Chemistry Reference
In-Depth Information
n
-Bu
Et
3
SiO
n
-Bu
MeO
OMe
MeO
OMe
Grubbs I, Grubbs II
or Schrock
MeO
OMe
OSiEt
3
n
-Bu
OSiEt
3
8.269
8.270
HO
n
-Bu
1. TBAF
2. H
2
, PtO
2
3. PhSH, K
2
CO
3
,
HO
OH
Δ
HO
OH
n
-Bu
OH
8.271
Scheme 8.73
the unreacted diene isomer could be recycled. Another example of the importance of proximity for RCM can
be found in Scheme 6.68.
In other circumstances, the failure of an RCM reaction may lead to dimerization. As many natural products
are dimers, this can be useful for their synthesis. This approach was used to prepare the cylindrocyclophanes
8.271
(Scheme 8.73).
83
The diene starting material
8.269
could not undergo simple RCM due to the
para
-
disubstituted aromatic ring. Instead, a cross-metathesis (see below) occurred, followed by a macrocyclic
RCM to give
8.270
. The natural product
8.271
could then be obtained by reduction of the two alkenes and
deprotection.
Even in cases where two similar alkenes both appear to be available, conformational factors may result
in valuable stereoselectivity, as in a synthesis of the AB rings
8.273
of ciguatoxin, one of the ladder toxins
(Scheme 8.74).
84
Donor atoms in the molecule may coordinate to the 14-electron ruthenium-catalytic species and, thereby,
take up a vacant site. Basic nitrogen atoms have this effect, although there are exceptions.
85
Nevertheless,
metathesis reactions have proved very effective for the synthesis of nitrogen heterocycles,
86
as this effect can
be suppressed. One way to suppress this effect is by use of an electron-withdrawing protecting group, such
as a sulfonamide,
87
a carbamate or an amide (Scheme 8.75).
88
Another way is to carry out the reaction in the
presence of acid, so that it is the salt
8.278
with no lone pair, that cyclizes.
89
The problem is less severe with
less-basic amines, including anilines.
90
OBn
OBn
H
O
O
Grubbs
I
OBn
O
OBn
O
H
OBn
OBn
8.272
8.273
Scheme 8.74
