Biomedical Engineering Reference
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O
NH
1. CCl
3
CN, DBU, CH
2
Cl
2
, 0°C
2. Xylenes, reflux, 18 h
78%
MeN
OAc
NH
HO
OAc
HO
O
N
NHCOCl
3
Wardrop
et al.
Br
(-)-Agelastatin A
1. CCl
3
CN, DBU
CH
2
Cl
2
, -20°C to rt
2. Na
2
CO
3
,
CCl
3
CCl
3
OH
O
NH
O
NH
-Xylene, 140°C
58%
Chida
et al.
o
PhS
PhS
PhS
OH
O
NH
NHCOCCl
3
CCl
3
CPBA
CH
2
Cl
2
, -20°
C
97%
m-
1. P(OMe)
3
, MeOH, reflux
2. (PCy
3
)
2
Cl
2
Ru=CHPh, CH
2
Cl
2
, rt
Cl
3
C
O
NHCOCCl
3
N
NHCOCCl
3
N
PhS
S
O
CCl
3
Ph
3. Ms
2
O, Py, CH
2
Cl
2
, 0°C to rt
NHCOCCl
3
NHCOCCl
3
O
58%
SCHEME 8.21
Syntheses of agelastatin A by Wardrop and Dickson as well as Chida and
coworkers.
rearrangement of cyclic enol acetals to the corresponding substituted tetrahydrofurans
and tetrahydropyrans [7].
From a synthetic point of view, the Petasis-Ferrier rearrangement is a three-step
process that involves the formation of a 1,3-dioxolane-4-one or a 1,3-dioxane-4-one
starting from an
a
/
b
-hydroxy acid or an aldehyde, respectively, followed by a
Cp
2
TiMe
2
-mediated methenylation and reaction with aluminum-type Lewis acids,
such as
i
-Bu
3
Al, Me
3
Al, or Me
2
AlCl.
In the last decade, Smith et al. demonstrated [130] the power of the Petasis-
Ferrier rearrangement by using it in the synthesis of a number of complex natural
products, such as (
þ
)-spongistatin 1 [131] (Scheme 8.23), (
þ
)-phorboxazole A [132],
(
)-okilactomycin [54,133] (Scheme 8.13), (
)-clavosolide A [134] (Scheme 8.23),
(
)-kendomycin [135]
(Schemes 8.18 and 8.23),
(
þ
)-dactylolide [136], and
(
þ
)-zampanolide [137] (Scheme 8.23).
8.6. THE PRINS-PINACOL REARRANGEMENT
The Prins-pinacol rearrangement is a tandem process that leads to the formation of
oxacyclic and carbocyclic derivatives by terminating a Prins cyclization with a
pinacol rearrangement [8]. It was first discovered by Mousset and Martinet when
reacting an allylic 1,2-diol with acetone to give the unexpected tetrahydrofuran shown
O
R
2
R
2
R
2
R
2
R
2
R
3
R
4
H
O
AlR
3
R
3
R
3
R
4
H
O
R
3
R
3
O
R
4
R
4
R
1
O
R
4
R
1
O
O
R
1
R
1
R
1
O
O
H
H
H
H
H
H
H
H
O
O
AlR
3
AlR
3
SCHEME 8.22
The Petasis-Ferrier rearrangement.
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