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CCl
3
CCl
3
HN
HN
O
OH
DBU, CCl
3
C
N
O
105°C
n
-Pr
MeO
n
-Pr
MeO
n
-Pr
MeO
OTBDPS
CH
2
Cl
2
HO
OTBDPS
O
OTBDPS
HN
O
NH
Cl
3
C
CCl
3
CCl
3
CCl
3
CO
2
Et
CH
3
C(OEt)
3
EtCO
2
H, 140°C
TBAF
HN
O
HN
O
Cl
3
COCHN
H
THF
n
-Pr
MeO
n
-Pr
MeO
n
-Pr
MeO
OTBDPS
OH
92%
82%
63%
HN
O
HN
O
NHCH
2
COCl
3
CCl
3
CCl
3
AcHN
CO
2
H
N
H
OMe
A-315675
SCHEME 8.19
Synthesis of compound A-315675.
H
N
O
O
HO
NH
2
OH
O
O
H
1. CCl
3
CN, DBU, CH
2
Cl
2
, -40°C
2. K
2
CO
3
, Xylene, reflux
84%
H
H
NH
NHCOCl
3
HO
OH
O
HO
11
OH
O
O
OTBDPS
OTBDPS
Tetrodotoxin
SCHEME 8.20
Synthesis of an intermediate of tetrodotoxin.
recently reported the synthesis of this natural product, both featuring an Overman
rearrangement as the key step (Scheme 8.21). Wardrop and Dickson started their
synthesis from
cis
-3-acetoxy-5-hydroxycyclopent-1-ene and prepared racemic age-
lastatin A in 14 steps with 8% overall yield [127]. Chida and coworkers, on the other
hand, started from commercially available 2,3-
O
-isopropylidene-
D
-threitol and
synthesized enantiomerically pure (
)-agelastatin A via sequence involving two
consecutive Overman rearrangements performed in a one-pot fashion, a Mislow-
Evans rearrangement and a ring-closing metathesis [128] (Scheme 8.21).
8.5. THE PETASIS-FERRIER REARRANGEMENT
In 1995, Petasis and Lu described a Lewis acid-mediated rearrangement of five-
membered enol acetals to tetrahydrofurans [129]. The next year, the same authors
reported the rearrangement of six-membered enol acetals to tetrahydropyrans [7a] in a
reaction that proceeds through the formation of oxocarbenium ion intermediates
similar to the ones described in the mechanism of the Ferrier-II rearrangement [7b]
(Scheme 8.22). The Petasis-Ferrier rearrangement is thus a Lewis acid-promoted
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