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I
R
2
I
7.68a
L
Pd
0
L
R
1
7.74
reductive
elimination
substrate
binding
L
I
Pd
II
L
R
2
Pd
0
L
I
7.70
R
1
7.73
oxidative
addition
alkene
insertion
I
Pd
II
L
L
alkyne
insertion
Pd
II
R
2
I
7.71
R
1
7.72
R
1
R
2
Scheme 7.35 Proposed mechanism for the Pd(0)-catalyzed conjunctive carboiodination.
Adapted from Ref. 108. Copyright 2013 WILEY-VCH Verlag GmbH & Co.
fashion.
63
When two of the same halogens are present, efforts to achieve se-
lectivity must rely on reactivity biases such as sterics, electronics or directing
groups. Despite the success of these strategies, catalyst deactivation by un-
desired, irreversible oxidative addition to a carbon-halogen bond is an in-
herent setback.
109
In 2013, Lautens and co-workers hypothesized that by using
Pd and QPhos, a combination well precedented to catalyze carboiodination,
off-cycle ArPd(II)X species 7.76 could undergo reductive elimination to re-
generate the active catalyst species (Scheme 7.36).
110
Employing this strategy, diiodinated aromatic compounds 7.79 could
undergo intramolecular carboiodination in moderate to good yields
(Scheme 7.37). In the substrates described, the more sterically accessible
para carbon-iodine bond cannot undergo intramolecular carbopalladation.
Thus, if the Pd catalyst oxidatively adds at this position, reductive elimin-
ation must occur in order to regenerate the active catalytic species so the
desired transformation can occur. In this reaction, the Pd/QPhos combi-
nation is required for both this reversible oxidative addition and the final sp
3
carbon-iodine reductive elimination.
As a means to increase product complexity, Lautens and co-workers ap-
plied this concept to a simultaneous intermolecular/intramolecular
Mizoroki-Heck/carboiodination reaction between diiodoaromatics and ac-
tivated olefins (Scheme 7.38).
108
Thus, diiodoolefin 7.79 can cyclize in
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