaine (
413
451
generated spiro
compound
452
with good diastereoselection, thereby establishing the quaternary
OTIPS
OMe
OMe
OTIPS
O
3
/O
2
PIFA
O
N
MeOH;
thiourea
MeOH-CH
2
Cl
2
-78°C to -30°C
MeO
HN
OMe
O
O
OMe
452
(99%, d.r. = 9:1)
451
OTIPS
OH
OTIPS
O
O
O
NaBH
4
7 steps
O
MeO
MeO
O
O
O
H
N
N
H
AcOH
OH
OMe
454
(91%)
NMe
3
OMe
O
453
(unstable)
(-)-Dysibetaine (
413
) (13%)
SCHEME 10.72.
