Chemistry Reference
In-Depth Information
R
2
R
3
L
n
NI
R
1
R
2
OMe
72
OMe
Ni(cod)
2
73
R
1
L
n
NI
R
3
R
1
(OC)
5
Cr
OMe
71
65
R
2
R
2
R
1
L
n
NI
R
1
R
1
R
2
SiO
2
74
R
3
R
3
76
R
3
75
O
OMe
OMe
Scheme 10.20
Proposed mechanism for the Nickel catalyzed [3
+
2] cycloaddition.
desired cyclopentenones. In this methodology (Scheme 10.21), nickel and palladium act as
the transition metal promoters and the double bond of the allyl halide serves as the alkene
component of a formal [2
1] cycloaddition. Although several examples of these pro-
cesses under mild conditions can be found in the literature, this reaction has attracted much
less interest than the Pauson-Khand reaction due to the fact that most of those cyclizations
demand the use of stoichiometric amounts of the hazardous Ni(CO)
4
complex.
33-37
+
2
+
O
Ni(CO)
4
Br
CO
2
Me
MeOH
77
72
14% yield
78
Scheme 10.21
Ni(0) catalyzed synthesis of cyclopentenones.
From the mechanistic point of view, the reaction proceeds via a well-defined sequence
of steps, supported by mechanistic studies (Scheme 10.22).
38
The first step corresponds
to the formation of the allyl nickel or allyl palladium complexes, generated by oxidative
addition of Ni(0) or Pd(0) into the allyl halide. Next, the allyl complex undergoes alkyne
insertion and concurrent carbonylation to render intermediate
81
. A 5-exo-trig cyclization
followed by a second carbonylation then furnishes the complex
82
, which evolves into the
final compound via methanol cleavage.
One important feature of the Ni(0)-catalyzed reaction is its high regioselectivity as a result
of the polarization of the triple bond. The
-allyl nickel complex acts as an electrophile
and adds to the most negative part of the alkyne. Importantly, the steric factors do not
seem to affect the mode of addition. The functional group tolerance in the alkyne is high
and this may be exploited to improve the yield and regioselectivity of the reaction. The
intermolecular counterpart of this reaction has been particularly useful for the synthesis
of bicyclo[3.3.0]octenine derivatives,
39
and the monocyclic antibiotic methylomycin B has
