Pd(0)-Catalyzed Carboiodination: Early Developments and Recent Advances - New Trends in Cross-Coupling: Theory and Applications - page 300

carbocyclization-intermolecular direct arylation protocol was developed by
Fagnou and co-workers, whereby the neopentylpalladium(II) intermediate
could be trapped by a sulfur-containing heterocycle, representing an early
contribution to the field of direct sp 3 -sp 2 arylations (Scheme 7.23b). 95 The
use of K 4 [Fe(CN) 6 ] in tandem cyclization-cyanations was also explored by Zhu
and co-workers (Scheme 7.23c). 96 This method provided access to the formal
carbocyanation product 7.40. All of the examples highlighted so far involve
an intramolecular carbopalladation step and thus have the advantage of
high regioselectivity. Examples featuring intermolecular carbopalladation on
to an olefin or alkyne followed by anionic trapping are rare. In such cases,
there are several competing mechanistic pathways: (a) direct intermolecular
coupling between the aryl halide and nucleophile, (b) standard Heck re-
action and (c) uncontrolled oligomerization terminated with random events
of nucleophilic trapping. Nevertheless, biased systems utilizing norbor-
nene 97 or symmetrical alkynes 98 as the Heck acceptor have been reported.
7.6.2 Development of a Palladium-Catalyzed Carboiodination
of Alkenes
The anion capture reactions discussed in Section 7.6.1 are a powerful
method for alkene and alkyne difunctionalization. Another interesting
mechanistic possibility that could arise from the RPd(II)X species would be
direct carbon-halogen reductive elimination (Scheme 7.24). Overall, this
carbohalogenation reaction would lead to the formation of two new bonds
(one carbon-carbon and one carbon-halogen bond) across an olefin, leaving
the reactive halogen functionality intact in the final product.
In 2011, Newman and Lautens reported the first carbohalogenation re-
action invoking carbon-halogen reductive elimination from an alkyl Pd(II)
halide intermediate. 2 To avoid the energetically favorable Heck reaction,
their method utilized biased aryl iodides 7.41 that were bound to a pendent
1,1-disubstituted olefin [eqn (7.7)]. In this particular system, the neo-
pentylpalladium(II) halide intermediate 7.43 that is formed after olefin
insertion cannot undergo b-hydride elimination, as there are no syn-
b-hydrogen atoms available. Notably, the use of 1,1-disubstituted olefins in
domino cyclic carbopalladations is well precedented in the literature. 90 For
the carbohalogenation studies, initial screening of well-defined PdL 2 cata-
lysts at 90 1C revealed that bulky phosphine ligands were essential for re-
activity, with QPhos giving the best results (Table 7.4, Entries 1-3). No basic
additives were required since the transformation does not generate HX as a
by-product, unlike the standard Heck reaction. Less bulky ligands, such a
PCy 3 and P(o-tol) 3 , did not provide any detectable amounts of the desired
carbohalogenation product (Table 7.4, Entries 4 and 5).
At elevated temperature (100 1C), the catalyst loading could be decreased
from 5.0 to 2.5 mol% (Table 7.4, entry 1). Using these optimized conditions,
a range of oxygen- and nitrogen-containing five- and six-membered hetero-
cycles were prepared in high yield (Scheme 7.25). The use of aryl chlorides