Chemistry Reference
In-Depth Information
The mechanism of the palladium-catalyzed Nazarov reaction is as follows: the reaction is
initiated by the complexation of a palladium salt with the double bond of the divinyl ketone.
Once formed, the
complex
154
undergoes intramolecular attack to produce a palladium
enolate
155
. Next, hydrolysis with loss of ethanol renders
156
and HCl. Decomposition of
the palladium enolate by the strong acid regenerates the Pd(II) catalyst and leads to
157
(Scheme 10.45).
Et
O
O
O
O
+
EtO
Me
Me
PdCl(MeCN)
2
Me
OEt
PdCl
2
(MeCN)
2
PdCl
2
(MeCN)
Ph
Ph
155
Ph
153
154
H
2
O
EtOH
PdCl(MeCN)
2
O
OH
O
O
Me
Me
156
Ph
157
Ph
PdCl
2
(MeCN)
2
Scheme 10.45
Proposed mechanism for the Pd(II) catalyzed Nazarov reaction.
This example represents the only Nazarov reaction reported thus far, in which the tran-
sition metal catalyst does not act as a simple Lewis acid. The existing literature contains
a large number of examples of catalytic Nazarov reactions promoted by Lewis acids. The
use of transition metals as simple Lewis acids is beyond the scope of this chapter and we
only highlight one very recent example of a Nazarov reaction catalyzed by chiral copper
salts, reported recently by Tang and co-workers.
81
Chiral tris(oxazoline) copper(II) catalysts
were found to promote the reaction of divinylketones rendering the final cyclopentenones
in excellent yields and enantioselectivities as shown in Scheme 10.46.
O
O
O
CuCl
2
,
160
,NaB
ArF
O
O
90% yield
92% ee
OMe
CO
2
Me
HFIP,
t
BuOMe
Ph
Ph
161
158
HFIP: hexafluoro-2-propanol
NaB
ArF
= sodium tetrakis[3,5-bis(trifluoromethyl)phenyl] borate
O
160
=
Me
O
N
N
ON
Scheme 10.46
Copper-catayzed Nazarov reaction.
