Pd(0)-Catalyzed Carboiodination: Early Developments and Recent Advances - New Trends in Cross-Coupling: Theory and Applications - page 296

To determine whether or not the Pd(II) species can generate a catalytically
active complex, 7.30a (5 mol%) was reacted under the standard reaction
conditions in the presence of 7.27. The desired C-N coupling product 7.29
was afforded in a yield comparable to the case when Pd(OAc) 2 and
P t Bu 3 HBF 4 are used as catalyst (Scheme 7.20). Therefore, 7.30a is a com-
petent precatalyst in the coupling reaction. Consistent with the findings of
Hartwig and co-workers, oxidative addition into the product is essentially
irreversible when phosphines less bulky than P t Bu 3 are employed.

7.6 Palladium-Catalyzed Carbohalogenation

7.6.1 New Reactivity Inspired by the Mizoroki-Heck Reaction
The Mizoroki-Heck reaction is a powerful method for coupling aryl halides
and alkenes. Since the coupling partner is not an organometallic reagent, as is
seen in more traditional cross-coupling reactions, a unique mechanism is
followed wherein the intermediate arylpalladium halide species undergoes
alkene carbopalladation and b-hydride elimination to generate the new C-C
bond. 88 Since its independent discovery by Heck and Mizoroki in the 1970s,
the Heck reaction has bloomed into an extensive area of research, which has
led to modern advances in substrate scope, enantioselective variants and
catalyst and ligand design. 23,87
The intermediate alkylpalladium halide species in a Heck reaction typically
undergoes rapid b-hydride elimination. However, if no syn-b-hydrogen atoms
are present or if an alkyne starting material is used to give a vinylpalladium
intermediate, the Heck pathway may be diverted by trapping this Pd(II) species
with a nucleophile (Scheme 7.21a and b). The exchange of the X-type ligand on
Pd with an exogenous nucleophile (i.e., transmetallation) facilitates reductive
elimination from the Pd(II) complex and regenerates the active Pd(0) catalyst.
Overall, the reaction constitutes a formal addition across an unsaturated
functionality. This type of reactivity was first reported by Grigg and co-workers
in 1988, where the vinylpalladium iodide intermediate 7.36 could be trapped
by a hydride nucleophile derived from formic acid (Scheme 7.21c). 89
This strategy was further developed by Grigg's group and others 90 to include
the trapping of neopentylpalladium halide intermediates with a number of
different nucleophiles such as boronic acids, 91 organotin reagents 92 and hy-
drides 93 (Scheme 7.22). The neopentylpalladium halide intermediates are
derived from intramolecular carbopalladation of a 1,1-disubstituted olefin.
Polyene cyclizations can also be combined with anionic trapping, providing
access to complex hetero- and carbocyclic frameworks (Scheme 7.22c). The
success of these reactions relies on the rate of intramolecular cyclization being
faster than the rate of premature nucleophilic trapping.
More modern examples of carbocyclization-anion capture cascades
have emerged. Zhu and co-workers combined an intramolecular carbo-
palladation with a direct C-H activation under Pd catalysis, which provided
access to the spirodihydroquinoline 7.38 (Scheme 7.23a). 94

The first