Chemistry Reference
In-Depth Information
Me
Me
[Ir(cod)Cl]
2
base
O
Ph
O
Ph
P
N
P
N
Ph
Ph
O
O
Ir
Me
cod
9.139
9.140
Scheme 9.41
MeO
2
C
CO
2
Me
[Ir(cod)Cl]
2
, L
MeO
2
C
CO
2
Me
Ph
OCO
2
Me
Ph
9.141
9.142
96% e.e.
Scheme 9.42
Palladium-catalysed reaction of the dibenzoate
9.131
with a chloropurine
9.134
gave either enantiomer
according to the choice of ligand. The remaining benzoate could then be replaced by a substituted malonate
to give the disubstituted product
9.135
, again with palladium catalysis. After dihydroxylation of the double
bond, the malonate moiety could be stripped down to provide the hydroxymethyl substituent. Substitution of
the chloride by ammonia and removal of the acetonide gave the nucleoside
9.137
.
With iridium catalysis, the nucleophile tends to attack the more substituted carbon (Section 9.2.1). Simple
allylic acetates, therefore, give rise to chiral products directly. These products will be racemic unless an
effective chiral ligand is added.
55
While a range of phosphorus-based catalysts have been studied, phos-
phoramidites
9.139
have been found to be especially effective. Interestingly, these act as more than simple
phosphorus ligands: attack of the iridium onto a C-H bond of one of the methyl groups generates the active
species
9.140
(Scheme 9.41).
56
The addition of an amine base promotes this reaction. Asymmetric allylation
using the phosphoramidite system (“L
*
”), or its analogues, can be applied to a range of nucleophiles, includ-
ing malonates (Scheme 9.42),
57
nitro compounds (Scheme 9.43),
58
bicarbonate, giving an hydroxy group
(Scheme 9.43),
59
and amines (Scheme 9.44).
60
An asymmetric, iridium-catalysed allylation of pyridine derivative
9.148
was employed for a synthesis of
nicotine (Scheme 9.45) - see Scheme 8.76 for later steps, including ring-closing metathesis.
61
Another application of this reaction is in a synthesis of the alkaloid xenovenine
9.150
(Scheme 9.46),
62
one of many isolated from tropical frogs, which acquire the compound from their diet. While asymmet-
ric allylation provided the original stereogenic centre, Suzuki coupling, the Wittig reaction and reductive
amination were each employed for key bond-forming reactions. Additional syntheses of xenovenine can
be found in Section 6.2. The readily available allylic carbonate
9.152
was reacted with the diacylammo-
nia derivative
9.153
in the presence of an iridium complex and the chiral pre-catalyst (Scheme 9.47). The
O
2
N
NO
2
[Ir(cod)Cl]
2
, L*, Cs
2
CO
3
Ph
9.144
Ph
OCO
2
Me
OH
9.143
[Ir(cod)Cl]
2
, L*,
KHCO
3
aq.
Ph
9.145
Scheme 9.43
