Chemistry Reference
In-Depth Information
MeO
2
C
CO
2
Me
MeO
2
C CO
2
Me
[Ir(COD)Cl]
2
, (PhO)
3
P
CO
2
Me
OCO
2
Me
97:3
CO
2
Me
9
.
9
.
4
9
.
7
5
Scheme 9.25
MeO
2
C
CO
2
Me
MeO
2
C CO
2
Me
[Ir(COD)Cl]
2
, (PhO)
3
P
CO
2
Me
OCOCF
3
CO
2
Me
9
7
9
7
95:5
9
7
Scheme 9.26
CO
2
Me
O
MeO
2
C
CO
2
Me
P
dL
2
+
C
O
2
HO
2
C
O
H
(Ph
3
P)
4
Pd
CO
2
M
e
9
.
9
.
8
9
Scheme 9.27
Steric factors can control the regioselectivity even in cyclization reactions, where ring size might also be
considered.
35
Even when the ring size is unfavourable, it is usually the less-substituted allyl terminus that
is attacked. An excellent example of a macrocyclization can be found in a synthesis of roseophilin
9.88
(Scheme 9.28).
36
Treatment of the molecule
9.82
, which has a sulfonyl ester as the nucleophile and a vinyl
epoxide as the electrophile, with a palladium(0) catalyst gave the thirteen-membered ring
9.83
. The functional
groups that served to stabilize the negative charge of the nucleophile both served a second function. The ester
group was incorporated into an allylic lactone
9.84
by cyclization onto the hydroxyl group derived from
the epoxide opening (see Section 9.2.6). This enabled a second palladium-catalysed reaction to establish
pyrrole
9.85
. The sulfonyl group underwent elimination at a later stage to allow introduction of the
iso
-propyl
substituent by
in situ
conjugate addition of an
iso
-propyl nucleophile. This gave the acyl pyrrole
9.87
, which
could be further elaborated to the natural product
9.88
.
9.2.2 Internal versus Terminal Attack
Following early examples,
37
a debate has continued sporadically over the possibility of attack at the central
carbon, rather than at a terminal carbon of the allyl system. It is now clear that internal attack is easily
possible. It is more efficient using simple ketone enolates or nitrile anions and is strongly favoured by the
use of chelating diamine ligands for palladium. Treatment of the isolated
-allyl palladium
9.89
with a
nitrile carbanion yielded a stable palladacyclobutane
9.90
that was characterized by X-ray crystallography
(Scheme 9.29). Exposure to CO triggered reductive elimination to give the cyclopropane
9.91
.
38
Numerous
additional examples have been reported.
39
Similarly, it has been found that the 2-chloroallyl complex
9.92
undergoes only terminal attack if triph-
enylphosphine is used as a ligand, but both central and terminal attack if bipyridyl or TMEDA is employed
(Scheme 9.30).
40
It is likely that the electron-accepting phosphine ligands increase the positive charge on the allyl ligand,
which is mostly on the terminal carbons as in allyl carbocations. A charge-controlled nucleophilic attack
yields the observed product. Amino ligands are good donors and are not
-acceptors, thus reducing the
